The Study of the Implantation Window From Endometrial Biopsy With Gene Expression Methods

Study Overview
=================
Brief Summary
-----------------
The objective of the study is to gain a better understanding of the gene expression changes in the endometrial biopsy especially whether the endometrium has reached a receptive status, i.e. the implantation window, or not.

Detailed Description
-----------------
The endometrium goes through huge gene expression changes during a cycle, the cells are transformed, the mucous membrane thickens, then loosens, and finally sheds. In this process, the expression of the genes also goes through significant changes, which can be determined from a small tissue sample. Endometrium biopsy samples can be used for endometrium phasing. A question of the study is the feasibility of using for endometrium phasing beside endometrium tissue biopsy also samples generated by endometrium lavage. The advantage of this latter method is that it is minimally invasive, it does not cause haemorrhage and has minimal side effects. In some selected cases endometrial lavage will be performed on the same day with endometrial tissue sampling together with the drawing of a peripheral blood sample. A list of potential biomarkers was proposed from the meta-analysis of published gene expression datasets. From the endometrium derived samples, RNA will be isolated and gene expression biomarkers will be measured. Expression profiles will be compared to published reference samples.

Official Title
-----------------
The Study of the Implantation Window From Endometrial Biopsy With Gene Expression Methods

Conditions
-----------------
Infertility, Female, IVF

Intervention / Treatment
-----------------
* Other: endometrium biopsy
* Other: endometrium lavage
* Other: repeated endometrium lavage


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: infertile women participating in the diagnostic evaluation of infertility. Exclusion Criteria: patients who are legally incapable or partially capable pregnancy should be excluded before sampling bleeding problems the active phase of severe psychiatric disorders

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| endometrium biopsy only<br>In these cases, only endometrium biopsy is investigated for the selected biomarkers gene expression profile. | Other: endometrium biopsy<br>* All patients will have endometrium biopsy.<br>|
| endometrium lavage followed by endometrium tissue biopsy<br>In these cases before the endometrium tissue biopsy, an endometrial lavage is performed and from both samples, the selected biomarkers gene expression profile are investigated. | Other: endometrium biopsy<br>* All patients will have endometrium biopsy.<br>Other: endometrium lavage<br>* In some selected cases biopsy is preceded by endometrium lavage.<br>|
| serial endometrium lavage followed by endometrium biopsy<br>In these cases before the endometrium tissue biopsy, at different days endometrial lavage samples are taken. From all samples, the selected biomarkers gene expression profile are investigated. | Other: endometrium biopsy<br>* All patients will have endometrium biopsy.<br>Other: repeated endometrium lavage<br>* Endometrium lavage is repeated during the same cycle.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gene expression profile | the endometrium derived samples are measured for the mRNA level expression of a selected list of biomarkers as it follows: ABCC3, ACTB, ADAMTS2, ADAMTS8, ARG2, ASPN, B2M, BAMBI, C10orf10, C1QTNF6, C2CD4A, CCDC71L, CD55, CEBPD, CP, CRISP3, CTHRC1, CYP24A1, CSRP2, DDX52, DPP4, DUOX1, DUOXA1, EDNRB, FCER1G, G0S2, GADD45G, GNG2, GNG4, GPX3, GRAMD1C, GREM2, GZMA, HPGD, HTR2B, IGFBP1, IGFBP3, IGFBP6, IL1B, IRX3, ITGA2, ITGB6, KAL1, KCND2, KCNK3, LCP2, LEFTY2, LRP4, LTBP2, LUM, MAOA, MAP2K6, MFSD4, MMP10, MS4A7, MT1M, MUC16, NID2, NNMT, OPRK1, PAEP, PDE4B, PHLDB2, PKHD1L1, PLAT, PLD1, POLR2A, PPIA, RARRES1, RDH10, RGS1, RHOB, RHPN2, RIMKLB, SGIP1, SLAIN1, SLC15A1, SLC15A2, SLC1A1, SLC26A7, SLC5A3, SOD2, SPP1, SYT11, TBP, TCN1, TFPI2, THBS1, TIMP3, TMC5, TMED6, TNFRSF11B, TSPAN8 | measurements are performed within 3 weeks after samples are shipped to the laboratory | 
| endometrium phase assesment | based on the gene expression profile endometrium samples are phase assigned based on published reference samples | phase assignment is performed within two weeks after the measurements are performed. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
gene expression, biomarkers, implantation window, embryo transfer, endometrium, biopsy, lavage, liquid biopsy