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Background: The phenotypic spectrum of PCOS has been broadened but the prevalence and clinical significance of PCOS phenotypes continue to challenge the scientific community., Objective: Analysis of the phenotypic spectrum of PCOS and determination of the association between metabolic, hormonal and new ultrasonographic criteria., Design: Clinical prospective study., Patients: Six hundred and thirty-four women with PCOS (18-35 years) and comparable body mass index (BMI), diagnosed by ESHRE/ASRM criteria, were categorized into two major groups of phenotypes: classic (NIH) and nonclassic (ESHRE/ASRM), and then subdivided into phenotypes with all possible combinations of diagnostic characteristics. One hundred and eight healthy women of reproductive age, matched for BMI, were recruited as the control group., Measurements: Ultrasonographic (ovarian follicle number and volume), hormonal and metabolic parameters., Results: Classic PCOS phenotype was more frequent (85.96%) than the nonclassic phenotype (14.04%). The patients were also classified according to the presence of biochemical (80.60%) or clinical hyperandrogenaemia (12.62%), and, in the newly introduced group, to absence of evidence of hyperandrogenaemia (6.78%). Subjects with classic PCOS with biochemical hyperandrogenaemia (74.76%) were more insulin resistant than controls. In women with PCOS, follicle number was positively related to both insulin resistance and biochemical hyperandrogenaemia. Additionally, women with PCOS had a 6.58-fold increased relative risk (RR) of > 12 follicles on intravaginal ultrasound and a 2.94-fold increased RR of ovarian volume > 10 cm(3) compared to controls., Conclusion: The most frequent PCOS phenotype is the subgroup with biochemical hyperandrogenaemia only within the classic phenotype, which is more insulin resistant than the control group. The follicle number, a newly introduced ultrasonographic marker, is related to both metabolic and hormonal features of PCOS.

Objective: To evaluate whether toremifene, a selective estrogen receptor modulator (SERM), has a beneficiary effect on all three main sperm parameters., Design: Prospective interventional clinical study., Setting: University hospital., Patient(s): One-hundred subfertile men with idiopathic oligozospermia., Intervention(s): Toremifene (60 mg daily) was administered to all men for 3 months. At baseline and at the end of each month, serum concentrations of follicle-stimulating hormone (FSH), testosterone, inhibin B, and sex hormone-binding globulin (SHBG) were measured. At baseline and at the end, semen analysis was performed and sperm concentration, spermatozoal motility and normal sperm forms were determined., Main Outcome Measure(s): Gonadotropin, testosterone, inhibin-B levels, total sperm count, sperm morphology and motility., Result(s): Toremifene administration resulted in a significant increase in FSH, testosterone, SHBG, and inhibin B levels, as well as in sperm concentration, percentage motility and normal sperm forms. Twenty-two men's partners achieved pregnancy within 2 months of the end of treatment. At the end of the third month, serum FSH levels were significantly higher in the men whose partners did not achieve pregnancy, and total sperm count and normal sperm forms were significantly lower compared with the group of men whose partners achieved pregnancy., Conclusion(s): Toremifene administration for a period of 3 months in men with idiopathic oligozoospermia is associated with significant improvements of sperm count, motility, and morphology, mediated by increased gonadotropin secretion and possibly a direct beneficial effect of toremifene on the testes. The above findings are also indicative of a better testicular exocrine (improved sperm parameters) response to treatment in men whose partners achieved pregnancy compared with those who did not. Further randomized, placebo-controlled trials should be conducted to determine whether this particular selective estrogen receptor modulator can be useful as an initial approach in men with oligozoospermia.

