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Evaluation of steroid receptors, coregulators, and molecules associated with uterine receptivity in secretory endometria from untreated women with polycystic ovary syndrome.

OBJECTIVE: To evaluate gene and protein expression of steroid receptors, nuclear receptor coregulators, and uterine receptivity markers in midsecretory phase endometria from untreated women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: Hospital research unit. PATIENT(S): Eight patients with PCOS and eight fertile women of similar age to those with PCOS. INTERVENTION(S): Endometrial samples were obtained from women with PCOS (PCOSE) and normal (NE) women during the midsecretory phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Expression studies (immunohistochemistry, reverse transcription-polymerase chain reaction [RT-PCR] and Western blot). RESULT(S): Endometria from PCOS exhibit higher levels of messenger RNA (mRNA) and protein for estrogen receptor alpha and coactivators than NE. Epithelial cells had a greater expression of progesterone receptor in PCOSE, whereas, no differences were observed in gene and protein expression of the nuclear corepressor (NcoR) and the antiadhesion molecule mucin type-1 (MUC-1) between PCOSE and NE. Immunodetection for the coactivator ARA70 was higher in PCOSE than in NE; in contrast, expression of beta3-integrin in epithelia was lower in PCOSE than in control endometria. CONCLUSION(S): The higher response to steroid hormones of endometria from untreated PCOS-women induces diminished expression of beta3 integrin, which partially explain implantation failure in PCOS patients.

Adult↗

Prevalence of polycystic ovarian changes and polycystic ovary syndrome in premenopausal women with treated type 2 diabetes mellitus.

OBJECTIVE: To investigate the prevalence of polycystic ovary syndrome (PCOS) and polycystic ovary (PCO) among premenopausal women with type 2 diabetes mellitus (DM). DESIGN: Case-control study of women with type 2 DM. SETTING: Tertiary referral university hospital. PATIENT(S): Ninety-two premenopausal women with DM, >or=30 years of age, and 20 age- and body mass index-matched healthy premenapousal eumenorrheic women were recruited into the study. INTERVENTION(S): An oral glucose tolerance test was performed according to the American Diabetes Association criteria for each healthy woman. After an overnight fasting, blood samples were obtained for the determination of fasting blood glucose, LH, FSH, free T, androstenedione (A(4)), 17-hydroxyprogesterone (17-OHP), DHEAS, PRL, free T(4), TSH, E(2), and sex hormone-binding globulin (SHBG) levels. A GnRH analog (buserelin) test was carried out in 36 patients with DM and PCO (including PCOS subjects), 20 patients with DM without PCO or PCOS, and 20 healthy subjects. MAIN OUTCOME MEASURE(S): The prevalence of PCO and PCOS in women with type 2 DM. RESULT(S): Fifty-seven (62%) of diabetic patients had normal ovaries, 31 (33.7%) had PCO, and 4 (4.3%) had PCOS. The women with DM (n = 92) and healthy women (n = 20) had similar basal A(4), FSH, E(2), 17-OHP, free T, and DHEAS levels. The LH and SHBG levels were lower and the hirsutism score higher in diabetic patients than in healthy women (P<.05). Peak and area under the curve LH and FSH levels after buserelin testing were significantly higher in healthy women than in the patients (P<.05). Peak A(4) levels after buserelin were significantly higher in the patients than in the healthy women (P<.05). Ovarian volume was significantly greater in the patients with PCO (10.1 +/- 0.7 mL) than in the healthy women (7.0 +/- 0.9 mL) (P<.05). CONCLUSION(S): We conclude that PCO but not PCOS is a common finding in premenopausal women with type 2 DM. Suppression of gonadotropins, particularly LH secretion, may play a role in the absence of increased PCOS prevalence among type 2 diabetic patients.

Adult↗

Failure of the homeostatic model assessment calculation score for detecting metabolic deterioration in young patients with polycystic ovary syndrome.

