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Do polycystic-appearing ovaries affect the risk of cardiovascular disease among women with polycystic ovary syndrome?

OBJECTIVE: To determine if polycystic-appearing ovaries (PAO) are associated with differences in risk factors for cardiovascular disease among women with polycystic ovary syndrome (PCOS). DESIGN: Case-control sub-study. SETTING: Division of Reproductive Endocrinology, Magee-Womens Hospital. PATIENT(S): Women with PCOS (n = 63) and non-PCOS controls (n = 56). INTERVENTION: Transvaginal ultrasonography and single sample venipuncture. MAIN OUTCOME MEASURE(S): Ultrasound ovarian appearance, fasting insulin, lipoproteins, androgens, LH/FSH ratio, anthropomorphic measurements, and blood pressure. RESULT(S): Women with PCOS had higher androgen and fasting insulin levels, a more adverse lipid profile, greater waist-hip and LH/FSH ratios, and a larger ovarian volume than controls. Thirty-three percent of the cases with PCOS, but only 5% of controls, showed PAO on ultrasound study (P<.01). PCOS cases with and without PAO had comparable levels of fasting insulin, lipids, and blood pressures. PCOS cases with PAO had a higher LH/FSH ratio (P=.028), increased levels of serum androstenedione (P=.029) and testosterone (P=.055), and greater ovarian volume (P=.024) compared to non-PAO patients. CONCLUSION: Women with PCOS have greater cardiovascular risk than controls. Within PCOS cases, however, the ultrasound appearance of polycystic ovaries does not appear to further intensify the cardiovascular disease risk profile of these women.

Adult↗

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↗

Immunolocalization of Fas and Fas ligand in the ovaries of women with polycystic ovary syndrome: relationship to apoptosis.

Both Fas (APO-1, CD95), an apoptosis-inducing receptor, and its ligand, Fas ligand (FasL, CD95L), have been localized to the ovary. Granulosa cell apoptosis occurs in antral follicular atresia. In polycystic ovary syndrome (PCOS), antral follicles accumulate with some atretic features. The ovarian expression of Fas and FasL was examined in PCOS by immunohistochemistry and correlated with immunodetection of apoptotic cells. Fas immunostaining was present in pre-antral follicle oocytes, some primary and secondary pre-antral follicle granulosa cells, and both granulosa and theca of antral follicles. Thecal staining persisted with advancing atresia, while granulosa staining declined. In antral follicles, abundant Fas-positive cells co-localized with scattered nuclei immunopositive for apoptosis. Ovarian vascular myocytes were strongly Fas-immunopositive. FasL immunostaining was present in pre-antral follicles in oocytes and variably in granulosa. In antral follicles, granulosa and thecal FasL staining increased with advancing atresia. Normal control ovaries showed follicular Fas and FasL staining patterns similar to those in PCOS, but vascular staining was less prominent. In one healthy follicle, Fas immunostaining was seen in the oocyte and weakly in mural granulosa and theca interna. The results suggest that in PCOS, an alteration in Fas-mediated apoptosis, does not cause abnormal folliculogenesis, but may promote ovarian vascular remodelling.

Adult↗

Laparoscopic electrocautery of the ovaries versus recombinant FSH in clomiphene citrate-resistant polycystic ovary syndrome. Impact on women's health-related quality of life.

BACKGROUND: Ovulation induction with gonadotrophins is the standard treatment strategy for women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). Laparoscopic electrocautery of the ovaries is an alternative treatment modality, leading to a comparable cumulative pregnancy rate. In deciding which treatment to opt for, women's health-related quality of life (HRQoL) should be taken into account. METHODS: A total of 168 CC-resistant women with PCOS were randomly assigned to receive either the electrocautery strategy, entailing laparoscopic electrocautery of the ovaries followed by CC and recombinant FSH (rFSH) if anovulation persisted, or ovulation induction with rFSH. We assessed women's HRQoL with the standard questionnaires Short Form-36, Rotterdam Symptom Checklist and Center for Epidemiological Studies Depression Scale, administered before randomization and 2, 12 and 24 weeks thereafter. RESULTS: The intention to treat analysis revealed no significant differences between the treatment groups on any of the scales at any point during follow-up. In women without an ongoing pregnancy, those treated with rFSH showed significantly more depressive symptoms than women allocated to the electrocautery strategy, with or without CC, although differences were small. CONCLUSIONS: Overall, HRQoL was not affected in both groups. In women still under treatment, rFSH was slightly more burdensome for women's HRQoL than electrocautery with or without CC.

