Oocyte Donation in Spain

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1 Oocyte Donation in Spain IVF Spain Ask the Experts Natalia Szlarb MD, Phd Lunteren, September 28th 2013

2 Socio-cultural delay of parenthood Social revolution 60 s Contraceptive pill Female s priorities: - Education and work Divorces New family models

3 Highest Efficiency regardless age

4 Highest Efficiency regardless age Cummulative pregnancy rates after 1, 2 and 3 attempts Recipients Years OD: highest implantation rates in ART (Cohen et al., 1999)

5 Highest Efficiency regardless indication Implantations- and Pregnancy Rates Data IVF Spain: 2009 P = N.S.

6 Obstetric complications assumable IVF Egg Donation Spontaneous P 1st trimester bleeding (86/252) 34,2%* (97/325) 29,8%* (27/403) 6,7% <0.001 Miscarriage < 24 weeks 179/932 19,2% 103/450 22,9% 45 /450 10% <0,05 Ectopic pregnancy 5/932 0,5% 5/450 1,1% 4/450 0,9% N.S. Preterm labour (82/253) 32,4% * (29/250) 11,6%* (24/402) 6% <0.001 Preterm labour, Singleton (50/185) 27%* (15/192) 7,8% * (9/326) 2.8% <0.001 Preterm labour, Multiples (32/68) 47.1%* 14/57) 24.6% (15/76) 19.7% Preterm birth (11/405) 27.4%* (90/265) 34%* (53/401) 13.2% <0.001 Glucose Intolerance (23/250) 9.1%* (11/250) 4,4% (19/402) 4,7% <0,05 PROM (59/253) 23,3% (31/245) 12,7%* (99/402) 24, PROM >/=32 weeks (55/245) 22,4% (28/222) 12,6% (97/392) 24.7% PIH (37/251) 14,7% * (44/251) 17.5%* (27/402) 6.7% <0,001 Placenta Previa (11/248) 4,4% * (13/254) 5,1% (3/402) 0,7% <0,05 Abruptio Placentae (7/248) 2,8% * (1/252) 0,4% (4/402) 1% <0,05 Bosch E., Aizpurua J, et al., Reproducción Humana, 2nd Edition, 2003

7 WHY in SPAIN

8 A unique constellation Friendly travel destination/infrastructures Open and advanced legislation Competitive high level clinic landscape High level scientific research Genetic compatibility Donor availability

9 The Well known reasons Excellent connections Direct flights from Amsterdam, Rotterdam,Eindhoven

10 Open and advanced legislation leading to technological advantages LAW 1988 ADVANCED RESEARCH

11 Law: Spain s reproductive legislation is among Europe s most advanced Country/ Treatment Anonymous donation Sperm donation Egg donation Genetic Selection of Embryos France yes yes yes yes Germany yes yes no no Holland no yes yes yes Italy no no no no UK no yes yes yes Spain yes yes yes yes

12 Law: Spain s reproductive legislation is among Europe s most advanced Anonymous Donation Economical Compensation

13 Specialised clinics KINDS OF CLINICS IN THE SPANISH LANDSCAPE IVF industries Mass production of treatments Good rates Impersonal Excellent R&D Economies of scale Massive marketing Expansion abroad Artisan clinics Few cycles Classical treatments Poorer rates Personal patient approach Try to enter in European markets, but no networks or marketing No R&D Boutique clinics Specialized either in kind of treatment or kind of patient (for instant international patient) Rates over average Patient centred and very personal Good R&D Marketing based on referral doctors, quality and word to mouth

14 Research and development 25 years egg donation 20% pubications of ESHRE publications are from Spanish scientists Examples from our clinic - sperm vitrification - embryo metabolomics - implantation immunology

15 Research and development Applied knowledge Fertility Prediction: Positive donor selection Improved Lab conditions Improved embryo selection Blastocyst culture Improved cryo programs Genetic selection of embryos Improved matching

16 Genetic compatibility mtdna analyyess reveals a major late Paleolithic population expanyeson from southwestern to northeastern Europe. Bandelt et al., Am J Hum Genet 1998 May;62(5):

17 Genetic compatibility A signal, from Human mtdna, Postglacial Recolonization in Europe. Torroni et al. in: The American Journal of Human Genetics, Bd. 69, S. 844, 2001.

