Implantation Test for Endometrial Receptivity

NCT03442335 | Completed

• 2 other identifiers: RG_17-179233994
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

Background Miscarriage is the most frequent complication of pregnancy and represents the spontaneous loss of the embryo or foetus before it is able to survive independently (24 weeks of gestation). It affects up to 50% of pregnancies with the vast majority (80%) occurring at pre-clinical stage before the woman recognises the pregnancy. Up to 5% of couples suffer recurrent miscarriage defined as 2-3 or more miscarriages leading to physical, emotional and financial consequences for couples, doctors and medical systems. Different maternal health problems (thyroid disease, sticky blood, autoimmune disease, anatomical anomalies of the womb) and embryo defects may be responsible for some of the miscarriages; however, more than 50% of the occurrences have no identifiable cause based on the current diagnostic tests. Aim The aim of the present research proposal is to understand the role of the lining of the womb in miscarriage and to explore the development of a potential implantation test that is cost-effective and may be implemented in clinical practice. Methods Over a period of two years, women who suffered recurrent miscarriage will be approached in the advanced miscarriage clinic at Birmingham Women's Hospital during their routine appointment. Participants will be invited to participate by undergoing chromohysteroscopy and/or a biopsy from the lining of the womb during an outpatient appointment. Chromohysteroscopy is based on a routine hysteroscopy which involves visualising the inside of the womb using a narrow telescope passed through the neck of the womb (cervix). "Chromo" comes from the fact that an iodine based dye will be injected to increase the power of the test. The biopsy will be taken using a narrow plastic tube passed through the cervix. It is a standard diagnostic test for women with abnormal bleeding. As part of the present research, different cells and molecules will be analysed from the biopsy sample.

Conditions

Pregnancy Loss; Miscarriage

Keywords

embryo implantation; endometrial receptivity; chromohysteroscopy; transcriptomics; proteomics; metabolomics; implantation window; luteal phase

Outcome Measures

Primary Outcomes (4)

• Iodine absorption

  Iodine interaction with the mid luteal phase endometrium.

  2 years

• Transcriptome profile

  Transcriptomics analysis of endometrial samples.

  2 years

• Proteome profile

  Proteomics analysis of endometrial samples.

  2 years

• Metabolome profile

  Metabolomics analysis of endometrial samples.

  2 years

Secondary Outcomes (2)

• Miscarriage rate

  5 years

• Live birth rate

  5 years

Study Arms (2)

Recurrent miscarriage: 2+ miscarriages

Women who suffered 2 or more unexplained recurrent miscarriages.

Diagnostic Test: Chromohysteroscopy; Diagnostic Test: Endometrial biopsy (Pipelle)

Extreme recurrent miscarriage: 5+ miscarriages

Women who suffered 5 or more unexplained recurrent miscarriages.

Diagnostic Test: Chromohysteroscopy; Diagnostic Test: Endometrial biopsy (Pipelle)

Interventions

Chromohysteroscopy DIAGNOSTIC_TEST

Standard hysteroscopy followed by injection of a dye, in this case iodine.

Extreme recurrent miscarriage: 5+ miscarriages; Recurrent miscarriage: 2+ miscarriages

Endometrial biopsy (Pipelle) DIAGNOSTIC_TEST

A narrow plastic tube (Pipelle) is passed through the cervix to aspirate a sample of endometrial tissue.

Also known as: Endometrial sampling

Extreme recurrent miscarriage: 5+ miscarriages; Recurrent miscarriage: 2+ miscarriages

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Women who suffered recurrent miscarriage (2+ miscarriages).
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

A cohort of women who suffered unexplained recurrent miscarriage will be sub grouped in two study populations: women who suffered two or more miscarriages and women who suffered five or more miscarriages (extreme recurrent miscarriage cohort). A total of 60 women will be recruited for the study investigations (30 for chromohysteroscopy and 30 for endometrial biopsy). We will select a very narrow phenotype in order to increase the study's sensitivity and power. Participants will be 18-35 years old, not pregnant and regularly menstruating in order to reduce the age effect on the pregnancy outcome. They will be diagnosed as having unexplained recurrent miscarriage by undertaking the standard miscarriage investigations.

You may qualify if:

• women diagnosed with unexplained recurrent miscarriage (2+ miscarriages with negative standard miscarriage investigations)
• regular menstrual cycles

You may not qualify if:

• women who have irregular menstrual cycles or those who require fertility treatments
• any positive finding or health issue that may explain the diagnosis of recurrent miscarriage
• women who are pregnant at the time of the study investigations
• women who are participants in other interventional studies or trials

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (6)

Tommy's National Centre for Miscarriage Research

Birmingham, B15 2TG, United Kingdom

Location

North Bristol NHS Trust

Bristol, United Kingdom

Location

Countess of Chester Hospital HNS Foundation Trust

Chester, United Kingdom

Location

Royal Devon and Exeter NHS Foundation Trust

Exeter, United Kingdom

Location

Saint Mary's Hospital

Manchester, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, United Kingdom

Location

Related Publications (3)

• Craciunas L, Pickering O, Chu J, Zurauskiene J, Coomarasamy A. Target Product Profile for an endometrial receptivity test: women's perspective. Eur J Obstet Gynecol Reprod Biol. 2020 Oct;253:42-47. doi: 10.1016/j.ejogrb.2020.07.058. Epub 2020 Aug 1.

  PMID: 32771887 RESULT

• Craciunas L, Pickering O, Chu J, Choudhary M, Zurauskiene J, Coomarasamy A. The transcriptomic profile of endometrial receptivity in recurrent miscarriage. Eur J Obstet Gynecol Reprod Biol. 2021 Jun;261:211-216. doi: 10.1016/j.ejogrb.2021.04.041. Epub 2021 Apr 30.

  PMID: 33971384 RESULT

• Craciunas L, Chu J, Pickering O, Mohiyiddeen L, Coomarasamy A. The metabolomic profile of endometrial receptivity in recurrent miscarriage. Minerva Obstet Gynecol. 2023 Dec;75(6):526-534. doi: 10.23736/S2724-606X.22.05151-X. Epub 2022 Oct 4.

  PMID: 36193833 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Endometrial samples taken during the implantation window (mid luteal phase, timed based on LH surge).

MeSH Terms

Conditions

Abortion, Spontaneous

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Laurentiu Craciunas

  Tommy's National Centre for Miscarriage Research

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 22, 2018
• Study Start: December 12, 2017
• Primary Completion: April 30, 2019
• Study Completion: October 31, 2022
• Last Updated: November 4, 2022

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share

Locations

GB (6)