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Infertility

This document discusses infertility, including its definition, types, causes, diagnosis, and prevalence. It defines infertility as the inability to conceive a child after two years of regular unprotected sex. The main types are primary infertility, which is the inability to conceive in couples who have never been pregnant, and secondary infertility, which is difficulty conceiving after already having a pregnancy. Causes can be related to both female and male factors, such as genetic issues, medical conditions, environmental exposures, or unexplained causes. Diagnosis involves medical history, physical exams, and tests like semen analysis. The prevalence of infertility is estimated to be between 3-7% of couples worldwide.

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INFERTILITY INTRODUCTION Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term. There are many biological causes of infertility, including some that medical intervention can treat.Womenwho are fertile experience a natural period of fertility before and during ovulation, and they are naturally infertile during the rest of the menstrual cycle. Fertility awareness methods are used to discern when these changes occur by tracking changes in cervical mucus or basal body temperature. DEFINITION The World Health Organization defines infertility as follows Infertility is the inability to conceive a child. A couple may be considered infertile if, after two years of regular sexual intercourse, without contraception, the woman has not become pregnant (and there is no other reason, such as breastfeeding or postpartum amenorrhoea). TYPES Primary infertility is infertility in a couple who have never had a child. Secondary infertility is failure to conceive following a previous pregnancy. Infertility may be caused by infection in the man or woman, but often there is no obvious underlying cause. Combined infertility-In some cases, both the man and woman may be infertile or sub-fertile, and the couple's infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance Unexplained infertility- In the US, up to 20% of infertile couples have unexplained infertility. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. Couples with primary infertility have never been able to conceive, while, on the other hand, secondary infertility is difficulty conceiving after already having conceived (and either carried the pregnancy to term or had a miscarriage). Secondary infertility is not present if there has been a change of partners (this follows tautologically from the convention of speaking of couples, rather than individuals, as being infertile; if there is a change of partners, then a new couple is created, with its own chances to be infertile.) PREVELANCE
Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive. Some estimates suggest that worldwide between three and seven per cent of all couples or women have an unresolved problem of infertility. Many more couples, however, experience involuntary childlessness for at least one year: estimates range from 12% to 28%.Women become less fertile as they get older. For women aged 35, about 94 out of every 100 who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only 77 out of every 100 do so. The effect of age upon men's fertility is less clear. .CAUSES Causes in either sex:Factors that can cause male as well as female infertility are:  DNA damage- DNA damage reduces fertility in female oocytes, as caused by smoking,other xenobiotic DNA damaging agents (such as radiation or chemotherapy)or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine. DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature.  Genetic factors - A Robertsonian translocation in either partner may cause recurrent spontaneous abortions or complete infertility.  General factors- Diabetes mellitus, thyroid disorders, adrenal disease  Hypothalamic-pituitary factors Hyperprolactinemia  Hypopituitarism  Environmental factors- Toxins such as glues, volatile organic solvents or silicones, physical agents, chemical dusts, and pesticides.Tobacco smokers are 60% more likely to be infertile than non-smokers. Causes in females: Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic, or strictly by location.  Acquired versus genetic- Although causes (or factors) of female infertility can be classified as acquired versus genetic, female infertility is usually more or less a combination of nature and nurture. Also, the presence of any single risk factor of female infertility (such as smoking, mentioned further below) does not necessarily cause infertility, and even if a woman is definitely infertile then the infertility cannot definitely be blamed on any single risk factor even if the risk factor is (or has been) present.  Acquired- According to the American Society for Reproductive Medicine (ASRM), Age, Smoking, Sexually Transmitted Infections, and Being Overweight or Underweight can all affect fertility.In broad sense, acquired factors practically include any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development, which may present as infertility many years later as an adult. - Age- A woman's fertility is affected by her age. The average age of a girl's first period (menarche) is 12-13, but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year.A woman's fertility peaks in the early and mid twenties, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, with research giving differing results. The chances of a couple to successfully conceive at an advanced
age depend on many factors, including the general health of a woman and the fertility of the male partner. - Tobacco smoking- Tobacco smoking is harmful to the ovaries, and the degree of damage is dependent upon the amount and length of time a woman smokes or is exposed to a smoke-filled environment. Nicotine and other harmful chemicals in cigarettes interfere with the body’s ability to create estrogen, a hormone that regulates folliculogenesis and ovulation. Also, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and the uterine myometrium. Some damage is irreversible, but stopping smoking can prevent further damage.Smokers are 60% more likely to be infertile than non-smokers. Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%. Also, female smokers have an earlier onset of menopause by approximately 1–4 years. - Sexually transmitted disease- Sexually transmitted diseases are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility. - Body weight and eating disorders- Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen, in addition to the primary sex organs. Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant. Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle.Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate.Proper nutrition in early life is also a major factor for later fertility.  Chemotherapy- Chemotherapy poses a high risk of infertility.Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine. Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin. On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluorouracil.Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles.This loss is not necessarily a direct effect of the chemotherapeutic agents, but could be due to an increased rate of growth initiation to replace damaged developing follicles.Antral follicle count decreases after three series of chemotherapy, whereas follicle stimulating hormone (FSH) reaches menopausal levels after four series. Other hormonal changes in chemotherapy include decrease in inhibin B and anti-Müllerian hormone levels.Patients may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of ovarian tissue, oocytes or embryos.  Other factors that can cause acquired infertility - Adhesions- secondary to surgery in the peritoneal cavity is the leading cause of acquired infertility - Diabetes mellitus. A review of type 1 diabetes came to the result that, despite modern treatment, women with diabetes are at increased risk of female infertility, such as reflected by delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause. - Significant liver or kidney disease
- Thrombophili - Cannabis smoking, such as of marijuana causes disturbances in the endocannabinoid system, potentially causing infertility - Radiation.- A dose of 8 Gy or more to the ovaries generally causes permanent female infertility.  Genetic factors-There are many genes wherein mutation causes female infertility. Also, there are additional conditions involving female infertility which are believed to be genetic but where no single gene has been found to be responsible, notably Mayer-Rokitansky-Küstner- Hauser Syndrome (MRKH). Finally, an unknown number of genetic mutations cause a state of subfertility, which in addition to other factors such as environmental ones may manifest as frank infertility.  Chromosomal abnormalities causing female infertility include Turner syndrome.Some of these gene or chromosome abnormalities cause intersexed conditions, such as androgen insensitivity syndrome  By anatomic location - Hypothalamic-pituitary factors- Hypothalamic dysfunction, Hyperprolactinemia - Ovarian factors-Polycystic ovary syndrome, - Anovulation- Female infertility caused by anovulation is called "anovulatory infertility", as opposed to "ovulatory infertility" in which ovulation is present.Diminished ovarian reserve,Premature menopause, Menopause, Luteal dysfunction, Gonadal dysgenesis (Turner syndrome), Ovarian cancer - Tubal (ectopic)/peritoneal factors- Endometriosis- Endometriosis can lead to anatomical distortions and adhesions (the fibrous bands that form between tissues and organs following recovery from an injury). However, the link between infertility and endometriosis remains enigmatic when the extent of endometriosis is limited.It has been suggested that endometriotic lesions release factors which are detrimental to gametes or embryos, or, alternatively, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it is preferable to speak of endometriosis-associated infertility in such cases. Pelvic adhesions, Pelvic inflammatory disease (PID, usually due to chlamydia), Tubal occlusion,Tubal dysfunction - Uterine factors-Uterine malformations,Uterine fibroids (leiomyoma),Asherman's Syndrome - Cervical factors- Cervical stenosis, Antisperm antibodies,Non-receptive cervical mucus - Vaginal factors-Vaginismus, Vaginal obstruction Causes in males:  Pre-testicular causes-Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including: Hypogonadotropichypogonadism due to various causes Obesity increases the risk of hypogonadotropichypogonadism  Drugs, alcohol  Strenuous riding (bicycle riding,horseback riding)  Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin  Genetic abnormalities such as a Robertsonian translocation  Tobacco smoking
 DNA damage-Common inherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility.As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage. These findings suggest that DNA damage is an important factor in male infertility.  Testicular factors-Testicular factors refer to conditions where the testes produce semen of low quantity and/or poor quality despite adequate hormonal support and include: Age , Genetic defects on the Y chromosome (Y chromosome microdeletions), Abnormal set of chromosomes (Klinefelter syndrome), Neoplasm, Idiopathic failure, Cryptorchidism,Varicocele,Trauma, Hydrocele, Mumps, Malaria, Testicular cancer  Acrosomal defects affecting egg penetration  Idiopathic oligospermia - unexplained sperm deficiencies account for 30% of male infertility.  Radiation therapy to a testis decreases its function, but infertility can efficiently be avoided by avoiding radiation to both testes.  Post-testicular causes- Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in ejaculation: - Vas deferens obstruction - Lack of Vas deferens, often related to genetic markers for Cystic Fibrosis - Infection, e.g. prostatitis - Retrograde ejaculation - Ejaculatory duct obstruction - Hypospadias - Impotence DIAGNOSIS For males The diagnosis of infertility begins with a medical history and physical exam by a physician, preferably a specialist with experience or who specializes in male infertility. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues.  Medical history-The history should include prior testicular or penile insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis), environmental factors (excessive heat, radiation, medications, and drug use (anabolic steroids, alcohol, smoking)  Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important.  Loss of libido and headaches or visual disturbances may indicate a pituitary tumor.  The past medical or surgical history may reveal thyroid or liver disease (abnormalities of spermatogenesis), diabetic neuropathy (retrograde ejaculation), radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury), or hernia repair (damage to the vas deferens or testicular blood supply).  A family history may reveal genetic problems.
 Physical examination- Usually, the patient disrobes completely and puts on a gown. The physician will perform a thorough examination of the penis, scrotum, testicles, anus and rectum.  Sperm sample  Semen analysis- The volume of the semen sample, approximate number of total sperm cells, sperm motility/forward progression, and % of sperm with normal morphology are measured. This is the most common type of fertility testing. Semen deficiencies are often labeled as follows: - Oligospermia or Oligozoospermia - decreased number of spermatozoa in semen - Aspermia - complete lack of semen - Hypospermia - reduced seminal volume - Azoospermia - absence of sperm cells in semen - Teratospermia - increase in sperm with abnormal morphology - Asthenozoospermia - reduced sperm motility - There are various combinations of these as well, e.g. Teratoasthenozoospermia, which is reduced sperm morphology and motility. Low sperm counts are often associated with decreased sperm motility and increased abnormal morphology, thus the terms "oligoasthenoteratozoospermia" or "oligospermia" can be used as a catch- all.  Blood sample  Common hormonal test include determination of FSH and testosterone levels. A blood sample can reveal genetic causes of infertility, e.g. Klinefelter syndrome, a Y chromosome microdeletion, or cystic fibrosis. For females  History  Physical examination  Lab tests- hormone testing, to measure levels of female hormones at certain times during a menstrual cycle,day 2 or 3 measure of FSH and estrogen, to assess ovarian reserve  Measurements of thyroid function (a thyroid stimulating hormone (TSH) level of between 1 and 2 is considered optimal for conception)  Measurement of progesterone in the second half of the cycle to help confirm ovulation  Examination and imaging an endometrial biopsy, to verify ovulation and inspect the lining of the uterus  laparoscopy, which allows the provider to inspect the pelvic organs  fertiloscopy, a relatively new surgical technique used for early diagnosis (and immediate treatment)  Pap smear, to check for signs of infection  pelvic exam, to look for abnormalities or infection  a postcoital test, which is done soon after intercourse to check for problems with sperm surviving in cervical mucous (not commonly used now because of test unreliability)  special X-ray tests  There are genetic testing techniques under development to detect any mutation in genes associated with female infertility.
TREATMENT Treatment depends on the cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for women include Clomiphene citrate, Human menopausal gonadotropin, Follicle- stimulating hormone, Human chorionic gonadotropin, Gonadotropin-releasing hormone analogs, Aromatase inhibitor, Metformin.  At-home conception kit In 2007 the FDA cleared the first at home tier one medical conception device to aid in conception. The key to the kit are cervical caps for conception. This at home [cervical cap] insemination method allows all the semen to be placed up against the cervical os for six hours allowing all available sperm to be placed directly on the cervical os. For low sperm count, low sperm motility, or a tilted cervix using a cervical cap aids conception. This is a prescriptive medical device, but not commonly prescribed by physicians.  At-home assessment Prior to expensive fertility procedures, many women and couples turn to online sources to determine their chances of success. A take-home baby assessment can provide a best guess estimate compared with women who have succeeded with in vitro fertilization, based on variables such as maternal age, duration of infertility and number of prior pregnancies.  Medical treatments Medical treatment of infertility generally involves the use of fertility medication, medical device, surgery, or a combination of the following. If the sperm are of good quality and the mechanics of the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring), physicians may start by prescribing a course of ovarian stimulating medication. The physician may also suggest using a conception cap cervical cap, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body.  ART If conservative medical treatments fail to achieve a full term pregnancy, the physician may suggest the patient undergo in vitro fertilization (IVF). IVF and related techniques (ICSI, ZIFT, GIFT) are called assisted reproductive technology (ART) techniques.ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer.  Other medical techniques are e.g. tuboplasty, assisted hatching, and Preimplantation genetic diagnosis. Treatments vary according to the underlying disease and the degree of the impairment of the male fertility. Further, in an infertility situation, the fertility of the female needs to be considered.Pre-
testicular conditions can often be addressed by medical means or interventions.Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved.Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF. The off-label use of Clomiphene citrate, an anti-estrogen drug designed as a fertility medicine for women, is controversial.Vitamin E helps counter oxidative stress,which is associated with sperm DNA damage and reduced sperm motility.A hormone-antioxidant combination may improve sperm count and motility.The Low dose Estrogen Testosterone Combination Therapy may improve sperm count and motility in some men including severe oligospermia.  Future potential treatments Researchers at Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation.If reproduced in humans, this could potentially enable infertile men to father children with their own sperm. PREVENTION Some cases of female infertility may be prevented through identified interventions:  Maintaining a healthy lifestyle- Excessive exercise, consumption of caffeine and alcohol, and smoking are all associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh fruits and vegetables (plenty of folates), and maintaining a normal weight are associated with better fertility prospects.  Treating or preventing existing diseases- Identifying and controlling chronic diseases such as diabetes and hypothyroidism increases fertility prospects. Lifelong practice of safer sex reduces the likelihood that sexually transmitted diseases will impair fertility; obtaining prompt treatment for sexually transmitted diseases reduces the likelihood that such infections will do significant damage. Regular physical examinations (including pap smears) help detect early signs of infections or abnormalities.  Not delaying parenthood- Fertility does not ultimately cease before menopause, but it starts declining after age 27 and drops at a somewhat greater rate after age . Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions, such as premature menopause, that can be mitigated by not delaying parenthood. ETHICS There are several ethical issues associated with infertility and its treatment.  High-cost treatments are out of financial reach for some couples.  Debate over whether health insurance companies (e.g. in the US) should be required to cover infertility treatment.  Allocation of medical resources that could be used elsewhere  The legal status of embryos fertilized in vitro and not transferred in vivo.
 Pro-life opposition to the destruction of embryos not transferred in vivo.  IVF and other fertility treatments have resulted in an increase in multiple births, provoking ethical analysis because of the link between multiple pregnancies, premature birth, and a host of health problems.  Religious leaders' opinions on fertility treatments.  Infertility caused by DNA defects on the Y chromosome is passed on from father to son. If natural selection is the primary error correction mechanism that prevents random mutations on the Y chromosome, then fertility treatments for men with abnormal sperm (in particular ICSI) only defer the underlying problem to the next male generation. PSYCHOLOGICAL IMPACT The consequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood.Infertility may have profound psychological effects. Partners may become more anxious to conceive, increasing sexual dysfunction. Marital discord often develops in infertile couples, especially when they are under pressure to make medical decisions. Women trying to conceive often have clinical depression rates similar to women who have heart disease or cancer.Even couples undertaking IVF face considerable stress.The emotional losses created by infertility include the denial of motherhood as a rite of passage; the loss of one’s anticipated and imagined life; feeling a loss of control over one’s life; doubting one’s womanhood; changed and sometimes lost friendships; and, for many, the loss of one’s religious environment as a support system.Emotional stress and marital difficulties are greater in couples where the infertility lies with the man. SOCIAL IMPACT In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether; middle-class men are the most likely to respond in this way.In an effort to end the shame and secrecy of infertility, Redbook in October 2011 launched a video campaign, The Truth About Trying, to start an open conversation about infertility, which strikes one in eight women in the United States. In a survey of couples having difficulty conceiving, conducted by the pharmaceutical company Merck, 61 percent of respondents hid their infertility from family and friends. Nearly half didn't even tell their mothers. The message of those speaking out: It's not always easy to get pregnant, and there's no shame in that.There are legal ramifications as well. Infertility has begun to gain more exposure to legal domains. An estimated 4 million workers in the U.S. used the Family and Medical Leave Act (FMLA) in 2004 to care for a child, parent or spouse, or because of their own personal illness. Many treatments for infertility, including diagnostic tests, surgery and therapy for depression, can qualify one for FMLA leave. It has been suggested that infertility be classified as a form of disability.
Oncofertility, fertility in cancer patients 1.^ a b Section "Defining infertility" in: Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013 2.^ http://www.fertilityfaq.org/_pdf/magazine1_v4.pdf 3.^ Anderson SE, Dallal GE, Must A (April 2003). "Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart". Pediatrics 111 (4 Pt 1): 844–50. doi:10.1542/peds.111.4.844. PMID 12671122. 4.^ http://www.ncbi.nlm.nih.gov/pubmed/21110899 1.^ "Men's Health - Male Factor Infertility". University of Utah Health Sciences Center. 2003-04-01. Archived from the original on 2007-07-04. Retrieved 2007-11-21. 2.^Brugh VM, Lipshultz LI (2004). "Male factor infertility". Medical Clinics of North America 88 (2): 367–85. doi:10.1016/S0025-7125(03)00150-0. PMID 15049583. 3.^ Hirsh A (2003). "Male subfertility". BMJ 327 (7416): 669–72. doi:10.1136/bmj.327.7416.669. PMC 196399.PMID 14500443. 4.^ Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C (2009). "World Health Organization reference values for human semen characteristics". Human Reproduction Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 5.^ Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA (2000). " 1.^ a b Section "Defining infertility" in: Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013 2.^ http://www.fertilityfaq.org/_pdf/magazine1_v4.pdf 3.^ Anderson SE, Dallal GE, Must A (April 2003). "Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart". Pediatrics 111 (4 Pt 1): 844–50. doi:10.1542/peds.111.4.844. PMID 12671122. 4.^ http://www.ncbi.nlm.nih.gov/pubmed/21110899
5.^ http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics% 20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf 6.^Apter D (February 1980). "Serum steroids and pituitary hormones in female puberty: a partly longitudinal study". Clinical Endocrinology 12 (2): 107–20. doi:10.1111/j.1365-2265.1980.tb02125.x. PMID 6249519. 7.^ Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H (2011). "Effects of cigarette smoking on reproduction". Hum. Reprod. Update 17 (1): 76– 95. doi:10.1093/humupd/dmq033. PMID 20685716.edit 8.^ a b c d e FERTILITY FACT > Female Risks By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009 9.^ http://dl.dropbox.com/u/8256710/ASRM%20Protect%20Your%20Fertility%20newsletter.pdf 10.^ a b Regulated fertility services: a commissioning aid - June 2009, from the Department of Health UK 11.^ Practice Committee of American Society for Reproductive Medicine (2008). "Smoking and Infertility".FertilSteril 90 (5 Suppl): S254–9. PMID 19007641. 12.^ Nelson LR, Bulun SE (September 2001). "Estrogen production and action". J. Am. Acad. Dermatol. 45 (3 Suppl): S116–24. doi:10.1067/mjd.2001.117432. PMID 11511861. 13.^Sloboda, D. M.; Hickey, M.; Hart, R. (2010). "Reproduction in females: the role of the early life environment". Human Reproduction Update 17 (2): 210–227. doi:10.1093/humupd/dmq048. PMID 20961922.edit 14.^Freizinger M, Franko DL, Dacey M, Okun B, Domar AD (November 2008). "The prevalence of eating disorders in infertile women".Fertil.Steril. 93 (1): 72–8. doi:10.1016/j.fertnstert.2008.09.055. PMID 19006795. 15.^Koning AM, Kuchenbecker WK, Groen H, et al. (2010). "Economic consequences of overweight and obesity in infertility: a framework for .
