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

Nanfang Hospital, Southern Medical University

Status and phase: Unknown; Phase 4

Conditions: Infertility

Treatments: Drug: progesterone; Drug: estrogen; Drug: hCG; Drug: Low Molecular Weight Heparin

Study type: Interventional

Funder types: Other

Identifiers

NCT03120715

NFEC-2017-024

Details and patient eligibility

About

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.

Full 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.

Enrollment: 342 estimated patients

Sex: Female

Ages: 20 to 43 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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342 participants in 2 patient groups, including a placebo group

NLMWH-A

Placebo Comparator group

Description:

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).

Treatment:

Drug: hCG

Drug: progesterone

Drug: estrogen

LMWH-B

Experimental group

Description:

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).

Treatment:

Drug: Low Molecular Weight Heparin

Drug: hCG

Drug: progesterone

Drug: estrogen