Live Birth Rates after Active Immunization with Partner Lymphocytes

Although many potential causes have been established for recurrent implantation failure (RIF) and recurrent miscarriage (RM), about 50% of these remain idiopathic. Scientific research is focused on immunological risk factors. In the present study, we aim to evaluate live birth rates after immunization with paternal lymphocytes (lymphocyte immunotherapy (LIT)). This retrospective study consisted of 148 couples with a history of RM and/or RIF. The women underwent immunization with lymphocytes of their respective partners from November 2017 to August 2019. Fifty-five patients (43%) had live births. Stratified by indication (RM, RIF, combined), live birth rates in the RM and the combined group were significantly higher than that in the RIF group (53%, 59% and 33%, respectively, p = 0.02). The difference was especially noticeable during the first 90 days after immunization (conception rate leading to live births: 31%, 23% and 8% for RM, the combined group and RIF, respectively; p = 0.005), while there was no difference between groups during the later follow-up. LIT was associated with high live birth rates, especially in women with recurrent miscarriage. In view of the limited data from randomized studies, LIT cannot be recommended as routine therapy. However, it may be considered in individual cases.

Intralipid Therapy and Adverse Reproductive Outcome: Is there Any Evidence?

Controversy exists regarding the benefits of intravenous intralipid therapy in patients with poor reproductive history. It is frequently reported that there is no evidence to support the effectiveness, utility or safety for this treatment. While individual studies may be perceived as weak, a systematic review and meta-analysis was performed to determine if there is any advantage to patients. PubMed, Embase and Scopus searches were performed with the target populations being either recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) undergoing assisted reproductive technology (ART) and receiving intralipid infusions. These cohorts were compared with either placebo, no intervention or alternative treatments. The most relevant outcome measures were considered to be clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR) and miscarriage rate (MR). Twelve studies encompassing 2,676 participants met the criteria for selection and were included and reviewed. Treatment of the target population with intralipid led to an improvement in IR (Odds Ratio (OR) 2.97, 2.05-4.29), pregnancy rate (OR 1.64, 1.31-2.04), and LBR (OR 2.36, 1.75-3.17), with a reduction in MR (OR 0.2, 0.14-0.30). Although intravenous intralipid is not recommended as a routine treatment for recurrent miscarriage or implantation failure, there is enough data to suggest consideration in selected patients where routine testing is unremarkable, standard treatments have failed and immunological risk factors are present. The presence of abnormal uterine natural killer (uNK) cells needs more study as a target marker to determine those who could benefit.

Immunological Risk Factors in Recurrent Pregnancy Loss: Guidelines Versus Current State of the Art

Around 1–5% of all couples experience recurrent pregnancy loss (RPL). Established risk factors include anatomical, genetic, endocrine, and hemostatic alterations. With around 50% of idiopathic cases, immunological risk factors are getting into the scientific focus, however international guidelines hardly take them into account. Within this review, the current state of immunological risk factors in RPL in international guidelines of the European Society of Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine (ASRM), German/Austrian/Swiss Society of Obstetrics and Gynecology (DGGG/OEGGG/SGGG) and the Royal College of Obstetricians and Gynecologists (RCOG) are evaluated. Special attention was drawn to recommendations in the guidelines regarding diagnostic factors such as autoantibodies, natural killer cells, regulatory T cells, dendritic cells, plasma cells, and human leukocyte antigen system (HLA)-sharing as well as treatment options such as corticosteroids, intralipids, intravenous immunoglobulins, aspirin and heparin in RPL. Finally, the current state of the art focusing on both diagnostic and therapeutic options was summarized.

The effect of progestagens on immunological risk factors of preterm birth

Aim. To determine the level of IgA and IgG to estradiol, progesterone, and benzo[a]pyrene in women with or without preterm labor and to assess whether the administration of progestagens affect these parameters.Materials and Methods. We measured the levels of IgA and IgG to estradiol, progesterone, and benzo[a]pyrene in serum of 199 pregnant women (68 with PL and 81 with normal delivery) with the following analysis of associations between progestagen administration and these parameters.Results. The level of IgA to estradiol in patients with preterm labor was significantly higher than in women with normal delivery, and the administration of progestagens did not reduce their level in women with preterm birth.Conclusions. Measurement of the antibodies to estradiol may help in predicting pregnancy complications such as preterm birth.

Comparative evaluation of markers of inflammation and fibrosis in patients with various clinical forms of atrial fibrillation

Aim. To identify and assess the significance of clinical and functional data characterizing cardiac remodeling, as well as inflammatory and fibrosis markers in patients with various clinical forms that promote the progression of atrial fibrillation (AF).Material and methods. We observed 213 patients with arterial hypertension or in combination with coronary artery disease, who were diagnosed with AF. For the clinical and functional assessment of various clinical forms of AF, the significance of certain clinical, hemodynamic, structural, functional, and immunological risk factors for AF was studied. We used the method of binary logistic regression and calculated the significance of the risk factors odds ratio (OR).Results. We made a database consisting of 33 indicators characterizing the clinical, hemodynamic and structural-functional heart condition, inflammatory and fibrosis markers, the significance of which was ambiguous in various clinical groups of AF patients. We identified enough informativeness of the OR significance for indicators of atrial electrical remodeling, which significantly increases from the paroxysmal AF to the persistent form. It confirms a significant role for the heterogeneity of pulses in the atria during the progression of AF. The degree of structural remodeling of both the atria and ventricles also significantly increases with the progression of AF. We also noted that inflammatory markers have statistically significant role with paroxysmal AF. With persistent AF, the significance of OR for inflammatory markers increases, and with permanent AF, their significance decreases. The significance of the OR in fibrosis marker is significantly high with AF and in the further AF progression, and it significantly increases with the persistent AF form.Conclusion. We determined different degrees of electrical and structural remodeling of the atria and ventricles in patients with various clinical forms of AF. At the same time, there is an increase in the reliability of OR in inflammatory and fibrosis markers. However, in patients with persistent AF, the duration of AF and increase in the significance of the OR in fibrosis marker come to the fore.

Immunologic Factors

The immune response is a highly complex system that has developed to protect individuals from morbidity and mortality induced by exogenous exposures, including infections. As summarized in this chapter, alterations in the immune response, whether due to immunosuppressive or immune stimulatory effects, have important consequences with respect to cancer risk. Individuals with inherited immunological defects, acquired immunological deficiencies, chronic unresolved infections, and autoimmune conditions are at considerably increased risk for multiple cancers, suggesting an important role for the immune response in the development of cancer at various anatomical sites. Studies that have directly evaluated immunogenetic and immunological factors and cancer risk are beginning to identify specific immunological risk factors associated with individual cancers. Furthermore, technological advances have made it increasingly feasible to evaluate specific immunological factors and their relationship to cancer risk, suggesting that additional insights are likely in the coming years.