Surgery and ART For Endometrioma

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Infertility, Female; Ovarian Endometrioma
• Intervention / Treatment: Procedure: Laparoscopic enucleation of ovarian endometrioma.; Procedure: Assisted Reproductive Technology (ART); Procedure: Prolonged pituitary downregulation

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Università degli Studi dell'Insubria

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2023
• Primary Completion (ANTICIPATED): October 1, 2025
• Study Completion (ANTICIPATED): October 1, 2027

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (ACTUAL): October 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Infertility; Laparoscopy; Endometrioma; GnRH-a; Assisted Reproduction Technology; Reproductive outcomes
• Additional Relevant MeSH Terms: Infertility; Endometriosis; Infertility, Female
• Other Study ID Numbers: SAFE-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No