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Ovarian Function After Use of Various Hemostatic Techniques During Treatment for Endometrioma (Endometrioma)

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ClinicalTrials.gov Identifier: NCT03430609
Recruitment Status : Recruiting
First Posted : February 13, 2018
Last Update Posted : October 7, 2019
Sponsor:
Collaborators:
Federal University of Paraíba
Irmandade da Santa Casa de Misericordia de Sao Paulo
Information provided by (Responsible Party):
Faculdade de Ciências Médicas da Santa Casa de São Paulo

Tracking Information
First Submitted Date  ICMJE October 31, 2017
First Posted Date  ICMJE February 13, 2018
Last Update Posted Date October 7, 2019
Actual Study Start Date  ICMJE April 1, 2018
Estimated Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2018)
  • AMH [ Time Frame: Before surgery ]
    Antimullerian hormone levels
  • AMH [ Time Frame: 1month after the surgery ]
    Antimullerian hormone levels
  • AMH [ Time Frame: 3 months after the surgery ]
    Antimullerian hormone levels
  • AMH [ Time Frame: 6 months after the surgery ]
    Antimullerian hormone levels
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03430609 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2019)
  • AFC [ Time Frame: Before surgery ]
    Ultrasound antral follicle counts
  • AFC [ Time Frame: 1month after the procedure ]
    Ultrasound antral follicle counts
  • AFC [ Time Frame: 3 months after the procedure ]
    Ultrasound antral follicle counts
  • AFC [ Time Frame: 6 months after the procedure ]
    Ultrasound antral follicle counts
Original Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2018)
  • FSH [ Time Frame: Before surgery ]
    Follicle-stimulating hormone levels
  • FSH [ Time Frame: 1 month after the procedure ]
    Follicle-stimulating hormone levels
  • FSH [ Time Frame: 3 months after the procedure ]
    Follicle-stimulating hormone levels
  • FSH [ Time Frame: 6 months after the procedure ]
    Follicle-stimulating hormone levels
  • AFC [ Time Frame: Before surgery ]
    Ultrasound antral follicle counts
  • AFC [ Time Frame: 1month after the procedure ]
    Ultrasound antral follicle counts
  • AFC [ Time Frame: 3 months after the procedure ]
    Ultrasound antral follicle counts
  • AFC [ Time Frame: 6 months after the procedure ]
    Ultrasound antral follicle counts
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ovarian Function After Use of Various Hemostatic Techniques During Treatment for Endometrioma
Official Title  ICMJE Ovarian Function After Use of Various Hemostatic Techniques During Treatment for Endometrioma: A Randomized Control Trial
Brief Summary

Background: Endometriosis is defined by the presence of endometrial tissue outside the uterine cavity due to causes not yet fully elucidated. The disease affects approximately 2% of women of reproductive age and is associated with infertility. Approximately 17% to 44% of women with endometriosis exhibit endometrioma, or ovarian endometriosis. Laparoscopic cystectomy is currently considered the gold standard treatment for this problem, resulting in improvement of symptoms, a lower recurrence rate and a higher pregnancy rate among infertile patients. However, several studies have shown that this treatment is not free from risks because it is associated with reduction of the ovarian reserve due to accidental removal of ovarian cortex during stripping of the capsule or damage caused by the coagulation energy during hemostasis, even when performed by experienced surgeons. There is still controversy in the literature as to the cause of the reduction of the ovarian reserve, as the mere presence of endometrioma reduces ovarian function by itself. The aim of this study is to compare the effects of different hemostatic methods on the ovarian function of women subjected to laparoscopic surgery for ovarian endometrioma.

Methods: Open-label randomized clinical trial to be conducted at Lauro Wanderley University Hospital from September 2017 to August 2020. Eighty-four patients will be randomly allocated to three groups according to the hemostatic technique used during laparoscopic surgery for ovarian endometrioma: bipolar coagulation, laparoscopic suture and hemostatic matrix. Ovarian function will be assessed by measuring serum anti-Mullerian hormone and follicle-stimulating hormone levels and by ultrasound antral follicle counts before surgery and 1, 3 and 6 months after surgery. The study was approved by the research ethics committee at the Medical Sciences Center, Federal University of Paraíba CAAE no. 71621717.9.0000.8069.

