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Trial registered on ANZCTR


Registration number
ACTRN12623000487617
Ethics application status
Approved
Date submitted
14/04/2023
Date registered
12/05/2023
Date last updated
3/04/2024
Date data sharing statement initially provided
12/05/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does fertility treatment change your vaginal microbiome?
Scientific title
Does gonadotropin stimulation during Assisted Reproductive Technology treatment alter the composition of the vaginal microbiome: a feasibility study
Secondary ID [1] 309460 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility 329714 0
Condition category
Condition code
Reproductive Health and Childbirth 326612 326612 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
To determine if there are detectable changes across the vaginal microbiome in patients undergoing gonadotropin therapy as part of their Assisted Reproductive Technology journey, from pre-exposure to the medication prior to treatment, to the end of treatment at embryo transfer.

Data collected from participants includes:
• Provide vaginal swabs at 3 timepoints (Enrolment, Egg Collection & Embryo Transfer). . 3 x lower vaginal swabs will be self-collected by the participant (an education sheet and video is provided for this), and 2 x high-vaginal swabs will be collected by a trained health professional at the time of egg collection and embryo transfer.
• Provide personal history such as date of birth, ethnicity, sexual orientation, relationship status
• Provide information on your menstrual cycle history (date of last menstrual period, regular/irregular, length of cycle)
• Provide information on past and current medical/surgical history
• Provide information on current medications used, and medications used throughout your participation. This will also include gonadotropin dose and schedule once prescribed
• Undertake a small physical examination including vital signs (temperature, blood pressure, heart rate, respiratory rate), height, weight, BMI, body composition and waist circumference.
• Answer a small questionnaire on environmental exposures including smoking, alcohol, illicit drug use, caffeine use, pets & animals/livestock, and sleep quality

All of this information is collected as it has been documented to impact on the composition of a person's microbiome.

You will be involved in this project for approximately 4 months.
Intervention code [1] 325882 0
Not applicable
Comparator / control treatment
Samples are collected pre-exposure to gonadotropin therapy, which will be used as the control samples
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334471 0
Identify detectable changes in the vaginal microbiome following gonadotropin stimulation compared to baseline (exposure vs no exposure).

3 x low vaginal swabs, and 2 x high vaginal swabs will be collected to assess the microbiome
Timepoint [1] 334471 0
Enrolment - Self collected, low vaginal swab ONLY
Egg collection - Self collected low vaginal swab, and clinician-collected high vaginal swab
Embryo transfer - Self collected low vaginal swab, and clinician-collected high vaginal swab
Secondary outcome [1] 420811 0
To assess the influence of maternal age on changes in the vaginal microbiome determined by participant self-report and clinician-collected high vaginal swabs.
Timepoint [1] 420811 0
Enrolment - Self collected, low vaginal swab ONLY
Egg collection - Self collected low vaginal swab, and clinician-collected high vaginal swab
Embryo transfer - Self collected low vaginal swab, and clinician-collected high vaginal swab
Secondary outcome [2] 420813 0
Relationship between pre-existing medical conditions and changes in the vaginal microbiome
Timepoint [2] 420813 0
Enrolment - Self collected, low vaginal swab ONLY
Egg collection - Self collected low vaginal swab, and clinician-collected high vaginal swab
Embryo transfer - Self collected low vaginal swab, and clinician-collected high vaginal swab
Secondary outcome [3] 421856 0
Relationship between dose of gonadotrophin therapy and changes in the vaginal microbiome
Timepoint [3] 421856 0
Enrolment - Self collected, low vaginal swab ONLY
Egg collection - Self collected low vaginal swab, and clinician-collected high vaginal swab
Embryo transfer - Self collected low vaginal swab, and clinician-collected high vaginal swab

Eligibility
Key inclusion criteria
• Women undergoing Assisted Reproductive Technology
• 18 or older
• Agree to adhere to all protocol requirements.
• Provide written informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
• < 18 years of age
• Oncology patients undergoing fertility treatments
• History of recurrent miscarriage
• Already pregnant
• Premature ovarian insufficiency/failure
• Currently on Antibiotic therapy or have taken in the 3 months prior to enrolment
• Highly dependent on medical care by virtue of major pre-existing mental and/or physical disabilities
• Require interpreter services for either her usual care or to understand the study information will not be recruited

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Sample Size Estimation
A single-factor, repeated measures design with a sample of 28 subjects, measured at 3 time points, achieves 81% power to detect differences among the means using a Geisser-Greenhouse Corrected F Test at a 0.05 significance level. The standard deviation across subjects at the same time point is assumed to be 250. This assumes constant correlation among all repeated measures of 0.50. Means of 950, 1000 and 1100 were specified. This sample size would allow for pairwise tests to detect a mean difference of 161.5 or greater, assuming alpha of 0.0167 to account for multiple comparisons. Sample Size calculations were performed using PASS (2020).

