Pregnancy and perinatal outcomes after modified natural cycle-frozen embryo transfers according to size of the dominant follicle on the hCG trigger day.

Abstract

Study question: Is there an association between the dominant follicle size on the day of the hCG ovulation trigger and reproductive, obstetric, and perinatal outcomes in modified natural cycle-frozen embryo transfer (NC-FET) cycles in which intensive luteal phase support (LPS) was utilized?

Summary answer: The dominant follicle size on the day of triggering, ranging from above 10 to 18 mm or larger, was not associated with negative live birth or perinatal outcomes in modified NC-FETs when an intensive LPS was provided.

What is known already: There is growing evidence concerning the optimal timing for triggering final oocyte maturation during IVF ovarian stimulation cycles to obtain mature oocytes. However, a consensus on the ideal follicle size for administering hCG in modified NC-FETs has yet to be established. Interestingly, it has been suggested that the presence of a mature oocyte may not be necessary for FET.

Study design size duration: A retrospective cohort study was conducted at a university-affiliated reproductive medicine center. The study included women with regular menstrual cycles who underwent autologous modified NC-FETs between 2013 and 2023 for potential analysis.

Participants/materials setting methods: Patients were categorized into eight groups based on the size of the dominant follicle at the time of hCG administration: <12, 12-12.9, 13-13.9, 14-14.9, 15-15.9, 16-16.9, 17-17.9, and ≥18 mm. The primary outcome measured was the live birth rate (LBR), while secondary outcomes included the rates of positive pregnancy tests, implantation, clinical pregnancy, and pregnancy loss, as well as perinatal and obstetric complications. A generalized estimating equation logistic regression model was employed to account for the clustered nature of the data and to adjust for potential confounding factors. The group with a follicle size ≥18 mm was designated as the reference group in the logistic regression analyses. An intensive LPS, consisting of 400 mg dydrogesterone plus 400 mg vaginal progesterone, was adopted.

Main results and the role of chance: A total of 14 431 cycles that met the inclusion criteria were analyzed. The LBRs were similar across the eight groups. Furthermore, there were no significant differences in LBRs when the reference group was compared to the other follicle-size categories in the unadjusted models. Even after adjusting for several key confounders, the LBRs remained comparable between the study cohorts and the reference controls. Additionally, other reproductive parameters, such as rates of positive pregnancy tests, implantation, clinical pregnancy, and pregnancy loss, showed similar results between the control group and all other groups in both the unadjusted and confounder-adjusted analyses. Finally, pregnancies derived from the other follicle-size groups did not show increased risks of adverse perinatal or obstetric outcomes when compared to the reference group, both before and after adjustment for covariates.

Limitations reasons for caution: The primary limitation of the current study lies in its retrospective and single-center design. Future prospective research is needed to confirm our findings. While this represents the largest investigation to date into cycle outcomes related to follicle size at ovulation trigger in modified NC-FETs, the sample sizes in certain subgroups were relatively small, which may limit the statistical power to identify differences among some groups. Therefore, caution is advised in the interpretation of these findings. Additionally, an intensive LPS was used, potentially reducing the external validity of our findings.

Wider implications of the findings: The current data suggest that with the administration of an intensive LPS, the hCG trigger can be given across a wide range of follicle sizes, from above 10 to 18 mm or larger in diameter, in modified NC-FETs. This approach not only simplifies patient monitoring but also offers greater flexibility and autonomy in scheduling the date of embryo transfer.

Study funding/competing interests: This study was supported by the National Natural Science Foundation of China (grant no. 82171685). The authors declare that they have no competing interests.

Trial registration number: N/A.