Influence of placental abnormalities and pregnancy-induced hypertension in prematurity associated with various assisted reproductive technology techniques

Objective. Assisted reproductive technology (ART)-treated women exhibit increased risk of premature delivery compared to fertile women. We evaluated whether ART treatment modalities increase prematurity and whether placental abnormalities and pregnancy-induced hypertensive (PIH) disorders mediate these risks. Method(s): This retrospective study of ART-treated and fertile deliveries (2004–2017) used an ART-cycle database linked to Massachusetts birth certificates and hospital discharges. Outcomes of late preterm birth (LPTB: 34–36 weeks gestation) and early preterm birth (EPTB: <34 weeks gestation) were compared with term deliveries (≥37 weeks gestation) in ART-treated (linked to the ART database) and fertile (no indicators of infertility or ART) deliveries. ART treatments with autologous oocyte, donor oocyte, fresh or frozen embryo transfer (FET), intracytoplasmic sperm injection (ICSI) and no-ICSI were separately compared to the fertile group. Adjusted odds ratios (AOR) were calculated with multivariable logistic regression: placental abnormalities or PIH were quantified in the pathway as mediators. Results: There were 218,320 deliveries: 204,438 fertile and 13,882 ART-treated. All treatment types increased prematurity (AOR 1.31–1.58, LPTB; AOR 1.34–1.48, EPTB). Placental abnormalities mediated in approximately 22% and 38% of the association with LPTB and EPTB, respectively. PIH mediated 25% and 33% of the association with LPTB and EPTB in FET and donor oocyte cycles, more than other treatments (<10% LPTB and <13% EPTB). Conclusions: ART-treatment and all ART modalities increased LPTB and EPTB when compared with fertile deliveries. Placental abnormalities modestly mediated associations approximately equally, while PIH was a stronger mediator in FET and donor oocyte cycles. Reasons for differences require exploration.