Francesca Sagnella

Effects of Nicotine on Human Luteal Cells In Vitro: A Possible Role on Reproductive Outcome for Smoking Women

Abstract We investigated the effect of nicotine and its methylated metabolite, N-methyl-nicotine (M-nicotine), on human luteal cells by measuring release of progesterone and prostaglandins (PGs) from cultured cells and by testing gene expression of vascular endothelial growth factor (VEGF), an angiogenic factor strictly involved in luteal pathophysiology. Primary cultures of human luteal cells were treated for 24 h with nicotine and M-nicotine (from 10−6 to 10−11 M) either alone or combined with hCG (25 ng/ml); progesterone and PGs were assayed in the culture medium. In another group of experiments, luteal cells were treated for 24 h with nicotine and M-nicotine (10−7 M) to perform reverse transcriptase-polymerase chain reaction on VEGF mRNA. Nicotine and M-nicotine negatively affected basal luteal steroidogenesis at all tested concentrations, but neither was able to affect hCG-induced progesterone release. Both substances were able to significantly increase PGF2α release from luteal cells, with a dose-related efficacy for M-nicotine. On the contrary, PGE2 release was significantly inhibited by both nicotine and its metabolite. Finally, nicotine was able to increase VEGF mRNA expression significantly, whereas M-nicotine was not. In conclusion, nicotine and M-nicotine can induce a sort of luteal insufficiency by inhibiting progesterone release, probably through modulation of the PG system.

Long-term metformin treatment is able to reduce the prevalence of metabolic syndrome and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome

Objective  The objective of this study is to determine the ability of metformin treatment in reducing the prevalence of metabolic syndrome (MS) and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome (PCOS).

The 312N variant of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) confers up to 2·7‐fold increased risk of polycystic ovary syndrome in a Sardinian population

Polycystic ovary syndrome (PCOS) is a frequent condition, affecting about 15% of women of reproductive age. Because of its familial occurrence, a multifactorial model of susceptibility, including both genetic and environmental factors, has been proposed. However, the identification of genetic factors has been elusive.

Ovarian volume and gluco-insulinaemic markers in the diagnosis of PCOS during adolescence

To evaluate the role of mean ovarian volume (MOV) in the diagnosis of polycystic ovary syndrome (PCOS) during adolescence, and its relationship with metabolic and endocrine parameters.

CD4+CD28null T lymphocytes are expanded in young women with polycystic ovary syndrome

Women affected by polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease. We demonstrated that women with PCOS showed an expansion of CD4(+)CD28(null) T cells, an aggressive population of T lymphocytes that has been recently associated with recurrent coronary instability and type 2 diabetes mellitus. This sheds new light on possible mechanisms responsible for the higher rate of cardiovascular disease among women with PCOS.

A prospective randomized noninferiority study comparing recombinant FSH and highly purified menotropin in intrauterine insemination cycles in couples with unexplained infertility and/or mild-moderate male factor.

OBJECTIVE To demonstrate the noninferiority of highly purified menotropin (HP-hMG) compared with recombinant FSH (rFSH) regarding clinical pregnancy rate (PR) in intrauterine insemination (IUI) cycles. DESIGN Prospective randomized noninferiority trial. SETTING Unit of physiopathology of human reproduction, university hospital. PATIENT(S) Five hundred twenty-three patients with unexplained infertility or mild male infertility undergoing controlled ovarian hyperstimulation for IUI. INTERVENTION(S) Patients were randomized for treatment with rFSH (262 patients) or HP-hMG (261 patients). Insemination was performed 34-36 hours after hCG injection. MAIN OUTCOME MEASURE(S) The primary outcome was clinical pregnancy rate (PR). The secondary outcome was the number of interrupted cycles for high risk of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. RESULT(S) The clinical PR was 19.7% (95% confidence interval [CI] 15.3%-25.1%) in the HP-hMG group and 21.4% (95% CI 16.9%-26.8%) in the rFSH group [absolute difference -1.7% (95% CI -8.6%-5.2%)]; therefore, the noninferiority was demonstrated. The number of interrupted cycles for OHSS risk and multiple pregnancy was significantLy higher in the rFSH group, 8.4% (95% CI 5.6%-12.4%) than in the HP-hMG group 1.2% (95% CI 0.4%-3.3%) [absolute difference -7.27% (95% CI -11.3 to -3.7)]. CONCLUSION(S) HP-hMG is not inferior compared with rFSH regarding clinical PR.

Low- and standard-estrogen dosage in oral therapy: dose-dependent effects on insulin and lipid metabolism in healthy postmenopausal women

Objective To evaluate the influences of different doses of daily oral unopposed 17β-estradiol compared with placebo, both on glucose tolerance and lipid metabolism in healthy postmenopausal women. Patients and methods Forty-eight normoinsulinemic postmenopausal women were enrolled in the study. Patients were assigned to receive randomly 1 mg (group A) or 2 mg (group B) of oral micronized estradiol therapy daily or to the placebo (group C), for 12 weeks. Results The low-dose estradiol treatment determined an improvement of the peripheral insulin sensitivity, made evident by a significant increase both in the metabolic index and oral glucose insulin sensitivity index (p < 0.01 and p < 0.05, respectively) as well as a decrease in the homeostasis model assessment-estimated insulin resistance (p < 0.01). Conversely, in the standard-dose group, the metabolic index significantly decreased (p < 0.05), showing a slight deterioration in insulin sensitivity. For lipid metabolism, the 1 mg dose showed a neutral effect, while 2 mg had a beneficial effect on low density lipoprotein cholesterol, but caused an increase in triglycerides (p < 0.01 and p < 0.05, respectively). Conclusions The oral low dose of unopposed estradiol therapy had a favorable effect on glycoinsulinemic metabolism in healthy postmenopausal women; however, the standard dose caused a slight but significant deterioration in insulin sensitivity.

Could antispasmodic drug reduce pain during hysterosalpingo-contrast sonography (HyCoSy) in infertile patients? A randomized double-blind clinical trial

To assess the effectiveness of an antispasmodic drug, hyoscine‐N‐butylbromide, in reducing pain during hysterosalpingo‐contrast sonography (HyCoSy).

Assessment of insulin resistance in lean women with polycystic ovary syndrome.

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 (RS=0.579) and the homeostasis-model assessment (HOMA)-M120 (RS=-0.576) in lean PCOS patients and with the Sib (RS=0.697) in ov-ob PCOS patients. The best predictive index of IR in lean PCOS was a HOMA-M120 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-M120 resulted as a very simple tool, validated specifically for the lean PCOS woman whose cardiometabolic impairment is more frequently misunderstood.

Effects of Drospirenone–Ethinylestradiol and/or Metformin on CD4+CD28null T Lymphocytes Frequency in Women With Hyperinsulinemia Having Polycystic Ovary Syndrome: A Randomized Clinical Trial

Objective: To evaluate the long-term effects of drospirenone (DRSP)/ethinylestradiol (EE) alone, metformin alone, and DRSP/EE-metformin on CD4+CD28null T lymphocytes frequency, a cardiovascular risk marker, in patients with hyperinsulinemic polycystic ovary syndrome (PCOS). Design: Randomized clinical trial. Interventions: 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. Main Outcome Measures: CD4+CD28null T-cell frequencies. Results: The DRSP/EE and metformin groups did not show any significant change in the CD4+CD28null frequency compared to the baseline. Interestingly, a statistically significant decrease in CD4+CD28null 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). Conclusions: In women with hyperinsulinemic PCOS, combined therapy with DRSP/EE and metformin may reduce cardiovascular risk.