IVF Versus Surgery for Endometriosis Related Infertility

Study Overview
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Brief Summary
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The management of endometriosis-related infertility remains controversial. In particular, there is an equipoise for infertile women with endometriotic lesions detected at ultrasound. These women can be managed with either surgery or in vitro fertilization (IVF). The two approaches radically differ and they have never been compared with a randomized trial. As a consequence, affected women currently receive contrasting information and the mode of treatment substantially differ among centres, reflecting the local expertise of physicians rather than clinical needs. The present study aims at clarify whether IVF could be superior to surgery in infertile women with endometriotic lesions detected at ultrasound. This topic will be addressed comparing the two approaches in terms of effectiveness and cost-effectiveness. In addition, the study will disentangling whether the endometriosis-related systemic inflammatory mechanisms may have an impact on the quality of folliculogenesis and on IVF outcomes. This specific objective will be pursued through the characterization and analysis of circulating extracellular vesicles (EV)-immunologic, proteomic and miRNA signatures and measurement of steroid hormones in follicular fluid.

Detailed Description
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Women accepting to enter the study will be randomized to either surgery and then natural pregnancy seeking or a program of three complete IVF cycles (i.e. three oocytes retrievals regardless of the number of embryo transfers performed). The initial time point will be the time of randomization. Women of both study groups will initiate treatment (surgery or IVF) in a shortest delay, maximum 3 months. Only live birth pregnancies and initiating within a 12-months period starting from this time point will be included in the primary outcome.

Official Title
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IVF Versus Surgery for the Treatment of Infertility Associated to Ovarian and Deep Peritoneal Endometriosis

Conditions
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Endometriosis

Intervention / Treatment
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* Procedure: Surgery
* Procedure: IVF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age < 40 years Pregnancy seeking for more than 12 months Regular menstrual cycle, i.e. mean cycle interval between 21 and 35 days Ultrasonographic diagnosis of ovarian endometriomas or deep peritoneal endometriosis. Normal seminal analysis based on WHO criteria Absence of ureteral stenosis or intestinal subocclusive symptoms Exclusion Criteria: Previous surgery for endometriosis Previous IVF cycles Contraindication to pregnancy Hydrosalpinx Endometriomas with a mean diameter > 4 cm Submucosal fibroids or large intramural or subserosal fibroids (≥ 5 cm). Doubtful sonographic findings that do not allow to reliably rule out malignancy. Obstacles to regular sexual intercourses (sexual disturbances or logistic problems)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 39 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgery<br>Patients undergoing surgery for endometriosis, after surgery, will receive indications for seeking for a natural pregnancy up to 12 months from the time of randomization | Procedure: Surgery<br>* Laparoscopic treatment of endometriotic lesions<br>|
| Active Comparator: In Vitro Fertilization<br>Patients included in the IVF arm will undergo three complete cycles of IVF (i.e. three oocytes retrievals regardless of the number of embryo transfers) | Procedure: IVF<br>* Up to three completed cycles of IVF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate from pregnancies started within 12 months since randomization | to assess whether IVF is more effective than surgery in obtaining a live birth and, if so, what is the magnitude of this benefit | up to 12 months since randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost-effectiveness evaluation of the two different approaches in the treatment of endometriosis | to assess whether or not IVF is more cost-effective than surgery. To this aim, costs will be calculated based on the local charges for treatments (Diagnostic-related groups) and the costs of drugs supported by the public health system. The perspective will be the one of the public health provider. | 12 months | 
| Detachment of inflammatory mediators that might interfere with IVF through analysis of extracellular vescicles (EV). | to understand whether the endometriosis-related systemic inflammatory milieu demonstrated by the presence of circulating EVs characterized by an inflammatory signature may influence the folliculogenesis quality and IVF outcomes. EVs will be assessed by: Nanoparticle Tracking analysis (NTA) to determine their total values and their distribution; specific markers for the various lymphocyte populations by flow cytometry to assess the immunological origin; miRNA profile and proteomic analysis. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IVF, surgery, endometriosis