18 75% of your genes come from ancestral basques By Peter Forster und Elisabeth Hamel In Spektrum der Wissenschaft May 2002, p.41,

19 Donor availibility: Economic, Religion and Social Acceptance Recessive economy Students and young people have few resources ECONOMIC Catholic tradition of spiritual investment Spain, among the highest volunteer and donation rate for NGOs Solidarity a rooted social value SOCIOCULTURAL AND RELIGIOUSS Spain world`s leader in organ donation Social values Advanced scientific, technological and logistical system for donations TRADITION IN ORGAN DONATION

20 SOCIOCULTURAL FACTORS Economics, Religion and Social Acceptance Anonymity versus non anonymity of donation

21 Economics, Religion and Social Acceptance Spain, world s leader in organ donation Spaniens Sonderfall weltfuehrend in Organspende ORGANS, TISSUES AND CELLS, (1), 9-12, 2006

22 Anonymity vs. non anonymity A very controversial issue. Several psychological studies show no difference in development and happiness perception between natural and IVF or OD children. Studies show disorders when truth is revealed in adolescence and early youth. Anonymity protects children and donors against trauma in adolescence.

23 ANONYMITY VS. NON ANONYMITY Countries promoting non- and anonymous donations USA Canada US Russia and Eastern Europe UK, BeNeLux & Scandinavia Germany, Austria, Switzerland, Italy Arab world, Africa Spain, France, Greece, Cyprus

24 ANONYMITY VS. NON ANONYMITY Countries promoting non anonymous donations Strong cultural family values = cultural comparison egg donation with wish for children Strong cultural individualistic values = cultural comparison egg donation with adoption

25 ANONYMITY VS. NON ANONYMITY Countries promoting non anonymous donations Children coming from family wish psychological background of love and support sometimes overprotected no identity problems when knowing about their origin Children coming from adoption psychological background of rejection tension of painful past with care in new environment identity conflicts when confronted with truth (where do I belong to ) In both cases: family environment plays a far more determinant role than genes Non anonymity loaded with genetic determinism

26 HOW TO GET 500 DONORS Alicante demographics Recruitment program Donor pool management

27 Alicante demographics women between 19 and 29 years European foreigners from EU countries 49% of them women Two Universities with female students - - British 18% German 7,8% Dutch 3,6%

28 Recruiting program social approach Yearly gynaecologic check for free Genetic and health check for free Social freezing for free Info days at university No publicity, only word of mouth recommendation

29 Donor management 150 leave every year 150 new every year 500 donors Restriction to 6 life births Strict donor testing and selection: Genetic (Recombine), psychologic, infectious diseases, fertility predictors, drug screening, only between years

30 Donor management 1. Word of mouth 2. In depth analysis of conditions of donor a) Health -) -) -) -) HIV Syphilis Hepatitis B&C CMV, toxoplasma etc. First class personal treatment b) Genetic diseases - Recombine test for over 200 monogenic hereditairy disorders. As a way to get mouth to mouth referrals 3. Genetic matching through Recombine! top donors

31 Phenotypic matching

32 100 donors 400 donors Legal requirements 20 donors Recipients preferences Doctors matching Doctors and genetic matching 4 donors

33 Recombine Recombine: 1500 SNPs covering: 980 SNPs for 174 genetic diseases and 520 random SNPs for genetic matching. Take the sample Prepare and process samples DNA extraction Report

34 1500 SNPs 520 Random SNPs Ancestral Fenotype 980 SNPs: Dominant Recessive Specific personal profiles

35 Phenotype SNPs Anonymous Ancestral SNPs Non Anonymous

36 The genetic matching advantages Herewith a genetic matching is possible which may close the gap between anonymous and non anonymous donations High patients acceptance through objetive information about the donor without opening their identity

37 DIFFERENT TREATMENT OPTIONS Model of shared risk and advantages Pregnancy guarantee Exclusive donor Shared donor Cryo preservation Alternatives to Oocyte Donation

