Effect of Low Molecular Weight Heparin in Freeze-thaw Embryo Transfer Cycles in Women With Recurrent Implantation Failure

Recurrent implantation failure (RIF) is considered a tough problem in assisted reproductive technology (ART) without effective treatments. The effect of low molecular weight heparin (LMWH) in pregnancy outcomes is controversial. In addition, there are few reports on the role of LMWH in population with RIF performing freeze-thaw embryo transfer (FET) cycles. The purpose of this study is to evaluate the effect of LMWH on pregnancy outcomes in women with FET cycles.

Study Overview

• Status: Completed
• Conditions: IVF; Recurrent Implantation Failure; FET; Low Molecular Weight Heparin
• Intervention / Treatment: Drug: Low Molecular Weight Heparine

• Study Type: Observational
• Enrollment (Actual): 392

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • The Second Hospital of Shandong University

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study analyzed the data from the hospital electronic database for patients undergoing FET between January, 2021 and November, 2024, a total of 392 transplant cycles, who undergoing at least two IVF or ICSI cycles from the Second Hospital of Shandong University.

Description

Inclusion Criteria:

• Women under or equal to the age of 40 when oocytes were retrieved;
• The history of at least 2 failed fresh embryo transfer/FET cycles and cumulative transfer of ≥ 3 high-quality embryos or cumulative transfer of ≥ 2 blastocysts;
• Planning to FET after IVF or ICSI cycles

Exclusion Criteria:

• Women with untreated hydrosalpinx, uterine cavity occupying lesions (uterine adhesions, submucous fibroids, endometrial polyps, et al.);
• Women with abnormal anatomical structure of uterus (unicornuate uterus, bipedal uterus, et al.);
• Women with endometrial thickness (EMT) < 6mm on the day of transplantation;
• Women or their partner with abnormal chromosome karyotype (not including chromosome polymorphisms);
• Women with the history of recurrent spontaneous abortion (RSA);
• Women with a history of autoimmune or coagulation disorders;
• Women with contraindications to LMWH

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
LMWH group; the LMWH group received injections of 4100 IU/d LMWH from the day of transplant	Drug: Low Molecular Weight Heparine; the LMWH group received injections of 4100 IU/d LMWH from the day of transplant
Control group; the control group received the routine luteal support protocol (without LMWH use)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing pregnancy rate	The number of ongoing pregnancies divided by the number of women who received a transfer	from transplantation to delivery (assessed up to 40 weeks of gestation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
biochemical pregnancy rate	The number of biochemical pregnancy cycles divided by the number of transplantation cycles	from transplantation to delivery (assessed up to 40 weeks of gestation)
clinical pregnancy rate	The number of clinical pregnancies divided by the number of women who received a transfer	from transplantation to delivery (assessed up to 40 weeks of gestation)
ectopic pregnancy rate	The number of ectopic pregnancies divided by the number of women who received a transfer	from transplantation to delivery (assessed up to 40 weeks of gestation)
Miscarriage rate	The number of miscarriages divided by the number of clinical pregnancies	from transplantation to delivery (assessed up to 40 weeks of gestation)

Collaborators and Investigators

• Sponsor: The Second Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): November 30, 2024
• Study Completion (Actual): March 1, 2025

Study Registration Dates

• First Submitted: April 29, 2025
• First Submitted That Met QC Criteria: May 18, 2025
• First Posted (Actual): May 28, 2025

Study Record Updates

• Last Update Posted (Actual): August 12, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Body Weight; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Fibrinolytic Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: KYLL2025342

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The investigators fully acknowledge the significance of data sharing as stipulated by SCI journals. However, owing to the policies and confidentiality agreements adhered to in our laboratory, the investigators regretfully cannot furnish the raw data. Nevertheless, the investigators have meticulously presented a comprehensive account of the experimental design, analysis, results, and the procedures employed for data analysis and processing.

Drug and device information, study documents

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