Perinatal outcomes in pregnancies conceived by fresh or frozen embryo transfer: a systematic review

Introduction: The use of Assisted Reproductive Technology (ART) has increased in the last two decades and continuous surveillance is needed. This systematic review aims to assess the risk of specific adverse neonatal outcomes (preterm birth [PTB], low birth weight [LBW], small-for-gestational-age [SGA] and large for gestational-age [LGA]), in singleton pregnancies using fresh or frozen embryo transfer compared to spontaneous conceptions.

Methods: Cohort studies were identified from MEDLINE, Embase, Cochrane Library (search up to January 2019). The inclusion criteria were women who became pregnant using in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI), fresh or frozen embryo transfer, singleton births, and spontaneous conceptions as a control group. Meta-analyses were performed to estimate Odds ratios (OR) using random-effects model in RevMan 5.3. Heterogeneity (I 2 > 50%) was considered high.

Results: A total of 3142 titles and abstracts were screened, 1135 full-text articles were assessed and 14 met the inclusion criteria. For fresh embryo transfer, the pooled ORs were: PTB 1.64 [95% CI 1.46, 1.84]; I2= 97 %; LBW 1.67 [95% CI 1.52, 1.85]; I2=94%; SGA 1.46 [95% CI 1.11, 1.92]; I2=99 %, LGA 0.88 [95% CI 0.80, 0.87]; I2= 80 %). For frozen embryo transfer, the pooled ORs were: PTB 1.39 [95% CI 1.34, 1.44]; I2= 0 %; LBW 1.38 [95% CI 0.91, 2.09]; I2=98%; SGA 0.83 [95% CI 0.57, 1.19]; I2= 0 %, LGA 1.57 [95% CI 1.48, 1.68]; I2= 22%). Sensitivity analyses revealed no significant changes in results.

Conclusion: When compared with spontaneous pregnancies, fresh, but not frozen embryo transfer was associated with LBW and SGA. Both, fresh or frozen embryo transfer were associated with PTB. Frozen embryo transfer was uniquely associated with LGA. Despite improvements in ART protocols in relation to pregnancy rates, attention is needed towards mitigating adverse neonatal outcomes in these pregnancies.