Metformin therapy in polycystic ovary syndrome (PCOS) improves metabolic and hormonal profiles. Its therapeutic effect on cardiovascular risk factors is under investigation. Advanced glycation end products (AGEs), well-known atherogenic molecules, were recently found to be elevated in plasma of women with PCOS. The purpose of the study was to investigate the effect of metformin treatment in plasma AGE levels of women with PCOS. This was a descriptive clinical trial. The study involved 22 patients with PCOS (age, 25.09 +/- 1.05 years; body mass index [BMI], 28.44 +/- 1.51 kg/m(2)) and 22 healthy women (age, 26.50 +/- 0.85 years; BMI, 25.62 +/- 1.30 kg/m(2)). Measurements of plasma AGE levels (U/mL) were performed, and the metabolic and hormonal profiles were determined in all subjects. All women with PCOS received a dose of 1700 mg metformin daily for 6 months. AGEs levels were reduced after metformin administration in 22 women with PCOS (9.98 +/- 0.13 [before metformin] vs 9.86 +/- 0.11 [after metformin], P = .05). In a subgroup analysis, of 16 women with PCOS and normal glucose tolerance, the drop of AGE levels was potentiated (9.98 +/- 0.19 [before] vs 9.81 +/- 0.15 [after], P = .02). Body mass index as well as the other parameters studied remained unchanged after metformin therapy apart from a drop of testosterone levels (P = .01) and free androgen index (P = .009). In conclusion, after metformin therapy, the atherogenic AGE molecules were reduced in the serum of women with PCOS . The clinical relevance of this finding in PCOS, a high-risk group for type 2 diabetes mellitus and cardiovascular disease, remains to be seen. Future studies are required to confirm the need of therapeutic intervention for short-term abnormalities and for prevention of long-term sequelae characterizing this syndrome.

Background: The study aim was to investigate the relationship between insulin resistance (IR), beta-cell function (betaF), hyperandrogenism and proinsulin levels during an oral glucose tolerance test (OGTT) in women with polycystic ovary syndrome (PCOS)., Methods: One hundred and twenty-six selected women were classified as follows: PCOS, BMI > 25 kg/m2 (n = 39); PCOS, BMI < 25 kg/m2 (n = 54); controls, BMI > 25 kg/m2 (n = 14); controls, BMI < 25 kg/m2 (n = 19). Blood samples were collected between the third and sixth day of a spontaneous menstrual cycle, at 9:00 a.m., after an overnight fast. Serum levels of FSH, LH, PRL, 17alpha-OH-progesterone, SHBG, testosterone, delta4-androstenedione, insulin, proinsulin and glucose were measured. A 75 g OGTT was performed, and concentrations of glucose, insulin and proinsulin were also measured at t = 30, 60, 90, and 120 min., Results: The markers of insulin secretion and the AUC for proinsulin were higher in obese and overweight women and in women with PCOS, respectively. The AUC for proinsulin was positively correlated with markers of IR, betaF and androgen levels. An inverse relationship between PI/I values and indices of IR and betaF was observed., Conclusions: Increased proinsulin levels reflect, most probably, insulin resistance, which is the key disorder in PCOS-associated metabolic abnormalities. Beta-cell function, pre-proinsulin mRNA processing and proinsulin conversion to insulin could be initially increased as a result of IR. An interaction between circulating proinsulin and androgen biosynthesis or action might also exist.

Background: Women with polycystic ovary syndrome (PCOS) have an increased prevalence of insulin resistance (IR) and related disorders. Elevated serum levels of cellular adhesion molecules (CAMs) reflect low-grade chronic inflammation and have been associated with several insulin-resistant states. The objective of this study is to investigate whether soluble inflammatory markers [soluble intercellular adhesion molecule-1 (sICAM-1), soluble endothelial leukocyte adhesion molecule-1 (sE-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1) and C-reactive protein (CRP)] are altered in PCOS and to further elucidate the effect of metformin treatment on their levels., Methods: Two young populations were studied [62 women with PCOS and 45 normal women of similar age, BMI and waist-to-hip ratio (WHR)]. Plasma levels of sICAM-1, sVCAM-1, sE-selectin and high-sensitivity CRP (hsCRP) were measured in both groups. Additionally, the effect of metformin on these molecules was investigated in 22 women with PCOS who accepted to metformin protocol (1700 mg daily for a 6-month period)., Results: In the total population studied, plasma levels of hsCRP (mg/l), sICAM-1 (ng/ml) and sE-selectin (ng/ml) were higher in the PCOS group compared with those in controls (hsCRP 1.31 +/- 0.22 versus 0.92 +/- 0.27, P = 0.014, sICAM-1 301.21 +/- 24.80 versus 209.86 +/- 17.05, P = 0.025, sE-selectin 57.37 +/- 4.08 versus 45.67 +/- 4.62, P = 0.045, respectively). sVCAM-1 (ng/ml) did not differ statistically among the two groups (P = 0.896). A significant reduction in hsCRP and sVCAM-1 was achieved after 6 months of metformin administration: PCOS pretreatment hsCRP 1.92 +/- 0.60 versus PCOS post-treatment hsCRP 0.52 +/- 0.26, P = 0.005; PCOS pretreatment sVCAM-1 668.09 +/- 98.38 versus PCOS post-treatment sVCAM-1 365.82 +/- 99.77, P = 0.039., Conclusion: These findings imply the presence of chronic inflammation in women with PCOS. Metformin decreases the levels of plasma inflammatory indices. Further investigation is required to determine whether these findings may prove to be of clinical significance for PCOS patients.

Objective: This study was designed to: [1] measure, for the first time, metastin (kisspeptin) levels in women with polycystic ovary syndrome (PCOS), a condition associated with hypersecretion of LH and hyperandrogenemia; and [2] investigate the possible correlations between metastin and PCOS-related reproductive and metabolic disturbances., Design: Clinical study., Setting: University hospital., Patient(s): Twenty-eight obese and overweight (body mass index [BMI] >25 kg/m2) women with PCOS, 28 normal weight (BMI <25 kg/m2) women with the syndrome, and 13 obese and overweight controls (ovulatory women without clinical or biochemical hyperandrogenemia) were selected., Intervention(s): Blood samples were collected between day 3 and day 6 of a spontaneous bleeding episode in the PCOS groups and a menstrual cycle of the controls, at 9:00 AM, after an overnight fast., Main Outcome Measure(s): Circulating levels of LH, FSH, PRL, T, Delta4-androstenedione (A), DHEAS, 17alpha-OH-P, sex hormone-binding globulin (SHBG), insulin, glucose, and metastin were measured., Result(s): Both normal weight women with PCOS and obese controls were less insulin resistant and had significantly higher metastin levels, compared to obese and overweight women with the syndrome. Plasma kisspeptin levels were negatively correlated with BMI, free androgen index, and indices of insulin resistance., Conclusion(s): These results indicate that metastin is negatively associated with free androgen levels. The PCOS-associated insulin resistance and consequent hyperinsulinemia probably contribute to this effect by [1] stimulating androgen synthesis by the polycystic ovary (PCO) and [2] suppressing SHBG production in the liver.

Objective: Although evidence on elevated creatine phosphokinase (CPK) as a tool for the diagnosis of ectopic pregnancy (EP) is rather conflictive, no previous study on CPK isoenzyme levels and their relative ratio was found in the literature., Study Design: Forty women with EP, 20 with intrauterine (IU) abortive gestation, and 20 regular pregnant women (controls) were studied. Serum total CPK, CPK-MB, and CPK-MM levels were measured at the time of presentation and 24 hours after surgery. Relative operating characteristic (ROC) curves were plotted., Results: Women with EP had significantly higher CPK concentrations and a significantly decreased CPK-MB relative ratio (CPK-MB%), compared with both women with IU abortive pregnancy and controls. The ROC curves demonstrated a significant discriminatory ability of both increased total CPK and decreased CPK-MB% ratio for the diagnosis of EP., Conclusion: Determination of CPK isoenzyme fractions can significantly enhance the diagnostic value of total maternal CPK in the prediction of ectopic pregnancy.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder characterized by hyperandrogenemia, hyperinsulinemia, insulin resistance, and chronic anovulation. It is the most common endocrine disorder in women of reproductive age with an enigmatic pathophysiologic and molecular basis. The high prevalence of affected individuals and the wide range of phenotypic expression can be explained by the interaction of a number of key genes with environmental factors. Heritability of PCOS has been inferred from studies of the syndrome in various population groups (ethnic groups, twins, and PCOS families). Although evidence of familial segregation and clustering of the disease in first-degree relatives of women diagnosed with PCOS has been presented, no particular pattern of inheritance has emerged. Some of the problems in genetic studies have been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features, and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify the propositus and to determine affected status in the kindred, the genetic studies available suggest a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants and environmental factors, during either prenatal or postnatal life.