Statistical Analysis Plan
Descriptive statistics at each time point will be reported, the means and standard deviations of continuous normally distributed variables, medians and Q1 and Q3 values for non-normal continuous variables, and frequencies and percentages of categorical variables.

Changes in diversity of vaginal microbiome will be examined using repeated measures ANOVA on the normal continuous outcome variables. If variables are not normal, a suitable transformation will be applied, or a non-parametric method will be used. Pairwise tests of differences between the time points will be run, at an alpha level of 0.05 / 3 to account for increase in Type I error due to multiple comparisons.

Total number of bacteria types detected at each time point and presence of particular individual bacteria at each time point will be examined using a generalized linear mixed model with appropriate distribution and link functions. Pairwise tests of difference between time points will be performed.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
9/05/2023
Date of last participant enrolment
Anticipated
1/06/2024
Actual
Date of last data collection
Anticipated
28/06/2024
Actual
Sample size
Target
35
Accrual to date
18
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 24532 0
Royal Hospital for Women - Randwick
Recruitment postcode(s) [1] 40124 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 313654 0
University
Name [1] 313654 0
UNSW Microbiome Research Centre
Country [1] 313654 0
Australia
Primary sponsor type
University
Name
University of New South Wales
Address
School of Clinical Medicine, UNSW Medicine & Health
St George & Sutherland Clinical Campuses
Level 2, Clinical Sciences Building (WR Pitney)
Short Street, St George Hospital
KOGARAH NSW 2217
Country
Australia
Secondary sponsor category [1] 315448 0
None
Name [1] 315448 0
Address [1] 315448 0
Country [1] 315448 0
Other collaborator category [1] 282631 0
Hospital
Name [1] 282631 0
Royal Hospital for Women, Fertility & Research Centre
Address [1] 282631 0
Fertility and Research Centre
Discipline of Women’s Health
School of Clinical Medicine, University of New South Wales
Level 1, Royal Hospital for Women, Barker Street, Randwick NSW 2031
Country [1] 282631 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312822 0
South Eastern Sydney Local Health District
Ethics committee address [1] 312822 0
SESLHD Research Directorate
Research Ethics and Governance Office

District Executive Unit, Level 4
The Sutherland Hospital & Community Health Service
Cnr The Kingsway and Kareena Road
CARINGBAH NSW 2229
Ethics committee country [1] 312822 0
Australia
Date submitted for ethics approval [1] 312822 0
03/03/2023
Approval date [1] 312822 0
24/04/2023
Ethics approval number [1] 312822 0
2023/ETH00395

Summary
Brief summary
IVF remains a difficult process – physically and emotionally - in part due to the ovarian stimulation protocols that stimulate the ovaries. It has been established that there is crosstalk between female gonadal hormones and the vaginal microbiome. This research aims to look at how the vaginal microbiome will respond when exposed to the physiologically abnormal doses of reproductive hormones introduced during Assisted Reproductive Technology treatment.

The purpose of this project is to investigate whether fertility treatment used to stimulate ovulation, changes the amount, or type, of microbes usually present in your vaginal microbiome. This study wants to know what a person's vaginal microbiome looks like prior to commencing gonadotropin fertility treatment, during treatment, and once the person has finished treatment.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126042 0
Prof William Ledger
Address 126042 0
Fertility and Research Centre
Discipline of Women’s Health
School of Clinical Medicine, University of New South Wales
Level 1, Royal Hospital for Women, Barker Street, Randwick NSW 2031
Country 126042 0
Australia
Phone 126042 0
+61 02 9382 6515
Fax 126042 0
Email 126042 0
w.ledger@unsw.edu.au
Contact person for public queries
Name 126043 0
Mrs Naomi Strout
Address 126043 0
UNSW Microbiome Research Centre
School of Clinical Medicine, UNSW Medicine & Health
St George & Sutherland Clinical Campuses
Level 2 Clinical Sciences (WR Pitney) Building
St George Hospital, Short St, Kogarah NSW 2217
Country 126043 0
Australia
Phone 126043 0
+61 02 9113 1832
Fax 126043 0
Email 126043 0
n.strout@unsw.edu.au
Contact person for scientific queries
Name 126044 0
Mrs Naomi Strout
Address 126044 0
UNSW Microbiome Research Centre
School of Clinical Medicine, UNSW Medicine & Health
St George & Sutherland Clinical Campuses
Level 2 Clinical Sciences (WR Pitney) Building
St George Hospital, Short St, Kogarah NSW 2217
Country 126044 0
Australia
Phone 126044 0
+61 02 9113 1832
Fax 126044 0
Email 126044 0
n.strout@unsw.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Consent not obtained for this purpose


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
18956Ethical approval  mothersbabies@unsw.edu.au
18957Statistical analysis plan  mothersbabies@unsw.edu.au
18958Informed consent form  mothersbabies@unsw.edu.au



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.