Clomiphene↗

Polycystic ovaries are inherited as an autosomal dominant trait: analysis of 29 polycystic ovary syndrome and 10 control families.

The aim of this study was to obtain evidence for the genetic basis of polycystic ovaries (PCO) and premature male pattern baldness (PMPB) by screening first-degree relatives of women affected by polycystic ovary syndrome (PCOS). Because of the high prevalence of PCO in the general population, we also studied first-degree relatives of ten asymptomatic control volunteers of reproductive age. The probands were recruited prospectively from infertility and endocrine clinics, where they presented with various clinical symptoms of PCOS. Each had PCO, on transvaginal ultrasound scan. The families of 29 probands and 10 volunteers agreed to take part in the study. Clinical, ultrasound, and biochemical parameters were used to define PCO/PCOS. All female relatives had an ovarian ultrasound scan and hormone profile performed. History was used to assign status in postmenopausal women. All male relatives were assessed for early onset (<30 yr old) male pattern baldness, by photographs. All relatives were assigned affected (PCO/PMPB) or nonaffected status, and segregation analysis was performed. Of the relatives of 29 PCOS probands, 15 of 29 mothers (52%), 6 of 28 fathers (21%), 35 of 53 sisters (66%), and 4 of 18 brothers (22%) were assigned affected status. First-degree female relatives of affected individuals had a 61% chance of being affected. Of the first-degree male relatives, 22% were affected. Of a total of 71 siblings of PCOS probands, 39 were affected, giving a segregation ratio of 39/32 (55%), which is consistent with autosomal dominant inheritance for PCO/PMPB. In the control families, 1 of 10 probands (10%), 1 of 10 mothers (10%), no fathers, 2 of 13 sisters (15%), and 1 of 11 brothers (9%) were affected. Of a total of 24 siblings, 3 were affected (13%), giving a segregation ratio (observed/expected) of 3/12, which was significantly different from autosomal dominant inheritance. The inheritance of PCO and PMPB is consistent with an autosomal dominant inheritance pattern in PCOS families, perhaps caused by the same gene. There was no such genetic influence in families of women without PCOS. Sisters of PCOS probands with polycystic ovarian morphology were more likely to have menstrual irregularity and had larger ovaries and higher serum androstenedione and dehydroepiandrosterone-sulfate levels than sisters without PCO. This suggests a spectrum of clinical phenotype in PCOS families. Men with PMPB had higher serum testosterone than those without. Collectively, these data are consistent with a role for genetic differences in androgen synthesis, metabolism, or action in the pathogenesis of PCOS.

Adult↗

[Laparoscopic electrocoagulation of the ovaries prior to in vitro fertilization in two females with polycystic ovary syndrome].

A 32-year-old woman with oligomenorrhoea/amenorrhoea and a 30-year-old woman with oligomenorrhoea as a result of the polycystic ovary syndrome (PCOS), with an active desire for children, were considered eligible for in-vitro fertilisation (IVF) because the semen of their partners was of inferior quality. However, the patients' polycystic ovaries proved to be difficult to stimulate. There was either no response to stimulation with gonadotropins or an excessive response, as a result of which treatment had to be stopped prematurely. However, when laparoscopic ovarian electrocautery was done and a stimulation cycle was subsequently started, adequate and controlled stimulation of the ovaries turned out to be quite possible in both cases. Afterwards, a follicle aspiration could be performed with success and intracytoplasmic sperm injection (ICSI) was carried out. Embryo transfer resulted in pregnancy only in the first patient. This procedure, which has never been described before in the Dutch literature, might also be effective in other women with PCOS who are eligible for IVF.

Adult↗

Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome.

