GnRH Agonist at Embryo Transfer: IVF Outcomes (GRAET)

Does a GnRH Agonist Given at Embryo Transfer Improve Clinical Pregnancy and Live Birth Rates of Women Undergoing In-Vitro Fertilization?

In ART (assisted reproductive technology) cycles, embryos are transferred to a woman's uterus after in-vitro fertilization (IVF) in a laboratory. Usually, hormones (progesterone) are given to the patient after transferring the embryo, as a supplement, in order to mimic the natural hormones that would normally be secreted in an unassisted pregnancy. This study will identify whether additional gonadotropin-releasing hormone (GnRH-agonist) administration, a natural hormone secreted from the hypothalamus, will improve the clinical pregnancy and live birth rates when using IVF.

Study Overview

• Status: Withdrawn
• Conditions: Infertility; Infertility, Female; Infertility, Male
• Intervention / Treatment: Drug: Saline Solution for Injection; Drug: Leuprolide Acetate

Detailed Description

This is a randomized, double-blinded, placebo-controlled study. On the day of embryo transfer (5-6 days after a fresh egg retrieval and on the 6th day of progesterone administration in a frozen embryo transfer cycle), patients will receive either a single injection of 20 Units (1mg) of Lupron or an identical placebo injection. Patients undergoing day 3 embryo transfers will not be eligible and will not be randomized.

Randomization will be in 22 blocks of 20 patients. Based on the power analysis with a power of 0.8 and alpha-error of 0.05, the investigators will need to enroll 352 patients, so the investigators will recruit 440 to account for attrition.

Randomization scheme will be computed via a computerized program accessible at randomization.com or via SPSS. There will be one randomization: both fresh and frozen embryo cycles will be randomized in the same group. Sequential cards with randomization allocation will be placed in doubly sealed, opaque envelopes, with a single sheet confirming eligibility status. Confirmation of the presence of the signed Informed Consent will be in the first envelope. The second envelope will be opened after there is confirmation that the patient is eligible and consented. This envelope will have a card stating the group the patient has been assigned to, with blank spaces designated to record patient information. This card will be completed by the study staff and saved for reference purposes. The card will state the group that the patient was randomized to, the date of embryo transfer, the patient's medical record number, name, and cycle type. There will also be a log book to record the information and medication lot numbers.

Injections will be prepared at the time of randomization by the research coordinator and will be administered by the clinical RN, who will not know its contents. The clinical staff assessing and planning care of the patient (attending physicians and nurses) will not know the contents of the syringe (either Lupron 20 IU or the same amount of normal saline).

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11204
      • Genesis Fertility Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women undergoing in-vitro fertilization who are receiving an embryo transfer of a day 5 blastocyst

Exclusion Criteria:

• Those who have a contraindication to receiving the medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Saline Solution for Injection; This arm will receive a one-time subcutaneous injection of 0.4mL normal saline solution at the time of embryo transfer. This arm will continue to receive all the same treatments that everyone routinely receives for the IVF cycle, e.g. estrogen and progesterone supplements.	Drug: Saline Solution for Injection; Placebo arm will receive a saline injection; Other Names: NS; NSS
EXPERIMENTAL: Leuprolide Acetate; This arm will receive a one-time subcutaneous injection of 0.4U (0.2mg=0.4mL) Leuprolide acetate at the time of embryo transfer. This arm will continue to receive all the same routine treatments for the IVF cycle, e.g. estrogen and progesterone supplements.	Drug: Leuprolide Acetate; Treatment arm will receive a Leuprolide injection; Other Names: Lupron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	Percentage of live births for all patients included.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Miscarriage rate	Percentage of pregnancies that ended in miscarriage	2 years
Clinical pregnancy rate	Percentage of patients who had a clinical pregnancy, i.e. positive urine pregnancy test	2 years

Collaborators and Investigators

• Sponsor: Maimonides Medical Center
• Investigators: Study Director: Antonios Likourezos, M.P.H., M.A., Maimonides Medical Center

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 15, 2019
• Primary Completion (ANTICIPATED): June 30, 2020
• Study Completion (ANTICIPATED): June 30, 2021

Study Registration Dates

• First Submitted: May 21, 2018
• First Submitted That Met QC Criteria: May 31, 2018
• First Posted (ACTUAL): June 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 16, 2019
• Last Update Submitted That Met QC Criteria: April 12, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: in-vitro fertilization
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Infertility, Male; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: 2018-03-14

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes