Pregnancies conceived through assisted reproductive technologies (ART) now account for over 1% of all pregnancies in the UK and it is predicted that this proportion will rise further in the next decade. This is largely because women are leaving it till later in life to start a family but find that ART is required because their reproductive potential has diminished with advancing age1.
It has long been recognised that pregnancies conceived through ART have poorer maternal and perinatal outcomes than natural conceptions but debate continues as to the causal factors. The factors that predispose them to adverse outcome may be inherent to the woman (and/or the male partner), including her age at conception, the treatment regimes or to the greater incidence of multiple pregnancy compared with natural conception and this paper will review the outcomes and attempt to put these in context where the evidence exists.
Maternal outcomes
All women undergoing ART should be considered at risk of developing ovarian hyperstimulation syndrome (OHSS) which is characterised by ovarian distension, fluid shift in to the extravascular space and, in the more severe forms, significant activation of the coagulation cascade with increased risk of DVT and pulmonary embolism.
Women with polycystic ovary syndrome, younger women and those using a GnRH-agonist downregulation protocol are at greater risk and that risk is increased further in conception cycles. However, The absolute incidence of OHSS is not known and, because of effective management strategies, maternal death from cardiovascular events is extremely rare2.
In the UK the background rate of ectopic pregnancy is about 1%3 whilst in assisted conceptions it is approximately 2-3%4. Naturally conceived heterotopic pregnancy is rare (1 in 7000) but, because of multiple embryo transfer, may be as high as 1% in ART pregnancies5.
By necessity, the available data on maternal outcomes in ART are retrospective and observational but by using national databases and comparing them with naturally conceived pregnancies, informative data can be derived.
All complications of pregnancy are increased with multiple gestation and include anaemia, pre-eclampsia, polyhydramnios, preterm labour, operative delivery and post partum haemorrhage. There is a ten-fold increase in multiple births in ART compared to spontaneous pregnancies and although most of these are related to replacing more than one embryo, there is also an increased risk of monozygotic multiple pregnancies which may be related to embryo manipulation during in vitro culture6. Undoubtedly many of the maternal complications of ART are related to multiple pregnancy but even amongst singletons the maternal risks are increased.
In a large Swedish study of all women known to have had IVF between 1982 – 2001, logistic regression analysis demonstrated that they had an increased risk of bleeding in early pregnancy (odds ratio = 4.59; 95% CI: 4.08-5.15) and of ovarian torsion (OR = 10.6; CI 5.69-10.7). They were more likely to develop pre-eclampsia (OR = 1.63; 1.53-1.74), placental abruption (OR = 2.17; CI 1.74-2.72), placenta praevia (OR = 3.65; CI 3.15-4.23) and preterm, prelabour rupture of membranes (OR = 2.54; CI 2.34-2.76). Furthermore, induction of labour (OR = 1.37; CI 1.29-1.46) and caesarean sections (OR = 1.38; CI 1.32-1.43) were more frequent7. All pregnancies are “precious” but some of the increase in intervention may be attributable to an inclination by the obstetrician not to “take risks” with ART pregnancies because they are deemed to be “more precious”, whether subconsciously or otherwise, but using different datasets these findings have been confirmed by others8, 9.
Perinatal outcomes
The published data on perinatal outcomes in babies born after IVF are conflicting but most studies suggest an increased risk of adverse outcome10,11. It has been suggested that these phenomena may be brought about by the in vitro process12 as animal studies have shown that manipulation of the in vitro embryo culture conditions can influence profoundly subsequent fetal growth and development13.
Multiple gestation is associated with substantially greater perinatal morbidity and mortality because of the higher incidence of preterm labour and delivery and, undoubtedly, the greater incidence of multiple pregnancy in ART conceptions contributes to the poorer perinatal outcomes overall. However, if we consider twin pregnancies, then, compared to naturally conceived twin pregnancies, there doesn’t appear to be a difference in perinatal outcome measures such as birthweight and preterm delivery once other confounding factors such as maternal age and parity are taken in to consideration14.
On the other hand, amongst singleton ART pregnancies, outcomes appear to be poorer compared to spontaneous singleton conceptions. In a meta-analysis, singleton IVF pregnancies were at increased risk of preterm delivery less than 33 weeks’ gestation (OR = 2.99; CI 1.54-5.80), preterm delivery less than 37 weeks’ gestation (OR = 1.93; CI 1.36-2.74), very low birth weight (< 1500 g) (OR = 3.78; CI 4.29-5.75), small for gestational age (OR = 1.59; CI 1.20-2.11), and congenital malformations (OR = 1.41; CI 1.06-1.88). Most studies show a trend towards higher perinatal mortality but as this is a relatively rare event, they are too small to show a statistical effect. However, the advantage of meta-analysis in this case is that it does demonstrate a h