A Preliminary Study About Unexplained Recurrent Miscarriage and Repeated Implantation Failure Patients Treated With Low-dose Lymphocyte Immunotherapy

NCT ID: NCT03081325

Last Updated: 2018-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 292 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2017-07-20

Brief Summary

Recurrent miscarriage(RM) and recurrent implantation failure (RIF) are clinical challenge for clinicians and patients who are desperate for a healthy child.The specific etiology contains chromosomal abnormalities, reproductive anatomical abnormalities, endocrine disorders, reproductive system infections, autoimmune and environmental factors. However there are still 50% to 60% RM and RIF which don't have a clear cause,mainly associated with alloimmune factors.Among various treatments,lymphocytes active immunotherapy is the most common treatment method, and its clinical efficacy is widely recognized although its action mechanism is not clear so far.

Detailed Description

The main mechanism of active immunotherapy includes upregulating Th2-type cytokines, downregulating Th1-type cytokines, making Th1 / Th2 shift to Th2, inducing maternal serum IL-6 and sIL6R, PIBF, EGF; inducing the expression of Fas / Fasl on lymphocyte surface; increasing the proportion of CD8 + cells, Th2-type cells and CD + CD25 + Treg cells, decreasing the activity of CD56 + CD16 + NK cell and so on.The purpose of this study is to observe the treatment effects of active immunotherapy on uRM and RIF patients. What's more,we will used flow cytometry, and quantitative real-time PCR (qPCR) methods to characterize Th1、Th2 and Treg cell populations after immunotherapy,ecpecting to find out the exact molecule mechanism of immunotherapy with paternal or third party lymphocytes.

Conditions

Unexplained Recurrent Miscarriage and Recurrent Implantation Failure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

lymphocyte immunotherapy on uRM and RIF

Donor (husband or third party) lymphocytes were prepared by Ficoll-Paque centrifugation; the cells were washed with sterile saline and resuspended in 1 ml at a concentration of 20-40 × 106 cells/ml. The cells were given to the female partner by 4-6 intradermal injected. In this study, the lymphocyte immunization therapies were performed every 3 weeks for 3 times. After that we test Th1/Th2/Treg, if they become normal, the patients can prepare for pregnancy.

Group Type: EXPERIMENTAL

low-dose lymphocyte immunotherapy

Intervention Type: PROCEDURE

Peripheral venous blood (PBMCs) was drawn from the husbands of uRM and RIF patients and then the PBMCs were resuspended and administered intradermally to uRM and RIF patients 3 times at 3-week intervals. Once conceived, the uRM and RIF patients undergo 2 rounds of treatment at 8-week intervals.

Interventions

low-dose lymphocyte immunotherapy

Peripheral venous blood (PBMCs) was drawn from the husbands of uRM and RIF patients and then the PBMCs were resuspended and administered intradermally to uRM and RIF patients 3 times at 3-week intervals. Once conceived, the uRM and RIF patients undergo 2 rounds of treatment at 8-week intervals.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Healthy except for their history of recurrent abortions and were negative for blocking antibodies
• Willing to receive follow up

Exclusion Criteria

• Patients with genetic impairment
• Patients with Mullerian anomaly
• Patients with hormonal deficiency
• Patients with metabolic disorder
• Patients with infectious disease
• Patients with autoimmune abnormalities

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Nanjing University

OTHER

Sponsor Role: lead

Responsible Party

Li-jun Ding

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

Countries

China

References

Liu M, Zhen X, Song H, Chen J, Sun X, Li X, Zhou J, Yan G, Ding L, Sun H. Low-dose lymphocyte immunotherapy rebalances the peripheral blood Th1/Th2/Treg paradigm in patients with unexplained recurrent miscarriage. Reprod Biol Endocrinol. 2017 Dec 16;15(1):95. doi: 10.1186/s12958-017-0315-9.

Reference Type: DERIVED

PMID: 29246150 (View on PubMed)

Other Identifiers

BL2015007

Identifier Type: -

Identifier Source: org_study_id