Obstetric and perinatal outcomes in singleton pregnancies following medicated, stimulated and natural, frozen embryo transfer cycles: an updated systematic review and meta-analysis

Frozen embryo transfer (FET) has been associated with higher risks of hypertensive disorders of pregnancy (HDP), large for gestational age and high birth weight. This systematic review and meta-analysis evaluates obstetric and perinatal outcomes in medicated, stimulated and natural FET cycles. A literature search was performed using MEDLINE, EMBASE, CINAHL and the Cochrane Library database; 152,590 FET cycles were analysed from 31 included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated using fixed and random effects models determined by the heterogeneity (I²). There was significantly higher risk of obstetric and perinatal complications, including HDP (RR 1.84, CI:1.48-2.29, I² 87%) and low birth weight (LBW) (RR 1.25, CI:1.12-1.39, I² 57%) following medicated compared to natural FET cycles. A higher risk of HDP (RR 1.50, CI:1.33-1.64, I² 32%) and macrosomia (RR 1.28, CI:1.17-1.40, I² 37%) was noted following medicated compared to stimulated cycles. Natural demonstrated lower risk of HDP (RR 0.77, CI:0.60-0.99, I² 32%), gestational diabetes (RR 0.78, CI:0.68-0.89, I² 43%), LBW (RR 0.78, CI:0.64-0.95, I² 48%) and small for gestational age (RR 0.83, CI:0.70-0.98, I² 12%) than stimulated cycles. These findings indicate that medicated FET cycles convey greater risks of obstetric and perinatal complications than natural or stimulated cycles.