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Introduction: A controversy exists about the accuracy of the cerebroplacental ratio (CPR) for the prediction of cesarean section for intrapartum fetal compromise (CS-IFC). Our aim was to evaluate whether the interval to delivery modifies the accuracy of CPR either as a single marker or combined with estimated fetal weight centile (EFWc), type of labor onset (TLO), and other clinical variables. Methods: This was a multicenter retrospective study of 5,193 women with singleton pregnancies who underwent an ultrasound scan at 35+0–41+0 weeks and gave birth within 1 month of examination, at any of the participating hospitals in Spain, UK, and Italy. CS-IFC was diagnosed in case of an abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH Results: The predictive ability of CPR MoM for CS-IFC worsened with the interval to delivery. In general, the best prediction was obtained prior to labor and by adding information related to EFWc and TLO (AUC 0.71 [95% CI: 0.64–0.79], 0.73 [95% CI: 0.66–0.80], and 0.75 [95% CI: 0.69–0.81]; p < 0.0001). Addition of more clinical data did not improve prediction. In addition, results did not vary when only cases with spontaneous onset of labor were studied. Conclusion: CPR MoM prediction of CS-IFC at the end of pregnancy worsens with the interval to delivery. Accordingly, it should be done in the short term and considering EFWc and TLO.

Purpose Patients with functional hypothalamic amenorrhea (FHA) could commonly have bone damage, often preceded by metabolic alterations due to a relative energy deficit state. To date, there are no markers capable of predicting osteopenia before it is manifested on DXA. Irisin is a myokine that promotes the differentiation of osteoblastic cells and appears to be inversely correlated with the incidence of bone fragility and fractures in postmenopausal women. The aim of this study was to measure irisin levels in FHA patients and to correlate it with bone density parameters. Methods Thirty-two patients with FHA and 19 matched controls underwent the same clinical and laboratory evaluation. Results Irisin and body mass index (BMI) were significantly lower in the case group than in healthy controls (2.03 ± 0.12 vs. 2.42 ± 0.09 p p 2) was significantly lower in the case group than in the healthy controls (1.09 ± 0.08 vs. 1.14 ± 0.05, p Conclusions The FHA group showed lower irisin levels associated with significantly reduced BMD parameters that did not reach the severity of osteopenia. Therefore, we could speculate that irisin could predict DXA results in assessing modifications of body composition parameters. Future research is warranted to study these parameters in a larger population to confirm our results, so that irisin could be used as a predictor and screening method for bone deprivation. Furthermore, irisin is strictly related to energy metabolism and could be an indirect marker of nutritional status in FHA patients, identifying earlier states of energy deficit.

The objective was to evaluate the best predictors of adverse perinatal outcome (APO) in foetuses examined up to 34 weeks and delivered by spontaneous or induced labour. This was a retrospective study of 129 pregnancies that underwent an ultrasound Doppler examination at 23-34 weeks and entered into labour within 30 days. Cerebroplacental ratio (CPR) and mean uterine artery pulsatility index (mUtA PI) were converted into multiples of the median (MoM) and estimated foetal weight (EFW) into centiles to adjust for gestational age (GA). Sonographic and clinical parameters were evaluated using logistic regression analysis.The multivariable model for the prediction of APO presented a notable accuracy: Detection rate (DR) was 39.5% for a false positive rate (FPR) of 5% and 56.8% for a FPR of 10%, AUC 0.82

