The Effect of Pre-treatment With GnRH Analogues Prior in Vitro Fertilization in Patients With Endometriosis (ENDOFIV)

October 21, 2015 updated by: Instituto de Investigacion Sanitaria La Fe

A Comparative Study, Randomized, Blinded, About the Effect of Pre-treatment With GnRH Analogues Versus Placebo in Infertile Patients With Endometriosis Undergoing in Vitro Fertilization Treatment

The purpose of this study is to determine whether the administration of an analogue of gonadotropin-releasing hormone (GnRH) during the three months prior to the performing of an IVF may improve the response to ovarian stimulation, implantation rate and clinical pregnancy rate in patients with endometriosis/ endometriomas.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Endometriosis is defined as the presence of ectopic endometrial tissue which induces a local inflammatory reaction. Usually, this tissue is located at any level in the pelvic region, but extrapelvic locations have been described. It is a chronic disease whose cause is unknown, although a genetic predisposition has been proven. It is estimated that endometriosis affects 7-15% of women of fertile age, and up to 30-40% of women with endometriosis have infertility.

Assisted reproduction techniques (ART) are the treatment of many causes of infertility, including endometriosis. The results of assisted reproduction in women with endometriosis appear to be somewhat worse than those obtained from women without endometriosis. Some authors have proven a significant reduction in implantation and pregnancy rates in these patients.

The worst pregnancy rate and implantation is believed to be originated in a poor oocyte quality, which can lead to a lower rate of fertilization. This poor oocyte quality produce poorer quality embryos with a reduced capacity to implant, particularly in severe endometriosis.

On the other hand, endometrial receptivity does not appear to contribute to the reduction of results of ART in these women.

In an attempt to improve ART outcomes in women with endometriosis, different strategies have been proposed prior to the cycle realization, with different results.

Surgical resection of endometriomas (endometriosis cysts) before the cycle of IVF/ICSI may adversely affect the results. On the other hand, careful laparoscopic cystectomy appears not to affect the ovarian response to stimulation.

In addition to surgical approaches, have been tried different medical treatments to improve the results of IVF / intracytoplasmatic sperm injection (ICSI) in women with endometriosis. It has been suggested that treatment with Danazol prior to IVF may improve results. Similarly, prolonged treatment with GnRH analogues few months before IVF could improve the implantation and pregnancy rates. Unfortunately, many of these studies were not randomized and / or controlled so that the true value of therapy with GnRH analogues before IVF in women with endometriosis still needs to be valued. A recent meta-analysis showed that a 3-6 month treatment with GnRH analogues before IVF increased 4 times the odds of clinical pregnancy in women with endometriosis. Nevertheless, these results were concluded from 165 patients and 78 pregnancies, included in 3 clinical trials, which was not specifically to patients with endometriomas.

The lack of studies with proper design, suggests that there is insufficient evidence at present to establish firm recommendations in this regard. This study will contribute to increasing scientific evidence to recommend or not pretreatment with GnRH agonists before IVF en patients with endometriosis.

Study Type

Interventional

Enrollment (Actual)

200

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

  • Spain
      • Valencia, Spain, 46026
        • Human Reproduction Unit of the La Fe University and Politechnic Hospital

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

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Infertile women with endometriosis diagnosed by surgery in the previous year to their inclusion in the study with signs of residual disease and/or by the existence of ovarian endometrioma in vaginal ecography who are susceptible to IVF treatment.
  • BMI < 28 Kg/m2
  • Age < 40 years old
  • Signed informed consent to perform IVF and participation in this study

Exclusion Criteria:

  • Follicle stimulating hormone (FSH) 2nd-5th cycle day > 12 IU/L
  • Liver disease (sALAT> 80 IU/L)
  • Kidney disease (creatinine > 130 nmol/L)
  • Other relevant disease that contraindicates a pregnancy

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: GnRHa
Triptorelin acetate 3,75 mg subcutaneous injection administered on days 1, 28 and 56 after menstrual cycle.
Drug: Triptorelin acetate
  • Triptorelin acetate Dosing regimen: 1 subcutaneous injection of 3,75 mg/28 days, total of 3 doses
  • Placebo Dosing regimen: subcutaneous injection of the same volume of physiological serum/28 days, total of 3 doses
Other Names:
  • Gonapeptyl Depot 3,75
Placebo Comparator: Physiological serum
physiological serum subcutaneous injection with same delivery device and same volume that active comparator ) administered on days 1, 28 and 56 after menstrual cycle.
Drug: Triptorelin acetate
  • Triptorelin acetate Dosing regimen: 1 subcutaneous injection of 3,75 mg/28 days, total of 3 doses
  • Placebo Dosing regimen: subcutaneous injection of the same volume of physiological serum/28 days, total of 3 doses
Other Names:
  • Gonapeptyl Depot 3,75

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate by started cycle
Time Frame: 2 weeks after biochemical diagnosis of pregnancy
Number of pregnancies with fetal hearth beat on ultrasound exam divided by total number of started cycle
2 weeks after biochemical diagnosis of pregnancy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of oocytes retrieved, total and metaphase II
Time Frame: In the moment of oocyte retrieval
In the moment of oocyte retrieval
Embryo quality
Time Frame: Two-three days after oocyte recovery and IVF
  • A Class: high quality; 4 equal cells, <11% fragmentation, display no irregularities (vacuoles and multinucleation) and normal zona pellucida.
  • B Class: good quality; 2 or 5 cells and <26% fragmentation or 4 cells and 12-25% fragmentation, same or similar size (cells even number), display no irregularities and normal zona pellucida.
  • C Class: intermediate quality; no multinucleation , 3 or 6 cells with <36% fragmentation or 2, 4 and 5 cells with 25-35% fragmentation or inequal size blastomeres or absence/low vacuoles cells or anormal zona pellucida.
Two-three days after oocyte recovery and IVF
Number and size of endometrioma(s)
Time Frame: Day of the Basal ultrasound
Total number in each ovary, uni or bilateral cysts and maximum diameter (mm) of the biggest endometrioma
Day of the Basal ultrasound
Rate of pregnancy to term in patients with endometriosis / endometriomas
Time Frame: 37 weeks after cycle
Number of deliveries at 37th to 41st weeks of pregnancy divided by total number of pregnancies
37 weeks after cycle
Miscarriage rate
Time Frame: 22nd week of pregnancy
Number of pregnancy losses divided by total number clinical pregnancies
22nd week of pregnancy
Rate of healthy and live births
Time Frame: 37th to 41st weeks of pregnancy
Number of healthy and live births divided by total number of started cycle
37th to 41st weeks of pregnancy
Fertilization rate
Time Frame: Two days after oocyte recovery and IVF
Number of cleavage embryos divided by total number of metaphase II oocytes
Two days after oocyte recovery and IVF
Total dose of gonadotropins and days of treatment
Time Frame: Day of the administration of human chorionic gonadotropin (hCG)
Total dose of gonadotropins in IU, and total days on treatment
Day of the administration of human chorionic gonadotropin (hCG)
Cancellation rate and causes
Time Frame: Last day of gonadotropin treatment
Number of cancelled cycles divided by total number or started cycles
Last day of gonadotropin treatment
Ovarian Hyperstimulation Syndrome (OHSS) incidence
Time Frame: One month after hCG
Number of patients diagnosed of OHSS divided by ended cycles. Classification in mild, moderate and severe
One month after hCG

Collaborators and Investigators

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

Sponsor

Instituto de Investigacion Sanitaria La Fe

Investigators

  • Principal Investigator: ANA Mª MONZÓ, MD, PhD, La Fe University Hospital

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

March 1, 2012

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

May 1, 2015

Study Registration Dates

First Submitted

March 20, 2012

First Submitted That Met QC Criteria

April 18, 2012

First Posted (Estimate)

April 20, 2012

Study Record Updates

Last Update Posted (Estimate)

October 22, 2015

Last Update Submitted That Met QC Criteria

October 21, 2015

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENDOFIV-010
  • 2010-022216-39 (EudraCT Number)

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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