O-069 Double vs. single stimulation in young poor prognosis patients followed by a fresh embryo transfer: a randomized controlled trial. Free

Does double stimulation, followed by a fresh ET (DUO-STIM fresh) improve outcomes as compared with a single stimulation in young poor prognosis patients?

Compared to single stimulation, DUO-STIM fresh leads to significantly higher number of good quality embryos, without hindering fresh embryo transfer outcomes.

Dual Stimulation (ovarian stimulation both in the follicular and luteal phase of the same cycle) is an innovative strategy to retrieve higher number of oocytes in a shorter time frame, thus it is particularly appealing for poor ovarian responders. Three current limitations of Dual-Stimulation are: (1) it is unclear whether outcomes of the second (luteal) wave results from the second stimulation, or a carry-over effect from previous follicular stimulation; (2) the desynchronization between endometrium and ovaries and, (3) lack of robust evidence. No previous studies explored Dual Stimulation starting from the luteal phase, and with a fresh embryo transfer (DUOSTIM-fresh).

This study is a prospective, randomized, controlled, single-center, superiority clinical trial comparing two different ovarian stimulation protocols: a double stimulation cycle vs. a single stimulation cycle followed by fresh ET. The primary outcome was the number of good quality embryos obtained, while secondary outcomes included results from fresh embryo transfer (clinical pregnancy, miscarriage). A total of 120 women were enrolled in this study between October 2020 and October 2022, with a 1:1allocation.

Only young (<40 years old) poor-prognosis (AMH<1.2 ng/mL) patients were recruited in the Fertility Clinic within a tertiary University Hospital. In the investigational group, DUOSTIM-fresh, the 1st stimulation was initiated in the luteal phase followed by a 2nd stimulation 5 days post first OPU, initiated in the follicular phase and a fresh ET of the best embryo generated (1st or 2nd cycle). The control group performed a follicular phase single stimulation cycle with fresh ET.

Overall, 107 patients were randomized, 53 in the investigational (DUO-STIM fresh) and 54 in the control arm (single stim).

DUO-STIM fresh resulted in a significantly higher number of good quality embryos as compared to single stim (difference of mean 0.81, 95% CI 0.12-1.49). The mean percentage of embryo transfer was comparable (62.3 and 51.9, respectively for double vs single stimulation). No significant differences were found for fresh embryo transfer outcomes (ongoing pregnancy rates: 24.5 and 22.2, respectively for DUO-STIM fresh vs conventional IVF).

Of interest comparisons between different stimulation cycles (A: luteal phase DUOSTIM-fresh, B: follicular phase DUOSTIM-fresh and C: single stim didn’t demonstrate any significant difference in terms of ovarian response with the mean (SD) number of mature oocytes being (A: 3.3 (2.9) B: 3.4 (3.4) C: 3.5 (2.9), respectively).

Study sample size was calculated to detect differences on the mean number of good-quality embryos. Therefore, results for secondary outcomes (embryo transfer rates and clinical pregnancy rates) should be interpreted with caution as exploratory findings that warrant future investigations.

Although DUOSTIM-fresh results in higher number of blastocysts as compared with a single stimulation in young poor-prognosis patients, the decision of performing dual stim should be evaluated with caution considering that whether this may improve embryo transfers rate and pregnancy outcomes is still unclear. Results on Cumulative-Live-Birth-Rate are warranted.

NCT04446845