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Biomarkers of Endometrial Receptivity (BIOMER)

Primary Purpose

IVF, Infertility Treatment, Fertility Disorders

Status
Recruiting
Phase
Not Applicable
Locations
Czechia
Study Type
Interventional
Intervention
Cervical mucus will be collected from patients undergoing IVF
Cervical mucus will be collected from patients undergoing transfer of cryopreserved embryos
Sponsored by
The Institute of Molecular and Translational Medicine, Czech Republic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IVF focused on measuring cervix, mucus, endometrium, receptivity, biomarker, proteomics, infertility, in-vitro, fertilisation

Eligibility Criteria

undefined - 36 Years (Child, Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria - Arm A - stimulated cycle:

  • female aged less than 37 years (maximally 36y + 364d)
  • no smoker
  • normal menstrual cycles lasting between 25 to 35 days
  • had been infertile for less than five years
  • normal responder
  • fewer than three failed cycles of assisted reproduction treatment, including fresh IVF/ intracytoplasmic sperm injection (ICSI) embryo transfer cycles and/or frozen-thawed embryo transfer cycles
  • sperm obtained through ejaculation
  • spermiogram more than 5 million sperm/mL
  • BMI 19-29 kg/m2
  • follicle stimulating hormone (FSH) < 10 IU/L on the third day
  • basal antral follicle count of 5-15
  • undergoing the same routine gonadotrophin-releasing hormone agonist (GnRHa) long depot or gonadotrophin-releasing hormone antagonist (GnRH-ant.) protocol
  • informed consent

Exclusion Criteria - Arm A - stimulated cycle:

  • genetic disease
  • metabolic and/or endocrine disorders
  • polycystic ovary syndrome (defined by the Rotterdam criteria)
  • women with prior diagnosis of endometriosis or adenomyosis
  • previous gynecological/pelvic surgery except for salpingectomy
  • repeated spontaneous abortions (two or more)
  • previously less than 5 oocytes and/or serum anti-Mullerian hormone value < 1.0 mIU/ml or more than 20 oocytes, milli-International unit (mIU)
  • previous ovarian hyperstimulation syndrome (OHSS)
  • presence of any structural abnormality of the reproductive system
  • donor oocyte cycles
  • severe male factor infertility < 5 million sperm/mL
  • low response to stimulation
  • endometrium < 8 mm at the day of human chorionic gonadotropin (hCG) or ET
  • number of retrieved oocytes 5 - 20
  • low fertilization capacity (rate of fertilization < 20% and late ICSI following IVF fertilization failure)
  • OHSS
  • IVF cycle cancelled before ET
  • other than easy one high-quality blastocyst transfer (at least grade 3BB)

Inclusion criteria - Arm B - substituted cycle:

  • female aged less than 37 years (maximally 36y + 364d)
  • no smoker
  • normal menstrual cycles lasting between 25 to 35 days
  • had been infertile for less than five years
  • normal responder at stimulation
  • fewer than three failed cycles of assisted reproduction treatment, including fresh IVF/ intracytoplasmic sperm injection (ICSI) embryo transfer cycles and/or frozen-thawed embryo transfer cycles
  • sperm obtained through ejaculation
  • spermiogram more than 5 million sperm/mL
  • BMI 19-29 kg/m2
  • FSH < 10 IU/L on the third day
  • undergoing the same routine estrogen/progesterone substituted cycle
  • informed consent

Exclusion criteria - Arm B - substituted cycle:

  • genetic disease
  • metabolic and/or endocrine disorders such as diabetes, metabolic syndrome, and thyroid disorders
  • polycystic ovary syndrome (defined by the Rotterdam criteria), hyperprolactinaemia
  • women with prior diagnosis of endometriosis or adenomyosis
  • previous gynecological/pelvic surgery except for salpingectomy
  • repeated spontaneous abortions (two or more)
  • previously less than 5 oocytes and/or serum anti-Mullerian hormone value < 0.5 mIU/ml in the stimulated cycle
  • previous OHSS
  • presence of any structural abnormality of the reproductive system
  • severe male factor infertility < 5 million sperm/mL in the stimulated cycle
  • number of retrieved oocytes 5 - 20 in the stimulated cycle
  • low fertilization capacity (rate of fertilization < 20% and late ICSI following IVF fertilization failure)
  • endometrium less than 8 mm at the day of thawing and transfer indication
  • thawed blastocyst cycle cancelled before ET
  • other than easy one best quality frozen/thawed blastocyst transfer (at least grade 3BB)

Sites / Locations

  • Brno University HospitalRecruiting
  • University Hospital OlomoucRecruiting
  • University Hospital OlomoucRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

A: Patients undergo cycle with the transfer of fresh embryos

B: Patients undergo cycle with the transfer of frozen embryos

Arm Description

In study group A the cervical mucus will be collected from patients undergoing the in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) cycle with the transfer of fresh embryos.

In study group B cervical mucus will be sampled from patients undergoing treatment cycles with the transfer of cryopreserved embryos.

Outcomes

Primary Outcome Measures

Mass spectrometer analysis of the proteins from cervical mucus
Highly sensitive mass analysis of the proteins from cervical mucus on Thermo Orbitrap Elite instrument for all collected samples.

Secondary Outcome Measures

Comparison of the protein analysis between the pregnant and not pregnant patients
Comparison of the protein analysis (qualitative and quantitative) will be done between the pregnant and not pregnant patients. Pregnant patients will be followed-up until child delivery.
Detection of the new endometrial receptivity biomarkers.
Proteomic endometrial receptivity biomarkers will be detected based on the analysis of measured data in relation to the successful implantation.

Full Information

First Posted
November 2, 2020
Last Updated
March 7, 2023
Sponsor
The Institute of Molecular and Translational Medicine, Czech Republic
Collaborators
University Hospital Olomouc, Brno University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04619524
Brief Title
Biomarkers of Endometrial Receptivity
Acronym
BIOMER
Official Title
Biomarkers of Endometrial Receptivity: A Prospective Multicenter Study on Proteomic Biomarkers of Endometrial Receptivity in Cervical Mucus ( PRO BIOMER - CM )
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 1, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Institute of Molecular and Translational Medicine, Czech Republic
Collaborators
University Hospital Olomouc, Brno University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Analysis of proteins from cervical mucus will be done in patients undergoing infertility treatment (fresh or frozen embryo transfer). Cervical mucus will be analysed for potential new biomarkers of endometrium receptivity. Comparison of the peptide spectrum will be done for the pregnant and not pregnant patients.
Detailed Description
Successful implantation depends on synchronization between a normal functional embryo at the blastocyst developmental stage and a receptive endometrium. The endometrium is receptive to blastocysts during a spatially and temporally restricted time window called the "window of implantation". Failure of the endometrium to attain receptivity is one cause of infertility, and this is not currently assessed during infertility workup due to a lack of reliable markers for receptivity. Better tests are required to assist the clinician with the decision when to defer a transfer and to freeze all embryos. Proteomics, or the analysis of the proteins in any sample, provides physiologically relevant information, since there are many regulatory steps between the transcriptome and functional proteins. Uterine fluid is a protein-rich histotroph that contains, among other components, secretions from the endometrial glands and cleavage products of both the secreted proteins and the glycocalyx. The aim of this study is to assess the highly sensitive mass spectrometer analysis of the proteins from cervical mucus for the detection of defects in endometrial receptivity and search for new endometrial receptivity biomarkers.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IVF, Infertility Treatment, Fertility Disorders, Embryo Transfer
Keywords
cervix, mucus, endometrium, receptivity, biomarker, proteomics, infertility, in-vitro, fertilisation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
476 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A: Patients undergo cycle with the transfer of fresh embryos
Arm Type
Experimental
Arm Description
In study group A the cervical mucus will be collected from patients undergoing the in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI)/embryo transfer (ET) cycle with the transfer of fresh embryos.
Arm Title
B: Patients undergo cycle with the transfer of frozen embryos
Arm Type
Experimental
Arm Description
In study group B cervical mucus will be sampled from patients undergoing treatment cycles with the transfer of cryopreserved embryos.
Intervention Type
Diagnostic Test
Intervention Name(s)
Cervical mucus will be collected from patients undergoing IVF
Intervention Description
Patients undergoing hormonal stimulation for IVF will be sampled for cervical mucus.
Intervention Type
Diagnostic Test
Intervention Name(s)
Cervical mucus will be collected from patients undergoing transfer of cryopreserved embryos
Intervention Description
Patients undergoing hormonal substitution for transfer of cryopreserved embryos will be sampled for cervical mucus.
Primary Outcome Measure Information:
Title
Mass spectrometer analysis of the proteins from cervical mucus
Description
Highly sensitive mass analysis of the proteins from cervical mucus on Thermo Orbitrap Elite instrument for all collected samples.
Time Frame
48 months
Secondary Outcome Measure Information:
Title
Comparison of the protein analysis between the pregnant and not pregnant patients
Description
Comparison of the protein analysis (qualitative and quantitative) will be done between the pregnant and not pregnant patients. Pregnant patients will be followed-up until child delivery.
Time Frame
48 months
Title
Detection of the new endometrial receptivity biomarkers.
Description
Proteomic endometrial receptivity biomarkers will be detected based on the analysis of measured data in relation to the successful implantation.
Time Frame
48 months

