Perinatal Complications and Live-birth Outcomes following Assisted Reproductive Technology: A Retrospective Cohort Study
Assisted reproductive technology (ART) has become a widely used method for treating infertility since the birth of Louise Brown in 1978. With millions of babies born worldwide through ART, concerns about its safety and potential adverse outcomes have grown. This retrospective cohort study aimed to explore the associations between ART and pregnancy/perinatal complications, as well as neonatal outcomes, compared to spontaneous conception. The study was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, between January 2013 and December 2015, involving 2256 ART-derived pregnancies and 6768 matched spontaneous pregnancies.
The study divided the ART group into in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) subgroups based on fertilization modes, and into fresh embryo transfer (ET) and frozen embryo transfer (FET) subgroups based on embryo transfer methods. The primary outcomes measured were pregnancy complications, perinatal complications, and neonatal outcomes. The data were analyzed using univariate analysis and multivariate logistic regression, adjusting for maternal age, gravidity, parity, maternal education, smoking, alcohol consumption, and body mass index (BMI).
The results indicated that pregnancies conceived by ART were associated with a significantly increased incidence of gestational diabetes mellitus (GDM; OR 1.88, 95% CI 1.56–2.27), gestational hypertension (OR 2.18, 95% CI 1.83–2.60), and intrahepatic cholestasis of pregnancy (ICP) (OR 2.79, 95% CI 2.15–3.64) compared to spontaneous conception. These associations were similar for singleton pregnancies. In twin pregnancies, only the incidence of ICP was significantly higher than in controls.
Perinatal complications, including placental abruption (OR 2.14, 95% CI 1.33–3.45), premature rupture of membranes (PROM; OR 1.24, 95% CI 1.06–1.45), postpartum hemorrhage (OR 2.89, 95% CI 2.33–3.59), and polyhydramnios (OR 2.01, 95% CI 1.29–3.16), were more likely to occur in ART pregnancies. The singleton group had similar results for placental abruption but not for PROM and polyhydramnios. There were no significant differences in the incidence of these perinatal complications in the twin group.
Neonatal outcomes, including preterm labor (OR 4.29, 95% CI 3.84–4.80) and low birth weight (OR 1.72, 95% CI 1.42–2.08), were more likely to occur in singleton births after ART. However, there were no significant differences for these outcomes in twin pregnancies. Perinatal complications and neonatal outcomes were consistent between the IVF and ICSI subgroups. The FET and ET subgroups showed a similar increase in complications, except for the incidence of placental abruption.
The study also stratified the analysis by nulliparous and multiparous women, maternal age, and different ART methods. Nulliparous women in the ART group had higher incidences of gestational hypertension, GDM, ICP, placental abruption, postpartum hemorrhage, and polyhydramnios compared to the control group. Multiparous women in the ART group had significantly increased incidences of gestational hypertension and complete placenta previa.
When stratified by maternal age, women younger than 35 years in the ART group had higher incidences of gestational hypertension, GDM, ICP, and postpartum hemorrhage. Women aged 35 years and older in the ART group also had increased risks of these complications. Neonatal outcomes, including preterm labor and low birth weight, were significantly higher in the ART group for both age groups.
The study compared the incidences of pregnancy and perinatal complications, and neonatal outcomes related to different types of ART, including IVF and ICSI. IVF pregnancies were more likely to suffer from gestational hypertension, GDM, ICP, placental abruption, PROM, postpartum hemorrhage, polyhydramnios, preterm labor, and low birth weight compared to spontaneous pregnancies. ICSI pregnancies showed similar increased incidences of these complications, except for PROM, which was significantly higher in the IVF group.
The study also considered different embryo transfer methods, including FET and ET. Both FET and ET subgroups showed significantly increased incidences of gestational hypertension, GDM, ICP, PROM, postpartum hemorrhage, polyhydramnios, preterm labor, and low birth weight compared to the control group. The only insignificant difference between the FET and ET groups was placental abruption, which was significantly lower in the FET group.
The study concluded that ART pregnancies are associated with increased risks of perinatal complications and poor neonatal outcomes, such as GDM, hypertension during pregnancy, ICP, placental abruption, PROM, postpartum hemorrhage, polyhydramnios, premature delivery, and low birth weight. Multiple pregnancies partly explain these adverse outcomes, and elective single embryo transfer (SET) should be promoted to reduce the risks. Infertility factors in women requiring ART procedures also contribute to adverse obstetric and perinatal outcomes. Further studies are needed to explore how the cause of sterility affects the pregnancy outcome of ART.
The study had several limitations, including its retrospective design, single-center data extraction, and lack of data on the cause of infertility and baseline endocrine levels. Future research should consider multi-center, prospective studies with larger sample sizes and include data on intrauterine insemination (IUI) outcomes.
In summary, women who conceive through ART have an increased risk for adverse obstetric and perinatal outcomes. Multiple pregnancies and underlying infertility factors contribute to these risks. Promoting elective single embryo transfer and further research on the impact of infertility causes on ART pregnancy outcomes are essential for improving maternal and neonatal health.
doi.org/10.1097/CM9.0000000000000484
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