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

Human Embryonic Stem Cell-derived Trophoblastic Spheroid (BAP-EB) as a Predictive Tool for Endometrial Receptivity and Pregnancy Outcome of in Vitro Fertilization Treatment

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.

Study Overview

• Status: Completed
• Conditions: Subfertility
• Intervention / Treatment: Procedure: endometrial biopsy

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.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • Department of Obstetrics and Gynaecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endometrial biopsy group; Women who have an endometrial biopsy 2-3 months prior to IVF	Procedure: endometrial biopsy; An endometrial biopsy taken 2-3 months prior to IVF cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative live birth rate	Cumulative birth rate: delivery of a live birth beyond 24 weeks of gestation in that episode of IVF treatment	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy	presence of at least one gestational sac on ultrasound at 6 weeks	6 weeks
Ongoing pregnancy	presence of at least one fetal heart pulsation on ultrasound beyond 20 weeks	20 weeks
Implantation rate	Number of ultrasound detected embryonic sacs divided by the number of embryos transferred.	6 weeks
Miscarriage rate	Number of miscarriages before 20 weeks divided by the number of women with a positive pregnancy test.	20 weeks
Multiple pregnancy	A pregnancy with more than one gestational sac detected on ultrasound at 6 weeks	6 weeks
Live birth rate	Live birth rate: delivery of a live birth beyond 24 weeks of gestation	42 weeks

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Kwong Wah Hospital; The University of Hong Kong-Shenzhen Hospital
• Investigators: Principal Investigator: Ernest HY Ng, The University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2017
• Primary Completion (Actual): July 4, 2020
• Study Completion (Actual): September 13, 2021

Study Registration Dates

• First Submitted: March 9, 2016
• First Submitted That Met QC Criteria: March 18, 2016
• First Posted (Estimate): March 21, 2016

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: In-vitro fertilization; Subfertility; BAP-EB; Endometrial epithelial cells; Repeated implantation failure
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: BAP-EB-2016-protocol-v1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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