Do women with severely diminished ovarian reserve undergoing modified natural cycles benefit from earlier trigger at smaller follicle size?

Would trigger and oocyte collection at smaller follicle sizes decrease the risk of premature ovulation while maintaining the reproductive potential of oocytes in women with severely diminished ovarian reserve in modified natural cycle IVF? Retrospective cohort study including women who had at least one unsuccessful cycle (due to no response) of conventional ovarian stimulation with a high dosage of gonadotropins and subsequently underwent a modified natural cycle with a solitary growing follicle (i.e., only one follicle above >10mm at the time of trigger). The association between follicle size at trigger and various cycle outcomes was tested with regression analyses. A total of 160 cycles from 110 patients were included in the analysis. Oocyte pick-up (OPU) was performed in 153 cycles, 7 cycles were canceled due to premature ovulation. Patients who received their trigger shot at smaller follicle sizes (≤15mm) had significantly lower premature ovulation and thus higher OPU rates (98.3% vs. 94.0%, adjusted OR: 8.55, 95% CI: 1.30 - 172.2, P=0.048) compared to those who received it at larger follicle sizes (>15mm). In the multivariable analyses, smaller follicle sizes at trigger (>10 to ≤13mm, >13 to ≤15mm, >15mm to ≤17mm) were not significantly associated with a lower rate of cumulus-oocyte-complex (COC), metaphase II oocytes (MIIs), or blastulation compared to the >17mm group. In sensitivity analyses including the first cycle of each couple, the maturity rate among those with a COC retrieval was highest in follicle sizes >15 to ≤17mm (92.3%) and >13 to ≤15mm (91.7%), followed by >10 to ≤13mm (85.7%) and lowest in the >17mm group (58.8%). Five euploid blastocysts developed from 48 fertilized MIIs during the study period with follicle sizes at trigger 12mm (3), 14 mm (1), and 16mm (1). Four were transferred resulting in two live births, both developing from follicles with a size at trigger of 12mm. The ideal follicle size for triggering oocyte maturation may be smaller in women with severely diminished ovarian reserve managed on a modified natural cycle compared to conventional cut-offs. The risk of OPU cancellation was higher in women triggered above 15 mm, and the yield of mature oocytes was not adversely affected in women triggered at >13 to ≤15mm compared to >15mm to ≤17mm. Waiting for follicles to reach sizes above 17mm may be detrimental to achieving optimal outcomes.