[edit] Psychological impact The consequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood.[36] Infertility may have profound psychological effects. Partners may become more anxious to conceive, increasing sexual dysfunction.[37] Marital discord often develops in infertile couples, especially when they are under pressure to make medical decisions. Women trying to conceive often have clinical depression rates similar to women who have heart disease or cancer.[38] Even couples undertaking IVF face considerable stress.[39] The emotional losses created by infertility include the denial of motherhood as a rite of passage; the loss of one’s anticipated and imagined life; feeling a loss of control over one’s life; doubting one’s womanhood; changed and sometimes lost friendships; and, for many, the loss of one’s religious environment as a support system.[40] Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.[41] [edit] Social impact In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether; middle-class men are the most likely to respond in this way.[42] In an effort to end the shame and secrecy of infertility, Redbook in October 2011 launched a video campaign, The Truth About Trying, to start an open conversation about infertility, which strikes one in eight women in the United States. In a survey of couples having difficulty conceiving, conducted by the pharmaceutical company Merck, 61 percent of respondents hid their infertility from family and
friends.[43] Nearly half didn't even tell their mothers. The message of those speaking out: It's not always easy to get pregnant, and there's no shame in that. There are legal ramifications as well. Infertility has begun to gain more exposure to legal domains. An estimated 4 million workers in the U.S. used the Family and Medical Leave Act (FMLA) in 2004 to care for a child, parent or spouse, or because of their own personal illness. Many treatments for infertility, including diagnostic tests, surgery and therapy for depression, can qualify one for FMLA leave. It has been suggested that infertility be classified as a form of disability.[44] [edit] Fictional representation Perhaps except for infertility in science fiction, films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing first in the latter part of the 2000s decade, although the techniques have been available for decades.[45] Yet, the amount of people that can relate to it by personal experience in one way or another is ever growing, and the variety of trials and struggles is huge.[45] Any individual examples are referred to individual subarticles of assisted reproductive technology [edit] See also Advanced maternal age Childlessness Conception device Inherited sterility in insects Medical ethics Oncofertility, fertility in cancer patients Surrogate marriage [edit] References 1.^Makar RS, Toth TL (2002). "The evaluation of infertility".Am J ClinPathol. 117 (Suppl): S95–103. PMID 14569805.
2.^ a b Gurunath, S.; Pandian, Z.; Anderson, R. A.; Bhattacharya, S. (2011). "Defining infertility--a systematic review of prevalence studies". Human Reproduction Update 17 (5): 575–88. doi:10.1093/humupd/dmr015. PMID 21493634. 3.^ http://www.who.int/topics/infertility/en/ 4.^ Cooper TG, Noonan E, von Eckardstein S, et al. (2010). "World Health Organization reference values for human semen characteristics". Hum. Reprod. Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 5.^ [1] Fertility: Assessment and Treatment for People with Fertility Problems. London: RCOG Press. 2004. ISBN 1-900364-97-2. 6.^ http://www.who.int/reproductivehealth/topics/infertility/DHS-CR9.pdf 7.^MedlinePlusEncyclopedia Infertility 8.^ Himmel, W.; Ittner, E; Kochen, MM; Michelmann, HW; Hinney, B; Reuter, M; Kallerhoff, M; Ringert, RH (1997). "Voluntary Childlessness and being Childfree". British Journal of General Practice 47 (1): 11. PMC 1312893.PMID 9101672. 9.^ a b NICE fertility guidance 10.^ HFEA Chart on reasons for infertility 11.^ Khan, Khalid; Janesh K. Gupta; Gary Mires (2005). Core clinical cases in obstetrics and gynaecology: a problem-solving approach. London: Hodder Arnold. p. 152.ISBN 0-340-81672-4. 12.^Sahlgrenska University Hospital. (translated from the Swedish sentence: "Cirka 10% avalla par har problem med ofrivilligbarnlöshet.") 13.^ a b Regulated fertility services: a commissioning aid – June 2009, from the Department of Health UK 14.^ a b Zenzes MT (2000). "Smoking and reproduction: gene damage to human gametes and embryos". Hum. Reprod. Update 6 (2): 122–31. PMID 10782570. 15.^ Mark-Kappeler CJ, Hoyer PB, Devine PJ (November 2011). "Xenobiotic effects on ovarian preantral follicles".Biol. Reprod. 85 (5): 871–83. doi:10.1095/biolreprod.111.091173. PMC 3197911.PMID 21697514. 16.^ Seino T, Saito H, Kaneko T, Takahashi T, Kawachiya S, Kurachi H (June 2002). "Eight- hydroxy-2'-deoxyguanosine in granulosa cells is correlated with the quality of oocytes and embryos in an in vitro fertilization-embryo transfer program". Fertil.Steril. 77 (6): 1184–90. PMID 12057726. 17.^Gharagozloo P, Aitken RJ (July 2011). "The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy". Hum. Reprod. 26 (7): 1628–40. doi:10.1093/humrep/der132. PMID 21546386. 18.^Nili HA, Mozdarani H, Pellestor F (2011). "Impact of DNA damage on the frequency of sperm chromosomal aneuploidy in normal and subfertile men". Iran. Biomed. J. 15 (4): 122–9. PMID 22395136.
19.^Shamsi MB, Imam SN, Dada R (November 2011). "Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility". J. Assist. Reprod. Genet. 28 (11): 1073–85. doi:10.1007/s10815-011-9631-8. PMC 3224170.PMID 21904910. 20.^ Van Den Boogaard, E.; Vissenberg, R.; Land, J. A.; Van Wely, M.; Van Der Post, J. A. M.; Goddijn, M.; Bisschop, P. H. (2011). "Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: A systematic review". Human Reproduction Update 17 (5): Male infertility refers to the inability of a male to achieve a pregnancy in a fertile [edit] Treatment Treatments vary according to the underlying disease and the degree of the impairment of the male fertility. Further, in an infertility situation, the fertility of the female needs to be considered. Pre-testicular conditions can often be addressed by medical means or interventions. Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved. Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF. The off-label use of Clomiphene citrate, an anti-estrogen drug designed as a fertility medicine for women, is controversial.[24] Vitamin E helps counter oxidative stress,[25] which is associated with sperm DNA damage and reduced sperm motility.[26] A hormone-antioxidant combination may
improve sperm count and motility.[27] The Low dose Estrogen Testosterone Combination Therapy may improve sperm count and motility in some men.[28] including severe oligospermia.[29][30] [edit] Future potential treatments Researchers at Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation.[31] If reproduced in humans, this could potentially enable infertile men to father children with their own sperm.[32][33] Spermatogenesis [edit] References 1.^ "Men's Health - Male Factor Infertility". University of Utah Health Sciences Center. 2003-04-01. Archived from the original on 2007-07-04. Retrieved 2007-11-21. 2.^Brugh VM, Lipshultz LI (2004). "Male factor infertility". Medical Clinics of North America 88 (2): 367–85. doi:10.1016/S0025-7125(03)00150-0. PMID 15049583. 3.^ Hirsh A (2003). "Male subfertility". BMJ 327 (7416): 669–72. doi:10.1136/bmj.327.7416.669. PMC 196399.PMID 14500443. 4.^ Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C (2009). "World Health Organization reference values for human semen characteristics". Human Reproduction Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 5.^ Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA (2000). "Chapter 2: History taking". WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge [England]: Published on behalf of the World Health Organization by Cambridge University Press. pp. 5–16. ISBN 0-521-77474-8. 6.^ a b Teerds KJ, de Rooij DG, Keijer J (2011). "Functional relationship between obesity and male reproduction: from humans to animal models". Hum. Reprod. Update 17 (5): 667–83. doi:10.1093/humupd/dmr017. PMID 21546379. 7.^Leibovitch I, Mor Y (2005). "The Vicious Cycling: Bicycling Related Urogenital Disorders". European Urology 47 (3): 277–86; discussion 286–7. doi:10.1016/j.eururo.2004.10.024. PMID 15716187. 8.^ "Preventing Smoking and Exposure to Secondhand Smoke Before, During, and After Pregnancy" (pdf). factsheet. United States Centers for Disease Control (CDC).Retrieved 2012-08-27.
9.^Agarwal A, Prabakaran SA, Said TM (2005). "Prevention of Oxidative Stress Injury to Sperm". Journal of Andrology 26 (6): 654–60. doi:10.2164/jandrol.05016. PMID 16291955. 10.^ Robbins WA, Elashoff DA, Xun L, Jia J, Li N, Wu G, Wei F (2005). "Effect of lifestyle exposures on sperm aneuploidy". Cytogenetic and Genome Research 111 (3–4): 371–7. doi:10.1159/000086914. PMID 16192719. 11.^Emsley J (2001). Nature's building blocks: an A-Z guide to the elements. Oxford [Oxfordshire]: Oxford University Press. p. 76.ISBN 0-19-850340-7. 12.^Ji G, Long Y, Zhou Y, Huang C, Gu A, Wang X (2012). Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility. BMC Med 10:49. doi: 10.1186/1741-7015-10-49. PMID: 22594646 13.^ Silva LF, Oliveira JB, Petersen CG, Mauri AL, Massaro FC, Cavagna M, Baruffi RL, Franco JG Jr (2012). The effects of male age on sperm analysis by motile sperm organelle morphology examination (MSOME).ReprodBiolEndocrinol 10:19. doi: 10.1186/1477-7827-10-19. PMID: 22429861 14.^ "Infertility in men". Retrieved 2007-11-21. 15.^Costabile RA, Spevak M (2001). "Characterization of patients presenting with male factor infertility in an equal access, no cost medical system". Urology 58 (6): 1021–4. doi:10.1016/S0090- 4295(01)01400-5. PMID 11744480. 16.^Masarani M, Wazait H, Dinneen M (2006). "Mumps orchitis". Journal of the Royal Society of Medicine 99 (11): 573–5. doi:10.1258/jrsm.99.11.573. PMC 1633545.PMID 17082302. 17.^ Zhang J, Qiu S-D, Li S-B, Zhou D-X, Tian H, Huo Y-W, Ge L, Zhang Q-Y (2007). "Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility". Asian Journal of Andrology 9 (6): 809–14. doi:10.1111/j.1745-7262.2007.00305.x. PMID 17968467. 18.^Cavallini G (2006). "Male idiopathic oligoasthenoteratozoospermia". Asian Journal of Andrology 8 (2): 143–57. doi:10.1111/j.1745-7262.2006.00123.x. PMID 16491265. 19.^Gutfeld O, Wygoda M, Shavit L, Grenader T (2007). "Fertility After Adjuvant External Beam Radiotherapy for Stage I Seminoma". The Internet Journal of Oncology 4 (2).doi:10.5580/2188. 20.^Hargreave TB, McGowan B, Harvey J, McParland M, Elton RA (April 1986). "Is a male infertility clinic of any use?".
Female infertility From Wikipedia, the free encyclopedia Jump to: navigation, search Female infertility Classification and external resources ICD-10 N97.0 ICD-9
628 DiseasesDB 4786 MedlinePlus 001191 eMedicine med/3535 MeSH D007247 Female infertility refers to infertility in female humans.
Contents [hide] 1 Definition 2 Causes and factors 2.1 Acquired versus genetic 2.1.1 Acquired 2.1.1.1 Age 2.1.1.2 Tobacco smoking 2.1.1.3 Sexually transmitted disease 2.1.1.4 Body weight and eating disorders 2.1.1.5 Chemotherapy 2.1.1.6 Other factors that can cause acquired infertility 2.1.2 Genetic factors 2.2 By anatomic location 2.2.1 Hypothalamic-pituitary factors 2.2.2 Ovarian factors 2.2.3 Tubal (ectopic)/peritoneal factors 2.2.4 Uterine factors 2.2.5 Cervical factors 2.2.6 Vaginal factors 3 Diagnosis 4 Prevention 5 See also 6 References
[edit] Definition There is no unanimous definition of female infertility, but NICE guidelines state that: "A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner."[1] It is recommended that a consultation with a fertility specialist should be made earlier if the woman is aged 36 years or over, or there is a known clinical cause of infertility or a history of predisposing factors for infertility.[1] [edit] Causes and factors Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic, or strictly by location. [edit] Acquired versus genetic Although causes (or factors) of female infertility can be classified as acquired versus genetic, female infertility is usually more or less a combination of nature and nurture. Also, the presence of any single risk factor of female infertility (such as smoking, mentioned further below) does not necessarily cause infertility, and even if a woman is definitely infertile then the infertility cannot definitely be blamed on any single risk factor even if the risk factor is (or has been) present. [edit] Acquired According to the American Society for Reproductive Medicine (ASRM), Age, Smoking, Sexually Transmitted Infections, and Being Overweight or Underweight can all affect fertility.[2] In broad sense, acquired factors practically include any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development, which may present as infertility many years later as an adult. [edit] Age
Main article: Age and female fertility A woman's fertility is affected by her age. The average age of a girl's first period (menarche) is 12-13 (12.5 years in the United States,[3] 12.72 in Canada,[4] 12.9 in the UK[5]), but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year.[6] A woman's fertility peaks in the early and mid twenties, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, with research giving differing results. The chances of a couple to successfully conceive at an advanced age depend on many factors, including the general health of a woman and the fertility of the male partner. [edit] Tobacco smoking See also: Women and smoking#Unique gender differences and health effects for Females Tobacco smoking is harmful to the ovaries, and the degree of damage is dependent upon the amount and length of time a woman smokes or is exposed to a smoke-filled environment. Nicotine and other harmful chemicals in cigarettes interfere with the body’s ability to create estrogen, a hormone that regulates folliculogenesis and ovulation. Also, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and the uterine myometrium.[7] Some damage is irreversible, but stopping smoking can prevent further damage.[8][9] Smokers are 60% more likely to be infertile than non-smokers.[10] Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.[10] Also, female smokers have an earlier onset of menopause by approximately 1–4 years.[11] [edit] Sexually transmitted disease Sexually transmitted diseases are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility.[8] [edit] Body weight and eating disorders Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen,[12] in addition to the primary sex organs. Too much body fat causes
production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant.[8] Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle.[8] Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate.[8] Proper nutrition in early life is also a major factor for later fertility.[13] A study in the US indicated that approximately 20% of infertile women had a past or current eating disorder, which is five times higher than the general lifetime prevalence rate.[14] A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs. In hypothetical groups of 1000 women undergoing fertility care, the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women. For ovulatory women, the study counted approximately 700 live births for normal weight, 550 live births for overweight and 530 live births for obese women. The increase in cost per live birth in anovulatory overweight and obese women were, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.[15] [edit] Chemotherapy Chemotherapy poses a high risk of infertility. Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine.[16] Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.[16] On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluorouracil.[16] Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles.[17] This loss is not necessarily a direct effect of the chemotherapeutic agents, but could be due to an increased rate of growth initiation to replace damaged developing follicles.[17] Antral follicle count decreases after three series of chemotherapy, whereas follicle stimulating hormone (FSH) reaches menopausal levels after four series.[18] Other hormonal changes in chemotherapy include decrease in inhibin B and anti-Müllerian hormone levels.[18]
Patients may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of ovarian tissue, oocytes or embryos.[19] [edit] Other factors that can cause acquired infertility Adhesions secondary to surgery in the peritoneal cavity is the leading cause of acquired infertility.[20] A meta-analysis in 2012 came to the conclusion that there is only little evidence for the surgical principle that using less invasive techniques, introducing less foreign bodies or causing less ischemia reduces the extent and severity of adhesions.[20] Diabetes mellitus. A review of type 1 diabetes came to the result that, despite modern treatment, women with diabetes are at increased risk of female infertility, such as reflected by delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause.[21] Animal models indicate that abnormalities on the molecular level caused by diabetes include defective leptin, insulin and kisspeptin signalling.[21] Significant liver or kidney disease Thrombophilia[22][23] Cannabis smoking, such as of marijuana causes disturbances in the endocannabinoid system, potentially causing infertility[24] Radiation. A dose of 8 Gy or more to the ovaries generally causes permanent female infertility.[25] [edit] Genetic factors There are many genes wherein mutation causes female infertility, as shown in table below. Also, there are additional conditions involving female infertility which are believed to be genetic but where no single gene has been found to be responsible, notably Mayer-Rokitansky-Küstner-Hauser Syndrome (MRKH).[26] Finally, an unknown number of genetic mutations cause a state of subfertility, which in addition to other factors such as environmental ones may manifest as frank infertility. Chromosomal abnormalities causing female infertility include Turner syndrome. Some of these gene or chromosome abnormalities cause intersexed conditions, such as androgen insensitivity syndrome Genes wherein mutation causes female infertility[27]
Gene Encoded protein Effect of deficiency BMP15 Bone morphogenetic protein 15 Hypergonadotrophic ovarian failure (POF4) BMPR1B Bone morphogenetic protein receptor 1B Ovarian dysfunction, hypergonadotrophichypogonadism and acromesomelicchondrodysplasia CBX2; M33
Chromobox protein homolog 2 ; Drosophila polycomb class Autosomal 46,XY, male-to-female sex reversal (phenotypically perfect females) CHD7 Chromodomain-helicase-DNA-binding protein 7 CHARGE syndrome and Kallmann syndrome (KAL5) DIAPH2 Diaphanous homolog 2 Hypergonadotrophic, premature ovarian failure (POF2A) FGF8 Fibroblast growth factor 8 Normosmichypogonadotrophichypogonadism and Kallmann syndrome (KAL6)
FGFR1 Fibroblast growth factor receptor 1 Kallmann syndrome (KAL2) FSHR FSH receptor Hypergonadotrophichypogonadism and ovarian hyperstimulation syndrome FSHB Follitropin subunit beta Deficiency of follicle-stimulating hormone, primary amenorrhoea and infertility FOXL2
Forkhead box L2 Isolated premature ovarian failure (POF3) associated with BPES type I; FOXL2 402C --> G mutations associated with human granulosa cell tumours FMR1 Fragile X mental retardation Premature ovarian failure (POF1) associated with premutations GNRH1 Gonadotropin releasing hormone Normosmichypogonadotrophichypogonadism GNRHR GnRH receptor
Hypogonadotrophichypogonadism KAL1 Kallmann syndrome Hypogonadotrophichypogonadism and insomnia, X-linked Kallmann syndrome (KAL1) KISS1R ; GPR54 KISS1 receptor Hypogonadotrophichypogonadism LHB Luteinizing hormone beta polypeptide LHCGR
