The Impact on Ovarian Reserve of Ovarian Cystectomy Versus Laser Vaporization in the Treatment of Ovarian Endometrioma: a Randomized Clinical Trial (Laser)

This is a prospective, multicentric (two centers: 1:San Raffaele Scientific institute, Milan, Italy; 2:Jagiellonian University, Collegium Medicum, Cracow, Poland), randomized (1:1) clinical trial that includes patients undergoing surgery for primary unilateral or bilateral symptomatic endometriomas.

The aim of the study is to determine whether and to what extent the two surgical procedures for endometrioma, cystectomy and laser vaporization, affect ovarian reserve. Recently, cystectomy has been questioned as an ideal surgical approach because it may involve excessive removal of ovarian tissue and the loss of follicles; laser vaporization has been proposed as a promising method to preserve ovarian function.

Study Overview

• Status: Unknown
• Conditions: Endometrioma
• Intervention / Treatment: Procedure: stripping technique; Device: CO2 laser (AcuPulse Duo, Lumenis)

Detailed Description

Excisional surgery is the recommended treatment for ovarian endometrioma because of higher pregnancy rate and lower recurrence rate compared with ablative techniques. From the standpoint of ovarian reserve, the efficiency of cystectomy remains a topic of considerable debate: in recent years, cystectomy has been questioned as an ideal surgical approach for endometriomas because it is associated with excessive removal of ovarian tissue and loss of ovarian follicles with subsequent reduction of ovarian reserve. According to a recent report, absence of follicular growth was observed in 13% of operated ovaries, although this event never occurred in the contralateral gonad.

In San Raffaele Scientific Institute, fear of ovarian failure after cystectomy resulted in the introduction of an ablative technique involving CO2 laser technology, which posses the ability to deliver energy with little thermal spread. More than 80 patients were treated with CO2 laser at this Institution during three-year experience. This surgical procedure was inspired by the one employed by Jacques Donnez for more than 20 years, in which CO2 laser is used to ablate endometriomas' inner wall, after 3-months GnRHa therapy. Laser vaporization, according to the ''three-step procedure", has also been proposed as the best method to preserve ovarian function; moreover, reassuring data on the rate of long-term recurrence after laser vaporization have recently been published.

However, no data are available about the single use of CO2 laser fiber vaporization (without GnRHa therapy) with respect to the ovarian reserve.

Since 2015, the investigators have continuously evaluated the benefits of CO2 laser vaporization through a clinical trial assessing the postoperative changes in ovarian reserve as indicated by antral follicle count (AFC) and anti-mullerian hormone (AMH); the results of this pilot study support the positive effects of CO2 laser on ovarian reserve as demonstrated by higher AFC and no change in AMH at 3-month follow-up. In order to provide more conclusive data about the potential advantage of CO2 laser ablation with respect to ovarian cystectomy in terms of fertility outcomes a prospective randomized trial has been planned; the aim of this prospective randomized study is to determine whether and to what extent the two surgical procedures for ovarian endometrioma (cystectomy versus C02 laser vaporization) affect ovarian reserve.

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

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Recruiting
    • San Raffaele Scientific Institute
    • Contact: Jessica Ottolina, MD; Email: ottolina.jessica@hsr.it
    • Sub-Investigator: Laura M Castellano, MD
    • Sub-Investigator: Jessica Ottolina, MD
    • Principal Investigator: Massimo Candiani, MD Prof
• Poland
  • Cracow, Poland
    • Recruiting
    • Jagiellonian University, Collegium Medicum, Cracow, Poland
    • Contact: Ewa Posadzka, ND; Email: ewaposs@gmail.com
    • Sub-Investigator: Ewa Posadzka, MD
    • Sub-Investigator: Robert Jach, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 37 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• unilateral or bilateral endometriomas
• pain and/or infertility associated with endometriomas
• largest diameter of the endometrioma ≥3 cm and ≤ 8 cm

Exclusion Criteria:

• intra-operative detection of deep infiltrating endometriosis
• evidence of adenomyosis at the preoperative ultrasound
• previous surgical procedures on the ovaries
• previous unilateral oophorectomy
• previous salpingectomy or hysterectomy
• thyroid disease
• hyperprolactinemia
• diabetes mellitus
• adrenal disorders
• suspected or proven ovarian malignancy
• evidence of premature ovarian failure (POF) or premature menopause
• hormonal treatment within 3 months from baseline ovarian reserve assessment and 3 months after surgery.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: stripping; standardized laparoscopic stripping technique	Procedure: stripping technique; The cyst is stripped from the healthy ovary by traction and countertraction; after the removal of the cyst, hemostasis is achieved by selective bipolar coagulation.
Experimental: CO2 laser vaporization; drainage of the cyst content and vaporization of the internal wall with CO2 laser	Device: CO2 laser (AcuPulse Duo, Lumenis); The cyst content is drained and the internal wall is vaporized with CO2 laser beam (AcuPulse Duo, Lumenis, Israel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in antral follicle count (AFC)	number of follicles with average diameter of 2-10 mm in both ovaries assessed on the second and fifth day of the menstrual cycle	baseline and 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in serum antimullerian hormone (AMH) levels	AMH is assessed on venous blood samples (Beckman-Coulter 2nd-generation; Gen II) obtained on day 2-5 of the menstrual cycle	baseline and 3 months

Collaborators and Investigators

• Sponsor: Scientific Institute San Raffaele
• Investigators: Principal Investigator: Massimo Candiani, MD Prof, San Raffaele Scientific Institute

Publications and helpful links

General Publications

• Candiani M, Ottolina J, Posadzka E, Ferrari S, Castellano LM, Tandoi I, Pagliardini L, Nocun A, Jach R. Assessment of ovarian reserve after cystectomy versus 'one-step' laser vaporization in the treatment of ovarian endometrioma: a small randomized clinical trial. Hum Reprod. 2018 Dec 1;33(12):2205-2211. doi: 10.1093/humrep/dey305.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): August 1, 2017
• Study Completion (Anticipated): January 1, 2018

Study Registration Dates

• First Submitted: July 9, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): July 24, 2017
• Last Update Submitted That Met QC Criteria: July 20, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endometriosis
• Other Study ID Numbers: LaserLuM

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