Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), the most common reproductive endocrine disorder of premenopausal women, is strongly associated with hyperinsulinemia and type 2 diabetes mellitus (T2DM). Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population. A total of 183 PCOS patients and 148 healthy controls participated. All participants were Greeks. Blood was taken before hormonal therapy. PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants. The T allele of the TCF7L2 rs7903146 variant was found to be marginally over-represented in Greek patients with PCOS. There was no association between KCNJ11 E23K polymorphism and PCOS in the present study. In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants. These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.

Serum adiponectin during pregnancy and postpartum in women with gestational diabetes and normal controls.

AIMS: To investigate changes in serum adiponectin during pregnancy and postpartum and assess its relationship with insulin resistance as measured by homeostasis model assessment (HOMA-IR). METHODS: Twenty-two normal pregnant women were compared with 22 women diagnosed with gestational diabetes mellitus (GDM). Serum adiponectin levels were measured at the time of the glucose challenge test as well as in the immediate postpartum period and the correlation of adiponectin to HOMA-IR was performed. RESULTS: Adiponectin was significantly lower in women with GDM than in controls during pregnancy (5381 vs. 8449 ng/dl, p = 0.004), as well as postpartum (3278 vs. 6958 ng/ml, p = 0.002). A significant reduction in adiponectin (3278 vs. 5381 ng/ml, p = 0.002) was observed postpartum in GDM women but not in controls. Using a lower cut-off value of 5253 ng/ml, maternal adiponectin could exclude GDM with a sensitivity of 86.4% and a specificity of 59.1% (area under the curve = 0.752, standard error = 0.77, 95% confidence interval 0.601-0.903, p = 0.004). Adiponectin levels during pregnancy were negatively correlated with HOMA-IR (r = -0.375, p = 0.012). CONCLUSION: GDM is associated with decreased serum adiponectin levels both in pregnancy as well as postpartum. Adiponectin is negatively correlated to HOMA-IR. A reduction in maternal adiponectin after delivery indicates a significant placental contribution to adiponectin production.

Human papilloma virus: diagnostic, treatment and preventive issues.

Human Papilloma Virus (HPV), a sexually transmitted virus, is usually found in the genital tract and causes various lesions at the mucosae of both men and women. It is considered as a causative factor of cervical cancer even if all women infected by HPV will not develop the disease. This article reviews diagnostic aspects and therapeutic alternatives for the treatment of HPV infected females, as well as aspects concerning the prophylactic HPV vaccines.

Effect of sperm treatment with exogenous platelet-activating factor on the outcome of intrauterine insemination.

OBJECTIVE: To evaluate the effect of sperm treatment with exogenous platelet-activating factor (PAF) on IUI clinical pregnancy rate. DESIGN: Prospective randomized study. SETTING: Assisted Reproduction Unit, 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece. SUBJECT(S): Fifty-two couples with unexplained infertility, candidates for IUI. INTERVENTION(S): Sperm treatment with an exogenous mixture of PAF (final concentration, 10(-7) mol/L) in sperm-washing medium, direct swim-up technique of sperm preparation, a maximum of six IUI cycles per couple with or without PAF treatment. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (pregnancies confirmed by ultrasonography per hundred cycles). RESULT(S): The overall clinical pregnancy rate after a maximum of six IUI cycles was significantly higher when sperm was treated with PAF compared with the rate after the direct swim-up technique (23.07% vs. 7.92%). CONCLUSION(S): Treatment of sperm with exogenous PAF might improve the clinical outcome of IUI in cases of unexplained infertility.

Full-term pregnancies after multiple hepatobiliary operations for choledochal cyst: a case report.

Choledochal cysts are rare congenital cystic dilatations of the biliary tree. Choledochal cysts in pregnancy are a rare entity and represent a diagnostic and therapeutic challenge. The authors present a case of two full-term pregnancies in a woman who underwent multiple hepatobiliary operations for a choledochal cyst. The patient had two major problems: a type IV(a) choledochal cyst with atrophy of the left side of the liver and a congenitally dilated pancreatic duct in the head of the gland. She underwent a drainage surgical procedure using a Roux loop of jejunum and a revision surgery in which complete excision of the cyst and hepaticojejunostomy was performed. The surgical management was completed by a left lateral hepatic segmentectomy. During her first pregnancy, she experienced an episode of cholangitis, most probably due to the remaining congenitally dilated pancreatic duct. In succeeding years, the patient presented with recurrent pancreatitis and finally she underwent a Whipple operation. After that, the patient had a second pregnancy without any complications from the biliary tract system. Although choledochal cysts rarely occur in pregnancy, clinicians should be aware of this condition, as delayed or inappropriate therapy may be catastrophic for both the mother and the fetus.

Treatment of sperm with platelet-activating factor does not improve intrauterine insemination outcome in unselected cases of mild male factor infertility: a prospective double-blind randomized crossover study.

OBJECTIVES: To evaluate the effect of sperm treatment with exogenous platelet-activating factor (PAF) on intrauterine insemination (IUI) clinical pregnancy rate in cases of mild male factor infertility. PAF is a phospholipid mediator, which is present in human sperm. METHODS: The study was performed in the Assisted Reproduction Unit of the 2nd Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece, and included 92 couples who presented with mild male factor infertility-all candidates for IUI. A maximum of 4 IUI cycles per couple with or without exogenous PAF treatment were performed and the main outcome measure was the clinical pregnancy rate (pregnancies confirmed by ultrasonography per 100 cycles). RESULTS: The overall clinical pregnancy rate after a maximum of 4 IUI cycles was comparable in cases with and without sperm treatment with PAF (12.24% vs 11.11%). Addition or exclusion of PAF sperm treatment in the same patients did not significantly alter the outcome. CONCLUSIONS: The generalized use of exogenous PAF for the preparation of sperm in unselected cases of mild male infertility does not improve the clinical outcome of IUI.

CSF and plasma cytokines at delivery and postpartum mood disturbances.

BACKGROUND: Immune activation has been shown to be involved in the pathophysiology of anxiety states and major depression and pregnancy is associated with a characteristic immune activation to sustain the fetus. Despite the possibility of a relation between immune parameters and postpartum mood disturbance, few studies have explored this association. Further, no study to-date has examined CSF. METHODS: Fifty-six Greek parturients were recruited and a detailed medical and obstetric history was recorded. All of them completed the Postpartum Blues Questionnaire (on admission and on days 1-4 postpartum) and the Edinburgh Postnatal Depression Scale (at first and sixth week postpartum). At delivery, a blood sample and a CSF sample while puncturing for epidural analgesia were taken from 33 participants; blood samples only were obtained from the rest of the 23 parturients. TNF-a and IL-6 were quantified with an ELISA assay. RESULTS: A multiple regression analysis of psychometric scores depending on cytokine levels revealed that cytokine levels were positively associated with depressive mood during the first four days postpartum (p=0.035 for CSF IL-6, p=0.025 for CSF TnF-a, p=0.023 for serum TnF-a) and also at sixth week postpartum (p=0.012 for CSF IL-6, p=0.072 for CSF TnF-a). Pregnancy duration had an adverse association to psychometric scores. CONCLUSIONS: It is suggested that immune mechanisms may play a role in the etiopathology of postpartum depressive mood shifts. The role of a "rebound" reaction of the maternal immune system postnatal should be further investigated.

Randomized controlled trial comparing superovulation with letrozole versus recombinant follicle-stimulating hormone combined with intrauterine insemination for couples with unexplained infertility who had failed clomiphene citrate stimulation and intrauterine insemination.

OBJECTIVE: To compare the efficacy of letrozole to recombinant FSH for ovarian stimulation combined with IUI in a group of patients that had failed to conceive after clomiphene citrate (CC) and IUI. DESIGN: Prospective randomized trial with human subjects. SETTING: University-based fertility center. PATIENT(S): Fifty couples with unexplained infertility that failed to conceive after three cycles of CC combined to IUI. INTERVENTION(S): Couples were randomized to undergo superovulation either with letrozole or with recombinant FSH combined to IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy per cycle of treatment and clinical pregnancy per couple. RESULT(S): Pregnancy rate (PR) per cycle was 8.9% in the letrozole group as compared with 14% in the gonadotropin IUI group. This resulted in a cumulative PR per couple of 24% versus 36% and a take home baby rate of 20% versus 28%. Endometrial thickness was significantly lower in the letrozole group (7.1 +/- 2.3 vs 8.6 +/- 1.8). CONCLUSION(S): Ovarian stimulation with letrozole is associated with acceptable PRs compared with gonadotropin with significant less cost, risks, and patient inconvenience.

Parity is associated with lower cervical E-cadherin expression in postmenopausal women.

AIM: Epithelial cadherin (E-cadherin), a transmembrane glycoprotein involved in calcium-dependent homophilic cell-cell adhesion, is expressed aberrantly during cervical carcinogenesis. E-cadherin expression and putatively implicated predictors in healthy women remain a rather under-investigated area. The objective of this study is to evaluate the possible associations between E-cadherin expression and reproductive/lifestyle factors in cervical epithelial cells from postmenopausal women. METHODS: A total of 105 healthy postmenopausal women (aged 45-68 years old) attending a university menopause clinic were enrolled in this cross-sectional study. Pap smears were derived and E-cadherin immunostaining was evaluated in squamous, glandular and squamous metaplastic cells, using a semi-quantitative method (rating scale: 0-3). Reproductive and lifestyle factors were obtained from patients' chart review. RESULTS: In squamous cells, women with a history of 0-1 deliveries presented with a higher score vs women with 2-4 deliveries (P = 0.003). Social drinkers and women drinking alcohol daily exhibited a higher E-cadherin immunostaining score in squamous cells vs non-drinkers (0.96 +/- 0.72 vs 0.56 +/- 0.65, P = 0.004). A higher dietary calcium intake was marginally correlated with a lower staining score in squamous cells (0.94 +/- 0.78 for low, 0.71 +/- 0.70 for average, 0.45 +/- 0.52 for high consumption, P = 0.073). CONCLUSIONS: E-cadherin expression seems to be associated with reproductive history and lifestyle habits in squamous cervical cells from healthy postmenopausal women. E-cadherin might participate in the molecular mechanisms underlying the role of parity as a risk factor for cervical cancer.

Association between serum tumor necrosis factor-alpha and corticotropin-releasing hormone levels in women with preterm labor.

AIM: To evaluate the association of serum corticotropin-releasing hormone (CRH) and tumor necrosis factor-alpha (TNF-alpha) in preterm labor. METHODS: Forty-nine primigravidas with a singleton viable pregnancy between 28 and 34 weeks of gestation were studied. They were divided into two groups. Group A consisted of 30 pregnant women (mean gestational age: 30.6 week) who presented with preterm labor and group B consisted of 19 pregnant women (mean gestational age: 29.8 week) with normal pregnancies. RESULTS: Women of group A had significantly higher serum CRH levels compared to those of group B (P < 0.01). Similarly, serum TNF-alpha levels were significantly higher in women of group A when compared to women of group B (7.8 +/- 3.72 pg/mL and 5.1 +/- 3.72 pg/mL, respectively). Furthermore, a positive correlation was found between serum CRH and TNF-alpha levels in both groups, which was stronger in women of group A. CONCLUSIONS: Our findings suggest that the increased levels of TNF-alpha and CRH found in pregnant women presenting with preterm labor may be involved in the pathophysiological mechanism of the latter. Furthermore, a positive interaction may exist between TNF-alpha and placental CRH, which may lead to enhanced production of the second and, therefore, facilitate the onset of labor.