10. Eligibility

Sex
Female
Gender Based
Yes
Maximum Age & Unit of Time
36 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria - Arm A - stimulated cycle: female aged less than 37 years (maximally 36y + 364d) no smoker normal menstrual cycles lasting between 25 to 35 days had been infertile for less than five years normal responder fewer than three failed cycles of assisted reproduction treatment, including fresh IVF/ intracytoplasmic sperm injection (ICSI) embryo transfer cycles and/or frozen-thawed embryo transfer cycles sperm obtained through ejaculation spermiogram more than 5 million sperm/mL BMI 19-29 kg/m2 follicle stimulating hormone (FSH) < 10 IU/L on the third day basal antral follicle count of 5-15 undergoing the same routine gonadotrophin-releasing hormone agonist (GnRHa) long depot or gonadotrophin-releasing hormone antagonist (GnRH-ant.) protocol informed consent Exclusion Criteria - Arm A - stimulated cycle: genetic disease metabolic and/or endocrine disorders polycystic ovary syndrome (defined by the Rotterdam criteria) women with prior diagnosis of endometriosis or adenomyosis previous gynecological/pelvic surgery except for salpingectomy repeated spontaneous abortions (two or more) previously less than 5 oocytes and/or serum anti-Mullerian hormone value < 1.0 mIU/ml or more than 20 oocytes, milli-International unit (mIU) previous ovarian hyperstimulation syndrome (OHSS) presence of any structural abnormality of the reproductive system donor oocyte cycles severe male factor infertility < 5 million sperm/mL low response to stimulation endometrium < 8 mm at the day of human chorionic gonadotropin (hCG) or ET number of retrieved oocytes 5 - 20 low fertilization capacity (rate of fertilization < 20% and late ICSI following IVF fertilization failure) OHSS IVF cycle cancelled before ET other than easy one high-quality blastocyst transfer (at least grade 3BB) Inclusion criteria - Arm B - substituted cycle: female aged less than 37 years (maximally 36y + 364d) no smoker normal menstrual cycles lasting between 25 to 35 days had been infertile for less than five years normal responder at stimulation fewer than three failed cycles of assisted reproduction treatment, including fresh IVF/ intracytoplasmic sperm injection (ICSI) embryo transfer cycles and/or frozen-thawed embryo transfer cycles sperm obtained through ejaculation spermiogram more than 5 million sperm/mL BMI 19-29 kg/m2 FSH < 10 IU/L on the third day undergoing the same routine estrogen/progesterone substituted cycle informed consent Exclusion criteria - Arm B - substituted cycle: genetic disease metabolic and/or endocrine disorders such as diabetes, metabolic syndrome, and thyroid disorders polycystic ovary syndrome (defined by the Rotterdam criteria), hyperprolactinaemia women with prior diagnosis of endometriosis or adenomyosis previous gynecological/pelvic surgery except for salpingectomy repeated spontaneous abortions (two or more) previously less than 5 oocytes and/or serum anti-Mullerian hormone value < 0.5 mIU/ml in the stimulated cycle previous OHSS presence of any structural abnormality of the reproductive system severe male factor infertility < 5 million sperm/mL in the stimulated cycle number of retrieved oocytes 5 - 20 in the stimulated cycle low fertilization capacity (rate of fertilization < 20% and late ICSI following IVF fertilization failure) endometrium less than 8 mm at the day of thawing and transfer indication thawed blastocyst cycle cancelled before ET other than easy one best quality frozen/thawed blastocyst transfer (at least grade 3BB)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Radovan Pilka, Prof.MD.PhD.
Phone
+420739329868
Email
radovan.pilka@fnol.cz
First Name & Middle Initial & Last Name or Official Title & Degree
Petr Dzubak, MD.PhD.
Phone
+420604851158
Email
dzubakp@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marian Hajduch, MD.PhD.
Organizational Affiliation
Palacky University in Olomouc, Faculty of Medicine and Dentristry
Official's Role
Study Director
Facility Information:
Facility Name
Brno University Hospital
City
Brno
State/Province
Jihomoravsky Kraj
ZIP/Postal Code
62500
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Igor Crha, MD, PhD
Phone
+420728159163
Email
crha.igor@fnbrno.cz
Facility Name
University Hospital Olomouc
City
Olomouc
ZIP/Postal Code
77900
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Petr Dzubak, MD, PhD
Phone
+420 585632150
Email
petr.dzubak@upol.cz
First Name & Middle Initial & Last Name & Degree
Marian Hadjuch, MD, PhD
Phone
+420 585632082
Email
marian.hajduch@upol.cz
Facility Name
University Hospital Olomouc
City
Olomouc
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Radovan Pilka, Prof.MD.
Phone
+420739329868
Email
radovan.pilka@fnol.cz

12. IPD Sharing Statement

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