1 Volvat Medical Center, Oslo, Norway, 2 Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, S-416 85 Göteborg, Sweden, 3 Department of Obstetrics and Gynecology, Karolinska Institutet, Huddinge Hospital, Stockholm, 4 Department of Obstetrics and Gynecology, Västerås Hospital, and 5 Department of Obstetrics and Gynecology, Linköping University Hospital, Linköping, Sweden
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Abstract |
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Key words: assisted reproductive technologies/IVF/multiple pregnancies
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Introduction |
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In IVF, the usual practice of transferring two or more embryos to achieve higher pregnancy rates results in a high incidence of multiple births. In the World Collaborative Report on IVF figures for 1995 showed that 24.7% of the pregnancies were twin, 4.1% were triplet and 0.2% were quadruplet (De Mouzon and Lancaster, 1997). Consequently, 4445% of the newborns were born as multiple birth babies.
Multiple pregnancy carries additional risks for both mother and offspring and more elaborate monitoring of the pregnancy is required. Obstetric complications associated with multiple pregnancy include prenatal screening problems, an increased incidence of pre-eclampsia and eclampsia, antepartum haemorrhage, preterm labour, intrauterine growth retardation and surgical and assisted delivery. Among neonatal complications the most common are low birth weight, due to prematurity and/or placental dysfunction and congenital malformations. The perinatal mortality is 56 times higher among twins compared with singletons.
The Swedish registry study showed a 20-fold increased risk of being born as a multiple birth baby for an IVF child compared with the general population (Bergh et al, 1999a). The pregnancy and neonatal complications observed in IVF pregnancies were almost entirely due to multiple pregnancies, the majority of which were twin pregnancies. The rate of prematurity (<37 weeks) among twin pregnancies was 47.3% compared with 11.2% among singletons. The corresponding figures for low birth weight were 43.8 and 8.9% respectively.
In the Swedish study, children born after IVF had an increased risk of malformations, relative risk 1.39 (95% confidence intervals, 1.251.54) compared with the general population. This increase could at least partly be explained by the much higher proportion of multiple birth babies in the IVF group. An increased incidence of anencephaly, hydrocephalus and atresia of the oesophagus was found. Ten infants (0.2%) in the IVF had neural tube defects (anencephaly or spina bifida) compared with the expected number of three to four. Seven of the 10 infants with neural tube defects and six out of seven children with hydrocephalus were from sets of twins.
Multiple pregnancies are also associated with increased infant and childhood morbidity such as cerebral palsy and mental retardation. Two recent studies of the incidence of cerebral palsy reported dramatically increased risks in multiple births: twins had risks approximately five times higher and triplets 17 times higher than in singletons (Peterson et al., 1993) and the risk of producing at least one child with cerebral palsy was estimated to 15% for twin, 8% for triplet and almost 50% for quadruplet pregnancies (Yokohama et al., 1995). Lower gestational age, lower birth weight distribution and being a twin all independently increased the risk of cerebral palsy in twin pregnancies (Pharoah and Cooke, 1996
; Williams et al., 1996
).
Most studies of child development after IVF carried out to date include relatively small numbers of children and have a limited period of follow-up and consequently the risks for long term handicap, e.g. cerebral palsy and mental retardation for children born after IVF compared with the general population have so far not been possible to evaluate. In an ongoing Swedish follow-up study of the national IVF birth cohort (n = 5856 children) from 19821995, childhood morbidity, i.e. cerebral palsy, mental retardation, severe neurological and visual impairment, will be analysed and compared with data in a control group from the general population.
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Which methods are available today to reduce the number of multiple births after ART? |
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Embryo/fetal reduction, as a third strategy to reduce the number of multiple births have been used worldwide. Despite that collaborative data (Evans et al., 1996) have reported satisfactory outcome for the children and limited risks for the mother this kind of intervention raises serious ethical and psychological problems (Schreiner-Engel et al., 1995
; Bergh et al., 1999b
). It may be indicated in cases of particularly high order multiple pregnancies but can never be justified as a method for reduction of twins.
A fourth strategy to reduce multiple births is the adoption by ART clinics of a new measure for success, `birth per embryo transferred'. The most common statistics used by ART units to indicate success and excellence both with regard to research or for the sake of prestige, unfortunately all promote the replacement of a high number of embryos. Pregnancy rate per treatment cycle, per aspiration or per replacement cycle, are all increased by increasing the number of embryos replaced. The same applies for `baby take home rate' and `number of babies born'. Unfortunately, the result is obtained at the expense of the increased fetal morbidity associated with high order multiple pregnancy.
`Birth per embryo transferred' is a statistical criterion that promotes a policy aiming at singleton pregnancies; it is negatively affected by the incidence of multiple pregnancies since results are best when a low number of embryos are transferred. A disadvantage of this statistic is that its significance is not yet understood by patients, patient organizations, politicians and clinicians. Clinics like to use statistics that indicate high success rates, such as pregnancy rate or number of babies born. `Birth per embryo transferred' appears at first sight to lower success rates, but actually reflects the chance of getting a healthy baby. High figures mean a high incidence of singleton pregnancies. To the couple with infertility problems results may easily be explained as the probability that they will become parents. ART results in Sweden, described in this manner, are shown in Figure 1. In ART units results are affected by the allocation of individual patients to optimal treatment, aiming at a singleton pregnancy. This is the reason for the declining number of embryos transferred. One explanation for the increasing births/embryo transferred may be a better selection of high quality embryos.
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Conclusions |
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Acknowledgments |
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Notes |
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This debate was previously published on Webtrack, March 1, 2000
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References |
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