The impact of assisted reproductive technology treatments on maternal and offspring outcomes in singleton pregnancies: a review of systematic reviews

Objective: Assisted reproductive technology (ART) treatments are commonly used to aid conception in subfertile couples. This study aimed to evaluate the risks of adverse maternal and offspring outcomes in singleton pregnancy conceived with different ART treatments and techniques. Evidence Review: We searched MEDLINE, Embase, CENTRAL, and HTA until December 2020 for all systematic reviews evaluating adverse outcomes in pregnancies conceived with various ART techniques, autologous or donor gametes, and embryo development stages. We assessed review quality using the AMSTAR 2 tool risk ratio (RR) or odds ratio (OR) with 95% confidence intervals (CIs) from the top quality reviews for each of the outcomes of interest across the identified ART treatments and population subgroups. Results: We included 24 systematic reviews, which mostly reported on observational studies. Compared with spontaneous conception, ART pregnancies had a higher risk of placenta previa (RR, 3.71; 95% CI, 2.67-5.16), antepartum hemorrhage (RR, 2.11; 95% CI, 1.86-2.38), preterm birth (PTB) (RR, 1.71; 95% CI, 1.59-1.83), very preterm birth (RR, 2.12; 95% CI, 1.73-2.59), small for gestational age (SGA) (RR, 1.35; 95% CI, 1.20-1.52), low birth weight (LBW) (RR, 1.61; 95% CI, 1.49-1.75), and very low birth weight (VLBW) (RR, 2.12; 95% CI, 1.84-2.43). Frozen vs. fresh embryo transfer was associated with a lower risk of PTB (RR, 0.90; 95% CI, 0.84-0.97), SGA (RR, 0.61; 95% CI, 0.56-0.67), LBW (RR, 0.72; 95% CI, 0.67-0.77), and VLBW (RR, 0.76; 95% CI, 0.69-0.82). Embryo transfer at blastocyst vs. cleavage showed a higher risk of PTB (RR, 1.10; 95% CI, 1.01-1.20) and large for gestational age (RR, 1.12; 95% CI, 1.03-1.21) with a lower risk of SGA (RR, 0.84; 95% CI, 0.76-0.92). Using donor vs. autologous oocytes increased the odds of PTB (OR, 1.57; 95% CI, 1.33-1.86), LBW (OR, 1.94; 95% CI, 1.10-3.41), and VLBW (OR, 1.37; 95% CI, 1.22-1.54) as well as maternal complications, including postpartum hemorrhage (OR, 1.96; 95% CI, 1.20-3.20), gestational diabetes (OR, 1.27; 95% CI, 1.03-1.56), hypertensive disorders of pregnancy (OR, 2.63; 95% CI, 2.17-3.18), and cesarean section (OR, 2.28; 95% CI, 2.14-2.42). Conclusions: Assisted reproductive technology treatments are associated with increased risks of adverse maternal and offspring outcomes, especially with donor oocytes. The characteristics of ART treatment should be incorporated into prenatal care planning to mitigate those risks. PROSPERO Registration: CRD42020182612, registered March 9, 2020. (c) 2021 by American Society for Reproductive Medicine.)