Fat intake pattern in women with polycystic ovary syndrome.

RESEARCH QUESTION: Do women with polycystic ovary syndrome (PCOS) have a different fat intake pattern to women without PCOS? DESIGN: Case-control study of 276 women between 20 and 35 years old from the Murcia region of Spain. Cases (n = 121) attended the Department of Gynaecology and Obstetrics of the University Clinical Hospital and were diagnosed with PCOS using Rotterdam criteria. Controls (n = 155) were women without PCOS attending the gynaecological outpatient clinic for routine gynaecological examinations. Data from clinical, gynaecological and analytical examinations were collected, including a food frequency questionnaire. Associations between fat intake and presence of PCOS and its phenotypes were examined using multiple logistic regression, adjusting for potential confounding factors. RESULTS: Although no association was found between fatty acid intake and PCOS, significant associations were observed for some PCOS phenotypes. The PCOS phenotype characterized by hyperandrogenism + oligo/amenorrhoea + polycystic ovarian morphology ('H+O+POM') was significantly associated with a higher intake of polyunsaturated fat (odds ratio [OR] 4.0; 95% confidence interval [CI] 1.1-14.2; fourth quartile of highest intake [Q4] versus lowest intake quartile as reference [Q1]) and omega-6 fatty acids (OR 3.5; 95% CI 1.01-12.4; Q3 versus Q1). The 'H+O' phenotype was positively associated with saturated fat intake (OR 6.9; 95% CI 1.1-41.6; Q4 versus Q1). CONCLUSION: This exploratory study suggests that higher intakes of specific fatty acids are related to some PCOS phenotypes although no association was found for PCOS on a global basis. It is recommended that studies with larger sample size be performed to further explore these associations, thus contributing to establishing recommendations about fat intake adapted to different PCOS phenotypes.

Associations between urinary concentrations of bisphenol A and sperm DNA fragmentation in young men.

BACKGROUND: Bisphenol A (BPA) is one of the most common endocrine disruptor compounds in our environment, promoting a xenoestrogenic state. Numerous studies have shown a relationship between exposure to BPA and male infertility problems. Spermatic DNA integrity is a critical factor for the correct transmission of paternal genetic material to the embryo. However, only a very few studies have investigated the association between urinary BPA concentrations and human sperm DNA fragmentation (SDF). METHOD: Cross-sectional study conducted with 158 healthy university students (18-23 years), recruited between 2010 and 2011 in the Region of Murcia (Spain). The subjects provided urine and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection, and SDF analysed using the Sperm Chromatin Dispersion test. Statistical analyses were made using linear regression adjusting for potential covariates and confounding factors. RESULTS: No association was found between urinary BPA concentrations and SDF index in the total group. However, in the subgroup of men with SDF index> 30%, significant positive associations across quartiles (p-trend=0.02) and as a continuous BPA levels were observed (ß = 0.055, 95%, CI: 0.002; 0.108). CONCLUSION: Our results show that, within the subgroup of men with relatively high SDF index, the higher the concentration of BPA the greater the SDF index. Nonetheless, more studies are required to confirm these results and draw conclusions in other male populations.

