Polycystic ovary syndrome: clinical and laboratory variables related to new phenotypes using machine-learning models.

PURPOSE: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrinopathy in women of reproductive age. Machine learning (ML) is the area of artificial intelligence with a focus on predictive computing algorithms. We aimed to define the most relevant clinical and laboratory variables related to PCOS diagnosis, and to stratify patients into different phenotypic groups (clusters) using ML algorithms. METHODS: Variables from a database comparing 72 patients with PCOS and 73 healthy women were included. The BorutaShap method, followed by the Random Forest algorithm, was applied to prediction and clustering of PCOS. RESULTS: Among the 58 variables investigated, the algorithm selected in decreasing order of importance: lipid accumulation product (LAP); abdominal circumference; thrombin activatable fibrinolysis inhibitor (TAFI) levels; body mass index (BMI); C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-c), follicle-stimulating hormone (FSH) and insulin levels; HOMA-IR value; age; prolactin, 17-OH progesterone and triglycerides levels; and family history of diabetes mellitus in first-degree relative as the variables associated to PCOS diagnosis. The combined use of these variables by the algorithm showed an accuracy of 86% and area under the ROC curve of 97%. Next, PCOS patients were gathered into two clusters in the first, the patients had higher BMI, abdominal circumference, LAP and HOMA-IR index, as well as CRP and insulin levels compared to the other cluster. CONCLUSION: The developed algorithm could be applied to select more important clinical and biochemical variables related to PCOS and to classify into phenotypically different clusters. These results could guide more personalized and effective approaches to the treatment of PCOS.

Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic.

PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.

B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice.

STUDY QUESTION: What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis? SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton's tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. WHAT IS KNOWN ALREADY: A polyclonal activation of B cells and the presence of anti-endometrial autoantibodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. PARTICIPANTS/MATERIALS, SETTING, METHODS: After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant of Institut National de la Santé et de la Recherche Médicale and Paris Descartes University. None of the authors has any conflict of interest to disclose.

Gonadotropin-releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta-analysis.

OBJECTIVE: To evaluate the effectiveness of gonadotropin-releasing hormone agonist (GnRHa) administration before and/or during cancer chemotherapy for the protection of ovarian reserve in premenopausal women without prior diagnosis of infertility. METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing administration of GnRHa before and/or during chemotherapy vs chemotherapy alone. Eligible participants were premenopausal women at any stage of cancer, without previous diagnosis of infertility. An electronic database search in MEDLINE, CENTRAL, LILACS and ClinicalTrials.gov was performed. After selecting eligible studies, the relative risk (RR) was assessed for primary ovarian insufficiency (POI)/amenorrhea and for spontaneous pregnancy after completion of treatment. RESULTS: Thirteen RCTs comparing concurrent use of GnRHa and chemotherapy (609 participants) with chemotherapy alone (599 participants) were eligible for meta-analysis. All trials were open-label and patients had been treated for breast cancer (n = 1099) or lymphoma (n = 109). GnRHa had a significant benefit on the risk of POI/amenorrhea (RR, 0.60; 95% CI, 0.45-0.79), which persisted in subgroup analysis for breast cancer (RR, 0.57; 95% CI, 0.43-0.77) but not for lymphoma patients (RR, 0.70; 95% CI, 0.20-2.47). The rate of spontaneous pregnancy after completion of treatment was higher in women receiving GnRHa plus chemotherapy compared with those receiving chemotherapy alone (RR, 1.43; 95% CI, 1.01-2.02). Overall, the quality of evidence was low due to the unclear risk of bias, short follow-up and lack of objective assessment of ovarian function and reserve. CONCLUSIONS: Evidence, albeit of low quality, supports the use of GnRHa before and/or during chemotherapy to reduce the risk of POI and increase the probability of spontaneous pregnancy in the short term. Further high quality RCTs with more accurate assessment of ovarian reserve are needed to support definitive recommendations for clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: systematic review and meta-analysis.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is an insidious pathologic condition that can manifest from simple steatosis to steatohepatitis (NASH) with potential progression to cirrhosis. Like the polycystic ovary syndrome (PCOS), NAFLD is associated with obesity, diabetes mellitus, insulin resistance and metabolic syndrome. PCOS women have an increased risk of NAFLD, but it is debatable which features of PCOS, either specific (androgen excess) or unspecific (metabolic derangements) affect the NAFLD risk. METHODS: We performed a systematic review and meta-analysis of studies that addressed the association of PCOS and NAFLD. We selected 17 studies published between 2007 and 2017 that included 2734 PCOS patients and 2561 controls of similar age and body mass index (BMI). RESULTS: PCOS patients have increased prevalence of NAFLD (odds ratio 2.54, 95% confidence interval 2.19-2.95). PCOS women with hyperandrogenism (classic phenotype) have a higher prevalence of NAFLD compared to women with PCOS without hyperandrogenism, even after correction for confounding variables. Among women with PCOS, those with NAFLD have higher serum total testosterone (mean difference 0.40 nmol/L, 95% CI 0.29-0.50 nmol/L) and free androgen index (mean difference 4.46, 95% CI 3.53-5.39) than those without NAFLD. The studies that used multivariate analysis controlling for age, BMI, triglycerides, and insulin resistance index confirmed that serum androgens are independent predictors of NAFLD in women with PCOS. CONCLUSION: The prevalence of NAFLD is increased in women with PCOS and the presence of NAFLD is associated with high serum androgen levels, in addition to obesity and insulin resistance.