Discussion: The present study intends to assess the ovarian function of patients with endometrioma subjected to laparoscopic surgical treatment, comparing different hemostatic techniques like bipolar coagulation versus suture versus hemostatic matrix with objective assessments of bipolar coagulation to avoid bias. Thus, the investigators expect to contribute data likely to dispel doubts on the subject.

Detailed Description

OBJECTIVES

To compare the effects of various hemostatic methods on the ovarian function of patients subjected to laparoscopic surgery for ovarian endometrioma through AMH and ultrasound antral follicle count (AFC).

METHODS

Study design

An open-label randomized clinical trial will be performed to compare the impact of hemostatic techniques like bipolar coagulation versus laparoscopic suture versus hemostatic matrix during laparoscopic surgery for ovarian endometrioma on the ovarian follicular reserve.

Study setting

The study will be conducted at the endoscopic gynecology unit of Lauro Wanderley University Hospital, Federal University of Paraíba in Brazil.

Study and data collection period

The study will be performed from September 2017 to August 2020. Data will be collected from October 2017 to April 2020.

Study population

Patients with ovarian cysts suggestive of endometrioma on ultrasound cared for at the outpatient clinic of the HULW endoscopic gynecology unit during the study period.

Sample

In compliance with the eligibility criteria, consecutive convenience sampling will be performed among patients with ovarian cysts suggestive of endometrioma on ultrasound subjected to laparoscopic surgery and randomized to receive different hemostatic techniques during surgery: bipolar coagulation, laparoscopic suture or hemostatic matrix.

Sample size. The sample size was calculated through resources available on the Laboratory of Epidemiology and Statistics website of the Dante Pazzanese Institute. The calculation was based on data provided by Sönmezer et al. In this article, the investigators detected significant difference in the first month postoperative, with 2.72±1.49 AMH measurement among patients who receive hemostatic matrix versus 1.64±0.93 among patients who receive bipolar coagulation. Then the statistical assume that the 1.49 standard deviation for AMH measurement in the first month was significant and was the number that provide a greater sample size when compared with other values from that article. The difference to be detected is 1.08, which corresponds to the mean difference in AMH in the first month between the patients who receive hemostatic matrix and bipolar coagulation. On those grounds, and to achieve adequate statistical power 80%; p=0.05, each group should consist of 23 participants. Considering possible losses, the sample will be increased by 20%, corresponding to 28 participants per group and a total of 84 women.

Following inclusion, the participants will be randomized as described below. The sample will be divided into three groups according to the hemostatic technique used:

  1. Bipolar coagulation (bipolar tweezers, Astus Medical ©, Copyright 2015, Tampa FL, USA) with 30 W power and a Valleylab generator Medronic ©, Copyright 2017, Medtronic Parkway, Minneapolis, USA; the number of coagulated points will be counted, and the time for coagulation will be measured in seconds.
  2. Laparoscopic suturing with simple suture 2-0/Vicryl polyglactin absorbable synthetic suture; Ethicon Inc., New Jersey, USA; the number of sutures will be recorded.
  3. Hemostatic matrix Surgicel® Original Absorbable Hemostat, Ethicon, USA.

Procedures for randomization. Randomization to receive the various hemostatic techniques bipolar coagulation, laparoscopic suture or hemostatic matrix during laparoscopic surgery for endometrioma will be performed based on a list of sequential numbers from 1 to 84 total number of participants to be randomized generated by a statistician using Random Allocation Software version 2.0 and the letters A, B and C; the statistician will be blinded as to their meaning.

Another individual not participating in the study will receive the list of random numbers prepared by the statistician and will attribute a letter to each technique bipolar coagulation, laparoscopic surgery and hemostatic matrix through the lottery method. Next, this same individual will prepare opaque envelopes numbered from 1 to 84, which will contain the group of allocation.

At the time of inclusion, each participant will be assigned a number corresponding to their order of entrance in the study. The envelope with the corresponding number will be opened by a nurse at the surgical theater at the time of hemostasis during surgery. Thus, allocation will remain concealed before surgery.

Procedures for assessment of the ovarian reserve. The ovarian reserve will be assessed through measurements of AMH levels and ultrasound antral follicle count. The AMH levels will be quantitatively measured via ELISA, Enzyme-Linked Immunosorbent Assay Diagnostic Systems Laboratories, Webster, TX, with a detection sensitivity of 0.006 ng/mL.

The participants' sera will be obtained from blood samples after centrifugation for 10 minutes to separate the cell contents and debris. Each serum sample will be transferred to polypropylene tubes and stored at -70ºC. Venous blood samples will be collected before surgery on the day ultrasound is performed for antral follicle count, approximately 1 month before surgery and 1, 3 and 6 months after surgery.

The participants will also be subjected to transvaginal ultrasound for antral follicle count before surgery 1 month before surgery and 1, 3 and 6 months after surgery. This test will be performed during the early proliferative stage days 3 to 6 of the menstrual cycle; the size of the endometrioma and the ovary volume will be recorded, and functional cysts or suspected malignant cysts will be ruled out. For measurement of cysts, the average diameter of the three perpendicular ovary dimensions will be considered. For antral follicle count, the total number of follicles with diameters under 9 mm will be considered. The ovary and cyst volumes will be calculated using the equation 4/3 x π x (d/2)3, where d is the average diameter. All ultrasound tests will be performed by the same operator using the same device.

Procedures for laparoscopic surgery. Surgery will be performed by the same surgeon, with the participants under general anesthesia and in a semi-lithotomy position. A 10-mm umbilical puncture will be performed for the camera after insufflation of the pneumoperitoneum; three additional 5-mm punctures will be performed on the right iliac fossa, left iliac fossa and suprapubic area for instruments. The intra-abdominal pressure will be kept at approximately 15 mmHg.

Endometriosis will be categorized according to the classification formulated by the American Society for Reproductive Medicine - ASRM. In all of the groups, endometrioma will be removed by means of the traction and countertraction techniques. Adhesiolysis will be performed to separate the ovary from the adjacent structures as needed. In case of cyst rupture, the contents will be aspirated, and the site where the endometrioma contents fell will be exhaustively rinsed.

In the group allocated to receive bipolar coagulation, hemostasis will be performed using bipolar tweezers as few times as possible, just to control any considerable bleeding, at 30 W; the number of coagulated points will be recorded, and the duration of the procedure at each bleeding point will measured. These parameters will help elucidate possible flaws in previous studies, in which assessments were subjective, without specification of the duration of the coagulation in each point or the number of coagulated points.

In the group allocated to receive hemostasis by means of laparoscopic surgery, bipolar coagulation will not be performed, and the procedure will involve simple intraovarian sutures 1 or 2 knots with 2-0 Vicryl; the number of sutures will be counted.

In the group allocated to receive hemostasis by means of hemostatic matrix, bipolar coagulation will not be performed, and the sealant will be applied on the ovarian wound surface.

Procedures for data collection

Data collection instrument. The data will be recorded on standardized forms containing closed-ended questions pre-encoded for entry into the computer.

The information corresponding to categorical variables will be pre-encoded. Continuous variables will be expressed in the corresponding numerical values; only at the time of analysis will some be categorized.

The forms will be duly stored in specific folders before and after typing and analysis. This task will be under the responsibility of the investigator, who will complete the forms at various time points.

Data collection. The data will be collected by the investigator and a collaborator, who is a student from the Institutional Program of Undergraduate Research Scholarships. The collaborator will apply the checklist to candidates according to the eligibility criteria. Next, the study protocol will be applied, and the forms will be completed to record all necessary information.

Once completed, the forms will be rigorously reviewed by the investigator to check the collected information against that in the medical records. The time-points for data collection, adequate form completion and review will comply with those indicated in the schedule.

Data analysis. Statistical analysis will be performed by the investigator, her supervisors and a statistician using Excel software and the statistical software SPSS for Windows, version 19.0.0. Originally, SPSS was the acronym for Statistical Package for the Social Sciences, but at the present time, it is a part of the software name IBM SPSS®, without indication of any particular meaning.

Numerical variables will be compared by means of one-way analysis of variance ANOVA or the Kruskal-Wallis tests according to the normality or non-normality of the distribution. The chi-square or Fisher's tests will be used for categorical variables.

