ESHRE 2024: Dydrogesterone versus Micronized Vaginal Progesterone for Luteal Phase Support in Hormone Replacement Therapy Frozen Embryo Transfer Cycles (REMODEL): An Exploratory Randomized Controlled Trial
Speaker Caroline Roelens
The use of frozen embryo transfer (FET) cycles has increased significantly due to advancements in cryopreservation techniques and expanding indications, particularly in patients with conditions like premature ovarian insufficiency (POI) or polycystic ovary syndrome (PCOS) resistant to conventional treatments. Artificial FET cycles, devoid of endogenous progesterone support from a corpus luteum, pose challenges such as the increased risk of conditions like preeclampsia due to the absence of vasoactive substances. Studies, including those like the LOTUS (Lutectomy versus Ovarian suppression Trial for uterine sparing surgery trials), have investigated alternatives such as dydrogesterone for luteal phase support in fresh and frozen cycles. Pharmacokinetic studies have highlighted dydrogesterone's rapid absorption and clearance, contrasting with more stable levels seen with vaginal progesterone. The variability underscores the need for further study to establish standardized protocols and optimize outcomes in Assisted Reproductive Technology (ART) settings.
The study aimed to compare oral dydrogesterone with micronized vaginal progesterone in artificial FET cycles, where endogenous progesterone is absent. Patients started with estradiol valerate from day two of their menstrual cycle, aiming for an endometrial thickness of 6.5 mm or more before randomization. Patients were randomized into two groups: one receiving 30 mg of oral dydrogesterone daily and the other receiving 800 mg of micronized vaginal progesterone daily. Inclusion criteria limited participants to those under 40 years old with a normal BMI (Body Mass Index) undergoing single blastocyst transfer of good quality. Patients with recurrent miscarriage or repeated implantation failure were excluded. It aimed to include approximately 150 patients and screened 167, with 150 ultimately randomized. In the intention-to-treat analysis, outcomes were analyzed for all 150 patients. However, a few patients were excluded from the per-protocol analysis: two received additional progesterone supplementation against protocol, and two switched treatments due to side effects. The study design helped evaluate the effectiveness and tolerability of both forms of progesterone supplementation in optimizing outcomes for FET cycles without natural progesterone support.
The study compared oral dydrogesterone with micronized vaginal progesterone in frozen embryo transfer cycles. Demographic and cycle characteristics were similar between groups, except for progesterone levels. Pregnancy outcomes, including hCG (Human Chronic Gonadotropin) positivity and ongoing pregnancy rates, showed no significant differences between the treatments. Analysis adjusting for various factors also found no significant impact of dydrogesterone levels on pregnancy outcomes, although the study's size limited definitive conclusions. Further study with larger cohorts is needed to validate these findings.
The study did not reveal significant differences in pregnancy outcomes between the groups. While early pregnancy loss and live birth rates showed potential clinical differences, these findings warrant further investigation in larger cohorts. In the study, plasma levels of dydrogesterone did not demonstrate a clear association with pregnancy outcomes, highlighting the need for more extensive study. In artificial cycles without endogenous progesterone, 30 mg of dydrogesterone did not achieve the expected results as monotherapy, suggesting potential efficacy in rescue or combination strategies, as observed in other studies.
The scientific exchange lastly focused on the rationale behind the 30 mg dosage of dydrogesterone, aligning with established guidelines for luteal phase support in IVF (In vitro fertilization). Consideration was given to the potential benefits of higher dosages, such as 40 mg, suggesting further investigation is warranted. The study was described as exploratory without non-inferiority testing, limiting definitive conclusions due to the arbitrary sample size. Progesterone supplementation strategies were emphasized, particularly regarding progesterone level monitoring and tailored adjustments based on measured thresholds, contrasting challenges between dydrogesterone and micronized vaginal progesterone. Limitations were acknowledged, stressing the need for subsequent study in larger populations. Subsequently, findings from a randomized trial on endometrial preparation strategies for frozen embryo transfer in obliterated women were presented.
European Society of Human Reproduction and Embryology, July 7-10, Amsterdam, The Netherlands