OBJECTIVE: To determine whether mutations in the FSH receptor gene are associated with premature ovarian failure (POF) or resistant ovary syndrome (ROS) in women in the UK. To determine whether an allelic variant of the FSH receptor gene affects fertility parameters in women with polycystic ovary syndrome (PCOS). DESIGN: A mutation screen using DNA from women with POF and ROS. Restriction digest of amplified DNA from women with POF, ROS, PCOS and controls to determine allelic variant status. Fertility parameters were compared between allelic variant subgroups of women with PCOS. PATIENTS: The study population comprised 49 women with POF, 5 with ROS, 93 with PCOS and 51 controls. MEASUREMENTS: In women with PCOS, fertility and menstrual status was recorded and serum FSH and ovarian volume were measured. RESULTS: No mutation of the FSH receptor gene was found in women with POF or ROS. The allelic variant Thr307/Ser680 was found to be similarly prevalent in all study groups. The Thr307/Ser680 variant was found to have no phenotype in terms of fertility parameters in women with PCOS. CONCLUSIONS: Mutations of the FSH receptor gene are rare in women with premature ovarian failure or resistant ovary syndrome in the UK. Polymorphisms of the FSH receptor gene do not appear to have pathophysiological significance with regard to ovarian function.

Adult↗

Insulin-mediated secretion of ecdysteroids from mosquito ovaries and molecular cloning of the insulin receptor homologue from ovaries of bloodfed Aedes aegypti.

The reproductive cycle of female mosquitoes is activated by ingestion of blood from vertebrate hosts. Shortly after feeding, neurohormones are released from the brain neurosecretory system and stimulate the ovaries to secrete ecdysteroids, which are necessary for vitellogenesis by the fat body. Because bombyxins, which are insulin-like peptides, stimulate ecdysteriodgenesis in silkworm larvae, we tested porcine insulin and found that it activates ecdysteroidogenesis and protein synthesis in ovaries isolated from unfed mosquitoes. To further characterize the regulation of ecdysteroidogenesis in female mosquitoes, we cloned the mosquito insulin receptor (MIR) homologue from ovarian mRNA. The sequence of the extracellular domain shows moderate homologies with vertebrate and Drosophila insulin receptor homologues, as well as with the insulin receptor-related receptor, the latter being an "orphan" receptor with an unknown function. In the intracellular domain, high homologies are observed, particularly in those subdomains that are responsible for ATP binding and kinase activity. Northern blot analysis of MIR demonstrated a highly specific expression in ovaries, and cloning experiments indicated its presence in the brain. Recombinant MIR extracts from a baculovirus expression system contained high constitutive kinase activity in the presence of manganese or magnesium. Activation was independent of a ligand. SDS-gel analysis suggested that the recombinant receptor was not post-translationally processed into an alpha- and beta-subunit as was expected from a putative cleavage signal. Enzymatic properties of the proreceptor are presented: the Km for ATP was between 15 and 50 microM in the presence of a synthetic substrate: maximal kinase activity to 100-fold over basic activity was reached in the presence of 1 mM manganese. Stimulation of key oogenic processes by porcine insulin and identification of a MIR indicate that insulin-like neurohormones may have an important regulatory role in mosquito oogenesis.

Aedes↗

Pregnancy after autografting and allografting vascularized ovaries and en bloc vascularized ovaries with adnexa in rabbits.

Initially, techniques for autografting ovaries with or without adnexa were developed but a 30% vascular failure rate was experienced by day 14. Of the technically successful grafts, 50% proved fertile. Single vascularized ovaries with their oviducts were then allografted into bilaterally ovariectomized rabbits by microsurgical techniques and the vascular failure rate was reduced to 5% of 40 grafts. The time-course of rejection in untreated recipients was mapped by histological examination and by 24-h culture of fallopian tubes after autopsy at different times after transplantation. Control allografts were consistently rejected by day 20. Striking prolongation of both types of graft was obtained with a short 17-day course of cyclosporin A at 10 or 15 mg day-1 kg-1. Indeed, significant evidence of rejection was found in only two ovaries out of 20 so far examined histologically. Mating behaviour, ovulation, ciliary function and transport of ova appeared normal in 80% of the recipients as long as 18 weeks after stopping cyclosporin A treatment. Only one of the ovarian allografted rabbits has so far been mated and this produced seven normal young 126 days after transplantation. However, none of the five animals mated after being allografted with en bloc adnexa have so far become pregnant.

