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: 2

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

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 (11)

• Live birth rate

  At delivery after 24 completed weeks of gestation

• 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.

• Endometrial thickness on the day of progesterone initiation

  On the day of progesterone initiation, approximately cycle day 10-18

• Serum estradiol concentration on the day of progesterone initiation

  On the day of progesterone initiation, approximately cycle day 10-18

• Biochemical pregnancy rate

  14 days after embryo transfer

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 from both centers in cairo and kafrelsheikh universities
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18-40 years.
• Body mass index \<30 kg/m².
• First autologous programmed HRT-FET cycle.
• Endometrial preparation planned using oral estradiol valerate only.
• Vitrified embryos derived from a previous autologous IVF or ICSI cycle.
• Planned transfer of vitrified-warmed day-5 blastocyst(s).
• Normal uterine cavity documented within the preceding 12 months.
• Baseline transvaginal ultrasonography on cycle day 2 or 3 showing no ovarian cyst, dominant follicle, or intracavitary pathology.
• Ability and willingness to provide written informed consent.
• Ovulatory-factor infertility, including polycystic ovary syndrome, will be eligible provided all other criteria are fulfilled.

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

• Kafrelsheikh University: collaborator
• Cairo University: lead

Study Sites (2)

Cairo University

Cairo, Al-Manial, 11956, Egypt

Location

Kafrelsheikh University, faculty of medicine

Kafr ash Shaykh, Kafr Elsheikh, 33516, 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. Participants were randomized in a 1:1 ratio to oral estradiol valerate 8 or 12 mg/day. Randomization was stratified by study center using separate computer-generated permuted-block sequences prepared by an independent statistician who had no role in participant enrollment, treatment, outcome assessment, or data analysis. Allocation was concealed using sequentially numbered, opaque, sealed envelopes prepared and retained by personnel independent of recruitment and clinical care. After eligibility confirmation and informed consent, the study coordinator opened the next envelope and dispensed the corresponding sequentially numbered medication pack. Participants, treating physicians, sonographers, embryologists, outcome assessors, and statisticians remained unaware of treatment allocation. No emergency unblinding occurred. Serum est
• Purpose: TREATMENT
• 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: April 25, 2022
• Primary Completion: April 29, 2025
• Study Completion: February 26, 2026
• Last Updated: August 13, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share

Locations

EG (2)