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Trial registered on ANZCTR


Registration number
ACTRN12620001201965
Ethics application status
Approved
Date submitted
16/09/2020
Date registered
12/11/2020
Date last updated
12/11/2020
Date data sharing statement initially provided
12/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Assessing change in Anti-Mullerian Hormone associated with surgical excision vs conservative management of endometrioma
Scientific title
Assessing change in Anti-Mullerian Hormone (ovarian reserve) associated with surgical excision vs conservative management of endometrioma: A longitudinal cohort study
Secondary ID [1] 302328 0
Nil known
Universal Trial Number (UTN)
U1111-1258-3461
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 319089 0
Endometrioma 319090 0
Condition category
Condition code
Reproductive Health and Childbirth 317042 317042 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
Patients with a diagnosis of one or more endometrioma will be asked to have a blood test to measure their serum anti-Mullerian hormone (AMH) and follicular stimulating hormone (FSH) levels as a marker of ovarian reserve prior to their planned intervention- either surgical excision or conservative management. The AMH and FSH will be measured at 7 time points- prior to surgery or at recruitment (for the conservative management group) and then 6 months, 1, 2, 3, 4 and 5 years following surgery or recruitment. The change in AMH and FSH over time will be assessed with a comparison between surgical or conservative management.
Intervention code [1] 318616 0
Diagnosis / Prognosis
Comparator / control treatment
Conservative management of endometrioma group (no surgery).
Control group
Active

Outcomes
Primary outcome [1] 325142 0
To assess and compare the change in serum AMH levels between women aged 25-37 with an endometrioma between 2-5cm over 6 months with and without surgical intervention.
Timepoint [1] 325142 0
6 months following surgery or recruitment depending on management arm.
Secondary outcome [1] 386980 0
To assess and compare the change in early follicular serum FSH levels between women aged 25-37 with an endometrioma between 2-5cm over 6 months with and without surgical intervention.
Timepoint [1] 386980 0
6 months following surgery or recruitment
Secondary outcome [2] 386981 0
To assess and compare the change in serum AMH levels between women aged 25-37 with an endometrioma >5cm and/or multiple endometriomas over 6 months with and without surgical intervention.
Timepoint [2] 386981 0
6 months following surgery or recruitment
Secondary outcome [3] 386982 0
To assess and compare the change in early follicular serum FSH levels between women aged 25-37 with an endometrioma >5cm and/or multiple endometriomas over 6 months with and without surgical intervention.
Timepoint [3] 386982 0
6 months following surgery or recruitment
Secondary outcome [4] 386983 0
To assess and compare the change in serum AMH levels at 1, 2, 3, 4 and 5 years following surgery or recruitment in women aged 25-37 with a single endometrioma with and without surgical intervention
Timepoint [4] 386983 0
1, 2, 3, 4 and 5 years following surgery or recruitment
Secondary outcome [5] 386984 0
To assess and compare the change in serum AMH levels at 1, 2, 3, 4 and 5 years following surgery or recruitment in women aged 25-37 with multiple endometriomas or a single endometrioma >5cm with and without surgical intervention
Timepoint [5] 386984 0
1, 2, 3, 4 and 5 years following surgery or recruitment
Secondary outcome [6] 386985 0
To assess and compare the change in early follicular serum FSH levels at 1, 2, 3, 4 and 5 years following surgery or recruitment in women aged 25-37 with a single endometrioma with and without surgical intervention
Timepoint [6] 386985 0
1, 2, 3, 4 and 5 years following surgery or recruitment
Secondary outcome [7] 386986 0
To assess and compare the change in early follicular serum FSH levels at 1, 2, 3, 4 and 5 years following surgery or recruitment in women aged 25-37 with multiple endometriomas or a single endometrioma >5cm with and without surgical intervention
Timepoint [7] 386986 0
1, 2, 3, 4 and 5 years following surgery or recruitment

Eligibility
Key inclusion criteria
Women aged 25-37 presenting to: general gynaecology outpatient clinic or Reproductive Services Unit at The Royal Women’s Hospital, or to a level 5 or 6 laparoscopic accredited gynaecologist or fertility specialist at Ramsay Health, Epworth Healthcare, Melbourne IVF or NewLife IVF, or the Endometriosis Centre at Hadassah-Hebrew University Medical Centre in Israel with an ultrasound (USS) diagnosis of endometrioma defined as: the presence of one or more ovarian cysts equal to or greater than 2cm diameter with regular margins and ground glass echogenicity that does not reduce in size over 4 or more weeks.
Minimum age
25 Years
Maximum age
37 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Endometrioma <2 cm diameter- these patients are more likely to be managed conservatively
Factors that can affect ovarian reserve, including previous ovarian surgery, oophorectomy, chemotherapy
Suspicion of malignancy- and will therefore be offered surgery
Inability to provide informed consent
Non-English speaking
Previous or planned hysterectomy- as hysterectomy is known to reduce AMH

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Given the multisite recruitment protocol of this study and those sites include both primarily surgical clinics and primarily fertility clinics, we expect similar recruitment numbers to both arms of the study. We therefore plan to continue recruitment until we have the same number in each arm.

