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Low Molecular Weight Heparin to Improve Pregnancy Outcome in Patients With Recurrent Implantation Failure (BRIF)

Primary Purpose

Sterility

Status

Completed

Phase

Phase 4

Locations

Lebanon

Study Type

Interventional

Intervention

Bemiparin sodium

About this trial

This is an interventional treatment trial for Sterility focused on measuring Recurrent Implantation Failure, Implantation, low molecular weight heparin, In vitro Fertilization, Assisted Reproductive Technology, Pregnancy

Eligibility Criteria

18 Years - 38 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

History of three or more consecutively failed In Vitro Fertilization (IVF) cycles after embryo transfer.
Normal uterine cavity (as assessed by hysteroscopy or HSG).
Normal hormonal investigation: TSH, PRL, FBS.
Normal acquired/inherited thrombophilia profile: LAC, ACA IgG/IgM, Prot S, Antithrombin III, beta-2 glycoprotein, Factors V, II, MTHFR.
Normal semen analysis and mild/moderate male factor (Total motile sperm count > 5 million/ml and/or normal WHO morphology >20%.
Patient provides written informed consent.

Exclusion Criteria:

Evidence of low ovarian reserve by at least one of the following: AMH ≤ 1,5 ng/mL and/or basal CD 3 FSH ≥ 10 mIU/mL and/or basal CD 3 Estradiol ≥ 60 ng/mL and/or previous egg collection yield ≤ 3 oocytes.
Preexisting medical condition (thyroid disease, diabetes mellitus, hypertension, pulmonary conditions, cardiac condition…).
Severe male factor infertility (Total motile sperm count < 5 million/ml and/or normal WHO morphology <20%).
Hypersensitivity to Heparin or its derivatives.
Acquired thrombophilia.
Active hemorrhage or increased risk of bleeding due to impairment of homeostasis.
Severe impairment of liver or pancreatic function.
Severe renal insufficiency (Creatinine Clearance < 30 ml/min).
Injuries to or operations on the central nervous system, eyes and ears within the last 2 months.
Disseminated Intravascular Coagulation (DIC) attributable to heparin-induced thrombocytopenia.
Acute bacterial endocarditis and endocarditis lenta.
Any organic lesion with high risk of bleeding (e.g.: active peptic ulcer, hemorrhagic stroke, cerebral aneurysm or cerebral neoplasms).

Sites / Locations

American University of Beirut Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Low molecular weight heparin

No intervention group

Arm Description

Bemiparin sodium 3,500 IU anti Xa/0.2 ml solution (Hibor; Laboratories Rovi Pharmaceuticals) for injection in pre-filled syringes.

Control group receiving standard care.

Outcomes

Primary Outcome Measures

Implantation rate (%)

Number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos

Secondary Outcome Measures

Live birth rate (%)

birth of live born

Ongoing pregnancy rate (%)

Fetal heart beat seen by ultrasound at 20 weeks gestation

Clinical pregnancy rate (%)

Fetal heart beat seen by ultrasound at 8 weeks gestation

Total pregnancy rate (%)

Positive hCG titer

Full Information

NCT ID

NCT02607319

First Posted

November 11, 2015

Last Updated

July 19, 2023

Sponsor

American University of Beirut Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT02607319

Brief Title

Low Molecular Weight Heparin to Improve Pregnancy Outcome in Patients With Recurrent Implantation Failure

Acronym

BRIF

Official Title

Effect of Low Molecular Weight Heparin (Bemiparin) on Implantation Rate in Patients With Recurrent Implantation Failure Undergoing IVF/ICSI - A Prospective Randomized Clinical Trial

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

November 2015 (Actual)

Primary Completion Date

July 2022 (Actual)

Study Completion Date

July 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

American University of Beirut Medical Center

4. Oversight

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The objective of this study is to determine the effect of Bemiparin, a low molecular weight heparin, on implantation rate in women with unexplained recurrent implantation failure undergoing IVF/ICSI treatment.

