Condition category
Pregnancy and Childbirth
Date applied
29/07/2019
Date assigned
09/08/2019
Last edited
09/08/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
In vitro fertilisation (IVF) is one of several techniques available to help people with fertility problems have a baby. During IVF, an egg is removed from the woman's ovaries and fertilised with sperm in a laboratory. The fertilised egg, called an embryo, is then returned to the woman's womb to grow and develop. Though IVF has been useful, its success rate is still far from satisfactory. Previous studies have shown that the amount of blood vessels (vascularity) and the thickness of the lining of the womb (endometrium) were good predictors of live birth in IVF. Since a thin endometrium limits embryo implantation and a key risk factor for women infertility, efforts have been made to augment endometrium thickness using hormonal manipulation, however, they result in modest improvement of endometrial thickness (ET), vascularity, and subsequent pregnancy rate.

Stem cell therapy is a key new concept for improving endometrium function, especially in refractory cases. Peripheral blood mononuclear cells (PBMCs) are a source of stem cells having the potential to divulge into cells of different types. In the present study, we investigated the safety and efficacy of intrauterine administration of PBMCs in the proliferative phase of endometrial development prior to embryo transfer in patients.

Who can participate?
Women aged 21-45 years, with primary and/or secondary infertility, who had at least 3 failed IVF-FET treatments in the past.

What does the study involve?
Participants will have a small amount of blood taken on day 5 or 6 of their menstrual cycle. This blood will be prepared to extract the PBMCs, which will then be infused into the uterus. After 6 or 7 days, endometrium thickness and vascularity will be assessed. Once the endometrium has reached acceptable thickness, the embryo implantation will be carried out as normal.

What are the possible benefits and risks of participating?
Benefits: Chances of higher rate of pregnancy in infertile women.
There are no risks associated with this study.

Where is the study run from?
Institute of Reproductive Medicine, Kolkata, India

When is the study starting and how long is it expected to run for?
April 2016 to April 2020

Who is funding the study?
Investigator initiated and funded

Who is the main contact?
1. Prof Baidyanath Chakravarty
bncirm@gmail.com
2. Prof Swarup Chakrabarti
swarupkchakrabarti@gmail.com

Trial website

Contact information

Type

Scientific

Primary contact

Prof Baidyanath Chakravarty

ORCID ID

Contact details

Institute of Reproductive Medicine
HB-36/A/3
Salt Lake City
Sector-III
Kolkata
700106
India
+91 (0)33-23215125
swarupkchakrabarti@gmail.com

Type

Scientific

Additional contact

Prof Swarup Chakrabarti

ORCID ID

Contact details

Institute of Reproductive Medicine
HB-36/A/3
Salt Lake City
Sector-III
Kolkata
700106
India
+91 (0)9831643038
scindus@gmail.com

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

IRM/IEC/BNC-IHP-51

Study information

Scientific title

Pregnancy outcome in infertile women following intrauterine administration of peripheral blood mononuclear cells: a prospective study

Acronym

Study hypothesis

Peripheral blood mononuclear cells (PBMCs) may be a promising therapy for recurrent implantation failures in female infertile patients

Ethics approval

Approved 07/04/2016, Institute of Reproductive Medicine Ethics Committee (HB-36/A/3, Sector-III, Salt Lake, Kolkata 700106; bncirm@gmail.com; (91)33-23215125-27), ref: IRM/IEC/BNC-IHP-51

Study design

Prospective clinical study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a participant information sheet.

Condition

Infertility

Intervention

All women patients included in this study had failed to achieve pregnancy previously after a minimum of three FET attempts using standard IVF procedure. In this study, each patient served as an internal control for autologous PBMC treatment and clinical outcomes were measured in each patient before and after the PBMC treatment.

All patients received estradiol valerate (EV) 6.0 mg daily in divided doses from day 2 of their cycle. The dosage of EV was increased sequentially with a maximum of 12 mg per day depending on the endometrial thickness measured by serial transvaginal ultrasonography (TVS). Intrauterine infusion of PBMCs was done at day 5 or day 6 in patients. 10 ml of patient’s blood was collected on day 5-6 of a FET cycle and PBMCs were prepared using Lymphoprep density gradient centrifugation. PMBCs were infused immediately into the uterine cavity using a sterile catheter.

Ultrasound examination of the endometrial thickness was done from day 12 or day 13 of the treatment cycle. Assessment of endometrial vascularity was started when the endometrial thickness had reached 7 mm. Applebaum scoring was done to evaluate the vascularity of the endometrium. Presence of blood flow in Zone 3 or Zone 4 of the endometrium was taken as favourable parameter for frozen embryo transfer. When adequate endometrial preparation was achieved in the treatment cycle in terms of favorable endometrial thickness, morphology, and vascularity, progesterone was administered. FET was done after three days of progesterone administration. Progesterone was continued even after FET for luteal phase support (LPS) and was discontinued once the pregnancy had been confirmed and is producing an adequate amount of progesterone on its own. Human chorionic gonadotropin (hCG) levels were measured 13 days after FET to confirm biochemical pregnancy. The cardiac activity of the fetus was monitored by trans vaginal ultrasound sonography (TVS) after 3 weeks of FET to confirm a viable clinical pregnancy.

Intervention type

Supplement

Phase

Drug names

Primary outcome measure

1. Pregnancy rate at 12-weeks
2. Miscarriage rate at 12-weeks

Secondary outcome measures

1. Endometrial thickness measured using ultrasound examination at baseline and 12-weeks
2. Endometrial vascularity measured by transvaginal sonography (TVS) and Applabaum scoring was done evaluate the vascularity at baseline and 12-weeks

Overall trial start date

15/03/2016

Overall trial end date

30/04/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Female
2. Aged 21-45 years
3. Primary and secondary infertility
4. At least 3 failed IVF-FET

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

95

Total final enrolment

95

Participant exclusion criteria

1. Adenomyosis
2. Congential uterine anomalies
3. Baseline FSH> 12 IU
4. Donor oocyte recipients
5. Gestational surrogates

Recruitment start date

16/04/2016

Recruitment end date

31/12/2018

Locations

Countries of recruitment

India

Trial participating centre

Institute of Reproductive Medicine
HB-36/A/3 Salt Lake City Sector-III
Kolkata
700106
India

Sponsor information

Organisation

Institute of Reproductive Medicine

Sponsor details

Institute of Reproductive Medicine
HB-36/A/3
Salt Lake City
Sector-III
Kolkata
700106
India
+91 (0) 33-23215125
bncirm@gmail.com

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Trial results have been communicated to a peer-reviewed journal.

IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication

Intention to publish date

15/08/2019

Participant level data

Other

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

30/07/2019: Trial’s existence confirmed by Institute of reproductive medicine, Kolkata.