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

This study is currently recruiting participants.
Verified April 2014 by Instituto de Investigacion Sanitaria La Fe
Sponsor:
Information provided by (Responsible Party):
Instituto de Investigacion Sanitaria La Fe
ClinicalTrials.gov Identifier:
NCT01581359
First received: March 20, 2012
Last updated: April 8, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to determine whether the administration of an analogue of 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.


Condition Intervention Phase
Endometriosis
Infertility
Drug: Triptorelin acetate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Instituto de Investigacion Sanitaria La Fe:

Primary Outcome Measures:
  • Rate of pregnancy to term in patients with endometriosis / endometriomas [ Time Frame: 37 weeks after cycle ] [ Designated as safety issue: No ]
    Number of deliveries at 37th to 41st weeks of pregnancy divided by total number of pregnacies


Secondary Outcome Measures:
  • Number of oocytes retrieved, total and metaphase II [ Time Frame: In the moment of oocyte retrieval ] [ Designated as safety issue: No ]
  • Embryo quality [ Time Frame: Two-three days after oocyte recovery and IVF ] [ Designated as safety issue: No ]
    • 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.

  • Number and size of endometrioma(s) [ Time Frame: Day of the Basal ultrasound ] [ Designated as safety issue: No ]
    Total number in each ovary, uni or bilateral cysts and maximun diameter (mm) of the biggest endometrioma

  • Clinical pregnancy rate by started cycle [ Time Frame: 2 weeks after bioquimical diagnosis of pregnancy ] [ Designated as safety issue: No ]
    Number of pregnancies with fetal hearth beat on ultrasound exam divided by total number of started cycle

  • Miscarriage rate [ Time Frame: 22nd week of pregnacy ] [ Designated as safety issue: No ]
    Number of pregnancy losses divided by total number clinical pregnacies

  • Rate of healthy and live births [ Time Frame: 37th to 41st weeks of pregnancy ] [ Designated as safety issue: No ]
    Number of healthy and live births divided by total number of started cycle

  • Fertilization rate [ Time Frame: Two days after oocyte recovery and IVF ] [ Designated as safety issue: No ]
    Number of cleavage embryos divided by total number of metaphase II oocytes

  • Total dose of gonadotropins and days of treatment [ Time Frame: Day of the administration of hCG ] [ Designated as safety issue: No ]
    Total dose of gonadotropins in IU, and total days on treatment

  • Cancellation rate and causes [ Time Frame: Last day of gonadotropin treatment ] [ Designated as safety issue: No ]
    Number of cancelled cycles divided by total number or started cycles

  • Ovarian Hyperstimulation Syndrome (OHSS) incidence [ Time Frame: One month after hCG ] [ Designated as safety issue: Yes ]
    Number of patients diagnosed of OHSS divided by ended cycles. Clasification in mild, moderate and severe


Estimated Enrollment: 272
Study Start Date: September 2011
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: GnRHa 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 Name: Gonapeptyl Depot 3,75
Placebo Comparator: Physiological serum 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 Name: Gonapeptyl Depot 3,75

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 / 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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01581359

Contacts
Contact: ANA Mª MONZÓ, MD, PhD +34-96-124-40-00 ext 244114 monzo_ana@gva.es
Contact: ELISABET RODRÍGUEZ, MD, RESIDENT +34-96-124-40-00 ext 244114 e.rodriguez.tarrega@gmail.com

Locations
Spain
Human Reproduction Unit of the La Fe University and Politechnic Hospital Recruiting
Valencia, Spain, 46026
Contact: ANA Mª MONZÓ, MD, PhD    +34-96-124-41-14 ext 244114    ana_monzo@gva.es   
Contact: ELISABET RODRÍGUEZ, MD, RESIDENT    +34-96-124-40-00 ext 244114    e.rodriguez.tarrega@gmail.com   
Principal Investigator: ANA Mª MONZÓ, MD, PhD         
Sub-Investigator: PATROCINIO POLO, MD, PhD         
Sub-Investigator: JOSÉ Mª RUBIO, MD, PhD         
Sub-Investigator: ELISABET RODRÍGUEZ, MD, RESIDENT         
Sub-Investigator: IRENE PEINADO, BIOLOGIST         
Sub-Investigator: PILAR PALACIOS, NURSE         
Sponsors and Collaborators
Instituto de Investigacion Sanitaria La Fe
Investigators
Principal Investigator: ANA Mª MONZÓ, MD, PhD La Fe University Hospital
  More Information

Publications:

Responsible Party: Instituto de Investigacion Sanitaria La Fe
ClinicalTrials.gov Identifier: NCT01581359     History of Changes
Other Study ID Numbers: ENDOFIV-010, 2010-022216-39
Study First Received: March 20, 2012
Last Updated: April 8, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Instituto de Investigacion Sanitaria La Fe:
Endometriosis
GnRH treatment
Infertility
IVF

Additional relevant MeSH terms:
Endometriosis
Infertility
Genital Diseases, Female
Genital Diseases, Male
Triptorelin
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 16, 2014