Detailed Description

Recurrent implantation failure (RIF), defined as failure of conception following three or more consecutive In Vitro Fertilization (IVF) cycles despite the transfer of good quality embryos, is a major cause of distress amongst infertile couples. While factors underlying implantation failure are many, most cases remain unexplained. In order to improve pregnancy outcomes and delivery rates in women with unexplained RIF, various investigational treatments have been proposed. The investigators propose a prospective controlled randomized comparative study to evaluate the effect of Bemiparin on implantation rates in women with unexplained RIF. A total of 200 patients will be recruited and randomized between two groups. The study group will receive Bemiparin plus standard care; while the control group will receive only standard care. Treatment will start on the day following embryo transfer and will be continued until 12 weeks gestation in the event of pregnancy. The primary objective is to determine the effect of Bemiparin on implantation rate in women with unexplained recurrent implantation failure.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sterility

Keywords

Recurrent Implantation Failure, Implantation, low molecular weight heparin, In vitro Fertilization, Assisted Reproductive Technology, Pregnancy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

165 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Low molecular weight heparin

Arm Type

Experimental

Arm Description

Bemiparin sodium 3,500 IU anti Xa/0.2 ml solution (Hibor; Laboratories Rovi Pharmaceuticals) for injection in pre-filled syringes.

Arm Title

No intervention group

Arm Type

No Intervention

Arm Description

Control group receiving standard care.

Intervention Type

Drug

Intervention Name(s)

Bemiparin sodium

Other Intervention Name(s)

Hibor

Intervention Description

Bemiparin sodium 3,500 IU will be started on the evening of the same day of embryo transfer and until the day of pregnancy test. If the test is positive, Bemiparin will be discontinued by the end of the 12th week of gestation.

Primary Outcome Measure Information:

Title

Implantation rate (%)

Description

Number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos

Time Frame

Vaginal ultrasound at 8 weeks gestation

Secondary Outcome Measure Information:

Title

Live birth rate (%)

Description

birth of live born

Time Frame

Time of delivery up to 42 weeks gestation

Title

Ongoing pregnancy rate (%)

Description

Fetal heart beat seen by ultrasound at 20 weeks gestation

Time Frame

Vaginal ultrasound at 20 weeks of gestation

Title

Clinical pregnancy rate (%)

Description

Fetal heart beat seen by ultrasound at 8 weeks gestation

Time Frame

Vaginal ultrasound at 8 weeks gestation

Title

Total pregnancy rate (%)

Description

Positive hCG titer

Time Frame

Up to 15 days from oocyte collection

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

38 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: History of three or more consecutively failed In Vitro Fertilization (IVF) cycles after embryo transfer. Normal uterine cavity (as assessed by hysteroscopy or HSG). Normal hormonal investigation: TSH, PRL, FBS. Normal acquired/inherited thrombophilia profile: LAC, ACA IgG/IgM, Prot S, Antithrombin III, beta-2 glycoprotein, Factors V, II, MTHFR. Normal semen analysis and mild/moderate male factor (Total motile sperm count > 5 million/ml and/or normal WHO morphology >20%. Patient provides written informed consent. Exclusion Criteria: Evidence of low ovarian reserve by at least one of the following: AMH ≤ 1,5 ng/mL and/or basal CD 3 FSH ≥ 10 mIU/mL and/or basal CD 3 Estradiol ≥ 60 ng/mL and/or previous egg collection yield ≤ 3 oocytes. Preexisting medical condition (thyroid disease, diabetes mellitus, hypertension, pulmonary conditions, cardiac condition…). Severe male factor infertility (Total motile sperm count < 5 million/ml and/or normal WHO morphology <20%). Hypersensitivity to Heparin or its derivatives. Acquired thrombophilia. Active hemorrhage or increased risk of bleeding due to impairment of homeostasis. Severe impairment of liver or pancreatic function. Severe renal insufficiency (Creatinine Clearance < 30 ml/min). Injuries to or operations on the central nervous system, eyes and ears within the last 2 months. Disseminated Intravascular Coagulation (DIC) attributable to heparin-induced thrombocytopenia. Acute bacterial endocarditis and endocarditis lenta. Any organic lesion with high risk of bleeding (e.g.: active peptic ulcer, hemorrhagic stroke, cerebral aneurysm or cerebral neoplasms).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Johnny Awwad, MD

Organizational Affiliation

AUBMC

Official's Role

Principal Investigator

Facility Information:

Facility Name

American University of Beirut Medical Center

City

Beirut

Country

Lebanon

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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Low Molecular Weight Heparin to Improve Pregnancy Outcome in Patients With Recurrent Implantation Failure

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