Effect of Anticoagulant Therapy on Endometrial Receptivity and Pregnancy Outcomes in Infertility

Evaluation of the Effect of Anticoagulant Therapy on Endometrial Receptivity and Pregnancy Outcomes in Patients With Infertility Using an Ultrasound Multimodal System

The purpose of this prospective observational cohort study is to evaluate the effect of routine clinical anticoagulant therapy on endometrial receptivity and subsequent pregnancy outcomes in women with infertility. Researchers will utilize an ultrasound multimodal system to systematically assess endometrial parameters, including thickness, morphology, peristalsis, and blood flow indices. The study aims to enroll approximately 300 infertile women aged 20 to 45 years. Participants will be observed and grouped based on whether they receive anticoagulant medications, such as aspirin or heparin sodium, as part of their standard clinical care. The study will track ultrasound-based receptivity indicators and follow up on pregnancy status and outcomes at 45 and 90 days of gestation. This study is purely observational, and all clinical treatment decisions are made independently of the study protocol.

Study Overview

• Status: Recruiting
• Conditions: Infertility
• Intervention / Treatment: Drug: Routine Anticoagulant Therapy (Aspirin or Heparin Sodium)

Detailed Description

Background and Rationale:

Endometrial receptivity plays a pivotal role in the success of embryo implantation for patients with infertility. Impaired endometrial perfusion is considered a significant contributing factor to implantation failure. In routine clinical practice, anticoagulant therapies, such as low-dose aspirin and low molecular weight heparin (e.g., heparin sodium), are frequently utilized to improve local hemodynamics and endometrial receptivity. However, a systematic, non-invasive, and quantitative evaluation of these therapeutic effects on the endometrium is still required.

Multimodal ultrasound provides a comprehensive, real-time, and non-invasive approach to assessing endometrial dynamics. By integrating conventional 2D ultrasound, 3D ultrasound, and Doppler imaging, this technology can meticulously quantify endometrial parameters, offering valuable predictive insights for clinical pregnancy outcomes.

Study Design and Methodology:

This is a single-center, prospective, observational cohort study. The objective is to evaluate the impact of routine anticoagulant therapy on endometrial receptivity and subsequent pregnancy outcomes in infertile women using an ultrasound multimodal system.

The study plans to enroll approximately 300 eligible infertile women aged 20 to 45 years. Participants will be categorized into two observational cohorts based solely on their routine clinical care plans:

Observation Group: Patients receiving anticoagulant therapy (e.g., aspirin, heparin sodium) in addition to conventional treatment.

Control/Comparison Group: Patients receiving conventional treatment only. Note: The decision to administer anticoagulant therapy is entirely at the discretion of the attending physicians based on clinical indications, independent of this study protocol. This study is strictly observational and involves no protocol-driven interventions.

Data Collection and Assessments:

During the clinically defined window of implantation, all participants will undergo comprehensive multimodal ultrasound examinations. The primary ultrasonographic parameters to be recorded include:

Endometrial thickness and morphological patterns.

Endometrial peristalsis characteristics.

Endometrial and subendometrial blood flow indices, including Vascularization Index (VI), Flow Index (FI), and Vascularization Flow Index (VFI) via 3D power Doppler.

Follow-up and Endpoints:

Following the ultrasound assessments and embryo transfer/conception, participants will be longitudinally followed. The clinical endpoints, specifically the pregnancy status and outcomes, will be rigorously tracked and documented at 45 days and 90 days of gestation. The collected data will be analyzed to determine the correlation between the multimodal ultrasound parameters of endometrial receptivity under anticoagulant therapy and the ultimate pregnancy success rates.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Li Zhang, MD; Phone Number: 86-29-84778860; Email: lilyzhang319_20@hotmail.com
• Study Contact Backup: Name: Zhengjun Ma, MM; Phone Number: +86-13072977233; Email: mazhengjun@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710038
      • Recruiting
      • Tangdu Hospital, Air Force Medical University
      • Contact: Zhengjun Ma, MM; Phone Number: +86-13072977233; Email: mazhengjun@fmmu.edu.cn
      • Contact: Li Zhang, MM; Phone Number: 86-29-84778860; Email: lilyzhang319_20@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult female patients, aged 20 to 45 years, who have been clinically diagnosed with infertility. These patients are seeking routine infertility treatments, such as in vitro fertilization (IVF) and embryo transfer or monitored conception cycles, at Tangdu Hospital. The population includes patients who receive standard conventional treatment as well as those who are prescribed adjunctive anticoagulant therapy based on their routine clinical care indications.

