Similar outcomes, different timings: luteal vs. follicular stimulation in in vitro fertilization

Abstract

Objective: To compare the impact of luteal-phase ovarian stimulation on embryo count, embryo ploidy, and embryo quality with that of follicular-phase stimulation. Design: Retrospective cohort study between March 2017 and November 2024. Subjects: Women who underwent ovarian stimulation, commenced either in the follicular or the luteal phase of the menstrual cycle. Exposure: Luteal-phase ovarian stimulation Main Outcome Measures: Counts of euploid embryos and embryo quality. Results: The initial cohort included 3,524 follicular-phase cycles and 552 luteal-phase cycles. After 2:1 propensity score matching on age, body mass index, antimüllerian hormone, antral follicle count, origin of semen, stimulation medication used, 1,058 follicular-phase cycles were matched to 550 luteal-phase cycles. Luteal-phase stimulations required a significantly longer duration (median 11.0 vs. 10 days) and higher total gonadotropin dose (median 4,050 IU vs. 3,300 IU). Median counts of cumulus-oocyte-complexes (COCs), mature (MII) and fertilized oocytes, total-, biopsied-, and euploid blastocysts did not differ significantly between groups before regression adjustment. Multivariable regression analyses on the matched cohort showed adjusted incidence rate ratios (IRRs) for MII count (luteal-phase vs. follicular-phase) of 1.04 (95% confidence interval [CI]: 1.00–1.09), for blastocyst count 1.05 (95% CI: 0.99–1.11), and for euploid blastocyst count 1.04 (95% CI: 0.94–1.14). Embryo quality distribution did not differ significantly between follicular-phase (N = 3,831: 8.4% top, 49.5% good, 22.1% fair, and 20.0% poor) and luteal-phase (N = 2,110: 9.4% top, 51.1% good, 20.9% fair, and 18.6% poor) groups. A total of 147 women with a luteal-phase and follicular-phase cycle within one year underwent a paired analysis. Again, luteal-phase cycles required significantly longer stimulation (median 11 vs. 10 days) and higher gonadotropin doses (median 4,050 IU vs. 3,600 IU). No statistically significant differences were found in the median number of COCs, MIIs, fertilized oocytes, total-, biopsied-, or euploid blastocysts between the paired luteal-phase and follicular-phase cycles for these women. Conclusion: Ovarian stimulation initiated in the luteal phase has no detrimental impact on ploidy number or embryo quality. The key advantage of luteal-phase stimulation is an extended duration for initiating ovarian stimulation, which can be useful for couples with time constraints. © 2025 Elsevier B.V., All rights reserved.