Clinical trial NCT02607319: Low Molecular Weight Heparin to Improve Pregnancy Outcome in Patients With Recurrent Implantation Failure
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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Sterility
Keywords: Recurrent Implantation Failure
Implantation
low molecular weight heparin
In vitro Fertilization
Assisted Reproductive Technology
Pregnancy
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
First posted: 2015-11-18
Enrollment: 165
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Implantation rate (%)
timeFrame: Vaginal ultrasound at 8 weeks gestation
Secondary outcomes:
measure: Live birth rate (%)
timeFrame: Time of delivery up to 42 weeks gestation
measure: Ongoing pregnancy rate (%)
timeFrame: Vaginal ultrasound at 20 weeks of gestation
measure: Clinical pregnancy rate (%)
timeFrame: Vaginal ultrasound at 8 weeks gestation
measure: Total pregnancy rate (%)
timeFrame: Up to 15 days from oocyte collection
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
Study officials:
affiliation: AUBMC
name: Johnny Awwad, MD
role: PRINCIPAL_INVESTIGATOR
References: