Endometrial Preparation in Frozen Embryo Transfer Cycles

February 23, 2024 updated by: Eman Elgindy, Rahem Fertility Center

Hormonal Replacement Therapy Plus Letrozole Incorporation Versus Letrozole Mild Ovarian Stimulation in Endometrial Preparation for Frozen Embryo Transfer: A Randomised Controlled Trial

In order to get optimal pregnancy rates after frozen embryo transfer (FET), the embryo stage and endometrium should be synchronized. Endometrial preparation is done by either natural, artificial (Hormonal replacement therapy HRT) , modified natural methods or mild ovarian stimulation. HRT cycle has a better schedualization however, there are some reports about higher rates of miscarriage, pregnancy induced hypertension (PIH) and preeclampsia (PET) in HRT cycles. A recent study has found that incorporation of the aromatase inhibitor (letrozole) to HRT cycles was associated with better FET outcomes in comparison to hormonal replacement therapy cycles alone. Meanwhile, mild ovarian stimulation protocol can be done either by oral drugs like letrozole or by letrozole plus gonadotropins . So this study aims to compare the reproductive outcomes in two endometrial preparation protocols for frozen embryo transfer cycles; letrozole mild ovarian stimulation versus HRT plus letrozole incorporation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In order to get optimal pregnancy rates after frozen embryo transfer (FET), the embryo stage and endometrium should be synchronized. This can be done by hormonal replacement therapy (HRT), natural cycles (NC), modified natural cycles or mild ovarian stimulation. In hormonal replacement therapy cycle, estrogen and progesterone are sequentially given to resemble the hormonal course of the natural cycle . Hormonal replacement therapy cycle has a better schedualization and is used for patients with irregular cycles as polycystic ovary syndrome ( PCOS). However, there are some reports about higher rates of miscarriage, pregnancy induced hypertension (PIH) and preeclampsia (PET) in HRT cycles.

A recent study has found that incorporation of the aromatase inhibitor (letrozole) to HRT cycles was associated with better FET outcomes in comparison to HRT cycles alone. Ongoing pregnancy rate (OPR) was higher in HRT plus letrozole group than HRT only group.

Letrozole is a third-generation aromatase inhibitor that leads to mono-ovulatory cycles with short half-life . Miller and his colleagues found that letrozole increased Integrin expression and improved pregnancy and implantation rates among women with endometrial receptivity defects . Another study found that ovarian stimulation with letrozole was associated with increase in the expression of uterine receptivity markers including integrin, leukemia inhibitory factor, and L-selectin.

Study Type

Interventional

Enrollment (Estimated)

210

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women aged between 18 and 37 years with either regular cycles or oligomenorrhoea or amenorrhoea.
  • Women undergoing FET cycles.
  • Participants should have at least one good-quality blastocyst available for vitrification and also for transfer after warming.
  • Participants having optimal endometrium before starting luteal phase support

Exclusion Criteria:

  • Women who will refuse to participate in in the study.
  • Women who will not reach the optimal endometrium.
  • Participants that don't have at least one good-quality blastocyst for transfer after warming.
  • PGT embryos will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A (HRT plus letrozole incorporation)

Exogenous oestradiol in the form of 2 mg oral oestradiol valerate , three times daily will be started on the 2nd or 3rd day of the cycle. Tri-laminar endometrium of ≥ 9 mm will be the targeted cut-off. If the endometrium does not yet reach the target, oestradiol supplementation will be continued with serial US assessment until the targeted cut-off will be reached. Upon reaching the target endometrium, oral letrozole tablets 2.5 mg will be started twice daily for 5 days only with continuation of 6 mg daily oestradiol supplementation. Then, daily intramuscular progesterone in oil (100 mg intramuscular progesterone) will be started once per day with continuation of 6 mg oestradiol

interventions:

Drug:estradiol valertae

Drug :letrozole 2.5 mg tablet
Drug: estradiol valerate and letrozole
hormone replacement therapy by estradiol valerate plus letrozole incorporation .
Active Comparator: Group B (Letrozole mild ovarian stimulation)

Oral letrozole 2.5-5 mg daily on cycle day(3-7) will be added . TVS will be performed from cycle day 8-10 to make sure that a dominant follicle has been recruited with the endometrium thickness ≥ 7 mm . Upon reaching the dominant follicle (18-20mm) , endometrial thickness will be measured on the day of ovulation trigger and blood sample will be withdrawn from each patient for assessment of E2 , P4 and LH levels. Patients with low LH level , high E2 level , low P4 level (<1 ng/ml) will continue in the RCT; 10,000unit HCG will be injected as ovulation trigger

intervention :

Drug :letrozole 2.5mg tablet

procedure: on the day of ovulation trigger blood sample will be withdrawn from each patient for assessment of E2 , P4 and LH levels.
Drug: letrozole 2,5 mg tablet
mild ovarian stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ongoing pregnancy rate (OPR)
Time Frame: 12 weeks
Number of pregnant women with viable fetus at 12 weeks gestation per woman randomized
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with Hypertensive disorders of pregnancy
Time Frame: 20 weeks gestation till postpartum
gestational hypertension or preeclampsia
20 weeks gestation till postpartum
Clinical pregnancy rate (CPR)
Time Frame: 5 weeks after embryo transfer
Number of gestational sacs with evident fetal pulsations per woman randomized,ectopic pregnancy is also includded pregnancy is aslo included
5 weeks after embryo transfer
Ectopic pregnancy
Time Frame: 7 week
pregnancy outside the uterine cavity diagnosed by ultrasound ,surgical visualization or histopathology
7 week
Miscarriage rate
Time Frame: 12 weeks
Number of miscarriages per woman with positive pregnancy tests
12 weeks
Implantation rate
Time Frame: 21 days after embryo transfer
Number of gestational sac recognized by ultrasound in uterus 3 weeks after embryo transfer
21 days after embryo transfer
live birth rate
Time Frame: 22 completed weeks of gestational age
The complete expulsion or extraction from a woman of a product of fertilization,after 22 complete weeks of gestational age;which,after such separation,breathes or shows any other evidence of life,such as heart beat,umblical cord pulsation or definite movement of voluntary muscles,irrespective of whether the umblical cord has been cut or the placenta is attached.A birth weight of 500 grams or more can be used if gestational age is unknown.Live births refer to the individual newborn ;for example,a twin delivery represents two live births
22 completed weeks of gestational age
Number of participants with Large for gestational age
Time Frame: from gestation till delivery
A birth weight greater than the 90th centile of the sex-specific birth weight for a given gestational age reference
from gestation till delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rahem Fertility Center

Investigators

  • Principal Investigator: Eman El-gindy, MD,PhD, Rahem fertility center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 24, 2024

Primary Completion (Estimated)

November 25, 2024

Study Completion (Estimated)

December 25, 2024

Study Registration Dates

First Submitted

December 12, 2023

First Submitted That Met QC Criteria

December 12, 2023

First Posted (Actual)

December 26, 2023

Study Record Updates

Last Update Posted (Estimated)

February 26, 2024

Last Update Submitted That Met QC Criteria

February 23, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • endometrial preparation

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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