BACKGROUND Despite significant advances in our understanding of the pathophysiology of preeclampsia (PE), there are still many unknowns and controversies in the field. Women undergoing frozen-thawed embryo transfer (FET) to a hormonally prepared endometrium have been found to have an unexpected increased risk of PE compared to women who receive embryos in a natural FET cycle. The differences in risk have been hypothesized to be related to the absence or presence of a functioning corpus luteum (CL). OBJECTIVE AND RATIONALE To evaluate the literature on secretory products of the CL that could be essential for a healthy pregnancy and could reduce the risk of PE in the setting of FET. SEARCH METHODS For this review, pertinent studies were searched in PubMed/Medline (updated June 2020) using common keywords applied in the field of assisted reproductive technologies, CL physiology and preeclampsia. We also screened the complete list of references in recent publications in English (both animal and human studies) on the topics investigated. Given the design of this work as a narrative review, no formal criteria for study selection or appraisal were utilized. OUTCOMES The CL is a major source of multiple factors regulating reproduction. Progesterone, estradiol, relaxin and vasoactive and angiogenic substances produced by the CL have important roles in regulating its functional lifespan and are also secreted into the circulation to act remotely during early stages of pregnancy. Beyond the known actions of progesterone and estradiol on the uterus in early pregnancy, their metabolites have angiogenic properties that may optimize implantation and placentation. Serum levels of relaxin are almost undetectable in pregnant women without a CL, which precludes some maternal cardiovascular and renal adaptations to early pregnancy. We suggest that an imbalance in steroid hormones and their metabolites and polypeptides influencing early physiologic processes such as decidualization, implantation, angiogenesis and maternal haemodynamics could contribute to the increased PE risk among women undergoing programmed FET cycles. WIDER IMPLICATIONS A better understanding of the critical roles of the secretory products of the CL during early pregnancy holds the promise of improving the efficacy and safety of ART based on programmed FET cycles.

Preeclampsia is a worldwide pregnancy complication with serious short and long-term maternal and neonatal consequences. Our understanding of preeclampsia pathophysiology has significantly evolved over the last decades with the recognition that impaired arterial function and structure may occur early in the course of pregnancy, preceding the clinic-humoral syndrome and driving long-term cardiovascular disease risk in the future of these patients. Although an early abnormal placentation may be the inciting event for a large proportion of cases, there is growing evidence that challenges the placental hypothesis in all affected women, since placental histopathology lesions thought to be characteristic are neither sensitive nor specific markers for the disorder. Recent hemodynamic investigations and studies on left ventricular function and structure in women with preeclampsia further challenge this universal paradigm and propose that placental dysfunction could be secondary to a maternal cardiovascular maladaptation to pregnancy in certain patients. Supporting this hypothesis, certain vascular features, which are characteristically enhanced in normal pregnancy allowing a healthy vascular adaptation are absent in preeclampsia and comparable to the non-pregnant population. However, arterial biomechanics in preeclampsia may only not cope with hemodynamic demands of pregnancy, but also impose additional detrimental loads to the maternal heart ("impaired left-ventricle-aorta coupling") and transmit pressure and flow disturbances into the fetoplacental circulation ("impaired large arteries-microcirculation coupling"). In this review, we analyze the major role of the arterial dysfunction in the cardiovascular maladaptation hypothesis of preeclampsia, shed light on its potential etiopathogenic link and discuss the complementary nature of the placental and cardiovascular theories.

