The Effect of Pre-treatment With GnRH Analogues Prior in Vitro Fertilization in Patients With Endometriosis (ENDOFIV)
|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|
- Clinical pregnancy rate by started cycle [ Time Frame: 2 weeks after biochemical 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
- 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 maximum diameter (mm) of the biggest endometrioma
- 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 pregnancies
- Miscarriage rate [ Time Frame: 22nd week of pregnancy ] [ Designated as safety issue: No ]Number of pregnancy losses divided by total number clinical pregnancies
- 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 human chorionic gonadotropin (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. Classification in mild, moderate and severe
|Study Start Date:||March 2012|
|Study Completion Date:||May 2015|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Active Comparator: GnRHa
Triptorelin acetate 3,75 mg subcutaneous injection administered on days 1, 28 and 56 after menstrual cycle.
Drug: Triptorelin acetate
Other Name: 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
Other Name: Gonapeptyl Depot 3,75
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01581359
|Human Reproduction Unit of the La Fe University and Politechnic Hospital|
|Valencia, Spain, 46026|
|Principal Investigator:||ANA Mª MONZÓ, MD, PhD||La Fe University Hospital|