OBJECTIVE: To verify whether the homeostatic model assessment (HOMA) test is a suitable method for the identification of metabolic deterioration in normal-weight patients affected by polycystic ovary syndrome (PCOS). DESIGN: Prospective clinical study. SETTING: Academic clinic and research environment in Cagliari, Italy. PATIENT(S): Forty-nine PCOS normal-weight adolescent subjects, and 50 eumenorrheic, normal-weight, nonhirsute controls matched for age and body mass index (BMI). INTERVENTION(S): History and physical examination, oral glucose tolerance test (OGTT) and blood sampling, ultrasound. MAIN OUTCOME MEASURE(S): The HOMA score and integrated secretory area under the curve of insulin values (I-AUC) during the OGTT were calculated. RESULT(S): Normal insulin sensitivity was defined as upper control 95th percentile by HOMA values <65.6, I-AUC at 180 minutes <16,921, and I-AUC at 120 minutes <11,817. When applying the calculated I-AUC cutoff, 27 PCOS patients were classified as normoinsulinemic and 22 as hyperinsulinemic, whereas using the calculated HOMA cutoff, only 9 PCOS patients could be classified as insulin resistant (IR). Thirteen of the 40 non-IR PCOS patients presented with hyperinsulinemia; fasting glucose and insulin levels and HOMA scores were not sufficient to identify these subjects. Thus, the HOMA test displayed a low sensitivity (41%) and specificity (100%) in the diagnosis of the metabolic disorder disclosed by I-AUC. Moreover, analysis of I-AUC after 120 and 180 minutes revealed how the shorter evaluation period did not suffice for identification of all hyperinsulinemic subjects, implying an unrecognized condition in 11 of 22 subjects. CONCLUSION(S): In young, normal-weight patients with PCOS, the prevalence of hyperinsulinemia is not detectable by HOMA studies. The prevalence of IR was 18% according to HOMA evaluation, whereas hyperinsulinemia was found in 44% of subjects examined by I-AUC. Normal-weight, young PCOS patients should undergo a 3-hour OGTT to detect early metabolic abnormalities.

Adolescent↗

Heritability of dehydroepiandrosterone sulfate in women with polycystic ovary syndrome and their sisters.

OBJECTIVE: To test the hypothesis that adrenal androgen (AA) secretion is an inherited trait in PCOS and that serum DHEAS concentrations, as a marker of AA secretion, will be correlated between women with PCOS and their sisters. DESIGN: Prospective case-control. SETTING: Tertiary care center. PATIENT(S): Sixty-two PCOS probands and 69 sisters. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The DHEAS concentrations and clinical phenotypes were obtained. Familial correlation between sisters was estimated. A variance components model was used to estimate the heritability (h(2)) of the DHEAS levels. Body mass index (BMI)-adjusted DHEAS levels were used in all of the analyses. RESULT(S): There was no difference in age between the proband and sister groups (28.7 +/- 8.1 years vs. 28.0 +/- 8.8 years, P=.65), and probands had higher BMI values (33.4 +/- 7.6 kg/m(2) vs. 27.9 +/- 7.0 kg/m(2), P<.001). Sixteen of the 69 (23.2%) sisters were affected by PCOS. The sister-sister correlation of DHEAS level was 0.28 +/- 0.12 for the whole group (P<.05), and this correlation was higher, at 0.38 +/- 0.14 (P< or =.05), after excluding 31% of the affected sisters and 34% of the unaffected sisters who received hormonal therapy at or within 3 months of the time of the study. The h(2) estimates of DHEAS were 0.43 (P=.037) and 0.44 (P=.062) when all sisters and only untreated sisters, respectively, were included in the analysis. CONCLUSION(S): The correlation of serum DHEAS levels between PCOS probands and their sisters suggests a familial component in the regulation of DHEAS levels and possibly AA production in PCOS. The h(2) estimates of 0.43-0.44 for BMI-adjusted DHEAS suggest that genetic factors account for between 40% and 50% of the overall variation in DHEAS levels in these women. Our results support the hypothesis that circulating AA levels represent an inherited trait in PCOS.

Adult↗

Polycystic ovary syndrome in post-menopausal women--marker of the metabolic syndrome.