Background Polycystic ovary syndrome (PCOS) is a low-grade inflammatory disease characterized by anovulation and hyperandrogenism, associated with insulin-resistance. The aim of our study was to investigate the effects of a treatment with alpha-lipoic acid on clinical, endocrine and metabolic features of women affected by PCOS. Methods In this pilot cohort study, 60 women (30 hyperinsulinemic and 30 normoinsulinemic patients; age 15-34 years) were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months treatment with alpha-lipoic acid 800 mg/daily. Investigations were performed during the early follicular phase of the menstrual cycles (spontaneous or progestin-induced cycles): after fasting overnight for 10-12 h, blood samples were collected for hormonal and metabolic assays and oral glucose tolerance test and pelvic ultrasound were performed. Total Antioxidant Capacity was expressed as LAG time. Results The treatment was able to increase the number of menstrual cycles during the 6 months considered in all patients and to reduce BMI in the normoinsulinemic population. In hyperinsulinemic patients we observed a statistically significant reduction in AUC-I as well as an increase of total antioxidant capacity. Conclusions The relevant results in restoring menstrual cyclicity in both groups, in addition to the antioxidant effect, confirm that hyperinsulinemia influences only the metabolic response to the treatment, without predict the ovarian function. Even if alpha-lipoic acid mechanisms of action is not clear and further studies are needed to confirm these results, it could be considered a valid therapeutic alternative to traditional drugs, without side effects as reported.

To investigate the possible role of melatonin on human luteal cell function. Corpora lutea were obtained from normally menstruating women (25–38 years old) in the midluteal phase (days 5–6 from ovulation) at the time of surgery for non-endocrine gynecologic diseases. The protocol was approved by the institutional review board of Universita Cattolica del Sacro Cuore in Rome and all patients provided written informed consent. The corpora lutea were dated on the basis of the presumptive day of ovulation (day 0) , determined by urinary luteinizing hormone (LH) peak, ultrasound detection of corpus luteum or disappearance of the dominant follicle, and a rise in the plasma P concentration. ELISA or EIA kit and immunohistochemistry were performed. Melatonin was able to increase progesterone release and to influence the balance between luteotrophic and luteolityc factors. In addition, melatonin expression and MT2 receptor were detected, confirming the direct action of this indoleamine on CL. Melatonin may play an intriguing role in direct regulation of CL function and in establishing and maintaining of initial pregnancy. In conclusion, melatonin could become a relevant medication for improving ovarian and luteal function and in the early stages of pregnancy, opening new opportunities for the management of several ovarian-luteal and pregnancy diseases.

Objectives: Small-for-gestational-age fetuses (SGA) are at high risk of intrapartum fetal compromise requiring operative delivery. In a recent study, we developed a model using a combination of thr...

Objective: The aim of this work was to compare the accuracy of the cerebroplacental ratio (CPR), Intergrowth 21st standards (IG21), customized growth (CG), and local population references (LPR) in the prediction of intrapartum fetal compromise (IFC). Methods: This was a prospective study of 714 fetuses that underwent an ultrasound examination at 34–41 weeks and were delivered within a 2-week interval. The CPR was converted into multiples of the median and the estimated fetal weight (EFW) transformed into CG, IG21, and LPR centiles. IFC was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean section, 5-min Apgar score, and admission to pediatric care units. The accuracies of the CPR and the EFW centiles for the prediction of IFC were evaluated alone and in combination with other gestational characteristics using univariate and multivariate analysis. Results: Individually, the CPR was the parameter that best predicted the existence of IFC (AUC = 0.66). The multivariate analysis showed that the best prediction was again achieved with the CPR, alone or in combination with any of the EFW centiles (AUC = 0.74). No significant differences were seen between the different centile methods. Conclusion: The best prediction of IFC is obtained with CPR. Evaluation of CPR should be encouraged in term and late-preterm fetuses.

The aim of the study was to investigate the influence of ethnicity and cerebroplacental ratio (CPR) on the birth weight (BW) of first generation Indo-Pakistan immigrants' newborns.This was a retrospective study in a mixed population of 620 term Caucasian and Indo-Pakistan pregnancies, evaluated in two reference hospitals of Spain and Italy. All fetuses underwent a scan and Doppler examination within two weeks of delivery. The influence of fetal gender, ethnicity, GA at delivery, CPR, maternal age, height, weight and parity on BW was evaluated by multivariable regression analysis.Newborns of first generation Indo-Pakistan immigrants were smaller than local Caucasian newborns (mean BW mean= 3048 ± 435 g versus 3269 ± 437 g,The propensity to a lower BW, explained by placental dysfunction but not by maternal ethnicity is transmitted to newborns of first generation immigrants. Whatever are the factors implied they persist in the new residential setting.