LH/choriogonadotrophin receptor Hypergonadotrophichypogonadism (luteinizing hormone resistance) DAX1 Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 X-linked congenital adrenal hypoplasia with hypogonadotrophichypogonadism; dosage-sensitive male-to-female sex reversal NR5A1; SF1 Steroidogenic factor 1 46,XY male-to-female sex reversal and streak gonads and congenital lipoid adrenal hyperplasia; 46,XX gonadal dysgenesis and 46,XX primary ovarian insufficiency POF1B Premature ovarian failure 1B
Hypergonadotrophic, primary amenorrhea (POF2B) PROK2 Prokineticin Normosmichypogonadotrophichypogonadism and Kallmann syndrome (KAL4) PROKR2 Prokineticin receptor 2 Kallmann syndrome (KAL3) RSPO1 R-spondin family, member 1 46,XX, female-to-male sex reversal (individuals contain testes)
SRY Sex-determining region Y Mutations lead to 46,XY females; translocations lead to 46,XX males SOX9 SRY-related HMB-box gene 9 Autosomal 46,XY male-to-female sex reversal (campomelic dysplasia) TAC3 Tachykinin 3 Normosmichypogonadotrophichypogonadism TACR3 Tachykinin receptor 3
Normosmichypogonadotrophichypogonadism [edit] By anatomic location [edit] Hypothalamic-pituitary factors Hypothalamic dysfunction Hyperprolactinemia[28] [edit] Ovarian factors Polycystic ovary syndrome, see infertility in polycystic ovary syndrome Anovulation. Female infertility caused by anovulation is called "anovulatory infertility", as opposed to "ovulatory infertility" in which ovulation is present.[29] Diminished ovarian reserve, also see Poor Ovarian Reserve Premature menopause Menopause Luteal dysfunction[30] Gonadal dysgenesis (Turner syndrome) Ovarian cancer [edit] Tubal (ectopic)/peritoneal factors Endometriosis[31] Endometriosis can lead to anatomical distortions and adhesions (the fibrous bands that form between tissues and organs following recovery from an injury). However, the link between infertility and endometriosis remains enigmatic when the extent of endometriosis is limited.[32] It has been suggested that endometriotic lesions release factors which are detrimental to gametes or embryos, or, alternatively, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it is preferable to speak of endometriosis-associated infertility[33] in such cases. Pelvic adhesions
Pelvic inflammatory disease (PID, usually due to chlamydia)[34] Tubal occlusion[35] Tubal dysfunction [edit] Uterine factors Uterine malformations[36] Uterine fibroids (leiomyoma) Asherman'sSyndrome[37] [edit] Cervical factors Cervical stenosis[38] Antispermantibodies[39] Non-receptive cervical mucus[40] [edit] Vaginal factors Vaginismus Vaginal obstruction [edit] Diagnosis Diagnosis of infertility begins with a medical history and physical exam. The healthcare provider may order tests, including the following: Lab tests hormone testing, to measure levels of female hormones at certain times during a menstrual cycle day 2 or 3 measure of FSH and estrogen, to assess ovarian reserve measurements of thyroid function[41] (a thyroid stimulating hormone (TSH) level of between 1 and 2 is considered optimal for conception) measurement of progesterone in the second half of the cycle to help confirm ovulation
Examination and imaging an endometrial biopsy, to verify ovulation and inspect the lining of the uterus laparoscopy, which allows the provider to inspect the pelvic organs fertiloscopy, a relatively new surgical technique used for early diagnosis (and immediate treatment) Pap smear, to check for signs of infection pelvic exam, to look for abnormalities or infection apostcoital test, which is done soon after intercourse to check for problems with sperm surviving in cervical mucous (not commonly used now because of test unreliability) special X-ray tests There are genetic testing techniques under development to detect any mutation in genes associated with female infertility.[27] Diagnosis and treatment of infertility should be made by physicians who are fellowship trained as reproductive endocrinologists. Reproductive Endocrinologists are usually Obstetrician-Gynecologists with advanced training in Reproductive Endocrinology & Infertility (in North America). These highly educated professionals and qualified physicians treat Reproductive Disorders affecting not only women but also men, children, and teens. Prospective patients should note that reproductive endocrinology & infertility medical practices do not see women for general maternity care. The practice is primarily focused on helping their patients to conceive and to correct any issues related to recurring pregnancy loss. [edit] Prevention Some cases of female infertility may be prevented through identified interventions: Maintaining a healthy lifestyle. Excessive exercise, consumption of caffeine and alcohol, and smoking are all associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh fruits and vegetables (plenty of folates), and maintaining a normal weight are associated with better fertility prospects. Treating or preventing existing diseases. Identifying and controlling chronic diseases such as diabetes and hypothyroidism increases fertility prospects. Lifelong practice of safer sex reduces the likelihood that sexually transmitted diseases will impair fertility; obtaining prompt treatment for sexually
transmitted diseases reduces the likelihood that such infections will do significant damage. Regular physical examinations (including pap smears) help detect early signs of infections or abnormalities. Not delaying parenthood. Fertility does not ultimately cease before menopause, but it starts declining after age 27 and drops at a somewhat greater rate after age 35.[42] Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions, such as premature menopause, that can be mitigated by not delaying parenthood. [edit] See also Infertility Male infertility Meiosis Oncofertility [edit] References 1.^ a b Section "Defining infertility" in: Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013 2.^ http://www.fertilityfaq.org/_pdf/magazine1_v4.pdf 3.^ Anderson SE, Dallal GE, Must A (April 2003). "Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart". Pediatrics 111 (4 Pt 1): 844–50. doi:10.1542/peds.111.4.844. PMID 12671122. 4.^ http://www.ncbi.nlm.nih.gov/pubmed/21110899 5.^ http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics% 20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf 6.^Apter D (February 1980). "Serum steroids and pituitary hormones in female puberty: a partly longitudinal study". Clinical Endocrinology 12 (2): 107–20. doi:10.1111/j.1365-2265.1980.tb02125.x. PMID 6249519. 7.^ Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H (2011). "Effects of cigarette smoking on reproduction". Hum. Reprod. Update 17 (1): 76– 95. doi:10.1093/humupd/dmq033. PMID 20685716.edit 8.^ a b c d e FERTILITY FACT > Female Risks By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009 9.^ http://dl.dropbox.com/u/8256710/ASRM%20Protect%20Your%20Fertility%20newsletter.pdf
10.^ a b Regulated fertility services: a commissioning aid - June 2009, from the Department of Health UK 11.^ Practice Committee of American Society for Reproductive Medicine (2008). "Smoking and Infertility".FertilSteril 90 (5 Suppl): S254–9. PMID 19007641. 12.^ Nelson LR, Bulun SE (September 2001). "Estrogen production and action". J. Am. Acad. Dermatol. 45 (3 Suppl): S116–24. doi:10.1067/mjd.2001.117432. PMID 11511861. 13.^Sloboda, D. M.; Hickey, M.; Hart, R. (2010). "Reproduction in females: the role of the early life environment". Human Reproduction Update 17 (2): 210–227. doi:10.1093/humupd/dmq048. PMID 20961922.edit 14.^Freizinger M, Franko DL, Dacey M, Okun B, Domar AD (November 2008). "The prevalence of eating disorders in infertile women".Fertil.Steril. 93 (1): 72–8. doi:10.1016/j.fertnstert.2008.09.055. PMID 19006795. 15.^Koning AM, Kuchenbecker WK, Groen H, et al. (2010). "Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care". Hum. Reprod. Update 16 (3): 246–54. doi:10.1093/humupd/dmp053. PMID 20056674. 16.^ a b c Brydøy M, Fosså SD, Dahl O, Bjøro T (2007). "Gonadal dysfunction and fertility problems in cancer survivors".ActaOncol 46 (4): 480–9. doi:10.1080/02841860601166958. PMID 17497315. 17.^ a b Morgan, S.; Anderson, R. A.; Gourley, C.; Wallace, W. H.; Spears, N. (2012). "How do chemotherapeutic agents damage the ovary?". Human Reproduction Update 18 (5): 525. doi:10.1093/humupd/dms022. edit 18.^ a b Rosendahl, M.; Andersen, C.; La CourFreiesleben, N.; Juul, A.; Løssl, K.; Andersen, A. (2010). "Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age". Fertility and Sterility 94 (1): 156–166. doi:10.1016/j.fertnstert.2009.02.043. PMID 19342041.edit 19.^Gurgan T, Salman C, Demirol A (October 2008). "Pregnancy and assisted reproduction techniques in men and women after cancer treatment". Placenta 29 (Suppl B): 152–9. doi:10.1016/j.placenta.2008.07.007. PMID 18790328. 20.^ a b Ten Broek, R. P. G.; Kok- Krant, N.; Bakkum, E. A.; Bleichrodt, R. P.; Van Goor, H. (2012). "Different surgical techniques to reduce post-operative adhesion formation: A systematic review and meta-analysis". Human Reproduction Update 19 (1): 12–25. doi:10.1093/humupd/dms032. PMID 22899657.edit 21.^ a b Codner, E.; Merino, P. M.; Tena-Sempere, M. (2012). "Female reproduction and type 1 diabetes: From mechanisms to clinical findings". Human Reproduction Update 18 (5): 568. doi:10.1093/humupd/dms024. edit 22.^Middeldorp S (2007). "Pregnancy failure and heritable thrombophilia".Semin.Hematol. 44 (2): 93–7. doi:10.1053/j.seminhematol.2007.01.005. PMID 17433901. 23.^Qublan HS, Eid SS, Ababneh HA, et al. (2006). "Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure". Hum. Reprod. 21 (10): 2694–8. doi:10.1093/humrep/del203. PMID 16835215.
24.^Karasu, T.; Marczylo, T. H.; MacCarrone, M.; Konje, J. C. (2011). "The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility". Human Reproduction Update 17 (3): 347–361. doi:10.1093/humupd/dmq058. PMID 21227997.edit 25.^ Chapter on Amenorrhea in: Bradshaw, Karen D.; Schorge, John O.; Schaffer, Joseph; Lisa M. Halvorson; Hoffman, Barbara G. (2008). Williams' Gynecology.McGraw-Hill Professional.ISBN 0- 07-147257-6. 26.^ Sultan C, Biason-Lauber A, Philibert P (January 2009). "Mayer-Rokitansky-Kuster-Hauser syndrome: recent clinical and genetic findings". GynecolEndocrinol 25 (1): 8–11. doi:10.1080/09513590802288291. PMID 19165657. 27.^ a b Unless otherwise specified in boxes, then reference is: Fauser, B. C. J. M.; Diedrich, K.; Bouchard, P.; Dominguez, F.; Matzuk, M.; Franks, S.; Hamamah, S.; Simon, C. et al. (2011). "Contemporary genetic technologies and female reproduction". Human Reproduction Update 17 (6): 829–847. doi:10.1093/humupd/dmr033. PMC 3191938.PMID 21896560.edit 28.^ Female Infertility 29.^ Hull MG, Savage PE, Bromham DR (June 1982). "Anovulatory and ovulatory infertility: results with simplified management". Br Med J (Clin Res Ed) 284 (6330): 1681–5. doi:10.1136/bmj.284.6330.1681. PMC 1498620.PMID 6805656. 30.^ Luteal Phase Dysfunction at eMedicine 31.^Tomassetti C, Meuleman C, Pexsters A, et al. (2006). "Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link?".Reprod. Biomed. Online 13 (1): 58–64. doi:10.1016/S1472-6483(10)62016-0. PMID 16820110. 32.^Speroff L, Glass RH, Kase NG (1999). Clinical Gynecologic Endocrinology and Infertility (6th ed.). Lippincott Willimas Wilkins. p. 1057.ISBN 0-683-30379-1. 33.^Buyalos RP, Agarwal SK (October 2000). "Endometriosis-associated infertility". Current Opinion in Obstetrics &Gynecology 12 (5): 377–81. doi:10.1097/00001703-200010000-00006. ISSN 1040-872X. PMID 11111879. 34.^ Guven MA, Dilek U, Pata O, Dilek S, Ciragil P (2007). "Prevalence of Chlamydia trochomatis, Ureaplasmaurealyticum and Mycoplasma hominis infections in the unexplained infertile women". Arch. Gynecol. Obstet. 276 (3): 219–23. doi:10.1007/s00404-006-0279-z. PMID 17160569. 35.^García-Ulloa AC, Arrieta O (2005). "Tubal occlusion causing infertility due to an excessive inflammatory response in patients with predisposition for keloid formation". Med. Hypotheses 65 (5): 908–14. doi:10.1016/j.mehy.2005.03.031. PMID 16005574. 36.^ Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simón C, Pellicer A (1997). "Reproductive impact of congenital Müllerian anomalies". Hum. Reprod. 12 (10): 2277–81. doi:10.1093/humrep/12.10.2277. PMID 9402295. 37.^Magos A (2002). "Hysteroscopic treatment of Asherman's syndrome".Reprod. Biomed. Online 4 (Suppl 3): 46–51. PMID 12470565.
38.^ Tan Y, Bennett MJ (2007). "Urinary catheter stent placement for treatment of cervical stenosis". The Australian & New Zealand journal of obstetrics & gynaecology 47 (5): 406–9. doi:10.1111/j.1479-828X.2007.00766.x. PMID 17877600. 39.^Francavilla F, Santucci R, Barbonetti A, Francavilla S (2007). "Naturally-occurring antisperm antibodies in men: interference with fertility and clinical implications. An update". Front. Biosci. 12 (8–12): 2890–911. doi:10.2741/2280. PMID 17485267. 40.^Farhi J, Valentine A, Bahadur G, Shenfield F, Steele SJ, Jacobs HS (1995). "In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests". Hum. Reprod. 10 (1): 85–90. doi:10.1093/humrep/10.1.85. PMID 7745077. 41.^Wartofsky L, Van Nostrand D, Burman KD (2006). "Overt and 'subclinical' hypothyroidism in women". Obstetrical &gynecological survey 61 (8): 535–42. doi:10.1097/01.ogx.0000228778.95752.66. PMID 16842634. 42.^ Hall, Carl T. "Study speeds up biological clocks / Fertility rates dip after women hit 27". The San Francisco Chronicle.Retrieved 2007-11-21. [show] v · t · e Female diseases of the pelvis and genitals (N70–N99, 614–629)
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About Wikipedia Disclaimers Mobile view How your infertility is treated depends on the cause, your age, how long you've been infertile and personal preferences. Although some women need just one or two therapies to restore fertility, it's possible that several different types of treatment may be needed before you're able to conceive. Treatments can either attempt to restore fertility — by means of medication or surgery — or assist in reproduction with sophisticated techniques. Fertility restoration: Stimulating ovulation with fertility drugs Fertility drugs, which regulate or induce ovulation, are the main treatment for women who are infertile due to ovulation disorders. In general, they work like the natural hormones — follicle- stimulating hormone (FSH) and luteinizing hormone (LH) — to trigger ovulation. Using fertility drugs carries some risks: Becoming pregnant with twins or other multiples. Oral medications carry a fairly low risk of multiples (less than 10 percent), but your chances increase to about 15 to 20 percent with injectable medications. Generally, the more fetuses you're carrying, the greater the risk of premature labor, low birth weight and later developmental problems. Sometimes the amount or timing of the medications will be altered in an attempt to lower the risk of multiples. Treatment cycles may be canceled if your doctor detects the development of too many follicles, which could result in ovulation of more than one egg. Developing enlarged ovaries. Ovarian hyperstimulation syndrome (OHSS) is a condition that can result from the use of fertility drugs. In response to the medication, your ovaries become overstimulated. Besides developing enlarged ovaries, you might experience abdominal pain and distention, gastrointestinal problems and shortness of breath. Signs and symptoms can develop while you're undergoing ovulation induction or during the early stages of pregnancy. There are several fertility drugs for abnormal LH and FSH production. These drugs include:
Clomiphene citrate (Clomid, Serophene). This drug is taken orally and stimulates ovulation in women who have PCOS or other ovulation disorders. It causes the pituitary gland to release more FSH and LH, which stimulate the growth of an ovarian follicle containing an egg. Clomiphene citrate also improves fertility in normally ovulating women, and is often used as an initial treatment for unexplained infertility. Gonadotropins. Instead of stimulating the pituitary gland to release more hormones, these treatments stimulate the ovary directly. Often, gonadotropin medications are used in combination with intrauterine insemination (IUI) — a procedure during which sperm is injected into your uterus via a thin tube (catheter) — to increase the odds of a pregnancy. Gonadotropin medications include: Human menopausal gonadotropin, or hMG, (Repronex, Menopur). This injected medication is for women who don't ovulate on their own due to the failure of the pituitary gland to stimulate ovulation. HMG contains both FSH and LH, and directly stimulates the ovaries to ovulate. Follicle-stimulating hormone, or FSH, (Gonal-F, Follistim, Bravelle). FSH works by stimulating the ovaries to produce mature egg follicles. Human chorionic gonadotropin, or HCG, (Ovidrel, Pregnyl). Used in combination with clomiphene, hMG or FSH, this drug stimulates the follicle to release its egg (ovulate). Metformin (Glucophage). This oral drug is used when insulin resistance is a known or suspected cause of infertility, usually in women with a diagnosis of PCOS. Metformin improves insulin resistance, normalizing the insulin level and making ovulation more likely to occur. Letrozole (Femara). Letrozole belongs to a class of drugs known as aromatase inhibitors. Letrozole, also used to treat some breast cancers, may induce ovulation. However, the effect the medication has on early pregnancy isn't yet known, so this medication isn't used for ovulation induction as frequently as others. Fertility restoration: Surgery Several surgical procedures can correct problems or otherwise improve female fertility. They include: Tissue removal. This surgery removes endometrial tissue or pelvic adhesions with lasers or ablation, which can improve your chances of achieving pregnancy. Tubal reversal surgery (microscopic). After a woman has had her tubes tied for permanent contraception (tubal ligation), surgery may be done to reconnect them and restore fertility. Your doctor will determine whether you're a good candidate for the surgery. Tubal surgeries. If your fallopian tubes are blocked or filled with fluid (called hydrosalpinx), tubal surgery may improve your chances of becoming pregnant. Laparoscopic surgery is performed to remove adhesions, dilate a tube or create a new tubal opening. Tubal surgery is more successful when
the blocked or narrowed part of the tube is closer to the ovary than to the uterus. Tubal blockage close to your uterus may increase your risk of ectopic pregnancy. In these and other severe cases of blockage or hydrosalpinx, removal of your tubes (salpingectomy) can improve your chances of pregnancy with in vitro fertilization. Reproductive assistance: In vitro fertilization This effective technique involves retrieving mature eggs from a woman, fertilizing them with a man's sperm in a dish in a laboratory and transferring the embryos in the uterus three to five days after fertilization. In vitro fertilization (IVF) often is recommended when both fallopian tubes are blocked. It's also widely used for a number of other conditions, such as endometriosis, unexplained infertility, cervical factor infertility, male infertility and ovulation disorders. IVF increases your odds of having twins or other multiples if more than one embryo is transferred to your uterus. IVF requires frequent blood tests and daily hormone injections. Coping and support Tests and diagnosis Mayo Clinic products and services Infertility treatment at Mayo Clinic Book: Mayo Clinic Family Health Book, 4th Edition Give today to find cures for tomorrow See Also In vitro fertilization (IVF) Intrauterine insemination (IUI) Ovarian hyperstimulation syndrome Sperm donation Fertility herbs: Do they enhance fertility?