DISCUSSION

The reduction of ovarian function among patients with endometrioma is still a subject of study, and its cause requires further elucidation. Some authors consider that the presence of endometrioma itself accounts for the impairment of ovarian function. According to other authors, the factor associated with such impairment is the hemostatic method used following stripping of the endometrioma capsule, as some studies indicate that bipolar coagulation causes greater ovarian damage. However, no study has objectively assessed either the number of points requiring coagulation or the duration of coagulation; furthermore, the energy used is not standardized among studies. The present study intends to assess the ovarian function of patients with endometrioma subjected to laparoscopic surgical treatment, comparing different hemostatic techniques (bipolar coagulation versus suture versus hemostatic matrix) with objective assessments of bipolar coagulation to avoid bias. Thus, the investigators expect to contribute data likely to dispel doubts on the subject.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Open-label randomized clinical trial to be conducted at Lauro Wanderley University Hospital, at Federal University of Paraiba, from September 2017 to August 2020. Eighty-four patients will be randomly allocated to three groups according to the hemostatic technique used during laparoscopic surgery for ovarian endometrioma: bipolar coagulation, laparoscopic suture and hemostatic matrix. Ovarian function will be assessed by measuring serum anti-Mullerian hormone and by ultrasound antral follicle counts before surgery and 1, 3 and 6 months after surgery.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Endometriosis Ovary
  • Laparoscopy
  • Ovary; Functional Disturbance
  • Hemostasis
Intervention  ICMJE
  • Procedure: Laparoscopic treatment for endometrioma Astus©
    Laparoscopic surgery will be performed by the same surgeon, according to the routine of the service.In all of the groups, endometrioma will be removed by means of the traction and countertraction techniques. Adhesiolysis will be performed to separate the ovary from the adjacent structures as needed. In case of cyst rupture, the contents will be aspirated, and the site where the endometrioma contents fell will be exhaustively rinsed. In the hemostasis , the investigators will use coagulation with bipolar tweezers Astus Medical© in this group.
    Other Name: Treatment for ovarian endometrioma with bipolar Astus©
  • Diagnostic Test: AMH Level

    The AMH levels will be quantitatively measured via ELISA, Enzyme-Linked Immunosorbent Assay (Diagnostic Systems Laboratories, Webster, TX), with a detection sensitivity of 0.006 ng/mL.

    The participants' sera will be obtained from blood samples after centrifugation for 10 minutes to separate the cell contents and debris. Each serum sample will be transferred to polypropylene tubes and stored at -70ºC. Venous blood samples will be collected before surgery (on the day ultrasound is performed for antral follicle count, approximately 1 month before surgery) and 1, 3 and 6 months after surgery.

