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

Phase 4

Completed

• Conditions: Sterility
• Interventions: Drug: Bemiparin sodium

• Registration Number: NCT02607319
• Lead Sponsor: American University of Beirut Medical Center

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.

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2015-11-11
• Study First Submitted QC: 2015-11-16
• Study First Posted: 2015-11-18
• Primary Completion: 2022-07
• Study Completion: 2022-07
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-19
• Last Update Posted: 2023-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 165

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low molecular weight heparin	Bemiparin sodium	Bemiparin sodium 3,500 IU anti Xa/0.2 ml solution (Hibor; Laboratories Rovi Pharmaceuticals) for injection in pre-filled syringes.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Total pregnancy rate (%)	Up to 15 days from oocyte collection	Positive hCG titer
Clinical pregnancy rate (%)	Vaginal ultrasound at 8 weeks gestation	Fetal heart beat seen by ultrasound at 8 weeks gestation
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

Trial Locations

Locations (1)

American University of Beirut Medical Center; 🇱🇧 Beirut, Lebanon