OBJECTIVES: To determine among post-menopausal women, the prevalence of polycystic ovary syndrome (PCOS) and to evaluate the endocrine and metabolic profile of these women in comparisons to women without PCOS. METHODS: All women attending two post-menopausal outpatient clinics, fulfilling the inclusion criteria, were evaluated by physical examination, detailed questionnaire and laboratory measurements of glucose, lipids and sex-hormone levels. RESULTS: Among 104 women 7 (6.7%) were diagnosed with PCOS. As compared to women without PCOS, central obesity was more common in the PCOS group (p=0.004), 4/7 had type 2 diabetes compared to 8/97 in the non-PCOS group (p=0.003) and 6/7 versus 31/97 had the characteristic dyslipidemia of the metabolic syndrome (p=0.047). CONCLUSIONS: PCOS is common in post-menopausal women attending outpatient's clinics, and is a marker for a metabolic profile that is associated with a high-risk for cardiovascular diseases (CVD).

Biomarkers↗

Plasminogen activator inhibitor activity, 4G5G polymorphism of the plasminogen activator inhibitor 1 gene, and first-trimester miscarriage in women with polycystic ovary syndrome.

We assessed whether hypofibrinolytic plasminogen activator inhibitor 1 (PAI-1 activity) showed an independent association with first-trimester miscarriage in the 430 women with polycystic ovary syndrome (PCOS) who had previous pregnancies (from a cohort of 967 women with PCOS). Prospectively, we hypothesized that Glucophage (Bristol-Myers Squibb, Princeton, NJ) promotes successful live births in women with PCOS by lowering PAI-1 activity before conception and maintaining further reductions of PAI-1 activity during the first trimester of pregnancy. We also assessed whether PAI-1 activity levels were independently related to PAI-1 genotype and to modifiable risk factors body mass index (BMI), insulin, and triglyceride. By stepwise logistic regression, with the dependent variable being previous pregnancy outcomes at 3 levels (live birth pregnancies only [n = 208]; both > or =1 live birth and > or =1 first-trimester miscarriage [n = 111]; or first-trimester miscarriages only [n = 71]) and explanatory variables PAI-1 genotype, PAI-1 activity, insulin, homeostasis model assessment of insulin resistance, BMI, and triglyceride, PAI-1 activity was positively associated with first-trimester miscarriage (P = .004). For each 5 IU/mL increment in PAI-1 activity, the risk being in an adverse first-trimester miscarriage category increased (odds ratio, 1.12; 95% confidence interval, 1.04-1.20). Prospectively, from pretreatment to the last preconception visit on Glucophage, in 30 women who subsequently had live births, PAI-1 activity fell 44%, but rose 19% in 23 women with first-trimester miscarriage (P = .03). In the 30 women with live birth pregnancies, median PAI-1 activity fell continuously from pretreatment through the first trimester (from 16.8 to 6.7 IU/mL), whereas PAI-1 activity was either unchanged or rose in women with first-trimester miscarriage. Of the 921 women with PCOS who had 4G5G data, 718 (78%) had 4G4G-4G5G genotypes vs 87 (69%) of 126 normal female controls (chi(2) = 4.95, P = .026). The 4G allele frequency was 53% in women with PCOS vs 46% in controls (chi(2) = 4.3, P = .04). Of the 866 women with PCOS who had PAI-1 activity data, by stepwise regression, positive independent determinants of PAI-1 activity included BMI (partial R(2) = 10.6%, P < .0001), insulin (partial R(2) = 2.8%, P < .0001), triglyceride (partial R(2) = 1.1%, P = .0009), and the 4G4G-4G5G genotype (partial R(2) = 1%, P = .0011). The PAI-1 gene 4G polymorphism is more common in women with PCOS than in normal women and, in concert with obesity, hyperinsulinemia, and hypertriglyceridemia, contributes to treatable, hypofibrinolytic, miscarriage-promoting, high PAI-1 activity. Preconception and first-trimester decrements in PAI-1 activity on Glucophage are associated with live births, whereas increments or no change in PAI-1 activity despite Glucophage appears to be associated with first-trimester miscarriage.

Abortion, Spontaneous↗

Acute phase proteins: C-reactive protein and fibrinogen in young women with polycystic ovary syndrome.

Females with polycystic ovary syndrome (PCOS) are characterized by several metabolic abnormalities that favor the development of atherosclerosis. Atherosclerosis is possibly a chronic inflammatory process, and the markers of the inflammatory state, such as C-reactive protein (CRP) and fibrinogen may be useful to assess the global risk of developing cardiovascular diseases. These proteins might be helpful in finding females with subclinical atherosclerosis. The purpose of this study was to assess the serum CRP and fibrinogen concentrations in young females with PCOS and to clarify the possible correlations between their levels and selected anthropometric, metabolic and hormonal indices. Study assessed a group of 57 females with PCOS (mean age 28.2+/-6.4 years). That group was further divided into two subgroups: the first with body mass index (BMI)</=25 (21 females of mean age 27.4+/-7.0 years) and second with BMI>25 (36 females of mean age 28.6+/-6.0 years). In the control group there were 22 healthy females (mean age 31.6+/-8.5 years). That group was again divided into two subgroups: the first with BMI</=25 (10 females, mean age 30.2+/-8.4 years) and second with BMI>25 (12 females, mean age 31.7+/-8.7 years). Results demonstrated statistically significantly higher CRP concentration in females with PCOS compared to healthy individuals in both BMI subgroups. PCOS females showed also higher plasma insulin levels. There was, however, no statistically significant difference in fibrinogen concentrations. The hormonal profile of females with PCOS seems to influence the concentration of CRP and fibrinogen in different ways. This was evident in the positive correlation between plasma fibrinogen and androstenedione and in the lack of correlation between CRP and androgens and in the positive correlation between CRP and estradiol and the negative correlation between fibrinogen and estradiol. In conclusion, high CRP concentration in females with PCOS probably speaks for a higher risk for cardiovascular diseases.

Journal Article↗

Multitarget interactions of bisphenol A in polycystic ovary syndrome: evidence from integrated network toxicology, mendelian randomization, and molecular docking.

OBJECTIVE: To study the potential pathogenic mechanisms of bisphenol A (BPA) in polycystic ovary syndrome (PCOS) using an integrative computational strategy. DESIGN: Integrative computational study combining network toxicology, Mendelian randomization (MR), and molecular docking. SUBJECTS: For MR analysis, genetic data were sourced from large European-ancestry cohorts, including plasma protein quantitative trait loci data and genome-wide association study summary statistics for PCOS (3,045 cases and 267,780 controls). EXPOSURE: In silico exposure to BPA for target prediction; genetically predicted plasma protein levels for causal inference. MAIN OUTCOME MEASURES: Identification of overlapping targets between BPA and PCOS; functional enrichment pathways; causal effects of prioritized proteins on PCOS risk (odds ratios with 95% confidence intervals); binding affinities between BPA and core targets (kcal/mol). RESULTS: Network toxicology identified 310 overlapping targets between BPA and PCOS. Enrichment analyses revealed significant involvement in endocrine signaling, inflammatory pathways (eg, IL-17), and cellular processes. MR demonstrated that genetically elevated levels of RET, CXCL8, HTR6, MMP1, MMP9, NTRK1, and TNNI2 were significantly associated with increased PCOS risk, whereas higher PSAP and SHBG levels were protective. Molecular docking confirmed stable binding between BPA and all nine key targets, with strongest affinity for SHBG (-8.4 kcal/mol), followed by NTRK1, TNNI2, and RET. CONCLUSION: This integrative investigation suggests that BPA may contribute to PCOS pathogenesis through multitarget interactions involving inflammatory mediators, endocrine regulators, and tissue remodeling proteins. The findings provide prioritized targets and mechanistic insights for future experimental validation and environmental risk assessment.

Female↗

Insulin resistance, polycystic ovary syndrome, and type 2 diabetes mellitus.

