Ovarian response in natural cycle, minimal stimulation and conventional IVF protocols in relation to anti-mullerian...

In addition to conventional in-vitro-fertilization IVF (cIVF) alternative protocols such as natural cycle (NC-) and minimal stimulation (Min stim-) protocols allow individualized IVF and oocyte freezing treatments. The objective was to develop a model to predict ovarian response in relation to different stimulation protocols and anti-mullerian hormone (AMH) levels.

International multi-centre retrospective cohort study including 1504 NC-IVF, 1287 Min stim IVF and 2048 cIVF cycles performed 01.2022-03.2023. Min stim protocols consisted of oral compounds such as low dose clomiphene citrate or aromatase inhibitors alone or in combination with low dose gonadotropins. Negative binomial regression models were used to assess the effect of protocol and AMH level on the number of oocytes and secondarily on zygotes. Predictions of outcomes were derived across protocols and different AMH categories (<1, ≥1-<2, ≥2 ng/ml).

AMH is an effective predictor of the number of oocytes in relation to IVF protocol. Number of oocytes increase in protocols including gonadotropins, but not in protocols with only oral compounds. Effect of stimulation increased with increasing AMH level but was less pronounced with low AMH level. For example, if AMH is < 1 ng/ml, the predicted number of oocytes is 0.85 and 4.04 in the NC- and cIVF protocols, whereas the difference is twice as large with AMH ≥ 2 ng/ml with predicted values of 0.83 and 10.54, respectively.

Based on AMH level, Min stim-protocols can be individualized by selecting specific stimulation protocols according to the predicted ovarian response, especially in cases with low ovarian reserve.