Background: Ghrelin is a novel peptide associated with energy balance, obesity, and perhaps gonadal function. The present study was designed in order: (i) to compare plasma ghrelin levels between women with PCOS, women who presented only with hyperandrogenaemia and healthy controls; and (ii) to investigate the relationship between circulating ghrelin and the heterogeneity of clinical and biochemical manifestations of PCOS., Methods: Two hundred and fifty-nine women with PCOS, 25 women who had only hyperandrogenaemia and 46 controls, were studied. Women with PCOS were further divided, based on the presence of chronic anovulation, biochemical hyperandrogenaemia, clinical hyperandrogenism, and polycystic ovary morphology on ultrasound evaluation. In all women, the basal levels of gonadotrophins, androgens, 17-OH-progesterone, sex hormone-binding globulin, glucose, insulin and ghrelin were measured., Results: Women with PCOS had lower ghrelin levels, compared to both women with hyperandrogenaemia and controls; women with hyperandrogenaemia had lower ghrelin levels, compared to controls, but not significantly so. While PCOS-associated hyperandrogenaemia was inversely related to ghrelin levels, anovulation and polycystic ovary morphology were associated with higher concentrations. Ghrelin levels were negatively correlated with 17-OH-progesterone levels., Conclusions: In PCOS, circulating ghrelin and androgens are inversely related and it is possible that this peptide is involved in steroidal synthesis and/or action. It is also likely that different clinical and biochemical manifestations of the syndrome are also associated with different ghrelin concentrations.

Purpose of Review: This review is timely and relevant for several reasons. The incidence of adenomyosis begins to rise from the mid-thirties. Moreover, more women are delaying their first pregnancy until later in their thirties or forties, and consequently adenomyosis is encountered more frequently in the fertility clinic during diagnostic work-up. Furthermore, it is difficult to diagnose adenomyosis before surgery, because there are no pathognomonic signs, symptoms or physical findings. Finally, reference data are very limited., Recent Findings: This review refers to adenomyosis of the uterus as a factor in female infertility. The clinical presentation of adenomyosis uteri is also reviewed, as well as animal and human studies concerning the effect of adenomyosis in female infertility. Different treatment options are discussed, especially those referring to patients who wish to maintain their fecundity., Summary: Uterine adenomyosis remains a fairly frequent and debilitating disease that will be encountered with increasing incidence in the infertile female population. While spectacular advances have been made in recent years in the non-invasive diagnosis of the condition, non-surgical treatment options for infertile patients with adenomyosis arise but need to be confirmed in larger series.

Background: Insulin resistance is a prominent feature of polycystic ovary syndrome (PCOS), independent of obesity. It is possible that insulin resistance in PCOS is genetically determined. Adiponectin is a protein that modulates insulin action and is regarded as a possible link between adiposity and insulin resistance. The objective of this study was to examine the role of the adiponectin gene T45G polymorphism, located in exon 2, in PCOS, since this polymorphism has been shown to be associated with obesity and insulin resistance., Subjects and Methods: Two hundred and thirty-two women were studied, and were classified as follows: 132 women with PCOS [62 with body mass index (BMI) > 25 kg/m2 and 70 with BMI < 25 kg/m2] and 100 ovulating women without hyperandrogenemia (controls: 19 with BMI > 25 kg/m2 and 81 with BMI < 25 kg/m2). From all subjects a whole-blood sample was taken and was used for isolation of peripheral blood leukocytes. The adiponectin T45G polymorphism, located in exon 2, was genotyped by amplification of genomic DNA. In all subjects, serum gonadotropin, androgen, 17-OH-progesterone, fasting glucose, insulin and adiponectin levels were measured between the third and sixth day of the menstrual cycle., Results: A statistically significant difference was observed in the frequency of GG and TG genotypes between women with PCOS (40/132; 30.3%) and controls (19/100; 19.0%). In a subgroup of PCOS women with high Delta4-androstenedione levels (Delta4A > 3.11 ng/ml), a statistically significant difference between the frequencies of the genotypes was also noticed compared with the control group, in contrast to the subgroup with relatively low Delta4-androstenedione levels (Delta4A < 3.11 ng/ml). No significant associations were found between this adiponectin polymorphism and BMI, testosterone level, adiponectin levels and glucose-to-insulin ratio., Conclusions: Our study suggests that adiponectin polymorphisms are not causatively involved in the metabolic disturbances of PCOS, but that an interaction between adiponectin and steroid synthesis or action might exist., (Copyright 2004 European Society of Human Reproduction and Embryology)

