The role of lymphocytic cells in infertility and reproductive failures in women with antiphospholipid antibodies.

BACKGROUND: The problem of pregnancy losses and infertility in autoimmune pathology is one of the most urgent problems of modern reproductive medicine. Antiphospholipid antibodies (aPL) are very often connected with reproductive failures such as miscarriage, antenatal fetal death, preeclampsia and even infertility and failure of in vitro fertilization (IVF) program. AIM: To evaluate the difference in immune status of aPL-positive women with infertility compared to healthy women and explain the possible mechanism of pathological effects of aPL, a correlation analysis between the level of aPL and the lymphocytes subpopulation was performed. STUDY DESIGN: We observed 280 women of reproductive age. Of these, 191 who met the inclusion and exclusion criteria were included in the study. All 191 women were tested for lupus anticoagulant (LA), antibodies (isotypes IgG, IgM) to cardiolipin (aCL), ß2-glycoprotein-1 (b2-GpI). Of these, 128 women had high level of aPL. The subpopulation of lymphocyte in aPL-positive women was compared with healthy women without reproductive pathology. RESULTS: In women with aPL, the absolute number of CD3+ lymphocytes, cytotoxic lymphocytes CD3+CD8+, T helpers CD3+CD4+, and the absolute levels of NK-cells and NK T-cells were significantly lower. In women with infertility and aPL circulation, we found the significantly higher absolute and relative level of CD19+ lymphocytes compared with healthy women. CONCLUSION: T-regulatory cells play an important role in inducing tolerance to fetal alloantigens and limiting the intensity of the immune response. NK cells play an important role in processes of trophoblast invasion and spiral artery remodeling. Significantly reduced level of T-cells found in women with aPL may be associated with insufficient decidualization of endometrium for embryo invasion, which is clinically manifested by IVF failure.

Neonatal thrombosis.

Neonatal thromboembolism in pediatric patients is a rare but life-threatening condition mainly caused by combinations of at least 2 prothrombotic triggering risk factors such as the central venous lines, septic condition, and prematurity. Other risk factors include asphyxia, dehydration, liver dysfunction, inflammation, and maternal condition. Neonatal hemostatic system is different from one of the older children and adults. Coagulation proteins do not cross the placenta but are synthesized in the fetus from an early stage. In the term neonate, concentrations of several procoagulant proteins, particularly the vitamin K dependent and contact factors are reduced when compared with adults. Conversely, levels of antithrombin, heparin cofactor II and protein C and S are low at birth and fibrinolysis system is characterized by the decreased level of plasminogen and alpha-1-antiplasmin, increased tissue plasminogen activator. These features all tend to be gestational dependent and are more present in the preterm infant. Primarily in this context neonates appear to be at a higher risk of thrombosis than older children. Thrombotic complications reach their peak in the group of children born at 22-27 weeks. The role of inherited thrombophilic risk factors in neonatal VTE development is poorly defined. The presence of inherited and acquired thrombophilia in mother and newborn is also responsible for the development of thrombosis in neonates and should be considered. Thrombophilia in the mother can lead to increased coagulation potential and prethrombotic conditions during pregnancy, causing thrombotic vasculopathy at the placental level. The benefit of identifying thrombophilia in the sick preterm newborns who are in the group of risk for development of thrombotic complications may facilitate the thromboprophylaxis. Further research regarding assessment of risk factors, diagnostics and treatment strategy is required.

Antepartum ultrasound prediction of failed vacuum-assisted operative delivery: a prospective cohort study.

