P-780 Longer follicular phase, more ultrasound scans, and higher cycle cancellation rate in immediate versus postponed modified natural cycle (mNC) FET

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Abstract Study question Do ovarian morphology and length of the follicular phase differ between immediate and postponed mNC-FET, and what are the clinical consequences hereof? Summary answer In immediate NC-FET, more cystic intraovarian structures were present, the follicular phase was longer, and the cycle cancellation rate was higher compared to postponed NC-FET. What is known already The timing of FET cycles after ovarian stimulation (OS) and oocyte pick-up (OPU) is still debated. In artificial cycle (AC) FET, studies suggest that FET in the cycle immediately following OS and OPU yields similar or even better reproductive outcomes compared to postponed FET cycles performed in the second or a subsequent cycle following OS and OPU. Concerns about the residual effects of OS on the subsequent natural cycle, have prompted clinicians to postpone NC-FET by at least one month. However, data on immediate NC-FET regarding cycle characteristics and reproductive outcomes are lacking. Study design, size, duration Data from this study is based on 324 women from an ongoing multicenter RCT investigating the optimal timing of mNC-FET. Patients were randomized in a 1:1 ratio to either an immediate mNC-FET following OS and OPU or a postponed mNC-FET with at least one month between treatments. Patients were included between April 2021 and June 2024 from six public fertility clinics in Denmark. Participants/materials, setting, methods Women aged 18-40 years, with a regular menstrual cycle, undergoing an autologous elective single blastocyst transfer in a mNC-FET after either a failed fresh transfer or a freeze-all cycle. Cystic ovarian structures > 10 mm were noted at the beginning of the treatment cycle and on the day of ovulation trigger. Serum progesterone, LH, FSH and estradiol were measured on the same timepoints. Main results and the role of chance In immediate FET, the time to ovulation trigger was longer compared to the postponed FET (mean (SD), 14.9 (3.8) vs. 12.9 (3.2) days; p < 0.001). Due to the longer follicular phase more follicular scans were needed in the immediate group (median (IQR), 3 (2–3) vs. 2 (1–3); p < 0.001). Finally, the cycle cancellation rate was higher in the immediate vs. postponed cycles (10.5% vs. 3.9%; p = 0.016). On cycle day 2-5 of the treatment cycle, more intraovarian cystic structures > 10 mm were observed in the immediate compared to postponed group (median (IQR), 3 (1-6) vs. 0 (0-1); p <0.001). These changes regressed to some extent at time of ovulation trigger but still differed significantly (median (IQR), 1 (0-2) vs. 0 (0-1); p <0.001). On cycle day 2-5, the plasma progesterone levels were higher (median (IQR), 1.0 (0.7-1.6) vs. 0.8 (0.6-1.4) nmol/L; p = 0.002) and plasma LH levels were lower (median (IQR), 4.2 (2.9–6.1) vs. 6.0 (4.9–7.7) IU/L; p < 0.001) in immediate vs. postponed cycles. Limitations, reasons for caution Power calculations has not been made on the reported endpoints prior to study initiation. How the results impact reproductive outcomes is yet to be discovered. Wider implications of the findings The findings contribute to the understanding of an immediate natural cycle following OS and OPU. Given the increased need for ultrasound scans and higher cycle cancellations, the clinical feasibility of immediate FET in natural cycles can be questioned. Trial registration number Yes

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