The Temporo-spatial Dynamics of Genital Tract Microbiota

The Temporo-spatial Dynamics of Genital Tract Microbiota - an Observational Study in IVF-Freeze All Patients Treated With Estradiol

The investigators aim to examine the endometrium with state of the art sequencing techniques to investigate the endometrial microbiota. The endometrial microbiota has been perceived to be sterile, however, this seems incorrect from recent studies. Thus, the primary outcome is to compare the rate of ascending infection from the semen to the vagina to the endometrium and to investigate which bacteria are capable of inhabiting these environments. Furthermore, cervical mucus will be obtained in order to test for immunological, microbiological and mechanical properties that may be involved in ascending infection. Finally, the study aim to characterize the temporal changes in the vaginal microbiota during estrogenic treatment with Estrofem® or Vivelle Dot (R) for preparation of the endometrium prior to embryo transfer.

Study Overview

• Status: Completed
• Conditions: Infertility, Female
• Intervention / Treatment: Drug: Estrofem

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• Denmark
  • Skive, Denmark, 7800
    • The Fertility Clinic, Regional Hospital of Skive
  • Skive, Denmark, 7800
    • The Fertility Clinic Skive

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Infertile couples attending IVF treatment and referred to a segmentation protocol.

Description

Inclusion Criteria:

• Patients in IVF Freeze-all/segmentation treatment protocol.
• Written informed consent.

Exclusion Criteria:

• Uterine malformations
• HIV, Hepatitis B or C positivity. HPV CIN 2 or higher. Chlamydia trachomatis positivity.
• Any uncontrolled concomitant disease (e.g. uncontrolled diabetes, uncontrolled hypertension etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal microbiota; Based on qPCR and Next gen sequencing
Abnormal microbiota; Based on qPCR and Next gen sequencing	Drug: Estrofem; Patients will be asked to obtain self-collected vaginal swabs from the mid-vagina from the beginning of their Estrofem® treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of ascending infection/sharing of bacteria in the genital tract	Seminal, vaginal, cervical and endometrial samples will be compared at the time of oocyte retrieval.	This outcome data is measured at the day of oocyte retrieval.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Next generation sequencing techniques will be used to assess the vaginal microbiota.I.e. measure of relative abundances	Vaginal microbiota changes throughout the preparation of the endometrium for frozen embryo transfer.	Examined longitudinally throughout the segmentation cycle. The estimated time to event is 40 days from oocyte retrieval until frozen embryo transfer following a strict protocol.
qPCR to assess the vaginal microbiota. I.e. a quantitative measure Copies/mL.	Vaginal microbiota changes throughout the preparation of the endometrium for frozen embryo transfer.	Examined longitudinally throughout the segmentation cycle. The estimated time to event is 40 days from oocyte retrieval until frozen embryo transfer following a strict protocol.
Number of participants with a Clinical pregnancy	Tested by clinical pregnancy scan by ultrasound in week 7-9	7-9 weeks after inclusion.
Number of participants with a Live birth	Tested by self-reported schemes	36-42 weeks after inclusion

Collaborators and Investigators

• Sponsor: Peter Humaidan
• Collaborators: Statens Serum Institut

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2017
• Primary Completion (Actual): September 23, 2019
• Study Completion (Actual): January 8, 2021

Study Registration Dates

• First Submitted: October 29, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (Actual): December 6, 2017

Study Record Updates

• Last Update Posted (Actual): February 9, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: 1-10-72-345-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Part of PhD project. Data will appear in the thesis and subsequent publications.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No