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.

Efficacy of progesterone and progestogens in management of premenstrual syndrome: systematic review.

OBJECTIVE: To evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome. DESIGN: Systematic review of published randomised, placebo controlled trials. STUDIES REVIEWED: 10 trials of progesterone therapy (531 women) and four trials of progestogen therapy (378 women). MAIN OUTCOME MEASURES: Proportion of women whose symptoms showed improvement with progesterone preparations (suppositories and oral micronised). Proportion of women whose symptoms showed improvement with progestogens. Secondary analysis of efficacy of progesterone and progestogens in managing physical and behavioural symptoms. RESULTS: Overall standardised mean difference for all trials that assessed efficacy of progesterone (by both routes of administration) was -0.028 (95% confidence interval -0.017 to -0.040). The odds ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically important difference between progesterone and placebo. For progestogens the overall standardised mean was -0.036 (-0.014 to -0.060), which corresponds to an odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically, significant improvement for women taking progestogens. CONCLUSION: The evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome.

Management of massive postpartum haemorrhage: use of a hydrostatic balloon catheter to avoid laparotomy.

Postpartum haemorrhage remains a significant complication of childbirth in the UK and worldwide. The most common cause of postpartum haemorrhage is uterine atony, but placent accreta is becoming more frequent. In these situations tamponade may be required. The successful use of the inflated stomach balloon (300ml) of a Sengstaken-Blakemore tube has been reported previously. We describe an innovative method of 'tamponade' which is simple and effective, using the Rüsch urological hydrostatic balloon catheter. In two cases of failed medical therapy for PPH, where the catheter has been tried, further surgical interventions have been avoided.

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.

Altered composition of high density lipoproteins in women with the polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) appear at increased cardiovascular risk due in part to a dyslipidemia characterized by increased plasma triglyceride and reduced high density lipoprotein (HDL) cholesterol levels. This is a detailed exploratory study of HDL composition in 35 obese [body mass index (BMI), > 27] and 22 nonobese subjects with PCOS and in 14 healthy obese and 18 nonobese women. Although we found reduced levels of total and HDL2 cholesterol in obese women with PCOS, HDL composition was modified by depletion of lipid relative to protein, with reduced ratios of HDL total cholesterol and HDL phospholipids to apolipoprotein A-I (apoA-I) compared to those in obese controls (P = 0.008 and P = 0.012, respectively). This was explained by reduced cholesterol (P = 0.004) and phospholipid (although not significant, P = 0.07) in HDL with no change in the content of apoA-I, its major protein. Obesity, insulin resistance, and hyperandrogenemia are features of PCOS and potentially affect lipid metabolism. Insulin sensitivity was assessed by the reduction in endogenous glucose concentration after exogenous insulin; the insulin, glucose, and fatty acid responses to oral glucose; and the fasting insulin concentration. When age, BMI, free androgen index, insulin sensitivity determined by all methods, and the presence of PCOS were subjected to stepwise multivariate regression analysis, the presence of PCOS was the most consistent predictor of lipid-depleted HDL (HDL total cholesterol/apoA-I and HDL phospholipids/apoA-I). We speculate that altered activity of hepatic lipase or lipid transfer protein could explain this aspect of the dyslipidemia. Obesity has an important influence on the lipid profile. Obese PCOS and control subjects had higher levels of cholesterol, triglyceride, apoB, and fatty acids than their lean counterparts, and BMI proved the best predictor of blood levels on multiple regression analysis. In contrast, lean PCOS patients had normal sensitivity to insulin and lipid profiles similar to those of the lean controls and did not manifest the HDL abnormalities. Although in PCOS, correlations were obtained between the free androgen index and cholesterol, triglyceride, and apoB levels and between the integrated glucose and insulin responses after oral glucose and fasting fatty acid and triglyceride levels, when age and adiposity were included as covariates only fatty acids and the integrated glucose response remained significantly correlated. Among the controls, total, low density lipoprotein cholesterol, triglycerides, and apoB were related to aspects of insulin sensitivity independent of age and BMI. Lipid metabolism in PCOS is dependent on several related factors, but subjects with PCOS who are obese show a specific reduction in HDL lipid, suggesting a reduced capacity for cholesterol removal from tissues with diminished antiatherogenic potential. Efforts should be directed toward reducing obesity in PCOS to improve the metabolic disturbance in addition to ameliorating the presenting symptoms.

The role of hysterosalpingography in modern gynaecological practice.

