Presence Of Polycystic Ovaries Research Articles

Do Polycystic Ovaries on Ultrasound Scan Indicate Decreased Insulin Sensitivity in Sisters of Women with Polycystic Ovary Syndrome?

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenemia, insulin resistance, altered lipid profile, and therefore with subsequently increased risk for metabolic complications such as type 2 diabetes and cardiovascular diseases. It has been reported that sisters of probands with PCOS, who themselves had PCOS or hyperandrogenemia with normal menses, were more insulin resistant than unaffected sisters. We have previously reported that 60% of first-degree relatives (premenopausal mothers and sisters) of PCOS probands had polycystic ovaries (PCO) on ultrascan. Sisters with PCO were more likely to have oligomenorrhea and increased androgen levels than sisters without PCO. The aims of this study were to assess insulin sensitivity status [homeostasis model of assessment, quantitative insulin sensitivity check index, glucose to insulin ratio (G/I)] and lipid profiles in probands with PCOS and their sisters with PCO and without PCO on ultrascan. Mixed model hierarchical regression analysis, to accommodate the nonindependent nature of the subjects (family relationships), with the three groups together did not show significant differences in insulin sensitivity, calculated as quantitative insulin sensitivity check index, homeostasis model of assessment, and G/I for PCOS probands, through sisters with PCO on ultrascan, to sisters without PCO on ultrascan. There was a significant association of measures of insulin sensitivity with body mass index. Lipid parameters did not differ between the groups. These data suggest that presence of PCO on ultrasound scan per se does not predispose to reduced insulin sensitivity in sisters of women with PCOS. Because about 20% of premenopausal women in the general population have PCO on ultrascan, and obesity/overweight is becoming more prevalent, it is important that future studies take full account of the contribution made by obesity to risk factors for metabolic/vascular complications.

Prevalence of polycystic ovaries in women with androgenic alopecia.

Although androgenic alopecia is recognised to be a symptom of polycystic ovary syndrome (PCOS), it is not known whether polycystic ovaries (PCO) and associated endocrine abnormalities are present in patients who present with alopecia as a primary complaint. We therefore set out to determine the strength of the association between androgenic alopecia and PCO. We examined the prevalence of ultrasound-based polycystic ovarian morphology and associated clinical and biochemical features in a large multiethnic group of women whose presenting complaint was of alopecia, and in a control group. We studied 89 women of mixed ethnic origin with androgenic alopecia and compared them to 73 control women. A detailed history was taken, anthropometry was performed and assessment of body-hair distribution was made. The presence of PCO was established by pelvic ultrasound scan. Serum gonadotrophins, testosterone, androstenedione, dihydrotestosterone and sex hormone binding globulin concentrations were measured. Women with alopecia had a higher prevalence of PCO and hirsutism than the control population (PCO: 67% vs 27%, P<0.00001; hirsutism: 21% vs 4%, P=0.003). Women with alopecia (with or without PCO) had higher testosterone, androstenedione and free androgen index than controls, even though few had frankly abnormal androgens. These findings confirm an association between androgenic alopecia and PCO, and other symptoms of hyperandrogenaemia. Thus most women who present with androgenic alopecia as their primary complaint also have PCO and have indices of abnormal androgen production. Since PCO is a well known risk factor for development of type 2 diabetes, this association has important implications for long-term management.

Ultrasonographic assessment of endometrial receptivity at embryo transfer in an in vitro maturation of oocyte program

Ultrasonographic assessment of endometrial receptivity at embryo transfer in an in vitro maturation of oocyte program

Basal serum levels of FSH and estradiol in ovulatory and anovulatory women undergoing treatment by in-vitro maturation of immature oocytes.