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Assisted reproductive technology (ART) is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments, otherwise known as 'fertility treatments'. Some forms of ART are also used in fertile couples for genetic reasons. ART is also used in couples who are discordant for certain communicable diseases, e.g. AIDS, to reduce the risk of infection when a pregnancy is desired. Examples of ART include in vitro fertilization, intracytoplasmic sperm injection (ICSI), cryopreservation, and intrauterine insemination (IUI). There is yet no strict definition of the term. Usage of the ART mainly belongs in the field of reproductive endocrinology and infertility. Contents [hide] 1 Definitions 2 Procedures 2.1 Medication 2.2 In vitro fertilization 2.3 Surrogacy 2.4 Others 3 Risks 4 Usage 5 Costs 5.1 United States of America 5.2 United Kingdom 5.3 Sweden 5.4 Canada 5.5 Israel 5.6 New Zealand 5.7 Germany
6 Ethics 7 Fictional representation 8 See also 9 References 10 External links [edit] Definitions While there is no consensus on the definition, generally the process of intercourse is bypassed either by artificial insemination or fertilization of the oocytes in the laboratory environment (i.e., in vitro fertilization). The Centers for Disease Control and Prevention (CDC)—which is required as a result of the 1992 Fertility Clinic Success Rate and Certification Act to publish the annual ART success rates at U.S. fertility clinics—defines ART to include "all fertility treatments in which both eggs and sperm are handled. In general, ART procedures involve surgically removing eggs from a woman's ovaries, combining them with sperm in the laboratory, and returning them to the woman's body or donating them to another woman." According to CDC, "they do not include treatments in which only sperm are handled (i.e., intrauterine—or artificial—insemination) or procedures in which a woman takes medicine only to stimulate egg production without the intention of having eggs retrieved." [edit] Procedures Procedures are mainly fertility medication, as well as ART techniques that use more substantial and forceful interventions, of which in vitro fertilization (IVF) and expansions of it (e.g. OCR, AZH, ICSI, ZIFT) are the most prevalent. However, there are also other manual ART, not necessarily dependent on IVF (e.g. PGD, GIFT, SSR). [edit] Medication Main article: Fertility medication Most fertility medication are agents that stimulate the development of follicles in the ovary. Examples are gonadotropins and gonadotropin releasing hormone.
[edit] In vitro fertilization Main article: In vitro fertilization In vitro fertilization (IVF) is the technique of letting fertilization of the male and female gametes (sperm and egg) occur outside the female body. Techniques usually used in in vitro fertilization include: Transvaginal ovum retrieval (OCR) is the process whereby a small needle is inserted through the back of the vagina and guided via ultrasound into the ovarian follicles to collect the fluid that contains the eggs. Embryo transfer is the step in the process whereby one or several embryos are placed into the uterus of the female with the intent to establish a pregnancy. Less commonly used techniques in in vitro fertilization are: Assisted zona hatching (AZH) is performed shortly before the embryo is transferred to the uterus. A small opening is made in the outer layer surrounding the egg in order to help the embryo hatch out and aid in the implantation process of the growing embryo. Intracytoplasmic Sperm Injection (ICSI) Intracytoplasmic sperm injection (ICSI) is beneficial in the case of male factor infertility where sperm counts are very low or failed fertilization occurred with previous IVF attempt(s). The ICSI procedure involves a single sperm carefully injected into the center of an egg using a microneedle. This method is also sometimes employed when donor sperm is used. Autologous endometrial coculture is a possible treatment for patients who have failed previous IVF attempts or who have poor embryo quality. The patient's fertilized eggs are placed on top of a layer of cells from the patient's own uterine lining, creating a more natural environment for embryo development. In zygote intrafallopian transfer (ZIFT), egg cells are removed from the woman's ovaries and fertilized in the laboratory; the resulting zygote is then placed into the fallopian tube.
Cytoplasmic transfer is the technique in which the contents of a fertile egg from a donor are injected into the infertile egg of the patient along with the sperm. Egg donors are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age. In the egg donor process, eggs are retrieved from a donor's ovaries, fertilized in the laboratory with the sperm from the recipient's partner, and the resulting healthy embryos are returned to the recipient's uterus. Sperm donation may provide the source for the sperm used in IVF procedures where the male partner produces no sperm or has an inheritable disease, or where the woman being treated has no male partner. Preimplantation genetic diagnosis (PGD) involves the use of genetic screening mechanisms such as Fluorescent In Situ Hybridization (FISH) or Comparative Genomic Hybridization (CGH) to help identify genetically abnormal embryos and improve healthy outcomes. Embryo splitting can be used for twinning to increase the number of available embryos.[1] [edit] Surrogacy Surrogacy via a gestational carrier is an option when a patient's medical condition prevents a safe pregnancy, when a patient has ovaries but no uterus due to congenital absence or previous surgical removal, and where a patient has no ovaries and is also unable to carry a pregnancy to full term. [edit] Others The following techniques don't necessarily involve IVF: In gamete intrafallopian transfer (GIFT) a mixture of sperm and eggs is placed directly into a woman's fallopian tubes using laparoscopy following a transvaginal ovum retrieval. Sex selection is the attempt to control the sex of offspring to achieve a desired sex. It can be accomplished in several ways, both pre- and post-implantation of an embryo, as well as at birth. Pre- implantation techniques include PGD, but also sperm sorting. Artificial insemination (AI) is when sperm is placed into a female's uterus (intrauterine) or cervix (intracervical) using artificial means rather than by natural copulation. N.B. This can be a very low- tech process, performed at home by the woman alone or with her partner.[2] Conception devices, such as a conception cap are used to aid conception by enhancing[vague] the natural process. Conception caps are used by placing semen into a small conception cap, then placing the cap onto the cervix. This holds the semen at the cervical os, protecting the semen from the acidic vaginal secretions and keeping it in contact with the cervical mucus. Artificial insemination by donor is used in situations where the woman doesn't have a partner with functional sperm. Instead, a sperm donor supplies the sperm.
Surrogacy, where a woman agrees to become pregnant and deliver a child for a contracted party. It may be her own genetic child, or a child conceived through natural insemination, in vitro fertilization or embryo transfer using another woman's ova. Reproductive surgery, treating e.g. fallopian tube obstruction and vas deferens obstruction, or reversing a vasectomy by a reverse vasectomy. In surgical sperm retrieval (SSR) the reproductive urologist obtains sperm from the vas deferens, epididymis or directly from the testis in a short outpatient procedure. By cryopreservation, eggs, sperm and reproductive tissue can be preserved for later IVF. [edit] Risks The majority of IVF-conceived infants do not have birth defects.[3] However, some studies have suggested that assisted reproductive technology is associated with an increased risk of birth defects.[4][5] In the largest U.S. study, which used data from a statewide registry of birth defects,[6] 6.2% of IVF-conceived children had major defects, as compared with 4.4% of naturally conceived children matched for maternal age and other factors (odds ratio, 1.3; 95% confidence interval, 1.00 to 1.67).[3] The main risks are: Genetic disorders. DNA damage increases in e.g. IVF and ICSI, which is reflected e.g. by upregulation of the gene expression of HNRNPC in the placenta.[7] Low birth weight. In IVF and ICSI, a risk factor is the decreased expression of proteins in energy metabolism; Ferritin light chain and ATP5A1.[7] Preterm birth. Low birth weight and preterm birth are strongly associated with many health problems, such as visual impairment and cerebral palsy, and children born after IVF are roughly twice as likely to have cerebral palsy.[8] Other risk factors are: Membrane damage, which is contributed to or reflected by increased expression of the membrane fusion proteins NAPA and Annexin A3.[7] Sperm donation is an exception, with a birth defect rate of almost a fifth compared to the general population.[9] It may be explained by that sperm banks accept only people with high sperm count.
Current data indicate little or no increased risk for postpartum depression among women who use ART.[10] [edit] Usage Assisted reproductive technology procedures performed in the U.S. has more than doubled since 10 years ago, with 140.000 procedures in 2006,[11] resulting in 55.000 infants born.[11] In Australia, 3.1% of babies now born are a result of ART.[12] In case of discontinuation of fertility treatment, the most common reasons have been estimated to be: postponement of treatment (39%), physical and psychological burden (19%, psychological burden 14%, physical burden 6.32%), relational and personal problems (17%, personal reasons 9%, relational problems 9%), treatment rejection (13%) and organizational (12%) and clinic (8%) problems.[13] [edit] Costs [edit] United States of America Not everyone in the U.S. has insurance coverage for fertility investigations and treatments. Many states are starting to mandate coverage, and the rate of utilization is 277% higher in states with complete coverage.[14] There are some health insurance companies that cover diagnosis of infertility but frequently once diagnosed will not cover any treatment costs. 2005 approximate treatment/diagnosis costs (United States, costs in US$): Initial workup: hysteroscopy, hysterosalpingogram, blood tests ~$2,000 Intrauterine Insemination (IUI) aka Artificial insemination ~ $200– 900 per. trial Sonohysterogram (SHG) ~ $600 – 1,000 Clomiphene citrate cycle ~ $ 200 – 500
IVF cycle ~ $10,000 -30,000 Use of a surrogate mother to carry the child – dependent on arrangements Another way to look at costs is to determine the expected cost of establishing a pregnancy. Thus if a clomiphene treatment has a chance to establish a pregnancy in 8% of cycles and costs $500, the expected cost is $6,000 to establish a pregnancy, compared to an IVF cycle (cycle fecundity 40%) with a corresponding expected cost of $30,000 ($12,000/.4). For the community as a whole, the cost of IVF on average pays back by 700% by tax from future employment by the conceived human being.[15] [edit] United Kingdom In the UK all patients have the right to preliminary testing, provided free of charge by the National Health Service. However, treatment is not widely available on the NHS and there can be long waiting lists. Many patients therefore pay for immediate treatment within the NHS or seek help from private clinics.[16] [edit] Sweden In Sweden, official fertility clinics provide most necessary treatments and initial workup, but there are long waiting lists, especially for egg donations, since the donor gets just as low reward as the receiving couple are charged. However, there are private fertility clinics.[citation needed] [edit] Canada See also: Assisted Human Reproduction Act Some treatments are covered by OHIP (public health insurance) in Ontario and others are not. Those undergoing artificial insemination or with bilaterally blocked fallopian tubes and under 40 have treatment is covered but are still required to pay lab fees (around $3,000–4,000). Coverage varies in other provinces. Most other patients are required to pay for treatments themselves.[17]
[edit] Israel Israel's National Health Insurance, which is mandatory for all Israeli citizens, covers nearly all fertility treatments. In-Vitro-Fertilization costs are fully subsidized up to the birth of two children for all Israeli women, including single women and lesbian couples. Embryo transfers for purposes of gestational surrogacy are also covered.[18] [edit] New Zealand The national public health system of New Zealand covers IVF treatment in specific circumstances only, based on a 'points for conception challenges' equation.[citation needed] Publicly funded IVF treatments are limited (between one and three treatments dependent on criteria) and are subject to substantial wait-lists, dependent on local health funding region, which raises potential inequity of ART support across the country.[citation needed] Infertility testing through blood tests can be covered by public funding, however in the absence of explicit gynecological complications, additional investigations are may not be covered publicly. Investigation such as a hysterosalpingogram may be covered, but the wait-list could be in excess of six weeks, whereas a privately sourced HSG can cost $NZ900 but is readily available. Many New Zealanders select self-funded IVF cycles, at approximately $NZ10,000 per cycle, and other forms of ART, such as IUI, at approximately $NZ1200, using the services of private fertility clinics, which in itself is a growing local industry. Individuals using private services are generally not covered under personal health insurance policies in New Zealand. [edit] Germany On 27 January 2009, the Federal Constitutional Court ruled that it is unconstitutional, that the health insurance companies have to bear only 50 percent of the cost for in vitro fertilization.[19] On 2 March 2012, the Federal Council has approved a draft law of some federal states, which provides that the federal government provides a subsidy of 25 percent to the cost. Thus, the share of costs borne for the pair would drop to just 25 percent.[20] [edit] Ethics Some couples find it difficult to stop treatment despite very bad prognosis, resulting in futile therapies. This may give ART providers a difficult decision of whether to continue or refuse treatment.[21]
For treatment-specific ethical considerations, see entries in individual subarticles, e.g. In vitro fertilisation, Surrogacy and Sperm donation [edit] Fictional representation Films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing in the latter part of the 2000s decade, although the techniques have been available for decades.[22] Yet, the amount of people that can relate to it by personal experience in one way or another is ever growing, and the variety of trials and struggles are huge.[22] For specific examples, refer to the fiction sections in individual subarticles, e.g. surrogacy, sperm donation and fertility clinic. In addition, reproduction and pregnancy in speculative fiction has been present for many decades. [edit] See also The Fertility Chase (medical documentary series) Religious response to ART Sperm donation Sperm bank Artificial uterus Human cloning Diethylstilbestrol Spontaneous conception, the unassisted conception of a subsequent child after prior use of assisted reproductive technology [edit] References 1.^Illmensee K, Levanduski M, Vidali A, Husami N, Goudas VT (February 2009). "Human embryo twinning with applications in reproductive medicine".Fertil.Steril. 93 (2): 423–7. doi:10.1016/j.fertnstert.2008.12.098. PMID 19217091.
2.^ Knock Yourself Up: A Tell-All Guide to Becoming a Single Mom by Louise Sloan. Reviewed in Newsweek 27 October 2007. 3.^ a b Van Voorhis BJ (2007). "Clinical practice.In vitro fertilization". N Engl J Med 356 (4): 379– 86. doi:10.1056/NEJMcp065743. PMID 17251534. 4.^Kurinczuk JJ, Hansen M, Bower C (2004). "The risk of birth defects in children born after assisted reproductive technologies". CurrOpinObstetGynecol 16 (3): 201–9. doi:10.1097/00001703- 200406000-00002. PMID 15129049. 5.^ Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk JJ (2005). "Assisted reproductive technologies and the risk of birth defects—a systematic review". Hum Reprod 20 (2): 328–38. doi:10.1093/humrep/deh593. PMID 15567881. 6.^ Olson CK, Keppler-Noreuil KM, Romitti PA, Budelier WT, Ryan G, Sparks AE, Van Voorhis BJ (2005). "In vitro fertilization is associated with an increase in major birth defects". FertilSteril 84 (5): 1308–15. doi:10.1016/j.fertnstert.2005.03.086. PMID 16275219. 7.^ a b c Zhang Y, Zhang YL, Feng C, et al. (September 2008). "Comparative proteomic analysis of human placenta derived from assisted reproductive technology". Proteomics 8 (20): 4344–56. doi:10.1002/pmic.200800294. PMID 18792929. 8.^ Hvidtjørn D, Schieve L, Schendel D, Jacobsson B, Sværke C, Thorsen P (2009). "Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis". Arch PediatrAdolesc Med 163 (1): 72–83. doi:10.1001/archpediatrics.2008.507. PMID 19124707. 9.^ motherearthnews.com – THE SPERM CRISIS 10.^ Ross, L. E.; McQueen, K.; Vigod, S.; Dennis, C. -L. (2010). "Risk for postpartum depression associated with assisted reproductive technologies and multiple births: a systematic review". Human Reproduction Update 17 (1): 96. doi:10.1093/humupd/dmq025. PMID 20605900.edit 11.^ a b chicagotribune.com Infertility by the numbers Colleen Mastony. June 21, 2009 12.^ 'More IVF babies but less multiple births' THE AUSTRALIAN. September 24, 2009 13.^Gameiro, S.; Boivin, J.; Peronace, L.; Verhaak, C. M. (2012). "Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment". Human Reproduction Update 18 (6): 652–669. doi:10.1093/humupd/dms031. PMC 3461967.PMID 22869759.edit 14.^ Jain T, Harlow BL, Hornstein MD (August 2002). "Insurance coverage and outcomes of in vitro fertilization". N. Engl. J. Med. 347 (9): 661–6. doi:10.1056/NEJMsa013491. PMID 12200554. 15.^ Connolly MP, Pollard MS, Hoorens S, Kaplan BR, Oskowitz SP, Silber SJ (September 2008). "Long-term economic benefits attributed to IVF-conceived children: a lifetime tax calculation". Am J Manag Care 14 (9): 598–604. PMID 18778175. 16.^ Infertility Treatment, NHS Direct Online (NHS Direct Online Health Enyclopaedia) 17.^ IVF Canada
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Infertility

  • 1.
    INFERTILITY INTRODUCTION Infertility primarily refersto the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term. There are many biological causes of infertility, including some that medical intervention can treat.Womenwho are fertile experience a natural period of fertility before and during ovulation, and they are naturally infertile during the rest of the menstrual cycle. Fertility awareness methods are used to discern when these changes occur by tracking changes in cervical mucus or basal body temperature. DEFINITION The World Health Organization defines infertility as follows Infertility is the inability to conceive a child. A couple may be considered infertile if, after two years of regular sexual intercourse, without contraception, the woman has not become pregnant (and there is no other reason, such as breastfeeding or postpartum amenorrhoea). TYPES Primary infertility is infertility in a couple who have never had a child. Secondary infertility is failure to conceive following a previous pregnancy. Infertility may be caused by infection in the man or woman, but often there is no obvious underlying cause. Combined infertility-In some cases, both the man and woman may be infertile or sub-fertile, and the couple's infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance Unexplained infertility- In the US, up to 20% of infertile couples have unexplained infertility. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. Couples with primary infertility have never been able to conceive, while, on the other hand, secondary infertility is difficulty conceiving after already having conceived (and either carried the pregnancy to term or had a miscarriage). Secondary infertility is not present if there has been a change of partners (this follows tautologically from the convention of speaking of couples, rather than individuals, as being infertile; if there is a change of partners, then a new couple is created, with its own chances to be infertile.) PREVELANCE
  • 2.
