The Rescue of Hormonal Replacement Frozen Embryo Transfer Cycle With Low Serum Progesterone.

March 4, 2023 updated by: Aly Hussein, El Shatby University Hospital for Obstetrics and Gynecology

How to Rescue Hormonal Replacement Frozen Embryo Transfer Cycle With Low Serum Progesterone? A Randomized Control Trial.

Frozen embryo transfer (FET) is increasingly adopted strategy in modern IVF. Among the many factors that have contributed to such change, the pursuit of an ovarian hyperstimulation syndrome free clinic has been strongly required. Improvements in the vitrification and warming processes and the excellent cryo-survival rates have turned FET in our main tool for preventing this complication. Moreover, a freeze all strategy has proven to provide excellent or even better pregnancy rates (PRs), not only in high but also in normal responders.

While ART have rapidly evolved in the areas of embryo culture, vitrification and understanding of the embryo development, little progress has been achieved regarding endometrial preparation for FET. Undoubtedly, correct implantation requires a good quality embryo and a suitable decidualized endometrium. Artificial cycles require hormone replacement treatment (HRT) with estradiol and progesterone (P4). However, there is not a single standardized treatment described for optimal endometrial preparation and no protocol has proven superiority in terms of reproductive outcomes.(5, 6) Although artificial preparation is the most convenient method to schedule FET cycles, recent reports have highlighted a potentially detrimental effect of low P4 levels prior to FET on miscarriage and live birth rates (LBRs). These results have been observed both in homologous and oocyte recipient FET cycles(7, 8), but also in FET cycles of embryos that had undergone PGT for aneuploidies (PGT-A).(9) Additional P4 supplementation may be a way to improve reproductive outcomes in these patients.

Our open labelled randomized control study aims to investigate whether patients with low serum P4 levels the day before FET under standard HRT can benefit in terms of clinical and ongoing pregnancy and implantation rates from an individualized luteal phase support consisting in the addition of oral dydrogesterone supplementation or daily subcutaneous P4 injection.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A randomized control trial which will be conducted at El-Shatby University Maternity Hospital and private two private ART centres in Alexandria, Egypt.

120 patients in which HRT-FET cycles with low serum progesterone levels will divided into two groups :

  • Group A: 60 patients will be given oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily or,
  • Group B: 60 patients will be given subcutaneous injection 25mg daily (Prolutex®, IBSA).

METHODS Investigation Basal hormonal profile before initiation of treatment, a basal hormonal profile will be performed in all patients (basal FSH, LH, and estradiol levels) Pelvic ultrasound using a transvaginal probe, to assess ovaries, tubes and document uterine size, shape and endometrial thickness.

Endometrial preparation:

A transvaginal scan will be performed on the second day of the menstrual cycle to document baseline endometrial thickness.

HRT preparation of endometrium will be started day two of the cycle by administration of estradiol valerate at dose 8 mg daily.

The endometrial thickness and pattern will be assessed starting from day 10 of estradiol supplementation. If the endometrial thickness is less than 7 mm, oestradiol valerate administration will be continued and reassessed every 3 days up to 21days and if no improvement the cycle will be cancelled.

When the endometrial thickness reaches a minimum of 7 mm with a triple-line appearance, patients will start progesterone supplementation. Vaginal progesterone at a daily dose of 800 mg will administered (cyclogest suppository 400mg. twice daily). Blastocyst transfer will be done after 5 complete days of progesterone administration.

A morning serum progesterone level will be measured 24 hours before embryo transfer. If the serum progesterone level is bellow <10 ng/mL (1) rescue progesterone dose will be started before blastocyst transfer.

Patients with low serum progesterone will be randomized to receive extra progesterone supplementation in the form of either:

  • Group A: oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily or,
  • Group B: subcutaneous injection 25mg daily (Prolutex®, IBSA). The serum progesterone will be measured again on the day of embryo transfer and the day after.

The HRT will be continued until a pregnancy test is performed, and in cases of a positive pregnancy test, estradiol valerate and progesterone will be continued till week 10 of gestation.

III. Measuring the level of beta HCG:

The level of HCG will be measured for diagnosis of pregnancy 14 days after embryo transfer.

IV. Detection of Clinical pregnancy rate:

Transvaginal ultrasonography will be used to detect the appearance of the gestational sac with a fetal pole in the uterus two weeks after positive pregnancy test.

Cases will be followed up till the end of first trimester to detect abortion rate.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 2
  • Phase 3

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 Locations

  • Egypt
      • Alexandria, Egypt
        • Recruiting
        • Faculty of Medicine, University of Alexandria
        • Contact:
      • Alexandria, Egypt
        • Recruiting
        • Elshatby University Maternity Hospital
        • Contact:
        • Principal Investigator:
          • Sherif S Gaafar, professor
        • Principal Investigator:
          • Emad A Darweesh, professor

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 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Patient prepared for frozen blastocyst transfer.
  2. Maternal age ranges from less than 40 years.
  3. BMI < 35kg/m2.
  4. Normal uterine cavity.

Exclusion Criteria:

  1. Uncorrected endometrial, uterine or pelvic pathology.
  2. Recurrent implantation failure cases.
  3. Patients suffering from recurrent miscarriages.
  4. Male factor infertility due to azoospermia

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
Active Comparator: Oral dydrogesterone
60 patients in HRT frozen embryo transfer with low serum progesterone less than 10 ng/ml 24 hours before the embryo transfer will be given oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily
Drug: Duphaston
10 mg tablet will be given twice
Active Comparator: subcutaneous progesterone
60 patients in HRT frozen embryo transfer with low serum progesterone less than 10 ng/ml 24 hours before the embryo transfer will be subcutaneous injection 25mg daily (Prolutex®, IBSA).
Drug: prolutex
subcutaneous injection daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: at the 6 th weeks of pregnancy
percentage of cases in which observation of a gestational sac with fetal heart beat by transvaginal ultrasound at 6 weeks of pregnancy
at the 6 th weeks of pregnancy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum progesterone level on the day of FET
Time Frame: on the day of embryo transfer(before transfer)
Serum progesterone level on the day of FET
on the day of embryo transfer(before transfer)
Implantation rate
Time Frame: at the 6 th week of pregnancy
it is calculated as the number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos at the 6 th week of pregnancy and then multiplied by 100
at the 6 th week of pregnancy
Ongoing pregnancy rate
Time Frame: At the 20 th week of gestation
Assessing the difference in the ongoing pregnancy rate when the pregnancy had completed ≥20 weeks of gestation
At the 20 th week of gestation

Collaborators and Investigators

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

Sponsor

El Shatby University Hospital for Obstetrics and Gynecology

Investigators

  • Study Chair: Aly A Hussein, Dr, University of Alexandria

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)

January 1, 2023

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 31, 2023

Study Registration Dates

First Submitted

February 8, 2023

First Submitted That Met QC Criteria

March 4, 2023

First Posted (Estimate)

March 7, 2023

Study Record Updates

Last Update Posted (Estimate)

March 7, 2023

Last Update Submitted That Met QC Criteria

March 4, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0305825

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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