Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000431820
Ethics application status
Approved
Date submitted
3/02/2021
Date registered
16/04/2021
Date last updated
23/09/2022
Date data sharing statement initially provided
16/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The long-term impact of endometriosis on reproductive outcomes.
Scientific title
A prospective longitudinal cohort study of the effect of conservative and surgical management for moderate to severe endometriosis on future fertility.
Secondary ID [1] 303245 0
None
Universal Trial Number (UTN)
Trial acronym
ELFS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 320424 0
Infertility 320425 0
Subfertility 320426 0
Condition category
Condition code
Reproductive Health and Childbirth 318317 318317 0 0
Fertility including in vitro fertilisation
Reproductive Health and Childbirth 318318 318318 0 0
Other reproductive health and childbirth disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
The study intervention/exposure is the surgical management for women with evidence of moderate/severe endometriosis.

This study remains an observational study. Participant's management, including the decision to perform surgery, will not be altered by participation in the study. The study aims to observe the impact of surgery vs conservative therapy, but does not dictate the requirement for surgery. Patients will be followed-up monthly from time of recruitment, until first live birth, or for 4 years, whichever occurs first.

Operative notes will be reviewed to assess surgical findings and what interventions are performed. Data from investigations and surgeries will be compiled by the research assistant.

Patients will be required to complete a baseline questionnaire, then a follow-up monthly (or cyclical questionnaire). The questionnaires are not validated. They have been developed for the purpose of the study. The primary assessable outcome is live-birth, with fertility data obtained along the way. Baseline questionnaire will take 20-30 minutes. Follow-up questionnaires should take less than 10minutes.
Intervention code [1] 319550 0
Not applicable
Comparator / control treatment
The control group includes women with evidence of moderate/severe endometriosis who are managed conservatively (no surgery).
- subgroup 1) women with moderate/severe endometriosis who try to conceive naturally
- subgroup 2) women with moderate/severe endometriosis who try to conceive with IVF

Participation requirements will be the same for women managed surgically and women managed conservatively. This will include a baseline questionnaire and brief monthly questionnaires until study conclusion.
Control group
Active

Outcomes
Primary outcome [1] 326288 0
For women with evidence of moderate-severe endometriosis (EMSE) and infertility who are attempting natural conception, to compare the “per cycle” live birth rate where EMSE is managed conservatively or surgically excised. This outcome is to be assessed by study-specific questionnaire.
Timepoint [1] 326288 0
Monthly observations over 4years, or until 1st live birth.
Primary outcome [2] 326289 0
For women with EMSE and infertility who are undergoing IVF to compare the “per cycle” live birth rate where EMSE is managed conservatively or surgically excised. This outcome is to be assessed by study-specific questionnaire.
Timepoint [2] 326289 0
Monthly observations over 4years, or until 1st live birth.
Secondary outcome [1] 390918 0
For women with EMSE who have been trying to conceive for less than 12 months or plan to in the future, to compare the “per cycle” clinical pregnancy rate and live birth rate where EMSE is managed conservatively or surgically excised. This is a composite outcome, to be assessed by study-specific questionnaire.
Timepoint [1] 390918 0
Monthly observations over 4years, or until 1st live birth.
Secondary outcome [2] 390919 0
To explore the characteristics of the menstrual cycle of women with EMSE who are or will be trying to conceive. This outcome is to be assessed by study-specific questionnaire.
Timepoint [2] 390919 0
Monthly observations over 4years, or until 1st live birth.
Secondary outcome [3] 390920 0
To explore the pregnancy outcomes of women with EMSE who successfully conceive. This is a composite outcome of adverse perinatal outcome including - premature birth, hypertensive disorders of pregnancy, caesarean delivery and fatal growth restriction. These outcomes are to be assessed by study-specific questionnaire.
Timepoint [3] 390920 0
Monthly observations over 4years, or until 1st live birth.
Secondary outcome [4] 392674 0
For women with EMSE and infertility who are undergoing IVF to compare the “per cycle” clinical pregnancy rate where EMSE is managed conservatively or surgically excised. This outcome is to be assessed by study-specific questionnaire.
Timepoint [4] 392674 0
Monthly observations over 4years, or until 1st live birth.
Secondary outcome [5] 392675 0
For women with evidence of moderate-severe endometriosis (EMSE) and infertility who are attempting natural conception, to compare the “per cycle” clinical pregnancy rate where EMSE is managed conservatively or surgically excised. This outcome is to be assessed by study-specific questionnaire.
Timepoint [5] 392675 0
Monthly observations over 4years, or until 1st live birth.

Eligibility
Key inclusion criteria
• <38 years of age at time of recruitment
• Desire for fertility (current or future)
• Evidence of untreated moderate or severe endometriosis on diagnostic laparoscopy or expert imaging (ultrasound or MRI)
• Own and use a mobile phone
Minimum age
18 Years
Maximum age
38 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• Inability to provide informed consent
• No desire for future fertility
• Findings suspicious of malignancy on imaging

Study design
Purpose
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Demographic continuous variables will be compared using the Welch t-test. Proportions will be compared using Chi-square test. P-values below 0.05 will be considered statistically significant.
Mixed effect analysis will be performed comparing clinical pregnancy and live birth rates, allowing for repeated measures (multiple months) within individual patients, as well as adjusting for length of infertility, age, type of cycle (natural vs IVF).

