Modification of Endometrial Receptivity After Vaginal Seminal Plasma Application

Study Overview
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Brief Summary
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The aim of the project is to investigate the effect of seminal plasma on the endometrium and to evaluate changes in the endometrial receptivity after exposure to seminal plasma. Implantation is still an important limiting factor for the improvement of pregnancy rate in the Assisted Reproductive Technology (ART). Usually, in fertility clinics, only the spermatozoa are used for the treatments while the rest of the seminal fluid is discarded. However, the importance of seminal fluid in fertility has gained interest in the last years but no conclusive that has been obtained yet. Experimental group: We decided to focus our attention on lesbian couples and single women undergoing ART procedures because they could benefice the most from this treatment since they usually do not have contact with seminal plasma. Moreover, to the best of our knowledge, they have more problems in achieving a pregnancy than heterosexual couples. Our observation is supported by a preliminary analysis of data from the Dansk fertilitetsselskab. Design Randomized, double-blinded, placebo-controlled study Group 1 treated: 20 healthy lesbian or single women receiving assisted reproduction Group 2 control: 20 healthy lesbian or single women receiving assisted reproduction Treatment One month before the IVF procedure: First seminal plasma/placebo application during ovulation period Same month of the IVF procedure: second seminal plasma/placebo application after ovum pick up 5 days after the first application an endometrial biopsy and one blood sample will be taken for analysis. Analysis: Endometrial transcriptome microarray analysis that will be verified through protein analysis. Differences in the transcriptome between the two groups will be compared with data in literature for an optimal endometrial receptivity. Moreover, clinical pregnancy rate and pregnancy outcome will be compared.

Official Title
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Modification of Endometrial Receptivity After Vaginal Seminal Plasma Application: a Randomized Clinical Trial

Conditions
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Endometrial Receptivity

Intervention / Treatment
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* Other: seminal plasma
* Other: saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy lesbian and single women receiving IVF assisted reproduction treatment at OUH Fertility Clinic Exclusion Criteria: Language problems to such an extent that subjects do not understand the scope of the study. Abnormal high follicle-stimulating hormone severe endometriosis, severe polycystic ovarian syndrome chronic diseases

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>500 µl of saline solution applied in the vaginal volt twice : one month before the IVF procedure during the ovulation period Same month of the IVF procedure after ovum pick up | Other: saline solution<br>* saline solution<br>|
| Active Comparator: seminal plasma<br>500 µl of seminal plasma applied in the vaginal volt twice : one month before the IVF procedure during the ovulation period Same month of the IVF procedure after ovum pick up | Other: seminal plasma<br>* Seminal plasma free of sperm, from donor men with normal sperm parameters, and tested for HIV1, HIV2, Hepatitis B, Hepatitis C, Syphilis, Chlamydia and Gonorrhea on blood and urine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial transcriptome profile: mRNA array (fold change) | mRNA array ( fold change). Endometrial mRNA expression will be compared between treated and control group mRNA expression expression will be compared between treated and control group mRNA expression profiles will be compared with literature data for an optimal endometrial receptivity. | 24 months | 
| Endometrial protein concentration of leukemia inhibitory factor (LIF) | LIF concentration measured by ELISA test. LIF concentration will be compared between treated and control group. LIF has been chosen for its importance in implantation. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial proteins concentration | protein concentration of relevant genes selected after transcriptome analysis will be measured using ELISA test. Proteins concentration will be compared between treated and control group. | 24 months | 
| clinical pregnancy rate | clinical pregnancy rate difference between treated and control group ( presence of a fetal heartbeat at 6-7 weeks of pregnancy) | 6 months | 
| pregnancy rate | pregnancy rate difference between treated and control group (number of live birth) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fertility, seminal plasma, endometrium