Accessible infertility care - From dream to reality:

1. Accessible infertility care - From dream to reality: first pregnancies with a simplified IVF procedure Willem Ombelet Genk, Belgium

2. 1st congress Male infertility 750 participants 34 countries

3. Howard Jones, US IVF pioneer Robert Edwards 2010 Nobel Prize winner 34 years IVF > 5.4 million IVF / ICSI babies worldwide SUCCESS ???

4. www.nightearth.com

5. www.ivf-worldwide.com/ivf-directory/ But what about … www.nightearth.com

6. 1st priority = Prevention Education Family-planning Developing Countries = overpopulation Limited budget ART = ethical issue Limited Resources Argument More important priorities: HIV, tbc, malaria, vaccinations … ART = expensive Limited or no interest for infertility in developing countries

7. Infection-related tubal block Asia 39 % Latin America Africa 44 % 65 - 85 % Tubal factor : why ? • Sexually transmitted diseases • Post-partum infections • Illegal abortions • Urbanisation -  mobility • Polygamy • Resistant micro-organisms …

8. World community statements “Men and woman of full age, without any limitation due to race, nationality or religion, have the right to marry and to raise a family”. This statement was adopted 60 years ago at the 1948UN Universal Declaration of Human Rights and can’t be misunderstood: it impliesthe right to access to fertility treatments when couples are unable to have children. 2. At the United Nations International Conference on Population and Development in Cairo in 1994 the following statement was made “Reproductive health therefore implies thatpeople have the capability to reproduce and the freedom to decide if, when and how often to do so … and to have the information and the means to do so …” 3. UN Millennium Declaration, signed in September 2000 : “Achieve, by 2015,universal access to reproductive health”. 4. In 2001, on the occasion of a WHO meeting on "Medical, Ethical and Social Aspects of Assisted Reproduction" in Geneva, a call forthe integration of infertility into existing sexual and reproductive health care programmes in developing countries was made. 5. In 2004 the World Health Assembly proposed five core statements, including “the provision of high-quality services for family-planning, including infertility services”.

9. Why should we care ? • Infertility not very prevalent in • developing countries • Infertility is not a serious problem for people in developing • countries • “Individual problem, not a public health problem, not a • problem of the nation…”

10. Prevalence of infertility Prevalence of infertility The estimate of the magnitude of the involuntary infertileDemographic definition - 5 years of childlessness (2004) (in developing countries minus China, data up to year 2000) Total: 186 million women 168 180 160 140 120 100 80 60 40 20 0 millions millions (Source:Rutstein and Shah, DHS Comparative Reports, no. 9, 2004) 18 Primary infertile Secundary infertile

11. Why should we care ? • Infertility not very prevalent in developing countries • Infertility is not a serious problem for • people in developing countries • “Individual problem, not a public health problem, not a • problem of the nation…”

12. Challenge: address infertility as an impairment of body function which is affected by societal features Level 6 Lost dignity in death Developing/ transitional societies Level 5 Violence-induced suicide Starvation / disease Level 4 Severe economic deprivation Moderate / severe violence Total loss social status Level 3 Mild marital / social violence Social isolation Level 2 Marital status Depression, helplessness Developed societies Level 1 Fear, guilt, self-blame WHO Current Practices and Controversies in Assisted Reproduction "Infertility and social suffering,"Daar & Merali, 2001, page 18, Figure 2.

13. Transactional sex • Concurrent partners • Multiple unions • No condom use • Early age at first sex • Gender based violence Poverty, low education, gender inequality, high value of children, limited health care Bad sexual health, obstetric and neonatal care STIs/HIV unintended pregnancies (unsafe abortions) INFERTILITY AND CHILDLESSNESS

14. Why should we care ? • Infertility not very prevalent in developing countries • Infertility is not a serious problem for people in developing countries • “Individual problem, not a public health problem, not a problem of the nation…”

15. Mother or nothing – the agony of infertilityProf dr M Fathalla, WHO Bulletin, December 2010 “In a world that needs vigorous control of population growth, concerns about infertility may seem odd, but the adoption of a small family norm makes the issue of involuntary infertility more pressing. If couples are urged to postpone or widely space pregnancies, it is imperative that they should be helped to achieve pregnancy when they so decide, in the more limited time they will have available.”

16. Social and psychological suffering How to prevent suffering? → accept pronatalism and try to help people to have children → fight pronatalism : reduce the negative socio-cultural and economic consequences of infertility Best solution → combination of both strategies on the basis of cost-effectiveness Pennings, 2010

17. International organisations: no interest • International Planned Parenthood Federation • Only family planning research and HIV prevention • The Population Council • Leading role in development new contraceptives • Family Planning International • Focus on family planning research and HIV prevention • World Health Organization • Focus on family planning & prevention STD’s // HIV

18. One-day clinic (diagnosis) Arusha (expert) meeting December 15-17, 2007 Make it SIMPLE EFFICIENT SAFE AFFORDABLE Ovarian stimulation for IVF IVF Laboratory

19. Convincing the scientific community Health Care Centres Family planning Mother care Infertility care

20. Holistic model of reproductive healthcare horizontal and infertility included

21. Arusha meeting 2007 One day clinic (diagnosis) Make it SIMPLE EFFICIENT SAFE AFFORDABLE IVF ovarian stimulation IVF laboratory

22. HIGH COST IVF Lab Expected price →1.5 - 3 Million €

23. t WE lab - a simplified IVF procedure Simplified Culturing System Two glass tubes connected by needles and tubing tube 1 = CO2 generator Citric acid + sodium bicarbonate -> CO2 tube 2 = medium equilibration / IVF Fertilisation and culturing in separate glass tubes CO2 incubator not needed Prof. Dr. Jonathan van Blerkom University of Colorado, Denver Prof. Dr. Willem Ombelet and Prof. Dr. Carin Huyser

24. Step 1: Set-up and equilibration 6.3 - 7.1 % CO2 12 - 13% O2 Citric acid + sodium bicarbonate + water produces carbondioxide to equilibrate culture medium to pH 7.25- 7.35

25. Step 1: Set-up and equilibration

26. Step 2: Insemination Day 0 Insertion of oocytes and sperm cells: 1 oocyte per tube with 1000-5000 good motile sperm cells

27. Step 3: Fertilisation check Fertilisation check through the glass tube wall Day 1

28. Step 4: Embryo visualisation Day 2 Day 3 Day 2 Day 3 Embryo transfer

29. Couple selected for first IVF trial ♀ < 36 years ♂ IMC> 1 million IMC < 1 mill ICSI Ovarium Stimulation (Rec FSH-antagonist) Oocyte retrieval (OR) < 8 oocytes Excluded ≥ 8 oocytes Regular Culturing (RC) Simplified Culturing (SC) If 1 top embryo SET day 3 Regular culturing Randomisation If ≥ 2 top embryos Cryo surplus embryos SET SET: RC embryo + + 1st TRIAL If no top embryo SET: SC embryo Serum HCG 9 – 11 days after OR Negative Positive If no fertilisation If no good quality embryo Ultrasound 5-6 weeks after OR No transfer Excluded

30. Interim report Age < 36yrs, min 8 oocytes, SET n= 28 4 excluded ET 17/28 t WE lab (60,7%) 11/28 RCS (39,3%) FR t WE lab: 60.8% FR SCS: 58.2% HCG+ 7/17 t WE lab (41,2%) 2/11 RCS (18,2%) 1 BC IR 2/11 RCS (18,2%) 6/17 t WE lab (35,3%) first pregnancy from Frozen ET

31. Simplified culturing system Until 31-12-12 12 ongoing pregnancies First delivery 07-11-12 – healthy boy – 3500 gr Day 3 Day 3

32. t WE lab - a simplified IVF procedure Direct costs IVF Laboratory 10 – 15 % Cost per IVF cycle (medication excluded) 2500 € → < 200 €

33. IVF Cost analysis per procedure in a private practice in South Africa C Huyser 2012 ICSI

34. Price Medication 25 - 120 Euro Price Medication Belgium per cycle 1075 Euro !! Modified IVF protocol hCG 5000 U Clomiphene 100 mg MENSES 35 h 7 3 4 5 6 8 9 X Day 0 Day 3 D1 >= 17 mm Pick-up ET US OVARIES US OVARIES Menopur 75 or Puregon 75 Low dose hCG

35. Current / future developments • Studies with low stimulation protocols (CC-low dose hCG) in t WE lab setting • Studies on sperm number needed for IVF in t WE lab setting • Cost – analysis … tWEtraining centre tWEIVF centre 2013 Solarenergy

36. Compton Foundation What about funding ?? http://nnadofoundation.webs.com/

37. www.thewalkingegg.com Mumbai Nairobi Lima Pretoria

38. Numbered Signed Registrated

39. The WalkingEgg Project Search forfunding Partners WHO ESHRE IFFS ESGE ISMAAR Level 1 (up to IUI) Level 2 (up to IVF) Study Genk Level 3 (cryo/ICSI) Packages Partners-Industry Gynetics Storz Esaote … TWE Manualdiagn. Phase Manual Training Business-Plan Registration system Support Socio-culturalStudy Group ESHRE Select pilot-centres India, Kenia, Peru … Building Personel Fixedcosts Running costs

40. When a thing was new, people said,“It is not true“Later when the truth became obvious, people said,“Anyway, it is not important“And when its importance could not be denied, people said,“Anyway, it is not new“ William James, 1842 - 1910