P-529 High Live Birth Rates After Low Dose Immunization Therapy (LIT) Pre and Post Pregnancy With Partner Lymphocytes In Patients With Recurrent Miscarriage (RM)
Authors: Palanivel V , Shrinivas C , Shyam N G 
Published: June 2023

Abstract

Study question
Could Lymphocyte Immunization Therapy effectively improve pregnancy and live birth rate in Unexplained Recurrent Miscarriage patients?

Summary answer
The use of paternal lymphocytes pre and post pregnancy significantly increases the pregnancy success and Live Birth Rate In Patients With Recurrent Miscarriage (RM)

What is known already
RM affects 1–2% of couples who attempt to conceive and has been defined as three consecutive pregnancy losses within 20 weeks of pregnancy confirmation. Although many potential causes have been established for RM, about 50% of these remain idiopathic and unexplained owing to immunology factors. Meta-analyses have observed better effectiveness and safety of LIT in treating couples with RM shown improvement in pregnancy outcomes. Still, results are conflicting due to different screening criteria and therapeutic protocols. Objective of present study is to evaluate effectiveness of low dose LIT in patients with uRM and Th1/Th2/Treg paradigm disorders

Study design, size, duration
In self-controlled, prospective study, after IEC clearance and obtaining Informed consent, 19 RM patients underwent immunization with partner lymphocytes from August 2021 to October 2022. Inclusion criteria were at least three clinical pregnancies that culminated in abortion before 20 weeks of gestation or at least three cycles of IVF/ICSI with at least two PGT+ embryos and &gt;8mm endometrium during ET and no pregnancy, normal coagulation tests, autoimmune antibodies negative, normal couple karyotyping.

Participants/materials, setting, methods
Maternal BMI of 30 and age of 45 was the upper limit with peripheral blood Th1/Th2/Treg cells proportions and concentrations of TNF-a, IFN-g, TGF-β1, IL-2, IL-4, IL-6, IL-10, and blocking antibodies were detected using flowcytometry/ELISA as per Seragen’s Immuno profiling platform. 30-50ml paternal blood was used to purify lymphocytes which were intradermally administered to the wife before Embryo Transfer and post-pregnancy confirmation.

Main results and the role of chance
Proportion of Th1 cells was significantly decreased while the proportions of Th2 cells and Treg cells were significantly increased in immunotherapy patients after treatment. In addition, the concentration of TGF-β1 in serum was significantly higher after immunotherapy than before. The concentration of TNF-a, IFN-g was significantly high before therapy were significantly decreased after therapy. LIT effectively induced the production of blocking antibodies in all the patients. 16/19 (84%) uRM patients underwent ET post LIT became pregnant and 4 of the pregnant patient had delivered healthy babies (21%). 42% (8/19) of patients have reported uneventful ongoing pregnancies crossed &gt;14weeks. 4 patients who were pregnant for more than 12-14 weeks had miscarriages (21%). 1 patient (5%) did not conceive. 1 patient (5%) conceived spontaneously and crossed 20 weeks of uneventful gestation. 1 patient (5%) opted to try to conceive naturally hence ET is not planned. The cumulative positive uneventful pregnancy outcome was 68%, approximately the same as the figures reported earlier. LIT is associated with high live birth rates, especially in women with RM. It not only ameliorates patient’s cellular immune function but also further increases patient’s pregnancy success rate with high safety, which is worthy of clinical application and promotion.

Limitations, reasons for caution
This prospective self-control study with small sample size lacks randomized control group. Beneficial effects observed in this study are in sync with published data. Larger study with patients recruited based on inclusion criteria of unexplained recurrent miscarriage due to immunological factors is proposed for recommending LIT as routine therapy.

Wider implications of the findings
Our study findings supports LIT as a beneficial treatment for RM/RIF in IVF patients. LIT may be considered safe and effective therapy in individual cases and based on the immunoprofiling (Th1/Th2/Treg paradigm disorders), after all other potential causes of RM or RIF have been ruled out.

Trial registration number
Not applicable