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

NCT07526207 | Completed Phase 4 DMC

• 1 other identifier: Cairo-MD-42-2022
• Study Type: interventional
• Target: 850
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

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

Keywords

frozen embryo transfer; hormone replacement therapy; estradiol valerate; endometrial preparation; clinical pregnancy; randomized trial; assisted reproductive technology

Outcome Measures

Primary Outcomes (1)

• clinical pregnancy rate

  Clinical pregnancy rate is defined as the proportion of participants with one or more gestational sacs detected by transvaginal ultrasound after frozen embryo transfer.

  6 to 8 weeks after embryo transfer

Secondary Outcomes (2)

• Cycle cancellation rate

  From treatment initiation until cycle cancellation before embryo transfer or embryo transfer if the cycle continued, assessed up to 8 weeks per treatment cycle.

• Live birth rate

  At delivery after 24 completed weeks of gestation

Study Arms (2)

Group A: received 8 mg daily oral estradiol valerate daily.

ACTIVE COMPARATOR

Women in the 8 mg group received four active 2 mg estradiol valerate tablets plus two matched placebo tablets.

Drug: Progynova®

Group B: received 12 mg daily oral estradiol valerate daily.

ACTIVE COMPARATOR

women in the 12 mg group received six active 2 mg estradiol valerate tablets

Drug: Progynova®

Interventions

Progynova® DRUG

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.

Group A: received 8 mg daily oral estradiol valerate daily.

Eligibility Criteria

• Age: 18 Years - 40 Years
• Gender Eligibility Details: Women aged 18-40 years with BMI \< 30 kg/m2 undergoing ART at the IVF Unit
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18 to 40 years
• Body mass index (BMI) less than 30 kg/m²
• Undergoing assisted reproduction treatment at the IVF Unit of Kasr Al-Ainy Teaching Hospital
• Scheduled for an autologous programmed hormone replacement frozen embryo transfer (HRT-FET) cycle
• Endometrial preparation planned using oral estradiol valerate only
• Embryos obtained from a previous IVF or ICSI cycle
• Planned transfer of vitrified-warmed day-5 blastocyst embryo(s)
• First frozen embryo transfer cycle
• Normal uterine cavity confirmed within the previous 12 months
• Baseline transvaginal ultrasound showing no ovarian cyst, dominant follicle, or uterine cavity abnormality
• Willing and able to provide informed consent

You may not qualify if:

• Contraindication to estrogen treatment
• History of breast cancer or endometrial cancer
• History of deep venous thrombosis, pulmonary embolism, or stroke
• Allergy to the study medication
• Irregular vaginal bleeding
• Thyroid disorder
• Hyperprolactinemia
• Uncontrolled diabetes mellitus
• Uncontrolled hypertension
• Significant liver disease
• Significant kidney disease
• Severe systemic illness
• Uterine abnormality
• Untreated hydrosalpinx
• Untreated pathology inside the uterine cavity

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University

Cairo, Al-Manial, 11956, Egypt

Location

MeSH Terms

Conditions

Infertility

Interventions

Estradiol

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, treating physicians, sonographers, embryologists, outcome assessors, and statisticians remained blinded to group assignment throughout the study.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: lecturer of obstetrics and gynecology

Model Details: Participants were randomized in a 1:1 ratio to one of two parallel groups for endometrial preparation in programmed HRT frozen embryo transfer cycles. One group received oral estradiol valerate 8 mg/day and the other received oral estradiol valerate 12 mg/day. Each participant contributed one treatment cycle only, and outcomes were compared between the two groups after the first frozen embryo transfer.

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: April 13, 2026
• Study Start: May 1, 2022
• Primary Completion: March 1, 2026
• Study Completion: April 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

EG (1)