Objective: The aim of this study was to investigate in the fetus the relationship between unexpected high middle cerebral artery peak systolic velocity (middle cerebral artery (MCA) peak sy...

To investigate a possible relation between fibulin-1 plasma levels and PCOS. ELISA quantitative determination of human fibulin-1. 50 women with PCOS and 40 control patients who attended the Unit of Human Reproductive Pathophysiology, Universita Cattolica del Sacro Cuore, Rome, were enrolled. Ultrasonographic pelvic examinations, hormonal profile assays, oral tolerance test OGTT, lipid profile and ELISA quantitative determination of human fibulin-1 were performed. Fibulin-1 levels were found to be statistically significantly higher in PCOS patients than in matched control women. No statistically significant positive correlation was found between fibulin-1 and AUCi, HOMA-IR, total cholesterol, LDL, AMH, androstenedione and FAI, whereas a statistically significant positive correlation was found between fibulin-1 and 17OHP (p = 0.016) in the PCOS group. However, multivariable linear regression analysis showed that 17 OH P did not independently predict fibulin-1 levels (p = 0.089). Our data could contribute to explain the hypothesized increased cardiovascular risk and vascular damage in patients with PCOS. A better understanding of the cellular and molecular mechanisms involved in cardiometabolic disorders associated with PCOS is mandatory to identify new therapeutic strategies to eventually prevent the progression of cardiovascular diseases in these patients.

Objective Women affected by PCOS and psoriasis are more likely to have insulin-resistance, hyperinsulinemia, reduced HDL cholesterol levels and a more severe degree of skin disease than those with psoriasis alone. The mechanism underlying this association between PCOS and psoriasis is currently unknown. The aim of the present study was to evaluate the features of psoriasis and the psoriasis severity scores in the different PCOS phenotypes and in age and body mass index (BMI)-matched psoriatic control patients. Study design A cross-sectional study was performed on 150 psoriatic patients: 94 PCOS and 56 age- and BMI-matched controls. PCOS patients were diagnosed and divided into four phenotypes according to Rotterdam criteria: A – patients with complete phenotype with hyperandrogenism (H) plus oligoamenorrhea (O) plus polycystic ovary (PCO) on ultrasound examination; B – patients with H plus O (without PCO); C – patients with H plus PCO (ovulatory phenotype); D – patients with O plus PCO (without H). The patient's Psoriasis Area and Severity Index (PASI) as well as the Physician's Global Assessment (PGA) were calculated. A PASI score ≥10 was correlated with common indicator of severe disease. A PGA ≥4 was considered as a condition of moderate to severe disease. Results Among the four phenotypes investigated, the group with complete phenotype (H plus O plus PCO) had a higher prevalence of patients with patient's PASI ≥10 compared to controls (Odds Ratio (OR) 4.71, 95% confidence intervals (CI) 1.59–13.95). The group with O plus PCO had a higher prevalence of patients with PGA ≥4 compared to controls (OR 26.79, 95% CI 3.40–211.02) while the ovulatory group had a lower prevalence of patients with PGA ≥4 (OR 0.06, 95% CI 0.01–0.51). Conclusions The ovulatory phenotype displays a milder psoriasis form than other phenotypes while the phenotypes with oligoamenorrhea presented higher severity scores of disease than other phenotypes and control group.

The aim of our study was to investigate the effects of a combined treatment with alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and metabolic features of women affected by polycystic ovary syndrome (PCOS). In this pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months combined treatment with ALA and MYO daily. Studied patients experienced a significant increase in the number of cycles in six months (p < 0.01). The free androgen index (FAI), the mean androstenedione and DHEAS levels significantly decreased after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A significant improvement in mean Ferriman-Gallwey (F-G) score (p < 0.01) and a significant reduction of BMI (p < 0.01) were also observed. A significant reduction of AMH levels, ovarian volume and total antral follicular count were observed in our studied women (p< 0.05). No significant changes occurred in gluco-insulinaemic and lipid parameters after treatment. The combined treatment of ALA and MYO is able to restore the menstrual pattern and to improve the hormonal milieu of PCOS women, even in the absence of apparent changes in insulin metabolism.

