Sms gynae letrozole treatment protocol o

Sms gynae letrozole treatment protocol o

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  LETROZOLE VERSUS CLOMIPHENECITRATE FOR OVULATION INDUCTION- A COMPARATIVE STUDY DR SANGEETA PAHWA (PROFESSOR AND HEAD) DR SANDEEP KAUR (SENIOR RESIDENT ) DR ANUPRIYA ARORA (JUNIOR RESIDENT)
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  INTRODUCTION • Infertility isa multidimensional health problem with social, psychological & economic sequels. • Infertility is defined as a failure to achieve pregnancy within 12 months of unprotected intercourse or therapeutic donor insemination in women younger than 35 years, or within 6 months in women older than 35 years. Infertility may be primary or secondary. Primary infertility denotes those patients who have never conceived. Secondary infertility indicates history of previous conception but failure to conceive subsequently. • The prevalence of infertility globally is about 10%– 15% of reproductive age couples. The overall prevalence of primary infertility in India is between 3.9 and 16.8%.
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  • Among thecauses of infertility, female factor (40%-55%) remains the premier cause followed by male factor (30%-40%), and combined factor (10%); whereas in 10% cases, etiology remains unexplained. • The most common identifiable female factors, which accounts for 81% of female infertility, are : ovulatory disorders (25%), endometriosis (15%), pelvic adhesions (11%), tubal blockage (11%), other tubal abnormalities (11%), hyperprolactinemia (7%). • As anovulatory infertility accounts for 25 to 30% cases of female infertility, we hereby envisage to study the efficacy of ovulation induction drugs in women with anovulatory infertility.
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  Who classifies ovulationdisorders into 3 groups Group 1 (Hypothalamic-pituitary failure) Group 2 (Hypothalamic-pituitary dysfunction) MOST COMMON Group 3 (Ovarian Failure) Amenorrhoea, low FSH & estrogen, normal/low prolactin Irregular or anovulatory cycles, normal FSH/ estrogen /prolactin Amenorrhoea, high FSH, low estrogen, normal prolactin Do not bleed to progestin challenge test Bleeds with progestin challenge test - Causes- kallman syndrome, anorexia nervosa, stress, excessive wieght loss PCOS > androgen disorders Diminished ovarian reserve Management- pulsatile GnRH infusions, injectable gonadotropins Insulin sensitizers, clomiphene citrate (SERM), letrozole (aromatase inhibitor) Oocyte donation
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  Ovulation induction drugs •CLOMIPHENE CITRATE- CC has been the most widely used drug for more than past 40 years for fertility enhancement.  Mechanism of action- It is a SERM and acts by competitive inhibition of the estrogen binding to ERs in the hypothalamus thus inhibiting the negative feedback from the circulating endogenous estradiol, resulting in increased GnRH pulse secretion and thereby increased serum concentration of FSH and LH.  Clomiphene acts primarily as an anti-estrogen at the uterus, cervix, and vagina. CC has a negative effect on the cervical mucus and endometrium, leading to the discrepancy between ovulation rate of 60-80% but a conception rate of only 20%.  Side Effects- multifollicular development, hyperstimulation syndrome and cyst formation.  Dose- lowest dose of Clomiphine citrate i.e. 50 mg for first cycle followed by 100 mg if no ovulation induction achieved with 50 mg CC , followed by 125 mg CC for one cycle and another cycle with 125mg in case of failure, i.e. total of four cycles.
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  • LETROZOLE- itis recommended as a first-line drug therapy for ovulation induction women with PCOS.  Mechanism of action- It is an aromatase inhibitor preventing conversion of testostrerone to estradiol and thus decreased estradiol sectretion via ovarian suppression and thereby a rise in FSH resulting in follicular development. Developing follicles secretes estrogen (as the effect of aromatase inhibitor diminishes). As the dominant follicle grows and estrogen levels rise, normal negative feedback occurs centrally because aromatase inhibitors do not deplete estrogen receptors in the brain. FSH is then suppressed, and the smaller-growing follicles become atretic, resulting in monofollicular ovulation in most cases.  Side effects- fatigue and dizziness  Dose- 2.5 mg for one cycle followed by 5 mg for next cycle in case of failure of ovulation, 7.5 mg for next cycle and another cycle with 7.5mg in case of failure, i.e. total of four cycles with each drug .
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  MATERIALS AND METHODS Ahospital-based double blinded RCT conducted at Obstetrics and Gynaecology Department of a tertiary care hospital, Sri Guru Ram Das Institute of Medical Sciences and Research ,Amritsar over a time period from AUGUST 2023 to NOVEMBER 2023. During the study period, out of total 126 patients recruited with infertility, 84 patients met the inclusion criteria and out of these 84 patients, 4 patients lost to follow up . Thus a total of 80 study participant’s data was subjected to the final analysis. • Inclusion criteria 1) All patients coming with anovulatory infertility with no other obvious cause of infertility • Exclusion criteria 1) Women with uncontrolled hypo/hyperthyroidism /pituitary causes of infertility. 2) Male factor infertility. 3) Women with bilateral tubal block identified at HSG or laproscopic chromoperteubation. 4) Patients with unexplained infertility.
