Maternal and Neonatal Complications After Natural vs. Hormone Replacement Therapy Cycle Regimen for Frozen Single Blastocyst Transfer

Objective: To evaluate the maternal and neonatal complications after frozen-thawed blastocyst transfer cycles utilizing different endometrial preparation regimens. Design: This is a retrospective cohort study and a secondary analysis of a multicenter, randomized, controlled trial comparing live birth rate after fresh vs. frozen single blastocyst transfer (Frefro-blastocyst). Setting: Reproductive medicine centers. Patient(s): A total of 800 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilization after frozen-thawed single blastocyst transfer. Intervention(s): Endometrium preparation was performed with a natural cycle regimen or hormone replacement therapy (HRT) cycle regimen, at the discretion of local investigators. All pregnancies were followed up until delivery. Main Outcome Measure(s): Maternal and neonatal complications. Result(s): 513 infertile patients who underwent natural cycles regimen and 287 who underwent HRT cycles regimen were analyzed. The incidences of maternal and neonatal complications were comparable between the natural cycle and HRT cycle regimen. Regarding the risk of gestational diabetes, gestational hypertension, pre-eclampsia, preterm delivery, small for gestational age and large for gestational age, the HRT cycle was still not a significant risk factor after adjusting for potential confounders. The natural cycle regimen yielded an insignificant higher total live birth rate [59.45 vs. 50.17%, P = 0.001, adjusted odds ratio (AOR) 1.366, 95% confidence interval (CI) 0.975-1.913], clinical pregnancy rate (68.23 vs. 58.89%, P = 0.008, AOR 1.406, 95% CI 0.992-1.991) and ongoing pregnancy rate (62.18 vs. 52.61%, P = 0.008, AOR 1.387, 95% CI 0.988-1.948) than did the HRT cycle regimen. However, compared to natural cycles, HRT cycles were associated with a significantly higher risk of biochemical miscarriage (6.86 vs. 18.18%, P < 0.001, AOR 0.328, 95% CI, 0.176-0.611). Conclusion(s): The incidence of maternal and neonatal complications in natural cycle and HRT cycle regimens after frozen single blastocyst transfer were comparable. Frozen-thawed single blastocyst transfer in a natural cycle was associated with lower biomedical miscarriage than the use of the HRT cycle. Clinical Trial Registration Number: Frefro-blastocyst was registered at Chinese Clinical Trial Registry, ChiCTR-IOR-14005405.