Abstract

Abstract Study question Do patients undergoing PGT-M benefit from the Duostim protocol? Summary answer PGT-M patients benefit because luteal phase stimulation is as effective as follicular phase stimulation in generating transferable embryos, thereby increasing the chances of treatment success. What is known already Patients undergoing PGT-M often require a larger number of embryos for pregnancy, with 25-50% deemed ineligible for transfer based on the disease indication (recessive, dominant, or sex-linked). DuoStim emerges as a valuable strategy for improving outcomes in poor responders. Progress in blastocyst culture, genetic testing, and vitrification motivates clinicians to optimize ovarian reserve exploitation through tailored stimulation protocols. Luteal Phase Stimulation (LPS) finds success in poor prognosis or oncological cases within DuoStim, a protocol widely used for poor prognosis patients necessitating both Follicular Phase Stimulation (FPS) and LPS. The potential benefits of DuoStim for PGT-M patients remain unexplored. Study design, size, duration Retrospective controlled case-control study conducted with paired FPS- and LPS-derived cohorts of oocytes collected in the same ovarian cycle (DuoStim). The study included 26 patients aged 36.53 ± 4,59 years old, undergoing DuoStim with the indication of PGT-M between July 2022 and October 2023. Participants/materials, setting, methods FPS and LPS were performed using the same daily dose of recombinant gonadotropins in an antagonist protocol. All zygotes underwent blastocyst culture, trophectoderm biopsy, vitrification, and subsequent thawing of one unaffected euploid blastocyst for transfer. The primary outcome was the mean number of transferable blastocysts (not affected euploid ones) obtained per oocyte retrieval from paired FPS- and LPS-derived cohorts. Secondary outcomes included the mean number of oocytes, blastocysts and implantation and pregnancy rates. Main results and the role of chance FPS and LPS were comparable regarding the mean number of mature oocytes collected (7.73 ± 4.27 vs. 7.57 ± 4.56) and the mean number of blastocysts obtained (3.27 ± 2.40 vs. 2.50 ± 1.98). The mean number of transferable blastocysts per retrieval were similar (FPS: 1.21 ± 1.31 vs. LPS: 0.78 ± 0.91). No significant differences in implantation or ongoing pregnancy rates were observed after transfers of euploid single blastocysts derived from FPS or LPS: 70.0% (7/10) vs. 57.14% (4/7). Three patients out of the 26 (11.54%) had transferable embryos only in the luteal phase. Limitations, reasons for caution Our findings warrant additional assessment through studies involving larger sample sizes. While our preliminary data indicate comparable implantation/pregnancy rates for PGT-M blastocysts from both FPS and LPS, further investigation is essential, especially in populations beyond those with a reduced number of usable blastocysts Wider implications of the findings These data underscore that oocytes obtained from LPS are as competent as those derived from FPS. Patients with unaffected euploid embryos solely due to FLS would not have had any transfer without DuoStim. This protocol could be advantageous for women abroad or with time constraints, potentially reducing dropout rates. Trial registration number Not applicable

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