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

Sterility Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02607319
• Other study ID #: AmericanUBMCRIF
• Status: Completed
• Phase: Phase 4
• Start date: November 2015
• Est. completion date: July 2022

Study information

• Verified date: July 2023
• Source: American University of Beirut Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 165
• Est. completion date: July 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

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).

Related Conditions & MeSH terms

• Infertility
• Sterility

Intervention

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.

Locations

Country	Name	City	State
Lebanon	American University of Beirut Medical Center	Beirut

Sponsors (1)

Lead Sponsor	Collaborator
American University of Beirut Medical Center

Country where clinical trial is conducted

Lebanon, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Implantation rate (%)	Number of intrauterine gestational sacs observed by transvaginal ultrasonography divided by the number of transferred embryos	Vaginal ultrasound at 8 weeks gestation
Secondary	Live birth rate (%)	birth of live born	Time of delivery up to 42 weeks gestation
Secondary	Ongoing pregnancy rate (%)	Fetal heart beat seen by ultrasound at 20 weeks gestation	Vaginal ultrasound at 20 weeks of gestation
Secondary	Clinical pregnancy rate (%)	Fetal heart beat seen by ultrasound at 8 weeks gestation	Vaginal ultrasound at 8 weeks gestation
Secondary	Total pregnancy rate (%)	Positive hCG titer	Up to 15 days from oocyte collection