The Outcome of Two Protocols Used to Prepare Endometrium for Frozen Embryo Transfer

April 20, 2022 updated by: Rahem Fertility Center

A Randomized Controlled Study to Compare the Outcome of Two Protocols Used to Prepare the Endometrium for Frozen Embryo Transfer

This is a RCT to test the outcome of two protocols used for preparation of the endometrium for frozen blastocyst embryo transfer

Study Overview

Detailed Description

Receptive endometrium and a good quality embryo at the blastocyst developmental stage are prerequisites for a successful implantation to occur. Blastocyst freezing techniques and survival have witnessed huge improvements in the last years. Trials to improve the outcome of frozen embryo transfer (FET) are not to be stopped. The transfer of a good quality blastocyst represents a vital part of the process. Optimization of endometrial receptivity and implantation is an everlasting challenge.

Hormone replacement therapy (HRT) is now proven to be successful for preparation of the endometrium to receive the vitrified warmed embryos. Most HRT protocols give estradiol (E2) first to reach a satisfactory endometrial thickness, then followed by progesterone to mimic the natural cycles. E2 is mostly given for 10 to 14 days and this duration might be prolonged to reach a satisfactory endometrial thickness without adversely affecting the outcome. Trans-vaginal ultrasound assessment of the endometrial thickness before the start of P supplementation has been traditionally used to predict FET cycle outcome. Clinical pregnancy rates (CPR) and live birth rates (LBR) were found to decrease for each millimetre of endometrial thickness below 7 mm. Endometrial thickness however of 9 mm was reported to be among major factors affecting LBR after FET in a large set of data.

Further, there is a recent concept that endometrial compaction (decreased thickness) between the end of estrogen phase and the day of ET has favorable impact on the outcome of FET. Different modalities were proposed to enhance endometrial compaction. One of these modalities was to decrease the dose of estrogen so as to change the estrogen- progesterone ratio as well as help in preventing further endometrial growth.

Aromatase inhibitor (AI) can be used to decrease estrogen before starting P supplementation. Additionally, there were also reports that their use had been associated with improved implantation. It appears interesting to combine the easy scheduled HRT protocol with aromatase inhibitor to maximize FET outcome.

This proposed protocol has not been tested before. In current study, HRT plus AI will be compared with HRT only. In both groups, daily intramuscular P will be given for luteal support as it was shown to give the highest ongoing pregnancy rate in FET cycles.

We did a secondary follow up analysis of some exploratory outcomes (not preregistered). These outcomes were analyzed after publication and they include Live birth rate, implantation rate, hypertensive disorders of pregnancy, large for gestation and congenital anomalies. The results of these outcomes are planned to be presented elsewhere. For openness and transparency, we felt the importance to report this follow up in the registry.

Study Type

Interventional

Enrollment (Actual)

112

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 Locations

    • Sharkia
      • Zagazig, Sharkia, Egypt, 44519
        • Rahem fertility center

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

18 years to 37 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:Inclusion criteria:

  • Women aged from18 - 37 years old undergoing FET using good quality blastocysts vitrified on day 5(3 BB and more) (according to Gardner and Schoolcraft 1999) (8).
  • Participants having at least one good quality blastocyst (3BB and more) available for transfer after warming.
  • Participants having trilaminar endometrium of 9 mm after E2 preparation.

Exclusion Criteria:

  • Women younger than 18 or older than 37 years old.
  • Women who have uterine abnormality or pathology.
  • Women who will not meet the inclusion criteria.
  • Women who will refuse to participate in in the study.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: HRT Plus Aromatase Inhibitor

Hormone replacement treatment (HRT) will be used in all cases. Exogenous estradiol will be started on day 2 or 3 of the cycle. In all participants, 2 mg oral estradiol valerate, will be administered three times daily. Ultrasound evaluation of endometrium will be performed 10 to 12 days after starting E2. Trilaminar endometrium of 9 mm will be the targeted cutoff . If not yet ready, E2 supplementation will be continued with serial US assessment until the desired cutoff is achieved. Thereafter, participants will be randomized to two groups:

Group A (HRT plus AI): will be given aromatase inhibitor for 5 days only (2.5 mg twice daily), along with the oral 6 mg E2. Then, daily intramuscular (IM) P in oil (100 mg IM P) will be started in addition to the daily dose of oral 6 mg E2.

In both groups, embryos will be warmed on the 6th day of P supplementation. Before undergoing FET, endometrial thickness will be re-evaluated. IM P and 6mg E2 will be continued thereafter.

2mg three times daily
100 mg daily intramuscular
2.5 mg twice daily for 5 days
Active Comparator: HRT Only

Hormone replacement treatment (HRT) will be used in all cases. Exogenous estradiol will be started on day 2 or 3 of the cycle. In all participants, 2 mg oral estradiol valerate, will be administered three times daily. Ultrasound evaluation of endometrium will be performed 10 to 12 days after starting E2. Trilaminar endometrium of 9 mm will be the targeted cutoff . If not yet ready, E2 supplementation will be continued with serial US assessment until the desired cutoff is achieved. Thereafter, participants will be randomized to two groups Group B (HRT only): will be administered daily intramuscular (IM) P in oil (100 mg IM P) in addition to the daily dose of oral 6 mg E2.

In both groups, embryos will be warmed on the 6th day of P supplementation. Before undergoing FET, endometrial thickness will be re-evaluated. IM P and 6mg E2 will be continued thereafter.

2mg three times daily
100 mg daily intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing Pregnancy Rate
Time Frame: at 12 weeks of gestation
visualization of fetal cardiac pulsation by ultrasound
at 12 weeks of gestation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
endometrial compaction
Time Frame: from the end of estradiol phase to the day of embryo transfer up to 11 days
change in endometrial thickness
from the end of estradiol phase to the day of embryo transfer up to 11 days
clinical pregnancy rate
Time Frame: 6 weeks gestation
visualization of fetal cardiac pulsation by ultrasound
6 weeks gestation
Live birth rate
Time Frame: 24 weeks
The birth of at least one newborn that exhibits any sign of life
24 weeks
Implantation rate
Time Frame: 6 weeks gestation
The number of gestational sacs observed divided by the number of embryos transferred expressed as a percentage, %
6 weeks gestation
Number of participants with Hypertensive disorders of pregnancy
Time Frame: 20 weeks gestation till postpartum
gestational hypertension or preeclampsia
20 weeks gestation till postpartum
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]
Rate of Congenital anomalies
Time Frame: during pregnancy and after birth (one month after birth)
Structural or functional disorders that occur during intra-uterine life and can be identified prenatally, at birth or later in life.
during pregnancy and after birth (one month after birth)

Collaborators and Investigators

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

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)

August 12, 2020

Primary Completion (Actual)

February 5, 2021

Study Completion (Actual)

February 5, 2021

Study Registration Dates

First Submitted

August 1, 2020

First Submitted That Met QC Criteria

August 5, 2020

First Posted (Actual)

August 10, 2020

Study Record Updates

Last Update Posted (Actual)

April 27, 2022

Last Update Submitted That Met QC Criteria

April 20, 2022

Last Verified

October 1, 2020

More Information

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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