OBJECTIVE: To review the definition and prevalence of two insulin resistance (IR)-associated phenotypes, polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus, as well as the risk and nature of their simultaneous presentation. DESIGN: Review of published literature. RESULT(S): Insulin resistance affects between 10% and 25% of the general population. Two common disorders frequently associated with IR are PCOS, affecting 4% to 6% of reproductive-aged women, and type 2 diabetes mellitus, which is observed in about 2% to 6% of similarly aged women. Overall, about 50% to 70% of women with PCOS and 80% to 100% of patients with type 2 diabetes mellitus have variable degrees of IR. Insulin resistance and its secondary hyperinsulinemia appear to underlie many of the endocrine features of PCOS in a large proportion of such patients. The risk of type 2 diabetes mellitus among PCOS patients is 5- to 10-fold higher than normal. In turn, the risk of PCOS among reproductive-aged type 2 diabetes mellitus patients appears to be similarly increased. CONCLUSION(S): It remains to be determined whether PCOS and type 2 diabetes mellitus represent no more than different clinical manifestations of the same IR syndrome, with their phenotypic differences due to the presence or absence of a coincidental genetic defect at the level of the ovary or pancreas, respectively, or representing the result of etiologically different subtypes of IR syndromes.

Diabetes Mellitus, Type 2↗

Self-selected women with polycystic ovary syndrome are reproductively and metabolically abnormal and undertreated.

OBJECTIVE: To determine whether self-selected women with polycystic ovary syndrome (PCOS) are abnormal compared with a control population. DESIGN: Case-control. SETTING: Support group meeting organized and initiated by patients. PATIENT(S): Forty-five self-selected women with PCOS and 80 control women. INTERVENTION(S): Self-selected women with PCOS at a peer support conference completed a questionnaire, had a brief physical, and gave a fasting blood sample. MAIN OUTCOME MEASURE(S): Historical, biometric, and assay results. RESULT(S): Sixty percent of the women attending the conference participated in the study. Most had been diagnosed with PCOS on the basis of ovarian morphology (35%). They were more likely to be nulliparous and have a history of oligomenorrhea (96%). They were hyperandrogenemic (significantly elevated testosterone and DHEAS levels) compared with control women. Self-selected women with PCOS displayed multiple metabolic abnormalities compared with control women, including elevations in blood pressure, waist-hip ratio, fasting insulin, fasting total cholesterol, and fasting low-density lipoprotein cholesterol levels, as well as a significant decrease in fasting glucose-insulin ratio and high-density lipoprotein cholesterol levels. CONCLUSION(S): Self-selected women with PCOS have reproductive and metabolic abnormalities. The majority of these women received inadequate treatment despite having risk factors for endometrial cancer, diabetes, and/or heart disease. Our study also suggests that women attending or participating in a PCOS support group are willing and likely to participate in clinical studies.

Adult↗

Evidence for competing effects of body mass, hyperinsulinemia, insulin resistance, and androgens on leptin levels among lean, overweight, and obese women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the relationships between leptin, body composition, insulin resistance, androgens, and reproductive indices among women with polycystic ovary syndrome (PCOS). DESIGN: Matched case-control study. SETTING: Academic reproductive endocrine practice; school of public health. PATIENT(S): Forty-six Caucasian women with PCOS and 46 population-based controls matched by age and body mass index (BMI). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Leptin, insulin, androgenic hormones, body composition parameters; reproductive parameters. RESULT(S): Overall, leptin levels among women with PCOS did not differ significantly from those of control women (20.4 +/- 14.9 vs. 21.9 +/- 14.3 ng/mL). However, within the lowest BMI tertile, women with PCOS had significantly lower leptin levels (9.6 vs. 18.3 ng/mL), comparable insulin, and higher testosterone concentrations than controls of similar body mass. Within the overweight and obese subgroups, both insulin and testosterone levels were increased among women with PCOS; leptin levels, although higher among obese cases, were not statistically different than those in controls. CONCLUSION(S): Below a certain BMI, hyperandrogenic women with PCOS have lower leptin levels than controls. Conversely, overweight and obese PCOS subjects appear to produce insufficient leptin for a given fat mass, relative to the degree of hyperinsulinemia, potentially because of the competing effects of adipocyte insulin resistance and androgens on leptin.

