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
Overview
- Phase
- Phase 4
- Intervention
- Triptorelin acetate
- Conditions
- Endometriosis
- Sponsor
- Instituto de Investigacion Sanitaria La Fe
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Clinical pregnancy rate by started cycle
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief 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.
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.
Investigators
Eligibility 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
- •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
Arms & Interventions
GnRHa
Triptorelin acetate 3,75 mg subcutaneous injection administered on days 1, 28 and 56 after menstrual cycle.
Intervention: Triptorelin acetate
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.
Intervention: Triptorelin acetate
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Total dose of gonadotropins and days of treatment(Day of the administration of human chorionic gonadotropin (hCG))
- Number of oocytes retrieved, total and metaphase II(In the moment of oocyte retrieval)
- Embryo quality(Two-three days after oocyte recovery and IVF)
- Rate of pregnancy to term in patients with endometriosis / endometriomas(37 weeks after cycle)
- Rate of healthy and live births(37th to 41st weeks of pregnancy)
- Fertilization rate(Two days after oocyte recovery and IVF)
- Number and size of endometrioma(s)(Day of the Basal ultrasound)
- Miscarriage rate(22nd week of pregnancy)
- Ovarian Hyperstimulation Syndrome (OHSS) incidence(One month after hCG)
- Cancellation rate and causes(Last day of gonadotropin treatment)