Description

Inclusion Criteria:

• Female patients aged 20 to 45 years.

Clinically diagnosed with infertility and planning to undergo embryo transfer or monitored conception cycles.

Patients who have complete baseline clinical data and are willing to undergo multimodal ultrasound evaluation of endometrial receptivity during the window of implantation.

Voluntarily agreed to participate in this observational study and signed the informed consent form for data collection.

Exclusion Criteria:

• Presence of congenital uterine malformations (e.g., septate uterus, bicornuate uterus, unicornuate uterus) that significantly alter the endometrial cavity.

Presence of untreated severe intrauterine lesions, such as submucosal fibroids, severe intrauterine adhesions, or endometrial polyps that may mechanically interfere with implantation.

Severe underlying systemic diseases, including but not limited to severe liver or kidney dysfunction, or malignant tumors.

Known severe bleeding disorders or strict contraindications to anticoagulant medications (for patients in the routine clinical care setting).

Patients who are unable to cooperate with the transvaginal multimodal ultrasound examination or complete the required follow-up for pregnancy outcomes.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Anticoagulant Therapy Cohort; Patients in this cohort receive routine clinical anticoagulant therapies (such as low-dose aspirin or low molecular weight heparin) in addition to their conventional infertility treatment. The use of anticoagulants is determined by the attending physician based on standard clinical indications, strictly independent of this observational study protocol.	Drug: Routine Anticoagulant Therapy (Aspirin or Heparin Sodium); Patients receive low-dose aspirin or low molecular weight heparin (e.g., heparin sodium) purely as part of their standard clinical care. The decision to initiate, adjust, or terminate this therapy is made entirely by the attending physician based on clinical indications, strictly independent of this observational study protocol. This is tracked solely as an observational exposure.
Conventional Treatment Cohort; Patients in this cohort receive conventional infertility treatment only, without the addition of anticoagulant therapies, as per standard clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Pregnancy Rate	The clinical pregnancy rate is defined as the proportion of patients with the presence of at least one intrauterine gestational sac with a visible fetal heartbeat, confirmed by transvaginal ultrasound.	Up to 90 days of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial Thickness	The maximum anteroposterior diameter of the endometrium measured in millimeters (mm) in the midsagittal plane using 2D transvaginal ultrasound.	During the window of implantation (prior to embryo transfer)
Endometrial Morphological Pattern	Evaluated via 2D transvaginal ultrasound and classified into three typical patterns: Type A (triple-line pattern), Type B (intermediate isoechogenic pattern), and Type C (homogeneous hyperechogenic pattern) to assess morphological receptivity.	During the window of implantation (prior to embryo transfer)
Endometrial and Subendometrial Blood Flow Indices	Quantitative assessment of local tissue perfusion using 3D power Doppler ultrasound. The parameters measured include Vascularization Index (VI, reflecting vessel density), Flow Index (FI, reflecting blood flow intensity), and Vascularization Flow Index (VFI, a combination of vascularity and flow intensity).	During the window of implantation (prior to embryo transfer)
Endometrial Peristalsis Frequency	The frequency of endometrial wave-like activity (contractions per minute) observed via continuous transvaginal ultrasound scanning for a duration of 3 to 5 minutes.	During the window of implantation (prior to embryo transfer)
Early Miscarriage Rate	The proportion of patients who experience a spontaneous pregnancy loss after the initial ultrasound confirmation of an intrauterine clinical pregnancy, prior to 90 days of gestation.	Up to 90 days of gestation

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Investigators: Principal Investigator: Li Zhang, MD, Tang-Du Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: March 20, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Endometrial Receptivity; Anticoagulant Therapy; Multimodal Ultrasound
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Glycosaminoglycans; Polysaccharides; Salicylates; Hydroxybenzoates; Aspirin; Heparin
• Other Study ID Numbers: K202508-28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) underlying the results reported in the published article will be shared. Data will be available to researchers who provide a methodologically sound proposal, purely for the purpose of achieving the aims in the approved proposal.
• IPD Sharing Time Frame: Data will be available beginning 6 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: To gain access, data requestors will need to contact the corresponding author and sign a formal data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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