Adult↗

Relation of intra-abdominal fat distribution to metabolic disorders in nonobese patients with polycystic ovary syndrome.

OBJECTIVE: To investigate the relation between intra-abdominal fat distribution and metabolic disorders in nonobese patients with the polycystic ovary syndrome (PCOS). DESIGN: Prospective case-control study. SETTING: University-based hospital. PATIENT(S): Thirty nonobese patients with PCOS and 30 lean women with regular menstrual cycles (controls). All participants had a body mass index < 25kg/m(2). MAIN OUTCOME MEASURES: Subcutaneous and intra-abdominal visceral and preperitoneal fat thicknesses were assessed by ultrasonography. Glucose tolerance and insulin sensitivity were evaluated by standard 75-g oral glucose tolerance test and area-under-the-curve analysis. Serum hormones and lipid profile were measured. RESULT(S): The mean preperitoneal and visceral fat thicknesses were significantly greater in nonobese patients with PCOS. Subcutaneous fat mass was similar between the PCOS and control groups. Nonobese patients with PCOS had glucose intolerance, hyperinsulinemia, and dyslipidemia, manifested by high serum levels of triglyceride, total cholesterol, and high-density lipoprotein (HDL) levels and low serum low-density lipoprotein (LDL) levels. No correlation existed between subcutaneous fat thickness and the metabolic variables in nonobese patients with PCOS. However, serum triglyceride levels correlated with visceral fat and preperitoneal fat thickness. The mean HDL level correlated negatively with visceral fat and preperitoneal fat thickness. The area under the curve for insulin and mean fasting insulin levels correlated positively with visceral fat thickness. In multiple regression analysis, visceral fat thickness contributed significantly to high serum triglyceride and fasting insulin levels. CONCLUSION(S): Intra-abdominal preperitoneal and visceral fat accumulation may contribute to the development of glucose and lipid metabolism disorders in nonobese patients with PCOS.

Abdomen↗

Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome.

OBJECTIVE: Insulin resistance is a common feature of both polycystic ovary syndrome (PCOS) and non-insulin-dependent diabetes mellitus (NIDDM); however, the persistent reproductive disturbances appear to be limited to the former, suggesting that insulin resistance in the ovary itself may confer this susceptibility. DESIGN: Prospective study. SETTING: University-affiliated department. PATIENT(S): Forty-four women undergoing IVF treatment, of whom 11 had polycystic ovaries and 33 had normal ovulation (NO). INTERVENTION(S): The various effects and signaling of insulin and insulin-like growth factor-1 (IGF-1) were examined in cultured ovarian granulosa cells treated with troglitazone (1 microg/mL) or with vehicle by reverse transcription-polymerase chain reaction, western blot, and in vitro functional analyses. MAIN OUTCOME MEASURE(S): Glycogen and DNA syntheses, mRNA and protein expression, and cellular localization of insulin/IGF-1 receptors and insulin receptor substrates (IRSs). RESULT(S): There were significant decreases in insulin-stimulated glucose incorporation into glycogen in PCOS cells, which is a metabolic action of insulin. However, IGF-1 stimulation was found to be greater in PCOS cells at all experimental concentrations with respect to thymidine incorporation compared with NO cells, which is a mitogenic action. Troglitazone increased the insulin-induced glycogen synthesis but reduced the IGF-1-augmented responses of DNA synthesis in PCOS cells to the range within those of NO granulosa cells. We then found that troglitazone treatment reversed the expression imbalance between IRS-1 and IRS-2 in PCOS cells. CONCLUSION(S): There is a selective defect in insulin actions in PCOS granulosa cells, which suggests ovarian insulin resistance, and this metabolic phenotype is associated with an enhanced IGF-1 mitogenic potential. Troglitazone could divergently alter expression of various IRS molecules and insulin actions and could be used as an ovarian insulin sensitizer and mitogen/steroidogenic inhibitor in PCOS.

