Neonatal outcomes in singleton pregnancies conceived by fresh or frozen embryo transfer compared to spontaneous conceptions: a systematic review and meta-analysis

Purpose The use of assisted reproductive technology (ART) has increased in the last 2 decades and continuous surveillance is needed. This systematic review aims to assess the risk of adverse neonatal outcomes (preterm birth [PTB], low birth weight [LBW], small-for-gestationalage [SGA] and large for gestational-age [LGA]), in singleton pregnancies conceived by fresh or frozen embryo transfer (FET) compared to spontaneous conceptions. Methods Cohort studies were identified from MEDLINE, Embase, Cochrane Library (January 2019), and manual search. Meta-analyses were performed to estimate odds ratios (OR) using random effects models in RevMan 5.3 and I-squared (I-2) test > 50% was considered as high heterogeneity. Results After 3142 titles and abstracts were screened, 1180 full-text articles were assessed, and 14 were eligible. For fresh embryo transfer, the pooled ORs were PTB 1.64 (95% CI 1.46, 1.84); I-2 = 97%; LBW 1.67 (95% CI 1.52, 1.85); I-2 = 94%; SGA 1.46 [95% CI 1.11, 1.92]; I-2 = 99%, LGA 0.88 (95% CI 0.80, 0.87); I-2 = 80%). For frozen, the pooled ORs were PTB 1.39 (95% CI 1.34, 1.44); I-2 = 0%; LBW 1.38 (95% CI 0.91, 2.09); I-2 = 98%; SGA 0.83 (95% CI 0.57, 1.19); I-2 = 0%, LGA 1.57 (95% CI 1.48, 1.68); I-2 = 22%). Conclusions When compared with spontaneous pregnancies, fresh, but not frozen was associated with LBW and SGA. Both fresh and frozen were associated with PTB. Frozen was uniquely associated with LGA. Despite improvements in ART protocols in relation to pregnancy rates, attention is needed towards monitoring adverse neonatal outcomes in these pregnancies.