Jan Holte

Serum lipoprotein lipid profile in women with the polycystic ovary syndrome: relation to anthropometric, endocrine and metabolic variables

OBJECTIVE Although often associated with insulin resistance and glucose intolerance, various lipoprotein abnormalities have been found in polycystic ovary syndrome (PCOS) but not Invariably so when the degree of obesity is taken into account. We have therefore Investigated the serum lipid profile in a group of women with polycystic ovary syndrome with and without obesity. DESIGN Cross‐sectional study of serum lipoprotein lipids and plasma free fatty acids in relation to anthropometric, metabolic and hormonal variables in women with PCOS and weight‐matched controls.

The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women

OBJECTIVE To investigate the basal levels of gonadotrophins and sex steroids, with special reference to the effects of obesity and body fat distribution, In premenopausal women, both those with polycystic ovary syndrome (PCOS) and those with normal ovaries and regular menstrual cycles.

Impaired cholecystokinin secretion and disturbed appetite regulation in women with polycystic ovary syndrome

Increased amount of abdominal fat and obesity are common in polycystic ovary syndrome (PCOS). A higher prevalence of bulimia nervosa and greater cravings for sweets have also been reported in these patients. The present study aimed to compare meal-related appetite and secretion of the ‘satiety peptide’ cholecystokinin (CCK) and glucose regulatory hormones in PCOS women and controls. Sixteen pairs of women with PCOS and controls matched for age and body mass index participated in the study. After an overnight fast, blood samples were collected during ingestion of a standardized meal. We determined basal and postprandial blood levels of CCK, insulin, C-peptide, glucagon, cortisol, growth hormone and glucose. Self-ratings of appetite were assessed by a visual analog scale. PCOS women had a significantly lower meal-related CCK response (p < 0.05) with no association with satiety, as in the controls (r = 0.64). There was a tendency to higher ratings of craving for sweets in PCOS women (p = 0.07) but no correlation with insulin, as in the controls (r = 0.50). Within the PCOS group, ratings of craving for sweets were inversely related to testosterone (r = −0.60) and the CCK response was positively correlated with levels of free testosterone (r = 0.50). We conclude that women with PCOS have reduced postprandial CCK secretion and deranged appetite regulation associated with increased levels of testosterone. Impaired CCK secretion may play a role in the greater frequency of binge eating and overweight in women with PCOS.

Antimüllerian Hormone Levels Are Strongly Associated With Live-Birth Rates After Assisted Reproduction

CONTEXT Previous studies have suggested that antimüllerian hormone (AMH) levels are positively associated with in vitro fertilization (IVF) outcome through their relationship with oocyte yield and not by reflecting oocyte or embryo quality. OBJECTIVE The aim was to investigate whether AMH levels are associated with pregnancy and live-birth rates and whether the results may also reflect qualitative aspects of oocytes and embryos. DESIGN The study was a prospective cohort study between April 2008 and June 2011. SETTING The study was done at a university-affiliated private infertility center. PATIENTS The study cohort consisted of 892 consecutive women undergoing 1230 IVF-intracytoplasmic sperm injection cycles. INTERVENTION(S) AMH levels, analyzed using the DSL ELISA kit, were statistically adjusted for repeated treatments and age and analyzed for associations with treatment outcome. MAIN OUTCOME MEASURES Pregnancy rates, live-birth rates, and stimulation outcome parameters were measured. RESULTS AMH was log-normally distributed with a mean (SD) of 2.3 (2.5) ng/mL. Live-birth rates per started cycle (mean [95% confidence interval]) increased log-linearly from 10.7% [7.2-14.1] for AMH < 0.84 ng/mL (25th percentile) to 30.8% [25.7-36.0] for AMH > 2.94 ng/mL (75th percentile), Ptrend < .0001, being superior in women with polycystic ovaries. These findings were significant also after adjustments were made for age and oocyte yield. AMH was also associated with ovarian response variables and embryo scores. CONCLUSIONS AMH is strongly associated with live-birth rates after IVF-intracytoplasmic sperm injection. AMH may therefore serve as a prognostic factor for the chance of a pregnancy and live birth. Treatment outcome was superior in patients with polycystic ovaries. The findings also indicate that AMH may partially comprise information about oocyte quality.

