BAP-EB as a Predictive Tool for Endometrial Receptivity and Pregnancy Outcome of IVF Treatment

NCT ID: NCT02713854

Last Updated: 2022-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-01
• Study Completion Date: 2021-09-13

Brief Summary

To determine the predictive value of attachment rate of human embryonic stem cells (hESC)-derived trophoblast spheroids (BAP-EB, embryo surrogate) onto endometrial epithelial cells (EEC) on success of IVF treatment and to use the model to identify EEC surface biomarkers for endometrial receptivity.

Detailed Description

Study Objectives and Purpose:

There are three objectives in this study:

1. To determine the predictive value of the attachment rate of BAP-EB onto EEC on success of IVF treatment. The attachment rate of BAP-EB onto EEC of subfertile women in a natural cycle preceding the IVF cycle will be determined and correlated with the cumulative live birth rate in a subsequent stimulated IVF cycle and the derived frozen-thawed embryo transfer (FET) cycles.

2. To identify the surface molecules on EEC responsible for attaching to BAP-EB. The biotin-labeled primary EEC surface proteins that bind onto BAP-EB will be purified and identified by mass spectrometry. The bound proteins from "receptive" and "non-receptive" endometrial cell lines will be compared. The expression of the surface proteins on endometrial samples obtained in Objective 1will be correlated with their BAP-EB attachment rate.

3. To compare the BAP-EB attachment rate and expression of the attachment-related "receptive" EEC surface molecules between pre-receptive and receptive endometrium and between women with repeated implantation failure (RIF) and subfertile women due to male factors. To identify women with endometrial defects, women with RIF and failed IVF after preimplantation genetic screening (PGS) will be recruited. The latter recruitment criterion excludes RIF due to embryo aneuploidy.

Subjects:

Patients will be recruited from the Centre of Assisted Reproduction and Embryology, the University of Hong Kong at Queen Mary Hospital (HKU-QMH CARE) and at University of Hong Kong-Shenzhen Hospital (HKU-SZH CARE), the Dr Stephen Chow Chun-kay Assisted Reproduction Centre, Kwong Wah Hospital (SCCARC).

Treatment of Subjects:

Endometrial biopsies will be collected from the subjects and the attachment rate of BAP-EB onto isolated EEC will be associated with the implantation and pregnancy outcomes in IVF and the expressions of the isolated surface proteins.

Study duration: 36 months

Assessment of Safety:

1. Specification of safety parameters. Abdominal pain after endometrial aspirate

2. The methods and timing for assessing, recording, and analysing safety parameters. Subjects will be asked to contact investigators if they notice abdominal pain after endometrial aspirate

3. Procedures for eliciting reports of and for recording and reporting adverse event and intercurrent illnesses. Any abdominal pain will be documented in subjects' medical notes and they will be asked for any adverse effects and intercurrent illness when receiving IVF treatment.

4. The type and duration of the follow-up of subjects after adverse events. Subjects will be followed up in the Department of Obstetrics and Gynaecology as long as they have the adverse events.

Conditions

Subfertility

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Endometrial biopsy group

Women who have an endometrial biopsy 2-3 months prior to IVF

Group Type: EXPERIMENTAL

endometrial biopsy

Intervention Type: PROCEDURE

An endometrial biopsy taken 2-3 months prior to IVF cycle

Interventions

endometrial biopsy

An endometrial biopsy taken 2-3 months prior to IVF cycle

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Subfertile women indicated for the first IVF or women with cryopreserved embryos at HKU-QMH CARE, HKU-SZH CARE and SCCARC
• Women indicated for IVF treatment with a normal uterine cavity as demonstrated by saline infusion sonogram or hysteroscopy
• Women with regular ovulatory cycles

Exclusion Criteria

• The presence of an endometrial polyp or fibroid distorting the uterine cavity
• The presence of untreated hydrosalpinx
• IVF treatment carried out for preimplantation genetic diagnosis
• The use of donor oocytes

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 42 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The University of Hong Kong-Shenzhen Hospital

OTHER

Sponsor Role: collaborator

Kwong Wah Hospital

OTHER

Sponsor Role: collaborator

The University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ernest HY Ng

Role: PRINCIPAL_INVESTIGATOR

The University of Hong Kong

Locations

Department of Obstetrics and Gynaecology

Hong Kong, Hong Kong, China

Countries

China

References

Lee YL, Ruan H, Lee KC, Fong SW, Yue C, Chen ACH, Lee KF, Lam MT, Yeung WSB, Li RHW, Ng EHY. Attachment of a trophoblastic spheroid onto endometrial epithelial cells predicts cumulative live birth in women aged 35 and older. Fertil Steril. 2023 Aug;120(2):268-276. doi: 10.1016/j.fertnstert.2023.03.013. Epub 2023 Mar 20.

Reference Type: DERIVED

PMID: 36940739 (View on PubMed)

Other Identifiers

BAP-EB-2016-protocol-v1

Identifier Type: -

Identifier Source: org_study_id