Adnexa Uteri↗

Supernumerary ovary found by ultrasonogram and FSH measurement after an extensive operation for a yolk sac tumor of the ovary.

A rare case of supernumerary ovary found by a transvaginal ultrasonogram and follicle-stimulating hormone (FSH) measurement is presented. The patient was a 32-year-old female who underwent an extensive operation for a yolk sac tumor of the ovary. An asymptomatic cystic tumor was found during follow-up. There was no evidence of recurrence or metastasis of the yolk sac tumor. Although histological confirmation was not possible because the patient refused removal of the mass, a diagnosis of supernumerary ovary was made because changes in the shape of the cystic mass completely correlated with changes in the serum FSH level.

Adult↗

The vascular anatomy of the ovary and the relative contribution of the ovarian and uterine arteries to the blood supply of the ovary in the guinea-pig.

Guinea-pig ovaries were supplied by paired ovarian arteries which on both sides were in close apposition to the corresponding ovarian veins along their course, and which formed end-to-end anastomoses with the cranial ends of the uterine arteries. A total of three or four spirally coiled branches of the ovarian artery entered the ovarian hilus and branched within the ovary to supply both cortex and medulla. Usually, each Graafian follicle and corpus luteum was supplied by a single arterial branch from one of the cortical vessels. The veins were less coiled than the arteries. One or occasionally two veins drained each corpus luteum. Several large veins draining each ovary joined to form a single ovarian vein, which finally joined the caudal vena cava on the right side and the left renal vein on the left side. The direction of blood flow in the utero-ovarian arterial anastomosis was studied by direct visual observation in anaesthetised guinea-pigs; blood flowed towards the uterus in all observations on all guinea-pigs studied. The functional significance of the above observations is discussed.

Animals↗

Changes in catalase activity and hydrogen peroxide level in rat ovary during estrous cycle and induction of catalase in rat ovary by estradiol-17 beta.

Catalase activity in the whole ovary homogenate and hydrogen peroxide level in the differentially centrifuged fractions of the ovary homogenate during each stage of estrous cycle were measured. The highest catalase activity was observed in the metestrous which declined in the estrous and proestrous and was lowest in the diestrous. An inverse relationship was found between catalase activity and hydrogen peroxide production. Treatment of immature (28-29 days old) female rats with estradiol-17 beta (5 micrograms in 0.2 ml oil/animal/day for consecutive 3 days, s.c.) increased the ovarian catalase activity. The findings indicate that the free radical-scavanger system may have functional role in the ovary.

Animals↗

Status of the contralateral ovary in encapsulated low grade malignant tumors of the ovary.

The incidence of bilateral involvement in carcinoma of the ovary is shown to be relatively high. This is true for the different histologic type of malignant lesions and even when the ovary is grossly normal in appearance and on palpation. Only when carcinoma of the ovary is low grade, intracystic, unruptured and nonadherent and is in a young woman desirous of childbirth can it be managed conservatively.

Adenocarcinoma↗

The silent ovary: a five year survey of cancer of the ovary at the Hutt Hospital 1973-1977.

Cancer of the ovary is the leading cause of death from gynaecological cancer. Forty-six cases are reported to re-emphasise certain features. These include the short history and the high mortality rate regardless of what treatment is used. Whereas improvement has occurred in the treatment of cancer of the corpus and the cervix, there has been no improvement over two decades in cancer of the ovary. The moral of this tale, is to advise your women folk to avoid cancer of the ovary.

