Modified Luteal Support for Frozen-Thawed Embryo Transfer - A Prospective Study

December 11, 2016 updated by: Dr. Eran Zilberberg, Sheba Medical Center
This study evaluates the outcomes of frozen-thawed embryo transfer (FET) success rate with modified luteal support - addition of a single injection of HCG and GnRH-agonist, on day of ET and 4 days later, respectively vs. traditional luteal support with vaginal progesterone only in ovulating women.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Background With the recent trend toward single embryo transfer (ET) adopted in an attempt to reduce the risk of multiple pregnancy, the remaining extra embryos are cryopreserved, providing further possibilities for conception after the initial fresh transfer. Moreover, several studies that compared fresh and frozen-thawed embryo transfer (FET) cycles in normal responders have demonstrated a significantly higher clinical pregnancy rate per transfer in the FET versus the fresh cycles.

There are several currently employed replacement protocols for FET. The choice of protocol depends on the individual woman's ovarian function and convenience of the method, as well as on the experience gained with the method by the physicians. Whatever protocol is used, the success requires optimal synchronization between the embryonic stage at thawing and date of the endometrium within the endometrial preparation cycle. While there is a consensus regarding the duration, route of delivery and dosage of estrogen supplementation, and the optimal ultrasonographic endometrial appearance and thickness, the effect of the different modes of luteal support remains unclear.

Prompted by the study demonstrating higher ongoing pregnancy rate following the transfer of frozen-thawed embryos in natural cycles with spontaneous LH rise compared with natural cycles controlled by hCG for final oocyte maturation and the reports showing improved pregnancy rate in patients who received a mid-luteal injection of a GnRH-agonist (0.1 mg triptorelin), the investigators started beginning at June 2014 to offer ovulatory patients with regular menstrual cycles a natural FET with modified luteal support. Starting on the day of spontaneous ovulation, patients received daily vaginal progesterone, supplemented by a single injection of HCG and GnRH-agonist, on day of ET and 4 days later, respectively.

The results for this study were very promising - the investigators were able to show a significant increase in implantation rate (30% vs. 17%; p<0.03), clinical pregnancy (48% vs. 26%; p<0.01) and ongoing pregnancy (39% vs. 20%; p<0.01) for the patients receiving the aforementioned modified luteal support protocol.

After the completion of this retrospective study the investigators are heading to prove the superiority of the modified luteal support protocol for ovulatory patients by conducting a prospective study.

Materials & Methods Study design - A prospective, randomized, blinded study. Primary endpoint - Ongoing pregnancy. Secondary endpoints - Implantation rate, clinical pregnancy. Study sample - According to the previous, retrospective study the investigators will need 31 patients in each study arm in order to show an increase from 20% clinical pregnancy to 39% (confidence level 5%, beta error level 50%).

The patients - The investigators will offer each patient treated in the unit for frozen-thawed embryo transfer to participate in the study. The randomization of the participants will be on the day of embryo transfer with a computer program on a 1:1 enrollment ratio.

All transfers will be performed by an experienced physician who will be blinded to the luteal support protocol.

Both groups will be treated with the accepted progesterone luteal support - starting on ovulation day - vaginal progesterone 90 mg (Crinone; Merck Serono, Hellerup, Denmark) once a day.

Study group - Patients in the study group will receive additional two injections - the first - recombinant hCG 250 mcg (Ovitrelle; Merck Serono) on the transfer day and the second - GnRH-agonist 0.1 mg (Decapeptyl; Ferring Pharmaceuticals Israel) 4 days after the embryo transfer day. Patients in the control group will receive no injection.

B-hCG levels will be examined 12 days after embryo transfer and if positive ultrasound examinations will be performed as usual to document pregnancy outcome.

The data - The investigators will use demographic data such as age, BMI, gynecological data as gravida, para, etiology of infertility and data about previous & current IVF treatments such as number of treatments, stimulation protocol, hormone levels, number of oocytes, embryos' characteristics, etc.

Statistics - Statistical analysis will be performed with Student's t-test and Chi square, as appropriate. Results will be presented as means ± standard deviations; p<0.05 will be considered significant.

Study Type

Interventional

Enrollment (Anticipated)

62

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

  • Israel
      • Ramat Gan, Israel
        • Recruiting
        • Sheba Medical Center
        • Contact:
          • Eran Zilberberg, MD
          • Phone Number: +97235302882

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

20 years to 40 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • 20-40 years old women
  • Spontaneously ovulating women
  • Treated in our IVF unit for frozen-thawed embryo transfer
  • At least one top quality embryo

Exclusion Criteria:

  • PGD patients
  • More than 4 previous embryo transfers

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: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Study group
hCG (Choriogonadotropin alfa; Ovitrelle 250 mcg) on day of embryo transfer & GnRH-agonist (Triptorelin acetate; Decapeptyl 0.1 mg) after 4 days In addition to the usual progesterone luteal support.
Drug: Choriogonadotropin alfa
Other Names:
  • Ovidrel
  • Ovitrelle
  • recombinant hCG
Drug: Triptorelin acetate
Other Names:
  • Decapeptyl
  • GnRH-Agonist
No Intervention: Control group
The usual progesterone only luteal phase support.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ongoing pregnancy
Time Frame: About 10-12 weeks after embryo transfer
Number of viable pregnancies at about 10-12 weeks of gestation.
About 10-12 weeks after embryo transfer

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Implantation rate
Time Frame: 2 weeks after embryo transfer
Positive BhCG blood test
2 weeks after embryo transfer
Clinical pregnancy
Time Frame: About 3-4 weeks after embryo transfer
Visible intrauterine gestational sacs on ultrasound exam
About 3-4 weeks after embryo transfer

Collaborators and Investigators

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

Sponsor

Sheba Medical 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

July 1, 2016

Primary Completion (Anticipated)

June 1, 2017

Study Completion (Anticipated)

June 1, 2017

Study Registration Dates

First Submitted

July 3, 2016

First Submitted That Met QC Criteria

July 6, 2016

First Posted (Estimate)

July 7, 2016

Study Record Updates

Last Update Posted (Estimate)

December 13, 2016

Last Update Submitted That Met QC Criteria

December 11, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2537-15-SMC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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