    Other Name: Antimulerian Hormone
  • Diagnostic Test: Transvaginal ultrasound for antral follicle count
    The participants will be subjected to transvaginal ultrasound for antral follicle count before surgery (1 month before surgery) and 1, 3 and 6 months after surgery. This test will be performed during the early proliferative stage (days 3 to 6 of the menstrual cycle); the size of the endometrioma and the ovary volume will be recorded, and functional cysts or suspected malignant cysts will be ruled out. For measurement of cysts, the average diameter of the three perpendicular ovary dimensions will be considered. For antral follicle count, the total number of follicles with diameters under 9 mm will be considered.
    Other Name: AFC
  • Procedure: Laparoscopic treatment for endometrioma Vicryl®
    Laparoscopic surgery will be performed by the same surgeon, according to the routine of the service.In all of the groups, endometrioma will be removed by means of the traction and countertraction techniques. Adhesiolysis will be performed to separate the ovary from the adjacent structures as needed. In case of cyst rupture, the contents will be aspirated, and the site where the endometrioma contents fell will be exhaustively rinsed. In the hemostasis , the investigators will perform suture with 2-0 Vicryl® in this group.
    Other Name: Treatment for ovarian endometrioma using vicryl suture
  • Procedure: Laparoscopic treatment for endometrioma Surgicel®
    Laparoscopic surgery will be performed by the same surgeon, according to the routine of the service.In all of the groups, endometrioma will be removed by means of the traction and countertraction techniques. Adhesiolysis will be performed to separate the ovary from the adjacent structures as needed. In case of cyst rupture, the contents will be aspirated, and the site where the endometrioma contents fell will be exhaustively rinsed. In this group, for hemostasis , the investigators will use matrix Surgicel®
    Other Name: Treatment for ovarian endometrioma using matrix Surgicel®
Study Arms  ICMJE
  • Active Comparator: Bipolar tweezers Astus Medical©
    Laparoscopic treatment for endometrioma Astus© will use Bipolar coagulation (bipolar tweezers, Astus Medical ©, Copyright 2015, Tampa FL, USA) with 30 W power and a Valleylab generator (Medronic ©, Copyright 2017, Medtronic Parkway, Minneapolis, USA); the number of coagulated points will be counted, and the time for coagulation will be measured in seconds. Transvaginal ultrasound for antral follicle count and blood collection will be performed in this group of patients before surgery, 1, 3 and 6 months after the procedure to dose AMH level, FSH level and to count the number of antral follicle.
    Interventions:
    • Procedure: Laparoscopic treatment for endometrioma Astus©
    • Diagnostic Test: AMH Level
    • Diagnostic Test: Transvaginal ultrasound for antral follicle count
  • Active Comparator: 2-0 Vicryl® Suture
    Laparoscopic treatment for endometrioma Vicryl® will use suturing with simple suture (2-0/Vicryl polyglactin absorbable synthetic suture; Ethicon Inc., New Jersey, USA); the number of sutures will be recorded. Transvaginal ultrasound for antral follicle count and blood collection will be performed in this group of patients before surgery, 1, 3 and 6 months after the procedure to dose AMH level, FSH level and to count the number of antral follicle.
    Interventions:
    • Diagnostic Test: AMH Level
    • Diagnostic Test: Transvaginal ultrasound for antral follicle count
    • Procedure: Laparoscopic treatment for endometrioma Vicryl®
  • Active Comparator: Surgicel®
    Laparoscopic treatment for endometrioma Surgicel® will use Hemostatic matrix (Surgicel® Original Absorbable Hemostat, Ethicon, USA). Transvaginal ultrasound for antral follicle count and blood collection will be performed in this group of patients before surgery, 1, 3 and 6 months after the procedure to dose AMH level, FSH level and to count the number of antral follicle.
    Interventions:
    • Diagnostic Test: AMH Level
    • Diagnostic Test: Transvaginal ultrasound for antral follicle count
    • Procedure: Laparoscopic treatment for endometrioma Surgicel®
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 6, 2018)
84
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 31, 2020
Estimated Primary Completion Date March 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18 to 43 years old.
  • Regular menstrual cycle (21 to 35 days).
  • Unilateral ovarian cyst suggestive of endometrioma.
  • Endometrioma and indication of laparoscopic surgery for cyst removal due to pelvic pain, infertility or cyst persistence.

Exclusion Criteria:

  • Previous ovarian surgery.
  • Endocrine dysfunction (diabetes, thyroid disorders, hyperprolactinemia, adrenal disease, polycystic ovary syndrome).
  • Use of hormones in the past 3 months.
  • Suspected ovarian malignant tumor requiring oophorectomy.
  • History of chemotherapy or radiotherapy.
  • Coagulation disorders.
  • Pregnancy.
  • Autoimmune disease.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 43 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Raquel Araujo, M.D. +5583993059773 raquel.silveira@gmail.com
Contact: Sabina Maia, M.D. +5583991974847 sabinamaia@hotmail.com
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03430609
Other Study ID Numbers  ICMJE U1111-1203-2508
71621717.9.0000.8069 ( Other Identifier: Certificate of Presentation for Ethical Assessment (CAAE) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Faculdade de Ciências Médicas da Santa Casa de São Paulo
Study Sponsor  ICMJE Faculdade de Ciências Médicas da Santa Casa de São Paulo
Collaborators  ICMJE
  • Federal University of Paraíba
  • Irmandade da Santa Casa de Misericordia de Sao Paulo
Investigators  ICMJE
Principal Investigator: Raquel Araujo, M.D. Faculdade de Ciências Médicas da Santa Casa de São Paulo; Universidade Federal da Paraíba
PRS Account Faculdade de Ciências Médicas da Santa Casa de São Paulo
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP