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

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.

• Routine Anticoagulant Therapy (Aspirin or Heparin Sodium) (Drug): 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.

Primary outcomes

• Clinical Pregnancy Rate [Up to 90 days of gestation]: 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.

Secondary outcomes

• Endometrial Thickness [During the window of implantation (prior to embryo transfer)]: The maximum anteroposterior diameter of the endometrium measured in millimeters (mm) in the midsagittal plane using 2D transvaginal ultrasound.
• Endometrial Morphological Pattern [During the window of implantation (prior to embryo transfer)]: 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.
• Endometrial and Subendometrial Blood Flow Indices [During the window of implantation (prior to embryo transfer)]: 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).
• Endometrial Peristalsis Frequency [During the window of implantation (prior to embryo transfer)]: The frequency of endometrial wave-like activity (contractions per minute) observed via continuous transvaginal ultrasound scanning for a duration of 3 to 5 minutes.
• Early Miscarriage Rate [Up to 90 days of gestation]: 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.

Sex: Female, ages: 20 Years to 45 Years

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.

• Li Zhang, MD, Principal investigator, Tang-Du Hospital