Plasma iron levels appraised 15 days after spinal cord injury in a limb movement animal model.

STUDY DESIGN: Experimental, controlled trial. OBJECTIVES: The purpose of this study was to evaluate plasma iron and transferrin levels in a limb movement animal model with spinal cord injury (SCI). SETTING: Universidade Federal de São Paulo, Departamento de Psicobiologia. METHODS: In all, 72 male Wistar rats aged 90 days were divided into four groups: (1) acute SCI (1 day, SCI1), (2) 3 days post-SCI (SCI3), (3) 7 days post-SCI (SCI7) and (4) 15 days post-SCI (SCI15). Each of these groups had corresponding control (CTRL) and SHAM groups. Plasma iron and transferrin levels of the different groups were analyzed using a one-way analysis of variance (ANOVA) followed by Tukey's test. RESULTS: We found a significant reduction in iron plasma levels after SCI compared with the CTRL group: SCI1 (CTRL: 175±10.58 µg dl(-1); SCI: 108.28±11.7 µg dl(-1)), SCI3 (CTRL: 195.5±11.00 µg dl(-1); SCI: 127.88±12.63 µg dl(-1)), SCI7 (CTRL: 186±2.97 µg dl(-1); SCI: 89.2±15.39 µg dl(-1)) and SCI15 (CTRL: 163±5.48 µg dl(-1); SCI: 124.44±10.30 µg dl(-1)) (P<0.05; ANOVA). The SHAM1 group demonstrated a reduction in iron plasma after acute SCI (CTRL: 175±10.58 µg dl(-1); SHAM: 114.60±7.81 µg dl(-1)) (P<0.05; ANOVA). CONCLUSION: Reduced iron metabolism after SCI may be one of the mechanisms involved in the pathogenesis of sleep-related movement disorders.

Reduction of serum serotonin precursors after veralipride treatment for postmenopausal hot flushes.