The objective of the study was to investigate the effects of 6 months of melatonin administration on clinical, endocrine, and metabolic features of women affected by polycystic ovary syndrome (PCOS). This is a prospective cohort study including 40 normal-weight women with PCOS between January and September 2016, enrolled in an academic research environment. Ultrasonographic pelvic examinations, hirsutism score evaluation, hormonal profile assays, oral glucose tolerance test, and lipid profile at baseline and after 6 months of melatonin administration were performed. Melatonin treatment significantly decreased androgens levels (free androgen index: P < .05; testosterone: P < .01; 17 hydroxyprogesterone: P < .01). Follicle-stimulating hormone levels significantly raised ( P < .01), and anti-Mullerian hormone serum levels significantly dropped after 6 months of melatonin treatment ( P < .01). No significant changes occurred in glucoinsulinemic and lipid parameters after treatment except a significant decrease of low-density lipoprotein cholesterol. Almost 95% of participants experienced an amelioration of menstrual cycles. Until now, only few data have been published about the role of melatonin in women with PCOS. This is the first study focused on the effects of exogenous oral melatonin administration on the clinical, endocrine, and metabolic characteristics of patients with PCOS. After 6 months of treatment, melatonin seems to improve menstrual irregularities and biochemical hyperandrogenism in women with PCOS through a direct, insulin-independent effect on the ovary. Based on our results, melatonin could be considered a potential future therapeutic agent for women affected by PCOS.

Objective To evaluate the influence of phthalates on human luteal cell function. Design Laboratory study. Setting University hospital. Patient(s) Twenty-three normally menstruating patients in the midluteal phase. Intervention(s) Human luteal cells isolated from corpora lutea for primary cultures. Main Outcome Measure(s) Progesterone (P4) and prostaglandin release assayed by enzyme immunoassay, vascular endothelial growth factor (VEGF) secretion by enzyme-linked immunosorbent assay (ELISA), and VEGF mRNA expression by real-time polymerase chain reaction. Result(s) We investigated the effect of di(2-ethylhexyl)phthalate (DEHP), di-n-butyl phthalate (DBP), and butyl benzyl phthalate (BBP) on basal and hCG-induced progesterone (P4) release, as well as DEHP effect on the balance between prostaglandin (PG) E2, vascular endothelial growth factor (VEGF)-luteotrophic factors, and the luteolitic PGF2α in isolated human steroidogenc cells. Phthalates influence on VEGF expression has been also evaluated. DEHP, DBP, and BBP were able to reduce both basal and hCG-stimulated P4 as well as PGE2 release. PGF2α release was reduced after DEHP incubation. VEGF protein release was decreased by the incubation with the tested phthalates. VEGF mRNA expression was not affected by DEHP, DBP, and BBP. As expected, both hCG and cobalt chloride were able to induce P4 release and VEGF release and mRNA expression in human luteal cells respectively. Conclusion(s) The results show the ability of phthalates to affect luteal steroidogenesis as well as the balance between luteotrophic and luteolytic factors suggesting an interference of phthalates in human luteal function. These data may contribute to clarify the classically known impaired reproductive health observed after phthalates exposure.

Objective To define the prevalence and the features of polycystic ovary syndrome (PCOS) in patients with psoriasis. To our knowledge, the association between PCOS and psoriasis has not been explored in previous studies. Psoriasis is linked with metabolic syndrome, insulin resistance, and non-alcoholic fatty liver disease, which are features often associated with PCOS. Design A cross-sectional analysis was performed between January 2010 and April 2012. Setting Unit of human reproductive pathophysiology, Catholic University Hospital. Patient(s) We prospectively analyzed 51 patients with psoriasis and 102 healthy age- and body mass index (BMI)-matched controls. Intervention(s) None. Main Outcome Measure(s) The prevalence and characteristics of PCOS women of reproductive age with chronic plaque psoriasis. Result(s) The prevalence of PCOS was greater in patients with psoriasis than in matched control subjects (47.05% and 11.76%, respectively; odds ratio, 6.66; 95% confidence interval 2.95–15.07). Among the women with psoriasis, the prevalence of Psoriasis Area and Severity Index ≥10 was higher in patients with PCOS than in subjects without PCOS (odds ratio, 3.5; 95% confidence interval 1.04–11.72). Conclusion(s) The prevalence of PCOS in women with psoriasis is remarkably greater than in age- and BMI-matched control women.

