The potential influence of follicle diameter on natural cycle in vitro fertilization among women with diminished ovarian reserve: a retrospective cohort study

BACKGROUND: Natural cycle- in vitro fertilization (NC-IVF) is particularly recommended for women with decreased ovarian reserve (DOR) or poor response to controlled ovarian hyperstimulation. In these cases, it can be challenging to determine the optimal timing for a trigger, and follicles of varying sizes are typically obtained. The influence of follicular size on IVF outcomes in women with DOR remains uncertain. This study aims to investigate the association between different follicular sizes and NC-IVF outcomes in women with DOR. METHODS: A retrospective cohort study involving 477 NC-IVF cycles from 2015 to 2021 was conducted at one of the largest reproductive medical centers in China. Follicular growth was monitored using transvaginal ultrasonography, and the follicles were categorized into three groups based on their diameters:12–15 mm; 16–17 mm and ≥ 18 mm. Laboratory outcomes were evaluated, including the number of canceled cycles, number of oocytes retrieved, 2PN fertilization, embryo and good-quality embryo, fresh embryo transfers, and frozen embryo. Additionally, clinical outcomes, such as the rates of biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth, were investigated and compared among the different follicular size groups. RESULTS: A total of 68 cycles with follicles sizes of 12-15 mm, 171 cycles with follicles sizes of 16-17 mm, and 236 cycles with follicles sizes ≥ 18 mm were included in this study. The basic characteristics, including female age, male age, infertility duration, infertility type, and parity, were comparable among the groups. The rate of cycle cancellation in the 12–15 mm group (27.9%) was higher compared to the other two groups. The 2PN fertilization rate for follicles with a diameter of 16-17 mm (75.0%) was higher than that of follicles with a diameter of 12-15 mm (61.3%) and ≥ 18 mm (56.6%) (P = 0.031). Other clinical outcomes, such as the number of oocytes retrieved, good-quality embryos, fresh embryo transfers, and frozen embryos, did not show significant differences between groups. Further analysis revealed no significant difference in the rates of clinical pregnancy, ongoing pregnancy, and live birth rate among the three groups. CONCLUSIONS: This study indicates that in women with DOR undergoing NC-IVF, if a premature LH surge occurs and small follicles are retrieved, these follicles can still be used in subsequent treatment and provide a comparable chance of clinical pregnancy to normal-sized follicles. These findings have important implications for guiding NC-IVF treatment in patients with severe DOR. TRIAL REGISTRATION NUMBER: N/A.