Adult↗

Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations.

OBJECTIVE: To investigate the impact of body weight (BW) and insulin levels on gonadotropin and androgen levels in women with the polycystic ovarian syndrome (PCOS). DESIGN: Comparative study of endocrinologic parameters in PCOS women. SETTING: University Hospital Reproductive Endocrinology Unit. PATIENTS: Thirty obese and 19 nonobese women with PCOS. Seven obese and 7 nonobese normal women. MAIN OUTCOME MEASURES: Serum concentrations of insulin, testosterone, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone. Serum LH response to gonadotropin-releasing hormone (GnRH) administration and assessment of insulin resistance by the continuous infusion of glucose with model assessment (CIGMA) test. RESULTS: Fasting insulin levels correlated with body mass index (BMI). Basal LH levels correlated inversely with BMI. Nonobese women with PCOS had a higher LH response to GnRH than obese women with PCOS. Only obese women with PCOS showed insulin resistance and fasting hyperinsulinemia. CONCLUSIONS: The data suggest that women with PCOS may be divided into two subgroups: those with obesity, insulin resistance, hyperinsulinemia, and normal/minimally elevated LH levels and those with normal BW, elevated LH levels, and normoinsulinemia.

Adult↗

In vitro fertilization and embryo transfer for the treatment of infertility associated with polycystic ovary syndrome.

OBJECTIVE: To examine the outcome of treatment with IVF-ET of women with polycystic ovarian syndrome (PCOS) who failed to conceive on conventional treatment. DESIGN: Retrospective analysis with an age-matched control group. SETTING: University hospital infertility clinic and IVF unit. PATIENTS. INTERVENTIONS: Sixty-eight women with PCOS who had failed to conceive on treatment with clomiphene citrate and during six ovulatory cycles on gonadotropins underwent 208 cycles of IVF-ET. An age-matched group of 68 women with a tubal mechanical factor who received 143 treatment cycles during the same period served as controls. MAIN OUTCOME MEASURES: Cumulative conception rates, the cumulative livebirth rates, and IVF-ET data were compared between the two groups. Results of treatment with and without GnRH agonist (GnRH-a) within the groups were also compared. RESULTS: A comparison of PCOS and mechanical factor (control) groups showed almost identical results at 6 months for cumulative conception rate (82% versus 85%) and cumulative livebirth rate (69% versus 65%). Significantly more oocytes were retrieved but a smaller percentage fertilized in PCOS, and the pregnancy rate per ET did not differ between the two groups (23% versus 26%). Treatment with GnRH-a and gonadotropins as opposed to gonadotropins alone improved the cumulative conception rate, miscarriage rate, and cumulative livebirth rate in the PCOS but not in the control group and improved fertilization rates in both groups. CONCLUSIONS: For patients with PCOS who fail to conceive with gonadotropin treatment, IVF-ET is a successful treatment alternative, producing results equal to those for women with a mechanical tubal factor. Better results were achieved with GnRH-a in women with PCOS but made no difference to those with a mechanical tubal factor compared with treatment with gonadotropins alone.

Adult↗

Evidence that an altered prolactin release is consequent to abnormal ovarian activity in polycystic ovary syndrome.