The study aim was to establish whether basal serum levels of FSH and estradiol are predictive of outcome in women undergoing treatment by in-vitro maturation (IVM) of immature oocytes. Data were obtained from 123 unstimulated IVM cycles. Serum was taken between cycle days 2-4 for analysis. Patients received 10 000 IU of HCG 36 h before immature oocyte recovery that was performed between cycle days 9-14. IVM was performed and mature oocytes fertilized by ICSI, followed 2-3 days later by embryo transfer. Outcome measures included the number of immature oocytes retrieved, and the rates of oocyte maturation, fertilization, cleavage and pregnancy. A median (range) of 8 (0-36) immature oocytes was retrieved per patient. Oocyte maturation, fertilization, cleavage and pregnancy rates were 83, 76, 93 and 17.9% respectively. Serum FSH levels and the presence of polycystic ovary were significant independent predictors of the number of immature oocytes retrieved, whilst patient age and basal estradiol level were not. A basal serum estradiol level >100 pmol/l was associated with a significantly higher pregnancy rate (26 versus 11% for estradiol <100 pmol/l; P = 0.032). Measurement of basal serum levels of FSH and estradiol are useful in predicting the number of immature oocytes retrieved and the pregnancy rate in women undergoing unstimulated IVM treatment.

Plasma homocysteine, fasting insulin, and androgen patterns among women with polycystic ovaries and infertility.

To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic-appearing ovaries in an infertility setting. Among women referred for infertility evaluation (n = 54), homocysteine, androstenedione, DHEAS, total testosterone, fasting insulin/glucose and methyltetrahydrofolate reductase (MTHFR) polymorphism status (C677T mutation) were studied. Ovaries were examined via transvaginal sonogram by one observer and scored as either normal (n = 18) or polycystic (n = 36). When polycystic ovaries were identified, mean total testosterone was significantly higher than when non-polycystic ovaries were present (p = 0.01), although no measured androgen was outside the normal reference range in either group. Average BMI was higher in the polycystic group, but the difference was not significant (p = 0.10). We observed a trend toward higher mean fasting insulin levels in women with polycystic ovaries, but this increase did not reach statistical significance (p = 0.07). Median plasma homocysteine was identical (7.0 mmol/l) in both populations, and no study subject exceeded the current recommended maximum reference value. In this population, the presence of polycystic ovaries was associated with higher serum androgens (especially total testosterone) although none of the measured androgens were above the normal range. While fasting insulin levels were also higher in this group, median plasma homocysteine levels were similar irrespective of ovarian morphology. Concomitant plasma homocysteine derangements in this population of young, lean patients with polycystic-appearing ovaries seem unlikely. Further studies are needed to clarify the role(s) of homocysteine in human reproductive physiology.

What's new in the pathogenesis and prevention of ovarian hyperstimulation syndrome?

Several pathophysiological mechanisms have been proposed for the development of ovarian hyperstimulation syndrome (OHSS), such as activation of the ovarian renin-prorenin-angiotensin system, release of ovarian cytokines and nitric oxide, but numerous reports now attest to the role of vascular endothelial growth factor (VEGF), an endothelial cell mitogen, as an important mediator of the syndrome. Luteinizing hormone (LH) or human chorionic gonadotrophin (hCG) regulates VEGF production by the ovary. Formation of multiple follicles, as seen in regimens of ovarian stimulation used for in vitro fertilization (IVF), and intensified sensitivity towards human menopausal gonadotrophin (hMG) and hCG, as seen in women with polycystic ovaries (PCO) or polycystic ovary syndrome (PCOS), result in increased serum VEGF concentrations, probably due to enhanced VEGF production by the ovaries. It is possible that the hypersecretion of VEGF in women with PCO is due to an increase in the number of VEGF secreting cells or that the cells individually hypersecrete VEGF. This hypothesis was tested by in vitro studies on granulosa lutein cells. After the cells were stimulated with gonadotrophins and hCG, VEGF production was higher in granulosa cells obtained from women with PCO compared with those obtained from women with normal ovaries under similar culture conditions. The studies performed in vivo and in vitro were consistent with increased VEGF expression as a constitutive feature of PCO. Increased VEGF may be responsible for the fluid shift from the vascular bed to the extravascular space, which characterizes OHSS. Prevention of OHSS focuses on predicting the possibility of developing OHSS. Markers such as serum oestradiol concentrations and number of follicles on the day of hCG administration, the presence of PCO and the number of oocytes retrieved may be subject to inter-observer and inter-operator variations. As individual markers of OHSS, each of these factors predicts less than a quarter of cases of the syndrome. It has been shown that a combination of pretreatment diagnosis of PCO along with number of follicles on the day of hCG administration and ‘VEGF rise’ gives the highest prediction rates for the risk of developing OHSS. Neither pathogenesis nor prevention and treatment of OHSS are specific. Therefore, at present, OHSS remains a condition that cannot be avoided altogether.