Objective To evaluate anti-Mullerian hormone (AMH) concentrations and antral follicle counts (AFCs) in the prediction of pregnancy outcomes after controlled ovarian stimulation among women undergoing intrauterine insemination. Methods A retrospective study included women with unexplained infertility aged 41 years or younger who attended a fertility clinic in Italy between December 2009 and May 2014. Ovarian stimulation was achieved with recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin. Receiver operating characteristic curves were generated to predict ongoing pregnancy. The primary outcome was the association between AMH/AFC and ongoing pregnancy, and was assessed by logistic regression. Results Overall, 276 women were included, of whom 43 (15.6%) achieved ongoing pregnancy. Multivariate analysis showed that women with a serum day-3 concentration of AMH higher than 2.3 ng/mL were more likely to have ongoing pregnancy than were those with a concentration lower than 2.3 ng/mL (odds ratio 5.84, 95% confidence interval 2.38–14.31; P Conclusion AMH should be used to predict the pregnancy outcome of intrauterine insemination.

Objective Tubal patency in women with endometriosis has traditionally been evaluated by laparoscopy. The aim of this study was to investigate the accuracy of hysterosalpingo-contrast-sonography (HyCoSy) in the assessment of tubal patency in these women. Study design A retrospective study was conducted at Physiopathology of Human Reproduction Unit. Infertile women who underwent HyCoSy and then a laparoscopy (dye test) within 6 months from the HyCoSy were included. Tubal patency was assessed by HyCoSy and the findings were compared with the results of laparoscopy, which was considered the gold standard for assessment of tubal patency. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) and positive and negative likelihood ratios (Lh+, Lh−) were calculated including the 95% confidence interval (CI). Results A total of 1452 women underwent HyCoSy and 126 of them received a laparoscopy within 6 months from the HyCoSy. Of the 126 women, 42 (33.3%) had a diagnosis of pelvic endometriosis and 84 (66.7%) had no endometriosis. In the endometriosis population, HyCoSy showed a sensitivity, specificity, PPV, NPV, Lh+ and Lh− of 85% (95% CI 62–96), 93% (95% CI 82–97), 81% (95% CI 58–94), 94% (95% CI 84–98), 12.6 (95% CI 4.8–33) and 0.15 (95% CI 0.05–0.4) respectively. In the non-endometriosis group, HyCoSy showed a sensitivity, specificity, PPV, NPV, LR+ and LR− of 85% (95% CI 65–95), 93% (95% CI 87–96), 71% (95% CI 53–85), 97% (95% CI 92–99), 13.2 (95% CI 6.9–25) and 0.15 (95% CI 0.06–0.3) respectively. The diagnostic accuracy of HyCoSy was 91% in the endometriosis group and 92% in the non-endometriosis patients. Conclusions HyCoSy showed high accuracy in evaluating tubal patency in infertile non-endometriosis women and in those affected by endometriosis.

