Use of in vitro maturation for fertility preservation

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1 Use of in vitro maturation for fertility preservation G. Arroyo Servei de Medicina de la Reproducció Departament d Obstetrícia, Ginecologia i Reproducció INSTITUT UNIVERSITARI DEXEUS

2 MEDICAL STRATEGY TO FERTILITY PRESERVATION Healthy with good vital prognosis Age of the patient < 35 years old (max 40) Good basal profile of ovarian reserve Type and stage of the pathology (cancer, others ) Therapeutic plan: - Chemotherapy: type, dose and duration of treatment - Radiotherapy: field, dose and duration of treatment - Surgery (gynaecological, not gynaecological)

3 To offer Fertility Preservation Time to start the medical treatment Possiblility or not of performing an ovarian stimulation Options/Efficiency: - Oocyte freezing: 20-45% PR - In Vitro Maturation - Ovarian tissue freezing: low

4 What role does IVM play in Fertility Preservation? Hormone-sensitive tumours Insuficient time to performe IVF and chemeotherapy Chian et al. Fertil Steril 2009

5 IN VITRO MATURATION Retrieval of immature oocytes without previous stimulation and in vitro maturation was presented as an alternative to conventional IVF. Despite controversial biological and medical aspects, it is an attractive technique for women that avoids the risks of ovarian stimulation. MADURACIÓN IN VITRO

6 PROTOCOL IU DEXEUS Regular cycles P D0 D1 D2 D3 Estradiol x x Pick up+ivm ICSI Transfer Ultrasound x x Estradiol Val. Progesterone UI HCG Tur et al., ASEBIR 2007

7 PROTOCOL IU DEXEUS Irregular cycles P D0 D1 D2 D3 Estradiol x x Pick up+ivm ICSI Transfer Ultrasound x x Estradiol Val. Progesterone Oral contraceptive UI HCG Tur et al., ASEBIR 2007

8 No MII recovered 4 GV 2MII (ICSI) 2 embryos * D2 24h IVM Oktay K. et al. Fertil Steril 2008

9 OVARIAN STIMULATION IN BREAST CANCER PATIENTS Antag-GnRH FSH r (150 UI/día) Letrozole (5 mgrs/día) A - G n R H Letrozole (5 mgrs/día) D? Protocol Dexeus

10 Demirtas et al. RBM Online 2008; 17:

11 Luteinization of small follicles LH and Prog levels do not affect small AF? LH receptors are not expressed on granulosa cells until the follicles reach follicular phase. Neither Prog nor LH receptors have been demonstrated on the surface of GV human oocytes. There may be a continuous follicular recruitment. The wave of small antral follicles of the luteal phase may not necessarly be atretic but could be in earlier phases of follicular growth.

12 IVM improves fertility preservation in breast cancer patients: relation to AFC Oktay K. et al. RBM Online 2010; 20:

13 Additional IVM in Breast cancer patients Fertility Preservation s cycles Oocytes collected 464 MII 274 (59%) GV & MI (cultivo) 174 (38%) Atresic oocytes 16 (3%) MII 125 (72%) Atresic oocytes 49 (28%) Oocytes cryopreserved Oocytes MII+ICSI Oocytes MII+ICSI Oocytes cryopreserved 25 (9%) 249 (91%) 87 (70%) 38 (30%) Oocytes fertilized (*) Oocytes fertilized (*) 187 (73%) 75 (86%) Total Oocytes and Embryos Cryopreserved 207 Total Oocytes and Embryos Cryopreserved after IVM 113 IVM Oocytes (*) P<0.05 Oktay et al. RBM Online 2010; 20:

14 Sönmezer et al. Fertil Steril May 2011

15 IVM from unstimulated ovaries Tan, Child and Gulekli Am J Obstet Gynecol 2000

16 IVM RESULTS IU DEXEUS / Average DS % Antral Follicles Oocytes collected MII inseminated Fertilization rate Evolutive embryos Transferred embryos Frozen embryos

17 IVM RESULTS IU DEXEUS / Patients 42 Cycles 60 Pregnancy / retrieval 17/58 (29,3 %) Pregnancy / transfer 17/52 (32,7 %) Implantation rate 18/113 (15,9 %) 11 children born 7 miscarriages 1st trimester (41,2%)

18 Jurema MW, Nogueira D.Fertil Steril 2006; 86:

19 Jurema MW, Nogueira D.Fertil Steril 2006; 86:

20 61 oocytes: 23 cultured 15 MII ICSI 8* 16 MII * 0/16 13 GV * 3/13 GV survive 2 MII 30h ICSI 2 T Tucker et al., Fertil Steril 1998

21 Freezing & IVM Freezing- IVM or IVM-freezing? GV IVM I.U.Dexeus Cao et al., Semin Reprod Med 2009

22 Freezing & IVM In vitro Maturation Rate of immature oocytes WITH or WITHOUT vitrification: < 20% Cao et al., Semin Reprod Med 2009

23 Freezing & IVM GV frozen before maturing : Cao et al., Semin Reprod Med 2009 ~ survival rate < maturation rate ~ fertilization rate ~ zygotes cleaved, blastocytes developed < embryo quality

24 Freezing & IVM

25 Freezing & IVM

26 Freezing & IVM

27 Fertility preservation: Combining methods IVM- Ovarian tissue cryopreservation Regular cycles 26 years old, Hodgkin s Lymphoma, D16 hemi-ovarectomy, before chemeotherapy 33 years old, cervical cancer, before radio and chemeotherapy Isachenko et al. RBM Online 2004

28 Fertility preservation: Combining methods IVM- Ovarian tissue cryopreservation Huang et al. Fertil Steril, 2008; 89:

29 I.U.Dexeus IVM- Fertility preservation Combining methods # Pathology Day Method Stimulation Collected Matured Total LFC Breast Cancer 30 VV Breast Cancer Ovarian tissue + IVM - 2 GV 3 IVM HCG 4 GV 2 MII * (100%) 2 MII* + Ov Tissue 3 MII* (75%) 3 MII * MBC Breast Cancer 13 IVF+IVM Letrozole+FS H+AntGnRH 4 MII* 5 GV 4 MII * (80%) 8 MII * MVB Breast Cancer 14 IVF+ IVM Letrozole+FS H+AntGnRH 14 MII * 13 GV 3 MII * (23%) 17 MII * NM G Hodgkins Lymphoma 13 IVF+ IVM Letrozole+FS H+AntGnRH 14 MII * 1 MI (0 %) 14 MII *

30 Discussion IVM has become an effective treatment option for many infertile women, resulting in the birth of over 2000 healthy infants without any increase in fetal abnormalities or miscarriage rates in comparable patients. Despite satisfactory pregnancy rates in appropriately selected patients, overall pregnancy rates remain lower than those of IVF cycles in general. There is no data yet on pregnancy rates in FP

31 Immature oocyte retrieval can be done within 2 10 days, depending on the patient s menstrual status. Also, immature oocytes can be collected even in the luteal phase. Immature oocytes can also be harvested from ovarian biopsy specimens and can be fertilized or vitrified following IVM. This combination of ovarian-tissue cryobanking and IVM represents a new strategy for fertility preservation.

32 An effective IVM program will avoid most of the problems and concerns associated with stimulated IVF cycles in cancer patients. It is necessary to inform the patient about the most efficient technique according to their individual profile and expectations.

33 Thank you for your attention G. Arroyo, F. Martínez, C. González, M. Devesa, M. Solé, M. Boada, A. Veiga, O. Carreras, R. Tur, B. Coroleu, P.N. Barri

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