Effect of Intrauterine Injection of HCG on Clinical Pregnancy Outcome in Repeated Implantation Failure Patients

Study Overview
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Brief Summary
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Repeated implantation failure（RIF） is a insurmountable bottleneck in assisted reproductive technology, many studies have considered that the cause of two-thirds of implantation failure is the decreased endometrial receptivity. After exclude some major local immune factors(NK,CD138 cells) and implantation window out of phase, There are still a part of patients infertile .Human chorionic gonadotropin (hCG) is an early pre-implantation signal molecule secreted by the embryo, it can promote endometrial proliferation, increase blood flow and promote embryonic adhesion and inhibit self-regulated apoptosis of trophoblast cells. Previous studies showed that: intrauterine injection of HCG before embryo transfer can improve clinical outcomes in IVF/Intracytoplasmic sperm injection(ICSI). But some studies found that the intrauterine injection of HCG can not significantly improve the success rate of blastocyst transfer, and the reason may be the intrauterine injection of HCG time is too late to significantly increase the implantation rate. Would ahead of intrauterine injection of HCG be more effective? Thus, the patients of repeated implantation frozen embryo cycle according to the random principle accepted two kinds of transplants ways: ①intrauterine injection of HCG before blastocyst transfer; ②blastocyst transfer. Try to understand whether intrauterine injection of HCG can significantly improve the clinical pregnancy rate of blastocyst transfer in repeated implantation failure patients.

Official Title
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Effect of Intrauterine Injection of Human Chorionic Gonadotropin Before Embryo Transfer on Clinical Pregnancy Outcome in Repeated Implantation Failure Patients With Normal Pathohistological Stage --Pilot Study

Conditions
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Infertility

Intervention / Treatment
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* Drug: HCG
* Other: culture medium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: repeated implantation failure patients: ≥ 3 times IVF-embryo transfer failed to help pregnancy (biochemical or non-pregnant) age ≤36 years old normal histopathological stage (+5-7) endometrial NK cell <4.5% 0 endometrial CD138 positive cell natural cycle frozen embryo transfer frozen blastocysts (≥4BC) embryos ≥ 1 Exclusion Criteria: Scar uterus (diverticulum or incision false lumen after cesarean section) intrauterine adhesions untreated hydrosalpinx adenomyosis (endometrial displacement) endometritis uterine fibroids compress the endometrium

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 36 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HCG group<br>All patients will accept HCG 500IU intrauterine injection 2 days before blastocyte transfer | Drug: HCG<br>* we will use the catheter to pass through the cervix, and after that, the experiment Group will accept 40 μl 500 IU HCG injection into the uterine cavity 2 days before the blastocyst transfer.<br>|
| Placebo Comparator: control group<br>All patients will accept same dose of culture medium intrauterine injection 2 days before blastocyte transfer | Other: culture medium<br>* The placebo group will accept 40 μl of culture medium injection into the uterine cavity 2 days before the blastocyst transfer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical pregnancy rate |  | 28 days after blastocyst transfer | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical implantation rate |  | 28 days after blastocyst transfer | 
| ongoing pregnancy rate |  | 70 days after blastocyst transfer | 
| ectopic pregnancy rate |  | within 3 months after blastocyst transfer | 
| abortion rate |  | within 28 weeks after blastocyst transfer |