Nutrition, inflammation and liver-spleen axis.

Chronic low-grade systemic inflammation represents a mechanism common to many diseases linked to atherosclerosis-related pathways. There is a growing body of evidence indicating that the combination of food quantity and quality along with genetic susceptibility are able to induce the aberrant activation of innate immune signalling, which initially contributes to chronic low-grade inflammation. Liver represents the central player to inflammatory response. Dietary/metabolic factors contribute to the pathogenesis of Non-alcoholic Fatty Liver Disease (NAFLD), the main causes of liver disease in the Western world. Enlargement of the spleen, central organ in regulating the inflammation-related immune response, is commonly seen in patients with of NAFLD, depicting the so called "liver-spleen axis." The aim of this review was to provide an at-a-glance overview of the possible bi-directional mechanisms linking nutrition and inflammation, particularly pinpointing the inflammatory effects stemmed by nutrition on "liver-spleen axis." In particular, the role of unhealthy diet, healthy dietary patterns, such as the Mediterranean diet style, dietary vitamins and micronutrients, such as vitamin D or Magnesium, and Glucagon-Like Peptide-1, a well-known incretin released in response to meal intake, will be discussed. The highly variability of the inflammatory response highlights the role of expert nutritionists in refining methodologies apt to assess nutritional epidemiology and to apply appropriate dietary intervention to counteract diet-induced inflammation mechanisms.

Gut: A key player in the pathogenesis of type 2 diabetes?

The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes. The intestinal microbiota may be responsible of the secretion of molecules that may impair insulin secretion/action. At the same time, intestinal milieu regulates the secretion of hormones such as GLP-1, GIP, ghrelin, gastrin, somatostatin, CCK, serotonin, peptide YY, GLP-2, all of which importantly influence metabolism in general and in particular glucose metabolism. Thus, the aim of this paper is to review the current evidence on the role of the gut in the pathogenesis of type 2 diabetes, taking into account both hormonal and microbiological aspects.

Source and amount of carbohydrate in the diet and inflammation in women with polycystic ovary syndrome.

High carbohydrate intake and low-grade inflammation cooperate with insulin resistance and hyperandrogenism to constitute an interactive continuum acting on the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age characterised by oligo-anovulatory infertility and cardiometabolic disorders. The role of insulin in PCOS is pivotal both in regulating the activity of ovarian and liver enzymes, respectively involved in androgen production and in triggering low-grade inflammation usually reported to be associated with an insulin resistance, dyslipidaemia and cardiometabolic diseases. Although an acute hyperglycaemia induced by oral glucose loading may increase inflammation and oxidative stress by generating reactive oxygen species through different mechanisms, the postprandial glucose increment, commonly associated with the Western diet, represents the major contributor of chronic sustained hyperglycaemia and pro-inflammatory state. Together with hyperinsulinaemia, hyperandrogenism and low-grade inflammation, unhealthy diet should be viewed as a key component of the 'deadly quartet' of metabolic risk factors associated with PCOS pathophysiology. The identification of a tight diet-inflammation-health association makes the adoption of healthy nutritional approaches a primary preventive and therapeutic tool in women with PCOS, weakening insulin resistance and eventually promoting improvements of reproductive life and endocrine outcomes. The intriguing nutritional-endocrine connections operating in PCOS underline the role of expert nutritionists in the management of this syndrome. The aim of the present review is to provide an at-a-glance overview of the possible bi-directional mechanisms linking inflammation, androgen excess and carbohydrate intake in women with PCOS.

Low vitamin D status and obesity: Role of nutritionist.

Low vitamin D status and obesity have concomitantly reached epidemic levels worldwide. Up to now the direction of the association between low vitamin D status and obesity, the exact mechanisms responsible for this association and the clinical usefulness to increase vitamin D status for reducing adiposity still warrant further evaluation. The aim of the present review was to examine the current evidence linking low vitamin D status and obesity in relation to the role of the nutritionist. On the one side, considering obesity as a causal factor, low sun exposure in obese individuals due to their sedentary lifestyle and less outdoor activity, vitamin D sequestration in adipose tissue, and volumetric dilution of ingested or cutaneously synthesized vitamin D3 in the large fat mass of obese patients, might represent some of the factors playing a major role in the pathogenesis of the low vitamin D status. On the other side, the expression of both vitamin D3 receptors and enzymes responsible for vitamin D3 metabolism in adipocytes depicted a role for the low vitamin D status per se in the development of obesity by modulating adipocyte differentiation and lipid metabolism. Nutritionists need to accurately address the aspects influencing the low vitamin D status in obesity and the vitamin D supplementation in obese individuals.

