Laparoscopic Sclerotherapy for the Management of Ovarian Endometriomas

Laparoscopic Sclerotherapy for Management of Endometriomas: A Pilot Study Evaluating Impact on Ovarian Reserve

The objective of this study is to evaluate the effect of laparoscopic sclerotherapy on ovarian reserve and its overall efficacy in the treatment of endometriomas. Ovarian reserve will be assessed using preoperative and postoperative anti-Müllerian hormone (AMH) levels and antral follicle count (AFC). Traditionally, ovarian endometriomas are managed by complete cystectomy; however, multiple studies including a large systematic review and meta-analysis-have demonstrated that cystectomy significantly reduces ovarian reserve, with an average decline in AMH of 1.77 ng/mL within one to six weeks postoperatively without recovery to baseline after many months. Sclerotherapy has historically been a potential alternative, typically performed by interventional radiology via transvaginal, transabdominal, or transgluteal drainage. This percutaneous approach, however, precludes direct visualization of the cyst and surgical management of concurrent conditions including endometriosis peritoneal disease, excision, adhesions, or tubal disease.

Several studies have explored the feasibility and effectiveness of laparoscopic sclerotherapy, reporting encouraging results regarding its safety, increased AFC compared with cystectomy, and comparable pregnancy rates. Nonetheless, none of these studies have been conducted in the United States, and few have utilized a laparoscopic approach. Further research is therefore warranted to establish the accessibility and reproducibility of this technique. The investigators aim to conduct the first U.S.-based study evaluating the impact of laparoscopic sclerotherapy on ovarian reserve. The primary outcome will be the change in AMH and AFC at six weeks postoperatively. Consistent with prior evidence, the investigators hypothesize that laparoscopic sclerotherapy will result in a smaller decline in ovarian reserve compared with traditional cystectomy.

Primary Endpoint:

- The change in pre op and post op AMH levels and Antral Follicle Count in patients with ovarian endometriomas.

Secondary Endpoints:

• Evidence of cyst resolution at 6-week ultrasound
• Recurrence of new endometriomas
• If any further surgical interventions are performed at the same time as sclerotherapy such as excision of endometriosis, tubal evaluation, hysteroscopy, etc.

Exploratory endpoints:

• Need for acute post op unplanned visits due to pain or concerns for infection
• Incidence of ER visits

STUDY INTERVENTION(S) / INVESTIGATIONAL AGENT(S):

This study involves the use of nearly 100% ethanol., also called ABLYSINOL, or an additional Brand name, currently in stock at the Northwestern Pharmacy- Avenacy Dehydrated alcohol ( ≥ 99% ethanol solution). Ethanol is available over the counter in 96% formulations. The Northwestern pharmacy does have 100% ethanol available for other surgical specialties that use the same agent for other sclerotherapy procedures. (Avenacy Dehydrated Alcohol, ≥ 99% ethanol solution).

IND Exemption using criteria: Category #1. Ethanol is lawfully marked in the U.S. The research is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in labeling for the drug. The research is not intended to support significant changes in advertising the product. The research does not involve a route, quantity, or patient population that significantly increases risk associated with the use of the drug product.

PROCEDURES INVOLVED:

Participants in this study will be screened through patients that present to the Center for Complex Gynecology at Northwestern Medicine. During their initial consultation for surgical management if they elect to proceed with surgical management of their endometriomas, the option for laparoscopic sclerotherapy and participation in this study will be offered if they meet all inclusion criteria. If the patient is not interested in participating in the study, they can still undergo surgical management with a cystectomy.

If patients express interest in participating in the study on laparoscopic sclerotherapy, a member of the study team will provide detailed information about the study during their clinic visit. Written informed consent will be obtained at that time, allowing participants adequate opportunity to ask questions and consider their decision.

