Selective reduction and termination of multiple pregnancies
Introduction
The incidence of multiple births in the developed world has increased substantially in recent decades with a doubling of twin and trebling of triplet births.1 Although the incidence of spontaneous multiple pregnancies has risen slightly,2 the overall rise in multiple births is primarily due to the increase in assisted reproduction techniques (ART). Bergh et al.3 attributed a third of the increase in multiple pregnancies in Sweden to in-vitro fertilisation (IVF), a third to ovulation induction and a third to maternal age. The latest clinic outcome data published by the Human Fertilisation and Embryology Authority (HFEA) website shows that although there had been a significant fall in the incidence of triplets from ART in 2001 the incidence of twins has remained stable over the last decade with 23–26% of all IVF pregnancies being a twin pregnancy. The data also show that the triplet pregnancy rate has not fallen further since 2002 and, although the twin pregnancy rate has remained stable, the number of patients having IVF has continued to rise and therefore the actual number of twins has increased progressively over the last decade.
The initial reduction in triplets and high order multiple pregnancies was largely due to the HFEA Code of Practice (2001), which restricted the number of embryos transferred at IVF/intracytoplasmic sperm injection (ICSI) cycle to two unless there are exceptional circumstances, which was further revised in 2004 to limiting embryo transfer to a maximum of two in women aged <40 years under any circumstance. However, the effect of this reduction has been eroded by the more recent phenomenon of ‘fertility tourism’, i.e. patients travelling abroad to have IVF treatment, which is often cheaper with donor eggs being more readily available, and then returning to the UK for their antenatal care. Often the countries where these IVF cycles are performed do not have the same regulatory restrictions on embryo transfers as the UK and hence the risk of high order multiple pregnancies is high. Many units in the UK are reporting 25% or more of triplet pregnancies seen in their units being conceived by IVF abroad.4
Many parents and physicians underestimate the negative consequences of multiple pregnancies. A triplet pregnancy has a 9.7% chance of perinatal mortality5 and a 7–8% chance of one or more of the triplets developing cerebral palsy.6 There are further significant adverse obstetric, neonatal, financial, emotional and social consequences of multiple pregnancies.7 Although triplet pregnancies are increasingly acknowledged as a failing of ART, most iatrogenic morbidity and mortality nevertheless results from twin pregnancies.
Prevention of higher order multiple pregnancies has to be the primary objective. Approaches such as ultrasound monitoring of ovulation induction and superovulation–intrauterine insemination cycles with cancellation or transfer to IVF, if excessive ovulation is predicted, and the restrictions on embryo transfer in IVF and ICSI cycles have been shown to reduce markedly the high order multiple birth rate without significantly reducing the pregnancy rate. Nonetheless, the most effective policy in terms of reducing the number of twins conceived from IVF treatment appears to be single embryo transfer. In 2006 the Braude report,8 commissioned by the HFEA, recommended that the only safe way to reduce the risk for IVF babies was to move towards transferring one embryo in those women with the best chance of IVF success.
Therefore, management of high order multiple pregnancies is now a common problem for all obstetricians in their day-to-day practice. Hence given the significant maternal and perinatal risks, once a high order multiple pregnancy has occurred or indeed a discordant, severe fetal anomaly has been diagnosed in a fetus of a multiple pregnancy, then the option of multifetal pregnancy reduction or selective fetal termination needs to be considered.
Section snippets
Multifetal pregnancy reduction (MFPR)
MFPR has been used over the last 20–25 years to reduce high order multiple pregnancies in the late first trimester, usually to twins, with the perinatal outcome of reduced twins approaching, but never quite ever reaching, that of spontaneous twins.9, 10 A finishing number of two has become standard practice, as the perinatal outcome of twin pregnancies is considered acceptable and as two fetuses still leaves an option of selective feticide if discordant fetal abnormalities manifest later on
Reduction to singleton
A number of studies have reported on the outcomes of triplet and higher order pregnancies reduced to singleton. An earlier report by Papageorghiou et al.32 suggested that in a series of 22 trichorionic triplets reduced to a singleton the risk of miscarriage <24 weeks (13.6%) was higher than trichorionic triplets reduced to twins (8.3%) or indeed expectantly managed triplets, although this did not reach significance. However, the risk of preterm delivery was lower when reduced to a singleton
Selective feticide for fetal anomaly
Selective termination for fetal anomalies, whether chromosomal or structural, differs from MFPR in terms of the usually later gestation in which anomalies are detected. Most karyotypic anomalies in multiple pregnancies are diagnosed following NT screening at 11–13 weeks or detailed anomaly scan at 20–22 weeks. Evens et al.34 published the largest series on selective termination in multiple pregnancies for structural or chromosomal anomalies. They reported that the miscarriage rate <24 weeks was
Selective feticide/MFPR in monochorionic pregnancies
Single intrauterine death (sIUD) of a fetus in a monochorionic multiple pregnancy has profound consequences for the surviving twin, including a 30–50% risk of death or neurological damage.35, 36, 37 Severe neurological injury was reported to be between 18% and 24% of monochorionic sIUD survivors.36, 37 The mechanism for brain damage in the co-twin is most likely to be due to massive blood loss from the survivor into the low pressure circulation of the dying/dead twin through vascular
Summary
The substantial increase in higher order multiple pregnancies as a result of ART has necessitated the development of MFPR as a mechanism of improving perinatal outcome. It is now certain that in pregnancies with starting numbers of >3, MFPR to twins significantly improves outcome. The question of MFPR in triplets remains somewhat contentious. It is apparent that expectant management of trichorionic triplets has improved significantly in the last two decades and now has reasonably good outcomes.
Conflict of interest statement
None declared.
Funding sources
None.
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2022, Fertility and SterilityCitation Excerpt :Consequently, a systematic review concluded that the data are insufficient to recommend a general policy of MFPR for women with a high-order multiple pregnancy (120). Nevertheless, several analyses have shown that MFPR does appear to benefit quadruplet and higher-order pregnancies wherein the procedure clearly prolongs the length of gestation for the remaining fetuses (109, 110, 120). Moreover, the results of one meta-analysis of 11 nonrandomized studies of triplet pregnancies of varying quality (109) showed that the pregnancy loss rate at <24 weeks was similar in triplet pregnancies reduced to twins and in unreduced triplets (7% vs. 7.4%; OR 0.95, 95% CI 0.66–1.4).
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2022, European Journal of Obstetrics and Gynecology and Reproductive BiologyCitation Excerpt :The risk of miscarriage following MFPR in triplets has always been a controversial issue. An earlier review of Papageorghiou et al. reported that the risk of miscarriage increased ∼2-fold following MFPR [6] but newer studies [7–9] reported similar risks of miscarriage for MFPR and expectant management in trichorionic triamniotic pregnancies. In the most recent metaanalysis about MFPR, Anthoulakis et al. reported that MFPR did not statistically significantly change miscarriage rate [10].
Comparisons between two methods of multifetal pregnancy reduction in women with a dichorionic triamniotic triplet pregnancy
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