Shedding new light on female fertility: The role of vitamin D.

In the last decades several studies suggested that vitamin D is involved in the modulation of the reproductive process in women due to the expression of VDR and 1α-hydroxylase in reproductive tissues such as ovary, uterus, placenta, pituitary and hypothalamus. Vitamin D has also a role in the regulation of sex hormone steroidogenesis. Increasing evidence suggests that vitamin D might have a regulatory role in polycystic ovary syndrome (PCOS)-associated symptoms, including ovulatory dysfunction, insulin resistance and hyperandrogenism. Vitamin D deficiency also has been reported to contribute to the pathogenesis of endometriosis due to its immunomodulatory and anti-inflammatory properties. Although most of the studies supported a role of vitamin D in the onset of these diseases, randomized controlled trials to assess the efficacy of vitamin D supplementation have never been performed. In this review we critically discuss the role of vitamin D in female fertility, starting from in vitro and in vivo studies, focusing our attention on the two most frequent causes of female infertility: PCOS and endometriosis.

Low serum vitamin D-status, air pollution and obesity: A dangerous liaison.

The aim of this review is to provide a general overview of the possible associations among the vitamin D status, air pollution and obesity. Sunlight exposure accounts in humans for more than 90 % of the production of vitamin D. Among emerging factors influencing sunlight-induced synthesis of vitamin D, prospective and observational studies proved that air pollution constitutes an independent risk factor in the pathogenesis of vitamin D hypovitaminosis. In addition, environmental pollutants can affect risk of obesity when inhaled, in combination with unhealthy diet and lifestyle. In turn, obesity is closely associated with a low vitamin D status and many possible mechanisms have been proposed to explain this association. The associations of air pollution with low vitamin D status on the hand and with obesity on the other hand, could provide a rationale for considering obesity as a further link between air pollution and low vitamin D status. In this respect, a vicious cycle could operate among low vitamin D status, air pollution, and obesity, with additive detrimental effects on cardio-metabolic risk in obese individuals. Besides vitamin D supplementation, nutrient combination, used to maximize the protective effects against air pollution, might also contribute to improve the vitamin D status by attenuating the "obesogen" effects of air pollution.

Current evidence on vitamin D deficiency and kidney transplant: What's new?

Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.

Vitamin D and pancreas: The role of sunshine vitamin in the pathogenesis of diabetes mellitus and pancreatic cancer.

Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence ß-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.

Vitamin D and chronic diseases: the current state of the art.

The objective was to provide the current state of the art regarding the role of vitamin D in chronic diseases (osteoporosis, cancer, cardiovascular diseases, dementia, autism, type 1 and type 2 diabetes mellitus, male and female fertility). The document was drawn up by panelists that provided their contribution according to their own scientific expertise. Each scientific expert supplied a first draft manuscript on a specific aspect of the document's topic that was subjected to voting by all experts as "yes" (agreement with the content and/or wording) or "no" (disagreement). The adopted rule was that statements supported by ≥75 % of votes would be immediately accepted, while those with <25 % would be rejected outright. Others would be subjected to further discussion and subsequent voting, where ≥67 % support or, in an eventual third round, a majority of ≥50 % would be needed. This document finds that the current evidence support a role for vitamin D in bone health but not in other health conditions. However, subjects with vitamin D deficiency have been found to be at high risk of developing chronic diseases. Therefore, although at the present time there is not sufficient evidence to recommend vitamin D supplementation as treatment of chronic diseases, the treatment of vitamin D deficiency should be desiderable in order to reduce the risk of developing chronic diseases.

Adrenocortical tumors and insulin resistance: What is the first step?

