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

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.

Study Overview

• Status: Completed
• Conditions: Infertility, Female; IVF
• Intervention / Treatment: Other: endometrium biopsy; Other: endometrium lavage; Other: repeated endometrium lavage

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.

• Study Type: Observational
• Enrollment (Actual): 67

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Infertile women participating in the diagnostic evaluation of infertility. The patients are contacted for participation in the study during the diagnostic evaluation of their infertility at specialized infertility or gynaecological clinic.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
endometrium biopsy only; In these cases, only endometrium biopsy is investigated for the selected biomarkers gene expression profile.	Other: endometrium biopsy; All patients will have endometrium biopsy.
endometrium lavage followed by endometrium tissue biopsy; 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; All patients will have endometrium biopsy.; Other: endometrium lavage; In some selected cases biopsy is preceded by endometrium lavage.
serial endometrium lavage followed by endometrium biopsy; 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; All patients will have endometrium biopsy.; Other: repeated endometrium lavage; Endometrium lavage is repeated during the same cycle.

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.

Collaborators and Investigators

• Sponsor: Prelife Kft
• Investigators: Principal Investigator: Balint L. Balint, MD, PhD, Prelife Kft

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2016
• Primary Completion (Actual): December 20, 2017
• Study Completion (Actual): August 28, 2018

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 8, 2019
• First Posted (Actual): August 9, 2019

Study Record Updates

• Last Update Posted (Actual): August 9, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: biomarkers; embryo transfer; endometrium; lavage; liquid biopsy; gene expression; biopsy; implantation window
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: PRELIFE-V8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared as the approval does not allow sharing of the individual participant data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No