studyquestion: Is the treatment with recombinant FSH (rFSH) plus recombinant LH (rLH) more effective than highly purified (HP)-hMG in terms of ongoing pregnancy rate (PR) in women ≥35 years of age undergoing intrauterine insemination (IUI) cycles? summaryanswer: The ongoing PR was not significantly different in women treated with rFSH plus rLH or with HP-hMG. whatisknownalready: Although previous studies have shown beneficial effects of the addition of LH activity to FSH, in terms of PR in patients aged over 34 years having ovulation induction, no studies have compared two different gonadotrophin preparations containing LH activity in women ≥35 years of age in IUI cycles. studydesign,size,duration: A single-centre RCT was performed between May 2012 and September 2013 with 579 women ≥35 years of age undergoing IUI cycles. The patients were randomly assigned to one of the two groups, rFSH in combination with rLH group or HPhMG (Meropur) group, by giving them a code number from a computer generated randomization list, in order of enrolment. The randomization visit took place on the first day of ovarian stimulation. participants/materials,setting,methods: Five hundred and seventy-nine patients with unexplained infertility or mild male factor undergoing IUI cycles were recruited in a university hospital setting. All women were enrolled in this study only for one cycle of treatment. Five hundred and seventy-nine cycles were included in the final analysis. Two hundred and ninety patients were treated with rFSH in combination with rLH and 289 patients were treated with HP-hMG. The ovarian stimulation cycle started on the third day of the menstrual cycle and the starting gonadotrophin doses used were 150 IU/day of rFSH plus 150 IU/day of rLH or 150 IU/day of HP-hMG. The drug dose was adjusted according to the individual follicular response. A single IUI per cycle was performed 34 –36 h after hCG injection. mainresultsandtheroleofchance: The main outcome measures were ongoing PR and number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS). Ongoing pregnancy rates were 48/290 (17.3%) in the recombinant group versus 35/289 (12.2%) in the HP-hMG group [(odds ratio (OR) 1.50, 95% CI 0.94 –2.41, P ¼ 0.09]. The number of interrupted cycles for high risk of OHSS was 13/290 (4.5%) in the rFSH plus rLH group and 2/289 (0.7%) in the HP-hMG group (OR 6.73, 95% CI 1.51 –30.12, P ¼ 0.013). limitations, reasons for caution: One of the limitations of this study was the early closure and the ongoing PR could be overestimated. Both patient and gynaecologist were informed of the assigned treatment. wider implications of the findings: Our results demonstrated the lack of differences in terms of ongoing PR between recombinant product and HP-hMG, in women ≥35 years undergoing controlled ovarian stimulation for IUI cycles. HP-hMG was safer than recombinant gonadotrophin concerning the risk of OHSS.

Objective To develop and validate a specific simple measure of insulin sensitivity using oral glucose tolerance test (OGTT) values for lean polycystic ovary syndrome (PCOS) women. Design Retrospective study. Setting Gynecologic Outpatient Clinic of University Hospital, affiliated with Unit of Gynecologic Endocrinology. Patient(s) Totals of 201 lean and 198 overweight/obese (ov-ob) nondiabetic PCOS patients were retrospectively selected. Intervention(s) None. Main Outcome Measure(s) All patients underwent OGTT, euglycemic-hyperinsulinemic clamp, and androgenic and biochemical assays. The predictive performance of each insulin resistance (IR) index was analyzed with the use of receiver operating characteristic (ROC) curves. Result(s) Higher correlation coefficients with clamp studies were obtained with the Belfiore Area ( R S = 0.579) and the homeostasis-model assessment (HOMA)-M 120 ( R S = −0.576) in lean PCOS patients and with the Sib ( R S = 0.697) in ov-ob PCOS patients. The best predictive index of IR in lean PCOS was a HOMA-M 120 value of ≥12.8 or more (area under the ROC curve [AUC] 92.4%). In the ov-ob PCOS population, the best predictive performance was obtained by a Sib of ≤10.2 or less (AUC 85.7%). Conclusion(s) IR should be assessed in all PCOS women, both lean and ov-ob subjects. The HOMA-M 120 resulted as a very simple tool, validated specifically for the lean PCOS woman whose cardiometabolic impairment is more frequently misunderstood.

Endocrine disruptors are well known to impair fertility. The aim of the present study was to investigate the effects of bisphenol A (BPA) and nonylphenol (p-NP) on human luteal function in vitro. In particular, in luteal cells isolated from 21 human corpora lutea progesterone, prostaglandin (PG) F2α, PGE2 and vascular endothelial growth factor (VEGF) release, as well as VEGF expression were evaluated. BPA and p-NP negatively affected both luteal steroidogenesis and luteotrophic/ luteolytic factors balance, without influencing VEGF mRNA expression. Actually, BPA and p-NP impaired human luteal cells function in vitro, underlining the already suggested correlation between phenols and reproductive failure.

