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

Objective: To 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. Design: Meta-analysis. Setting: University-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; I-2 = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I-2 = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I-2 = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I-2 = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I-2 = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I-2 = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I-2 = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I-2 = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I-2 = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I-2 = 80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I-2 = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I-2 = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I-2 = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I-2 = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I-2 = 45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I-2 = 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. (C) 2016 by American Society for Reproductive Medicine.