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 statementWhat 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.

Medroxyprogesterone acetate used in ovarian stimulation is associated with reduced mature oocyte retrieval and blastocyst development: a matched cohort study of 825 freeze-all IVF cycles.

PURPOSE: To compare the effectivity of flexible-start medroxyprogesterone acetate (MPA) co-treatment ovarian stimulations (OS) with flexible-start gonadotropin-releasing hormone antagonist (GnRH-ant) co-treatment OS, in blastocyst freeze-all IVF cycles. METHOD: This matched cohort study was performed at a single IVF center. Study cycles were extracted from freeze-all IVF cycles performed between February 2015 and June 2018 with cycles grouped according to the co-treatment protocol (MPA and GnRH-ant groups) used. MPA cycles were matched 1:1 using antral follicle count, female age, infertility duration, and female body mass index, with GnRH-ant cycles, resulting in 825 matched cycles. MPA or CET co-treatment was started when leading follicles reached 11-12 mm. RESULTS: Duration of OS was significantly longer, and total FSH dose was significantly higher in the MPA group. Numbers of mature oocytes retrieved were similar; however, the mature oocyte retrieval rate (83.8 vs. 97.1%; p < 0.001), number of blastocysts, blastocyst rate (36.4 vs. 41.4%; p < 0.001) and > 2 viable blastocyst rate were all significantly lower in the MPA group. The live birth (LB) per transfer rates (51.6 vs. 55.7%; p = 0.155) were similar; however, the LB rate per treatment was significantly lower (40.9 vs. 45.8%; p = 0.05). A linear regression included the OS co-treatment protocol (GnRH-ant; 1.4 (1.07-1.81); p = 0.013) in the final model to predict having > 2 viable blastocysts. CONCLUSION: Flexible-start MPA co-treatment OS was as effective in freeze-all IVF cycles as GnRH-ant co-treatment, with similar LB per transfer rates; however, increased cycle cancellation and reduced blastocyst numbers reduced LB per treatment rates significantly.