Modzelewski, J., Kajdy, A., & Rabijewski, M. (2019). The role of lymphocytes in fetal development and recurrent pregnancy loss. Ginekologia Polska, 90(2), 109-113. https://doi.org/10.5603/GP.2019.0019
Modzelewski J, Kajdy A, Rabijewski M. The role of lymphocytes in fetal development and recurrent pregnancy loss. Ginekol Pol. 2019;90(2):109-113. doi:10.5603/GP.2019.0019
Modzelewski, Jan, et al. "The role of lymphocytes in fetal development and recurrent pregnancy loss." Ginekologia Polska, vol. 90, no. 2, 2019, pp. 109-113.
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RRM Academy Synopsis
Immune Cell Imbalance Is Linked to Recurrent Pregnancy Loss
Women with unexplained recurrent pregnancy loss had more Th17 immune cells than fertile women, according to a 2019 review in a medical journal. The review also describes immune therapy trials and a 2018 guideline on immune testing.
Key Findings
In one study, fertile women had a higher Treg percentage (9.5% ± 0.52) than women with unexplained recurrent pregnancy loss (5.66% ± 0.21), and a lower Th17 percentage (1.82% vs 2.8%).
A trial of intravenous immunoglobulin in 78 women with recurrent pregnancy loss found an 86.8% live birth rate in the treatment group versus 45% in controls (p = 0.0006).
A meta-analysis of six other meta-analyses on paternal or donor lymphocyte therapy found four reported improved live birth rates, with odds ratios ranging from 1.16 to 4.02.
A study of 121 women with MTHFR gene mutations found low molecular weight heparin was linked to a higher live birth rate (69.8% vs 48.5%) and fewer congenital anomalies (3.3% vs 17.6%).
The ESHRE 2018 guideline on recurrent pregnancy loss recommends only antiphospholipid syndrome screening and HLA class II determination in selected women, stating other immunological tests should not be performed.
Interpretation
This is a review of research on immune cells and recurrent pregnancy loss, covering lab studies, treatment trials, and guidelines. Immune cell patterns differed between women with recurrent pregnancy loss and fertile women. Several treatment trials found higher live birth rates with immune-based treatments. The authors note that immune causes of pregnancy loss likely involve many factors, which makes them hard to study. The ESHRE 2018 guideline limits immune testing to two markers in selected women and advises these treatments be used only in a clinical trial. The findings support larger trials of immune-based treatments for recurrent pregnancy loss.
RRM Context
Restorative reproductive medicine's root-cause approach looks for the cause of repeat pregnancy loss before treating it. This review adds immune cell imbalance as another possible cause still being studied. About half of repeat pregnancy loss cases have no clear cause found through testing today. The ESHRE guideline this review cites limits immune testing to two markers in selected women and advises that IVIG and lymphocyte therapy be used only within a clinical trial. Limiting testing this way fits a root-cause, evaluation-before-treatment approach.
Our editorial summary of this paper, not the article's abstract.
Abstract
Fetal survival and development is supported by the maternal immune system. Questions regarding those mechanisms have risen from development of transplantation medicine and observation of graft rejection. Initial theories of anatomic division, fetal immune immaturity and maternal immune system inertia were found incorrect. Rejection of fetal "semi-allograft" by maternal immune system could result in pregnancy loss. Two pregnancy losses of any etiology are considered recurrent and effort should be made to name the probable cause. Immune causes of pregnancy loss are probably multifactorial, thus difficult to research and implement findings in clinical practice. Although a full understating of pregnancy loss is not established, new therapies are being developed. This review summarizes the role of lymphocytes in pregnancy develop- ment, presents data from studies on recurrent pregnancy loss patients, evidence of new therapies and ESHRE guidelines regarding immunologic investigations.
Miscarriage affects approximately 15% of clinically confirmed pregnancies. Recurrent pregnancy loss (RPL), defined as two or more clinical losses, affects 2 to 5% of couples. Most causes are diagnosable and treatable. This guide covers what the standard workup misses, what RRM-trained clinicians evaluate, and what outcomes look like after cause-based treatment.
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