4 Complications of ovarian stimulation

We review three complications of ovarian stimulation, namely ovarian hyperstimulation syndrome, thromboembolic disease in relation to fertility treatment and multiple pregnancy. Current views on the ovarian hyperstimulation syndrome emphasize its association with the presence of polycystic ovaries. We review here the pathophysiological background of this association and focus on the central role of vascular endothelial growth factor (VEGF). Overexpression of VEGF in the polycystic ovary is thought to contribute to its characteristic multifollicular response to gonadotrophic stimulation. Release of large amounts of VEGF into the circulation is thought to account for the development of the clinical syndrome of ovarian hyperstimulation. The implications of this understanding are explored and the clinical features of the condition and its management are described. Thromboembolic disease is increasingly recognized as a serious if rare complication of infertility treatment. The subject is reviewed here with special reference to two recently published and important papers. The most concerning complication of infertility treatment is multiple pregnancy. Few doctors seem to be aware of the dire statistics: every index of obstetric outcome is adversely affected. The survival, health and family circumstances of children born as the result of multifetal gestation are all impaired. Infertility patients need a clear understanding of the risks involved so that they can appreciate the need for intensive monitoring of ovarian stimulation. In our opinion a knowledge of the rate of multiple pregnancy is quite as important as knowing the clinic's 'success' rate.

Polycystic ovaries and associated metabolic abnormalities in Indian subcontinent Asian women.

To determine the prevalence of polycystic ovaries (PCO) in Asian women living in England who are of Indian subcontinent origin or ancestry and to investigate the relationship between the presence of PCO and/or non-insulin dependent diabetes mellitus (NIDDM) and insulin sensitivity and other metabolic parameters. A random sample of Indian subcontinent Asian women was obtained from the lists of local General Practitioners and a translating service. These women were invited to attend for a medical history questionnaire, examination, venous blood sample for hormonal assessment and transvaginal ovarian ultrasonography. Groups of women without PCO or NIDDM, with NIDDM but not PCO, with PCO but not NIDDM and with both NIDDM and PCO were drawn at random from this population and from Indian subcontinent Asian women attending the Diabetes Unit. They underwent further studies, including measurement of insulin sensitivity using a short intravenous insulin tolerance test. 212 Indian subcontinent Asian women aged 18-40 took part in the initial study. Insulin sensitivity was measured in 13 women without PCO or NIDDM, 13 women with NIDDM but not PCO, 15 women with PCO but not NIDDM and 12 women with both NIDDM and PCO. The main outcome measures were prevalence of polycystic ovaries, clinical features of hyperandrogenism, fertility, blood pressure, serum gonadotrophins, testosterone and sex hormone binding globulin, fasting blood lipids, glucose and insulin, and insulin sensitivity. The prevalence of PCO in Indian subcontinent Asian women was 52% (110/212). There were significant associations between PCO and menstrual irregularity; infertility; the Ferriman and Gallwey score for body hair distribution; the presence of acanthosis nigricans and the fasting blood glucose concentration. There were no differences between women with PCO and those with normal ovarian morphology with respect to systolic and diastolic blood pressure, fasting total, HDL and LDL cholesterol and triglyceride concentrations. The subgroup of women without PCO or NIDDM had the highest insulin sensitivity (189.1 +/- 46.4 mumol glucose/l/min, mean +/- SD) and the women with both PCO and NIDDM had the lowest insulin sensitivity (80.5 +/- 30.9 mumol glucose/l/min). There was no significant difference in insulin sensitivity between those with PCO but not NIDDM (125.0 +/- 59.5 mumol glucose/l/min) and those with NIDDM but not PCO (120.8 + 38.0 mumol glucose/l/min). The effects of NIDDM and PCO on insulin sensitivity were independent; the effect of PCO on insulin sensitivity was -60 mumol glucose/l/min (95% confidence interval -100 to -21, P = 0.004) and the effect of NIDDM was -68 mumol glucose/l/min (95% confidence interval -105 to -31, P < 0.001). There were no significant relationships between insulin sensitivity and fasting plasma insulin, systolic or diastolic blood pressure, fasting serum cholesterol or triglyceride. The prevalence of polycystic ovaries in Indian subcontinent Asian women is very high and it has significant clinical associations. Polycystic ovaries and non-insulin dependent diabetes mellitus are associated with similar degrees of reduced insulin sensitivity in this population. Their effects are independent suggesting that these changes in insulin sensitivity involve different mechanisms. Polycystic ovaries unlike non-insulin dependent diabetes mellitus, are not associated with a defect in the secretion of insulin.