    Prevalence of infertilityvaries depending on the definition, i.e. on the time span involved in the failure to conceive. Some estimates suggest that worldwide between three and seven per cent of all couples or women have an unresolved problem of infertility. Many more couples, however, experience involuntary childlessness for at least one year: estimates range from 12% to 28%.Women become less fertile as they get older. For women aged 35, about 94 out of every 100 who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only 77 out of every 100 do so. The effect of age upon men's fertility is less clear. .CAUSES Causes in either sex:Factors that can cause male as well as female infertility are:  DNA damage- DNA damage reduces fertility in female oocytes, as caused by smoking,other xenobiotic DNA damaging agents (such as radiation or chemotherapy)or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine. DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature.  Genetic factors - A Robertsonian translocation in either partner may cause recurrent spontaneous abortions or complete infertility.  General factors- Diabetes mellitus, thyroid disorders, adrenal disease  Hypothalamic-pituitary factors Hyperprolactinemia  Hypopituitarism  Environmental factors- Toxins such as glues, volatile organic solvents or silicones, physical agents, chemical dusts, and pesticides.Tobacco smokers are 60% more likely to be infertile than non-smokers. Causes in females: Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic, or strictly by location.  Acquired versus genetic- Although causes (or factors) of female infertility can be classified as acquired versus genetic, female infertility is usually more or less a combination of nature and nurture. Also, the presence of any single risk factor of female infertility (such as smoking, mentioned further below) does not necessarily cause infertility, and even if a woman is definitely infertile then the infertility cannot definitely be blamed on any single risk factor even if the risk factor is (or has been) present.  Acquired- According to the American Society for Reproductive Medicine (ASRM), Age, Smoking, Sexually Transmitted Infections, and Being Overweight or Underweight can all affect fertility.In broad sense, acquired factors practically include any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development, which may present as infertility many years later as an adult. - Age- A woman's fertility is affected by her age. The average age of a girl's first period (menarche) is 12-13, but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year.A woman's fertility peaks in the early and mid twenties, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, with research giving differing results. The chances of a couple to successfully conceive at an advanced
  • 3.
    age depend onmany factors, including the general health of a woman and the fertility of the male partner. - Tobacco smoking- Tobacco smoking is harmful to the ovaries, and the degree of damage is dependent upon the amount and length of time a woman smokes or is exposed to a smoke-filled environment. Nicotine and other harmful chemicals in cigarettes interfere with the body’s ability to create estrogen, a hormone that regulates folliculogenesis and ovulation. Also, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and the uterine myometrium. Some damage is irreversible, but stopping smoking can prevent further damage.Smokers are 60% more likely to be infertile than non-smokers. Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%. Also, female smokers have an earlier onset of menopause by approximately 1–4 years. - Sexually transmitted disease- Sexually transmitted diseases are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility. - Body weight and eating disorders- Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen, in addition to the primary sex organs. Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant. Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle.Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate.Proper nutrition in early life is also a major factor for later fertility.  Chemotherapy- Chemotherapy poses a high risk of infertility.Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine. Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin. On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluorouracil.Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles.This loss is not necessarily a direct effect of the chemotherapeutic agents, but could be due to an increased rate of growth initiation to replace damaged developing follicles.Antral follicle count decreases after three series of chemotherapy, whereas follicle stimulating hormone (FSH) reaches menopausal levels after four series. Other hormonal changes in chemotherapy include decrease in inhibin B and anti-Müllerian hormone levels.Patients may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of ovarian tissue, oocytes or embryos.  Other factors that can cause acquired infertility - Adhesions- secondary to surgery in the peritoneal cavity is the leading cause of acquired infertility - Diabetes mellitus. A review of type 1 diabetes came to the result that, despite modern treatment, women with diabetes are at increased risk of female infertility, such as reflected by delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause. - Significant liver or kidney disease
  • 4.
    - Thrombophili - Cannabissmoking, such as of marijuana causes disturbances in the endocannabinoid system, potentially causing infertility - Radiation.- A dose of 8 Gy or more to the ovaries generally causes permanent female infertility.  Genetic factors-There are many genes wherein mutation causes female infertility. Also, there are additional conditions involving female infertility which are believed to be genetic but where no single gene has been found to be responsible, notably Mayer-Rokitansky-Küstner- Hauser Syndrome (MRKH). Finally, an unknown number of genetic mutations cause a state of subfertility, which in addition to other factors such as environmental ones may manifest as frank infertility.  Chromosomal abnormalities causing female infertility include Turner syndrome.Some of these gene or chromosome abnormalities cause intersexed conditions, such as androgen insensitivity syndrome  By anatomic location - Hypothalamic-pituitary factors- Hypothalamic dysfunction, Hyperprolactinemia - Ovarian factors-Polycystic ovary syndrome, - Anovulation- Female infertility caused by anovulation is called "anovulatory infertility", as opposed to "ovulatory infertility" in which ovulation is present.Diminished ovarian reserve,Premature menopause, Menopause, Luteal dysfunction, Gonadal dysgenesis (Turner syndrome), Ovarian cancer - Tubal (ectopic)/peritoneal factors- Endometriosis- Endometriosis can lead to anatomical distortions and adhesions (the fibrous bands that form between tissues and organs following recovery from an injury). However, the link between infertility and endometriosis remains enigmatic when the extent of endometriosis is limited.It has been suggested that endometriotic lesions release factors which are detrimental to gametes or embryos, or, alternatively, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it is preferable to speak of endometriosis-associated infertility in such cases. Pelvic adhesions, Pelvic inflammatory disease (PID, usually due to chlamydia), Tubal occlusion,Tubal dysfunction - Uterine factors-Uterine malformations,Uterine fibroids (leiomyoma),Asherman's Syndrome - Cervical factors- Cervical stenosis, Antisperm antibodies,Non-receptive cervical mucus - Vaginal factors-Vaginismus, Vaginal obstruction Causes in males:  Pre-testicular causes-Pre-testicular factors refer to conditions that impede adequate support of the testes and include situations of poor hormonal support and poor general health including: Hypogonadotropichypogonadism due to various causes Obesity increases the risk of hypogonadotropichypogonadism  Drugs, alcohol  Strenuous riding (bicycle riding,horseback riding)  Medications, including those that affect spermatogenesis such as chemotherapy, anabolic steroids, cimetidine, spironolactone; those that decrease FSH levels such as phenytoin; those that decrease sperm motility such as sulfasalazine and nitrofurantoin  Genetic abnormalities such as a Robertsonian translocation  Tobacco smoking
  • 5.
     DNA damage-Commoninherited variants in genes that encode enzymes employed in DNA mismatch repair are associated with increased risk of sperm DNA damage and male infertility.As men age there is a consistent decline in semen quality, and this decline appears to be due to DNA damage. These findings suggest that DNA damage is an important factor in male infertility.  Testicular factors-Testicular factors refer to conditions where the testes produce semen of low quantity and/or poor quality despite adequate hormonal support and include: Age , Genetic defects on the Y chromosome (Y chromosome microdeletions), Abnormal set of chromosomes (Klinefelter syndrome), Neoplasm, Idiopathic failure, Cryptorchidism,Varicocele,Trauma, Hydrocele, Mumps, Malaria, Testicular cancer  Acrosomal defects affecting egg penetration  Idiopathic oligospermia - unexplained sperm deficiencies account for 30% of male infertility.  Radiation therapy to a testis decreases its function, but infertility can efficiently be avoided by avoiding radiation to both testes.  Post-testicular causes- Post-testicular factors decrease male fertility due to conditions that affect the male genital system after testicular sperm production and include defects of the genital tract as well as problems in ejaculation: - Vas deferens obstruction - Lack of Vas deferens, often related to genetic markers for Cystic Fibrosis - Infection, e.g. prostatitis - Retrograde ejaculation - Ejaculatory duct obstruction - Hypospadias - Impotence DIAGNOSIS For males The diagnosis of infertility begins with a medical history and physical exam by a physician, preferably a specialist with experience or who specializes in male infertility. Typically two separate semen analyses will be required. The provider may order blood tests to look for hormone imbalances, medical conditions, or genetic issues.  Medical history-The history should include prior testicular or penile insults (torsion, cryptorchidism, trauma), infections (mumps orchitis, epididymitis), environmental factors (excessive heat, radiation, medications, and drug use (anabolic steroids, alcohol, smoking)  Sexual habits, frequency and timing of intercourse, use of lubricants, and each partner's previous fertility experiences are important.  Loss of libido and headaches or visual disturbances may indicate a pituitary tumor.  The past medical or surgical history may reveal thyroid or liver disease (abnormalities of spermatogenesis), diabetic neuropathy (retrograde ejaculation), radical pelvic or retroperitoneal surgery (absent seminal emission secondary to sympathetic nerve injury), or hernia repair (damage to the vas deferens or testicular blood supply).  A family history may reveal genetic problems.
  • 6.
     Physical examination-Usually, the patient disrobes completely and puts on a gown. The physician will perform a thorough examination of the penis, scrotum, testicles, anus and rectum.  Sperm sample  Semen analysis- The volume of the semen sample, approximate number of total sperm cells, sperm motility/forward progression, and % of sperm with normal morphology are measured. This is the most common type of fertility testing. Semen deficiencies are often labeled as follows: - Oligospermia or Oligozoospermia - decreased number of spermatozoa in semen - Aspermia - complete lack of semen - Hypospermia - reduced seminal volume - Azoospermia - absence of sperm cells in semen - Teratospermia - increase in sperm with abnormal morphology - Asthenozoospermia - reduced sperm motility - There are various combinations of these as well, e.g. Teratoasthenozoospermia, which is reduced sperm morphology and motility. Low sperm counts are often associated with decreased sperm motility and increased abnormal morphology, thus the terms "oligoasthenoteratozoospermia" or "oligospermia" can be used as a catch- all.  Blood sample  Common hormonal test include determination of FSH and testosterone levels. A blood sample can reveal genetic causes of infertility, e.g. Klinefelter syndrome, a Y chromosome microdeletion, or cystic fibrosis. For females  History  Physical examination  Lab tests- hormone testing, to measure levels of female hormones at certain times during a menstrual cycle,day 2 or 3 measure of FSH and estrogen, to assess ovarian reserve  Measurements of thyroid function (a thyroid stimulating hormone (TSH) level of between 1 and 2 is considered optimal for conception)  Measurement of progesterone in the second half of the cycle to help confirm ovulation  Examination and imaging an endometrial biopsy, to verify ovulation and inspect the lining of the uterus  laparoscopy, which allows the provider to inspect the pelvic organs  fertiloscopy, a relatively new surgical technique used for early diagnosis (and immediate treatment)  Pap smear, to check for signs of infection  pelvic exam, to look for abnormalities or infection  a postcoital test, which is done soon after intercourse to check for problems with sperm surviving in cervical mucous (not commonly used now because of test unreliability)  special X-ray tests  There are genetic testing techniques under development to detect any mutation in genes associated with female infertility.
  • 7.
    TREATMENT Treatment depends onthe cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for women include Clomiphene citrate, Human menopausal gonadotropin, Follicle- stimulating hormone, Human chorionic gonadotropin, Gonadotropin-releasing hormone analogs, Aromatase inhibitor, Metformin.  At-home conception kit In 2007 the FDA cleared the first at home tier one medical conception device to aid in conception. The key to the kit are cervical caps for conception. This at home [cervical cap] insemination method allows all the semen to be placed up against the cervical os for six hours allowing all available sperm to be placed directly on the cervical os. For low sperm count, low sperm motility, or a tilted cervix using a cervical cap aids conception. This is a prescriptive medical device, but not commonly prescribed by physicians.  At-home assessment Prior to expensive fertility procedures, many women and couples turn to online sources to determine their chances of success. A take-home baby assessment can provide a best guess estimate compared with women who have succeeded with in vitro fertilization, based on variables such as maternal age, duration of infertility and number of prior pregnancies.  Medical treatments Medical treatment of infertility generally involves the use of fertility medication, medical device, surgery, or a combination of the following. If the sperm are of good quality and the mechanics of the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring), physicians may start by prescribing a course of ovarian stimulating medication. The physician may also suggest using a conception cap cervical cap, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body.  ART If conservative medical treatments fail to achieve a full term pregnancy, the physician may suggest the patient undergo in vitro fertilization (IVF). IVF and related techniques (ICSI, ZIFT, GIFT) are called assisted reproductive technology (ART) techniques.ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer.  Other medical techniques are e.g. tuboplasty, assisted hatching, and Preimplantation genetic diagnosis. Treatments vary according to the underlying disease and the degree of the impairment of the male fertility. Further, in an infertility situation, the fertility of the female needs to be considered.Pre-
  • 8.
    testicular conditions canoften be addressed by medical means or interventions.Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved.Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF. The off-label use of Clomiphene citrate, an anti-estrogen drug designed as a fertility medicine for women, is controversial.Vitamin E helps counter oxidative stress,which is associated with sperm DNA damage and reduced sperm motility.A hormone-antioxidant combination may improve sperm count and motility.The Low dose Estrogen Testosterone Combination Therapy may improve sperm count and motility in some men including severe oligospermia.  Future potential treatments Researchers at Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation.If reproduced in humans, this could potentially enable infertile men to father children with their own sperm. PREVENTION Some cases of female infertility may be prevented through identified interventions:  Maintaining a healthy lifestyle- Excessive exercise, consumption of caffeine and alcohol, and smoking are all associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh fruits and vegetables (plenty of folates), and maintaining a normal weight are associated with better fertility prospects.  Treating or preventing existing diseases- Identifying and controlling chronic diseases such as diabetes and hypothyroidism increases fertility prospects. Lifelong practice of safer sex reduces the likelihood that sexually transmitted diseases will impair fertility; obtaining prompt treatment for sexually transmitted diseases reduces the likelihood that such infections will do significant damage. Regular physical examinations (including pap smears) help detect early signs of infections or abnormalities.  Not delaying parenthood- Fertility does not ultimately cease before menopause, but it starts declining after age 27 and drops at a somewhat greater rate after age . Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions, such as premature menopause, that can be mitigated by not delaying parenthood. ETHICS There are several ethical issues associated with infertility and its treatment.  High-cost treatments are out of financial reach for some couples.  Debate over whether health insurance companies (e.g. in the US) should be required to cover infertility treatment.  Allocation of medical resources that could be used elsewhere  The legal status of embryos fertilized in vitro and not transferred in vivo.
  • 9.
     Pro-life oppositionto the destruction of embryos not transferred in vivo.  IVF and other fertility treatments have resulted in an increase in multiple births, provoking ethical analysis because of the link between multiple pregnancies, premature birth, and a host of health problems.  Religious leaders' opinions on fertility treatments.  Infertility caused by DNA defects on the Y chromosome is passed on from father to son. If natural selection is the primary error correction mechanism that prevents random mutations on the Y chromosome, then fertility treatments for men with abnormal sperm (in particular ICSI) only defer the underlying problem to the next male generation. PSYCHOLOGICAL IMPACT The consequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood.Infertility may have profound psychological effects. Partners may become more anxious to conceive, increasing sexual dysfunction. Marital discord often develops in infertile couples, especially when they are under pressure to make medical decisions. Women trying to conceive often have clinical depression rates similar to women who have heart disease or cancer.Even couples undertaking IVF face considerable stress.The emotional losses created by infertility include the denial of motherhood as a rite of passage; the loss of one’s anticipated and imagined life; feeling a loss of control over one’s life; doubting one’s womanhood; changed and sometimes lost friendships; and, for many, the loss of one’s religious environment as a support system.Emotional stress and marital difficulties are greater in couples where the infertility lies with the man. SOCIAL IMPACT In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether; middle-class men are the most likely to respond in this way.In an effort to end the shame and secrecy of infertility, Redbook in October 2011 launched a video campaign, The Truth About Trying, to start an open conversation about infertility, which strikes one in eight women in the United States. In a survey of couples having difficulty conceiving, conducted by the pharmaceutical company Merck, 61 percent of respondents hid their infertility from family and friends. Nearly half didn't even tell their mothers. The message of those speaking out: It's not always easy to get pregnant, and there's no shame in that.There are legal ramifications as well. Infertility has begun to gain more exposure to legal domains. An estimated 4 million workers in the U.S. used the Family and Medical Leave Act (FMLA) in 2004 to care for a child, parent or spouse, or because of their own personal illness. Many treatments for infertility, including diagnostic tests, surgery and therapy for depression, can qualify one for FMLA leave. It has been suggested that infertility be classified as a form of disability.
  • 10.
    Oncofertility, fertility incancer patients 1.^ a b Section "Defining infertility" in: Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013 2.^ http://www.fertilityfaq.org/_pdf/magazine1_v4.pdf 3.^ Anderson SE, Dallal GE, Must A (April 2003). "Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart". Pediatrics 111 (4 Pt 1): 844–50. doi:10.1542/peds.111.4.844. PMID 12671122. 4.^ http://www.ncbi.nlm.nih.gov/pubmed/21110899 1.^ "Men's Health - Male Factor Infertility". University of Utah Health Sciences Center. 2003-04-01. Archived from the original on 2007-07-04. Retrieved 2007-11-21. 2.^Brugh VM, Lipshultz LI (2004). "Male factor infertility". Medical Clinics of North America 88 (2): 367–85. doi:10.1016/S0025-7125(03)00150-0. PMID 15049583. 3.^ Hirsh A (2003). "Male subfertility". BMJ 327 (7416): 669–72. doi:10.1136/bmj.327.7416.669. PMC 196399.PMID 14500443. 4.^ Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C (2009). "World Health Organization reference values for human semen characteristics". Human Reproduction Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 5.^ Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA (2000). " 1.^ a b Section "Defining infertility" in: Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013 2.^ http://www.fertilityfaq.org/_pdf/magazine1_v4.pdf 3.^ Anderson SE, Dallal GE, Must A (April 2003). "Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart". Pediatrics 111 (4 Pt 1): 844–50. doi:10.1542/peds.111.4.844. PMID 12671122. 4.^ http://www.ncbi.nlm.nih.gov/pubmed/21110899
  • 11.
    5.^ http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics% 20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf 6.^Apter D (February1980). "Serum steroids and pituitary hormones in female puberty: a partly longitudinal study". Clinical Endocrinology 12 (2): 107–20. doi:10.1111/j.1365-2265.1980.tb02125.x. PMID 6249519. 7.^ Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H (2011). "Effects of cigarette smoking on reproduction". Hum. Reprod. Update 17 (1): 76– 95. doi:10.1093/humupd/dmq033. PMID 20685716.edit 8.^ a b c d e FERTILITY FACT > Female Risks By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009 9.^ http://dl.dropbox.com/u/8256710/ASRM%20Protect%20Your%20Fertility%20newsletter.pdf 10.^ a b Regulated fertility services: a commissioning aid - June 2009, from the Department of Health UK 11.^ Practice Committee of American Society for Reproductive Medicine (2008). "Smoking and Infertility".FertilSteril 90 (5 Suppl): S254–9. PMID 19007641. 12.^ Nelson LR, Bulun SE (September 2001). "Estrogen production and action". J. Am. Acad. Dermatol. 45 (3 Suppl): S116–24. doi:10.1067/mjd.2001.117432. PMID 11511861. 13.^Sloboda, D. M.; Hickey, M.; Hart, R. (2010). "Reproduction in females: the role of the early life environment". Human Reproduction Update 17 (2): 210–227. doi:10.1093/humupd/dmq048. PMID 20961922.edit 14.^Freizinger M, Franko DL, Dacey M, Okun B, Domar AD (November 2008). "The prevalence of eating disorders in infertile women".Fertil.Steril. 93 (1): 72–8. doi:10.1016/j.fertnstert.2008.09.055. PMID 19006795. 15.^Koning AM, Kuchenbecker WK, Groen H, et al. (2010). "Economic consequences of overweight and obesity in infertility: a framework for .