In cases where the participant is unable to complete the consent process during the clinic visit, they will be provided with the consent form in advance and given time to review it. If the preoperative visit occurs via telehealth and the patient expressed interest in the study, the participant will be emailed a copy of the consent form and recruitment document. One of the members of the study team will also call the patient prior to the day of surgery to ensure all of their questions are answered; the consent form will then be signed on the day of surgery. As all patients are required to arrive 2 hours prior to their surgical time, there is plenty of time allotted to ensure a thorough review and discussion of the consent form and surgical plan is completed with the research team prior to surgery. Written consent will then be obtained on the day of surgery, prior to any study-related procedures, ensuring that participants have had sufficient time to consider their participation and have all questions addressed.

PRE OP PROTOCOL:

Patients will obtain pre-op AMH and an ultrasound guided AFC as it is the standard of care.

If a patient consents to the study, their AMH, AFC, size and laterality of the ovarian cyst will be documented.

Other information obtained from the chart will include age, parity, history of prior ovarian cystectomy, reproductive history including if patient is currently undergoing fertility treatment, history of prior endometriosis surgery, MRI evidence of deep infiltrating endometriosis.

SURGICAL PROTOCOL:

1. Enter the abdomen laparoscopically as per routine.
2. Perform a survey of the abdomen and pelvis as as per routine.
3. Evaluate the ovarian cyst as per routine.
4. Place lap pads in the abdomen and cover the bowel underlying the cyst that the participant will be working on to help protect it from incidental spillage.
5. Make a small incision within the capsule of the cyst to be able to fit suction and drain the cyst, as indicated for any other case.
6. Irrigate the inner wall of the cyst with saline, as is standing of care for cyst drainage.
7. Place a 16 fr silicone foley catheter through the trocar to the cyst (or smaller silicone catheter if indicated by the size of the cyst. Guide the cyst wall over the foley tip and fill the balloon so that the catheter stays in place within the cyst wall.
8. Fill the cyst with the Avenacy Dehydrated Alcohol (≥ 99% ethanol solution)ethanol solution, approximately 60% of the estimated volume of the cyst. Based on size estimates to calculate Volume, the investigators anticipate using approximately 40 mL for a 5 cm cyst with the amount needed varying based on the size of the ovarian cyst up to 100 mL. As the cyst is aspirated prior to the sclerotherapy this will also serve as a mechanism to know the volume capacity of the cyst. For example if 100 mL of endometriotic fluid is aspirated from the cyst, 60 mL of Avenacy Dehydrated Alcohol (≥ 99% ethanol solution) would then be used to fill the cyst of sclerotherapy.
9. Leave the solution in place for 15 minutes (dwell time).
10. The remainder of the endometriosis excision or evaluation of the pelvis can be performed at this time.
11. After 15 minutes has elapsed aspirate the contents of the cyst.
12. Evaluate the nonexposed walls of the cyst, resect any areas that did not receive any of the sclerosing agent.
13. Continue remainder of the laparoscopy as indicated by the patient's clinical factors.

POST OP PROTOCOL:

Patients may be discharged from same day surgery as that is the standard of care. They will follow up for a 2-week and 6-week post-op visit as that is the standard of care. At the 6-week post op visit an AMH will be drawn, and an ultrasound Antral follicle count will be obtained. The blood draw will be completed in the lab by phlebotomy within the Lavin Pavillion. Approximately 5 mL will be drawn to obtain an AMH level. Any prior ER visits or sooner follow-ups due to patient concerns will be documented.

INCLUSION AND EXCLUSION CRITERIA

Inclusion criteria:

• English speaking
• Age of 18 or greater
• At least one ovarian endometrioma > 4 cm in size
• Desires to proceed with surgical management of the endometrioma

Exclusion Criteria:

• Known diminished ovarian reserve (AMH < 1.0)
• Known allergies to ethanol solutions
• Pregnancy

Inclusion Criteria:

• English speaking
• Age of 18 or greater
• At least one ovarian endometrioma > 4 cm in size
• Desires to proceed with surgical management of the endometrioma

Exclusion Criteria:

• Known diminished ovarian reserve (AMH < 1.0)
• Known allergies to ethanol solutions
• Pregnancy