BACKGROUND: Failed vacuum-assisted delivery (VD) is associated with increased risk of maternal perineal trauma and neonatal morbidity. Knowledge of the risk factors related to failed VD is essential in the clinical decision-making. OBJECTIVE: To elucidate the strength of association and the predictive accuracy of different ante-partum ultrasound parameters in predicting the risk of failed VD prior to the onset of Labor and to test the diagnostic performance of a multiparametric model including pregnancy and Labor characteristics, ante and intra-partum ultrasound in anticipating failed VD. STUDY DESIGN: Prospective study of consecutive singleton pregnancies complicated by VD undergoing a dedicated ultrasound assessment at 36-38 weeks of gestation. Head circumference (HC), estimated fetal weight (EFW) and subpubic angle and (SPA) were recorded before the onset of Labor. At the time of the VD, occiput position, head perineum distance (HPD) and angle of progression (AOP) were also recorded. Multivariate logistic regression and area under the curve (AUC) analyses were used to explore the strength of association and test the diagnostic accuracy of different maternal, Labor and ultrasound characteristics in predicting g failed VD. RESULTS: Four hundred eight pregnancies with successful and 26 with failed VD were included in the analysis. Fetuses experiencing failed VD had a larger HC (1.21 versus 1.07 MoM; p = .0001), a higher EFW z-value (0.56 versus 0.33 z values; p = .002) and a narrower SPA (114 versus 122 p = .0001) compared to those having a successful VD. At multivariable logistic regression analysis, maternal height (aOR 0.89 95% CI 0.76-0.98), nulliparity (aOR: 1.14 95% CI 1.06-1.36), HC MoM (aOR: 1.24 95% CI 1.13-1.55) and SPA angle (aOR: 0.82 95% CI 0.67-0.95), but not EFW (p = .08) were independently associated with failed VD. When intrapartum ultrasound variables were added to the multivariate model, fetal occipital position (aOR: 1.45 95th CI 1.11-1.99) and HPD (aOR: 0.77 95th CI 0.44-0.96) were independently associated with failed VD. A multiparametric model integrating pregnancy and Labor characteristics and ante-partum ultrasound variables had an AUC of 0.837 (95% CI 0.797-0.876) for the prediction of failed VE. The addition of intra-partum ultrasound variables to the prediction model, improved the accuracy for failed VD provided by maternal and antepartum ultrasound characteristics with an AUC of 0.913 (0.888-0.937). CONCLUSION: Antepartum prediction of failed VD is feasible. HC, SPA but not EFW are independently associated and predictive of failed VD. Adding these variables to a multiparametric model including maternal and intrapartum ultrasound parameters improves the diagnostic accuracy for failed VD.

Ultrasound assessment of the cervix in predicting successful membrane sweeping: a prospective observational study.

OBJECTIVE: Membrane sweeping has been shown to potentially reduce the need for formal induction of labor. The primary aim of this study was to elucidate the role of ultrasound assessment of the cervix in predicting successful membrane sweeping in singleton pregnancies at term; the secondary aim was to build a multiparametric prediction model integrating, maternal, pregnancy and ultrasound characteristics, able to anticipate spontaneous delivery at term. METHODS: Prospective observational study including singleton pregnancies at term undergoing membrane sweeping. Cervical length (CL) and posterior cervical angle (PCA) were assessed on ultrasound immediately before the procedure. Primary outcome was successful membrane sweeping, defined as spontaneous vaginal birth without formal induction within the 24hours. A subgroup analysis was computed considering women experiencing spontaneous vaginal birth within 48 hours from the procedure. The secondary outcome was to explore the diagnostic performance of a multiparametric model including maternal, pregnancy, and ultrasound assessment of the cervix in predicting spontaneous vaginal birth following membrane sweeping. Multivariate logistic regression and area under the curve (ROC) analyses were used to compute the data. RESULTS: One hundred fifty-nine singleton pregnancies undergoing membrane sweeping were included in the analysis. Successful membrane sweeping within 24 hours occurred in 68/159 women (36.5%). Parity (aOR = 1.87, 95% confidence interval [CI] 1.2-2.44), gestational age (aOR = 1.32, 95% CI 1.14-1.76), CL (aOR = 0.47, 95%CI 0.31-0.69) and PCA (aOR = 1.22, 95%CI 1.07-1.41) were independently associated with spontaneous vaginal birth within 24 hours from sweeping. The AUC of the constructed model was 0.796 (95% CI 0.727-0.865). Likewise, CL (aOR = 0.80, 95%CI 0.72-0.89), PCA (aOR = 1.19, 95%CI 1.10-1.28) and gestational age at the procedure (aOR = 1.65, 95%CI 1.09-1.86; p = .04) were independently associated with delivery within 48 hours with an AUC of 0.737 (95%CI 0.659-0.815). CONCLUSIONS: Cervical ultrasound assessment of the cervix prior to membrane sweeping is associated with spontaneous vaginal birth within 24 and 48 hours from the procedure. The combination of cervical ultrasonographic parameters with parity and gestational age can predict the chances of delivery within 24 or 48 hours from membrane sweeping. The findings from this study support the use of ultrasound assessment of the cervix prior to membrane sweeping in order to more accurately predict the likelihood of spontaneous vaginal delivery.

