NCT03701750

Brief Summary

Low-Molecular-Weight-Heparin (LMWH) has been used empirically in patients undergoing in-vitro fertilization embryo transfer (IVF-ET) with the purpose to aid in improving pregnancy outcomes. The potential mechanism is that LMWH could exert its anticoagulant effect by inhibiting factor Xa, reducing the risk of insufficiency blood supply in the very early stage of pregnancy. Moreover, LMWH is supposed to play a role in manipulating blastocyst supposition, adhesion, and implantation, as well as trophoblast differentiation and invasion. However, limited high-quality clinical trials focus on the effectivity of LMWH in IVF-ET, and the published evidence is not consensus, leading to considerable controversy in the clinical application of LMWH in IVF-ET patients. Here, investigators try to evaluate the effect of LMWH on pregnancy outcome in women with multiple failures of IVF-ET via a multi-center randomized controlled trial.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
240

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Nov 2018

Longer than P75 for phase_4

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 7, 2018

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 10, 2018

Completed
22 days until next milestone

Study Start

First participant enrolled

November 1, 2018

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2021

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

October 31, 2022

Completed
Last Updated

July 29, 2020

Status Verified

July 1, 2020

Enrollment Period

3 years

First QC Date

October 7, 2018

Last Update Submit

July 27, 2020

Conditions

Keywords

IVFpregnancyLMWHLow Molecular Weight HeparinAssisted Reproductive TechnologyImplantation

Outcome Measures

Primary Outcomes (1)

  • Live birth rate

    Birth of liveborn

    Time of delivery up to 42 weeks gestation

Secondary Outcomes (4)

  • Embryo implantation rate

    4 weeks

  • Clinical pregnancy rate

    7-8 weeks

  • Miscarriage rate

    Up to 28 weeks

  • Ovarian hyperstimulation syndrome (OHSS) rate

    Up to 3 weeks after COH

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Low Molecular Weight Heparin (enoxaparin sodium) + routine luteal phase support

Drug: Low Molecular Weight Heparin (enoxaparin sodium)

Control Arm

NO INTERVENTION

routine luteal phase support

Interventions

enoxaparin sodium 40mg/day subcutaneously after oocyte collection, and routine luteal phase support after embryo transfer until clinical pregnancy confirmed by ultrasound

Experimental Arm

Eligibility Criteria

Age20 Years - 38 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • ≥2 consecutive IVF/ICSI-ET without clinical pregnancy
  • ≥2 oocytes retrieval cycles
  • \<BMI≤25
  • Normal ovarian reserve ( AMH\> 1, FSH \<10 )
  • Willing and able to sign the informed consent.

You may not qualify if:

  • Uterine abnormalities confirmed by hysterosalpingography or hysteroscopy
  • Parental chromosomal abnormalities
  • PCOS
  • Anti-phospholipid Syndrome
  • Endocrine disorder
  • Endometriosis
  • Hydrosalpinx
  • Chronic disease (liver, renal, thyroid, and thrombocytopenia)
  • Regular anticoagulation or antiplatelet treatment
  • Patients who had contraindication for unfractionated heparin therapy
  • History of tuberculosis, HIV, HBV, HCV or tests indicating carriage of HBV or HCV, or positive interferon-gamma release assay in any of the couple
  • Enrollment in another clinical trial

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Clinical Research Center for Reproductive Medicine, Fertility Center, Shenzhen Zhongshan Urology Hospital

Shenzhen, Guangdong, 518045, China

RECRUITING

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430060, China

NOT YET RECRUITING

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

NOT YET RECRUITING

Related Publications (3)

  • Urman B, Ata B, Yakin K, Alatas C, Aksoy S, Mercan R, Balaban B. Luteal phase empirical low molecular weight heparin administration in patients with failed ICSI embryo transfer cycles: a randomized open-labeled pilot trial. Hum Reprod. 2009 Jul;24(7):1640-7. doi: 10.1093/humrep/dep086. Epub 2009 Apr 8.

    PMID: 19357135BACKGROUND
  • Noci I, Milanini MN, Ruggiero M, Papini F, Fuzzi B, Artini PG. Effect of dalteparin sodium administration on IVF outcome in non-thrombophilic young women: a pilot study. Reprod Biomed Online. 2011 Jun;22(6):615-20. doi: 10.1016/j.rbmo.2011.03.016. Epub 2011 Mar 22.

    PMID: 21498125BACKGROUND
  • Stern C, Chamley L, Norris H, Hale L, Baker HW. A randomized, double-blind, placebo-controlled trial of heparin and aspirin for women with in vitro fertilization implantation failure and antiphospholipid or antinuclear antibodies. Fertil Steril. 2003 Aug;80(2):376-83. doi: 10.1016/s0015-0282(03)00610-1.

    PMID: 12909502BACKGROUND

MeSH Terms

Conditions

Infertility

Interventions

Heparin, Low-Molecular-Weightenoxaparin sodium

Condition Hierarchy (Ancestors)

Genital DiseasesUrogenital Diseases

Intervention Hierarchy (Ancestors)

HeparinGlycosaminoglycansPolysaccharidesCarbohydrates

Study Officials

  • Haixiang Sun, M.D. Ph.D

    The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

    PRINCIPAL INVESTIGATOR
  • Jing Yang, M.D. Ph.D

    Renmin Hospital of Wuhan University

    PRINCIPAL INVESTIGATOR
  • Ruochun Lian, M.D. Ph.D

    Shenzhen Zhongshan Urology Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Lianghui Diao, Ph.D.

CONTACT

Songchen Cai, M.Phil.

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER GOV
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of Hospital

Study Record Dates

First Submitted

October 7, 2018

First Posted

October 10, 2018

Study Start

November 1, 2018

Primary Completion

October 31, 2021

Study Completion

October 31, 2022

Last Updated

July 29, 2020

Record last verified: 2020-07

Locations