Diagnosis, prevention and management of ovarian hyperstimulation syndrome

The overall incidence of clinically important (moderate to severe) OHSS ranges from 1% to 10% of IVF cycles, but only a small proportion (0.5% to 2%) of the cases are severe. In extreme but rare cases, secondary complications such as deep vein thrombosis, respiratory distress and acute hepato-renal failure may occur. The main risk factors are the presence of polycystic ovaries, high ovarian response to superovulation therapy, the use of hCG to trigger the ovulatory process or for luteal phase support, and the endogenous production of hCG by an early pregnancy. The pathogenesis of OHSS is unknown, although the predominant biochemical mediator is thought to be the renin-angiotensin system. Ovarian stimulation should always be carefully monitored to identify those women at risk. In IVF cycles, the hCG injection should be withheld if the risk is judged to be too great. Some women will benefit from a policy of proceeding to collect oocytes, but electively cryopreserving any resulting embryos, thus allowing the ovarian stimulation cycle not to be wasted. The administration of albumin at the time of oocyte collection will reduce the chance of severe OHSS occurring. If a decision is made to proceed with oocyte recovery and embryo transfer, it may be advisable to give 5000 IU of hCG, rather than 10,000 IU, as the ovulatory trigger. Progesterone, and not hCG, should be given in the luteal phase. Women developing mild or moderate OHSS should be kept under outpatient surveillance to detect the minority that may progress to severe OHSS. Those with severe OHSS should be hospitalised for fluid and electrolyte management. Paracentesis under ultrasound guidance is recommended where there are tense ascites, but further surgical intervention should rarely be undertaken and only when there is good clinical evidence of ovarian torsion or haemorrhage.

Polycystic ovaries and levels of gonadotrophins and androgens in recurrent miscarriage: prospective study in 50 women.

To compare the serum levels of gonadotrophins and androgens, as well as ovarian morphology, in 50 women with a history of recurrent miscarriage and in 20 healthy controls. Prospective study on women with a history of at least three consecutive miscarriages in Department I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Finland. The recurrent miscarriage group as a whole exhibited gonadotrophin and androgen levels comparable to those seen in the controls. Ultrasound examination revealed polycystic ovaries (PCO) in 22 patients (44%) and in four control women (20%, P = 0.06) but no differences in the levels of gonadotrophins and androgens emerged between the patients with or without PCO. During follow up, 33 (66%) women with a history of recurrent miscarriage who became pregnant; 16 miscarried again (48.5%), whereas 17 (51.5%) succeeded. The presence of PCO did not predict miscarriage, but the patients who miscarried had higher levels of total testosterone, free testosterone and dehydroepiandrosterone sulphate than RSA women with continuing pregnancies. PCO and hyperandrogenism may be associated with repeated miscarriage.

Does elective cryopreservation of all embryos from women at risk of ovarian hyperstimulation syndrome reduce the incidence of the condition?

