Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies

ObjectiveTo determine whether there are any increases in pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies after assisted reproductive technology (ART) compared with those conceived naturally.DesignMeta-analysis.SettingUniversity-affiliated teaching hospital.Patient(s)Singleton pregnancies conceived with ART and naturally.Intervention(s)PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through March 2015 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Main Outcome Measure(s)Pregnancy-related complications and adverse pregnancy outcomes.Result(s)Fifty cohort studies comprising 161,370 ART and 2,280,241 spontaneously conceived singleton pregnancies were identified. The ART singleton pregnancies had a significantly increased risk of pregnancy-induced hypertension (relative risk [RR] 1.30, 95% confidence interval [CI] 1.04-1.62; I2 = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I2 = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I2 = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I2 = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I2 = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I2 = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I2 = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I2 = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I2 = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I2=80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I2 = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I2 = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I2 = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I2 = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I2=45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I2=41%). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed.Conclusion(s)The ART singleton pregnancies are associated with higher risks of adverse obstetric outcomes. Obstetricians should manage these pregnancies as high risk.