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  <div style=\" width:425px\" id=\" __ss_643868\" ><strongstyle=\" display:block;margin:12px 0 4px\" ><a href=\" http://www.slideshare.net/7260678/new-developments-in-reproductive-medicine-presentation\" title=\" New Developments In Reproductive Medicine\" >New Developments In Reproductive Medicine</a></strong><object id=\" __sse643868\" width=\" 425\" height=\" 355\" ><param name=\" movie\" value=\" http://static.slidesharecdn.com/swf/ssplayer2.swf?doc=new-developments-in-reproductive-medicine-1223465441980978-8&stripped_title=new-developments-in-reproductive-medicine-presentation\" /><param name=\" allowFullScreen\" value=\" true\" /><param name=\" allowScriptAccess\" value=\" always\" /><embed name=\" __sse643868\" src=\" http://static.slidesharecdn.com/swf/ssplayer2.swf?doc=new-developments-in-reproductive-medicine-1223465441980978-8&stripped_title=new-developments-in-reproductive-medicine-presentation\" type=\" application/x-shockwave-flash\" allowscriptaccess=\" always\" allowfullscreen=\" true\" width=\" 425\" height=\" 355\" ></embed></object><div style=\" padding:5px 0 12px\" >View more <a href=\" http://www.slideshare.net/\" >presentations</a> from <a href=\" http://www.slideshare.net/7260678\" >求子 大全</a>.</div></div><br />New Developments In Reproductive Medicine - Presentation Transcript<br />New Developments in Reproductive Medicine Prof. Dr. med. K. Diedrich Dept. of Obstetrics & Gynecology University of Schleswig-Holstein, Campus Lübeck, Germany Infertility Meeting, Misurata, 26 th October 2007 <br /> <br />Number of infertile couples in Germany: approx. 15 - 20% of all couples (1.2 – 1.6 Millions) <br />Once upon a time… 07/78 Louise Brown was born Birth after reimplantation of a human embryo Steptoe P.C. / Edwards R.G. Lancet 2 (1978): 366 <br />Milestones in reproductive medicine <br />1960 - ovarian stimulation with clomifene and gonadotrophins - radioimmunoassay <br />1970 - secretion, synthesis, mechanism of GnRH a. gonadotrophins - in vitro fertilisation <br />1980 - GnRH-agonists and gonadotrophins - cryopreservation <br />1990 - recombinant gonadotrophins - preimplantation genetic diagnosis - intracytoplasmatic sperm injection (ICSI) <br />- GnRH-antagonists <br />2000 - in vitro maturation of oocytes - embryonic stemcells - SET (single embryo transfer) <br />- vitrification <br />Probability of successfull infertility treatment after: Dor et al., 1996 71.4% male 63.3% tubal 57.7% ovarian pregnancy rate cause of infertility <br />1.9 Millions after ivF <br />800 000 after ICSI <br />Germany (1982-2004): 108 000 <br />Children after ART until 2004 worldwide C. Nygren, 2004 <br />birthrate per cycle : <br />after ivF 21% (DIR, 2004) <br />after in vivo fertilisation 24% <br />New Developments in Reproductive Medicine <br />Ovarian stimulation: GnRH-antagonists <br />Elective single embryotransfer (eSET) <br />Blastocyst transfer <br />In-vitro-maturation <br />Cryopreservation and vitrification <br />Preimplantation genetic diagnosis and screening <br />History of ovarian stimulation <br />1970 Clomifen <br />hMG <br />1980 GnRH-agonist / hMG <br />1990 recFSH <br />GnRH-antagonist / hMG or recFSH <br />2000 long acting FSH <br />Structure of GnRH and analogues <br /> <br />„ long protocol“ „ Lübeck protocol“ GnRH-agonist and antagonist protocol 0 2 4 6 8 Ampoules Gonadotropins d 6 Menses Cetrorelix OPU HCG 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 ET day of cycle -16 -14 -12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 0 2 4 6 8 Ampoules HMG OPU d -14 LHRH-agonist: daily injection/ depot/ nasal spray Menses ET HCG 17 day of cycle <br />Odds ratio:0.859 p=0. 0 85 LIVE BIRTH Rate difference 2.7% Griesinger et al., 2006 <br />simple stimulation <br />fixed initiation of GnRH-antagonist on day 6 <br />no LH supplementation <br />no increase of gonadotrophin dose at GnRH-antagonist initiation <br />ovulation induction for ART by dominant follicle of ≥ 17mm <br />luteal phase supplementation is mandatory <br />Advantages of GnRH-antagonists <br />fits into the normal cycle <br />(„the patients like it“) <br />less side effects in comparison to the long protocol: <br />Ø cysts <br />Ø hormonal withdrawl <br />less OHSS <br />no significant difference in the probability of live birth between GnRH-agonists and antagonists <br />Advantages of GnRH-antagonists <br />long acting FSH 1 2 3 4 5 6 7 8 9 10 11 12 13 14 …. 