1. Safety issues in assisted reproduction technology The children of assisted reproduction confront the responsible conduct of assisted reproductive technologies Obstétrique et gynécologie Faculté de médecine R D Lambert, Laval University, Québec, Canada M J Mélançon, University of Québec, Chicoutimi, Canada Unité de bioéthique Sciences humaines

5. Multiple pregnancies. Data Number of children born alive after an IVF or an ovarian stimulation in Canada and USA OS: Ovarian stimulation 27 665 (21.9%) 3 192 (≈9%) 15 411 (44%) 16 422 (46.9%) ≈ 2 094 ( ≈ 21.9%) ≥ 147 (7%) 994 (46%) 1014 (47%) Twins & + Triplets & + Twins Single-tons Twins & + Triplets & + Twins Single-tons OS IVF/ICSI: 35 025 babies OS IVF/ICSI: ≥2155 babies 126 325 9 561 USA (2000) Canada (2002)

6. Multiple pregnancies. Data Frequency of health problems in IVF babies and in the general population %: frequency among all pregnancies. 1) Stromberg et al (2002). Lancet 359:461-5. 2) Hansen et al (2002). NEJM 346(10):725-30. 3) Koivurova et al (2002). Hum Reprod 17(5):1391-8. 4) Schieve et al (2002). NEJM 346(10):731-7. 5) Olivennes et al (2002). Hum Reprod Update 8(2):117-28. 6) Calculated from Moll et al (2003). Lancet 361:309-10. Suggestive data from multiple and single pregnancies. 7) Calculated from Maher et al (2003). J Med Genet 40:62-4. Suggestive data from multiple and single pregnancies. 8) DeBaun et al (2003). Am J Hum Genet 72:156-60. Suggestive data from multiple and single pregnancies. 0.014% 0.0033% Beckwith-Wiedemann Syndrome 7,8 0.03-.04% 0.006% Retinoblastoma 6 0.39% 0.1% Child dveloppement 1 16-28% 8.9-14% Néonatal mortality 3,5 0.39-6.6% 8.9-14% Multiple birth defects 1,3 2.6-8% 0.9-1.4% Very low birth weight (<1500g) 2,3,4 13-30% 4.6-7.3% Low birth weight ( <2500g) 2,3,4 31-32% 7-7.8% Prematurity (<37) 2,3 5.3% 1.1% Prematurity (<32) 2 0.55% 0.15% Cerebral palsy 1 All IVF babies Whole population Pathology

7. Multiple pregnancies. Data Frequency of health problems in twins and triplets conceived spontaneously or through IVF %: frequency among all pregnancies. 1) Helmerhorst et al (2004). « Matched studies only. 2) Pinborg et al (2004). NEJM 346(10):725-30. 3) Nowak et al (2003). Tables I, II and IV . 0.6% 0.6% Child development 39.5% 20.8% 7.6% 10.6% 15.4% 23% 43.3% Neonatal mortality 23.5% 31.9% 5.4% 10.1% 1.2% 1.1% 5-25% 3.8-10.4% Low birth weight ( <1500g) - France - USA 28.4% 41.3% 7.8% 13.9% 1.6% 1.7% 6.8% 7.1% Prematurity (<32) - France - USA 0.4% 0.3% Cerebral palsy Triplets Twins Singletons IVF Spontaneous IVF Spontaneous IVF 3 Twins 2 Twins 1 Pathology

8. Multiple pregnancies. Data Estimation of the number of babies born with health problems from iatrogenic multiple pregnancies in 2002 in Canada %: frequency among all pregnancies. *: <1500g. 1: n=994, see slide No 4; 2: The lowest frequency as reported in the previous slide; 3: n=147, see slide No 4; 4: Nowak et al ., (2003); (): No of infants who would have been affected if the incidence had been the same as in the whole population (slide No 5) 16 13 (2) 0.6% --- --- 6 (1) 0.6% Child development 98 222 (186) 10.6% 58 (13) 39.5% 105 (88) 10.6% Neonatal mortality 173 105 (19) 5% 47 (1.3) 31.9% 50 (9) 5% Very low birth weight* 236 143 (23) 6.8% 61 (1.6) 41.3% 68 (11) 6.8% Prematurity (<32 weeks) 7 8 (3) 0.4% --- --- 4 (1.5) 0.4% Cerebral palsy Total number in excess Affected infants Selected frequen-cy 2 Affected infants Selected frequen-cy 4 Affected infants Selected frequen-cy 2 IVF + OS Twins & + OS IVF triplets 3 IVF twins 1 Pathology

9. Multiple pregnancies. Data Estimation of the number of babies born with health problems from iatrogenic multiple pregnancies in 2002 in USA %: frequency among all pregnancies. *: <1500g. 1: n=15 411, see slide No 4; 2: The lowest frequency as reported in the previous slide; 3: n=3 192, see slide No 4; 4: Nowak et al ., (2003); (): No of infants who would have been affected if the incidence had been the same as in the whole population (slide No 5) 215 166 (28) 0.6% --- --- 92 (15) 0.6% Child development 1696 2932 (2462) 10.6% 1245 (281) 39.5% 1634 (1372) 10.6% Neonatal mortality 2743 1383 (249) 5% 1005 (28) 31.9% 771 (139) 5% Very low birth weight* 3722 1881 (304) 6.8% 1302 (35) 41.3% 1048 (170) 6.8% Prematurity (<32) 1 107 111 (42) 0.4% --- --- 62 (23) 0.4% Cerebral palsy Total number in excess Affected infants Selected frequen-cy 2 Affected infants 7 Selected frequen-cy 4 Affected infants Selected frequen-cy 2 IVF + OS Twins & + OS IVF triplets 3 IVF twins 1 Pathology

21. Singleton pregnancies. Data * : % of all pregnancies; 1: Schieve et al ., 2002; 2: Strömberg et al ., 2002; 3: Hansen et al ., 2002; 4: Koivurova et al ., 2002; Poikkeus et al ., 2007 2 2 0.19 2 0.09 2 Growth retardation 2.2 2 2.3 3 0.35 2 9.5 3 0.16 2 4.2 3 Birth defects 1.8 1 2.7 3 2.8 4 1.8 5 2.6 1 3 3 2.0 4 1.1 5 1.4 1 1.1 3 0.7 4 0.6 5 VLBW 1.8 1 1.7 3 1.6 4 13.2 1 7 3 4.0 4 7.3 1 4.2 3 2.5 4 LBW 1.8 4 1.6 5 2 4 1.1 5 1.1 4 0.7 5 Prematurity ≤ 32 sem 2.2 3 1.5 4 12.5 3 8.6 4 5.8 3 5.6 4 Prematurity ≤ 37 sem 2.8 2 0.38 2 0.14 2 Cerebral palsy Risk IVF General population Incidence and risks* Health problems