A new mNC protocol that allows a 7-day window for FET planning

Abstract Study question Is triggering necessary at 17 mm follicle diameter in a modified natural cycle (mNC), or does it allow flexible planning? Summary answer Embryo transfer can be scheduled when follicles measure 13 to 20 mm if endometrium is ready without impacting clinical outcome. What is known already Current practice is shifting, moving frozen embryo transfers (FET) from artificial cycles to natural cycles, which may complicate planning. The standard mean diameter to trigger in a mNC has classically been stablished in 17 mm, mimicking the size needed to obtain mature oocytes. Interestingly, research on triggering at different follicle sizes in a mNC has been limited. A previous study initiated progesterone based only on endometrial ultrasonographic characteristics and the presence of a dominant follicle of at least 12 mm and showed good results in ongoing pregnancy rates. However, it had a small sample size and rhCG was not administered. Study design, size, duration This is a multicenter, retrospective, observational study of 3,087 single frozen blastocyst transfers in mNCs carried out in 2,764 patients at our centers from January 2020 to September 2022. Participants/materials, setting, methods Selection criteria were the following: blastocyst on day 5/6 (minimum quality 3BB attending Gardner classification), regular menstrual cycles (26-35 days), normal uterine cavity assessed by ultrasound, serum progesterone <1.5 ng/mL and endometrial thickness ≥7 mm on the day of administration of rhCG, and absence of fluid in endometrial cavity. Triggering was done with a single dose of 250 µg sc rhCG, natural micronized progesterone 200mg bid was started two days later, then SET was performed. Main results and the role of chance Follicle size at time of triggering was stratified into three groups (13.0–15.9 mm; 16.0–18.9 mm; and ≥19.0 mm). No differences were seen regarding age, body mass index (BMI) and years of infertility, however, there were differences regarding egg donation (39.5%; 27.9%; and 27.4% respectively; p = 0.02) and the use of Preimplantational Genetic Testing for Aneuploidies (PGT-A) (19.4%; 34.01%; and 37.3%; p < 0.01). We found no differences in pregnancy rate (64.5%; 60.2%; and 57.4%; p = 0.19), clinical pregnancy rate (60.5%; 52.8%; and 50.6%; p = 0.10), implantation rate (62.10%; 52.9%; and 51.0%; p = 0.05) and miscarriage rate (15.0%; 22.2%; and 25.0%; p = 0.11), but differences were found in the ongoing pregnancy rate (OPR) (54.9%; 46.8%; and 43.1%; p = 0.02). however, those differences were not seen after adjusting for the use of PGT-A and egg donation: OPR at 16.0–18.9 mm vs 13.0–15.9 mm (aOR 2.37; 95% CI: 0.73–7.60; p = 0.15) and at 16.0–18.9 mm vs > 19mm (aOR 0.75; 95% CI: 0.54–1.05; p = 0.10). Finally, OPR was assessed by follicle size by each millimeter from 13 mm (80,0%; 95% CI 29.9—99.0%) to 22 mm (54.6%; 95% CI 39.0—69.3%). Limitations, reasons for caution Follicle size at time of triggering 15 to 19 mm accounted for 84.7% of the mNCs included in this study, which leaves only a minority of cases in which triggering was done at “non conventional” follicle sizes. This results need to be confirmed by future prospective studies. Wider implications of the findings Our findings show that rhCG could be administrated from a follicle size of 13 to 22mm. Considering a follicular growth rate of 1-1.5mm per day, this approach could allow a flexibility of five to seven days, facilitating the planning of mNC FET in clinical practice. Trial registration number Not applicable