  • 12.
    [edit] Psychological impact Theconsequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood.[36] Infertility may have profound psychological effects. Partners may become more anxious to conceive, increasing sexual dysfunction.[37] Marital discord often develops in infertile couples, especially when they are under pressure to make medical decisions. Women trying to conceive often have clinical depression rates similar to women who have heart disease or cancer.[38] Even couples undertaking IVF face considerable stress.[39] The emotional losses created by infertility include the denial of motherhood as a rite of passage; the loss of one’s anticipated and imagined life; feeling a loss of control over one’s life; doubting one’s womanhood; changed and sometimes lost friendships; and, for many, the loss of one’s religious environment as a support system.[40] Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.[41] [edit] Social impact In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether; middle-class men are the most likely to respond in this way.[42] In an effort to end the shame and secrecy of infertility, Redbook in October 2011 launched a video campaign, The Truth About Trying, to start an open conversation about infertility, which strikes one in eight women in the United States. In a survey of couples having difficulty conceiving, conducted by the pharmaceutical company Merck, 61 percent of respondents hid their infertility from family and
  • 13.
    friends.[43] Nearly halfdidn't even tell their mothers. The message of those speaking out: It's not always easy to get pregnant, and there's no shame in that. There are legal ramifications as well. Infertility has begun to gain more exposure to legal domains. An estimated 4 million workers in the U.S. used the Family and Medical Leave Act (FMLA) in 2004 to care for a child, parent or spouse, or because of their own personal illness. Many treatments for infertility, including diagnostic tests, surgery and therapy for depression, can qualify one for FMLA leave. It has been suggested that infertility be classified as a form of disability.[44] [edit] Fictional representation Perhaps except for infertility in science fiction, films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing first in the latter part of the 2000s decade, although the techniques have been available for decades.[45] Yet, the amount of people that can relate to it by personal experience in one way or another is ever growing, and the variety of trials and struggles is huge.[45] Any individual examples are referred to individual subarticles of assisted reproductive technology [edit] See also Advanced maternal age Childlessness Conception device Inherited sterility in insects Medical ethics Oncofertility, fertility in cancer patients Surrogate marriage [edit] References 1.^Makar RS, Toth TL (2002). "The evaluation of infertility".Am J ClinPathol. 117 (Suppl): S95–103. PMID 14569805.
  • 14.
    2.^ a bGurunath, S.; Pandian, Z.; Anderson, R. A.; Bhattacharya, S. (2011). "Defining infertility--a systematic review of prevalence studies". Human Reproduction Update 17 (5): 575–88. doi:10.1093/humupd/dmr015. PMID 21493634. 3.^ http://www.who.int/topics/infertility/en/ 4.^ Cooper TG, Noonan E, von Eckardstein S, et al. (2010). "World Health Organization reference values for human semen characteristics". Hum. Reprod. Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 5.^ [1] Fertility: Assessment and Treatment for People with Fertility Problems. London: RCOG Press. 2004. ISBN 1-900364-97-2. 6.^ http://www.who.int/reproductivehealth/topics/infertility/DHS-CR9.pdf 7.^MedlinePlusEncyclopedia Infertility 8.^ Himmel, W.; Ittner, E; Kochen, MM; Michelmann, HW; Hinney, B; Reuter, M; Kallerhoff, M; Ringert, RH (1997). "Voluntary Childlessness and being Childfree". British Journal of General Practice 47 (1): 11. PMC 1312893.PMID 9101672. 9.^ a b NICE fertility guidance 10.^ HFEA Chart on reasons for infertility 11.^ Khan, Khalid; Janesh K. Gupta; Gary Mires (2005). Core clinical cases in obstetrics and gynaecology: a problem-solving approach. London: Hodder Arnold. p. 152.ISBN 0-340-81672-4. 12.^Sahlgrenska University Hospital. (translated from the Swedish sentence: "Cirka 10% avalla par har problem med ofrivilligbarnlöshet.") 13.^ a b Regulated fertility services: a commissioning aid – June 2009, from the Department of Health UK 14.^ a b Zenzes MT (2000). "Smoking and reproduction: gene damage to human gametes and embryos". Hum. Reprod. Update 6 (2): 122–31. PMID 10782570. 15.^ Mark-Kappeler CJ, Hoyer PB, Devine PJ (November 2011). "Xenobiotic effects on ovarian preantral follicles".Biol. Reprod. 85 (5): 871–83. doi:10.1095/biolreprod.111.091173. PMC 3197911.PMID 21697514. 16.^ Seino T, Saito H, Kaneko T, Takahashi T, Kawachiya S, Kurachi H (June 2002). "Eight- hydroxy-2'-deoxyguanosine in granulosa cells is correlated with the quality of oocytes and embryos in an in vitro fertilization-embryo transfer program". Fertil.Steril. 77 (6): 1184–90. PMID 12057726. 17.^Gharagozloo P, Aitken RJ (July 2011). "The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy". Hum. Reprod. 26 (7): 1628–40. doi:10.1093/humrep/der132. PMID 21546386. 18.^Nili HA, Mozdarani H, Pellestor F (2011). "Impact of DNA damage on the frequency of sperm chromosomal aneuploidy in normal and subfertile men". Iran. Biomed. J. 15 (4): 122–9. PMID 22395136.
  • 15.
    19.^Shamsi MB, ImamSN, Dada R (November 2011). "Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility". J. Assist. Reprod. Genet. 28 (11): 1073–85. doi:10.1007/s10815-011-9631-8. PMC 3224170.PMID 21904910. 20.^ Van Den Boogaard, E.; Vissenberg, R.; Land, J. A.; Van Wely, M.; Van Der Post, J. A. M.; Goddijn, M.; Bisschop, P. H. (2011). "Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: A systematic review". Human Reproduction Update 17 (5): Male infertility refers to the inability of a male to achieve a pregnancy in a fertile [edit] Treatment Treatments vary according to the underlying disease and the degree of the impairment of the male fertility. Further, in an infertility situation, the fertility of the female needs to be considered. Pre-testicular conditions can often be addressed by medical means or interventions. Testicular-based male infertility tends to be resistant to medication. Usual approaches include using the sperm for intrauterine insemination (IUI), in vitro fertilization (IVF), or IVF with intracytoplasmatic sperm injection (ICSI). With IVF-ICSI even with a few sperm pregnancies can be achieved. Obstructive causes of post-testicular infertility can be overcome with either surgery or IVF-ICSI. Ejaculatory factors may be treatable by medication, or by IUI therapy or IVF. The off-label use of Clomiphene citrate, an anti-estrogen drug designed as a fertility medicine for women, is controversial.[24] Vitamin E helps counter oxidative stress,[25] which is associated with sperm DNA damage and reduced sperm motility.[26] A hormone-antioxidant combination may
  • 16.
    improve sperm countand motility.[27] The Low dose Estrogen Testosterone Combination Therapy may improve sperm count and motility in some men.[28] including severe oligospermia.[29][30] [edit] Future potential treatments Researchers at Münster University developed in vitro culture conditions using a three-dimensional agar culture system which induces mouse testicular germ cells to reach the final stages of spermatogenesis, including spermatozoa generation.[31] If reproduced in humans, this could potentially enable infertile men to father children with their own sperm.[32][33] Spermatogenesis [edit] References 1.^ "Men's Health - Male Factor Infertility". University of Utah Health Sciences Center. 2003-04-01. Archived from the original on 2007-07-04. Retrieved 2007-11-21. 2.^Brugh VM, Lipshultz LI (2004). "Male factor infertility". Medical Clinics of North America 88 (2): 367–85. doi:10.1016/S0025-7125(03)00150-0. PMID 15049583. 3.^ Hirsh A (2003). "Male subfertility". BMJ 327 (7416): 669–72. doi:10.1136/bmj.327.7416.669. PMC 196399.PMID 14500443. 4.^ Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C (2009). "World Health Organization reference values for human semen characteristics". Human Reproduction Update 16 (3): 231–45. doi:10.1093/humupd/dmp048. PMID 19934213. 5.^ Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA (2000). "Chapter 2: History taking". WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge [England]: Published on behalf of the World Health Organization by Cambridge University Press. pp. 5–16. ISBN 0-521-77474-8. 6.^ a b Teerds KJ, de Rooij DG, Keijer J (2011). "Functional relationship between obesity and male reproduction: from humans to animal models". Hum. Reprod. Update 17 (5): 667–83. doi:10.1093/humupd/dmr017. PMID 21546379. 7.^Leibovitch I, Mor Y (2005). "The Vicious Cycling: Bicycling Related Urogenital Disorders". European Urology 47 (3): 277–86; discussion 286–7. doi:10.1016/j.eururo.2004.10.024. PMID 15716187. 8.^ "Preventing Smoking and Exposure to Secondhand Smoke Before, During, and After Pregnancy" (pdf). factsheet. United States Centers for Disease Control (CDC).Retrieved 2012-08-27.
  • 17.
    9.^Agarwal A, PrabakaranSA, Said TM (2005). "Prevention of Oxidative Stress Injury to Sperm". Journal of Andrology 26 (6): 654–60. doi:10.2164/jandrol.05016. PMID 16291955. 10.^ Robbins WA, Elashoff DA, Xun L, Jia J, Li N, Wu G, Wei F (2005). "Effect of lifestyle exposures on sperm aneuploidy". Cytogenetic and Genome Research 111 (3–4): 371–7. doi:10.1159/000086914. PMID 16192719. 11.^Emsley J (2001). Nature's building blocks: an A-Z guide to the elements. Oxford [Oxfordshire]: Oxford University Press. p. 76.ISBN 0-19-850340-7. 12.^Ji G, Long Y, Zhou Y, Huang C, Gu A, Wang X (2012). Common variants in mismatch repair genes associated with increased risk of sperm DNA damage and male infertility. BMC Med 10:49. doi: 10.1186/1741-7015-10-49. PMID: 22594646 13.^ Silva LF, Oliveira JB, Petersen CG, Mauri AL, Massaro FC, Cavagna M, Baruffi RL, Franco JG Jr (2012). The effects of male age on sperm analysis by motile sperm organelle morphology examination (MSOME).ReprodBiolEndocrinol 10:19. doi: 10.1186/1477-7827-10-19. PMID: 22429861 14.^ "Infertility in men". Retrieved 2007-11-21. 15.^Costabile RA, Spevak M (2001). "Characterization of patients presenting with male factor infertility in an equal access, no cost medical system". Urology 58 (6): 1021–4. doi:10.1016/S0090- 4295(01)01400-5. PMID 11744480. 16.^Masarani M, Wazait H, Dinneen M (2006). "Mumps orchitis". Journal of the Royal Society of Medicine 99 (11): 573–5. doi:10.1258/jrsm.99.11.573. PMC 1633545.PMID 17082302. 17.^ Zhang J, Qiu S-D, Li S-B, Zhou D-X, Tian H, Huo Y-W, Ge L, Zhang Q-Y (2007). "Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility". Asian Journal of Andrology 9 (6): 809–14. doi:10.1111/j.1745-7262.2007.00305.x. PMID 17968467. 18.^Cavallini G (2006). "Male idiopathic oligoasthenoteratozoospermia". Asian Journal of Andrology 8 (2): 143–57. doi:10.1111/j.1745-7262.2006.00123.x. PMID 16491265. 19.^Gutfeld O, Wygoda M, Shavit L, Grenader T (2007). "Fertility After Adjuvant External Beam Radiotherapy for Stage I Seminoma". The Internet Journal of Oncology 4 (2).doi:10.5580/2188. 20.^Hargreave TB, McGowan B, Harvey J, McParland M, Elton RA (April 1986). "Is a male infertility clinic of any use?".
  • 18.
    Female infertility From Wikipedia,the free encyclopedia Jump to: navigation, search Female infertility Classification and external resources ICD-10 N97.0 ICD-9
  • 19.
  • 20.
    Contents [hide] 1 Definition 2Causes and factors 2.1 Acquired versus genetic 2.1.1 Acquired 2.1.1.1 Age 2.1.1.2 Tobacco smoking 2.1.1.3 Sexually transmitted disease 2.1.1.4 Body weight and eating disorders 2.1.1.5 Chemotherapy 2.1.1.6 Other factors that can cause acquired infertility 2.1.2 Genetic factors 2.2 By anatomic location 2.2.1 Hypothalamic-pituitary factors 2.2.2 Ovarian factors 2.2.3 Tubal (ectopic)/peritoneal factors 2.2.4 Uterine factors 2.2.5 Cervical factors 2.2.6 Vaginal factors 3 Diagnosis 4 Prevention 5 See also 6 References
  • 21.
    [edit] Definition There isno unanimous definition of female infertility, but NICE guidelines state that: "A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner."[1] It is recommended that a consultation with a fertility specialist should be made earlier if the woman is aged 36 years or over, or there is a known clinical cause of infertility or a history of predisposing factors for infertility.[1] [edit] Causes and factors Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic, or strictly by location. [edit] Acquired versus genetic Although causes (or factors) of female infertility can be classified as acquired versus genetic, female infertility is usually more or less a combination of nature and nurture. Also, the presence of any single risk factor of female infertility (such as smoking, mentioned further below) does not necessarily cause infertility, and even if a woman is definitely infertile then the infertility cannot definitely be blamed on any single risk factor even if the risk factor is (or has been) present. [edit] Acquired According to the American Society for Reproductive Medicine (ASRM), Age, Smoking, Sexually Transmitted Infections, and Being Overweight or Underweight can all affect fertility.[2] In broad sense, acquired factors practically include any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development, which may present as infertility many years later as an adult. [edit] Age
  • 22.
    Main article: Ageand female fertility A woman's fertility is affected by her age. The average age of a girl's first period (menarche) is 12-13 (12.5 years in the United States,[3] 12.72 in Canada,[4] 12.9 in the UK[5]), but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year.[6] A woman's fertility peaks in the early and mid twenties, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, with research giving differing results. The chances of a couple to successfully conceive at an advanced age depend on many factors, including the general health of a woman and the fertility of the male partner. [edit] Tobacco smoking See also: Women and smoking#Unique gender differences and health effects for Females Tobacco smoking is harmful to the ovaries, and the degree of damage is dependent upon the amount and length of time a woman smokes or is exposed to a smoke-filled environment. Nicotine and other harmful chemicals in cigarettes interfere with the body’s ability to create estrogen, a hormone that regulates folliculogenesis and ovulation. Also, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and the uterine myometrium.[7] Some damage is irreversible, but stopping smoking can prevent further damage.[8][9] Smokers are 60% more likely to be infertile than non-smokers.[10] Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.[10] Also, female smokers have an earlier onset of menopause by approximately 1–4 years.[11] [edit] Sexually transmitted disease Sexually transmitted diseases are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility.[8] [edit] Body weight and eating disorders Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen,[12] in addition to the primary sex organs. Too much body fat causes
  • 23.
    production of toomuch estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant.[8] Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle.[8] Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate.[8] Proper nutrition in early life is also a major factor for later fertility.[13] A study in the US indicated that approximately 20% of infertile women had a past or current eating disorder, which is five times higher than the general lifetime prevalence rate.[14] A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs. In hypothetical groups of 1000 women undergoing fertility care, the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women. For ovulatory women, the study counted approximately 700 live births for normal weight, 550 live births for overweight and 530 live births for obese women. The increase in cost per live birth in anovulatory overweight and obese women were, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.[15] [edit] Chemotherapy Chemotherapy poses a high risk of infertility. Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine.[16] Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.[16] On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluorouracil.[16] Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles.[17] This loss is not necessarily a direct effect of the chemotherapeutic agents, but could be due to an increased rate of growth initiation to replace damaged developing follicles.[17] Antral follicle count decreases after three series of chemotherapy, whereas follicle stimulating hormone (FSH) reaches menopausal levels after four series.[18] Other hormonal changes in chemotherapy include decrease in inhibin B and anti-Müllerian hormone levels.[18]
  • 24.
    Patients may choosebetween several methods of fertility preservation prior to chemotherapy, including cryopreservation of ovarian tissue, oocytes or embryos.[19] [edit] Other factors that can cause acquired infertility Adhesions secondary to surgery in the peritoneal cavity is the leading cause of acquired infertility.[20] A meta-analysis in 2012 came to the conclusion that there is only little evidence for the surgical principle that using less invasive techniques, introducing less foreign bodies or causing less ischemia reduces the extent and severity of adhesions.[20] Diabetes mellitus. A review of type 1 diabetes came to the result that, despite modern treatment, women with diabetes are at increased risk of female infertility, such as reflected by delayed puberty and menarche, menstrual irregularities (especially oligomenorrhoea), mild hyperandrogenism, polycystic ovarian syndrome, fewer live born children and possibly earlier menopause.[21] Animal models indicate that abnormalities on the molecular level caused by diabetes include defective leptin, insulin and kisspeptin signalling.[21] Significant liver or kidney disease Thrombophilia[22][23] Cannabis smoking, such as of marijuana causes disturbances in the endocannabinoid system, potentially causing infertility[24] Radiation. A dose of 8 Gy or more to the ovaries generally causes permanent female infertility.[25] [edit] Genetic factors There are many genes wherein mutation causes female infertility, as shown in table below. Also, there are additional conditions involving female infertility which are believed to be genetic but where no single gene has been found to be responsible, notably Mayer-Rokitansky-Küstner-Hauser Syndrome (MRKH).[26] Finally, an unknown number of genetic mutations cause a state of subfertility, which in addition to other factors such as environmental ones may manifest as frank infertility. Chromosomal abnormalities causing female infertility include Turner syndrome. Some of these gene or chromosome abnormalities cause intersexed conditions, such as androgen insensitivity syndrome Genes wherein mutation causes female infertility[27]
  • 25.
    Gene Encoded protein Effect ofdeficiency BMP15 Bone morphogenetic protein 15 Hypergonadotrophic ovarian failure (POF4) BMPR1B Bone morphogenetic protein receptor 1B Ovarian dysfunction, hypergonadotrophichypogonadism and acromesomelicchondrodysplasia CBX2; M33
  • 26.
    Chromobox protein homolog2 ; Drosophila polycomb class Autosomal 46,XY, male-to-female sex reversal (phenotypically perfect females) CHD7 Chromodomain-helicase-DNA-binding protein 7 CHARGE syndrome and Kallmann syndrome (KAL5) DIAPH2 Diaphanous homolog 2 Hypergonadotrophic, premature ovarian failure (POF2A) FGF8 Fibroblast growth factor 8 Normosmichypogonadotrophichypogonadism and Kallmann syndrome (KAL6)
  • 27.