The pathogenetic mechanisms underlying the onset of adrenocortical tumors (ACTs) are still largely unknown. Recently, more attention has been paid to the role of insulin and insulin-like growth factor (IGF) system on general tumor development and progression. Increased levels of insulin, IGF-1 and IGF-2 are associated with tumor cell growth and increased risk of cancer promotion and progression in patients with type 2 diabetes. Insulin resistance and compensatory hyperinsulinemia may play a role in adrenal tumor growth through the activation of insulin and IGF-1 receptors. Interestingly, apparently non-functioning ACTs are often associated with a high prevalence of insulin resistance and metabolic syndrome. However, it is unclear if ACT develops from a primary insulin resistance and compensatory hyperinsulinemia or if insulin resistance is only secondary to the slight cortisol hypersecretion by ACT. The aim of this review is to summarize the current evidence regarding the relationship between hyperinsulinemia and adrenocortical tumors.

Metformin, oral contraceptives or both to manage oligo-amenorrhea in adolescents with polycystic ovary syndrome? A clinical review.

The management of oligo-amenorrhea in adolescent patients with polycystic ovary syndrome (PCOS) represents an important and difficult challenge. Metformin and/or oral contraceptives (OCs) are different strategies widely proposed in these patients. The objective of the current review was to provide an overview on the use of metformin and/or OCs for the management of oligo-amenorrhea in adolescents with PCOS underlining their potential risks and benefits in order to help the clinician to choose the best patients' tailored treatment.

The good and bad effects of statins on insulin sensitivity and secretion.

AIMS: Statins are the main lipid-lowering treatment in both primary and secondary prevention populations. Whether statins deteriorates glycemic control, predisposing to the onset of diabetes mellitus has been a matter of recent concern. Statins may accelerate progression to diabetes via molecular mechanisms that impact insulin sensitivity and secretion. In this review, we debate the relative effect of statins in driving insulin resistance and the impairment of insulin secretion. METHODS: Narrative overview of the literature synthesizing the findings of literature was retrieved from searches of computerized databases, hand searches, and authoritative texts employing the key words "Statins", "Randomized Clinical Trial", "Insulin sensitivity", "Insulin resistance", "Insulin Secretion", "Diabetes Mellitus" alone and/or in combination. RESULTS: The weight of clinical evidence suggests a worsening effect of statins on insulin resistance and secretion, anyway basic science studies did not find a clear molecular explanation, providing conflicting evidence regarding both the beneficial and the adverse effects of statin therapy on insulin sensitivity. CONCLUSIONS: Although most of the clinical studies suggest a worsening of insulin resistance and secretion, the cardiovascular benefits of statin therapy outweigh the risk of developing insulin resistance, thus the data suggest the need to treat dyslipidemia and to make patients aware of the possible risk of developing type 2 diabetes or, if they already are diabetic, of worsening their metabolic control.

Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells.

Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT.

Bisphenol A in polycystic ovary syndrome and its association with liver-spleen axis.

CONTEXT: Bisphenol A, one of the highest-volume chemicals currently available, is known to act as endocrine disruptor and alters several metabolic functions, including inflammatory pathways. Elevated serum levels of bisphenol A have been found in women with polycystic ovary syndrome (PCOS) and a role of low-grade chronic inflammation has been recently reported in the pathogenesis of this syndrome. Increased spleen volume, a reliable and stable index of chronic inflammation, was strictly associated with the severity of hepatic steatosis (HS) in obese subjects, determining the so-called liver-spleen axis. OBJECTIVE: To evaluate the contribution of increased serum bisphenol A levels to low-grade chronic inflammation, HS and hyperandrogenism in women with PCOS. DESIGN, SETTING AND PARTICIPANTS: Forty lean and overweight/obese premenopausal women with PCOS and 20 healthy age-matched women were consecutively enrolled in a cross-sectional study from 2009 to 2011 at the Federico II University Hospital in Naples. MEASUREMENTS: Bisphenol A, homoeostasis model assessment of insulin resistance (HoMA-IR), laboratory liver tests, testosterone, sex hormone-binding globulin, free androgen index (FAI), C-reactive protein, interleukin-6, and the ultrasound quantification of HS and spleen longitudinal diameter. RESULTS: Independently of body weight, higher bisphenol A levels in PCOS women were associated with higher grades of insulin resistance, HS, FAI and inflammation, spleen size showing the best correlation. At multivariate analysis, spleen size and FAI were the best predictors of bisphenol A (ß coefficients 0.379, P = 0.007 and 0.343, P = 0.014, respectively). CONCLUSIONS: In premenopausal women with PCOS, we evidenced an association of serum bisphenol A levels with HS and markers of low-grade inflammation, in particular with spleen size, unravelling the presence of the liver-spleen axis in this syndrome.

Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study.

OBJECTIVE: Foetal exposure to high testosterone concentrations seems to be involved in the development of mammalian brain and related to pervasive developmental disorders (PDDs). The aim of the current study was to test the hypothesis that children born from hyperandrogenic women with polycystic ovary syndrome (PCOS) are at higher risk of PDDs. DESIGN: Longitudinal case-control study. PATIENTS: Thirty pregnant PCOS patients with hyperandrogenaemia and other 45 pregnant healthy women were followed during pregnancy. All women had a healthy baby. MEASUREMENTS: Clinical evaluations and biochemical assays of the mothers during pregnancy and after delivery were performed. The children's versions of the Autism-Spectrum Quotient (AQ-C), the Empathy Quotient (EQ-C) and Systemizing Quotient (SQ-C) tests were administered. RESULTS: Total AQ-C and communication scores were significantly higher for children of PCOS patients. Stratifying our population according to sex, total AQ-C, communication and attention switching subscores were significantly higher only for daughters of PCOS patients. EQ-C and SQ-C scores resulted in significantly lower and higher scores, respectively, only in daughters of PCOS patients in comparison with those of healthy non-PCOS controls. AQ-C, EQ-C and SQ-C scores, irrespective of the studied group and/or subclassification by gender, were significantly influenced by amniotic testosterone levels. CONCLUSIONS: Daughters of mothers affected by hyperandrogenic PCOS seem to have a higher risk for PDDs probably due to an unbalanced prenatal exposure to high levels of testosterone.

Silicon determination in human ventricular whole blood: a possible marker of drowning.

This article presents the first results demonstrating that total silicon trace concentration in human ventricular whole blood may be used as a further marker in the diagnosis of drowning. The difference in silicon content between the left and right ventricles was significantly higher for drowning cases than that from individuals who had not drowned. These findings were in full agreement with autoptic responses, supporting silicon as a marker of freshwater drowning. The procedure entails an alkaline microwave-assisted digestion using tetramethylammonium hydroxide (TMAH) in the presence of H(2)O(2) followed by dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS) detection, whose accuracy was obtained for Seronorm whole blood reference material. Satisfactory recoveries (91-98%) were gained on whole ventricular blood, with a silicon content lower than the method detection limit (MDL), spiked at 5 to 7µgg(-1) with materials consistent with drowning media constituents, that is, freshwater plankton (CRM [certified reference material] 414), silicon dioxide, diatomaceous earth powder, and a silicon standard solution. Good within-lab reproducibility (4-10%) and sensitivity (MDL=0.46µgg(-1)) were achieved as well. The procedure was applied to blood samples from 18 different real cases of death.

Metformin administration in patients with polycystic ovary syndrome who receive gonadotropins for in vitro fertilization cycles: 10-year experience in a large infertile population.

The study aim was to evaluate our personal experience regarding the use and the reproductive effect of metformin administration in a large population of infertile patients with polycystic ovary syndrome (PCOS) undergoing gonadotropins ovarian stimulation for in vitro fertilization (IVF). Infertile patients with PCOS undergoing gonadotropins ovarian stimulation with (metformin group, n = 191) or without (control group, n = 187) metformin and IVF were evaluated. Treatment characteristics, patients' data and reproductive outcomes were evaluated. In all cases, metformin with an immediate-release formulation was administered, and in most of cases it was given as pre- and co-treatment (74.9%) and at a dosage of 1700 mg/day (59.7%). Stimulation length and gonadotropins doses were significantly (p < 0.05) higher in metformin group than in control group. The number of dominant follicles on day of ovarian maturation triggering and peak oestradiol levels were significantly (p < 0.05) lower in metformin group than in control group. Cycle cancellation rate under metformin resulted significantly influenced by interaction with body mass index (BMI), age and basal follicle-stimulating hormone (FSH) levels. Notwithstanding, metformin use in infertile PCOS patients who receive gonadotropins for IVF is not standardized, it seems to modulate the ovarian response to stimulation. This effect may benefit or harm on the basis of ovarian reserve and patients' characteristics.

Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females.

