Pregnancy Outcome of Women Using Low Molecular Weight Heparin Before Frozen-thawed Embryo Transfer

April 14, 2017 updated by: Nanfang Hospital of Southern Medical University

Comparison of Clinical Pregnancy Rates Between Two Protocols, With or Without Low Molecular Weight Heparin Administration Before Frozen Embryo Transfer in Hormonal Replacement Cycles: a Prospective Randomized Controlled Trial

Embryo freezing is a technique used commonly to optimize the pregnancy rate in assisted reproduction techniques (ART). Hormone replacement therapy (HRT) regimen is applied to prepare endometrium for frozen embryo transfer (FET) commonly.At present, It is unclear whether preimplantation low molecular weight heparin (LMWH) improves live birth and pregnancy rates in subfertile women undergoing FET. The study is a prospective randomized controlled trial to compare the pregnancy outcomes of FET in hormonal replacement therapy(HRT) cycles with or without LMWH administration before implantation.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

This study is a prospective randomized controlled trial. Patients undergoing FET in Center for Reproductive Medicine of Nanfang Hospital, Southern Medical University are recruited.

They are randomly allocated to be prepared for transfer by using HRT cycle, with(low molecular weight heparin-group B(group LMWH-B)) or without( non-low molecular weight heparin-group A(group NLMWH-A)) administration of low molecular weight heparin (LMWH) before frozen embryo transfer (FET).

Both groups use the same protocol of HRT-FET. The oral estrogen replacement is 4mg per day (2 mg twice daily), 4 days; 6 mg per day, 4 days. Then, the patient's endometrial thickness is evaluated through vaginal ultrasound and if the endometrial thickness is <7 mm, increasing estrogen by 2 mg is given to patients until the endometrial thickness is >9 mm.In group NLMWH-A, If the endometrial thickness is greater than 9 mm, human chorionic gonadotropin (hCG)10000 IU will be administered via intramuscular injection. Then on the next day(D0), progesterone in oil 60 mg will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later(D3). In group LMWH-B, If the endometrial thickness is greater than 9 mm, hCG 10000 IU will be administered via intramuscular injection. And low molecular weight heparin (LMWH) will be injected subcutaneously 4100 IU (WHO) every other day before FET. Then on the next day(D0), progesterone in oil 60 mg will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later(D3).

This study was approved by the medicine ethics committee of Nanfang Hospital.

Study Type

Interventional

Enrollment (Anticipated)

342

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Recruiting
        • Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University
        • Contact:
        • Principal Investigator:
          • Xin Chen, M.D, Ph.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 41 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Aged between 20 to 43 years;
  • Body mass index (BMI) between 19 kg/m2 and 25 kg/m2;
  • At least one good quality D3 embryos for transfer;
  • prepare endometrium by hormone replacement therapy(HRT)protocal;
  • capable of giving informed consent.

Exclusion Criteria:

  • Women or their partner with abnormal chromosome karyotype including chromosome polymorphism;
  • Women diagnosed as uterus abnormality: malformed uterus (uterus unicorns, septate uterus, duplex uterus, uterus bicornis), adenomyosis, submucous myoma, intrauterine adhesion;
  • Women who underwent unilateral ovariectomy or with history of ovarian tumor surgery ;
  • infection factors: TORCH virus (including Toxoplasma virus, rubella virus, cytomegalovirus,herpes simplex infection),Chlamydia and Mycoplasma, etc;
  • Endometriosis;
  • Having hydrosalpinx ;
  • Low molecular weight heparin contraindications: thrombocytopenia, hemophilia and other bleeding disorders, liver and kidney dysfunction, with a clear history of heparin allergy or allergic constitution, etc.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: NLMWH-A
non-low molecular weight heparin-group A(group NLMWH-A).Without administration of low molecular weight heparin (LMWH) before FET.The oral estrogen replacement is 4mg per day (2 mg twice daily), 4 days; 6 mg per day, 4 days. Then, the patient's endometrial thickness is evaluated through vaginal ultrasound and if the endometrial thickness is <7 mm, increasing estrogen by 2 mg is given to patients until the endometrial thickness is >9 mm.If the endometrial thickness is greater than 9 mm, Human Chorionic Gonadotropin（hCG） 10000 IU will be administered via intramuscular injection.on the next day(D0), progesterone in oil 60 mg will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later(D3).
Drug: estrogen
The oral estrogen replacement is 4mg per day (2 mg twice daily), 4 days; 6 mg per day, 4 days. Then, the patient's endometrial thickness is evaluated through vaginal ultrasound and if the endometrial thickness is <7 mm, increasing estrogen by 2 mg is given to patients until the endometrial thickness is >9 mm.
Other Names:
  • estrodiol
Drug: hCG
If the endometrial thickness is greater than 9 mm, Human Chorionic Gonadotropin（hCG） 10000 IU will be administered via intramuscular injection.
Other Names:
  • Human Chorionic Gonadotropin
Drug: progesterone
on the next day(D0), progesterone in oil 60 mg will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later(D3).
Experimental: LMWH-B
low molecular weight heparin-group B(group LMWH-B).With administration of low molecular weight heparin (LMWH) before FET.The oral estrogen replacement is 4mg per day (2 mg twice daily), 4 days; 6 mg per day, 4 days. Then, the patient's endometrial thickness is evaluated through vaginal ultrasound and if the endometrial thickness is <7 mm, increasing estrogen by 2 mg is given to patients until the endometrial thickness is >9 mm.If the endometrial thickness is greater than 9 mm, Human Chorionic Gonadotropin（hCG） 10000 IU will be administered via intramuscular injection.on the next day(D0), progesterone in oil 60 mg will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later(D3).
Drug: estrogen
The oral estrogen replacement is 4mg per day (2 mg twice daily), 4 days; 6 mg per day, 4 days. Then, the patient's endometrial thickness is evaluated through vaginal ultrasound and if the endometrial thickness is <7 mm, increasing estrogen by 2 mg is given to patients until the endometrial thickness is >9 mm.
Other Names:
  • estrodiol
Drug: hCG
If the endometrial thickness is greater than 9 mm, Human Chorionic Gonadotropin（hCG） 10000 IU will be administered via intramuscular injection.
Other Names:
  • Human Chorionic Gonadotropin
Drug: progesterone
on the next day(D0), progesterone in oil 60 mg will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later(D3).
Drug: Low Molecular Weight Heparin
If the endometrial thickness is greater than 9 mm, hCG 10000 IU will be administered via intramuscular injection.And low molecular weight heparin (LMWH) will be injected subcutaneously 4100 IU (WHO) every other day before FET.Then on the next day(D0), progesterone in oil 60 mg will be administered via intramuscular injection. Transfer of thawed embryos will be performed 3 days later(D3).
Other Names:
  • LMWH

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical pregnancy rate
Time Frame: 4-6 weeks
The pregnancy rate will be evaluated in patients of each groups 4-6 weeks after embryo transfer.
4-6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Implantation rate
Time Frame: 4-6 weeks
Evaluation the implantation rate in patients of each groups 4-6 weeks after frozen embryo transfer
4-6 weeks
Ongoing pregnancy
Time Frame: 12 weeks
Evaluation the ongoing pregnancy by monitoring pregnant bursa and fetal heart through ultrasound in patients of each group 12 weeks after embryo transfer.
12 weeks
miscarriage rate
Time Frame: Evaluation the miscarriage rate in patients of each group 12 weeks after embryo transfer.
12 weeks
Evaluation the miscarriage rate in patients of each group 12 weeks after embryo transfer.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanfang Hospital of Southern Medical University

Investigators

  • Principal Investigator: Xin Chen, M.D, Ph.D, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2016

Primary Completion (Anticipated)

June 30, 2017

Study Completion (Anticipated)

September 5, 2017

Study Registration Dates

First Submitted

April 5, 2017

First Submitted That Met QC Criteria

April 14, 2017

First Posted (Actual)

April 19, 2017

Study Record Updates

Last Update Posted (Actual)

April 19, 2017

Last Update Submitted That Met QC Criteria

April 14, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NFEC-2017-024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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