The effects of natural versus programmed frozen embryo transfer cycles on placental histopathology

Determine if type of endometrial preparation protocol for frozen embryo transfer (FET), whether natural cycle (NC) or programmed with hormone replacement therapy (HRT), affects placental histopathology.

Retrospective cohort study of 375 live singleton births following in vitro fertilization-FET with autologous oocytes between 2009 and 2017 in one academic hospital. Placental histopathology of pregnancies resulting from HRT-FET were compared with those resulting from NC-FET. Placental findings were categorized according to the Amsterdam Placental Workshop Group Consensus and included anatomic, inflammatory, maturation and vascular disorders. Multivariate logistic regression adjusted for confounders potentially associated with the placental pathologies examined.

331 cases in the HRT-FET group were compared to 44 cases in the NC-FET group. Other than gravidity and parity, which were higher in the NC-FET group, patient demographics, infertility etiology and cycle course were comparable between groups. After adjustment, rates of anatomic, inflammatory, maturation and vascular placental disorders were similar between groups.

Pregnancies resulting from HRT-FET do not show significant differences in placental histopathology compared to pregnancies resulting from NC-FET. This study ultimately reassures clinicians and patients about the relative safety of various FET preparation protocols in regard to most placental pathologies. This conclusion and its clinical significance merit further study.