Recurrent miscarriage is frustrating for the physician and a heartbreaking experience for the patient. Approximately 5% of couples trying to conceive have two consecutive miscarriages. Despite a thorough study of patients, the aetiology of this common obstetric complication is unknown in 50% of cases. Known causes include abnormal chromosomes, endocrinological disorders and uterine abnormalities. Although antiphospholipid antibodies have been demonstrated in miscarriages, the role played by alloimmune mechanisms remains unclear. New immunological approaches such as natural killer cells, regulatory T cells, tumour necrosis factor α, cell-derived microparticles, leptin, certain glycoproteins and cytokines should be considered. The management of thyroid diseases and immunological disorders is continuously evolving. Several genetic diagnostic procedures such as parental karyotyping and preimplantation genetic screening should probably not be used routinely. Antiphopholipid syndrome and some recurrent miscarriage-related endocrinological disorders can be effectively treated. Finally, new therapeutic approaches and the pleiotropic effects of old ones have led to improved fetal-maternal outcomes.

Objectives To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS). Methods This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome. Results A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C). Conclusion Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.

Pregnancy is a proinflammatory and hypercoagulable state. Miscarriage concerns approximately 15% of pregnancies. Recurrent miscarriage is a rather rare condition with an estimated incidence of 1% to 3%. However, despite years of investigation, the etiology is not established in up to 50% of cases. A multidisciplinary approach in the evaluation of miscarriage is essential to understand the cause and risk of recurrence. Although genetic factors are the major cause of spontaneous miscarriages, their relationship with recurrent miscarriage is less frequent. Recently, many kinds of genetic polymorphisms have also been found to be associated. Endocrine disorders such as poorly controlled diabetes, polycystic ovary syndrome, and hypothyroidism are linked with recurrent miscarriage. The relationship between recurrent miscarriage and subclinical thyroid disorders and thyroid autoimmunity is disputed, especially in early miscarriages. Uterine malformations should be considered as a cause of recurrent miscarriage. Although autoimmune-based recurrent miscarriage has been described, mainly antiphospholipid antibodies, the role of alloimmune mechanisms remains poorly understood. The influence of congenital thrombophilia is controversial. Antiphospholipid syndrome or antiphospholipid antibody-related recurrent miscarriage, and some endocrinologic disorders, have a specific and effective treatment. Still, the effectiveness of some common treatments needs to be demonstrated.

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Preeclampsia is caused by placental impairment with increased expression of sFlt-1 (soluble fms-like tyrosine kinase 1) and decreased PlGF (placental growth factor); it has been associated with cardiovascular morbidity and mortality later in life, but the underlying mechanism remains unknown. The aim of this study was to determine whether sFlt-1 and PlGF levels during preeclampsia are associated to long-term cardiovascular risk. We prospectively recruited 43 women with previous preeclampsia and 21 controls with uncomplicated pregnancies. Cardiovascular risk assessment ≈12 years later included maternal hemodynamic, cardiac function and structure, biomarker analysis, and carotid-intima thickness evaluation. Women with previous preeclampsia had higher prevalence of hypertensive disorders and dyslipidemia than controls. In addition, they had worse global longitudinal strain, thicker left ventricular septal and posterior walls, more myocardial mass and increased carotid intima-media thickness compared with controls. PlGF during pregnancy correlated positively with high-density lipoprotein ( r =0.341; P =0.006), and negatively with global longitudinal strain ( r =−0.581; P <0.001), carotid intima-media thickness ( r =−0.251; P =0.045), and mean arterial blood pressure ( r =−0.252; P =0.045), when adjusted by study group. sFlt correlated negatively with high-density lipoprotein ( r =−0.372; P =0.002) and apolipoprotein A-1 ( r =−0.257; P =0.040), and positively with carotid intima-media thickness ( r =0.269; P =0.032) and left ventricular posterior wall thickness ( r =0.368; P =0.003). The antiangiogenic state present in preeclampsia is related to greater prevalence of cardiovascular risk factors ≈12 years after delivery. The knowledge of altered angiogenic factors may help detect women with a higher risk for premature cardiovascular disease, who will require earlier follow-up after delivery.