Health-related quality of life in women with polycystic ovary syndrome attending to a tertiary hospital in Southeastern Spain: a case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a chronic condition with symptoms affecting many women at reproductive age and evaluating their health-related quality of Life (HRQoL) is an important issue. Moreover, differences in the HRQoL between women with different PCOS phenotypes have never been analyzed. Therefore, the aim of our study was to compare the HRQoL between women with PCOS -and its phenotypes- and controls attending to a tertiary hospital. METHODS: A group of 117 women with PCOS and 153 controls were studied between 2014 and 2016. Controls were women without PCOS attending the gynecological outpatient clinic for routine examinations. Cases were women attending the same setting and diagnosed with PCOS. PCOS diagnose was performed following the Rotterdam Criteria and women were further classified by anovulatory or ovulatory phenotypic subtype. Women underwent physical and gynecological exams and completed health questionnaires including the Short Form-12v2. Eight scales and two component summary scores [Physical (PCS) and Mental (MCS), respectively] were calculated. Bivariate and multivariate analyses were performed to assess differences in HRQoL between women with PCOS and controls. RESULTS: All women with PCOS and anovulatory PCOS presented lower score in PCS compared to controls [mean (95%CI): 53.7 (52.5-54.9) and 52.9 (51.5-54.4) vs. 55.8 (54.8-56.8); p-values< 0.01], as well as lower scores for five out of the eight scales (p-values < 0.05) after adjusting by age, body mass index, infertility, educational level and current occupation. No significant differences were observed for the MCS between women with or without PCOS or its phenotypic subtypes. CONCLUSIONS: HRQoL was significantly decreased in adult women with PCOS and its anovulatory phenotype compared to controls attending the outpatient clinic of a tertiary hospital. These results may have implications for the clinical practice and suggest the need for specific interventions in women with PCOS.

Adherence to diet quality indices in relation to semen quality and reproductive hormones in young men.

STUDY QUESTION: Is adherence to an a priori defined diet quality indices [Alternate Healthy Index 2010 (AHEI-2010), relative Mediterranean diet score (rMED) or dietary approaches to stop hypertension (DASH)] associated with semen quality and reproductive hormone levels in young men? SUMMARY ANSWER: Greater adherence to the DASH diet is related to higher sperm counts. WHAT IS KNOWN ALREADY: Studies assessing the relationship between dietary intake and male reproductive function have mainly been focused on specific nutrients, food groups or data-driven dietary patterns, but the evidence on a priori defined dietary indices is still scarce. STUDY DESIGN, SIZE, DURATION: Cross-sectional study of 209 male university students recruited from October 2010 to November 2011 in Murcia Region (Southern Spain). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthy young men aged 18-23 years were included in this study. Diet was assessed using a validated food frequency questionnaire and three a priori-defined dietary indices (AHEI-2010, rMED and DASH) were calculated. Linear regression was used to analyze the relation between the three dietary indices and semen quality parameters and reproductive hormone levels accounting for potential confounders and covariates. MAIN RESULTS AND THE ROLE OF CHANCE: We found statistically significant positive associations between the DASH index and sperm concentration (P, trend = 0.04), total sperm count (P, trend = 0.04) and total motile sperm count (P, trend = 0.02). No associations were observed for other semen parameters or male reproductive hormones. LIMITATIONS, REASONS FOR CAUTION: Even though we adjusted for several known and suspected confounders we cannot exclude the possibility of residual or unmeasured confounding or chance findings. Subjects were blinded to the study outcomes thus reducing the potential influence on their report of diet. Our sample size may be too small to rule out associations with other semen parameters or reproductive hormones. Causal inference is limited, as usual with all observational studies. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest that greater adherence to the DASH may help improve sperm counts. This study was carried out on young men from the general population. However, results may differ among other populations (e.g. infertile men). Therefore, further research is needed to confirm these findings and extend these results to other populations. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Fundación Séneca, grants No 08808/PI/08 and No 19443/PI/14; Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (AES), grants No PI10/00985 and No PI13/01237; and grant P30DK046200 from the National Institutes of Health. Authors have no competing interests to declare.

Are there differences in basal thrombophilias and C-reactive protein between women with or without PCOS?

