Uterine Microbiome in Recurrent Pregnancy Loss

Study Overview
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Brief Summary
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The female genital tract microbiome may reflect female reproductive health and may be related to pregnancy outcomes. Disturbances in this microbiome may be associated with adverse reproductive outcomes. The investigators hypothesize that the endometrial and vaginal microbiome composition in women with a history of recurrent pregnancy loss are different, compared with those in normal fertile women.

Detailed Description
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The investigators want to describe the endometrial microbiome composition in normal fertile women and women with a history of recurrent pregnancy loss by analyzing mid-luteal phase vaginal swab and endometrial biopsy samples using 16S rRNA sequencing.

Official Title
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Reproductive Tract Microbiome in Women With Recurrent Pregnancy Loss

Conditions
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Recurrent Pregnancy Loss, Not Pregnant, Vaginal Microbiome

Intervention / Treatment
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* Other: Vaginal swab and endometrial biopsy


Participation Criteria
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Eligibility Criteria
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Recurrent pregnancy loss patients Inclusion Criteria: 18-38 years old Having a regular menstrual cycle, from 28 to 30 days Having ≥ 2 recurrent pregnancy loss and Couples with normal karyotype results Having no condition causing pregnancy loss such as antiphospholipid syndrome, abnormal thyroid function. Agree to participate in the study Exclusion Criteria: Irregular menstrual cycle Having uterine abnormalities (e.g., adenomyosis, intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus; unremoved hydrosalpinx, endometrial polyp, submucosal fibroid) Using intrauterine device within the last 3 months Using antibiotic/vaginal pessary/contraceptive pills within 2 weeks Having sexual intercourse within 48 hours Healthy control patients Inclusion Criteria: 18-38 years old Having a regular menstrual cycle, from 28 to 30 days No history of pregnancy loss Having 1 or more live birth, with the youngest child ≥ 6 months old Agree to participate in the study Exclusion Criteria: Irregular menstrual cycle Having uterine abnormalities (e.g., adenomyosis, intrauterine adhesions, unicornuate/ bicornuate/ arcuate uterus; unremoved hydrosalpinx, endometrial polyp, submucosal fibroid) Using intrauterine device within the last 3 months Using antibiotic/vaginal pessary/contraceptive pills within 2 weeks Having sexual intercourse within 48 hours

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Recurrent pregnancy loss<br>Women with history of recurrent pregnancy loss | Other: Vaginal swab and endometrial biopsy<br>* A vaginal swab (DNA/RNA shield collection tube with swab - Zymo Research, CatNo R1107) and endometrial biopsy (Endobrush® - Lab CCD, Paris, France) will be obtained during 18th - 22nd day of the menstrual cycle.<br>|
| Control<br>Normal fertile women | Other: Vaginal swab and endometrial biopsy<br>* A vaginal swab (DNA/RNA shield collection tube with swab - Zymo Research, CatNo R1107) and endometrial biopsy (Endobrush® - Lab CCD, Paris, France) will be obtained during 18th - 22nd day of the menstrual cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midluteal bacterial composition of endometrium in women with recurrent pregnancy loss and control group | Bacterial composition in the endometrium in midluteal phase are analysed using 16S rRNA gene sequencing | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Midluteal bacterial composition of vagina in women with recurrent pregnancy loss and control group | Bacterial composition in the vaginal in midluteal phase are analysed using 16S rRNA gene sequencing | 1 week | 
| Phylogenetic tree of endometrial microorganisms in women with recurrent pregnancy loss and control group | Phylogenetic tree based on 16S rRNA gene sequences | 1 week | 
| Phylogenetic tree of vaginal microorganisms in women with recurrent pregnancy loss and control group | Phylogenetic tree based on 16S rRNA gene sequences | 1 week |