38 Cryopreserved oocytes OOCYTE DONATION WITH CRYOPRESERVED OOCYTES from current oocyte bank (100 donors) 6 8 Guaranteed oocytes , Guaranteed oocytes ,00 Easy treatment planning, ideal for those couples with good prognosis and limited time availability. Short stay in Spain: 5 days in case of fresh semen sample or 2 days with frozen semen sample, fixed date Possibility to do an advanced hotel and flight booking with possibility to do the transfer during weekend. Individual donor matching with Phenotype matching (genetic matching is not possible). Embryo Cryopreservation if possible, but without guarantee. Medical treatment of the donor and her medication. Treatment of the recipient and online medical following. Includes the ICSI fertilization technique, but charged additional with cryo transfers Best embryo choice by using the modern technology Time Lapse. Embryo transfer on day 3-4 (or day 5 of embryonic development if possible). No waiting list for treatment, minimum preparation time of 1 month. Good pregnancy rate * (5-8 oocytes) Pregnancy rate in fresh transfer of 2 embryos: 60% Cumulative rate child at home of 1-2 transfers: 55-60% High pregnancy rate * (9-12 oocytes) Pregnancy rate in fresh transfer of 2 embryos: 65% Cumulative child at home rate of 2-3 transfers: 60-70%

39 Shared Donor Oocyte Donation: Shared donor , guaranteed fresh oocytes from the oocyte donor cycle. I deal for couples with a good prognosis / family planning in order to obtain a single child pregnancy. Individual donor matching with tested fertility. Cryopreservation of embryos if possible, but without guarantee. Medical treatment and medication for the donor. Treatment of the recipient and online medical following. Blood tests and ultrasounds at the clinic. Includes the ICSI fertilization technique, but charged separately from Cryo transfers Best embryo choice by using the modern technology Time Lapse. Embryo transfer on day 3-4 or day 5 of embryonic development. No waiting list for treatment, minimum preparation time of 1 month. High pregnancy rate * Pregnancy rate by fresh transfer of 2 embryos: 65-75%. Cumulative child at home rate of 2 transfers: 65-70%

40 Exclusive Donor Oocyte donation: Exclusive ,00 Individual donor matching with tested fertility from complete donor pool of 500 donors. Phenotype matching Genetic matching possible (400,00 ) + Recombine testing of the donor, descriptive report. Medical treatment and medication for the donor. Treatment of the recipient and online medical following. Blood tests/ultrasounds at the clinic. No waiting list for treatment, minimum preparation time of 1 month oocytes on average per donor cycle. Donor with tested fertility. Blastocyst culture under hypoxia, embryo selection using time lapse technology. Assisted hatching if necessary, PID possible. Fertilization techniques MACS, ICSI / IMSI (if necessary). Guaranteed transfer on day 5 of embryonic development Embryo transfer guaranteed on day 5 of embryonic development. Cryotransfers organised separately. Family planning options Guaranteed cryopreservation of at least 2-3 embryos, in case of less than 4 blastocytes, we stimulate the same donor or another donor without any additional costs. Embryos from the same cohort will be ready for the future family planning. Very high pregnancy rate*. Pregnancy rate in fresh transfer of 2 blastocysts: 75-80% Cumulative child at home rate of 3 transfers: 80-90%

41 Diamond Oocyte donation: Diamond ,00 Pregnancy rate * 100% or Money Back Guarantee. The commitment to participate in the treatment program depends on the evaluation from the Medical Committee. Includes: 3 exclusive oocytes donation cycles with cryopreservation of embryos Genetic Matching (recombine test donor-recipient) PGD (genetic diagnosis with Full Array CGH and techniques) in all blastocysts Cryotransfer; except the thaw cost. Guaranteed pregnancy (defined as unremarkable pregnancy to 7-8 pregnancy week with a positive heartbeat) 50% refund in case of no success The rest of techniques and treatments from the exclusive program are included.

42 HOW DOES IT WORK Logistics First visit Pre Treatment Second stay for transfer Post treatment

43 Cycle planning and process First contact Pilll Ultrasound Endometrium mm Phone Mail Progynova 2 mg Ovarian cystc? Skype P4 May be Estradiol Progesteron 800 mg First visit GnRHa Depot at clinic 1 day Mock cycle P4 2-6 weeks Anamnesis Preliminary results 1 Pregnancy Test P4 P4 P4 P4 P4 12th pregnancy week analysis results Planned Treatment stay 1-2 weeks confirmation of donor matching and availability

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