The Temporo-spatial Dynamics of Genital Tract Microbiota

Study Overview
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Brief Summary
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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.

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

Conditions
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Infertility, Female

Intervention / Treatment
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* Drug: Estrofem


Participation Criteria
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Eligibility Criteria
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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.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 |