A total sample size of 200 patients provides 80% power with a two-sided alpha of 0.05 to detect a minimum difference of 0.56 in mean AMH (primary outcome) at 6 months (primary time-point) between participants managed conservatively and those who received endometrioma excision, after controlling for baseline. This assumes an equal standard deviation in each group of 3.2 and a correlation of 0.9 between baseline and 6-month follow-up measurements, estimated from data provided by Kasapoglu et al 2018. Their study detected a difference of 0.71 in mean AMH at 6 months between groups after accounting for baseline so this study is powered to detect a difference of this magnitude. As this sample size is sensitive to the estimated correlation from the Kasapoglu et al., the calculations were also conducted assuming a more conservative correlation of 0.7 (it is assumed in this context that correlation is likely to be at least 0.7) between baseline and 6-month follow-up. This sample size would enable a minimum difference of 0.91 in mean AMH at 6 months between groups to be detected after controlling for baseline. Allowing for 30% drop out, a total sample size of 286 (143 per group) will be recruited.

Multilevel modelling will be used to examine change in AMH over time, allowing for clustering of time within individuals. The model will include factors representing group (conservative vs. surgery), time (baseline, 6 months, 12 months, 24 months) and a group by time interaction. Models will be fitted with and without adjustment for key confounders (e.g., age, body mass index, hormone use). Separate models will be fitted for the primary (i.e., women with endometrioma between 2-5cm) and secondary analysis (i.e., women with endometrioma between >5cm and/or multiple endometriomas). The absolute difference between the conservative and surgical groups in mean change from baseline will be estimated (including two-sided 95% confidence intervals) at 6 months (primary time point). The same approach will be used to analyse the secondary outcome FSH.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 17543 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 17544 0
Epworth Freemasons (Victoria Parade) - East Melbourne
Recruitment hospital [3] 17545 0
Epworth Richmond - Richmond
Recruitment postcode(s) [1] 31277 0
3052 - Parkville
Recruitment postcode(s) [2] 31278 0
3002 - East Melbourne
Recruitment postcode(s) [3] 31279 0
3121 - Richmond
Recruitment outside Australia
Country [1] 22991 0
Israel
State/province [1] 22991 0
Jerusalem

Funding & Sponsors
Funding source category [1] 306751 0
Government body
Name [1] 306751 0
The Australian Government Department of Health Medical Research Future Fund
Address [1] 306751 0
Australian Government Department of Health
GPO Box 9848
Canberra ACT 2601
Country [1] 306751 0
Australia
Primary sponsor type
Individual
Name
Keryn Harlow
Address
Gynaecology Unit 2
The Royal Women's Hospital
20 Flemington Road
Parkville
Victoria 3052
Country
Australia
Secondary sponsor category [1] 307307 0
None
Name [1] 307307 0
Address [1] 307307 0
Country [1] 307307 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306923 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 306923 0
Austin Hospital
145 Studley Road
PO Box 5555
Heidelberg
Victoria 3084
Ethics committee country [1] 306923 0
Australia
Date submitted for ethics approval [1] 306923 0
06/07/2020
Approval date [1] 306923 0
02/09/2020
Ethics approval number [1] 306923 0
HREC/66582/Austin-2020

Summary
Brief summary
Endometriomas are a type of endometriosis consisting of fluid filled benign cysts of the ovary. Endometriomas are associated with an increased risk of infertility and may require medical interventions to conceive. Management of these cysts prior to fertility treatment is controversial. On the one hand, leaving them has the potential for the cyst to get bigger and further damage ovarian tissue including eggs, as well as the very rare risks of malignancy and serious infection due to egg collection from the ovaries during fertility treatment. On the other hand, surgically removing the cyst has been shown to decrease the ovarian reserve, or the number of eggs left in the ovary and puts the patient through the risks of surgery.
This study aims to investigate how the ovarian reserve changes over time in patients with endometriomas left alone compared to those patients who have endometriomas surgically removed. This will help clinicians to decide the best way to manage these cysts in the future where fertility is desired. We plan to assess the ovarian reserve using a blood test to measure anti-mullerian hormone (AMH), which is secreted by the ovary and correlates with the number of available follicles (hosting future eggs).
Participants in this study will already have a management plan for their endometrioma and we will observe the change in the ovarian reserve over time by taking blood samples at 7 time points: at recruitment, 6 months post-surgery or recruitment, 12 months post- surgery or recruitment and then again at 2, 3, 4 and 5 years. These time points will be similar for both groups (cyst removal or not) to ensure comparable times between recruitment
and follow-up in both study arms. The results will be available to the participants and any abnormal results will be discussed with them by the investigative team and appropriate referrals made. The initial management plan will not be affected by this study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105462 0
Dr Keryn Harlow
Address 105462 0
Gynaecology 2 Unit
The Royal Women's Hospital
20 Flemington Road
Parkville
Victoria 3054
Country 105462 0
Australia
Phone 105462 0
+61449726564
Fax 105462 0
Email 105462 0
keryn.hoogervorst@gmail.com
Contact person for public queries
Name 105463 0
Dr Keryn Harlow
Address 105463 0
Gynaecology 2 Unit
The Royal Women's Hospital
20 Flemington Road
Parkville
Victoria 3054
Country 105463 0
Australia
Phone 105463 0
+61449726564
Fax 105463 0
Email 105463 0
keryn.hoogervorst@gmail.com
Contact person for scientific queries
Name 105464 0
Dr Keryn Harlow
Address 105464 0
Gynaecology 2 Unit
The Royal Women's Hospital
20 Flemington Road
Parkville
Victoria 3054
Country 105464 0
Australia
Phone 105464 0
+61449726564
Fax 105464 0
Email 105464 0
keryn.hoogervorst@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
To ensure participant privacy
What supporting documents are/will be available?
No other documents available
Summary results
No Results