OBJECTIVE: The pathogenesis of hot flushes involves several brain neurotransmitter systems, and changes in serotonin turnover have been hypothesized. Veralipride is an anti-dopaminergic agent that relieves hot flushes and putatively also modulates serotonergic neurons. To further elucidate this relationship, in the present study we evaluated whether administration of veralipride for relief of hot flushes is able to affect serum levels of the serotonin precursor tryptophan in postmenopausal women. METHODS: Twenty-four postmenopausal women were randomly assigned to receive veralipride (100 mg/day) or similar placebo tablets for 3 months (n = 12 per group). Free tryptophan and total tryptophan (free + protein-bound) levels were assayed before and monthly by high pressure liquid chromatography. Data were analyzed with repeated measures ANOVA and Student-Newman-Keuls post hoc test. RESULTS: Relief of hot-flushes was achieved with complete suppression of symptoms after veralipride, but not placebo, treatment. In the veralipride group, total tryptophan levels significantly (p < 0.05) decreased from baseline (11.2 +/- 0.4 microg/ml) to 3 months (8.0 +/- 0.3 microg/ml), as well as free tryptophan concentrations (baseline 2.1 +/- 0.1 microg/ml; after 3 months 1.3 +/- 0.1 microg/ml; p < 0.05). No changes were recorded in the placebo group. CONCLUSION: Women treated with veralipride for relief of menopausal symptoms show a decrease in serum levels of serotonin precursors, suggesting that the brain serotonergic system may be involved in the pathogenesis of postmenopausal vasomotor symptoms.

Activin-related proteins in bovine mammary gland: localization and differential expression during gestational development and differentiation.

Bovine mammary gland morphogenesis and differentiation are regulated by actions of growth factors including members of the transforming growth factor ß superfamily. Activins A and B, which are members of the transforming growth factor ß superfamily, bind selectively to ActRIB and ActRIIA receptors and their biological effects are antagonized by inhibins and follistatins. In the present paper we evaluated gene and protein expression of the activin and inhibin subunits ßA, ßB, and α-inhibin and follistatin and ActRIB and ActRIIA receptors in the mammary gland of nonpregnant and pregnant heifers. Mammary glands were obtained from nonpregnant Nelore (Bos indicus) heifers (n=9) and from primigravid Nelore heifers during early (n=9), mid (n=6), and late (n=5) pregnancy. Specimens of mammary tissue were analyzed by real-time PCR and immunohistochemistry. The ßA and α-inhibin subunits and ActRIB and ActRIIA mRNA expression was higher in the early-pregnancy group compared with the nonpregnant group. In the mid-pregnancy group, the subunits ßA, ßB, and α-inhibin as much as follistatin mRNA expression was higher compared with the nonpregnant group, whereas ActRIB transcripts were absent in the late-pregnancy group. Immunostaining of these proteins, with the exception of ActRIB, was observed in the mammary tissue sections at all time points analyzed; these findings are in agreement with the observed pattern of mRNA expression. Staining and mRNA expression for ActRIB were undetected in the late-pregnancy group. In summary, the present study demonstrated that the activin-related proteins, ßA, ßB, and α-inhibin subunits, as much as follistatin and ActRIB and ActRIIA receptors display different patterns of expression regarding time of gestation in the bovine mammary gland. The modulation of the expression pattern during gestation suggests that activin-related proteins may play a key role in regulating bovine mammary branching morphogenesis and epithelial differentiation.

High serum follistatin levels in women with ovarian endometriosis.

