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

• ClinicalTrials.gov Identifier: NCT03365466
• Recruitment Status: Unknown
• First Posted: December 7, 2017
• Last Update Posted: December 7, 2017
• Sponsor: Shanghai First Maternity and Infant Hospital
• Information provided by (Responsible Party): Shihua Bao, Shanghai First Maternity and Infant Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment
Recurrent Implantation Failure	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 Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Anticoagulation Therapies Effect on the Endometrial Blood Flow and Pregnancy Outcomes in Unexplained Recurrent Implantation Failure Women
• Estimated Study Start Date: December 2017
• Estimated Primary Completion Date: December 2018
• Estimated Study Completion Date: February 2019

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Clinical pregnancy rate [ Time Frame: until 12 weeks ]
   Ongoing pregnancy beyond the 12th gestational week rate

Secondary Outcome Measures :

1. Uterine artery blood flow [ Time Frame: luteal phase before ET and one day before ET ]
   by transvaginal sonography
2. Implantation rate [ Time Frame: 8 weeks ]
   by transvaginal sonography

Eligibility Criteria

• Ages Eligible for Study: 25 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No
• 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.

Criteria

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.

Contacts and Locations

Contacts

Contact: Shihua Bao, PhD; 86-21-20261430 ext 2012; baoshihua@tongji.edu.cn

Locations

China

Shanghai first Maternity and Infant health hospital, Tong Ji University

Shanghai, China, 200051

Sponsors and Collaborators

Shanghai First Maternity and Infant Hospital

More Information

• Responsible Party: Shihua Bao, Principal Investigator, Shanghai First Maternity and Infant Hospital
• ClinicalTrials.gov Identifier: NCT03365466
• Other Study ID Numbers: ShanghaiFMIH-uRIF
• First Posted: December 7, 2017
• Last Update Posted: December 7, 2017
• Last Verified: September 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shihua Bao, Shanghai First Maternity and Infant Hospital:

recurrent implantation failure; aspirin; low molecular weight heparin

Additional relevant MeSH terms:

Aspirin; Heparin; Calcium heparin; Heparin, Low-Molecular-Weight; Tinzaparin; Dalteparin; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Antipyretics; Anticoagulants