The study is designed as a prospective longitudinal cohort study, We aim to recruit 700 participants:
• 400 participants attempting natural conception – 200 in each of conservative group & surgical group
• 300 participants attempting conception through IVF – 150 in each of conservative group & surgical group

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/05/2021
Actual
1/11/2021
Date of last participant enrolment
Anticipated
31/10/2024
Actual
Date of last data collection
Anticipated
31/10/2028
Actual
Sample size
Target
700
Accrual to date
45
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 18496 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 18497 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [3] 18498 0
Sunshine Hospital - St Albans
Recruitment hospital [4] 18499 0
Epworth Richmond - Richmond
Recruitment hospital [5] 18500 0
Epworth Freemasons (Clarendon Street) - East Melbourne
Recruitment hospital [6] 18501 0
Frances Perry House - Parkville
Recruitment hospital [7] 18502 0
Warringal Private Hospital - Heidelberg
Recruitment hospital [8] 18880 0
East Melbourne Specialist Day Hospital - East Melbourne
Recruitment postcode(s) [1] 32814 0
3052 - Parkville
Recruitment postcode(s) [2] 32815 0
3084 - Heidelberg
Recruitment postcode(s) [3] 32816 0
3021 - St Albans
Recruitment postcode(s) [4] 32817 0
3121 - Richmond
Recruitment postcode(s) [5] 32818 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 23401 0
Israel
State/province [1] 23401 0
Jerusalem

Funding & Sponsors
Funding source category [1] 307655 0
Government body
Name [1] 307655 0
Medical Research Future Fund, Department of Health, Australian Government
Country [1] 307655 0
Australia
Primary sponsor type
Hospital
Name
Royal Womens Hospital
Address
20 Flemington Road
Parkville, VIC 3050
Country
Australia
Secondary sponsor category [1] 308348 0
None
Name [1] 308348 0
Address [1] 308348 0
Country [1] 308348 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307693 0
Austin Health
Ethics committee address [1] 307693 0
Austin Hospital
145 Studley Road
PO Box 5555
Heidelberg Victoria 3084
Ethics committee country [1] 307693 0
Australia
Date submitted for ethics approval [1] 307693 0
Approval date [1] 307693 0
10/09/2020
Ethics approval number [1] 307693 0
65683

Summary
Brief summary
This study is one of nine projects being run as part of a program of endometriosis research recently funded by Medical Research Future Fund

Infertility is associated with an increased rate of endometriosis. Surgically treating mild endometriosis has been demonstrated to improve fertility outcomes but studies assessing moderate and severe endometriosis are limited. Even the best studies, however, show that pregnancy rates via natural conception are substantially lower than those seen in fertile women.

Laparoscopic surgery to remove endometriosis exposes women to surgical risks including infections, adhesion formation and damage to a major organ. Exposing women to this risk can only be justified if there is a real benefit, either in symptom reduction or with improved fertility.

This study will explore the impact of surgical treatment of moderate to severe endometriosis on pregnancy and live birth rates from both natural conception and IVF. In addition, it will seek to clarify whether pre-emptive surgical treatment of endometriosis has an impact on future fertility.
Trial website
Trial related presentations / publications
Public notes
Endometriosis is a condition where tissue similar to the lining of the uterus (endometrium) is found developing in other areas of the pelvis. Women who have difficulty becoming pregnant are more likely to have endometriosis. In women with minimal to mild endometriosis, there is evidence that surgery to remove it increases the chance of becoming pregnant naturally. There is, however, no clear evidence about the effect of surgically removing moderate and severe endometriosis on the chance of pregnancy. Many women express a strong desire to protect their future ability to become pregnant. This puts them in a difficult situation if they are diagnosed with endometriosis – do they have it treated surgically, with the associated risks (including loss of tissue from the ovary and/or pelvic scarring) or do they leave it alone, in which case it might grow and be a greater risk to their dreams of future children?
The current study aims to provide clearer information for women with known endometriosis who have already been trying for pregnancy for at least 12 months. It will document their monthly chance of pregnancy from trying naturally and compare this between women who have surgery and those that don’t. The same comparison will also be done for women trying for pregnancy through in vitro fertilization (IVF). In addition, this study will assess the effect of watching compared to surgery on future pregnancy in women who are not yet trying to start a family.
Women who enroll in this study will be asked to complete an initial questionnaire and then will complete a short questionnaire (maximum of 10 questions) each month at the time of their period. This will be undertaken either through an online questionnaire or via a mobile phone app.

Contacts
Principal investigator
Name 108166 0
A/Prof Martin Healey
Address 108166 0
The Royal Womens' Hospital
Grattan St and Flemington Rd, Parkville, VIC 3052, Australia
Country 108166 0
Australia
Phone 108166 0
+61 488334519
Fax 108166 0
Email 108166 0
[email protected]
Contact person for public queries
Name 108167 0
Dr Samantha Mooney
Address 108167 0
Mercy Hospital for Women
163 Studley Road
Heidelberg VIC 3084
Country 108167 0
Australia
Phone 108167 0
+61 402923861
Fax 108167 0
Email 108167 0
[email protected]
Contact person for scientific queries
Name 108168 0
Dr Samantha Mooney
Address 108168 0
Mercy Hospital for Women
163 Studley Road
Heidelberg VIC 3084
Country 108168 0
Australia
Phone 108168 0
+61 402923861
Fax 108168 0
Email 108168 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.