BACKGROUND: Follistatin is an activin-binding protein produced by several tissues, including endometrium and endometriotic implants. We aimed to quantify follistatin in patients with ovarian endometriosis and investigate its value as a diagnostic marker. METHODS: Women undergoing laparoscopic excision of ovarian endometrioma (n = 52) or other benign ovarian cysts (n = 52) were studied, plus women with non-ovarian endometriosis (n = 11) and healthy controls (n = 27). Serum was collected from all subjects, and peritoneal and cystic fluid from a subset with endometrioma. Follistatin was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of follistatin to detect endometrioma was evaluated by receiver operating characteristic (ROC) curve and compared with cancer antigen (CA)-125. RESULTS: Serum follistatin was increased in women with ovarian endometrioma (2080 +/- 94 pg/ml) compared with controls (545 +/- 49 pg/ml, P < 0.001), other benign ovarian cysts (795 +/- 60 pg/ml, P < 0.001) or non-ovarian endometriosis (1271 +/- 115 pg/ml, P < 0.001). Cystic fluid showed a higher concentration of follistatin (9850 +/- 4461 pg/ml) than peritoneal fluid (1885 +/- 261 pg/ml, P < 0.001) and serum (P < 0.001). Follistatin levels detected 48/52 cases of endometrioma (92% sensitivity) at 1433 pg/ml cut-off, corresponding to 92% specificity. CA-125 detected only 44% of endometriomas with 90% specificity. ROC curve comparison showed follistatin was more accurate than CA-125 to discriminate women with endometrioma either from controls or women with other benign ovarian cysts (P < 0.0001). CONCLUSIONS: Serum follistatin is increased in women with endometriosis and allows clear distinction between endometrioma and other benign ovarian cysts. Follistatin has the sensitivity and specificity to become a useful clinical marker of ovarian endometrioma.

Activin A increases invasiveness of endometrial cells in an in vitro model of human peritoneum.

The aim of this study was to investigate whether activin A has an effect on the attachment and/or invasion of endometrial cells in a modeled peritoneum in vitro. Cultured endometrial stromal cells (ESCs) and endometrial epithelial cells (EECs) were treated with activin A (6.25-50 ng/ml) and with activin A (25 ng/ml) with and without inhibin A or follistatin. Fluorescent labeled cells were added to confluent peritoneal mesothelial cells (PMCs) and to a monolayer of confluent PMCs grown in a Matrigel invasion assay. The rate of endometrial cell attachment and invasion through PMCs was assessed. The expression of cell adhesion proteins N- and E-cadherin was evaluated with real-time RT-PCR. Activin A (25 ng/ml) promoted invasion of the endometrial cells through the modeled peritoneum (>2-fold versus control) and this effect was partially reversed by inhibin A and follistatin. Activin A had no effect on the rate of attachment of the endometrial cells to the PMCs or in the rate of proliferation. In addition, activin A induced a decreased mRNA expression of E-cadherin in cultured EECs. In conclusion, activin A increases invasion of EECs and ESCs into modeled peritoneum. In EECs, this effect may be related to down-regulation of E-cadherin expression. Further studies are warranted to evaluate the role of activin-A in the genesis of the endometriotic lesion.

Androgen receptor and 5alpha-reductase are expressed in pelvic endometriosis.

The aim of this study was to evaluate whether androgen receptor (AR) and the enzymes that convert testosterone into the more potent androgen dihydrotestosterone, 5alpha-reductases (5alpha-R1 and 5alpha-R2) are expressed in pelvic endometriosis. The study involved 21 infertile women who underwent laparoscopy and were divided into two groups: control (n= 13) and endometriosis (n= 8) according to the histological and laparoscopic findings. Endometrial and endometriotic implant biopsies were performed. By reverse transcription polymerase chain reaction and immunohistochemistry, AR, 5alpha-R1 and 5alpha-R2 messenger RNA and protein were detected in biopsies of pelvic endometriosis, as well as in the eutopic endometrium of both groups. These findings suggest that active androgens may be formed within the endometriotic tissue and that both local and systemic androgens have the potential to act on endometriotic cells.

Placental neurokinin B mRNA expression increases at preterm labor.

INTRODUCTION: Neurokinin B (NKB) is a neuropeptide belonging to the family of tachykinins-related peptides that elicits contractility of human myometrial strips in vitro. The present study evaluates whether placental mRNA and peptide expression of NKB change in women at preterm labor. METHODS: A group of 26 women with singleton pregnancies were enrolled in the study. Placental tissue specimens were collected from pregnant women delivering after elective cesarean section, after labor at term, or after preterm labor. Changes in placental NKB mRNA and protein expression were evaluated by real-time quantitative RT-PCR analysis and by immunofluorescence respectively. RESULTS: Placental mRNA expression of NKB was significantly higher after term and preterm labor (P<0.001) than cesarean section, and highest after preterm labor. Immunofluorescent staining in placentas from preterm or term labor was more intense than after cesarean section (P<0.001). In particular, NKB protein expression was higher in placentas collected after preterm labor than those collected after term labor. DISCUSSION: Neurokinin B mRNA and protein are highly expressed in placenta at term and preterm labor; thus, the involvement of this neuropeptide in the events cascade leading to parturition may be suggested.

Maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) levels in post-term pregnancy: effect of prostaglandin administration.

OBJECTIVE: Placental corticotropin-releasing factor (CRF) affects myometrial contractility and the secretion of several uterotonins such as prostaglandins (PGs); however, the activity of CRF is counteracted by CRF-binding protein (CRF-BP). At term and pre-term labor, CRF levels in maternal plasma are highest whereas those of CRF-BP are falling, and the cause of this fall is unknown. Thus, in this study, we investigated the effect of PG administration for labor induction on maternal plasma CRF and CRF-BP concentrations. DESIGN: Maternal plasma CRF and CRF-BP levels were assayed before and after (2 h later) induction of labor by intracervical administration of prostaglandin E(2) (PGE(2)), and at delivery in a group of healthy post-term pregnancies (n=18). Controls were women at term out of labor (n=22), who subsequently progressed to deliver a healthy singleton baby. METHODS: CRF was measured by two-site immunoradiometric assay, and CRF-BP was assayed by radioimmunoassay. RESULTS: Maternal plasma CRF levels were significantly (P<0.0001) lower and CRF-BP significantly (P<0.0005) higher in post-term than in term pregnancies. With respect to induction of labor, 2 mg PGE(2) were sufficient to increase maternal plasma CRF levels at delivery (P<0.005). While 0.5 mg PGE(2) significantly decreased maternal plasma CRF-BP levels at delivery (P<0.001), 2.0 mg PGE(2) significantly reduced CRF-BP concentrations both after 2 h (P<0.05) and at delivery (P<0.0001). CONCLUSIONS: In the light of the well-known stimulation of prostaglandin release by CRF, these data suggest a positive feedback effect of PGE(2) on maternal CRF release during induced labor.

The detection of anti-beta2-glycoprotein I antibodies is associated with increased risk of pregnancy loss in women with threatened abortion in the first trimester.

OBJECTIVE: This study was designed to evaluate whether the detection of serum antiphospholipid autoantibodies may be useful in predicting pregnancy outcome in women with threatened abortion in the first trimester. STUDY DESIGN: A group of 77 pregnant women of between 8 and 12 weeks' gestation with vaginal bleeding was tested for serum antiphospholipid, lupus anticoagulants, anticardiolipin, antinuclear antibodies, and anti-beta2-glycoprotein I antibodies, and was followed up until the spontaneous end of pregnancy. A control group composed of 15 healthy women with uncomplicated gestation was tested contemporarily for the same antibody panel. RESULTS: Of the 77 patients with threatened abortion, 32 (41.5%) progressed to deliver at term and 45 (58.5%) experienced early pregnancy loss. Among the antibodies evaluated, only anti-beta2-glycoprotein I was significantly more frequent in those women whose pregnancy resulted in spontaneous abortion (22/45, 49%) than in those who progressed to term (6/32, 19%) or in the control group (2/15, 13%; p=0.004). This difference was specific to the IgM isotype (p=0.001). After adjustment by multivariate analysis, the odds ratio for pregnancy loss associated with a positive beta2-glycoprotein I antibody test was 5.18 (p=0.001). CONCLUSION: The detection of anti-beta2-glycoprotein I antibodies is associated with an increased risk of pregnancy loss in women with threatened abortion in the first trimester.