Long-term follow-up of patients with polycystic ovary syndrome: reproductive outcome and ovarian reserve

BACKGROUND The purpose of the present study was to examine long-term reproductive outcome and ovarian reserve in an unselected population of women with polycystic ovary syndrome (PCOS). METHODS A total of 91 patients with confirmed PCOS and 87 healthy controls were included in the study. Patients had been diagnosed between 1987 and 1995 and at the time of the follow-up, subjects were 35 years of age or older. RESULTS Among women who had attempted a pregnancy, 86.7% of PCOS patients and 91.6% of controls had given birth to at least one child. Among PCOS patients who had given birth, 73.6% had done so following a spontaneous conception. Mean ovarian volume and the number of antral follicles in PCOS patients were significantly greater than in control women (P < 0.001, respectively). PCOS patients also had higher serum concentrations of anti-Müllerian hormone and lower follicle-stimulating hormone levels. CONCLUSIONS Most women with PCOS had given birth, and the rate of spontaneous pregnancies was relatively high. Together with the ultrasound findings and the hormonal analyses, this finding could imply that PCOS patients have a good fecundity, and an ovarian reserve possibly superior to women with normal ovaries.

Polycystic ovary syndrome and insulin resistance: Thrifty genes struggling with over-feeding and sedentary life style?

Almost two decades of research have greatly increased our knowledge in the complex field of metabolic aberrations in polycystic ovary syndrome, but still many problems remain unsolved. The statistical association between insulin levels and androgens originally put the focus on possible direct cause- and-effect relationships between these factors. Indeed there is evidence that insulin may affect ovarian functions in multiple ways, presumably in some cases causing anovulation and hyperandrogenism. Clearly, insulin may increase biologically active testosterone through reducing SHBG levels. Conversely, major increases in androgen levels may induce muscular changes leading to reduced insulin-mediated glucose uptake. There are suggestions of increased steroidogenesis in both ovarian and adrenal pathways, with the net result of increased androgen production. There are also findings supporting increased corticosteroid production, which could contribute to insulin resistance directly or through promoting accumulation of abdominal fat, a typical feature of over-weight women with PCOS. Free fatty acids, released in great amounts from abdominal fat, may induce insulin resistance. Insulin resistance may also be due to a primary aberration in the insulin receptor. Putatively increased serine phosphorylation may cause both impairment of the insulin signal and increased 17,20 lyase activity, thus suggesting a common cause for insulin resistance and increased androgen production. There are also findings supporting a high prevalence of beta-cell dysfunction in PCOS, ranging from increased insulin secretion, not explained by insulin resistance or BMI, to failing beta-cell function, mainly in obese women during progress to glucose intolerance and NIDDM. Recent genetic findings also support a multifactorial genesis to PCOS, notably with positive findings both in genes regulating steroidogenesis and insulin secretion. It is suggested that PCOS is the result of “thrifty” genes, providing advantages in times of shortage of nutrition such as muscular strength, moderate abdominal fatness and decreased insulin sensitivity, i.e. an anabolic, energy saving constitution. However, when this constitution is exposed to unlimited food supplies and modern sedentary life style a full-blown PCOS with insulin resistance and infertility is triggered, presumably via several mechanisms, which follow a logical amplification system between two basic anabolic hormones, insulin and testosterone.

