Endometrial Effects of Lipiodol

Study Overview
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Brief Summary
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The goal is to investigate whether endometrial flushing with Lipiodol enhances fertility. Therefore, anatomo-pathological, histochemical and transcriptional changes of the endometrium after Lipiodol bathing in a general population of healthy volunteers will be determined.

Detailed Description
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A single-centre, cross-over, open-label trial will be performed. Healthy volunteers, fulfilling the inclusion/exclusion criteria, will be asked to do blood samples and ultrasounds for the detection of the LH (luteinizing hormone) surge in a natural cycle. The intervention group will undergo endometrial flushing with Lipiodol between day 6 and 8 of the cycle, while the control group between day 6 and 8 of the cycle will have a mock catheter introduction without any Lipiodol flush. An endometrial biopsy will be performed 7 days after the LH peak in all the participants. Furthermore, all the participants will undergo one cycle with flushing and one cycle with introduction of a mock catheter but without flushing with any medication. The wash-out period between the 2 biopsies will be 3 months.

Official Title
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Histological and Transcriptional Changes Caused by Endometrial Flushing With Lipiodol: A Cross Over Study

Conditions
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Female Infertility

Intervention / Treatment
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* Drug: Lipiodol
* Device: Mock catheter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged ≥18 and <36 years Regular cycle (25-35 days) Signed informed consent Participants can be included only once in the trial Contraceptive: barrier method only. Exclusion Criteria: known iodine allergy Body mass index 30 or ≤18.5 Smoking Previous diagnosis of PCO (Polycystic Ovary Syndrome) (>12 antral follicles in one ovary, Rotterdam criteria 2003) Previous diagnosis of endometriosis, uterine malformations or intrauterine pathologies (submucosal fibroids, endometrial polyps, and intrauterine adhesions) Systemic diseases such as thyroid dysfunction Breast-feeding or pregnancy within the last 6 months Intrauterine devices (IUD) History of recurrent miscarriage Known history of infertility Previous uterine surgery Pregnancy wish during the course of the study Women who have been previously enrolled in the trial Those unable to comprehend the investigational nature of the proposed study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 36 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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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control group<br>The control group wille have a mock catheter introduction between day 6 and 8 of the cycle without any Lipiodol flush | Device: Mock catheter<br>* Introduction of a mock catheter in the uterus between day 6 and 8 of the cycle<br>|
| Experimental: Intervention group<br>The intervention group will undergo endometrial flushing with Lipiodol between day 6 and 8 of the cycle | Drug: Lipiodol<br>* Endometrial flushing with Lipiodol between day 6 and 8 of the cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anatomo-pathological changes of the endometrium after Lipiodol bathing | To determine whether the treatment with lipiodol alters the leukocyte population. Changes in the uterine dendritic cell population, collections of macrophages and an increased number of inflammatory cells will be investigated. A sub-ephitelial re-location of lymphocytes (CD3-CD7 and CD8 (CD: Cluster of Differentiation)) will be looked for. | 7 days after LH peak | 
| Histochemical changes of the endometrium after Lipiodol bathing | The immunohistochemistry for the key implantation factors, the subsequent molecular markers will be examined: estrogen receptors (ER) (α/β), progesterone receptors (PR) (A, B), prolactine (PRL), insulin-like growth factor binding protein-1 (IGF-BP1), leukaemia inhibitory factor (LIF), Mucins (MUC1), integrin αVβ3, vascular endothelial growth factor (VEG-F), transforming growth factor (TGF-β1). | 7 days after LH peak | 
| Transcriptional changes of the endometrium after Lipiodol bathing | RNA sequencing | 7 days after LH peak |