NCT07526207

Estradiol 8 vs 12 mg for Endometrial Preparation in HRT-FET

Oral Estradiol Dose for Endometrial Preparation in Hormone Replacement Frozen Embryo Transfer Cycles: A Randomized Comparative Clinical Trial Comparing 8 mg and 12 mg on Clinical Pregnancy Rate

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 850 (actual)
• Sponsor: Cairo University · Academic / Other
• Sex: Female
• Age: 18 Years – 40 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn whether 12 mg or 8 mg of oral estradiol valerate is better for preparing the endometrium in women undergoing hormone replacement frozen embryo transfer (HRT-FET) cycles. It also aims to assess how these two doses affect pregnancy outcomes and cycle success. The main questions it aims to answer are: Does oral estradiol 12 mg/day improve the clinical pregnancy rate compared with 8 mg/day? Do the two doses differ in endometrial thickness, cycle cancellation, miscarriage, and embryo transfer outcomes? Researchers will compare oral estradiol valerate 12 mg/day with oral estradiol valerate 8 mg/day to see whether the higher dose leads to better endometrial preparation and higher clinical pregnancy rates. Participants will: Be randomly assigned to receive either oral estradiol 8 mg/day or 12 mg/day Undergo endometrial preparation before frozen embryo transfer Have endometrial thickness assessed before starting progesterone Undergo embryo transfer and follow-up to assess clinical pregnancy and other outcomes

Detailed description

Frozen embryo transfer (FET) in programmed hormone replacement therapy (HRT) cycles is widely used in assisted reproduction because it allows scheduling of endometrial preparation and embryo transfer independent of spontaneous ovulation. Although oral estradiol is commonly prescribed for proliferative endometrial priming in these cycles, the optimal daily dose remains uncertain. This trial was designed to evaluate whether increasing oral estradiol valerate from 8 mg/day to 12 mg/day during programmed HRT-FET cycles improves endometrial development and reproductive outcomes in women undergoing autologous frozen blastocyst transfer after a previous IVF/ICSI cycle. This was a prospective, parallel-group, randomized controlled trial conducted at the Department of Obstetrics and Gynecology, Kasr Al-Ainy Teaching Hospital, Faculty of Medicine, Cairo University, during the period from \[month year\] to \[month year\]. Women undergoing their first programmed frozen embryo transfer cycle were randomized in a 1:1 ratio to receive oral estradiol valerate at a total daily dose of either 8 mg or 12 mg. Treatment was initiated early in the menstrual cycle after baseline clinical and ultrasound assessment. Endometrial reassessment was performed after 10 days of estrogen treatment. If adequate endometrial development was achieved, luteal phase support was started, and embryo transfer was scheduled according to the developmental stage of the vitrified-warmed day-5 blastocyst(s). If the endometrium remained below the protocol threshold, estradiol was continued for an additional short interval with repeat ultrasound assessment; cycles that failed to meet continuation criteria were cancelled according to protocol. To reduce treatment variability, all transfers were performed in programmed HRT cycles using oral estradiol only for endometrial preparation, followed by a standardized progesterone regimen for luteal support. All embryos were derived from previous autologous IVF/ICSI cycles and were cryopreserved by vitrification. Embryo warming, grading, and transfer procedures were performed according to the unit's standard laboratory and clinical protocols. Pregnancy follow-up included serum beta-hCG testing after embryo transfer and subsequent transvaginal ultrasonographic confirmation of intrauterine gestation. The study used concealed random allocation and a double-blind design. Participants, treating clinicians, sonographers, embryologists, and outcome assessors were masked to treatment assignment. The trial was designed to provide comparative evidence on whether a higher oral estradiol dose offers measurable benefit over a commonly used standard-dose regimen for endometrial preparation in programmed HRT-FET cycles while maintaining a uniform clinical pathway for embryo transfer and follow-up.

Conditions

• Infertility (IVF Patients)
• Infertility Assisted Reproductive Technology
• Frozen Embryo Transfer (FET)
• Endometrial Preparation
• Clinical Pregnancy Rates

Interventions

Type	Name	Description
DRUG	Progynova®	Oral estradiol valerate 8 mg/day Oral estradiol valerate administered as 2 mg tablets for a total daily dose of 8 mg (four active tablets daily), starting on cycle day 2 for endometrial preparation in programmed HRT frozen embryo transfer cycles. Endometrial thickness was reassessed after 10 days; if the endometrium remained \<7 mm, treatment could be continued for an additional 3 to 5 days. After adequate endometrial preparation, progesterone was initiated, and estradiol was continued through embryo transfer and until 12 completed weeks of gestation if pregnancy was confirmed.
DRUG	Progynova®	Oral estradiol valerate 12 mg/day Oral estradiol valerate administered as 2 mg tablets for a total daily dose of 12 mg (six active tablets daily), starting on cycle day 2 for endometrial preparation in programmed HRT frozen embryo transfer cycles. Endometrial thickness was reassessed after 10 days; if the endometrium remained \<7 mm, treatment could be continued for an additional 3 to 5 days. After adequate endometrial preparation, progesterone was initiated, and estradiol was continued through embryo transfer and until 12 completed weeks of gestation if pregnancy was confirmed.

Timeline

• Start date: 2022-05-01
• Primary completion: 2026-03-01
• Completion: 2026-04-01
• First posted: 2026-04-13
• Last updated: 2026-04-13

Locations

1 site across 1 country: Egypt