    FGFR1 Fibroblast growth factorreceptor 1 Kallmann syndrome (KAL2) FSHR FSH receptor Hypergonadotrophichypogonadism and ovarian hyperstimulation syndrome FSHB Follitropin subunit beta Deficiency of follicle-stimulating hormone, primary amenorrhoea and infertility FOXL2
  • 28.
    Forkhead box L2 Isolatedpremature ovarian failure (POF3) associated with BPES type I; FOXL2 402C --> G mutations associated with human granulosa cell tumours FMR1 Fragile X mental retardation Premature ovarian failure (POF1) associated with premutations GNRH1 Gonadotropin releasing hormone Normosmichypogonadotrophichypogonadism GNRHR GnRH receptor
  • 29.
    Hypogonadotrophichypogonadism KAL1 Kallmann syndrome Hypogonadotrophichypogonadism andinsomnia, X-linked Kallmann syndrome (KAL1) KISS1R ; GPR54 KISS1 receptor Hypogonadotrophichypogonadism LHB Luteinizing hormone beta polypeptide LHCGR
  • 30.
    LH/choriogonadotrophin receptor Hypergonadotrophichypogonadism (luteinizinghormone resistance) DAX1 Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 X-linked congenital adrenal hypoplasia with hypogonadotrophichypogonadism; dosage-sensitive male-to-female sex reversal NR5A1; SF1 Steroidogenic factor 1 46,XY male-to-female sex reversal and streak gonads and congenital lipoid adrenal hyperplasia; 46,XX gonadal dysgenesis and 46,XX primary ovarian insufficiency POF1B Premature ovarian failure 1B
  • 31.
    Hypergonadotrophic, primary amenorrhea(POF2B) PROK2 Prokineticin Normosmichypogonadotrophichypogonadism and Kallmann syndrome (KAL4) PROKR2 Prokineticin receptor 2 Kallmann syndrome (KAL3) RSPO1 R-spondin family, member 1 46,XX, female-to-male sex reversal (individuals contain testes)
  • 32.
    SRY Sex-determining region Y Mutationslead to 46,XY females; translocations lead to 46,XX males SOX9 SRY-related HMB-box gene 9 Autosomal 46,XY male-to-female sex reversal (campomelic dysplasia) TAC3 Tachykinin 3 Normosmichypogonadotrophichypogonadism TACR3 Tachykinin receptor 3
  • 33.
    Normosmichypogonadotrophichypogonadism [edit] By anatomiclocation [edit] Hypothalamic-pituitary factors Hypothalamic dysfunction Hyperprolactinemia[28] [edit] Ovarian factors Polycystic ovary syndrome, see infertility in polycystic ovary syndrome Anovulation. Female infertility caused by anovulation is called "anovulatory infertility", as opposed to "ovulatory infertility" in which ovulation is present.[29] Diminished ovarian reserve, also see Poor Ovarian Reserve Premature menopause Menopause Luteal dysfunction[30] Gonadal dysgenesis (Turner syndrome) Ovarian cancer [edit] Tubal (ectopic)/peritoneal factors Endometriosis[31] Endometriosis can lead to anatomical distortions and adhesions (the fibrous bands that form between tissues and organs following recovery from an injury). However, the link between infertility and endometriosis remains enigmatic when the extent of endometriosis is limited.[32] It has been suggested that endometriotic lesions release factors which are detrimental to gametes or embryos, or, alternatively, endometriosis may more likely develop in women who fail to conceive for other reasons and thus be a secondary phenomenon; for this reason it is preferable to speak of endometriosis-associated infertility[33] in such cases. Pelvic adhesions
  • 34.
    Pelvic inflammatory disease(PID, usually due to chlamydia)[34] Tubal occlusion[35] Tubal dysfunction [edit] Uterine factors Uterine malformations[36] Uterine fibroids (leiomyoma) Asherman'sSyndrome[37] [edit] Cervical factors Cervical stenosis[38] Antispermantibodies[39] Non-receptive cervical mucus[40] [edit] Vaginal factors Vaginismus Vaginal obstruction [edit] Diagnosis Diagnosis of infertility begins with a medical history and physical exam. The healthcare provider may order tests, including the following: Lab tests hormone testing, to measure levels of female hormones at certain times during a menstrual cycle day 2 or 3 measure of FSH and estrogen, to assess ovarian reserve measurements of thyroid function[41] (a thyroid stimulating hormone (TSH) level of between 1 and 2 is considered optimal for conception) measurement of progesterone in the second half of the cycle to help confirm ovulation
  • 35.
    Examination and imagingan endometrial biopsy, to verify ovulation and inspect the lining of the uterus laparoscopy, which allows the provider to inspect the pelvic organs fertiloscopy, a relatively new surgical technique used for early diagnosis (and immediate treatment) Pap smear, to check for signs of infection pelvic exam, to look for abnormalities or infection apostcoital test, which is done soon after intercourse to check for problems with sperm surviving in cervical mucous (not commonly used now because of test unreliability) special X-ray tests There are genetic testing techniques under development to detect any mutation in genes associated with female infertility.[27] Diagnosis and treatment of infertility should be made by physicians who are fellowship trained as reproductive endocrinologists. Reproductive Endocrinologists are usually Obstetrician-Gynecologists with advanced training in Reproductive Endocrinology & Infertility (in North America). These highly educated professionals and qualified physicians treat Reproductive Disorders affecting not only women but also men, children, and teens. Prospective patients should note that reproductive endocrinology & infertility medical practices do not see women for general maternity care. The practice is primarily focused on helping their patients to conceive and to correct any issues related to recurring pregnancy loss. [edit] Prevention Some cases of female infertility may be prevented through identified interventions: Maintaining a healthy lifestyle. Excessive exercise, consumption of caffeine and alcohol, and smoking are all associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh fruits and vegetables (plenty of folates), and maintaining a normal weight are associated with better fertility prospects. Treating or preventing existing diseases. Identifying and controlling chronic diseases such as diabetes and hypothyroidism increases fertility prospects. Lifelong practice of safer sex reduces the likelihood that sexually transmitted diseases will impair fertility; obtaining prompt treatment for sexually
  • 36.
    transmitted diseases reducesthe likelihood that such infections will do significant damage. Regular physical examinations (including pap smears) help detect early signs of infections or abnormalities. Not delaying parenthood. Fertility does not ultimately cease before menopause, but it starts declining after age 27 and drops at a somewhat greater rate after age 35.[42] Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions, such as premature menopause, that can be mitigated by not delaying parenthood. [edit] See also Infertility Male infertility Meiosis Oncofertility [edit] References 1.^ a b Section "Defining infertility" in: Fertility: assessment and treatment for people with fertility problems. NICE clinical guideline CG156 - Issued: February 2013 2.^ http://www.fertilityfaq.org/_pdf/magazine1_v4.pdf 3.^ Anderson SE, Dallal GE, Must A (April 2003). "Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart". Pediatrics 111 (4 Pt 1): 844–50. doi:10.1542/peds.111.4.844. PMID 12671122. 4.^ http://www.ncbi.nlm.nih.gov/pubmed/21110899 5.^ http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics% 20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf 6.^Apter D (February 1980). "Serum steroids and pituitary hormones in female puberty: a partly longitudinal study". Clinical Endocrinology 12 (2): 107–20. doi:10.1111/j.1365-2265.1980.tb02125.x. PMID 6249519. 7.^ Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H (2011). "Effects of cigarette smoking on reproduction". Hum. Reprod. Update 17 (1): 76– 95. doi:10.1093/humupd/dmq033. PMID 20685716.edit 8.^ a b c d e FERTILITY FACT > Female Risks By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009 9.^ http://dl.dropbox.com/u/8256710/ASRM%20Protect%20Your%20Fertility%20newsletter.pdf
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    10.^ a bRegulated fertility services: a commissioning aid - June 2009, from the Department of Health UK 11.^ Practice Committee of American Society for Reproductive Medicine (2008). "Smoking and Infertility".FertilSteril 90 (5 Suppl): S254–9. PMID 19007641. 12.^ Nelson LR, Bulun SE (September 2001). "Estrogen production and action". J. Am. Acad. Dermatol. 45 (3 Suppl): S116–24. doi:10.1067/mjd.2001.117432. PMID 11511861. 13.^Sloboda, D. M.; Hickey, M.; Hart, R. (2010). "Reproduction in females: the role of the early life environment". Human Reproduction Update 17 (2): 210–227. doi:10.1093/humupd/dmq048. PMID 20961922.edit 14.^Freizinger M, Franko DL, Dacey M, Okun B, Domar AD (November 2008). "The prevalence of eating disorders in infertile women".Fertil.Steril. 93 (1): 72–8. doi:10.1016/j.fertnstert.2008.09.055. PMID 19006795. 15.^Koning AM, Kuchenbecker WK, Groen H, et al. (2010). "Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care". Hum. Reprod. Update 16 (3): 246–54. doi:10.1093/humupd/dmp053. PMID 20056674. 16.^ a b c Brydøy M, Fosså SD, Dahl O, Bjøro T (2007). "Gonadal dysfunction and fertility problems in cancer survivors".ActaOncol 46 (4): 480–9. doi:10.1080/02841860601166958. PMID 17497315. 17.^ a b Morgan, S.; Anderson, R. A.; Gourley, C.; Wallace, W. H.; Spears, N. (2012). "How do chemotherapeutic agents damage the ovary?". Human Reproduction Update 18 (5): 525. doi:10.1093/humupd/dms022. edit 18.^ a b Rosendahl, M.; Andersen, C.; La CourFreiesleben, N.; Juul, A.; Løssl, K.; Andersen, A. (2010). "Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age". Fertility and Sterility 94 (1): 156–166. doi:10.1016/j.fertnstert.2009.02.043. PMID 19342041.edit 19.^Gurgan T, Salman C, Demirol A (October 2008). "Pregnancy and assisted reproduction techniques in men and women after cancer treatment". Placenta 29 (Suppl B): 152–9. doi:10.1016/j.placenta.2008.07.007. PMID 18790328. 20.^ a b Ten Broek, R. P. G.; Kok- Krant, N.; Bakkum, E. A.; Bleichrodt, R. P.; Van Goor, H. (2012). "Different surgical techniques to reduce post-operative adhesion formation: A systematic review and meta-analysis". Human Reproduction Update 19 (1): 12–25. doi:10.1093/humupd/dms032. PMID 22899657.edit 21.^ a b Codner, E.; Merino, P. M.; Tena-Sempere, M. (2012). "Female reproduction and type 1 diabetes: From mechanisms to clinical findings". Human Reproduction Update 18 (5): 568. doi:10.1093/humupd/dms024. edit 22.^Middeldorp S (2007). "Pregnancy failure and heritable thrombophilia".Semin.Hematol. 44 (2): 93–7. doi:10.1053/j.seminhematol.2007.01.005. PMID 17433901. 23.^Qublan HS, Eid SS, Ababneh HA, et al. (2006). "Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure". Hum. Reprod. 21 (10): 2694–8. doi:10.1093/humrep/del203. PMID 16835215.
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    24.^Karasu, T.; Marczylo,T. H.; MacCarrone, M.; Konje, J. C. (2011). "The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility". Human Reproduction Update 17 (3): 347–361. doi:10.1093/humupd/dmq058. PMID 21227997.edit 25.^ Chapter on Amenorrhea in: Bradshaw, Karen D.; Schorge, John O.; Schaffer, Joseph; Lisa M. Halvorson; Hoffman, Barbara G. (2008). Williams' Gynecology.McGraw-Hill Professional.ISBN 0- 07-147257-6. 26.^ Sultan C, Biason-Lauber A, Philibert P (January 2009). "Mayer-Rokitansky-Kuster-Hauser syndrome: recent clinical and genetic findings". GynecolEndocrinol 25 (1): 8–11. doi:10.1080/09513590802288291. PMID 19165657. 27.^ a b Unless otherwise specified in boxes, then reference is: Fauser, B. C. J. M.; Diedrich, K.; Bouchard, P.; Dominguez, F.; Matzuk, M.; Franks, S.; Hamamah, S.; Simon, C. et al. (2011). "Contemporary genetic technologies and female reproduction". Human Reproduction Update 17 (6): 829–847. doi:10.1093/humupd/dmr033. PMC 3191938.PMID 21896560.edit 28.^ Female Infertility 29.^ Hull MG, Savage PE, Bromham DR (June 1982). "Anovulatory and ovulatory infertility: results with simplified management". Br Med J (Clin Res Ed) 284 (6330): 1681–5. doi:10.1136/bmj.284.6330.1681. PMC 1498620.PMID 6805656. 30.^ Luteal Phase Dysfunction at eMedicine 31.^Tomassetti C, Meuleman C, Pexsters A, et al. (2006). "Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link?".Reprod. Biomed. Online 13 (1): 58–64. doi:10.1016/S1472-6483(10)62016-0. PMID 16820110. 32.^Speroff L, Glass RH, Kase NG (1999). Clinical Gynecologic Endocrinology and Infertility (6th ed.). Lippincott Willimas Wilkins. p. 1057.ISBN 0-683-30379-1. 33.^Buyalos RP, Agarwal SK (October 2000). "Endometriosis-associated infertility". Current Opinion in Obstetrics &Gynecology 12 (5): 377–81. doi:10.1097/00001703-200010000-00006. ISSN 1040-872X. PMID 11111879. 34.^ Guven MA, Dilek U, Pata O, Dilek S, Ciragil P (2007). "Prevalence of Chlamydia trochomatis, Ureaplasmaurealyticum and Mycoplasma hominis infections in the unexplained infertile women". Arch. Gynecol. Obstet. 276 (3): 219–23. doi:10.1007/s00404-006-0279-z. PMID 17160569. 35.^García-Ulloa AC, Arrieta O (2005). "Tubal occlusion causing infertility due to an excessive inflammatory response in patients with predisposition for keloid formation". Med. Hypotheses 65 (5): 908–14. doi:10.1016/j.mehy.2005.03.031. PMID 16005574. 36.^ Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simón C, Pellicer A (1997). "Reproductive impact of congenital Müllerian anomalies". Hum. Reprod. 12 (10): 2277–81. doi:10.1093/humrep/12.10.2277. PMID 9402295. 37.^Magos A (2002). "Hysteroscopic treatment of Asherman's syndrome".Reprod. Biomed. Online 4 (Suppl 3): 46–51. PMID 12470565.
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    38.^ Tan Y,Bennett MJ (2007). "Urinary catheter stent placement for treatment of cervical stenosis". The Australian & New Zealand journal of obstetrics & gynaecology 47 (5): 406–9. doi:10.1111/j.1479-828X.2007.00766.x. PMID 17877600. 39.^Francavilla F, Santucci R, Barbonetti A, Francavilla S (2007). "Naturally-occurring antisperm antibodies in men: interference with fertility and clinical implications. An update". Front. Biosci. 12 (8–12): 2890–911. doi:10.2741/2280. PMID 17485267. 40.^Farhi J, Valentine A, Bahadur G, Shenfield F, Steele SJ, Jacobs HS (1995). "In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests". Hum. Reprod. 10 (1): 85–90. doi:10.1093/humrep/10.1.85. PMID 7745077. 41.^Wartofsky L, Van Nostrand D, Burman KD (2006). "Overt and 'subclinical' hypothyroidism in women". Obstetrical &gynecological survey 61 (8): 535–42. doi:10.1097/01.ogx.0000228778.95752.66. PMID 16842634. 42.^ Hall, Carl T. "Study speeds up biological clocks / Fertility rates dip after women hit 27". The San Francisco Chronicle.Retrieved 2007-11-21. [show] v · t · e Female diseases of the pelvis and genitals (N70–N99, 614–629)
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    [show] v · t · e Assistedreproductive technology · · ·
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  • 53.
    Categories: Fertility medicine Infertility Fertility Noninflammatorydisorders of female genital tract Navigation menu Create account Log in
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    Main page Contents Featured content Currentevents Random article Donate to Wikipedia Interaction Help About Wikipedia Community portal Recent changes Contact Wikipedia Toolbox
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    Print/export Languages ‫ية‬ ‫عرب‬ ‫ال‬ Español Magyar Editlinks This page was last modified on 18 March 2013 at 14:39. Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization. Contact us Privacy policy
  • 57.
    About Wikipedia Disclaimers Mobile view Howyour infertility is treated depends on the cause, your age, how long you've been infertile and personal preferences. Although some women need just one or two therapies to restore fertility, it's possible that several different types of treatment may be needed before you're able to conceive. Treatments can either attempt to restore fertility — by means of medication or surgery — or assist in reproduction with sophisticated techniques. Fertility restoration: Stimulating ovulation with fertility drugs Fertility drugs, which regulate or induce ovulation, are the main treatment for women who are infertile due to ovulation disorders. In general, they work like the natural hormones — follicle- stimulating hormone (FSH) and luteinizing hormone (LH) — to trigger ovulation. Using fertility drugs carries some risks: Becoming pregnant with twins or other multiples. Oral medications carry a fairly low risk of multiples (less than 10 percent), but your chances increase to about 15 to 20 percent with injectable medications. Generally, the more fetuses you're carrying, the greater the risk of premature labor, low birth weight and later developmental problems. Sometimes the amount or timing of the medications will be altered in an attempt to lower the risk of multiples. Treatment cycles may be canceled if your doctor detects the development of too many follicles, which could result in ovulation of more than one egg. Developing enlarged ovaries. Ovarian hyperstimulation syndrome (OHSS) is a condition that can result from the use of fertility drugs. In response to the medication, your ovaries become overstimulated. Besides developing enlarged ovaries, you might experience abdominal pain and distention, gastrointestinal problems and shortness of breath. Signs and symptoms can develop while you're undergoing ovulation induction or during the early stages of pregnancy. There are several fertility drugs for abnormal LH and FSH production. These drugs include:
  • 58.
