The effect of ovarian stimulation protocol on follicular asynchrony during in vitro fertilization – A retrospective cohort study

OBJECTIVE: To examine the effect of controlled ovarian stimulation (COS) protocol on follicular synchrony in a subsequent in vitro fertilization (IVF) cycle in patients whose previous cycle was canceled due to asynchrony. METHODS: A single-center retrospective-cohort study (January 2018-March 2024), including women undergoing IVF who had: (1) a COS cycle canceled without oocyte-pick-up (OPU) due to follicular asynchrony; and (2) a subsequent COS cycle with OPU performed. Patients were grouped as: Group 1-same protocol repeated; Group 2-protocol switched. Follicular asynchrony was defined as ≤50% of stimulated follicles ≥14 mm at cancellation. Women with ≤3 total stimulated follicles at cancellation were excluded. Follicular maturation rate in each cycle was the proportion of follicles ≥14 mm among all stimulated follicles at cancellation/trigger. Primary outcome was the difference in follicular maturation rate between the OPU and canceled cycles, representing synchrony improvement. Treatment outcomes were compared; analysis of variance (ANOVA) controlled for confounders. RESULTS: Overall, 95 patients met the inclusion criteria: 43 (45.26%) in Group 1, and 52 (54.74%) in Group 2. Group 1 versus Group 2 had higher parity and antral follicle count (AFC), and lower endometriosis prevalence and daily recombinant-luteinizing-hormone (rLH) dose in the OPU cycle (p < 0.05). Follicular maturation rate difference was significantly lower in Group 1 versus Group 2 (0.17 [0.05-0.28] vs. 0.3 [0.15-0.39], p = 0.03). Utilizing ANOVA adjusting for group, parity, endometriosis, daily rLH dose in the OPU cycle, and AFC, only group designation remained significantly associated with improved follicular maturation, with increased improvement in Group 2 (least squares mean 0.27 vs. 0.12, p = 0.01). CONCLUSION: Switching COS protocols after a cycle canceled for asynchrony was associated with improved follicular synchrony, suggesting consideration for protocol modification in a subsequent cycle.