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

Sponsor

American University of Beirut Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02607319

Collaborator

(none)

200

Enrollment

Location

Arms

Duration (Months)

2.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Sterility	Drug: Bemiparin sodium	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2015

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low molecular weight heparin Bemiparin sodium 3,500 IU anti Xa/0.2 ml solution (Hibor; Laboratories Rovi Pharmaceuticals) for injection in pre-filled syringes.	Drug: Bemiparin sodium 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. Other Names: Hibor
No Intervention: No intervention group Control group receiving standard care.

Arm

Intervention/Treatment

Experimental: Low molecular weight heparin

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

Drug: Bemiparin sodium

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.

Other Names:

Hibor

No Intervention: No intervention group

Control group receiving standard care.

Outcome Measures

Primary Outcome Measures

Implantation rate (%) [Vaginal ultrasound at 8 weeks gestation]
Number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos

Secondary Outcome Measures

Live birth rate (%) [Time of delivery up to 42 weeks gestation]
birth of live born
Ongoing pregnancy rate (%) [Vaginal ultrasound at 20 weeks of gestation]
Fetal heart beat seen by ultrasound at 20 weeks gestation
Clinical pregnancy rate (%) [Vaginal ultrasound at 8 weeks gestation]
Fetal heart beat seen by ultrasound at 8 weeks gestation
Total pregnancy rate (%) [Up to 15 days from oocyte collection]
Positive hCG titer

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 38 Years

Sexes Eligible for Study:

Female

Accepts 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).