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THE OUTCOME OF ASSISTED CONCEPTION - PREGNANCIES, BIRTHS AND MALFORMATIONS Following the demonstration in the mid 1970s that some cases of infertility in humans could be effectively treated by in vitro fertilisation, the Medical Research Council working group recommended that a register of births of infants conceived by this process should be set up, so that later the health of the children could be assessed. Such a register was instituted at the London School of Hygiene and Tropical Medicine in 1983, and in the seven years that have since elapsed sufficient data have been collected by the MRC working group to allow an adequate analysis. The MRC working party has now reported on the characteristics of those children born in Great Britain as a result of assisted conception 1978-1987. All clinics in Britain which offered in vitro fertilisation (IVF) and were registered with the Voluntary Licensing Authority were asked to supply data to the register and, if the clinic agreed, the parents of all liveborn and stillborn (³ 28 weeks gestation) babies conceived by IVF were approached for permission to obtain details of the delivery and the condition of the infants at birth from their doctors. Births occurring up to the end of 1987 to women living in England, Scotland or Wales at the time of delivery were included. Also children conceived as a result of gamete intrafallopian transfer (GIFT) were also included. If an abnormality or illness was reported, additional clinical data were obtained from the paediatricians, surgeons or other doctors who cared for them. It was of course impossible to obtain a control group of children matched by place of birth, plurality, parental history of infertility, social class, etc., so comparisons were made with national statistics. The thirteen centres which participated reported 1180 deliveries resulting from IVF conceptions and 87 from GIFT conceptions in the period 1978 to 1987. These deliveries produced 1581 births, live or stillborn. Of the 1267 parents, 86% agreed to participate in the register. Unfortunately a disproportionate number of perinatal deaths or malformations occurred among the offspring of couples who did not respond or agree to participate but in these cases, although the children were not included in the register, the clinics provided anonymous statistical summaries of deaths and malformations. Data on mortality and malformations are therefore based on all 1581 babies, and on sex and plurality of birth for 1092. The characteristics of the parents were quite different from average parents in the UK. On the average these parents had been infertile for 6.3 years, 61% on account of tubal damage. Fifty-one percent had previously attempted assisted conception, and 48% had had at least one previous pregnancy though only 23% had had a liveborn child. The average age of the 1016 mothers was 33.9 years, and of the 890 fathers 36.1 years. As regards complications of pregnancy and delivery, 10% of the mothers had had an amniocentesis, 18% were admitted to hospital on account of bleeding and 16% because of hypertension. Of the deliveries only 31% were normal vaginal deliveries, 49% were by caesarean section, in 79% there were cephalic and in 15% breech presentations. The mean number of embryos transferred for the IVF deliveries was 2.9 and of ova for the GIFT deliveries 6.3. The number of IVF deliveries increased rapidly over the period, 12% before 1984, 27% in 1986 and 29% in 1987. Most of the GIFT deliveries occurred in 1987. Of the 1092 deliveries 23% were plural (19% twins, 4% triplets and higher order), multiple pregnancy being more common with GIFT (38%) than IVF (22%). There was no significant variation in sex ratio overall or by type of conception or birth plurality. As regards gestational age and birth weight, 24% of deliveries were pre-term (before 37 weeks) compared with 6% amongst all deliveries in England and Wales. For singletons 13% were pre-term, compared with 6% in England and Wales, and for twins 57% as compared with 38%. Small for date babies were common, 32% weighing less than 2500g as compared with 7% for all births in England and Wales. Seven percent weighed less than 1500g compared with 1% in the normal population. Birth weights of singletons were significantly lower than those of all singletons born in England and Wales, birth weights of twins only slightly lower. For singletons the average gestational age and birth weight diminished with the number of embryos replaced, and were lower for babies of women admitted to hospital on account of bleeding and hypertension. These diminutions were not associated with maternal age, cause of infertility, previous reproductive history, the freezing of embryos, the use of donor sperm, or the preconceptional use of hormonal drugs. Rates of stillbirths, neonatal and infant deaths were about twice the national average, and mortality increased greatly with plurality. Perinatal mortality rates increased from 11.7 per thousand in singletons, 39.7 per thousand in twins, to 79.3 per thousand in those of higher order. Infant mortality rates were respectively 10.7, 34.1 and 69.2 per thousand. The overall excess fetal and infant mortality is therefore accounted for by the high proportion of multiple births. The reason for the high frequency of pre-term delivery and low birth weight is not known. It is not due to the high proportion of induced labour, but whether assisted conception increases the risk of hypertension or bleeding during pregnancy, and so promotes it, is not clear. The number of embryos replaced may be a factor, but even when only one embryo was replaced the mean gestational age and birth weight were lower than for singletons in England and Wales. The overall perinatal and infant mortality rate, about twice the national average, was accounted for entirely by the high percentage of multiple births. The findings for congenital malformations are difficult to interpret; overall 2.2% of the births had one or more major malformations diagnosed in the first week of life, a figure comparable with that of the general population. But interpreting the findings overall is not easy. Couples who seek assisted conception are not typical of all parents. They are older, presumably have higher incomes than average, and their infertility may indicate genetic or other medical disorders. The mothers receive special treatment to induce ovulation, their pregnancies are monitored in detail, and their deliveries carefully managed. The children are examined more thoroughly than others and the data available for comparison are not ideal. The evidence suggests however that the most important determinant of the progress of pregnancy and of health of the children is the high frequency of multiple births. 1. Report of the MRC working party on children conceived by in vitro fertilisation. BMJ, 1990; 300: 1299. | ||||||