To evaluate the long-term effects of drospirenone (DRSP)/ethinylestradiol (EE) alone, metformin alone, and DRSP/EE-metformin on CD4(+)CD28(null) T lymphocytes frequency, a cardiovascular risk marker, in patients with hyperinsulinemic polycystic ovary syndrome (PCOS).Randomized clinical trial.Ninety three patients with hyperinsulinemic PCOS were age matched and body mass index matched and randomized to receive a 6 months daily treatment with DRSP (3 mg)/EE (0.03 mg), or metformin (1500 mg), or DRSP/EE combined with metformin.CD4(+)CD28(null) T-cell frequencies.The DRSP/EE and metformin groups did not show any significant change in the CD4(+)CD28(null) frequency compared to the baseline. Interestingly, a statistically significant decrease in CD4(+)CD28(null) frequency occurred after 6 months of DRSP/EE-metformin (median 3-1.5; P.01). Of note, this statistically significant association was confirmed after adjusting for baseline values in DRSP/EE-metformin group by analysis of covariance (P.05).In women with hyperinsulinemic PCOS, combined therapy with DRSP/EE and metformin may reduce cardiovascular risk.

Objective To study the frequency of CD4 + CD28 null T cells, which are aggressive T lymphocytes associated with recurrent coronary instability and type 2 diabetes mellitus, in different polycystic ovary syndrome (PCOS) phenotypes and in age- and body mass index–matched healthy women. Design Retrospective cohort observational study. Setting Unit of human reproductive pathophysiology, university hospital. Patient(s) A total of 167 PCOS patients and 102 control subjects. Intervention(s) None. Main Outcome Measure(s) CD4 + CD28 null T cell frequency, high-sensitive C-reactive protein levels, and other glucose-metabolic parameters. Result(s) CD4 + CD28 null frequency was significantly higher in all PCOS groups than in control subjects. CD4 + CD28 null frequency was significantly higher in nonhyperandrogenic phenotype (5.7%, range 3.2–7.1) than in phenotypes with hyperandrogenism (H) + oligoamenorrhea (O) + polycystic ovary (PCO) (3.5%, range 1–5.8), H + O (3%, range 1.8–4.7), and H + PCO (2.63%, range 1.2–4.1). The relative risk of non-H phenotype for PCOS women in the highest quartile for CD4 + CD28 null frequency compared with PCOS women with the lowest quartile was 3.2 (95% confidence interval 1.9–5.8). Conclusion(s) Cardiovascular risk evaluation should be performed in all PCOS phenotypes. In particular, we demonstrated that the non-H phenotype has potentially increased cardiovascular risk in terms of CD4 + CD28 null frequency.

Objective To evaluate whether unacylated ghrelin and obestatin were able to influence human luteal cell function. The effect of these two ghrelin-related peptides on progesterone (P4), prostaglandin (PG) F 2α , PGE 2 , and vascular endothelial growth factor (VEGF) release and on VEGF expression in isolated human steroidogenic cells has been investigated. Design Prospective laboratory study. Setting University hospital. Patient(s) Corpora lutea were obtained from 23 normally menstruating patients in the midluteal phase of the menstrual cycle. Intervention(s) Human luteal cells were isolated from corpora lutea, and primary cultures were established. Main Outcome Measure(s) P4 and PGs release was assayed by enzyme immunoassay, VEGF secretion by ELISA, and VEGF mRNA expression by real-time polymerase chain reaction. Result(s) P4 and VEGF release were significantly reduced by both unacylated ghrelin and obestatin. Moreover, the highest concentration of obestatin was able to reduce the release of PGE 2 and PGF 2α . VEGF mRNA expression was not affected by the incubation with any of these ghrelin-related peptides. As expected, CoCl 2 was able to induce VEGF release and mRNA expression in luteal cells. Conclusion(s) Our results suggest that, similar to ghrelin, both unacylated ghrelin and obestatin might play a role in regulating the luteal cell function that affects both luteal steroidogenesis and luteotrophic/luteolytic imbalance. These results further underline the pivotal correlation between the ghrelin system and reproduction.