Objective: To measure serum resistin levels in women with polycystic ovary syndrome (PCOS) and assess possible correlations of resistin to the hormonal and metabolic parameters of the syndrome., Design: Clinical study., Setting: University hospital., Patient(s): Ninety selected women were classified as follows: group I: 35 anovulatory women with PCOS (body mass index [BMI] >25 kg/m(2)); group II: 35 anovulatory women with PCOS (BMI <25 kg/m(2)); group III: 20 ovulating women (controls) without hyperandrogenemia (BMI <25 kg/m(2)); women of group III were volunteers., Intervention(s): Blood samples were collected between the 3rd and the 6th day of the menstrual cycle of the ovulating women, and between the 3rd and the 6th day of a spontaneous bleeding of the anovulatory women, at 9 a.m., after an overnight fast., Main Outcome Measure(s): Serum levels of FSH, LH, PRL, 17alpha-hydroxyprogesterone, sex hormone-binding globulin, androgens, insulin, resistin, and glucose., Result(s): Resistin levels were found to be significantly increased in group I compared with those of group II and those of group III. No significant difference in resistin levels was found between groups II and III, despite significant differences in insulin levels and the glucose-to-insulin ratio. Multiple regression analysis showed that resistin levels do not correlate with any parameter independent of BMI., Conclusion(s): Based on the above findings, we presume that resistin is unlikely to be a major determining factor of PCOS-associated insulin resistance and is not actively involved in the pathogenesis of the syndrome.

Background: Adiponectin is regarded as a possible link between adiposity and insulin resistance. The study aim was to measure serum adiponectin levels in women with polycystic ovary syndrome (PCOS) and to assess possible correlations between adiponectin and the hormonal or metabolic parameters of the syndrome., Methods: Eighty-five selected women were classified as: Group I (n = 35) with PCOS + body mass index (BMI) >25 kg/m(2); group II (n = 35) with PCOS + BMI <25 kg/m(2); and group III (controls; n = 15) ovulating without hyperandrogenaemia and BMI <25 kg/m(2). Blood samples were collected between the days 3 and 6 of a spontaneous menstrual cycle, at 09:00, after an overnight fast. Serum levels of FSH, LH, prolactin, 17alpha-OH-progesterone, sex hormone-binding globulin (SHBG), androgens, insulin, adiponectin and glucose were measured., Results: Adiponectin levels were significantly decreased in group I compared with groups II and III. No significant difference in adiponectin levels was found between groups II and III, despite significant differences in insulin levels and glucose:insulin ratio. Multiple regression analysis showed that Delta(4)-androstenedione levels and BMI values were the only significant determinants of serum adiponectin levels., Conclusions: Serum adiponectin levels are reduced in obese women with PCOS. Although adiponectin does not seem to be actively involved in the pathogenesis of PCOS, there seems to be an interaction between adiponectin and steroid synthesis or action.

Design: We examined 16 men who had been subjected to unilateral orchiectomy owing to seminoma and to preventive radiotherapy, in order to investigate the morphologic abnormalities of the spermatozoa (headless and small-round-headedness) that may contribute to infertility., Results: The same morphologic abnormalities of the head and neck found in the semen samples of fertile men were also found in the semen samples of the patients, albeit in higher percentages; the morphologic abnormalities of the tail in the semen samples of the patients were similar to those of the fertile men, both qualitatively and quantitatively., Conclusion: No specifically characteristic morphologic abnormalities of the spermatozoa were detected in men who were subjected to unilateral orchiectomy and to preventive radiotherapy in comparison with fertile men. The percentage rate of morphologic tail abnormalities is not affected by preventive radiotherapy.

Objective: To investigate the frequency of round-headed, or acrosomeless, spermatozoa, determine the percentage and evaluate the possible correlation with other semen parameters., Study Design: Semen specimens from 114 subfertile men aged 24-53 years (mean +/- SD 33.3 +/- 6.3) and from 60 fertile men aged 24-44 years (33.1 +/- 4.2) were studied. Two semen specimens were examined from each individual, with a six- to eight-week interval. Sperm morphology was evaluated from Papanicolaou-stained smears, and the classification of abnormal sperm forms was made according to WHO guidelines., Results: The percentage of round-headed spermatozoa was 2.3% +/- 0.5 in subfertile and 0.5% +/- 0.1 in fertile men. Round-headed spermatozoa existed in semen specimens from 36.8% of subfertile and 25.0% fertile men. Of subfertile men, 14.9% had round-headed spermatozoa at a higher percentage than the highest normal limit found in sperm smears from fertile men., Conclusion: In some subfertile men with a high percentage of round-headed spermatozoa, infertility could be attributed to the cause of this morphologic abnormality. Moreover, morphologic abnormalities in the neck were significantly more frequent in round-headed spermatozoa than in spermatozoa with normal heads.