Comparison of Two Protocols in Frozen Embryo Transfer

NCT ID: NCT07003373

Last Updated: 2025-06-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

NA

Total Enrollment

112 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-05

Study Completion Date

2026-07-05

Brief Summary

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This randomized clinical trial evaluates two different endometrial preparation protocols-hormone replacement therapy (HRT) and natural cycle-for frozen embryo transfer (FET) in infertile women undergoing assisted reproductive technology (ART). The goal is to compare implantation, clinical pregnancy, and ongoing pregnancy outcomes.

Detailed Description

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This prospective, randomized controlled clinical trial is conducted on women aged 18 to 42 years undergoing frozen embryo transfer (FET) during in vitro fertilization (IVF) cycles. Eligible participants meet the inclusion criteria and provide written informed consent.

Participants are randomized into two groups using a permuted block method:

HRT Group (Control): Estradiol valerate is initiated at 4 mg/day on day 2 of the menstrual cycle and is adjusted to 8 mg/day based on endometrial thickness. Once the endometrial thickness reaches ≥8 mm, progesterone supplementation is started (400 mg vaginal suppositories twice daily and 50 mg intramuscular injections daily) for 5 days before blastocyst transfer.

Natural Cycle Group: A transvaginal ultrasound is performed on cycle day 2 or 3 to rule out ovarian cysts and confirm an endometrial thickness \<5 mm. If eligible, patients are monitored from day 8 onward. Ovulation is tracked by assessing dominant follicle growth (≥15 mm), LH surge (≥17 IU/L), and serum progesterone (\>1.5 ng/mL). Once ovulation is confirmed and endometrial thickness reaches ≥7 mm, FET is scheduled for 6 days post-LH surge or 5 days post-follicle collapse. Serum progesterone is measured one day before transfer; if \<10 ng/mL, 400 mg/day progesterone is administered.

Embryos are cultured in Blastocyst medium (Origio, Denmark) and assessed daily. High-quality embryos (Grade A) are defined by a 4-cell stage on day 2, a 7-8 cell stage on day 3, uniform cell size, and \<20% fragmentation. Blastocyst grading follows Gardner's criteria. One or two top-quality embryos are transferred using a Cook catheter under abdominal ultrasound guidance. If no blastocyst is available by day 5, the most advanced embryo is transferred.

Conditions

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IVF Outcomes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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natural cycle group

A transvaginal ultrasound is performed on cycle day 2 or 3 to rule out ovarian cysts and confirm an endometrial thickness \<5 mm. If eligible, patients are monitored from day 8 onward. Ovulation is tracked by assessing dominant follicle growth (≥15 mm), LH surge (≥17 IU/L), and serum progesterone (\>1.5 ng/mL). Once ovulation is confirmed and endometrial thickness reaches ≥7 mm, FET is scheduled for 6 days post-LH surge or 5 days post-follicle collapse. Serum progesterone is measured one day before transfer; if \<10 ng/mL, 400 mg/day progesterone is administered

Group Type NO_INTERVENTION

No interventions assigned to this group

Hormone Replacement Therapy (HRT)

Group Type EXPERIMENTAL

hormone replacement therapy (HRT) group

Intervention Type DRUG

Estradiol valerate is initiated at 4 mg/day on day 2 of the menstrual cycle and is adjusted to 8 mg/day based on endometrial thickness. Once the endometrial thickness reaches ≥8 mm, progesterone supplementation is started (400 mg vaginal suppositories twice daily and 50 mg intramuscular injections daily) for 5 days before blastocyst transfer.

Interventions

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hormone replacement therapy (HRT) group

Estradiol valerate is initiated at 4 mg/day on day 2 of the menstrual cycle and is adjusted to 8 mg/day based on endometrial thickness. Once the endometrial thickness reaches ≥8 mm, progesterone supplementation is started (400 mg vaginal suppositories twice daily and 50 mg intramuscular injections daily) for 5 days before blastocyst transfer.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Regular menstrual cycles

Maternal age between 18 and 42 years

Normal intrauterine cavity confirmed by pretreatment ultrasound or hysteroscopy

Body Mass Index (BMI) less than 30 kg/m²

No ovulation disorders

Exclusion Criteria

No embryos available for transfer (no embryo thawing)

Withdrawal of patient consent to continue treatment

Failure of dominant follicle development (in natural cycle group)

Inadequate endometrial response for transfer

No endometriosis grade 3 or higher

The participant provided written informed consent
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Malihe Mahmoudinia

OTHER

Sponsor Role lead

Responsible Party

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Malihe Mahmoudinia

Associate Professor of obstetrics & Gynecology, Fellowship of infertility, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Responsibility Role SPONSOR_INVESTIGATOR

Central Contacts

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Malihe Mahmoudinia, Prof

Role: CONTACT

09153047813

Other Identifiers

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IR.MUMS.IRH.REC.1403.221

Identifier Type: -

Identifier Source: org_study_id

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