RESEARCH QUESTION: Polycystic ovary syndrome (PCOS) women have increased cardiovascular risks, although it is unclear whether the haemostatic system and coagulation contribute to that increased risk. DESIGN: Women attending the Gynecology Unit of the 'Virgen de la Arrixaca' University Hospital (Murcia, Spain) for routine gynaecological examinations between September 2014 and May 2016 were assessed for PCOS using the Rotterdam criteria (hyperandrogenism [H], oligo/amenorrhoea [O] and polycystic ovarian morphology [POM]) and were classified into four phenotypic. In total, 126 cases were identified and 159 control women were selected. All women underwent physical and gynaecological examinations, and blood tests between the second and fifth day of the menstrual cycle. Differences in hormonal, basal thrombophilia and metabolic parameters, and C-reactive protein (CRP) between PCOS and controls were analysed. RESULTS: After adjusting by BMI and age, PCOS women had higher LH (P < 0.001), testosterone (P < 0.001), free testosterone (P = 0.01) and anti-Müllerian hormone (P < 0.001) and lower FSH (P = 0.03) compared with controls, whereas sex hormone-binding globulin was no different. Cases showed significantly higher protein S, glucose, insulin and insulin resistance (HOMA-IR) compared with controls (P < 0.05). There were no differences in protein C levels, antithrombin III, prothrombin time, homocysteine, D-dimer, factor V Leyden, prothrombin G20210A polymorphism or CRP. The H+O phenotype showed the poorest results for insulin and HOMA-IR (P = 0.04 and 0.05). CONCLUSIONS: The results suggest that there are no differences in the basal thrombophilias between women with and without PCOS. However, PCOS with H+O shows the poorest metabolic profile.

New approach to the evaluation of perineal measurements to predict the likelihood of the need for an episiotomy.

INTRODUCTION AND HYPOTHESIS: Episiotomy is performed selectively during vaginal delivery. Among the maternal anthropometric factors for episiotomy, the length of the perineal body (pb) and genital hiatus (gh) defined as per the POP-Q system have been studied. The objective of our study was to compare two perineal measurements (defined as per the POP-Q system and the anogenital distance [AGD] concept) to determine which of these can predict the likelihood of an episiotomy being performed. METHODS: An observational prospective cohort study was designed. Anthropometric data (pb, gh, symphysis-coccyx distance, distance between ischial tuberosities, AGDaf [anus-fourchette], and AGDac [anus-clitoris]), duration of the second stage of labor, and neonatal biometric data were collected from 119 women included in this study. Statistical analysis was performed using Student's t test for unpaired data, Mann-Whitney, and Chi-squared tests. Receiver operating characteristic (ROC) curves were generated to compare AGDaf, AGDac, and "gh + pb" with the presence of episiotomy. RESULTS: A shorter "gh + pb" length and AGDac were risk factors for episiotomy. Compared with AGDac, gh + pb was a slightly better predictor in ROC curve analysis. Furthermore, a longer duration of second-stage labor was evident in the episiotomy group. CONCLUSIONS: This study introduces measures of AGD as risk factors for episiotomy. We propose that "gh + pb" length <77 mm and AGDac <93 mm may predict the likelihood of requiring episiotomy and may be useful for diminishing subjectivity in the decision to perform an episiotomy.

Assessment of anogenital distance as a diagnostic tool in polycystic ovary syndrome.

RESEARCH QUESTION: Is anogenital distance (AGD) a useful clinical tool for predicting polycystic ovarian syndrome (PCOS) and its main National Institutes of Health (NIH) phenotypes? DESIGN: Case-control study conducted between September 2014 and May 2016 at the Department of Obstetrics and Gynecology of the University Clinical Hospital 'Virgen de la Arrixaca' in the Murcia region (south-eastern Spain). One hundred and twenty-six cases of PCOS and 159 controls without PCOS were included. AGD measurements were taken from the anterior clitoral surface to the upper verge of the anus (AGDAC), and from the posterior fourchette to the upper verge of the anus (AGDAF). Parametric and non-parametric tests and receiver operating characteristic (ROC) curves were used to assess associations between AGD and the presence of PCOS and its phenotypes. RESULTS: AGDAC, but not AGDAF, was associated with PCOS and all its phenotypes (P-values < 0.001 to 0.048). The highest area under the curve (0.62; 95% confidence interval 0.55 to 0.71) was obtained for all PCOS with AGDAC with a sensitivity and specificity of 50.0% and 73.0%, and positive and negative predictive value of 59.0% and 64.4%, respectively. CONCLUSIONS: AGDAC could moderately discriminate the presence of PCOS and may be a useful clinical tool.