BACKGROUND: Fat mass (FM) in overweight/obese subjects has a primary role in determining low-grade chronic inflammation and, in turn, insulin resistance (IR) and ectopic lipid storage within the liver. Obesity, aging, and FM influence the growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could affect the IGF-I axis status in overweight/obese, independently of HS. METHODS: The study population included 48 overweight/obese women (age 41 ± 13 years; BMI: 35.8 ± 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high-sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF-I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were also calculated. FM was determined by bioelectrical impedance analysis. HS severity grading (score 0-4 according liver hyperechogenicity) and spleen longitudinal diameter (SLD) were evaluated by ultrasound. RESULTS: Metabolic syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA, ALT, CRP, were significantly higher in patients with severe HS than in those with mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1 (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At multivariate analysis the best determinants of IGF-I were FM% (ß = -0.49; p = 0.001) and IGFBP-1 (ß = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3 ratio (ß = -0.43; p = 0.004). CONCLUSIONS: The present study suggests that lower IGF-I status in our study population is associated with higher FM, SLD, CRP and more severe HS.

Systemic and local effects of metformin administration in patients with polycystic ovary syndrome (PCOS): relationship to the ovulatory response.

BACKGROUND: Several data have demonstrated the efficacy of metformin in inducing ovulation in patients with polycystic ovary syndrome (PCOS), however, the exact mechanism by which this drug acts remains unknown. The aim of the present study was to evaluate whether the efficacy of the drug in patients with PCOS is related to a systemic hormonal-metabolic improvement, or to a local action on the ovary. METHODS: Twenty-four normal weight patients with PCOS, who were treated with metformin, were enrolled. Of these, 12 subjects were anovulatory (Group A1), whereas the other 12 were ovulatory but had failed to conceive (Group A2). A further 24 untreated subjects who were scheduled for laparoscopic surgery were enrolled as controls, 12 anovulatory patients with PCOS scheduled for laparoscopic myomectomy (Group B1) and a further 12 non-PCOS participants were scheduled for diagnostic laparoscopy (Group B2). Clinical assessments and biochemical evaluations in blood and antral follicular fluid were performed in each participant. RESULTS: In 1/12 and 9/12 participants from Groups A1 and A2, respectively, the ovarian morphology was changed, and a significant (P < 0.05) reduction in the ovarian dimensions was observed only in Group A2. In both of these groups, and without difference between them, serum androgens and indices of insulin resistance improved significantly (P < 0.05) after metformin treatment. On the other hand, significant differences (P < 0.05) between the two groups were detected with respect to the same biochemical parameters in antral follicular fluid. In Groups A1 and A2, levels of androgens and indices of insulin resistance in the antral follicular fluid were significantly (P < 0.05) better than in Group B1, but worse than in Group B2. CONCLUSIONS: Irrespective of its systemic effects, the efficacy of metformin in the induction of ovulation is probably due to a direct action on the ovary, and the ovulatory response to the drug seems to be related to local sensitivity or resistance to the drug.

Laparoscopic ovarian diathermy vs clomiphene citrate plus metformin as second-line strategy for infertile anovulatory patients with polycystic ovary syndrome: a randomized controlled trial.

OBJECTIVE: The purpose of this study was to compare the effectiveness of laparoscopic ovarian diathermy (LOD) vs clomiphene citrate (CC) plus metformin in infertile patients with CC-resistant polycystic ovary syndrome (PCOS). STUDY DESIGN: Fifty primary infertile patients with CC-resistant PCOS were assigned randomly to receive LOD followed by a 6-month observation (group A) or 6-cycle course of CC plus metformin (group B). Reproductive and safety outcomes were analyzed. RESULTS: No significant difference between 2 groups in pregnancy (15/92 women [16.3%] vs 14/107 women [13.1%]; P = .521) and live-birth (13/92 women [14.1%] vs 12/107 women [11.2%]; P = .536) rates per cycle was observed. With the use of a Cox regression analysis, patients under medical treatment, compared with patients who received surgical treatment, had a relative risk of pregnancy of 1.2 (95% confidence interval, 0.61-2.44; P = .582) and a relative risk of live-birth of 1.4 (95% confidence interval, 0.63-2.96; P = .425). CONCLUSION: LOD and CC plus metformin seem to be 2 effective approaches to treat infertility in patients with CC-resistant PCOS.