To analyse the incidence and factors associated with the ovarian hyperstimulation syndrome (OHS) in our IVF/GIFT programme before and after the introduction of a strategy to cryopreserve all embryos from women judged to be at risk. Two hundred forty-one consecutive IVF/GIFT cycles from January to December 1989. Specialist fertility unit, Manchester, UK. Pituitary suppression was effected by a daily subcutaneous injection of buserelin (500 micrograms) beginning 7 days before the expected menses. The ovarian stimulation was with variable amounts of human menopausal gonadotrophin. Ovulation was induced with 10,000 i.u. human chorionic gonadotrophin (hCG). From January to May (period A), gametes/embryos were replaced and 2000 i.u. hCG given, irrespective of the serum oestradiol (E2) concentration. From June to December (period B), all the embryos from women with an E2 > 3500 pg/ml on the day of ovulatory trigger were electively cryopreserved. Serum E2, features of moderate or severe OHS, clinical pregnancies. The OHS occurred in 10/105 (9.5%) and 12/136 (8.8%) cycles in periods A and B, respectively. Fewer women (6% versus 60%, P < 0.05) who had their embryos cryopreserved developed severe OHS compared with women with an E2 > 3500 pg/ml who became pregnant after gamete/embryo transfer in period A. The main factors associated with the development of OHS were serum E2 concentrations > 3500 pg/ml, whether gamete/embryos were replaced and the additional hCG given, the occurrence of a pregnancy and the presence of polycystic ovary disease. The elective cryopreservation of all embryos from women with high E2 levels reduced the severity, but not the incidence of symptomatic OHS.

The ubiquitous polycystic ovary

The importance of polycystic ovary syndrome (PCOS) as a cause of anovulatory infertility and of hirsutism has been recognized for more than half a century but it has become increasingly obvious that the presence of polycystic ovaries has wider implications within and beyond the field of reproductive function. This is largely due to recent advances in ultrasound imaging of the ovaries. It is clear that polycystic ovaries are not only much more prevalent in patients with anovulation or hirsutism than would be predicted from endocrine investigation alone (Adams, Poison & Franks, 1986; Fox, Corrigan, Thomas & Hull, 1991) but also occur in over 80% of 'fertile' women who have a history of recurrent early pregnancy loss (Sagle, Bishop, Ridley et al. 1988) and in a significant proportion (22%) of the normal population (Polson, Adams, Wadsworth & Franks, 1988). The latter findings have called into question the specificity of the polycystic

Most women with acne have polycystic ovaries

Out of 98 female referrals with acne vulgaris it was possible to define ovarian morphology by high resolution ultrasound imaging of the pelvis in 82 (84%). Sixty-eight (83%) were shown to have polycystic ovaries, compared with 19% in a control group without acne. The presence of polycystic ovaries in the acne patients did not correlate with acne severity, infertility, menstrual disturbance, hirsutes, or biochemical endocrinological abnormalities.

Hormonal characteristics of women with clinical features of the polycystic ovary syndrome

The aim of the present study was to determine whether a group of patients selected on the basis of clinical features only is characterized by the typical hormonal findings as discussed in the literature concerning the PCO-syndrome. PCO patients had oligomenorrhea, secondary amenorrhea or otherwise evidence of chronic anovulation, as well as hirsutism and/or obesity. Control women had regular menstrual cycles and a normal body weight. Since androgen and estrogen production in women depends on the stage of follicular development, an effort was made to obtain endocrinological data under standardized conditions. Under well-defined circumstances the PCO group ( n = 20) had higher LH levels and lower FSH levels as compared with the control group ( n =10). Consequently the LH FSH ratio was significantly elevated in the PCO group. Serum estrone and estradiol levels were significantly elevated in the PCO group, as were the serum levels of androstenedione and testosterone. Despite these differences a marked degree of overlap existed in the PCO patients and the control women for gonadotrophin, estrogen and androgen levels. It was concluded that although the presence of polycystic ovaries in the investigated PCO group of women was not confirmed by laparoscopy, laparotomy or histological examination of the ovaries, these women had basal endocrinological characteristics similar to those found in well-proven PCO patients reported in the literature.