Unusual thrombosis or pregnancy complications associated to ovarian cancers: two clinical cases.

AIM: Using illustrative cases of two patients with ovarian cancer who developed unusual thrombosis in pregnancy, to describe the difficulties in diagnosing and managing such patients. METHODS: We present the analysis of two cases of thrombosis of unusual localization (central artery of the retina and transverse and sigmoid sinus thrombosis) during pregnancy in women with hidden ovarian cancer. RESULTS: In both cases, the symptomatic of unususal thrombosis was interpreted as a manifestation of eclampsia, leading to a choice of non-optimal obstetric tactics on a background of hidden ovarian cancer, which in both cases were diagnosed only postpartum. CONCLUSIONS: Pregnancy itself is a risk factor for thrombotic complications and in case malignancy develops in parallel with pregnancy, this risk is multiplied. In patients with ovarian cancer, difficulties arise both in detecting the tumor itself due to the enlarged uterus and in interpreting some of the symptoms, which can be regarded as a manifestation of pregnancy complications.

COVID-19, neutrophil extracellular traps and vascular complications in obstetric practice.

An issue of the novel coronavirus infection spreading is currently in the first place among others in the list of the international medical community. Due to lack of information, conflicting research findings, multicomponent effect of the virus on the body host, as well as various consequences that the virus triggers in the body, now every medical specialty does study the viral attack pathogenesis. Recent months showed that vascular complications are the most severe in the Coronavirus Disease 2019 (COVID-19) and are the main cause of death in the patients. The mechanisms of vascular complications are complex and affect both the hemostatic system and immune responses, "inflammatory storm", disorders of the renin-angiotensin-aldosterone system, endotheliopathy, etc. Due to the leading role of vascular complications in the viral infection pathogenesis, several groups of patients are at extra risk, including pregnant women, patients with a burdened obstetric history, with hereditary thrombophilia and antiphospholipid syndrome, and patients after in vitro fertilization (IVF). In this category of pregnant women, use of low-molecular-weight heparins (LMWH) is particularly important for both prevention of vascular and obstetric complications, and for pathogenetic therapy of COVID-19.

Prenatal care and labor in patients with mesenchimal dysplasias (Marfan syndrome, Ehlers-Danlos syndrome, hereditary hemorrhagic telangiectasia).

