Abstract

Abstract Study question Does AMH/AFC ratio correlate to the number of follicles on the day of trigger and to the number of oocytes retrieved after ovarian stimulation? Summary answer The AMH/AFC ratio correlates significantly to the number of pre-ovulatory follicles and the number of oocytes collected after ovarian stimulation (OS). What is known already Although AFC is a robust marker of oocyte yield after OS, its combination with Anti-Mullerian hormone (AMH) seems to improve the predictability. Besides, Follicular Output Rate [FORT: (number of pre-ovulatory follicles on day of trigger/AFC at baseline) x 100] and Follicle-to-Oocyte Index [FOI: (number of retrieved oocytes/AFC) × 100] evaluate the ovarian responsiveness to gonadotropins during OS, representing its sensitivity to exogenous FSH. Both parameters take antral follicle count (AFC) only into consideration. AMH and AFC as a ratio might optimize the accuracy of FORT and FOI metrics, helping to predict which patients are at higher risk of suboptimal results. Study design, size, duration This retrospective study analyzed 2,163 ovarian stimulation cycles for IVF/ICSI, performed between May 2015 and October 2023 in a tertiary referral IVF centre. For all the cycles, measurement of AMH using Elecsys (Roche®) no longer than 6 months before starting OS, AFC at baseline, number of pre-ovulatory follicles on the day of trigger, and the treatment outcomes were available. Participants/materials, setting, methods Couples with primary/secondary infertility who underwent OS with antagonist protocol, starting on day 2/3 for IVF/ICSI were included, independent of their age or ovarian reserve parameters. Exclusion criteria were patients with body mass index (BMI) >40 kg/m2, non-vaginal ultrasound measurement for AFC and/or follicles during OS, cycles with previous estradiol priming or oral contraceptives. Ethical approval was obtained from the Research Ethics Committee. Main results and the role of chance 2,163 ovarian stimulation cycles were included in the analysis. The mean age, BMI, AMH, AFC, FOI and FORT of the included women were: 35.6±6.1 years, 27.5±4.7 kg/m2, 2.4±2.1 ng/mL, 12±7 follicles, 1.02±0.66 and 1.38±0.79. The correlation of AMH/AFC ratio (coefficient: 0.62, 95% CI: 0.59 to 0.65, p<0.001) to FOI was stronger than the correlation of AMH (coefficient: 0.31, 95% CI: 0.27 to 0.34, p<0.001) or AFC alone (coefficient: -0.09, 95% CI: -0.14 to -0.05, p<0.001). The correlation of AMH/AFC ratio (coefficient: 0.62, 95% CI: 0.59 to 0.64, p<0.001) to FORT was also stronger than the correlation of AMH (coefficient: 0.21, 95% CI: 0.16 to 0.25, p<0.001) or AFC alone (coefficient: -0.23, 95% CI: -0.27 to -0.19, p<0.001). AMH/AFC ratio was better at predicting stimulation efficiency parameters, FOI and FORT, compared to joint use of AMH and AFC (p>0.001 for both). However, regression analysis showed stand-alone use of the AMH/AFC ratio did not provide a better prediction for collected oocyte count compared to joint use of AMH and AFC. In fact, prediction errors were significantly larger for the AMH/AFC ratio (median: -0.4, range: -11 to 11) compared to the model using AMH and AFC separately (median: -0.2, range: -6 to 7). Limitations, reasons for caution Although clinical assessment was performed in the same centre following the same methodology, inter-observer variability for AFC is a limitation. Additionally, AMH levels used in the study were not obtained in the same cycles, which may adversely affect the performance of the ratio. Wider implications of the findings While AMH/AFC ratio was better at predicting stimulation efficiency compared to FOI and FORT parameters, it was not significantly better at predicting absolute oocyte yield. This may imply AMH/AFC ratio can represent the ovarian sensitivity to exogenous FSH. Trial registration number Not applicable

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