10000 IE hCG follicle aspiration after 36h GnRH-Antagonist LF 10 mm LF 14 mm LF 17mm FSH-CTP <br />Children after ART: 1997-2002 DIR 2001 100 39366 19878 19488 Total 0.08 31 8 23 Quadruplet 6.22 2449 1221 1228 Triplet 33.87 13335 6553 6782 Twin 59.83 23551 12096 11455 Singleton % Total ICSI IVF <br /> <br />Problems of multiple pregnancies <br />pregnancy related diseases <br />prematurity <br />increase of neonatal morbidity and mortality <br />costs <br />Aims <br />To avoid multiple pregnancies <br />Improve the pregnancy and life birth rate <br />Solution : Transfer of one selected embryo <br />Embryo selection > 30% < 5% Implantation <br />eSET = 40.3% pregnancy rate <br />1% gemini <br />eDET = 44% pregnancy rate <br />32% gemini <br />Pregnancy rate after elective single embryo transfer (eSET) and elective double embryo transfer (eDET) Gerris, 2005 ESHRE <br />Karlström u. Bergh, HumRep 22: 2007 Birth rate and MBR in relation to the percentage of SET and triple embryo transfer (TET) in Sweden 1991–2004 <br />Karlström u. Bergh, HumRep 22: 2007 Birth per embryo transfer (%) and MBR in Sweden and USA <br />§ 1, Abs. 1, Nr. 5 „ a person fertilizing more oocytes than he or she intends to tranfer in the course of one treatment cycle“ § 1, Abs. 1, Nr. 3 „ a person transfering more than 3 embryos to the womb in the course of one treatment cycle“ Prison sentence up to three years or financial penalty for <br />Metaanalysis of blastocyst transfer: day 2/3 versus day 5/6 of embryo transfer Blake et al. 2004 <br />no significant difference (OR=0,91; 95% CI 0,71-1,17) <br />disadvantage of long-term cultivation <br />Preimplantation genetic screening (PGS) University of Brussels <br />Inclusion criteria : <br />37 yrs and older <br />prospective randomized controlled study <br />examined chromosomes: X, Y, 13, 18, 21 <br />Results PG-Screening University of Brussels Devroey, 2006 8% 10% Implantation rate per embryo 3.1 (210) 2.1 (100) No of embryos per ET 18 (26.5%) 10 (20.9%) Pregnancies per embryo transfer 20 Abnormal embryos 70 (85%) 48 (55%) Embryo transfer 82 86 Patients control Preimplantation genetic screening (PGS) <br />Conclusion of the Brussels study: A positive effect of PGS on implantation and abortion rate of this study and others is not clearly documented. <br />Methods of cryopreservation <br />slow cooling <br />vitrification <br />Clin. pregnancies / ET after cryo transfer (1996-2004) German IVF Index 2004 21.64 % Abortion rate after cryo transfer 15.5 % Clin. pregnancy / ET 67,257 Cryo transfer <br /> <br />after Kuwayama, RBM-online 2005, pp.300-308 a. Polypropylen strip b. Hartplastik-Griffstück <br />Schutz für LN 2 Lagerung <br />c. Hartplastik-Schutzhülle Cryotop for vitrification <br />Lübeck Results (till 01/2007) survival rate pregnancy rate n=752 n=155 <br />The Lancet 1965 <br />„ Oocytes from antral follicles can finalize their meiotic maturation in vitro in 24 – 48 hours“ <br />R.G. Edwards et al. <br />First oocyte maturation in vitro Edwards RG et al. 1965 <br />Development of IVM 1983 Veeck First birth after IVM 1991 Cha IVM on immature oocyte extracted by using ovarian biopsy during a cesarean section resulted in healthy twins 2000 Cha birth of 20 healthy children afte IVM 2003 Mikkelsen birth of 33 healthy children after IVM today >300 children after IVM <br />Early oocyte retrieval from antral follicles before <br />selection and atresia . . . <br />Physiological basics of IVM day 3 day 8 - 12 d>10mm <br />PCOS <br />high responder with a risk for OHSS <br />normo-cyclic patients <br />cryopreservation of oocytes (oncology) <br />low responder <br />implantation failure <br />Therapeutic indications for IVM Mikkelsen et al. 2003, Smitz 2005, von Otte 2005 <br />IVM oocyte maturation (24 h) Tag 1 2 3 4 5 6 7 8 9 10 …. first Examination: basic ultrasound and hormone level embryo culture ( 2- 3 days) Embryo transfer 2-3 days after ovum aspiration Menses Exam. 2,3, … ultrasound and hormone level Treatment protocol Fertilization via ICSI ♂ Male: sperms 4 days of low dose hMG („priming“ with 75IE hMG/day) primordial follicle ≥ 12mm and E ≥7mm 10.000 IE hCG 36h later aspiration of small antral follicles Estradot 100 Crinone 8% <br />Fertilization and outcome 4.2 ± 3.4 310 Mature oocytes/ ovum aspiration Mean ± SD % total N= 100 cycles 5.9% 4 Cryopreservation 13% 13 Pregnancies/ transfer 2.2 122 Embryos/ transfer 67% 55/85 Cycles with embryo transfers 1.77 ± 1.44 44 138 Pronuclei/ ovum aspiration <br />ovarian biopsy and cryopreservation <br />in vitro Growth („IVG“) followed by In vitro Maturation („IVM“) <br />in the future: „TESE“ for the woman? Oktay et al. 2004 <br />Future of Reproductive Medicine <br />new embryo protection law (european?) <br />improvement of pregnancy rate by the elective single embryo transfer (morphological criteria) <br />avoid multiple pregnancies <br />vitrification <br />in vitro maturation <br />aim of infertility treatment: simple, safe, comfortable, successful and cheap <br />