Similar Outcomes, Different Timings: Luteal versus Follicular Stimulation in IVF.

OBJECTIVE To compare the impact of luteal-phase ovarian stimulation on embryo count, embryo ploidy, and embryo quality to that of follicular-phase stimulation. DESIGN Retrospective cohort study between 03/2017 and 11/2024. SUBJECTS Women who underwent an 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 3524 cycles follicular-phase - and 552 luteal-phase cycles. Following 2:1 propensity score matching on age, BMI, AMH, AFC, origin of semen, stimulation medication used, 1058 follicular-phase cycles were matched to 550 luteal-phase cycles. Luteal-phase stimulations required a significantly longer duration (median 11.0 vs 10 days, p<0.001) and higher total gonadotropin dose (median 4050 IU vs 3300 IU, p<0.001). Median counts of Cumulus-oocyte-complexes (COC), 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, p=0.062), for blastocyst-count 1.05 (95%CI:0.99-1.11, p=0.116), and for euploid blastocyst-count 1.04 (95%CI:0.94-1.14, p=0.459). Embryo quality distribution did not differ significantly between follicular-phase (N=3831: 8.4% top, 49.5% good, 22.1% fair, 20.0% poor) and luteal-phase (N=2110: 9.4% top, 51.1% good, 20.9% fair, 18.6% poor) groups (p=0.231). One-hundred-and-forty-seven 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, p<0.001) and higher gonadotropin doses (median 4050 IU vs 3600 IU, p<0.001). 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 (p>0.05 for all). 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.