OBJECTIVE: To investigate whether endogenous dopaminergic activity is impaired in polycystic ovary syndrome (PCOS)-affected women and is normalized by medical ovariectomy. PATIENTS: Women with PCOS untreated (n = 23) and treated for 3 months with GnRH analogue (GnRH-a) administration (n = 10) and normal cycling young women (n = 23) as controls. INTERVENTIONS: Acute blockade of dopaminergic receptors by the IV administration of 5 mg of the dopaminergic receptor blocking agent sulpiride (sulpiride test) was performed 3 to 7 days after the initiation of spontaneous menses in cycling women or medroxyprogesterone acetate-induced menses in PCOS women. In PCOS women treated with GnRH-a administration (goserelin depot, 3.6 mg SC every 28 days), the sulpiride test was repeated 10 to 15 days after the third GnRH-a administration. MAIN OUTCOME MEASURE: Basal PRL levels and PRL increase induced by sulpiride. RESULTS: Basal PRL levels and the PRL response to sulpiride were increased in women with PCOS. In women with PCOS medical ovariectomy induced by GnRH-a administration reversed to normal both basal and sulpiride-stimulated PRL levels. CONCLUSIONS: In women with PCOS the abnormal regulation of PRL and presumably of hypothalamic neurotransmitters controlling PRL secretion is not a primary alteration but it is likely dependent on abnormal ovarian functionality.

Delayed-Action Preparations↗

Polycystic ovary syndrome: pathophysiology and outcome with in vitro fertilization.

OBJECTIVE: To assess the efficacy of IVP-ET in infertile women with the polycystic ovary syndrome (PCOS) and to provide a comprehensive review of contemporary therapeutic options and their complications as reflected in the current literature. DESIGN: Pertinent studies in medical literature identified through computerized bibliographic search and via manual review of relevant scientific publications. RESULTS: In vitro fertilization and ET is an effective therapy for PCOS patients who are refractory to ovulation induction in vivo or who have coexisting infertility factors. The use of GnRH agonist (GnRH-a) is associated with significant reductions in the incidence of pregnancy loss and may improve fertilization and cleavage rates. In the PCOS patient, the use of purified FSH preparations does not appear to improve pregnancy rates nor other clinical parameters when compared with hMG. Severe ovarian hyperstimulation syndrome (OHSS) is an important consideration when PCOS patients undergo superovulation protocols. Strategies for OHSS prevention include the use of intravenous albumin immediately after oocyte retrieval, triggering of ovulation with a GnRH-a, or withholding menotropin therapy for several days before hCG administration. Cryopreservation of all embryos for future transfer in an artificial cycle has also proven to be an effective alternative in PCOS patients at high risk for severe OHSS. CONCLUSIONS: Pregnancy rates for PCOS patients undergoing IVF-ET are comparable with those for women with tubal factor infertility. Therefore, IVF-ET should be offered to patients with PCOS who are refractory to conventional infertility modalities.

Embryo Transfer↗

Intrafollicular insulin-like growth factor-II levels in normally ovulating women and in patients with polycystic ovary syndrome.

OBJECTIVE: To investigate intrafollicular insulin-like growth factor II (IGF-II) in patients affected with polycystic ovary syndrome (PCOS) in comparison with normal women. DESIGN: Insulin-like growth factor-II was determined in 103 follicular fluids (FF) from normally ovulating women and in 102 FF from patients with PCOS. Ribonucleic acid was extracted from granulosa cells of follicles obtained from control and PCOS patients and from tissue from polycystic ovaries. SETTING: Procedures were performed in a university laboratory. PATIENTS: Twenty-nine normally ovulating women and 19 patients with PCOS underwent ovulation induction for IVF-ET with LH-releasing hormone (LH-RH) analog and gonadotropins. Eleven of them, 4 to 8 months later, underwent ovulation induction with approximately the same dosage of gonadotropins plus a standard dosage of GH. MAIN OUTCOME MEASURES: Intrafollicular IGF-II, IGF-I, epidermal growth factor (EGF), transforming growth factor beta 2, (TGF-beta 2), inhibin, and steroids were evaluated by appropriate RIA, immunoenzymatic assay (EIA), and ELISA assays. The expression of the gene encoding IGF-II was analyzed by Northern blot. RESULTS: Intrafollicular IGF-II was lower in PCOS than in controls. Accordingly, IGF-II messenger RNA expression was lower in PCO than in normal granulosa cells. Several differences in FF IGF-I, EGF, inhibin, and TGF-beta 2 concentrations were observed between PCOS and controls. CONCLUSIONS: Both IGF-II and IGF-I were reduced in PCOS, confirming a possible role of an IGF imbalance in the development of this disease.

Adult↗