    Clomiphene citrate (Clomid,Serophene). This drug is taken orally and stimulates ovulation in women who have PCOS or other ovulation disorders. It causes the pituitary gland to release more FSH and LH, which stimulate the growth of an ovarian follicle containing an egg. Clomiphene citrate also improves fertility in normally ovulating women, and is often used as an initial treatment for unexplained infertility. Gonadotropins. Instead of stimulating the pituitary gland to release more hormones, these treatments stimulate the ovary directly. Often, gonadotropin medications are used in combination with intrauterine insemination (IUI) — a procedure during which sperm is injected into your uterus via a thin tube (catheter) — to increase the odds of a pregnancy. Gonadotropin medications include: Human menopausal gonadotropin, or hMG, (Repronex, Menopur). This injected medication is for women who don't ovulate on their own due to the failure of the pituitary gland to stimulate ovulation. HMG contains both FSH and LH, and directly stimulates the ovaries to ovulate. Follicle-stimulating hormone, or FSH, (Gonal-F, Follistim, Bravelle). FSH works by stimulating the ovaries to produce mature egg follicles. Human chorionic gonadotropin, or HCG, (Ovidrel, Pregnyl). Used in combination with clomiphene, hMG or FSH, this drug stimulates the follicle to release its egg (ovulate). Metformin (Glucophage). This oral drug is used when insulin resistance is a known or suspected cause of infertility, usually in women with a diagnosis of PCOS. Metformin improves insulin resistance, normalizing the insulin level and making ovulation more likely to occur. Letrozole (Femara). Letrozole belongs to a class of drugs known as aromatase inhibitors. Letrozole, also used to treat some breast cancers, may induce ovulation. However, the effect the medication has on early pregnancy isn't yet known, so this medication isn't used for ovulation induction as frequently as others. Fertility restoration: Surgery Several surgical procedures can correct problems or otherwise improve female fertility. They include: Tissue removal. This surgery removes endometrial tissue or pelvic adhesions with lasers or ablation, which can improve your chances of achieving pregnancy. Tubal reversal surgery (microscopic). After a woman has had her tubes tied for permanent contraception (tubal ligation), surgery may be done to reconnect them and restore fertility. Your doctor will determine whether you're a good candidate for the surgery. Tubal surgeries. If your fallopian tubes are blocked or filled with fluid (called hydrosalpinx), tubal surgery may improve your chances of becoming pregnant. Laparoscopic surgery is performed to remove adhesions, dilate a tube or create a new tubal opening. Tubal surgery is more successful when
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    the blocked ornarrowed part of the tube is closer to the ovary than to the uterus. Tubal blockage close to your uterus may increase your risk of ectopic pregnancy. In these and other severe cases of blockage or hydrosalpinx, removal of your tubes (salpingectomy) can improve your chances of pregnancy with in vitro fertilization. Reproductive assistance: In vitro fertilization This effective technique involves retrieving mature eggs from a woman, fertilizing them with a man's sperm in a dish in a laboratory and transferring the embryos in the uterus three to five days after fertilization. In vitro fertilization (IVF) often is recommended when both fallopian tubes are blocked. It's also widely used for a number of other conditions, such as endometriosis, unexplained infertility, cervical factor infertility, male infertility and ovulation disorders. IVF increases your odds of having twins or other multiples if more than one embryo is transferred to your uterus. IVF requires frequent blood tests and daily hormone injections. Coping and support Tests and diagnosis Mayo Clinic products and services Infertility treatment at Mayo Clinic Book: Mayo Clinic Family Health Book, 4th Edition Give today to find cures for tomorrow See Also In vitro fertilization (IVF) Intrauterine insemination (IUI) Ovarian hyperstimulation syndrome Sperm donation Fertility herbs: Do they enhance fertility?
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  • 65.
    Assisted reproductive technology(ART) is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments, otherwise known as 'fertility treatments'. Some forms of ART are also used in fertile couples for genetic reasons. ART is also used in couples who are discordant for certain communicable diseases, e.g. AIDS, to reduce the risk of infection when a pregnancy is desired. Examples of ART include in vitro fertilization, intracytoplasmic sperm injection (ICSI), cryopreservation, and intrauterine insemination (IUI). There is yet no strict definition of the term. Usage of the ART mainly belongs in the field of reproductive endocrinology and infertility. Contents [hide] 1 Definitions 2 Procedures 2.1 Medication 2.2 In vitro fertilization 2.3 Surrogacy 2.4 Others 3 Risks 4 Usage 5 Costs 5.1 United States of America 5.2 United Kingdom 5.3 Sweden 5.4 Canada 5.5 Israel 5.6 New Zealand 5.7 Germany
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    6 Ethics 7 Fictionalrepresentation 8 See also 9 References 10 External links [edit] Definitions While there is no consensus on the definition, generally the process of intercourse is bypassed either by artificial insemination or fertilization of the oocytes in the laboratory environment (i.e., in vitro fertilization). The Centers for Disease Control and Prevention (CDC)—which is required as a result of the 1992 Fertility Clinic Success Rate and Certification Act to publish the annual ART success rates at U.S. fertility clinics—defines ART to include "all fertility treatments in which both eggs and sperm are handled. In general, ART procedures involve surgically removing eggs from a woman's ovaries, combining them with sperm in the laboratory, and returning them to the woman's body or donating them to another woman." According to CDC, "they do not include treatments in which only sperm are handled (i.e., intrauterine—or artificial—insemination) or procedures in which a woman takes medicine only to stimulate egg production without the intention of having eggs retrieved." [edit] Procedures Procedures are mainly fertility medication, as well as ART techniques that use more substantial and forceful interventions, of which in vitro fertilization (IVF) and expansions of it (e.g. OCR, AZH, ICSI, ZIFT) are the most prevalent. However, there are also other manual ART, not necessarily dependent on IVF (e.g. PGD, GIFT, SSR). [edit] Medication Main article: Fertility medication Most fertility medication are agents that stimulate the development of follicles in the ovary. Examples are gonadotropins and gonadotropin releasing hormone.
  • 67.
    [edit] In vitrofertilization Main article: In vitro fertilization In vitro fertilization (IVF) is the technique of letting fertilization of the male and female gametes (sperm and egg) occur outside the female body. Techniques usually used in in vitro fertilization include: Transvaginal ovum retrieval (OCR) is the process whereby a small needle is inserted through the back of the vagina and guided via ultrasound into the ovarian follicles to collect the fluid that contains the eggs. Embryo transfer is the step in the process whereby one or several embryos are placed into the uterus of the female with the intent to establish a pregnancy. Less commonly used techniques in in vitro fertilization are: Assisted zona hatching (AZH) is performed shortly before the embryo is transferred to the uterus. A small opening is made in the outer layer surrounding the egg in order to help the embryo hatch out and aid in the implantation process of the growing embryo. Intracytoplasmic Sperm Injection (ICSI) Intracytoplasmic sperm injection (ICSI) is beneficial in the case of male factor infertility where sperm counts are very low or failed fertilization occurred with previous IVF attempt(s). The ICSI procedure involves a single sperm carefully injected into the center of an egg using a microneedle. This method is also sometimes employed when donor sperm is used. Autologous endometrial coculture is a possible treatment for patients who have failed previous IVF attempts or who have poor embryo quality. The patient's fertilized eggs are placed on top of a layer of cells from the patient's own uterine lining, creating a more natural environment for embryo development. In zygote intrafallopian transfer (ZIFT), egg cells are removed from the woman's ovaries and fertilized in the laboratory; the resulting zygote is then placed into the fallopian tube.
  • 68.
    Cytoplasmic transfer isthe technique in which the contents of a fertile egg from a donor are injected into the infertile egg of the patient along with the sperm. Egg donors are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age. In the egg donor process, eggs are retrieved from a donor's ovaries, fertilized in the laboratory with the sperm from the recipient's partner, and the resulting healthy embryos are returned to the recipient's uterus. Sperm donation may provide the source for the sperm used in IVF procedures where the male partner produces no sperm or has an inheritable disease, or where the woman being treated has no male partner. Preimplantation genetic diagnosis (PGD) involves the use of genetic screening mechanisms such as Fluorescent In Situ Hybridization (FISH) or Comparative Genomic Hybridization (CGH) to help identify genetically abnormal embryos and improve healthy outcomes. Embryo splitting can be used for twinning to increase the number of available embryos.[1] [edit] Surrogacy Surrogacy via a gestational carrier is an option when a patient's medical condition prevents a safe pregnancy, when a patient has ovaries but no uterus due to congenital absence or previous surgical removal, and where a patient has no ovaries and is also unable to carry a pregnancy to full term. [edit] Others The following techniques don't necessarily involve IVF: In gamete intrafallopian transfer (GIFT) a mixture of sperm and eggs is placed directly into a woman's fallopian tubes using laparoscopy following a transvaginal ovum retrieval. Sex selection is the attempt to control the sex of offspring to achieve a desired sex. It can be accomplished in several ways, both pre- and post-implantation of an embryo, as well as at birth. Pre- implantation techniques include PGD, but also sperm sorting. Artificial insemination (AI) is when sperm is placed into a female's uterus (intrauterine) or cervix (intracervical) using artificial means rather than by natural copulation. N.B. This can be a very low- tech process, performed at home by the woman alone or with her partner.[2] Conception devices, such as a conception cap are used to aid conception by enhancing[vague] the natural process. Conception caps are used by placing semen into a small conception cap, then placing the cap onto the cervix. This holds the semen at the cervical os, protecting the semen from the acidic vaginal secretions and keeping it in contact with the cervical mucus. Artificial insemination by donor is used in situations where the woman doesn't have a partner with functional sperm. Instead, a sperm donor supplies the sperm.
  • 69.
    Surrogacy, where awoman agrees to become pregnant and deliver a child for a contracted party. It may be her own genetic child, or a child conceived through natural insemination, in vitro fertilization or embryo transfer using another woman's ova. Reproductive surgery, treating e.g. fallopian tube obstruction and vas deferens obstruction, or reversing a vasectomy by a reverse vasectomy. In surgical sperm retrieval (SSR) the reproductive urologist obtains sperm from the vas deferens, epididymis or directly from the testis in a short outpatient procedure. By cryopreservation, eggs, sperm and reproductive tissue can be preserved for later IVF. [edit] Risks The majority of IVF-conceived infants do not have birth defects.[3] However, some studies have suggested that assisted reproductive technology is associated with an increased risk of birth defects.[4][5] In the largest U.S. study, which used data from a statewide registry of birth defects,[6] 6.2% of IVF-conceived children had major defects, as compared with 4.4% of naturally conceived children matched for maternal age and other factors (odds ratio, 1.3; 95% confidence interval, 1.00 to 1.67).[3] The main risks are: Genetic disorders. DNA damage increases in e.g. IVF and ICSI, which is reflected e.g. by upregulation of the gene expression of HNRNPC in the placenta.[7] Low birth weight. In IVF and ICSI, a risk factor is the decreased expression of proteins in energy metabolism; Ferritin light chain and ATP5A1.[7] Preterm birth. Low birth weight and preterm birth are strongly associated with many health problems, such as visual impairment and cerebral palsy, and children born after IVF are roughly twice as likely to have cerebral palsy.[8] Other risk factors are: Membrane damage, which is contributed to or reflected by increased expression of the membrane fusion proteins NAPA and Annexin A3.[7] Sperm donation is an exception, with a birth defect rate of almost a fifth compared to the general population.[9] It may be explained by that sperm banks accept only people with high sperm count.
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    Current data indicatelittle or no increased risk for postpartum depression among women who use ART.[10] [edit] Usage Assisted reproductive technology procedures performed in the U.S. has more than doubled since 10 years ago, with 140.000 procedures in 2006,[11] resulting in 55.000 infants born.[11] In Australia, 3.1% of babies now born are a result of ART.[12] In case of discontinuation of fertility treatment, the most common reasons have been estimated to be: postponement of treatment (39%), physical and psychological burden (19%, psychological burden 14%, physical burden 6.32%), relational and personal problems (17%, personal reasons 9%, relational problems 9%), treatment rejection (13%) and organizational (12%) and clinic (8%) problems.[13] [edit] Costs [edit] United States of America Not everyone in the U.S. has insurance coverage for fertility investigations and treatments. Many states are starting to mandate coverage, and the rate of utilization is 277% higher in states with complete coverage.[14] There are some health insurance companies that cover diagnosis of infertility but frequently once diagnosed will not cover any treatment costs. 2005 approximate treatment/diagnosis costs (United States, costs in US$): Initial workup: hysteroscopy, hysterosalpingogram, blood tests ~$2,000 Intrauterine Insemination (IUI) aka Artificial insemination ~ $200– 900 per. trial Sonohysterogram (SHG) ~ $600 – 1,000 Clomiphene citrate cycle ~ $ 200 – 500
  • 71.
    IVF cycle ~$10,000 -30,000 Use of a surrogate mother to carry the child – dependent on arrangements Another way to look at costs is to determine the expected cost of establishing a pregnancy. Thus if a clomiphene treatment has a chance to establish a pregnancy in 8% of cycles and costs $500, the expected cost is $6,000 to establish a pregnancy, compared to an IVF cycle (cycle fecundity 40%) with a corresponding expected cost of $30,000 ($12,000/.4). For the community as a whole, the cost of IVF on average pays back by 700% by tax from future employment by the conceived human being.[15] [edit] United Kingdom In the UK all patients have the right to preliminary testing, provided free of charge by the National Health Service. However, treatment is not widely available on the NHS and there can be long waiting lists. Many patients therefore pay for immediate treatment within the NHS or seek help from private clinics.[16] [edit] Sweden In Sweden, official fertility clinics provide most necessary treatments and initial workup, but there are long waiting lists, especially for egg donations, since the donor gets just as low reward as the receiving couple are charged. However, there are private fertility clinics.[citation needed] [edit] Canada See also: Assisted Human Reproduction Act Some treatments are covered by OHIP (public health insurance) in Ontario and others are not. Those undergoing artificial insemination or with bilaterally blocked fallopian tubes and under 40 have treatment is covered but are still required to pay lab fees (around $3,000–4,000). Coverage varies in other provinces. Most other patients are required to pay for treatments themselves.[17]
  • 72.
    [edit] Israel Israel's NationalHealth Insurance, which is mandatory for all Israeli citizens, covers nearly all fertility treatments. In-Vitro-Fertilization costs are fully subsidized up to the birth of two children for all Israeli women, including single women and lesbian couples. Embryo transfers for purposes of gestational surrogacy are also covered.[18] [edit] New Zealand The national public health system of New Zealand covers IVF treatment in specific circumstances only, based on a 'points for conception challenges' equation.[citation needed] Publicly funded IVF treatments are limited (between one and three treatments dependent on criteria) and are subject to substantial wait-lists, dependent on local health funding region, which raises potential inequity of ART support across the country.[citation needed] Infertility testing through blood tests can be covered by public funding, however in the absence of explicit gynecological complications, additional investigations are may not be covered publicly. Investigation such as a hysterosalpingogram may be covered, but the wait-list could be in excess of six weeks, whereas a privately sourced HSG can cost $NZ900 but is readily available. Many New Zealanders select self-funded IVF cycles, at approximately $NZ10,000 per cycle, and other forms of ART, such as IUI, at approximately $NZ1200, using the services of private fertility clinics, which in itself is a growing local industry. Individuals using private services are generally not covered under personal health insurance policies in New Zealand. [edit] Germany On 27 January 2009, the Federal Constitutional Court ruled that it is unconstitutional, that the health insurance companies have to bear only 50 percent of the cost for in vitro fertilization.[19] On 2 March 2012, the Federal Council has approved a draft law of some federal states, which provides that the federal government provides a subsidy of 25 percent to the cost. Thus, the share of costs borne for the pair would drop to just 25 percent.[20] [edit] Ethics Some couples find it difficult to stop treatment despite very bad prognosis, resulting in futile therapies. This may give ART providers a difficult decision of whether to continue or refuse treatment.[21]
  • 73.
    For treatment-specific ethicalconsiderations, see entries in individual subarticles, e.g. In vitro fertilisation, Surrogacy and Sperm donation [edit] Fictional representation Films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing in the latter part of the 2000s decade, although the techniques have been available for decades.[22] Yet, the amount of people that can relate to it by personal experience in one way or another is ever growing, and the variety of trials and struggles are huge.[22] For specific examples, refer to the fiction sections in individual subarticles, e.g. surrogacy, sperm donation and fertility clinic. In addition, reproduction and pregnancy in speculative fiction has been present for many decades. [edit] See also The Fertility Chase (medical documentary series) Religious response to ART Sperm donation Sperm bank Artificial uterus Human cloning Diethylstilbestrol Spontaneous conception, the unassisted conception of a subsequent child after prior use of assisted reproductive technology [edit] References 1.^Illmensee K, Levanduski M, Vidali A, Husami N, Goudas VT (February 2009). "Human embryo twinning with applications in reproductive medicine".Fertil.Steril. 93 (2): 423–7. doi:10.1016/j.fertnstert.2008.12.098. PMID 19217091.
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    2.^ Knock YourselfUp: A Tell-All Guide to Becoming a Single Mom by Louise Sloan. Reviewed in Newsweek 27 October 2007. 3.^ a b Van Voorhis BJ (2007). "Clinical practice.In vitro fertilization". N Engl J Med 356 (4): 379– 86. doi:10.1056/NEJMcp065743. PMID 17251534. 4.^Kurinczuk JJ, Hansen M, Bower C (2004). "The risk of birth defects in children born after assisted reproductive technologies". CurrOpinObstetGynecol 16 (3): 201–9. doi:10.1097/00001703- 200406000-00002. PMID 15129049. 5.^ Hansen M, Bower C, Milne E, de Klerk N, Kurinczuk JJ (2005). "Assisted reproductive technologies and the risk of birth defects—a systematic review". Hum Reprod 20 (2): 328–38. doi:10.1093/humrep/deh593. PMID 15567881. 6.^ Olson CK, Keppler-Noreuil KM, Romitti PA, Budelier WT, Ryan G, Sparks AE, Van Voorhis BJ (2005). "In vitro fertilization is associated with an increase in major birth defects". FertilSteril 84 (5): 1308–15. doi:10.1016/j.fertnstert.2005.03.086. PMID 16275219. 7.^ a b c Zhang Y, Zhang YL, Feng C, et al. (September 2008). "Comparative proteomic analysis of human placenta derived from assisted reproductive technology". Proteomics 8 (20): 4344–56. doi:10.1002/pmic.200800294. PMID 18792929. 8.^ Hvidtjørn D, Schieve L, Schendel D, Jacobsson B, Sværke C, Thorsen P (2009). "Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis". Arch PediatrAdolesc Med 163 (1): 72–83. doi:10.1001/archpediatrics.2008.507. PMID 19124707. 9.^ motherearthnews.com – THE SPERM CRISIS 10.^ Ross, L. E.; McQueen, K.; Vigod, S.; Dennis, C. -L. (2010). "Risk for postpartum depression associated with assisted reproductive technologies and multiple births: a systematic review". Human Reproduction Update 17 (1): 96. doi:10.1093/humupd/dmq025. PMID 20605900.edit 11.^ a b chicagotribune.com Infertility by the numbers Colleen Mastony. June 21, 2009 12.^ 'More IVF babies but less multiple births' THE AUSTRALIAN. September 24, 2009 13.^Gameiro, S.; Boivin, J.; Peronace, L.; Verhaak, C. M. (2012). "Why do patients discontinue fertility treatment? A systematic review of reasons and predictors of discontinuation in fertility treatment". Human Reproduction Update 18 (6): 652–669. doi:10.1093/humupd/dms031. PMC 3461967.PMID 22869759.edit 14.^ Jain T, Harlow BL, Hornstein MD (August 2002). "Insurance coverage and outcomes of in vitro fertilization". N. Engl. J. Med. 347 (9): 661–6. doi:10.1056/NEJMsa013491. PMID 12200554. 15.^ Connolly MP, Pollard MS, Hoorens S, Kaplan BR, Oskowitz SP, Silber SJ (September 2008). "Long-term economic benefits attributed to IVF-conceived children: a lifetime tax calculation". Am J Manag Care 14 (9): 598–604. PMID 18778175. 16.^ Infertility Treatment, NHS Direct Online (NHS Direct Online Health Enyclopaedia) 17.^ IVF Canada