A retrospective review of hysterosalpingography (HSG) in a major gynaecological centre was carried out. 324 patients attended (95%) for HSG out of 341 patients referred for this investigation. 189 examinations (58.3%) were abnormal. The requests and radiological findings were reviewed and the results compared with laparoscopy. HSG remains an integral part of gynaecological investigation and its value has not diminished in modern practice.

Flow cytometric comparison between swim-up and Percoll gradient techniques for the separation of frozen-thawed human spermatozoa.

Viable human spermatozoa were recovered from cryopreservation by either swim-up or Percoll density gradient techniques and their cell-surface oligosaccharide components were compared to those of fresh sperm. Sperm were labeled with FITC-Con A and analyzed by fluorescence microscopy and flow cytometry. By fluorescence microscopy, fresh sperm were uniformly labeled in the neck region alone. Frozen-thawed sperm, obtained by either swim-up or Percoll density gradients, showed two patterns of staining: one sperm population was stained in the neck region only, whilst another showed staining in both the neck and acrosome regions. No difference between sperm recovered by the two techniques was apparent. Flow cytometry profiles of fresh sperm revealed a single peak of fluorescence, whereas cryopreserved sperm gave two peaks of fluorescence. Samples recovered by Percoll density gradient contained significantly more sperm with the same fluorescence pattern as that observed for fresh sperm than did those recovered by swim-up. Cryopreservation alters the cell-surface oligosaccharide components of spermatozoa. Recovery of cryopreserved sperm by Percoll density gradient yields a greater proportion of sperm which resemble fresh sperm than does swim-up.

Hormonal studies on women with polycystic ovaries diagnosed by ultrasound.

Eighty-six patients were diagnosed by ultrasound to have polycystic ovaries. Twelve have fairly regular but anovular cycles (P1), 56 had oligomenorrhoea (P2) and eight had primary or secondary amenorrhoea (P3). The remaining 10 patients had raised progesterone concentrations and were excluded from the hormonal studies. Gonadotrophins, steroid hormones and sex hormone binding globulin (SHBG) were measured in all patients and the results were compared with those of 29 normal women who acted as controls. A high LH:FSH ratio was the most frequently found abnormality (raised in 68.4% of patients) followed by LH (65.8%), free testosterone (FT, calculated from total testosterone (T) and SHBG) (59.2%) and 17-OHP (48.7%). Each of these four estimations was above the normal ranges in 25% of patients: proportionally most of the results outside the normal range occurred in group P3 followed by P2 and P1 respectively. To obtain a quantitative measure of the abnormalities, results were expressed as percentages of the mean control value for each hormone and these percentages were then summated. The four measurements, LH:FSH ratio, LH, FT and 17-OHP gave abnormality scores ranging from a mean of 667 in P1 to 1189 in P3 compared with 405 in controls. Twenty-one of the 76 patients were hirsute with significantly higher androgens than the nonhirsute patients. Their mean abnormality score was 1141 compared with 855 in the non-hirsute group and they all had at least one hormonal abnormality. The study demonstrates that there is a relationship between the degree of hormonal abnormality and the menstrual irregularities and hirsutism in women with PCOS suggesting that there may be a progressive nature to the syndrome.

Caesarean section for the birth of the second twin.

Twin pregnancies delivered after 28 weeks gestation between 1980 and 1988 were reviewed. Of 510 twin pregnancies, 184 (36%) were delivered by caesarean section. There were 22 (4.3%) combined vaginal/abdominal deliveries which comprised 12% of the 184 twin pregnancies delivered by caesarean section. Persistent transverse lie or a high breech presentation was the commonest indication for caesarean section for the second twin.

Antisperm antibodies and sperm motility: a study using timed exposure photomicrography.

This study examined the effect of antisperm antibodies on sperm motility. Antisperm antibodies present in seminal plasmas with different sperm agglutinating titres were transferred passively to normal donor sperm, and the effects on movement characteristics (velocity of forward progression, amplitude of lateral head displacement, percentage progressive motility and percentage non-progressive motility) were analysed using timed exposure photomicrography. There was no significant association between sperm movement characteristics and the presence of titre of antisperm antibodies in seminal plasma. Furthermore, no differences were detected between those samples that possessed sperm agglutinating versus sperm immobilizing activity. These findings do not support the common belief that antisperm antibodies are a cause of poor sperm motility in semen.

Parvovirus infection in pregnancy.

A case is presented of serologically proved parvovirus infection leading to intrauterine death of the hydropic fetus at 20 weeks' gestation. Although serologic studies of the population indicate that 30-50% of women are susceptible to parvovirus infection, the prevalence of parvovirus infection in pregnancy and the consequences of such an infection are not well understood. A review of reported cases in the world literature indicates a high risk to the fetus once the virus crosses the placenta.