Dydrogesterone versus medroxyprogesterone acetate co-treatment ovarian stimulation for IVF: a matched cohort study of 236 freeze-all-IVF cycles

This matched cohort study was retrospectively performed, with cycles extracted from freeze-all-IVF treatments performed between March and November 2019, to compare the efficacy of flexible-start dydrogesterone (DYG) co-treatment ovarian stimulations (OS) with flexible-start medroxyprogesterone acetate (MPA) co-treatment OS. DYG cycles were matched 1:1 with MPA cycles using female age and antral follicle count, resulting in 236 matched cycles. OS durations and total FSH doses were similar in DYG and MPA OS cycles. The numbers of mature oocytes retrieved were similar; however, the mature oocyte retrieval rate was significantly lower (66.7 vs. 78.2%; p = .001) and the cycle cancellation rates were higher (29.2 vs. 21.2%; p = .056) in DYG co-treatments. A linear regression selected OS co-treatment protocol (0.53 DYG (0.356-0.776), p = .001) into the final model to predict a >= 80% mature oocyte retrieval rate. The per transfer (47.2 vs. 49.7; p = .721) and per treatment ongoing pregnancy rates (32.2 vs. 38.1%, p = .210) were similar in the two co-treatment groups. Flexible-start DYG co-treatment OS was as effective in blastocyst freeze-all-IVF cycles as MPA co-treatment, with similar ongoing pregnancy rates; however, mature oocyte retrieval was significantly decreased and cycle cancellation increased in DYG cycles. Impact statement What is already known on this subject? Progestin (i.e. artificial progesterone) co-treatment has long been known to be a feasible alternative to conventional GnRH-analogue co-treatment in OS for IVF, because of the long-standing evidence that progestin formulations have in oral contraceptive therapies. The recent evolution of effective freeze-all-IVF (in which high mid-cycle progesterone levels is not of concern because of the postponement of embryo transfer) has now made it possible to investigate progestin co-treatment OS in IVF. What do the results of this study add? Ongoing pregnancy rates from blastocyst frozen embryo transfers in flexible-start dydrogesterone (DYG) co-treatment ovarian stimulation (OS) cycles were similar to rates in flexible-start medroxyprogesterone acetate (MPA) co-treatment OS cycles. The mature oocyte retrieval rate was significantly lower and the cycle cancellation rate higher in DYG than in MPA cycles. What are the implications of these findings for clinical practice and/or further research? The evidence suggests that MPA co-treatment should be preferred in OS for IVF. Further investigation is required to refine progestin co-treatment protocols, because of their potential to reduce the number of viable blastocysts.