Anticoagulation Therapies Effect on the Endometrial Blood Flow and Pregnancy Outcomes in Unexplained Recurrent Implantation Failure Women

The aim of the study is to investigate whether Low Dose Aspirin and Low Molecular Weight Heparin could increase the uterine perfusion, and finally improve the implantation and pregnancy rates in patients with unexplained recurrent implantation failure.

Study Overview

• Status: Unknown
• Conditions: Recurrent Implantation Failure
• Intervention / Treatment: Drug: Low dose aspirin; Drug: Low molecular weight heparin; Drug: Low dose aspirin plus low molecular weight heparin; Drug: no treatment

Detailed Description

Infertility is a growing issue for many couples all over the world. Nowadays, Assisted reproductive technology is widely used to treat couples affected by infertility, but, the success rate is still very low. Recurrent implantation failure is an important cause of repeated IVF failure. In addition to the embryo quality, a functioning and receptive endometrium is crucial for embryo implantation. There is a growing amount of evidence shows that uterine perfusion playing an important part in regulating endometrial receptivity and in successful pregnancy.

Recently, transvaginal ultrasonography is often used to examine endometrial thickness, pattern and blood flow status to predict uterine receptivity. Some studies have demonstrated that uterine artery blood flow resistance in RM (Recurrent miscarriage) patients is significantly higher than in normal fertile patients. It has been postulated that abnormal uterine perfusion could be related to the reproductive failure, enhancing the uterine perfusion may improve the successful pregnancy. In accordance with this hypothesis, some therapeutic approaches including low dose aspirin (LDA), nitric oxide donor, low molecular weight heparin, sildenafil are applying in clinic. Low molecular weight heparin (LMWH) is derived from unfractionated heparin. It also has anticoagulation or the antithrombin effect. Aspirin has analgesic, antipyretic, and anti-inflammatory properties. Initially, aspirin and low molecular weight heparin have been used either as single agents or in combination to treat patients with recurrent miscarriage, diagnosed with antiphospholipid syndrome. The treatment confers a significant benefit in live births rate. Furthermore, various studies have shown that thrombophilia are more common in women with RIF compared with healthy fertile controls. In these women, heparin treatment could potentially enhance the implantation process, and may finally improve the live birth rate. The aim of the study is to investigate whether Low Dose Aspirin and Low Molecular Weight Heparin could increase the uterine perfusion, and finally improve the implantation and pregnancy rates in patients with unexplained recurrent implantation failure.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200051
    • Shanghai first Maternity and Infant health hospital, Tong Ji University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

This is a prospective cohort study on unexplained recurrent implantation failure patients with abnormal uterine perfusion in our clinic from September 2017 to December 2018.

Description

Inclusion Criteria:

1. ≥3 pervious IVF-ET failures or failure with transfer of at least 10 frozen embryos in multiple transfers;
2. 25-45 years old;
3. Having a regular menstrual cycle and BBT;
4. Top-quality frozen embryos for transfer;
5. Endometrial thickness 8-14mm；
6. Abnormal uterine perfusion(PI>2.5)；
7. Decided to recieve LMWH or LDA or a combination of LMWH and LDA therapy.

Exclusion Criteria:

1. Chromosome aberrations in anyone of the couple;
2. Abnormal uterine cavity;
3. Hydrosalpinx;
4. Chronic systemic disease(liver,renal,heart,thyroid and thrombocytopenia)
5. Having experienced severe allergies, trauma history；
6. With a history of mental illness;
7. Any contraindication for LDA or LMWH.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; Patients who received a daily dose of 75mg LDA per day after menstruation prior to ET.	Drug: Low dose aspirin; LDA 25mg tid
Group B; Patients who received a daily dose of 5000u LMWH after menstruation prior to ET.	Drug: Low molecular weight heparin; LMWH 5000u IH qd
Group C; Patients who received a daily dose of 75 mg LDA plus 5000u LMWH after menstruation prior to ET.	Drug: Low dose aspirin plus low molecular weight heparin; LDA 25mg tid + LMWH 5000u IH qd
Group D; Patients who did not receive any treatment.	Drug: no treatment; Patients who did not receive any treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Ongoing pregnancy beyond the 12th gestational week rate	until 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine artery blood flow	by transvaginal sonography	luteal phase before ET and one day before ET
Implantation rate	by transvaginal sonography	8 weeks

Collaborators and Investigators

• Sponsor: Shanghai First Maternity and Infant Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2017
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): February 1, 2019

Study Registration Dates

• First Submitted: December 2, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 7, 2017

Study Record Updates

• Last Update Posted (Actual): December 7, 2017
• Last Update Submitted That Met QC Criteria: December 6, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: aspirin; low molecular weight heparin; recurrent implantation failure
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Anticoagulants; Aspirin; Heparin; Calcium heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin
• Other Study ID Numbers: ShanghaiFMIH-uRIF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No