Comparability between adult female anogenital distance and perineal measurements standardized by POP-Q system (GH and PB).

AIMS: Anogenital distance (AGD) has been proposed as a marker of the prenatal hormonal milieu and potential environmental insults. The measures of the Pelvic Organ Prolapse-Questionnaire (POP-Q) system is being widely used in the evaluation of the perineum in women with POP pathologies. Genital hiatus (GH) and perineal body (PB) lengths have been related to both prolapse incidence and recurrence and for pessary treatment failure. The use of AGD in female human studies is now emerging and its comparability with other anthropometric measurements could be relevant. The aim of the study was to compare AGD and POP-Q system in adult females. METHODS: The study included 155 pregnant women in the first stage of labor. Perineal measurements were performed on women in the lithotomy position: AGD from the anus to the clitoris (AGDAC ); AGD from the anus to the fourchette (AGDAF ); GH from the external urethral meatus to the posterior midline hymen, and length of the PB from the posterior midline hymen to the mid-anal opening. Coefficients of variations (CV) were calculated. Intraclass correlation coefficients (ICC) and Bland-Altman graphs were used to compare both set of measurements. RESULTS: CV were below 15% for AGDAC and GH + PB, though higher for AGDAF and PB (20% and 17%, respectively). ICCs for each pair of measurements were above 80%, (excellent agreement between methods). Concordance between measurements was confirmed by Bland-Altman graphs. CONCLUSIONS: Comparable measurements were obtained using AGDs and POP-Q system. Further studies are needed to explore clinical and epidemiological implications of these findings.

Urinary bisphenol A concentrations are associated with reproductive parameters in young men.

Bisphenol A (BPA) is a pervasive environmental toxicant with known reproductive effects on sperm parameters and hormone levels. Several observational studies have investigated the associations between BPA exposure and male reproductive function, but findings are inconsistent. The objective of this study was to assess the associations between urinary BPA concentrations and semen quality and reproductive hormone levels in a cross-sectional study with 215 healthy young university students (18-23 years old), investigated between 2010 and 2011 in Southern Spain (Murcia Region). All subjects provided urine, blood serum and semen samples on a single day. Urinary BPA concentrations were measured by dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography with tandem mass spectrometry detection. Semen quality was evaluated by measuring volume, concentration, motility, morphology and total sperm count (TSC). Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, inhibin B and estradiol. Relationships between urinary BPA concentrations and semen quality parameters and reproductive hormone levels were examined using linear regression, adjusting for potential confounders and covariates. Ninety-five percent of the men had detectable urinary BPA concentrations with unadjusted median (5th-95th) of 2.8 (0.16-11.5) ng/mL. After adjustment for important covariates, there was a significant positive association between urinary BPA concentrations and serum LH levels (ß = 0.07, 95%CI: 0.02;0.12, p-value < 0.01). Urinary BPA concentration was also significantly and inversely associated with sperm concentration (ß = - 0.04, 95%CI: - 0.07;- 0.02, p-value < 0.01) and TSC (ß = - 0.05, 95%CI: - 0.08;- 0.02, p-value < 0.01). No significant associations were found between BPA and other semen parameters or reproductive hormone levels. Our results support the hypothesis that BPA exposure may be associated with a reduction in Leydig cell capacity (increased LH levels) and decreased sperm counts in young men.

Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study.

BACKGROUND & AIMS: Prenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. METHODS: Data come from 325 mother-child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. RESULTS: A reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (-0.50; 95% CI: -0.91, -0.09; P = 0.016), and from preconception up to 12 weeks of gestation (-0.48; 95% CI: -0.88, -0.08; P = 0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (-0.77; 95% CI: -1.52, -0.02; P = 0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth. CONCLUSIONS: Maternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth.

Urinary concentrations of bisphenol A, parabens and benzophenone-type ultra violet light filters in relation to sperm DNA fragmentation in young men: A chemical mixtures approach.

People are daily exposed to multiple endocrine disruptor compounds (EDCs) that may interfere with different molecular and cellular processes, promoting a potential estrogenic, androgenic, or anti-androgenic state. However, most epidemiological studies attempting to establish relationships between EDCs exposure and health effects are still considering individual compounds. A few studies have shown associations between exposure to individual non-persistent EDCs and sperm DNA fragmentation (SDF) in different male populations. Thus, the aim of this study was to investigate associations between combined exposure to non-persistent EDCs and SDF index in young men. A cross-sectional study was conducted with 158 healthy university students from Southeaster Spain. The participants provided spot urine and semen samples on the same day. The concentrations of urinary bisphenol A (BPA), benzophenones [2,4-dihydroxybenzophenone (BP-1); 2,2',4,4'-tetrahydroxybenzophenone (BP-2), 2-hydroxy-4-methoxybenzophenone (BP-3), 2,2'-dihydroxy-4-methoxybenzophenone (BP-8), 4-hydroxybenzophenone (4OHBP)], and parabens (methylparaben, ethylparaben, propylparaben, butylparaben) were measured by dispersive liquid-liquid microextraction and ultrahigh-performance liquid chromatography with tandem mass spectrometry detection. SDF was analysed using a Sperm Chromatin Dispersion test. Statistical analyses were carried out using Bayesian Kernel Machine Regression models to evaluate associations between combined exposure to these compounds and SDF index while adjusting by relevant covariates. The increase in urinary concentration of 4OHBP was found to be the most important contributor to the negative association between urinary EDCs concentrations and SDF index, being of -5.5 % [95 % CI: -10.7, -0.3] for those in percentile 50, and - 5.4 % [95 % CI: -10.8, -0.1] for those in percentile 75. No significant associations were observed between other EDCs and SDF index. Our findings show that urinary 4OHBP levels may be associated with a decrease in the SDF index. Nonetheless, the effects we observed were likely to be small and of uncertain clinical significance. Further research is needed to replicate our findings in other male populations.

Immune checkpoint inhibitors-associated thrombosis in patients with head and neck cancer: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with Immune Checkpoint Inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS: /Patients. This retrospective, multicenter study was promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with head and neck cancer who initiated ICI between 01/01/2015 and 31/12/2021 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT, with secondary objectives including the analysis of their impact on survival and the identification of variables predictive of VTE/AT. RESULTS: A total of 143 patients with head and neck cancer were enrolled. The incidence of VTE/AT during follow-up (median 8.6 months) was 2.8%. Survival analysis showed no significant differences (p = 0.644) between the group that developed VTE/AT (median 7.13 months, 95% CI 0-22.9) and the group that did not (median 9.86 months, 95% CI 6.3-13.4). The presence of liver metastases was predictive of VTE/AT (p < 0.05). CONCLUSIONS: Thromboembolic disease associated with immunotherapy in patients with head and neck neoplasia does not significantly impact survival. The presence of liver metastases can predict these events.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos 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). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

Sugar-sweetened beverage intake in relation to reproductive parameters in young men.

BACKGROUND: There has been a decrease in sperm concentration in recent years. Concurrently, there were important dietary changes, including an increase in sugar-sweetened beverage intake (SSB). The relation between SSB and male reproduction functions in humans are barely described in the literature. METHODS: Cross-sectional study with 209 participants (18-23 years old) recruited during one year in Murcia, Spain. All men provided semen and blood samples the same day. SSB consumption was evaluated using a 101-item validated food frequency questionnaire. Reproductive hormones were analysed from serum samples, obtaining levels of follicle-stimulating hormone, inhibin B, luteinizing hormone, estradiol, and testosterone. The evaluation of semen analysis followed the WHO guidelines and consisted of seminal volume, sperm concentration, total sperm count, percentage of morphologically normal sperm, and percentage of motile sperm. SSB intake association with semen parameters and hormone levels were examined using multiple linear regression. RESULTS: Men in the highest quartile of the SSB intake had a higher percentage of morphologically normal sperm, 37.4% [6.1, 68.3] (p, trend=0.047) and higher estradiol levels (9.5% [-3.5, 22.5] (p, trend=0.047) than those in the first quartile. SSB intake was unrelated to other semen quality parameters or reproductive hormone levels. CONCLUSIONS: Our results indicate that sperm morphology and estradiol levels may be associated with sugar-sweetened beverage intake. These findings might be explained by physiological metabolism homeostasis, though more studies are required to confirm these results and draw conclusions in other male populations.