Background: Mesenchymal dysplasias or inherited connective tissue diseases are the group of diseases with deficiency of various components of connective tissue. Connective tissue disorders can affect different organs: skeleton, sight organ, skin, lungs, heart. But the most dangerous is vascular wall insufficiency leading to high risk of hemorrhage, especially during pregnancy and delivery due to hemodynamic and hormonal effects on the walls of the modified vessels.Aim: To evaluate the risk of complications during the pregnancy and delivery in patients with mesenchymal dysplasias.Study design: Fifty-six pregnancies in patients with mesenchymal dysplasias, including subclinical forms of diseases: 23 with Marfan syndrome (I group), 22 with Ehlers-Danlos syndrome (II group), and 11 with Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia) (III group) of the age from 18 to 36. The study included retrospective analysis (for the period from 1993 to 2005) and prospective study. Results of study showed high risk of life-threatening complications during pregnancy and delivery, especially the risk of hemorrhage and cardiovascular complications. In all the patients, we observed the progression of bleeding or development of bleeding in new localizations (epistaxis in 27 patients, easy brushing in 22, skin and mucosa telangiectasia in 20, gastrointestinal bleedings in 4, hemoptysis in 4, hematomas for minor traumas in 14, conjunctivas hemorrhages in 5).Conclusion: The pathogenesis of bleeding in such patients has mixed pattern: besides vascular wall pathology coagulation deficiency plays some role. The preferred delivery method for such patients is caesarean section. Deep vaginal ruptures and serious hemorrhage accompany vaginal delivery.

In vitro fertilization outcomes in women with antiphospholipid antibodies circulation.

Background: Antiphospholipid antibodies (aPL) have a multifaceted effect on the hemostatic system, damaging all its protective links.Aim: To study the effect of APA on outcomes of assisted reproductive technologies (ART).Study design: We examined 267 women with infertility, who planned pregnancy using ART. They included 178 women with IVF failure (I group) and 89 women with pregnancy after the IVF program (II group). The comparison group consisted of 80 pregnant women after IVF (male factor); a control group included 80 pregnant women with physiological pregnancy. Results of study demonstrated a high frequency of aPL circulation in a group of women with IVF failures. Overall, the proportion of aPL among all 267 women who planned pregnancy with ART was 32.6%. Elevated levels of aPL in the structure of causes of IVF failures (group I) were observed in 42.1% of them. Among women whose pregnancy occurred with ART (II group) the rate of APA was 19.1%. In the comparison group, in 6.3% of cases, aPL circulation was observed. In the control group, the rate was 3.4%.Conclusion: Considering the high percentage of aPL circulation in the case of IVF failures, authors think that high titers of aPL are a temporary contraindication for IVF. Patients with a history of aPL circulation are required to receive anticoagulant therapy from the first days of the hormonal protocol. The drug of choice is a group of low molecular weight heparins (LMWH). An individual approach is extremely important with the possible identification of causes of IVF failures and selective therapy, which leads to a significant improvement in the outcomes of the IVF program.

Skin pathologies in pregnancy.

Progesterone is a hormone responsible for pregnancy maintenance and the amount of progesterone increases in a woman's body during pregnancy, as well as the level of female sex hormones, estrogens are also upregulated. Due to these changes the cutaneous sensitivity to external stimuli (meteorological factors, bacteria, etc.) increases. In general, all skin changes during pregnancy can be divided into three groups: physiological changes (hormone-associated), nonspecific or dermatoses that existed before pregnancy or were triggered by it, and specific pregnancy-related dermatoses, which appear during pregnancy and resolve in the postpartum period. In this brief  review, we describe the dermatoses commonly seen in pregnancy and present our own clinical examples. We hope the review will be of some practical help for dermatologists and obstetricians.

Catastrophic antiphospholipid syndrome (Ronald Asherson syndrome) and obstetric pathology.

BACKGROUND: Catastrophic antiphospholipid syndrome (CAPS) is an uncommon, often fatal, variant of the antiphospholipid syndrome (APS) that results in a widespread coagulopathy and high titres of antiphospholipid antibodies (aPL) and affects predominantly small vessels supplying organs with the development of multiorgan failure. It remains unclear why some patients develop the typical clinical picture of APS (thrombosis of large vessels), whereas others show the development of progressive microthrombosis, which the authors called "thrombotic storm" and multiple organ failure, that is, CAPS. MATERIALS AND METHODS: Since 2001-2016, we discovered 17 patients with CAPS development. CONCLUSION: CAPS is life-threatening condition, but optimal treatment for CAPS is not developed yet and the mortality rate is as high as 30%-40%.