Microparticles: Inflammatory and haemostatic biomarkers in Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is associated with a chronic low-grade inflammation and predisposition to hemostatic and atherosclerotic complications. This case-control study evaluated the microparticles (MPs) profile in patients with the PCOS and related these MPs to clinical and biochemical parameters. MPs derived from platelets (PMPs), leuckocytes (LMPs) and endothelial cells (EMPs) were evaluated, as well as MPs expressing tissue factor (TFMPs), by flow cytometry, comparing women with PCOS (n = 50) and a healthy control group (n = 50). PCOS women presented increased total MPs, PMPs, LMPs and EMPs levels when compared to control group (all p < 0.05). TFMPs was similar between the groups (p = 0.379). In conclusion, these MPs populations could be useful biomarkers for association with thrombosis and cardiovascular disease in PCOS women.

Umbilical cord serum activin A levels are increased in pre-eclampsia with impaired blood flow in the uteroplacental and fetal circulation.

The aims of the present study were to evaluate the umbilical cord serum activin A concentrations in complicated pregnancies and also to explore the relationship between activin A levels and blood flow velocity in fetal arteries. Umbilical cord blood samples were obtained postpartum after a full term uneventful gestation (control group, n=40), and from pregnancies complicated by gestational diabetes (n=13), preterm labour (n=18), or pre-eclampsia (n=19). Cord serum activin A levels were three-fold higher in pregnancies complicated by pre-eclampsia (1.17+/-0.14 ng/ml, p<0.01) than in the control group (0.43+/-0.03 ng/ml), but were unaltered in the diabetes and preterm labour groups. The pre-eclampsia group had a marked increase of umbilical artery pulsatility index (PI) and also a decrease of middle cerebral artery PI (p<0.01). Furthermore, activin A concentration correlated directly with the umbilical artery PI (r=0.540, p=0.021), with the length of stay in the Neonatal Intensive Care Unit (r=0.857, p<0.001) and also with cord blood pH (r=-0.886, p<0.001). In conclusion, umbilical cord serum activin A levels are increased in the presence of pre-eclampsia and provide an indirect marker of impaired blood flow in the uteroplacental and fetal circulation.

Luteal phase of the menstrual cycle increases sweating rate during exercise.

The present study evaluated whether the luteal phase elevation of body temperature would be offset during exercise by increased sweating, when women are normally hydrated. Eleven women performed 60 min of cycling exercise at 60% of their maximal work load at 32 degrees C and 80% relative air humidity. Each subject participated in two identical experimental sessions: one during the follicular phase (between days 5 and 8) and the other during the luteal phase (between days 22 and 25). Women with serum progesterone >3 ng/mL, in the luteal phase were classified as group 1 (N = 4), whereas the others were classified as group 2 (N = 7). Post-exercise urine volume (213 +/- 80 vs 309 +/- 113 mL) and specific urine gravity (1.008 +/- 0.003 vs 1.006 +/- 0.002) changed (P < 0.05) during the luteal phase compared to the follicular phase in group 1. No menstrual cycle dependence was observed for these parameters in group 2. Sweat rate was higher (P < 0.05) in the luteal (3.10 +/- 0.81 g m-2 min-1) than in the follicular phase (2.80 +/- 0.64 g m(-2) min(-1)) only in group 1. During exercise, no differences related to menstrual cycle phases were seen in rectal temperature, heart rate, rate of perceived exertion, mean skin temperature, and pre- and post-exercise body weight. Women exercising in a warm and humid environment with water intake seem to be able to adapt to the luteal phase increase of basal body temperature through reduced urinary volume and increased sweating rate.

ATP-binding cassette transporters in reproduction: a new frontier.

BACKGROUND: The transmembrane ATP-binding cassette (ABC) transporters actively efflux an array of clinically relevant compounds across biological barriers, and modulate biodistribution of many physiological and pharmacological factors. To date, over 48 ABC transporters have been identified and shown to be directly and indirectly involved in peri-implantation events and fetal/placental development. They efflux cholesterol, steroid hormones, vitamins, cytokines, chemokines, prostaglandins, diverse xenobiotics and environmental toxins, playing a critical role in regulating drug disposition, immunological responses and lipid trafficking, as well as preventing fetal accumulation of drugs and environmental toxins. METHODS: This review examines ABC transporters as important mediators of placental barrier functions and key reproductive processes. Expression, localization and function of all identified ABC transporters were systematically reviewed using PubMed and Google Scholar websites to identify relevant studies examining ABC transporters in reproductive tissues in physiological and pathophysiological states. Only reports written in English were incorporated with no restriction on year of publication. While a major focus has been placed on the human, extensive evidence from animal studies is utilized to describe current understanding of the regulation and function of ABC transporters relevant to human reproduction. RESULTS: ABC transporters are modulators of steroidogenesis, fertilization, implantation, nutrient transport and immunological responses, and function as 'gatekeepers' at various barrier sites (i.e. blood-testes barrier and placenta) against potentially harmful xenobiotic factors, including drugs and environmental toxins. These roles appear to be species dependent and change as a function of gestation and development. The best-described ABC transporters in reproductive tissues (primarily in the placenta) are the multidrug transporters p-glycoprotein and breast cancer-related protein, the multidrug resistance proteins 1 through 5 and the cholesterol transporters ABCA1 and ABCG1. CONCLUSIONS: The ABC transporters have various roles across multiple reproductive tissues. Knowledge of efflux direction, tissue distribution, substrate specificity and regulation of the ABC transporters in the placenta and other reproductive tissues is rapidly expanding. This will allow better understanding of the disposition of specific substrates within reproductive tissues, and facilitate development of novel treatments for reproductive disorders as well as improved approaches to protecting the developing fetus.

Congenital dacryocystocele with intranasal extension.

PURPOSE: Congenital dacryocystocele is a rare anomaly in the newborn child. The swelling of lachrymal sac is observed by birth and it is associated with obstruction of lachrymal system either above or below lachrymal sac. METHODS: Diagnosis was made by clinical observation. Some ancillary examinations, such as ultrasonography, tomography, and rhinoscopy, were useful. RESULTS: The authors describe the clinical case of a newborn with a unilateral congenital dacryocystocele. This anomaly was successfully treated with probing and marsupialization of the nasal cyst. CONCLUSIONS: Treatment of this congenital anomaly is by light compressive massage, probing with silicone intubation of lachrymal system to assure prolonged permeability of the system, or with marsupialization of the nasal cyst. In some cases with intranasal extension of dacryocystocele, collaboration with an otolaryngologist may be necessary.

Estrogen receptor αlpha gene (ESR1) PvuII and XbaI polymorphisms are associated to metabolic and proinflammatory factors in polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that involves multiple factors. Although the etiology of PCOS is unknown, there is an involvement of sex steroid hormones in the pathophysiology of this syndrome. Therefore, polymorphisms in genes involved in the action of estrogen may contribute to a woman's susceptibility to PCOS. AIM: This study aimed to evaluate the association between the polymorphisms PvuII and XbaI in the estrogen receptor alpha (ESR1) gene and the occurrence of PCOS. The study also aimed to assess the influence of these polymorphisms on the metabolic and inflammatory profiles of women with PCOS. MATERIAL AND METHODS: This case-control study included 99 women with PCOS, diagnosed according to the Rotterdam criteria, and 104 age-matched healthy women. The polymorphisms were evaluated using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No association between the ESR1 gene polymorphisms and the presence of PCOS was observed. However, we found associations between the PvuII polymorphism and C-reactive protein levels, testosterone levels, family history of diabetes, and waist circumference. The XbaI polymorphism was associated with fasting glucose and a family history of hypertension. CONCLUSION: These polymorphisms are not associated with PCOS development, but they are involved in the phenotype of complications of the syndrome. Therefore, prior knowledge of these genomic variants might contribute to taking preventive measures that could delay the metabolic and reproductive complications commonly seen in women with PCOS.