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  Patients were randomizedin 2 groups GROUP A GROUP B Received lowest dose of CC- 50 mg Received lowest dose of letrozole-2.5mg On day 3-5 of menses On day 3-5 of menses Both the groups were followed on day 9 for follicular monitoring on TVS If size of follicle > 18-20 mm was achieved and ET > 8 mm, then 5000 0r 10,000IU HCG was given TVS was done after 24-48 hours to look for ovulation- atretic follicle, free fluid in POD If no ovulation- then repeat TVS after 72 hours to look for ovulation If no ovulation- cycle was cancelled and higher dose of the drug was given for the next cycle GROUP A GROUP B CC- 100 mg Letrozole- 5 mg
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  No ovulation Noovulation 125 mg CC in the next cycle 7.5 mg letrozole in next cycle No ovulation Ovulation No ovulation (failure) (failure) 125 mg CC in the next cycle 7.5 mg letrozole in next cycle No ovulation No ovulation Patient counselled for other options Patient counselled for other options IF OVULATION OCCURED AT ANY STEP, THE SAME DRUG DOSE WAS GIVEN FOR NEXT 3 CYCLES. Timed intercourse was advised, 24 to 48 hours after hCG on two consecutive days and the luteal phase was supplemented with micronized progesterone.
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  Outcome Primary outcome: 1. Numberand maximum size of mature follicles. 2. Ovulation rate 3. The endometrial thickness on the day of HCG administration, Secondary outcome: 4. The occurrence of pregnancy (biochemical / ultrasonography) by measuring beta- HCG levels in urine/blood. Statistical analysis was performed using (SPSS) version 26 to draw relevant conclusions. Student t-test was applied to compare the effects of letrozole and clomiphene citrate (CC) for ovulation induction. The Chi-square test was applied to see the association between outcome and demographic characteristics. The Receiver Operating Curve (ROC) was constructed. Level of significance was determined as p≤0.05 as significant and p≤0.001 as highly significant.
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  RESULTS 1. There wereno statistically significant differences between the two groups in age, duration of infertility, BMI, and endocrine status at baseline level as seen in table 1. PARAMETERS CLOMIPHENE CITRATE LETROZOLE p- value Age (years) 29.75±4.47 28.48±3.37 0.154 Duration of mean years of infertility 3.86±2.51 3.71±2.23 0.778 BMI (kg/m2) 24.59±3.14 23.9±2.29 0.265 FSH (IU/ml) on d-2 6.24±1.82 6.47±1.61 0.554 LH(IU/ml)on d-2 8.27±2.08 8.91±2.39 0.203 TSH (IU/ml) 2.41±1.02 2.52±1.06 0.650 Prolactin (ng/ml) 19.19±8.52 17.21±4.7 0.201
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  2. The numberof follicles ≥18 mm was statistically significantly higher in the letrozole group (90%) as compared with the CC group (72.5%) ,p value -0.045 3. Mono follicular development was highly significantly higher in Letrozole Group (CC 22.5%, Let 60%) , p value-0.001 4. The pregnancy rate was higher in letrozole group as compared to clomiphene (L- 37.5% versus CC-25%) 5. There was no statistically significant difference in pretreatment endometrial thickness between the two groups
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  Discussion STUDY CC GROUPLETROZOLE GROUP P- Value In this study 1. No. Of follicles>18 mm 2. Monofollicular response 3. Multi follicular development 72.5% 22.5% 70% 90% 60% 30% 0.045 <0.05 0.001 Soni et al in 2020 1. ovulation rate 2. Monofollicular response 62% 18% 82% 66% 0.045 0.01 Legro et al in 2014- ovulation rate 41.3% 61.7% <0.05 Wafa Y. S. et al in 2017, multi- follicular development 48% 26% 0.023
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  Conclusion • This studysuggests letrozole is potential alternative in terms of ovulation induction and conception rates, with significantly better mono follicular development and it may be recommended as the first-line drug for ovulation induction in cases with anovulatory infertility.
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  References 1. American Collegeof Obstetricians and Gynecologists . reVitalize. Gynecology data definitions (version 1.0) . Washington, DC : American College of Obstetricians and Gynecologists ; 2017 2. Mosher WD, Pratt WF. The demography of infertility in united states. In: Asch RH, Stubb Jw,eds. Annual progress in reproductive medicine. Park Ridge, NJ: The Parthenon Publishing Group,1993;37-43 3. 7. Ganguly S, Sayeed U. Trends of Infertility and Childlessness in India: Findings from NFHS Data. Facts, Views Vis Obgyn. 2010;2:131-8. 4. Casper RF, Mitwally MF. Aromatase Inhibitors for Ovulation Induction. The Journal of Clinical Endocrinology & Metabolism. 2006;91:760-71 5. . Wafa YA, Labib MM, Fatah AG. Role of Letrozole Versus Clomiphene Citrate in Induction of Ovulation in Patients with Polycystic Ovarian Syndrome. J Gynecol Reprod Med. 2017;1:1-6. 15. 6. Soni M, Kalal GK, Meena A, Sharma A. Clomiphene citrate versus letrozole for ovulation induction in anovulatory infertility: a prospective study. Int J Reprod Contracept Obstet Gynecol 2020;9(5):2004. 7. Elsemary MY, Mostafa WF, El Taher OS. Ovulation induction in women with polycystic ovarian syndrome: Clomiphene citrate or letrozole?. Journal of Medicine in Scientific Research. 2018;1:26 8. Bansal S, Goyal M, Sharma C, Shekhar S. Letrozole versus clomiphene citrate for ovulation induction in anovulatory women with polycystic ovarian syndrome: A randomized controlled trial. Int J Gynaecol Obstet 2021;152(3):345–50.