Introduction Increased soluble fms‐like tyrosine kinase to placental growth factor ratio (sFlt‐1/PlGF) has been demonstrated in early‐onset fetal growth restriction (FGR) and small for gestational age (SGA). sFlt‐1/PlGF cut‐offs have been described to assess preeclampsia severity; however, sFlt‐1/PlGF values present in early‐onset SGA and different FGR severity stages remain unknown. Hence, the objective of this study was to describe and compare the sFlt‐1/PlGF values and pregnancy outcomes among early‐onset SGA/FGR stages. Material and methods This is a prospective case‐control study conducted at Vall d’Hebron University Hospital. Singleton pregnancies with estimated fetal weight <10th centile and a control group of uncomplicated pregnancies between 20+0 and 31+6 weeks of gestation were enrolled. Study women were classified at diagnosis into different stages, according to estimated fetal weight centile and Doppler ultrasound. sFlt‐1/PlGF serum concentrations were measured at diagnosis and, together with pregnancy outcomes, were compared among FGR severity stages, SGA, and controls. Finally, correlations between sFlt‐1/PlGF values and time to delivery, gestational age at delivery, days of neonatal admission, and birthweight z‐scores were investigated. Results Among the 207 women enrolled, 32 (15.4%) had uncomplicated pregnancies, 49 (23.7%) pregnancies showed SGA, and 126 (60.9%) involved FGR (92 being stage I, 17 stage II, and 17 stage III). SGA and controls had similar median sFlt‐1/PlGF values (25.7 vs 27.1, P > .05) and pregnancy outcomes. However, all FGR stages had significantly poorer outcomes and greater sFlt‐1/PlGF values than those of SGA and controls. Furthermore, median values differed significantly among all FGR severity stages (9.76 for stage I; 284.3 for stage II, and 625.02 for stage III, P < .05) increasing with FGR severity as well as the frequency of adverse pregnancy outcomes. Additionally, a significant correlation was found between greater sFlt‐1/PlGF ratio values and gestational age at delivery, time from diagnosis to delivery, birthweight z‐scores, and time in neonatal intensive care unit (r = −.637, r = −.576, r = −.161, and r = .311, respectively). Conclusions Values of sFlt‐1/PlGF at diagnosis permit early‐onset FGR/SGA severity classification with good correlation with Doppler ultrasound findings and the occurrence of adverse outcomes. Thus, sFlt‐1/PlGF could aid in early‐onset FGR/SGA severity classification and clinical management when Doppler assessment is not feasible.

Purpose Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice. Methods/patients Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT. Results 665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84–19.16 vs. 19 months 95% CI 16.11–21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p < 0.05). 291 patients with melanoma were enrolled. There was a 5.8% incidence rate of VTE/AT during follow-up. Median OS was lower in the VTE/AT group (10 months 95% CI 0.0–20.27 vs. 29 months 95% CI 19.58–36.42; p = 0.034). NLR and lactate dehydrogenase (LDH) at the beginning of ICI were predictor variables for VTE/AT (p < 0.05). Conclusions ICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS.

Background: Vasa previa consists in the presence of extraplacental fetal vessels overlying the cervix. This condition is commonly associated with fatal outcome if prenatally undiagnosed. Two types of vasa previa have been classically described, associated with well-established risk factors. However, a rare third type of vasa previa has also been reported. Case: We present a case of type 3 vasa previa diagnosed in the second trimester, with two fetal vessels overlying the cervix. The placenta was unilobed, not previa, and the cord insertion was marginal. Placental examination after delivery confirmed the prenatal findings. Conclusion: This case suggests that vasa previa can occur in the absence of cord or placental anomalies. A review of vasa previa classification and screening strategies for this condition is needed.