Recurrent pregnancy losses (RPL) is a common reproductive disorder with various underlying etiologies. In recent years, rapid progress has been made in exploring the immunological mechanisms for RPL. A propensity toward Th2 over Th1 and regulatory T (Treg) over Th17 immune responses may be advantageous for reproductive success. In women with RPL and animals prone to abortion, an inordinate expression of cytokines associated with implantation and early embryo development is present in the endometrium or decidua secreted from immune and non-immune cells. Hence, an adverse cytokine milieu at the maternal-fetal interface assaults immunological tolerance, leading to fetal rejection. Similar to T cells, NK cells can be categorized based on the characteristics of cytokines they secrete. Decidual NK (dNK) cells of RPL patients exhibited an increased NK1/NK2 ratio (IFN-γ/IL-4 producing NK cell ratios), leading to pro-inflammatory cytokine milieu and increased NK cell cytotoxicity. Genetic polymorphism may be the underlying etiologies for Th1 and Th17 propensity since it alters cytokine production. In addition, various hormones participate in cytokine regulations, including progesterone and estrogen, controlling cytokine balance in favor of the Th2 type. Consequently, the intricate regulation of cytokines and hormones may prevent the RPL of immune etiologies. Local or systemic administration of cytokines or their antagonists might help maintain adequate cytokine milieu, favoring Th2 over Th1 response or Treg over Th17 immune response in women with RPL. Herein, we provided an updated comprehensive review regarding the immune-regulatory role of pro- and anti-inflammatory cytokines in RPL. Understanding the roles of cytokines involved in RPL might significantly advance the early diagnosis, monitoring, and treatment of RPL.

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B₆ and B₁₂ deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

Listeria monocytogenes (LM) is an intracellular, aerobic and facultative anaerobic, Gram-positive bacterium, which is primarily transmitted to humans orally via food. LM could occur in asymptomatic pregnant women; however, fetal infection is a serious condition, entailing premature birth, abortion, sepsis, central nervous system (CNS) involvement, or even death. If a pregnant woman exhibits symptoms, the performance is almost like influenza, such as fever, headache, diarrhea, myalgia, or other digestive-related symptoms. This review collected clinical and empirical results regarding the mechanism, clinical manifestations, obstetrical outcome, diagnosis, treatment, vertical transmission, neonatal infection, and prevention of listeriosi according to articles published in PubMed from January 1, 1980, to March 20, 2021. The early detection and diagnosis of pregnancy-associated listeriosis are significant since sensitive antibiotics are effective at enhancing the prognosis of newborns. Listeriosis can be diagnosed using positive cultures from maternal or neonatal blood, neonatal cerebrospinal fluid (CSF), amniotic fluid, intrauterine mucosa, or the placenta. Two weeks of high-dose intravenous amoxicillin (more than 6 g/day) is recommended for LM pregnant women without allergy. Terminating the pregnancy to save the mother’s life should be considered if maternal and fetal conditions aggravate. Neonatal Listeria infection is primarily transmitted through the placenta, which is a critical illness associated with a high mortality rate. The necessary dietary guidance for pregnant women can reduce the incidence rate of pregnancy-related listeriosis.

The invasion of trophoblasts into the uterine decidua and decidual vessels is critical for the formation of placenta. The defects of placentation are related to the etiologies of preeclampsia (PE), fetal growth restriction (FGR), and small-for-gestational age (SGA) neonates. It is possible to predict significant vascular events during pregnancy through uterine artery Doppler (UAD). From the implantation stage to the end of pregnancy, detecting changes in uterine and placental blood vessels can provide a favorable diagnostic instrument for pregnancy complications. This review aims to collect literature about the roles of UAD in pregnancy complications. We consider all relevant articles in English from January 1, 1983 to October 30, 2021. Predicting pregnancy complications in advance allows practitioners to carry out timely interventions to avoid or lessen the harm to mothers and neonates. Administering low-dose aspirin daily before 16 weeks of pregnancy can significantly reduce the incidence of pregnancy complications. From early pregnancy to late pregnancy, UAD can combine with other maternal factors, biochemical indicators, and fetal measurement data to identify high-risk population. The identification of high-risk groups can also lessen maternal mortality. Besides, through moderate risk stratification, stringent monitoring for high-risk pregnant women can be implemented, decreasing the incidence of adversities.

Preeclampsia (PE) is a disease that is unique to pregnancy and affects multiple systems. It can lead to maternal and perinatal mortality. The precise etiology of PE is unclear. Patients with PE may have systemic or local immune abnormalities. A group of researchers has proposed that the immune communication between the fetus and mother is primarily moderated by natural killer (NK) cells as opposed to T cells, since NK cells are the most abundant immune cells in the uterus. This review examines the immunological roles of NK cells in the pathogenesis of PE. Our aim is to provide obstetricians with a comprehensive and updated research progress report on NK cells in PE patients. It has been reported that decidual NK (dNK) cells contribute to the process of uterine spiral artery remodeling and can modulate trophoblast invasion. Additionally, dNK cells can stimulate fetal growth and regulate delivery. It appears that the count or proportion of circulating NK cells is elevated in patients with or at risk for PE. Changes in the number or function of dNK cells may be the cause of PE. The Th1/Th2 equilibrium in PE has gradually shifted to an NK1/NK2 equilibrium based on cytokine production. An improper combination of killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA)-C may lead to insufficient activation of dNK cells, thereby causing PE. In the etiology of PE, NK cells appear to exert a central effect in both peripheral blood and the maternal-fetal interface. To maintain immune equilibrium both locally and systemically, it is necessary to take therapeutic measures directed at NK cells.