Adolescent↗

Laparoscopic "drilling" by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Problems in inducing ovulation in women with polycystic ovary syndrome (PCOS) and anovulation (failure to ovulate) are well recognised. Surgical ovarian wedge resection was the first established treatment for anovulatory PCOS patients but was largely abandoned of the risk of post-surgical adhesion formation. It was replaced by medical ovulation induction with clomiphene and gonadotrophins. However patients with PCOS treated with gonadotrophins often have a polyfollicular response and are exposed to the risks of ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. Although effective, it is an expensive, stressful and time consuming form of treatment requiring intensive monitoring. A new surgical therapy, laparoscopic ovarian "drilling", may avoid or reduce the need, or facilitate the use, of gonadotrophins for inducing ovulation. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions. It has been claimed in many uncontrolled observational studies that it is followed, at least temporarily, by a high rate of spontaneous postoperative ovulation and conception, or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness of laparoscopic ovarian drilling for ovulation induction in subfertile women with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS). SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group was used for the identification of randomised controlled trials (RCTS). A computerised MEDLINE search was used to identify non randomised controlled trials. SELECTION CRITERIA: Trials were eligible for inclusion if treatment consisted of laparoscopic ovarian drilling in order to induce ovulation in subfertile women with PCOS and compared with a concurrent control group. DATA COLLECTION AND ANALYSIS: Fourteen trials were identified; eight were included in the review of which seven were randomised. All trials were assessed for quality criteria. The main studied outcomes were ovulation and pregnancy rates. Miscarriage rate, multiple pregnancy rate, and incidence of overstimulation and ovarian hyperstimulation syndrome rate were secondary outcomes. MAIN RESULTS: With the exception of multiple pregnancy rates no differences were demonstrated for any of the interventions studied but the numbers of patients who have been randomised to controlled studies at this time is insufficient to conclude that laparoscopic ovarian drilling is more effective than gonadotrophin therapy for other outcomes. REVIEWER'S CONCLUSIONS: The value of laparoscopic ovarian drilling as a primary treatment for subfertile patients with anovulation (failure to ovulate) and polycystic ovarian syndrome (PCOS) is undetermined. There is insufficient evidence to determine a difference in ovulation or pregnancy rates when compared to gonadotrophin therapy as a secondary treatment for clomiphene resistant women. Multiple pregnancy rates are reduced in those women who conceive following laparoscopic drilling. None of the studied modalities of drilling technique had any obvious advantages.

Anovulation↗

Changes in sympathetic nerve activity of the mammalian ovary during a normal estrous cycle and in polycystic ovary syndrome: Studies on norepinephrine release.

Although it has been known for many years that the ovary is innervated by catecholaminergic nerve fibers and much experimental evidence has strengthened the notion that catecholamines are physiologically involved in the control of ovarian function, scarce evidence has been presented as to the role of sympathetic activity in ovarian pathologies that affect reproductive function. The purpose of this article is to provide a succinct overview of the findings in this area and discuss them relative to the pathology of polycystic ovary syndrome, the most common ovarian pathology in women during their reproductive years.

Animals↗

Effects of ovary suppression by a long-acting GnRH-agonist on circulating GH, insulin-like growth factor I and insulin levels in women with polycystic ovary syndrome.

Our aim was to investigate the effect of GnRH-agonist (GnRH-a) induced suppression of plasma sex steroids on serum GH, insulin like growth factor-I (IGF-I) and insulin levels after an oral glucose load (OGTT) in women with polycystic ovary syndrome (PCOS). Serum insulin, GH and IGF-I levels during a 75-g 4-h OGTT were measured in 3 nonobese and 7 obese hyperandrogenic women with PCOS and normal glucose tolerance before and after 10 weeks of treatment with the GnRH-a triptorelin (3,75 mg im every 28 days). Basal estrogen and androgen levels were also measured at time 0 of the first and the second OGTT. After the therapy serum estrogens and androgens were significantly suppressed. Body weight remained unchanged. Basal GH significantly increased after the treatment while fasting IGF-I and insulin levels decreased from (mean +/- SE) 349.3 +/- 31.8 to 278.7 +/- 33.2 ng/mL and from 22.4 +/- 4.1 to 18.8 +/- 4.4 microU/mL, respectively. The insulin response to OGTT (area under curve) was also reduced (from 16,017 +/- 2598 to 11,736 +/- 2317 microU/mL/240 min). Our results suggest that the GnRH-a induced suppression of ovary secretion may modify the serum GH and IGF-I levels and the insulin response to an OGTT in women with PCOS.

Adolescent↗