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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| NLMWH-A | Placebo Comparator | 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). |
|
| LMWH-B | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| estrogen | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical pregnancy rate | The pregnancy rate will be evaluated in patients of each groups 4-6 weeks after embryo transfer. | 4-6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Implantation rate | Evaluation the implantation rate in patients of each groups 4-6 weeks after frozen embryo transfer | 4-6 weeks |
| Ongoing pregnancy | Evaluation the ongoing pregnancy by monitoring pregnant bursa and fetal heart through ultrasound in patients of each group 12 weeks after embryo transfer. |
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Inclusion Criteria:
Exclusion Criteria:
Female
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xin Chen, M.D, Ph.D | Contact | 8620-61641908 | zhiduoxinrun@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Xin Chen, M.D, Ph.D | Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University | Recruiting | Guangzhou | Guangdong | 510515 | China |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Sep 25, 2019 | |
| Reset | Oct 18, 2019 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Sep 25, 2019 | Oct 18, 2019 |
| ID | Term |
|---|---|
| D007246 | Infertility |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D004967 | Estrogens |
| D006495 | Heparin, Low-Molecular-Weight |
| D006063 | Chorionic Gonadotropin |
| D011374 | Progesterone |
| ID | Term |
|---|---|
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
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Parallel Assignment
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|
|
| Low Molecular Weight Heparin | Drug | 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). |
|
|
| hCG | Drug | If the endometrial thickness is greater than 9 mm, Human Chorionic Gonadotropin(hCG) 10000 IU will be administered via intramuscular injection. |
|
|
| progesterone | Drug | 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). |
|
| 12 weeks |
| miscarriage rate | 12 weeks | Evaluation the miscarriage rate in patients of each group 12 weeks after embryo transfer. |
| D020164 | Chemical Actions and Uses |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
| D006062 | Gonadotropins |
| D036361 | Peptide Hormones |
| D010926 | Placental Hormones |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011257 | Pregnancy Proteins |
| D011506 | Proteins |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D003339 | Corpus Luteum Hormones |
| D042341 | Gonadal Hormones |
| D045167 | Progesterone Congeners |
| D012739 | Gonadal Steroid Hormones |