Mediterranean Diet and Oxidative Stress: A Relationship with Pain Perception in Endometriosis.

BACKGROUND: Endometriosis is a chronic and inflammatory disease associated with pelvic pain. Dietary changes may be therapeutic for chronic inflammatory processes, reducing visceral input. The aim was to evaluate the role of dietary changes according to the Mediterranean Diet (MD) on pain perception in endometriosis and their relationship with oxidative stress. METHODS: in this prospective study, we included 35 endometriosis women. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated pain intensity with VAS (Visual Analogue Scale, from 0 to 10), vitamin profile, and oxidative stress. RESULTS: we found a significant increase in the diet score (p < 0.001). At T1, patients reduced pain in terms of dyspareunia (p = 0.04), non-menstrual pelvic pain (p = 0.06), dysuria (p = 0.04), and dyschezia (p < 0.001). Dyspareunia (p = 0.002) and dyschezia (p < 0.001) were further significantly reduced also at T2. We observed a significant positive correlation between lipid peroxidation and VAS non-menstrual pelvic pain and dysuria and a significant negative correlation between Oxygen radical absorbance capacity and VAS non-menstrual pain and dyschezia. CONCLUSIONS: our findings show a clear tendency toward a relationship between pain relief in endometriosis and MD. This appears promising to treat endometriosis-related symptoms and could be considered a new effective strategy for chronic pain management in the long term.

Comorbidities, risk factors and maternal/perinatal outcomes in oocyte donation pregnancies.

RESEARCH QUESTION: To evaluate pre-existing comorbidities, obstetric risk factors and adverse obstetric and neonatal outcomes in pregnancies conceived by oocyte donation, compared with naturally conceived pregnancies or by conventional IVF/intracytoplasmic sperm injection (IVF/ICSI). DESIGN: This retrospective single-centre contemporary cohort study reviewed data from singleton deliveries at the University Hospital of Careggi, Florence, from 2009 to 2017. Maternal and perinatal outcomes were analysed. RESULTS: The study included 25,851 pregnancies and newborns: 276 (1.1%) children were conceived after oocyte donation, 925 (3.6%) after IVF/ICSI and 24,650 (95.4%) after natural conception. Women in the oocyte donation group were significantly older compared with IVF/ICSI and natural conception groups (P < 0.0001) and had a higher prevalence of chronic hypertension compared with the natural conception group (P = 0.0090). They were administered anticoagulant medications more frequently during pregnancy. The incidence of gestational hypertension was significantly higher than in natural conception (aOR 3.6) and IVF/ICSI pregnancies (aOR 2.7). The incidence of Caesarean section in oocyte donation pregnancies was higher than in natural conception and IVF/ICSI groups (aOR 3.4 and 2.3, respectively). An 11-fold increased risk of post-partum haemorrhage (PPH) was found in oocyte donation versus natural conception and an almost four-fold increased risk was found in oocyte donation versus IVF/ICSI; prematurity and low birthweight were more frequent after oocyte donation versus natural conception (aOR 2.4 and 1.8, respectively). CONCLUSIONS: Patients undergoing oocyte donation represent a group with increased comorbidities and risk factors for adverse obstetric outcomes. Oocyte donation seems to be independently associated with gestational hypertension and PPH. Pregnancies after oocyte donation warrant clinical surveillance with proper screening and, possibly, preventive strategies.

Autoantibodies against ß1-Adrenergic Receptors: Response to Cardiac Resynchronization Therapy and Renal Function.

