Abstract

Abstract Study question Is there any association between serum human chorionic gonadotropin (hCG) levels after trigger at previous fresh cycles and pregnancy outcomes of frozen-thawed embryo transfer (FET) cycles? Summary answer Low adjusted serum hCG level after hCG trigger at fresh cycles is negatively associated with clinical pregnancy rates (CPR) of hormone replacement treatment-FET (HRT-FET). What is known already: Literature showed that low serum hCG levels after the same dose of hCG trigger was associated with reduced pregnancy outcomes of the fresh cycles. However, the relationship between hCG levels after trigger at fresh cycles and pregnancy outcomes of FET cycles remains unknown. Study design, size, duration This matched retrospective study was conducted at a Reproductive Medicine Center between 2016 and 2018. Subjects performing HRT-FET cycles, whose previous fresh cycles used a bolus of hCG alone or a bolus of GnRHa combined with hCG for trigger were included. A total of 186 HRT-FET cycles with complete data was included for the final analysis. Participants/materials, setting, methods The study population was grouped into women with intramuscular injection of hCG prior to secretory transformation (hCG group, n = 93) and a comparison group (control group, n = 93) of women without hCG addition matched for patients’ age and duration of infertility. At the previous fresh cycles, serum hCG levels were measured 12 hours later after hCG trigger (defined as the “hCG+12 h” timepoint), and were adjusted for doses (defined as adjusted hCG levels). Main results and the role of chance: For patients achieving clinical pregnancy, the adjusted hCG level significantly increased (P < 0.05). Meanwhile, the ROC curve also showed a significantly predictive value of adjusted serum hCG levels at the “hCG+12 h” timepoint for CPR in HRT- FET cycles (AUC=0.626, 95%CI: 0.512–0.740) and the optimal hCG threshold proposed by ROC for CPR was 46.31 mIU/mL with sensitivity of 71.4% and specificity of 56.9%. For all patients, the CPR in hCG group was significantly higher than that in control group (61.3% vs. 44.1%). Furthermore, all cycles were then divided into four groups based on the injection of hCG prior to secretory transformation in HRT-FET cycles and this cut-off value of hCG levels at the “hCG+12 h” timepoint. For patients with adjusted hCG levels ≤46.31 mIU/mL, the CPR was significantly improved in hCG group compared with control group (61.1% vs. 29.3%). But for patients with adjusted hCG levels >46.31 mIU/mL, no statistically significant difference was observed between the hCG and control group (61.4% vs. 55.8%). Limitations, reasons for caution Although the results achieved statistically significant, the sample size was relatively small, which limits our ability to draw a definitive conclusion. The reason of the small sample size may be that to reduce the risk of OHSS, doctors would give preference to trigger with GnRH agonist in our center. Wider implications of the findings: Adjusted serum hCG levels might represent a potential factor to guide adequate support in the subsequent HRT-FET cycles. Meanwhile, for patients with low adjusted serum hCG levels, intramuscular hCG injection prior to secretory transformation may be a good compensation way to rescue pregnancy impair in the subsequent HRT-FET cycles. Trial registration number N/A.

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