Maternal urinary concentrations of bisphenol A during pregnancy are associated with global DNA methylation in cord blood of newborns in the "NELA" birth cohort.

Endocrine disrupting chemicals (EDCs) set a public health risk through disruption of normal physiological processes. The toxicoepigenetic mechanisms of developmental exposure to common EDCs, such as bisphenol A (BPA), are poorly known. The present study aimed to evaluate associations between perinatal maternal urinary concentrations of BPA, bisphenol S (BPS) and bisphenol F (BPF) and LINE-1 (long interspersed nuclear elements) and Alu (short interspersed nuclear elements, SINEs) DNA methylation levels in newborns, as surrogate markers of global DNA methylation. Data come from 318 mother-child pairs of the `Nutrition in Early Life and Asthma´ (NELA) birth cohort. Urinary bisphenol concentration was measured by dispersive liquid-liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection. DNA methylation was quantitatively assessed by bisulphite pyrosequencing on 3 LINEs and 5 SINEs. Unadjusted linear regression analyses showed that higher concentration of maternal urinary BPA in 24th week's pregnancy was associated with an increase in LINE-1 methylation in all newborns (p = 0.01) and, particularly, in male newborns (p = 0.03). These associations remained in full adjusted models [beta = 0.09 (95 % CI = 0.03; 0.14) for all newborns; and beta = 0.10 (95 % CI = 0.03; 0.17) for males], including a non-linear association for female newborns as well (p-trend = 0.003). No associations were found between maternal concentrations of bisphenol and Alu sequences. Our results suggest that exposure to environmental levels of BPA may be associated with a modest increase in LINE-1 methylation -as a relevant marker of epigenomic stability- during human fetal development. However, any effects on global DNA methylation are likely to be small, and of uncertain biological significance.

Nitrite and Nitrate Levels in Follicular Fluid From Human Oocyte Donors Are Related to Ovarian Response and Embryo Quality.

Nitric oxide, a key regulatory molecule in the follicular fluid, has been suggested as a possible biomarker to predict ovarian response in stimulated cycles and the potential of the retrieved oocytes for developing high-quality embryos. Nevertheless, a consensus on whether or not nitric oxide can help in this context has not been reached. We simultaneously measured the oxidation products of nitric oxide, nitrite, and nitrate, via high-performance liquid chromatography (HPLC)-UV in follicular fluid samples from 72 oocyte donors. We found no associations of follicular fluid nitrite, nitrate, total nitric oxide, or nitrate/nitrite ratio with total or metaphase II (MII) oocyte yield. However, nitrite and nitrate levels were related to the yield of MII oocytes when this outcome was expressed as a proportion of all oocytes retrieved. The adjusted MII proportion in the lowest and highest nitrite levels were 68% (58-77%) and 79% (70-85%), respectively (p, linear trend = 0.02), whereas the adjusted MII proportion in extreme tertiles of nitrate levels were 79% (70-85%) and 68% (57-77%) (p, linear trend = 0.03). In addition, nitrate levels showed a suggestive inverse correlation with embryos with maximum or high potential of implantation (p = 0.07). These results suggest that the follicular fluid concentrations of nitrite and nitrate may be a useful tool in predicting how healthy oocyte donors respond to superovulation and the implantation potential of the embryos produced from their oocytes.