BACKGROUND: Cardiac resynchronization therapy (CRT) nonresponse remains a major clinical problem. Autoantibodies specific for the ß1-adrenergic (ß1-AAbs) and muscarinic (M2-AAbs) receptors are found in patients with chronic heart failure (HF) of various etiologies. MATERIALS AND METHODS: We retrospectively analyzed 73 HF patients (median age 67 years, 84% males, New York Heart Association II-IV, in sinus rhythm, left ventricular ejection fraction <35%) who received CRT defibrillator (CRT-D) from 2010 to 2013. ß1-AAbs and M2-AAbs were measured by enzyme-linked immunosorbent assay. Echocardiography was used to assess CRT response (reduction >15% in left ventricular end-systolic volume at 6 months follow-up). Renal function (RF) parameters (creatinine [Cr], blood urea nitrogen [BUN], estimated glomerular filtration rate [eGFR Modified Diet in Renal Disease], cystatin C [Cys-C], and neutrophil gelatinase-associated lipocalin [NGAL]) were also evaluated. RESULTS: A significantly higher percentage of patients positive for ß1-AAbs (OD sample/OD reference ratio >2.1) in nonresponders than in responder patients was observed (57% vs 27%, P = 0.004). No influence of M2-AAbs on CRT-D response was demonstrated. ß1-AAbs were predictive of a poor CRT-D response (odds ratio [OR] [95% confidence interval (CI)] 3.64 [1.49-8.88], P = 0.005), also after adjustment for RF parameters (OR [95% CI] 4.95 [1.51-16.26], P = 0.008) observed to influence CRT-D response (Cr P = 0.03, BUN P = 0.009, Cys-C P = 0.02). The positive rates of ß1-AABs in patients with abnormal blood level of Cr, eGFR, Cys-C, and NGAL were significantly higher than those with normal levels (P = 0.03, P = 0.02, P = 0.001, P = 0.007, respectively). CONCLUSIONS: Our study suggests that (1) the evaluation of ß1-AAb is useful to identify responders to CRT-D; (2) the presence of ß1-AAbs is in relationship with elevated renal function parameters.

Detrimental effects of niacin/laropiprant on microvascular reactivity and red cell deformability in patients with elevated lipoprotein(a) levels.

Several studies have found a beneficial effect of nicotinic acid on lipid profile, but there remains a limitation in the clinical use of nicotinic acid due to its side effects. In this study, 46 (F/M = 22/24, age = 58.74 ± 10.02 years) patients with Lp(a) ≥500 mg/L and with a previous arterial thrombotic event were treated with nicotinic acid/laropiprant (Tredaptive®). We found a significant reduction in the Lp(a) values at T1 (after 12 months), with a decrease of 32.3 % from baseline levels. At T1, 11 patients (23.9 %) showed Lp(a) levels to be <500 mg/L. PAT values were significantly decreased after treatment (2.13 ± 0.81 vs 1.74 ± 0.42, p = 0.001), showing a worsening of endothelial function in 27 (58.6 %) patients. A significantly higher number of patients had RHI <1.5 after the treatment [18 (39.1 %) vs 8 (17.4 %)]. Blood rheology worsened as ED was impaired (p < 0.0001) after 12 months, whereas WHV, plasma viscosity, and red cell aggregation did not show any significant differences in comparison to baseline. Patients with a worsening in microvascular reactivity in comparison to baseline showed a marked impairment in ED (0.3327 ± 0.037 vs 0.3091 ± 0.0351; p < 0.0001), while others showed only a mild, even though significant, reduction (0.3347 ± 0.0299 vs 0.3272 ± 0.0235; p = 0.044). In the light of the results of HPS2-THRIVE study, we may hypothesize that the addition of laropiprant to niacin might be responsible for these negative effects. In turn, these effects might explain, at least in part, the lack of a clinical net benefit of niacin/laropiprant in the trial.

Impact of COVID-19 Pandemic on Women's Health and Obstetric Outcomes after Assisted Reproduction: A Survey from an Italian Fertility Center.

BACKGROUND: the restrictive measures that were adopted during three waves of the COVID-19 pandemic had an impact on both the emotional state and lifestyle of the general population. We evaluated the impact of COVID-19 pandemic on lifestyles and emotional states of women planning assisted reproductive technology (ART), and whether these changes affected ART outcomes. METHODS: quantitative research, using a web-based survey, was performed on 289 Caucasian women. RESULTS: In preconception, we observed higher percentage of women with positive obstetric outcomes who reduced body weight (52.4% vs. 27.2%, p = 0.09). Over 60% of women with positive outcomes practiced physical activity vs. 47% of women with negative outcomes (p = 0.03), as well as having better quality of sleep (45% vs. 35%), and a more solid relationships with their partners (65.1% vs. 51.7%, p = 0.03). Women who increased their intake of whole grains, fruits, vegetables, and legumes (p < 0.05), according to the Mediterranean diet, showed positive outcomes. We observed that participants who experienced "very much" or "extreme" anxiety, sadness, and fear (p < 0.05) during pandemic were clearly more numerous in the group with negative pregnancy outcomes. CONCLUSIONS: healthy lifestyle together with a positive emotional state in preconception can positively influence the obstetric outcomes after ART.

Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder.

Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective study, we included 35 women with endometriosis. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated cardiometabolic parameters, lifestyle and oxidative stress. Results: After a 3-month intervention with MD, we observed a significant reduction in total cholesterol (p = 0.01) and LDL-c (p = 0.003). We observed at T1 an increase in B12 and E vitamins, folate and zinc. After 6 months, zinc (p = 0.04) and folate (p = 0.08) increased in comparison to T0. A reduction in homocysteine from T0 to T1 (p = 0.01) was found. After 3 months, an increase in Rapid Assessment of Physical Activity tool 1 (RAPA) (p < 0.001) and RAPA 2 was observed (p = 0.009). We observed high levels of oxidative stress markers at baseline. After 6 months of MD, a significant improvement in lymphocyte Reactive Oxygen Species (ROS) (p < 0.001) and total antioxidant capacity was observed (p = 0.02). Conclusions: The improvement of lifestyle, and in particular the Mediterranean dietary intervention, allowed the improvement of the metabolic and oxidative profile and overall health-related quality of life.

Evidence for caveolin-1 as a new susceptibility gene regulating tissue fibrosis in systemic sclerosis.

OBJECTIVE: Caveolin-1 (CAV1) is an inhibitor of tissue fibrosis and has been implicated in the pathogenesis of systemic sclerosis (SSc). The aim of the study was to analyse the possible association of CAV1 gene single nucleotide polymorphisms (SNP) with SSc. METHODS: A total population of 3974 individuals (1355 SSc patients, 2619 controls) was studied. Genotype data for 23 SNP spanning the CAV1-CAV2 gene locus were obtained from a genome-wide scan conducted in a French population (564 SSc patients, 1776 controls). Three CAV1 SNP (rs926198, rs959173, rs9920) displaying the most significant associations with SSc and/or clinical phenotypes were then genotyped in an Italian population (791 SSc patients, 843 controls). CAV1 protein expression in skin biopsies was investigated by immunohistochemistry and western blotting. RESULTS: In the French population, the CAV1 rs959173 C minor allele showed a significant protective association with susceptibility to SSc (OR 0.71, 95% CI 0.59 to 0.86, p(adjusted)=0.009), and with the subset of patients with limited cutaneous SSc (OR 0.71, 95% CI 0.56 to 0.89, p(adjusted)=0.018). The association was replicated in the Italian population and strengthened in the combined populations through Cochran-Mantel-Haenszel meta-analysis (SSc: pooled OR 0.81, 95% CI 0.71 to 0.92, p=0.0018; limited cutaneous SSc: pooled OR 0.80, 95% CI 0.69 to 0.93, p=0.0053). Genotype/protein expression correlations revealed that the rs959173 C protective allele was associated with increased CAV1 protein expression. CONCLUSIONS: These results add CAV1 to the list of SSc susceptibility genes and provide further evidence for the contribution of this pathway in the fibrotic process that characterises SSc pathogenesis.

A genetic variation located in the promoter region of the UPAR (CD87) gene is associated with the vascular complications of systemic sclerosis.

OBJECTIVE: The UPAR gene encodes a pleiotropic receptor (urokinase-type plasminogen activator receptor [uPAR]) involved in fibrosis, immunity, angiogenesis, and vascular remodeling. Previous studies have implicated uPAR in systemic sclerosis (SSc) vasculopathy and impaired angiogenesis. We undertook this study to investigate whether UPAR gene promoter polymorphisms might be associated with SSc phenotypes in the European Caucasian population. METHODS: We studied a total population of 1,339 individuals. The Italian discovery cohort comprised 388 SSc patients and 391 healthy controls. The French replication cohort consisted of 344 SSc patients and 216 healthy controls. The UPAR rs344781 and rs4251805 single-nucleotide polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: In the Italian cohort, the rs344781 G allele was associated with SSc-related digital ulceration (odds ratio [OR] 1.39), pulmonary arterial hypertension (PAH) (OR 1.81), anticentromere antibody (ACA) positivity (OR 1.45), and limited cutaneous SSc (lcSSc) (OR 1.37). The rs344781 GG genotype was associated with SSc-related (OR 3.79), ACA-positive SSc (OR 2.17), and lcSSc (OR 1.96). Allelic and genotypic associations with SSc-related digital ulceration and ACA-positive SSc were replicated in the French sample. Combined analyses showed an association of the rs344781 G allele and GG genotype with SSc-related digital ulceration (allele OR 1.41, genotype OR 2.15), SSc-related PAH (allele OR 1.65, genotype OR 3.16), ACA-positive SSc (allele OR 1.47, genotype OR 2.40), and lcSSc (allele OR 1.34, genotype OR 1.77). In a multivariate logistic regression analysis model including the above associated phenotypes of SSc patients, the rs344781 GG genotype remained an independent risk factor for SSc-related digital ulceration (OR 1.96) and SSc-related PAH (OR 2.68). CONCLUSION: The UPAR rs344781 gene variant is associated with the SSc vascular phenotype.

Preconception period in women and men undergoing Assisted Reproduction: A gender approach for reproductive health.

OBJECTIVE: To evaluate lifestyle and risk factors playing a role in increasing the burden of cardiovascular diseases and to increase attention of clinicians who should envision a broader preconception approach in ART, not only in women but also in men. STUDY DESIGN: In this cross-sectional study we investigated 90 Caucasian couples, referred to the Internal Medicine Clinic at the Assisted Reproductive Technology Centre, in order to better define in preconceptional period their cardiovascular risk profile, based on metabolic parameters and lifestyle behaviours. RESULTS: We observed two-fold increase of overweight in men in comparison to women (p = 0.006). Values of waist ≥ 94 cm in men and ≥ 80 cm in women were present in 53.3% of men and 32.2% of women (p = 0.007). Similarly, values of WHR according to gender cut-off, were present in 64.4% of men and in 32.2% of women (p < 0.0001). In men we observed a significantly higher prevalence of hypertension (p = 0.02), significantly lower HDL-c (p = 0.001) and higher levels of total cholesterol (p = 0.01), LDL-c and triglycerides (p = 0.001). Sedentary behaviour was observed in about 60% of both genders. Alcohol consumption was reported by 42.2% of men and 26.7% of women (p = 0.04) and smokers were more prevalent among women (26.7%) than men (24.4%). We observed a lower adherence to Mediterranean Diet related to consumption of red meat and meat products (p = 0.02), as well as of legumes consumption (p = 0.01) in men, whereas sweet/pastries (p = 0.05) and fruits (p = 0.06) in women. Men and women with normal BMI, waist and WHR, showed a higher Mediterranean diet adherence in comparison to overweight/obese study population(p < 0.001). Finally, higher education level predicted the higher Mediterranean diet adherence in both gender (p = 0.01 for men, p = 0.03 for women). CONCLUSIONS: This study paid attention on preconceptional health in couples planning ART. Women have a greater biological role in childbearing, whereas the role of men is underestimated. The need to conceive through ART offers a window of opportunity not only to evaluate cardiovascular profile and lifestyle factors in couples prior to conception, but also to manage comorbidities and promote health behaviours in order to improve fertility and health outcomes in both women and men at short and long-term.

Role of endometriosis in defining cardiovascular risk: a gender medicine approach for women's health.

The relationship between endometriosis and subclinical atherosclerosis represents an emerging topic in women's health, as women with endometriosis are at higher risk of cardiovascular disease later in life. We investigated metabolic parameters and indirect endothelial markers related to atherosclerosis, in women suffering from stage III/IV of endometriosis compared with women without endometriosis. The study population comprised 643 women: 92 women (14.3%) with stage III/IV of endometriosis and 551 (85.7%) without endometriosis. By analyzing biohumoral parameters we observed a significant increased total cholesterol (p = 0.01), LDL-C (p = 0.01), triglycerides (p = 0.05) and homocysteinaemia (p = 0.04), lower vitamin B6 and folate (p = 0.07 and p = 0.03, respectively) values, and higher high-sensitive C reactive protein (p = 0.05) concentrations in stage III/IV in comparison to those observed in women without endometriosis. After adjustment for traditional cardiovascular risk factors, the poorer lipid profile (total cholesterol, LDL-C), as well as Lipoprotein (a), remained significantly associated with severity of endometriosis (p = 0.01 and p = 0.03, respectively). Our findings highlight the role of endometriosis as a gender-specific cardiovascular risk factor. The clinical relevance of our study lies in identifying women with stage III/IV of endometriosis at higher risk of atherosclerotic disease, who could benefit from an early cardiovascular screening to control future cardiovascular risk.

Association between polymorphisms of the renin angiotensin system and carotid stenosis.

OBJECTIVE: Carotid stenosis is a common manifestation of systemic atherosclerosis. Apart from traditional risk factors, genetic determinants, such as polymorphisms of the renin angiotensin system (RAS), may be relevant in modulating the atherosclerotic process leading to carotid stenosis. In this study, we investigated the role of angiotensin-converting enzyme (ACE) I/D and -240A>T, angiotensinogen (AGT) M235T, and angiotensin type 1 receptor (AGTR1) 1166A > C polymorphisms in modulating the susceptibility to the disease. METHODS: Eight hundred twenty-one consecutive patients with severe carotid stenosis (≥70%) and 847 control subjects were investigated. RESULTS: A significant difference in genotype distribution (P < .0001) and allele frequency (P < .0001) between patients and controls for the ACE I/D polymorphism, but not for the other single-nucleotide polymorphisms investigated, was observed. The ACE D allele frequency was significantly higher in patients without traditional risk factors in comparison with that observed in those with at least one risk factor (0.71 vs 0.61; P = .04). The ACE D allele significantly influenced carotid stenosis under dominant, recessive, and additive model of inheritance at both univariate (P < .0001) and multivariate analysis (P < .0001). When the combined effect of RAS unfavorable alleles was considered, patients carrying less than three alleles had a lower risk of carotid stenosis (odds ratio [OR], 0.79 [0.63-0.99]; P = .05), while carriers of more than four unfavorable alleles had an increased risk (OR, 1.44 [1.12-1.84]; P = .004), in comparison with subjects carrying three or four unfavorable alleles. ACE D allele frequency was similar in patients with and without additional atherosclerotic localizations (0.61 vs 0.62, respectively). CONCLUSIONS: Our findings evidence a role for ACE I/D polymorphism in influencing the susceptibility to carotid stenosis, even in the absence of traditional risk factors. Interestingly, our findings provided further information concerning the role of this polymorphism in modulating the atherosclerotic process apart from its different localizations.

Homocysteine, vitamin B status and MTHFR polymorphisms in Italian infertile women.

OBJECTIVE: The purpose of this study was to evaluate the vitamin B status related to the homocysteine pathway and the prevalence of polymorphisms of the MTHFR gene in infertile women programming homologous or heterologous ART. STUDY DESIGN: We investigated 393 consecutive Caucasian women, referred to the Internal Medicine Clinic at the Center for Assisted Reproductive Technology, in order to be framed for their vascular risk before starting homologous or heterologous (oocyte donation) procedures. Total homocysteine, Vitamin B12, folate and vitamin B6 were measured. The women were divided into quartiles of serum concentration of folate, vitamin B12 and vitamin B6. The C677T and A1298C polymorphisms of the MTHFR gene were genotyped by an electronic microchip technology. RESULTS: Sixty-one women (15.5%) had hyperhomocysteinemia, 22.9% had reduced levels of vitamin B12, 4.1% had reduced levels of serum folate and 0.1% had a deficiency of vitamin B6. Women in the highest quartile of vitamin B12 and folates had lower homocysteine ​​levels than women in the first and second quartiles (p < 0.0001). The homozygosity for MTHFR C677T polymorphism was detected in 33.3% (131), and heterozygosity for MTHFR C677T polymorphism in 45.3% (178) of women. We observed a significant association between hyperhomocysteinemia and 677T allele, but not 1298C, of the MTHFR polymorphisms (p = 0.04). CONCLUSIONS: We found inadequate vitamin B status related to the homocysteine ​​pathway in women planning Assisted Reproductive Technology. Moreover, interesting association was found regarding hyperhomocysteinemia in women carrying T allele of the C677T MTHFR polymorphism. A specific supplementation with 5-MTHF and adequate vitamin B12 concentrations before Assisted Reproductive Technology warrant serious consideration, in particular in women carrying T allele of the C677T MTHFR polymorphism.

Ectopic Fat Depots and Cardiometabolic Burden: A Possible Dangerous Liaison in Women Planning Assisted Reproduction.

Objective: We evaluated cardiometabolic burden in women planning assisted reproduction in order to identify subgroups at higher risk of pregnancy complications and cardiovascular disease. Materials and methods: In this cross-sectional study we investigated 60 infertile women with BMI≥25 kg/m2 referred to the Center for Assisted Reproduction. All women underwent metabolic, anthropometric parameters and ultrasound evaluation of ectopic fat depots. Results: All women had waist ≥80 cm. We found that 93.3% of women had pathological subcutaneous, 58.3% visceral and 80% para-perirenal fat; all women had fatty liver. Visceral fat and severity of steatosis were significantly related to the presence of metabolic syndrome (OR =5.7; p=0.03).A significant negative correlation between low HDL-c and para-perirenal fat (p<0.0001), a significant positive correlation with fasting plasma glucose and para-perirenal fat (p=0.001) were found. We observed a significant positive correlation between visceral fat and hs-CRP (p=0.002), HOMA-IR (p=0.04) and triglycerides (p=0.002), a significant negative correlation with HDL-c (p=0.05). Conclusion: This study by highlighting a clinically "dangerous liaison" between ectopic fat depots and metabolic/inflammatory markers, might permit to identify women with a worse metabolic phenotype and encourage lifestyle changes for improving their general and reproductive health together.

5-Methyltetrahydrofolate and Vitamin B12 Supplementation Is Associated with Clinical Pregnancy and Live Birth in Women Undergoing Assisted Reproductive Technology.

The homocysteine pathway in the preconception period should be evaluated to highlight micronutrient deficiencies and warrants optimal multivitamin supplementation, before Assisted Reproduction, as preconception care. We conducted a retrospective study aimed at investigating the role of vitamin B complex (5-methyltetrahydrofolate, vitamin B12, vitamin B6) supplement use compared with the role of only folic acid supplement use, in relation to clinical pregnancy and live birth in infertile women undergoing homologous ART. We investigated 269 Caucasian women referred to the Centre for Assisted Reproductive Technology for homologous ART. In these women, 111 (Group A) were daily supplemented with vitamin B complex and 158 (Group B) with only folic acid. In group A the mean number of Metaphase II oocytes and the 2PN Fertilization Rate were higher in comparison to group A (p = 0.04; p = 0.05, respectively). A higher percentage of women in group A had a clinical pregnancy and live birth in comparison to group B (p = 0.01; p = 0.02, respectively). Vitamin B complex supplementation remained independently associated, after multivariable adjustment, with clinical pregnancy (OR 2.03, p = 0.008) and live birth (OR 1.83, p = 0.03). Women supplemented with 5-MTHF and vitamin B12, have a higher chance of clinical pregnancy and live birth in comparison to those supplemented with only folic acid.

Impact of cardiovascular burden on coagulation pathway in apparently healthy women planning oocyte donation.

BACKGROUND: Hormonal fertility treatments are associated with increased coagulation factors inducing procoagulant milieu and possibly thrombotic risk. OBJECTIVE: To assess coagulation by ROTEM and coagulation tests in apparently healthy infertile women before oocyte donation procedure. METHODS: We enrolled 51 women (Assisted Reproductive Technology Centre, Florence). ROTEM and coagulation parameters were assessed before the start of infertility treatment. RESULTS: We divided women in 3 groups according to the number of cardiovascular risk factors: Group A (n = 10), Group B (n = 16), and Group C (n = 25). By considering ROTEM Extem test, a significantly increased of MCF, TPI, and G were observed in groups B (p = 0.005, p = 0.03, and p = 0.007) and C (p = 0.01, p = 0.05, and p = 0.005) in comparison to group A. As regards ROTEM Intem test, the TPI and G values were significantly higher in groups B and C in comparison to group A (p < 0.01). MCF by Fibtem test significantly increased in groups B and C than in group A (p = 0.004 and p = 0.002, respectively). FVIII, vWF:Ag and D-dimer values significantly increase according to the presence of≥2 risk factors. CONCLUSIONS: Data from coagulative assessment permit to sensitively identify women with potentially procoagulable state, which represents a risk factor of thromboembolic event during hormone treatment.

The effects of COVID-19 lockdown on lifestyle and emotional state in women undergoing assisted reproductive technology: Results of an Italian survey.

PURPOSE: On March 8, 2020, the Italian Government implemented extraordinary measures to limit viral transmission of COV-19/SARS-CoV-2. We evaluated the impact of COVID-19 lockdown on lifestyle and emotional state in women planning infertility treatments. BASIC PROCEDURES: We performed a quantitative research study using a web-based survey, in 140 women referred to Assisted Reproductive Technologies Center. MAIN FINDINGS: We observed changes in body weight during lockdown in 80 % of women, and a significant increase in BMI in comparison to that observed before (p=.001). We observed a high percentage of non-adherence to the Mediterranean pattern during lockdown due to higher frequency of consumption of sweet/pastries, cheese and meat, rather than fruit, vegetables and legumes. Before lockdown 36.4 % women were snack consumers while during lockdown 55 % (p=.002). By considering individuals' attitude to snack consumption, we observed an increase related to boredom (p=<.0001) and anxiety (p=.05) during lockdown. Increased levels of anxiety and sadness were observed in about 30 %, and of boredom in 25 %. The percentage of women worried about their planning infertility treatment was more than 50 %. PRINCIPAL CONCLUSIONS: Quarantine-related restrictions strongly influenced lifestyle psychological behavior leading to an increased burden of cardiovascular disease.

Cardiometabolic and Thrombotic Risk Profile in Women Undergoing Oocyte Donation for Assisted Reproduction.

Background: The last two decades have seen a growing number of pregnancies in women who needed the donation of oocytes. With oocyte donation pregnancies, studies on obstetric outcomes among these women revealed an increased incidence of pre-eclampsia and pregnancy-induced hypertension. Furthermore, several studies have found a higher incidence of low birth weight, preterm birth, and delivery by cesarean section in oocyte donation rather than in women subjected to assisted reproduction techniques (ART) with autologous oocytes. Numerous studies have also shown a deep connection between cardiovascular and thrombotic risk factors and adverse pregnancy outcomes. In this setting, to strictly assess the preconceptional risk for women who undergo egg donation to achieve pregnancy, the aim of our study is to draw a detailed assessment of the vascular risk profile of patients with gamete donation ART indications through the evaluation of comorbidities and cardiometabolic and thrombophilic markers Materials and Methods: Patients undergoing ART with oocyte or sperm donation or double donation of gametes underwent a careful clinical assessment through a detailed personal and family anamnesis and they were evaluated for cardiometabolic and thrombophilic profile. Clinical and demographic characteristics, comorbidities, and biohumoral parameters were collected. The study was approved by the Regional Ethical Committee(Em 2018-017 CINECA 10189). Results: We evaluated 525 women. Around 73.1% were >40 years and 35% of them were older than 45 years. There was a high prevalence of dyslipidemias (58.1%), smoking habit (24.6%), a body mass index >25 in 28.6% of patients, a high abdominal circumference in 58.1% of cases, a prevalence of acquired thrombophilia in about 7% and hereditary of 19.2%. Around 39.2% of patients had total cholesterol >200 mg/dL, 19.5% had high-density lipoprotein <48 mg/dL and 43.6% had low-density lipoprotein >115 mg/dL, and 6.9% had triglyceride values >150 mg/dL. Conclusions: A careful assessment of the preconceptional status of patients undergoing ART programs with oocyte donation can be highly recommended.

eNOS and ACE genes influence peripheral arterial disease predisposition in smokers.

OBJECTIVE: Several biologic mediators and genetic predisposing factors may contribute to the development of peripheral arterial disease (PAD). The eNOS gene, encoding for endothelial nitric oxide synthase, has been proposed as a candidate gene in the predisposition to the disease. In this study, we evaluated the role of eNOS-786T>C, -894G>T and 4a/4b polymorphisms as markers of PAD per se and in the presence of the ACE D allele in patients previously investigated. METHODS: We analyzed 281 consecutive patients (220 men, 61 women; median age, 72 years) with PAD and 562 healthy controls, comparable for sex and age. RESULTS: eNOS-786C, but not -894T and 4a, allele frequency was significantly higher in PAD patients than in controls (P = .03). An association with the predisposition to PAD was found for the eNOS-786C allele (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.11-2.09; P = .009) and the eNOS -786C/4a haplotype (OR, 1.41; 95% CI, 1.02-1.94, P = .04) at univariate analysis but not after adjustment for traditional risk factors. When smoking habit was considered, we observed that eNOS-786C/4a haplotype, but not the eNOS-786C allele, influenced PAD predisposition after adjustment for traditional risk factors in smokers (OR, 2.71; 95% CI, 1.38-5.30; P = .004). The eNOS-786C and eNOS-786C/4a haplotype did not modify the susceptibility to PAD in patients carrying the ACE D allele. Nevertheless, the presence of the eNOS-786C/4a haplotype increased PAD predisposition in smokers also carrying ACE D allele (OR, 2.71 to 3.79; P > .05 for interaction). CONCLUSIONS: This study demonstrated an association between eNOS and ACE genes in increasing PAD susceptibility in smokers, thus providing evidence for a gene-environment interaction in modulating predisposition to the disease.

Lifestyle and Comorbidities: Do We Take Enough Care of Preconception Health in Assisted Reproduction?

Objective: The preconception period is largely neglected, whereas it represents an opportunity to identify and modify clinical and behavioral risks, particularly in infertile women characterized by an unfavorable vascular burden. The present study was performed to strengthen previous findings and to increase the awareness of clinicians who should envision a broader preconception approach in infertile women, beyond their reproductive health. Materials and methods: In this cross-sectional study, we investigated 1003 Caucasian women, referred to the Internal Medicine Clinic at the Assisted Reproductive Technologies Center, Florence. Results: A high prevalence of dyslipidemia (57.4%), overweight/obesity (29.1%) and, smoking habit (26.6%) were found. We provided evidence of unhealthy lifestyle habits, represented by a closer adherence to the Mediterranean diet in the 9.5% only and by a sedentary behavior in 73%. A significant correlation between the Mediterranean Diet score and both anthropometric and metabolic parameters was found. We also observed a lower score adherence with both metabolic syndrome and diabetes (for both p=0.02), but not with hypertension. Conclusion: Before infertility treatment, the correction and the management of modifiable and non-modifiable cardiovascular risk factors are mandatory and represent the main goal for a safe pregnancy, and lifetime women's health.

Multilocus analysis in candidate genes ACE, AGT, and AGTR1 and predisposition to peripheral arterial disease: role of ACE D/-240T haplotype.

OBJECTIVE: Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis. Apart from traditional cardiovascular risk factors, several novel biologic mediators and genetic predisposing factors appear relevant in determining the atherogenetic process leading to PAD. Genes encoding for renin angiotensin system (RAS) components have been proposed as candidate in atherosclerosis. This study investigated four polymorphisms in angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II receptor type 1 (AGTR1), genes of RAS, in both predicting PAD and modulating the severity of the disease. METHODS: The ACE I/D and -240A>T, AGT M235T, and AGTR1 1166A>C polymorphisms were analyzed in 281 PAD patients and in 485 controls comparable for age and sex. RESULTS: The ACE D and -240T alleles both significantly influenced the predisposition to PAD. The ACE D, but not -240 T, allele remained associated with PAD after Bonferroni correction (P = .004) and adjustment for cardiovascular risk factors (P = .03). The ACE D allele influenced PAD predisposition with a dose-dependent effect (odds ratio for ACE ID vs II genotype, 1.77; P = .006; ACE DD vs II genotype, 2.15; P = .001). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T haplotype significantly and independently influenced the predisposition to PAD (P = .02). In 190 PAD patients with no additional atherosclerotic localizations (isolated PAD), a significant association between ACE D and -240T alleles and PAD was observed. Only the ACE D allele remained associated with isolated PAD after Bonferroni correction (P = .02) and after adjustment for cardiovascular risk factors (P = .02). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T, but not the D/-240A haplotype significantly influenced the predisposition to PAD (P = .0003). No influence of the polymorphisms analyzed on the severity of the disease, according to Rutherford categories, was found. CONCLUSIONS: The present study contributes data to highlight the role of the ACED/-240T haplotype in predisposing to PAD, also in the absence of other atherosclerotic comorbidities.