Double stimulation in the same menstrual cycle (DuoStim): a comparative evaluation of follicular and luteal phase response

Abstract

Objective Double ovarian stimulation (DuoStim) protocols, in which both follicular and luteal phase stimulations are performed within the same menstrual cycle, have emerged as a promising strategy for patients with diminished ovarian reserve. The aim of this study is to compare the outcomes of follicular and luteal phase stimulations in patients undergoing DuoStim protocols. Material and Methods This retrospective intra-patient paired comparative study included patients who underwent DuoStim between January 2018 and December 2024 at a university-based infertility clinic. Stimulation protocols, gonadotropin doses and trigger types were evaluated. Primary outcomes were retrieved oocyte and metaphase II (MII) oocyte numbers across both stimulation phases. Clinical pregnancy rates achieved by embryos derived separately from each stimulation phase were evaluated as a secondary outcome. Duration of stimulation, total gonadotropin doses administered, cumulative oocyte yield and embryos obtained, fertilization rates, implantation rates, and live birth rates were also assessed. Results The study included 120 patients. Retrieved oocytes numbers [2 (1-3) and 2 (1-5) in follicular phase and luteal phase], MII oocytes [1 (1-2) and 2 (0-4)], and frozen cleavage stage embryos [1 (0-1) and 1 (0-2) in follicular phase and luteal phase] were higher in the luteal phase stimulation (p<0.001, p=0.001, and p=0.005 respectively). Oocyte yield, fertilization rates, implantation rates, and clinical pregnancy rates were similar between the two phases. Total gonadotropin doses and stimulation duration were significantly higher during follicular phase stimulation. Conclusion In patients with diminished ovarian reserve undergoing DuoStim, luteal phase stimulation yielded significantly more retrieved oocytes and MII oocytes despite requiring lower gonadotropin doses and shorter stimulation duration. Fertilization rates, embryo development, and clinical pregnancy rates were comparable between phases, suggesting that luteal phase-derived embryos are equally competent. These findings support DuoStim as an effective strategy to maximize oocyte yield within a single menstrual cycle in this challenging population. Further prospective studies are warranted to evaluate cumulative reproductive outcomes.