1. 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

3. Number of infertile couples in Germany: approx. 15 - 20% of all couples (1.2 – 1.6 Millions)

4. 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

6. Probability of successfull infertility treatment after: Dor et al., 1996 71.4% male 63.3% tubal 57.7% ovarian pregnancy rate cause of infertility

10. Structure of GnRH and analogues

12. „ 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

13. Odds ratio:0.859 p=0. 0 85 LIVE BIRTH Rate difference 2.7% Griesinger et al., 2006

16. 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

17. 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

21. Embryo selection > 30% < 5% Implantation

23. 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

24. Karlström u. Bergh, HumRep 22: 2007 Birth per embryo transfer (%) and MBR in Sweden and USA

25. § 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

28. 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)

29. Conclusion of the Brussels study: A positive effect of PGS on implantation and abortion rate of this study and others is not clearly documented.

31. 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

34. Lübeck Results (till 01/2007) survival rate pregnancy rate n=752 n=155

36. 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

39. 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%

40. 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