Diabetes and impaired glucose tolerance in patients with polycystic ovary syndrome—a long term follow-up

BACKGROUND The overall risk of developing diabetes mellitus and glucose intolerance seems to be higher in women with polycystic ovary syndrome (PCOS) than in healthy women. The aim of this long-term follow-up study was to examine glucose tolerance and insulin sensitivity in middle-aged women previously diagnosed with PCOS in comparison with age-matched healthy controls. METHODS Women diagnosed with PCOS between 1987 and 1995 were invited to participate in the study. A total of 84 PCOS patients and 87 control subjects participated. Anthropometric (BMI, waist/hip ratio) and metabolic parameters (oral glucose tolerance test) were measured. Insulin sensitivity was expressed by the Matsuda index and beta cell function by the insulinogenic index. PCOS women were subgrouped according to phenotype at the index assessment (with or without hyperandrogenism) and persistence of PCOS symptoms at the follow-up (persisting or resolved PCOS). RESULTS Eighteen (21.4%) PCOS patients and four (4.5%) controls had developed type 1 or type 2 diabetes or impaired glucose tolerance (IGT) at the follow-up investigation (P < 0.05). Matsuda insulin sensitivity index was lower and the insulinogenic index was increased in women with previously diagnosed PCOS compared with control subjects. In addition, PCOS patients with or without hyperandrogenism, and PCOS patients with persisting and resolved PCOS all had lower Matsuda insulin sensitivity index and increased insulinogenic index in comparison with controls. CONCLUSIONS IGT and type 2 diabetes occurred more often in PCOS patients. Independent on PCOS phenotype at index assessment and persistence of PCOS symptoms at the follow-up investigation, women with PCOS had lower insulin sensitivity but a well-preserved beta cell function in comparison with control subjects.

Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up

OBJECTIVE To examine the prevalence of the metabolic syndrome (MetS) according to the scientific statement of the American Heart Association and the US National Cholesterol Education Program/Adult Treatment Panel III in middle-aged Swedish women previously diagnosed with polycystic ovary syndrome (PCOS) in comparison with age-matched healthy controls. DESIGN Long-term follow-up study. SETTING Department of Obstetrics and Gynecology, Uppsala University. PATIENT(S) Eighty-four women diagnosed with PCOS between 1987 and 1995; and 87 controls randomly selected from the general population. INTERVENTION(S) Anthropometric measurements and blood tests. MAIN OUTCOME MEASURE(S) Body mass index, waist circumference, blood pressure, lipids, and glucose. RESULT(S) The prevalence of MetS in women with PCOS (mean ± SD age, 43.0 ± 5.8 years) was 23.8% and in controls was 8.0%, and it did not differ according to PCOS phenotype at the index assessment (polycystic ovaries [PCO], oligomenorrhea, and hirsutism: 10 [22.7%]; PCO and oligomenorrhea: 8 [22.2%]) or according to the persistence of PCOS features at follow-up (persisting PCOS: 25.8%; resolved PCOS: 16.7%). CONCLUSION(S) The MetS occurred more often in patients with PCOS than in controls and did not depend on phenotypic presentation at the index assessment or the persistence of PCOS at follow-up.

Ovarian endometriomas and IVF: a retrospective case-control study

We performed this retrospective case-control study analyzing 428 first-attempt in vitro fertilization (IVF) cycles, among which 254 involved women with a previous or present diagnosis of ovarian endometriosis. First, the results of these 254 cycles were compared with 174 cycles involving patients with proven non-endometriotic tubal infertility having similar age and body mass index. Women with ovarian endometriosis had a significantly higher cancellation rate, but similar pregnancy, implantation and delivery rates as patients with tubal infertility. Second, among the women with ovarian endometriosis, the women with a history of laparoscopic surgery for ovarian endometriomas prior to IVF and no visual endometriosis at ovum pick-up (n = 112) were compared with the non-operated women and visual endometriomas at ovum pick-up (n = 142). Patients who underwent ovarian surgery before IVF had significantly shorter period, lower antral follicle count and required higher gonadotropin doses than patients with non-operated endometriomas. The two groups of women with a previous or present ovarian endometriosis did, however, have similar pregnancy, implantation and live birth rates. In conclusion, ovarian endometriosis does not reduce IVF outcome compared with tubal factor. Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins.

Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem

OBJECTIVE To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns. DESIGN Retrospective cross-sectional study. SETTING University-affiliated private center. PATIENT(S) The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist-recombinant FSH protocol). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome. RESULT(S) OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield. CONCLUSION(S) The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns.