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

Infertility Clinical Trial

— ENDOFIV  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01581359
• Other study ID #: ENDOFIV-010
• Secondary ID: 2010-022216-39
• Status: Completed
• Phase: Phase 4
• First received: March 20, 2012
• Last updated: October 21, 2015
• Start date: March 2012
• Est. completion date: May 2015

Study information

• Verified date: April 2014
• Source: Instituto de Investigacion Sanitaria La Fe
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: May 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Endometriosis
• Infertility

Intervention

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

Locations

Country	Name	City	State
Spain	Human Reproduction Unit of the La Fe University and Politechnic Hospital	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto de Investigacion Sanitaria La Fe

Country where clinical trial is conducted

Spain, 

References & Publications (53)

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* Note: There are 53 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical pregnancy rate by started cycle	Number of pregnancies with fetal hearth beat on ultrasound exam divided by total number of started cycle	2 weeks after biochemical diagnosis of pregnancy	No
Secondary	Number of oocytes retrieved, total and metaphase II		In the moment of oocyte retrieval	No
Secondary	Embryo quality	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	No
Secondary	Number and size of endometrioma(s)	Total number in each ovary, uni or bilateral cysts and maximum diameter (mm) of the biggest endometrioma	Day of the Basal ultrasound	No
Secondary	Rate of pregnancy to term in patients with endometriosis / endometriomas	Number of deliveries at 37th to 41st weeks of pregnancy divided by total number of pregnancies	37 weeks after cycle	No
Secondary	Miscarriage rate	Number of pregnancy losses divided by total number clinical pregnancies	22nd week of pregnancy	No
Secondary	Rate of healthy and live births	Number of healthy and live births divided by total number of started cycle	37th to 41st weeks of pregnancy	No
Secondary	Fertilization rate	Number of cleavage embryos divided by total number of metaphase II oocytes	Two days after oocyte recovery and IVF	No
Secondary	Total dose of gonadotropins and days of treatment	Total dose of gonadotropins in IU, and total days on treatment	Day of the administration of human chorionic gonadotropin (hCG)	No
Secondary	Cancellation rate and causes	Number of cancelled cycles divided by total number or started cycles	Last day of gonadotropin treatment	No
Secondary	Ovarian Hyperstimulation Syndrome (OHSS) incidence	Number of patients diagnosed of OHSS divided by ended cycles. Classification in mild, moderate and severe	One month after hCG	Yes