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.