Are Dietary Indices Associated with Polycystic Ovary Syndrome and Its Phenotypes? A Preliminary Study.

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder which impairs ovarian function. The adherence to healthy dietary patterns and physical exercise are the first line of recommended treatment for PCOS patients, but it is yet unclear what type of diet is more adequate. In this case-control study, we explored associations between adherence to five dietary quality indices and the presence of PCOS. We enrolled 126 cases of PCOS and 159 controls living in Murcia (Spain). Diagnostic of PCOS and its phenotypes were established following the Rotterdam criteria (hyperandrogenism (H), oligoanovulation (O), polycystic ovaries morphology (POM)). We used a validated food frequency questionnaires to calculate the scores of five dietary indices: alternate Healthy Eating index (AHEI), AHEI-2010, relative Mediterranean Dietary Score (rMED), alternate Mediterranean Dietary Score (aMED) and Dietary Approaches to Stop Hypertension (DASH). We used multivariable logistic regression to estimate adjusted odds ratios and confidence intervals. In the multivariable analysis, AHEI-2010 index was inversely associated with Hyperandrogenism + Oligoanovulation PCOS phenotype (ORQ3 vs. Q1 = 0.1; 95% CI: (0.0; 0.9); Pfor trend = 0.02). We did not find any statistical significant association between dietary indices and total anovulatory or ovulatory PCOS. However, further studies with higher sample sizes exploring these associations among the diverse phenotypes of PCOS are highly warranted.

Health-Related Quality of Life in Adult Spanish Women with Endometriomas or Deep Infiltrating Endometriosis: A Case-Control Study.

Endometriosis is a disabling disease that may significantly compromise a woman's social relationships, sexuality, and mental health. Considering the impact of endometriomas and deep infiltrating endometriosis (DIE) on quality of life and the limited number of papers on this topic, the objective of this study was to assess health-related quality of life (HRQoL) in adult Spanish women with the condition. A case-control study was conducted on a group of 99 patients with ovarian endometriomas or DIE and 157 controls. Women underwent physical and gynecological examinations, and they completed health questionnaires including the Short Form-12v2 (SF-12v2), a survey for HRQoL. Eight scales and two component summary scores (Physical (PCS) and Mental (MCS), respectively) were calculated. Women with endometriomas or DIE had significantly worse PCS: 47.7 ± 9.7 vs. 56.1 ± 5.9, respectively (p < 0.001) compared to controls, as well as lower scores on seven out of the eight scales (p < 0.01). No significant differences were found for the MCS. Conclusions: HRQoL was significantly lower in patients with endometriomas or DIE compared to controls. If confirmed, these results may have important implications for prevention, clinical practice, and intervention.

Is dispositional optimism associated with endometriomas and deep infiltrating endometriosis?

INTRODUCTION: Endometriosis is a chronic painful condition characterized by high prognostic uncertainty, as well as the threat of infertility and emotional symptoms that may affect many aspects of women, including psychological characteristics like dispositional optimism. Considering the impact of endometriosis on psychological health and the paucity of papers on this topic, the aim of this study is to explore optimism and associated factors in endometriosis. METHODS: A case-control study was performed on a group of 95 women with endometriosis and 156 controls. All participants completed the Life Orientation Test-Revised (LOT-R), a self-administered tool for assessing dispositional optimism. Pain severity, medication, gynecological and socio-demographic information was also collected. RESULTS: Low optimism was observed for women with endometriosis compared to controls even after covariate adjustment (LOT-R global scores: 14.5 vs. 15.9 points, p = .045). CONCLUSIONS: This study provides the first evidence that a personality dimension with many prognostic implications may be altered in women with endometriosis. Our findings highlight the importance of a broader understanding of this condition, treating this disorder from a biopsychosocial perspective and suggests the need for non-medical attention within a multidisciplinary team.

Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort.

Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred-the recall of paracetamol intake independent of AGD measurements-introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.