Surgery and ART For Endometrioma

Study Overview
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Brief Summary
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Endometriosis is an estrogen-dependent chronic disease, characterized by the presence of endometrial-like tissue, glands and stroma outside the uterine cavity. Although endometriosis is classified in four stage (minimal, mild, moderate, severe), from the clinical point of view it is possible to subdivide among peritoneal superficial lesions, ovarian endometriomas and Deep Infiltrating Endometriosis (DIE). According to the European Society for Human Reproduction and Embryology (ESHRE) Guideline on the management of women with endometriosis, it is recommended to clinicians that in infertile women with endometrioma larger than 3 cm, cystectomy should be considered prior to Assisted Reproduction Technology (ART) to improve endometriosis-associated pain or the accessibility of follicles. They further recommend that clinicians counsel women with endometrioma regarding the risks of reduced ovarian function after surgery, the possible loss of the ovary, and consider that the decision to proceed with surgery should be taken carefully if the woman has had previous ovarian surgery. In addition, this Guideline suggests that clinicians can prescribe prolonged (3-6 months) pituitary downregulation with Gonadotropin Releasing Hormone-agonists (GnRH-a) prior to ART, in order to increase live birth rate by four-fold. Despite these recommendations, to date there is not robust evidence to choose between the two strategies prior to ART in order to improve reproductive outcomes. For this reason, the aim of the current study will be to compare reproductive outcomes in infertile women affected by ovarian endometrioma, undergoing laparoscopic enucleation or prolonged pituitary downregulation with GnRH-a, prior to ART.

Official Title
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Evaluation of Reproductive Outcomes After Different Management of Ovarian Endometrioma Prior to Assisted Reproduction Technology (ART): Laparoscopic Enucleation Vs Prolonged Pituitary Downregulation With Gonadotropin Releasing Hormone (GnRH)-Agonists

Conditions
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Ovarian Endometrioma, Infertility, Female

Intervention / Treatment
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* Procedure: Laparoscopic enucleation of ovarian endometrioma.
* Procedure: Prolonged pituitary downregulation
* Procedure: Assisted Reproductive Technology (ART)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Indication for ART: compromised tubal function, male factor infertility, other treatments have failed and/or prolonged infertility of more than 4 years. Age between 18 and 35 years. Ultrasound diagnosis of one ovarian endometriotic cyst with a diameter of 30 mm or more, according to the International Ovarian Tumor Analysis (IOTA)-criteria for reliable diagnosis of endometriomas in premenopausal women. Exclusion Criteria: Any comorbidity other than ovarian endometrioma. Deep Infiltrating Endometriosis. Previous ovarian surgery. Bilateral endometriomas. The use of donor oocytes/sperm. ART with preimplantation genetic testing, as the number of embryos suitable. for transfer or cryopreservation is significantly lower compared to normal ART.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Controlled Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Surgery<br>Laparoscopic enucleation of ovarian endometrioma (stripping of the peripheral capsule and coagulation using the lowest energy source available). | Procedure: Laparoscopic enucleation of ovarian endometrioma.<br>* Laparoscopic enucleation of ovarian endometrioma (stripping of the peripheral capsule and coagulation using the lowest energy source available).<br>Procedure: Assisted Reproductive Technology (ART)<br>* Fresh ART cycle: ovarian stimulation, oocyte retrieval, in vitro fertilization and embryo transfer.<br>|
| Active Comparator: Prolonged pituitary downregulation<br>Treatment with GnRH-a (triptorelin, goserelin, and leuprolide), with add-back therapy (combined oral contraceptive) for 3-6 months. | Procedure: Prolonged pituitary downregulation<br>* Treatment with GnRH-a (triptorelin, goserelin, and leuprolide), with add-back therapy (combined oral contraceptive) for 3-6 months.<br>Procedure: Assisted Reproductive Technology (ART)<br>* Fresh ART cycle: ovarian stimulation, oocyte retrieval, in vitro fertilization and embryo transfer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy with fetal heartbeat | Ultrasound-confirmed intrauterine pregnancy with fetal heartbeat | Within 8 weeks from embryo transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical pregnancy | Positive HCG serum testing | Within 8 weeks from embryo transfer | 
| Miscarriage | Ultrasound-confirmed abortion | Within 12 weeks from embryo transfer | 
| Live birth rate | Delivered fetus after 28 gestational weeks | Within 41 weeks from embryo transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endometrioma, Infertility, Laparoscopy, GnRH-a, Assisted Reproduction Technology, Reproductive outcomes