Clinical trial NCT02713854: BAP-EB as a Predictive Tool for Endometrial Receptivity and Pregnancy Outcome of IVF Treatment
Official title: Human Embryonic Stem Cell-derived Trophoblastic Spheroid (BAP-EB) as a Predictive Tool for Endometrial Receptivity and Pregnancy Outcome of in Vitro Fertilization Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Subfertility
Keywords: Subfertility
In-vitro fertilization
BAP-EB
Endometrial epithelial cells
Repeated implantation failure
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: The University of Hong Kong-Shenzhen Hospital
name: Kwong Wah Hospital
First posted: 2016-03-21
Enrollment: 240
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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

Primary outcomes:
measure: Cumulative live birth rate
timeFrame: 36 months
Secondary outcomes:
measure: Clinical pregnancy
timeFrame: 6 weeks
measure: Ongoing pregnancy
timeFrame: 20 weeks
measure: Implantation rate
timeFrame: 6 weeks
measure: Miscarriage rate
timeFrame: 20 weeks
measure: Multiple pregnancy
timeFrame: 6 weeks
measure: Live birth rate
timeFrame: 42 weeks
Other outcomes:
Locations:
city: Hong Kong
country: China
facility: Department of Obstetrics and Gynaecology
state: Hong Kong
Study officials:
affiliation: The University of Hong Kong
name: Ernest HY Ng
role: PRINCIPAL_INVESTIGATOR
References: