Clinical trial NCT04743167: IVF Versus Surgery for Endometriosis Related Infertility
Official title: IVF Versus Surgery for the Treatment of Infertility Associated to Ovarian and Deep Peritoneal Endometriosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Endometriosis
Keywords: IVF
surgery
endometriosis
Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Sponsor class: OTHER
Collaborators: name: IRCCS San Raffaele
name: ASST Fatebenefratelli Sacco
name: Ministero della Salute, Italy
First posted: 2021-02-08
Enrollment: 206
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Live birth rate from pregnancies started within 12 months since randomization
timeFrame: up to 12 months since randomization
Secondary outcomes:
measure: Cost-effectiveness evaluation of the two different approaches in the treatment of endometriosis
timeFrame: 12 months
measure: Detachment of inflammatory mediators that might interfere with IVF through analysis of extracellular vescicles (EV).
timeFrame: 3 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: ASST-FBF-Sacco, Presidio Ospedaliero Macedonio Melloni
state: MI
city: Milan
country: Italy
facility: IRCCS San Raffaele
state: MI
city: Milan
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
state: MI
Study officials:
affiliation: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Laura Benaglia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ottolina J, Vignali M, Papaleo E, Vigano P, Somigliana E, Ferrari S, Liprandi V, Belloni G, Reschini M, Candiani M, Vercellini P, Benaglia L. Surgery versus IVF for the treatment of infertility associated to ovarian and deep endometriosis (SVIDOE: Surgery Versus IVF for Deep and Ovarian Endometriosis). Clinical protocol for a multicenter randomized controlled trial. PLoS One. 2022 Aug 3;17(8):e0271173. doi: 10.1371/journal.pone.0271173. eCollection 2022.