Abstract
Study question
What is the best progesterone administration for luteal phase support (LPS) in frozen-thawed embryo transfer cycle?
Summary answer
Different modes of hormonal luteal phase support do not affect clinical pregnancy rate (CPR) or live birth rate (LBR) in frozen-thawed embryo transfer (FET) cycles.
What is known already
FET has increased substantially over the last years. To support implantation, endometrial and embryo maturities must be synchronized; therefore, endometrial and follicular maturation are monitored either within the artificial cycle. Estrogen and progesterone are sequentially administered. The optimal endometrial preparation strategy remains unclear; this study aims to compare the reproductive and pregnancy outcomes between five different regimens of hormonal LPS for FET treatment.
Study design, size, duration
Single centre retrospective cohort study conducted between 2013 and 2019. Included were women (N = 402) aged 18–45 years undergoing FET. After an optimal endometrial preparation and endometrial thickness, the LPS was started. Thereafter, five different progesterone applications were compared: (1) oral dydrogesterone (10mg tid), (2) vaginal progesterone gel (90mg/d), (3) dydrogesterone (10mg tid) plus vaginal progesterone gel (90mg/d), (4) vaginal progesterone capsules (200mg tid), or (5) subcutaneous injection of 25mg daily.
Participants/materials, setting, methods
An ultrasound was performed 14 days of estrogene ( > =4mg/d) preparation. If the endometrial thickness was ≥7 mm and there was no dominant follicle, luteal support commenced four days before FET. Fourteen days after transformation, a serum beta-hCG test was performed. If positive (> 50 IU/L), a transvaginal ultrasound was performed to confirm clinical pregnancy, defined as gestational sac with fetal heart movement. CPR was assessed and delivery reports for LBR were collected later.
Main results and the role of chance
In total, 402 patients on an artificial cycle were included (mean age, 35 years (y); range, 26–46 y; standard deviation, 4.1 y). No differences in endometrial thickness and cause of infertility were found between groups. Multivariate logistic regression analysis revealed that the odds ratios (ORs) with 95% confidence intervals (CIs) for the CPR was significantly higher in the dydrogesterone only group (OR, 3.25; 95% CI, 1.7–6.2; p < 0.001) and in the combined group (3) (OR, 7.55; 95% CI, 2.7–21.10; p < 0.001). Statistically significant differences in live birth rate could not be found between the five groups; they were 33%, 54%, 8.3%, 4%, 0% for groups 1, 2, 3, 4, and 5 respectively. Overall satisfaction and tolerability were significantly higher in oral dydrogesterone compared to the vaginal progesterone.
Limitations, reasons for caution
This is a retrospective single-center study. Also, potentially confounding variables like ethnicity, parity, BMI were not accounted for, possibly contributing to bias. Further prospective randomized studies are needed.
Wider implications of the findings: Oral dydrogesterone was found to be effective with equal CPR and LBR. Benefit is well-tolerated and accepted among patients; however we did not observe significant differences in the rates of live birth between the five regimens for used for LPS in women undergoing frozen-thawed embryo transfers.
Trial registration number
BASEC Switzerland 2020–01527
Adding Weekly Intramuscular Progesterone to a Twice Daily Vaginal Progesterone Capsule for Luteal Phase Support in IVF/ICSI Cycles Results in Similar Live Birth Rates