ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Infertility

Condition category

Condition code

Reproductive Health and Childbirth

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]

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]

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]

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]

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]

Secondary outcome [2]

Relationship between pre-existing medical conditions and changes in the vaginal microbiome

Timepoint [2]

Secondary outcome [3]

Relationship between dose of gonadotrophin therapy and changes in the vaginal microbiome

Timepoint [3]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Royal Hospital for Women - Randwick

Recruitment postcode(s) [1]

2031 - Randwick

Funding & Sponsors

Funding source category [1]

University

Name [1]

UNSW Microbiome Research Centre

Address [1]

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 [1]

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]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Hospital

Name [1]

Royal Hospital for Women, Fertility & Research Centre

Address [1]

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]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

South Eastern Sydney Local Health District

Ethics committee address [1]

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]

Australia

Date submitted for ethics approval [1]

03/03/2023

Approval date [1]

24/04/2023

Ethics approval number [1]

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

Prof William Ledger

Address

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

Australia

Phone

+61 02 9382 6515

Fax

[email protected]

Contact person for public queries

Name

Naomi Strout

Address

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

Australia

Phone

+61 02 9113 1832

Fax

[email protected]

Contact person for scientific queries

Name

Naomi Strout

Address

Country

Australia

Phone

+61 02 9113 1832

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Consent not obtained for this purpose

What supporting documents are/will be available?

Doc. No.	Type	Email
18956	Ethical approval	[email protected]
18957	Statistical analysis plan	[email protected]
18958	Informed consent form	[email protected]

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.

Trial Review

Documents added manually

Documents added automatically