Background: Non-pregnant (NP) women have a progressive increase in arterial stiffness from central-to-peripheral arteries [“stiffness gradient” (SG)], which is of physiologic importance since excessive pulsatility is filtered by the creation of wave reflections. If the aorta gets stiff with minimal or no change in the periphery, the SG is dissipated transmitting pressure disturbances to the microcirculation. It remains unknown the status of the SG in both women with healthy pregnancies (HP) and complicated by pregnancy-associated hypertension (PAH).Objective: To determine whether HP and PAH are associated with changes in SG. Secondarily, we aim at identifying potential differences between the subgroups of PAH (pre-eclampsia and gestational hypertension).Methods: HP (n = 10), PAH (n = 16), and healthy NP women (n = 401, to be matched for age, and cardiovascular risk with the pregnant women) were included. Carotid-to-femoral (cfPWV) and carotid-to-radial pulse wave velocity (crPWV), common carotid artery (CCA) and brachial artery (BA) diameters and elastic modulus (EM), and regional (cfPWV/crPWV or “PWV ratio”) and local (CCA EM/BA EM or “EM ratio”) SG were quantified.Results: HP showed no changes in PWV ratio compared with NP, in the presence of significantly lower cfPWV and crPWV. HP exhibited higher arterial diameters and lower CCA EM/BA EM compared to NP, without differences with PAH. PAH was associated with a significant increase in the PWV ratio that exceeded the levels of both NP and HP, explained by a lower (although significant) reduction of cfPWV with respect to that observed in HP with respect to NP, and a higher reduction in crPWV with respect to that observed between HP and NP. The blunted reduction in cfPWV observed in PAH coincided with an increase in the CCA EM.Conclusions: Compared with NP, HP was associated with unchanged PWV ratio but with a reduction in CCA EM/BA EM, in the setting of a generalized drop in arterial stiffness. Compared with NP and HP, PAH was associated with an “exaggerated rise” in the PWV ratio without changes in CCA EM/BA EM, in the setting of a blunt reduction in cfPWV but exaggerated crPWV drop. The SG attenuation/reversal in PAH was mainly driven by pre-eclampsia.

Introdução: Estima-se que os distúrbios hipertensivos na gravidez afetam 6-8% das gestantes nos Estados Unidos e são considerados um dos principais fatores de mortalidade materna. No Brasil, de acordo com o DATASUS, se considerarmos as categorias O13 a O16 do CID-10, os distúrbios hipertensivos representaram cerca de 20,22% das mortes maternas no período de 2004 a 2014. Objetivos: O objetivo da revisão é demonstrar os tratamentos mais atuais para o tratamento de distúrbios hipertensivos durante a gravidez. Métodos: Foram consultadas as bases de dados Medline/Pubmed, LILACS/SciELO, Cochrane e Scopus, procurando artigos nacionais e internacionais publicados entre 2006 e 2016, em inglês e português, bem como os consensos estabelecidos pela Organização Mundial da Saúde e as estatísticas do DATASUS. Resultados: As medidas recomendadas para prevenir a pré-eclâmpsia (PE) foram a suplementação de cálcio para gestantes com baixa ingestão dietética e a administração de baixas doses de aspirina. Na PE, se acontecer no termo, o tratamento é induzir o parto, mas se ocorrer pré-termo, é monitorar, administrar sulfato de magnésio (SM), anti-hipertensivos e corticóide. Em caso de eclâmpsia, a SM é muito eficaz para reduzir as convulsões eclâmpticas. Os fármacos utilizados no tratamento da hipertensão crônica grave são metildopa em associação ou não, com nifedipina ou hidralazina. A crise hipertensiva aguda é tratada com fármacos de primeira linha, como nifedipina e hidralazina, e alternativamente com nitroprussiato de sódio. Conclusão: Os principais protocolos mundiais seguem basicamente a mesma orientação, mudando apenas detalhes específicos de conduta de acordo com os recursos do sistema de saúde de cada país. O controle da pressão arterial materna apresenta resultados satisfatórios para o binômio materno-fetal, pois reduz o risco de PE e eclâmpsia. O tratamento definitivo para PE e eclâmpsia é a indução de parto, sendo utilizado apenas medidas terapêuticas para controle, já que não têm cura.

Bioelectrical impedance analysis (BIA)-derived indexes [e.g., fat (FMI) and fat-free mass indexes (FFMI), visceral fat level (VFL)] are used to characterize obesity as a cardiovascular risk factor (CRF). The BIA-derived index that better predicts arterial variability is still discussed.AimsTo determine: (1) the association of classical [weight, height, body mass index (BMI), basal metabolic rate (BMR)] and BIA-derived indexes, with arterial properties deviations from expected values (arterial z-scores); (2) maximum arterial variations attributable to BIA-derived indexes; (3) whether the composition of total body, trunk and/or limbs is most closely associated with arterial variations.MethodsHemodynamic, structural, and functional parameters of different histological types of arteries were assessed (n = 538, 7–85 years). Classical and BIA-derived indexes [fat mass and percentage, FMI, VFL, muscle mass percentage (PMM), FFMI, and percentage] were measured (mono- and multi-segmental devices). Arterial z-scores were obtained using age-related equations derived from individuals not-exposed to CRFs (n = 1,688).ResultsFirst, regardless of the classical index considered, the associations with the arterial properties showed a specific hierarchy order: diameters and local stiffness > aortic and brachial blood pressure (BP) > regional stiffness. Second, all the associations of FMI and FFMI with z-scores were positive. Third, FFMI exceeded the association obtained with BMI and BMR, considering structural z-scores. In contrast, FMI did not exceed the association with z-scores achieved by BMI and BMR. Fourth, regardless of CRFs and classical indexes, arterial z-scores would be mainly explained by FFMI, VFL, and PMM. Fifth, regardless of the body-segment considered, the levels of association between FMI and z-scores did not exceed those found for classic and FFMI. Total fat mass and trunk indexes showed a greater strength of association with z-scores than the FMI of limbs. Sixth, compared to lower limb FFMI indexes, total and upper limbs FFMI showed higher levels of association with z-scores.ConclusionsFFMI (but not FMI) exceeded the strength of association seen between BMI or BMR and structural z-scores. Regardless of the body segment analyzed, the associations between FMI and z-scores did not exceed those found with classic and FFMI. Arterial z-scores could be independently explained by FFMI, VFL, and PMM.

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: Preeclampsia (PE) is a worldwide pregnancy complication with serious maternal and neonatal consequences. Our understanding of PE pathophysiology has significantly evolved over the last decades by recognizing that endothelial dysfunction and systemic inflammation, with an associated angiogenic imbalance, are key pieces of this still incomplete puzzle. In the present era, where no single treatment to cure or treat this obstetric condition has been developed so far, PE prevention and early prediction poses the most useful clinical approach to reduce the PE burden. Although most PE episodes occur in healthy nulliparous women, the identification of specific clinical conditions that increase dramatically the risk of PE provides a critical opportunity to improve outcomes by acting on potential reversible factors, and also contribute to better understand this pathophysiologic enigma. In this review, we highlight major clinical contributors of PE and shed light about their potential link with endothelial dysfunction and inflammation.

BackgroundIncreased wave reflections assessed by pulse wave analysis (PWA) was proposed as one of the potential culprits of hypertension seen in women with pregnancy-associated hypertension (PAH). However, this statement has never been confirmed with “Wave Separation Analysis” (WSA), a more sophisticated mathematical approach that analyzes the amplitude and interaction between forward and backward aortic pressure waveform components.ObjectiveTo characterize potential changes in pressure wave components of PAH compared to healthy non-pregnant (NP) women and women with normal pregnancies (HP) by using WSA and compared these findings with PWA-derived indexes; secondarily, to evaluate differences in WSA-derived indexes between subgroups of PAH (i.e., preeclampsia [PE] and gestational hypertension [GH]).MethodsUsing radial and carotid applanation tonometry, we quantified in HP (n = 10), PAH (n = 16), and NP (n = 401): (i) PWA-derived indexes; (ii) WSA-derived indexes: forward (Pf) and backward (Pb) waveform components, backward component arrival time (PbAT), reflection magnitude (RM = Pb/Pf) and index [RIx = Pb/(Pf + Pb)].ResultsWhile PAH was associated with a higher Pf compared to HP and NP, Pb and PbAT were similar between the groups. Both GH and PE showed a higher Pf compared to HP, but only PE had a trend of presenting with higher Pb and lower PbAT compared to the other groups. Finally, PAH showed a trend of having lower RM and RIx compared to NP and HP, with no differences between GH and PE.ConclusionPAH was associated with higher Pf, but not higher Pb, compared to NP and HP, although PE also demonstrated a trend of higher Pb.