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Background: Female abdominal obesity is associated with hyperandrogenemia (HA), but few studies have addressed the possible association between HA and metabolic syndrome (MetS) among obese women. Some studies indicate that insulin resistance may cause HA through different mechanisms. On the other hand, a bidirectional relationship between HA and insulin resistance has been suggested. Thus, we aimed to investigate if morbidly obese women with HA had higher odds of MetS and its components than those without HA (controls), independent of polycystic ovarian syndrome (PCOS) status. Methods: This cross-sectional study comprised 1900 consecutive treatment seeking morbidly obese women <50 years. Free testosterone index (FTI) >0.6 defined HA. Women with previously diagnosed PCOS and those with oligo- / anovulation combined with clinical or biochemical hyperandrogenism were defined as having PCOS. Multiadjusted associations between HA and MetS were assessed by logistic regression analysis. Results: Out of 1900 morbidly obese women, 1089 (57 %), 846 (45 %) and 312 (16 %) had MetS, HA and PCOS, respectively. Compared with controls (without HA), women with HA were younger (34 [1] years vs. 39 [2], p < 0.001) had a higher prevalence of MetS (62 % vs. 53 %, p < 0.001), type 2 diabetes (18 % vs. 15 %, p = 0.045), low HDL-cholesterol (65 % vs. 48 %, p < 0.001) and hypertriglyceridemia (48 % vs. 41 %, p = 0.004), but a lower prevalence of raised blood pressure (53 % vs. 59 %, p = 0.014). Multivariable analyses showed that HA was associated with increased odds of MetS (OR 1.61 [95 % CI 1.27, 2.02]), dysglycemia (1.65 [1.28, 2.11]), low HDL-cholesterol (1.58 [1.27, 1.97]), and hypertriglyceridemia (1.43 [1.15, 1.79]). After stratification for the presence of PCOS, the results remained largely unchanged in women without PCOS; MetS (1.52 [1.18, 1.96), dysglycemia (1.71 [1.30, 2.25]), low HDL-cholesterol (1.55 [1.22, 1.98]) and hypertriglyceridemia (1.36 [1.06, 1.74]). Conclusion: Morbidly obese women with HA had an approximately 1.5-fold increased odds of having MetS even in the absence of PCOS. Randomized controlled clinical trials, including therapeutic strategies to lower free testosterone levels, are however necessary to explore any cause-and-effect relationship. [ABSTRACT FROM AUTHOR]

In this study we assessed how insulin resistance affects pregnancy rates in infertile women with the polycystic ovary syndrome (PCOS) treated with laparoscopic ovarian electrocautery. Sixty-four PCOS women were included in the study in a consecutive fashion. Following the CIGMA (continuous infusion of glucose with model assessment) test, 28 women were classified as insulin resistant and 36 women as non-insulin resistant. After the ovarian electrocautery patients were observed for 12-18 months. If pregnancy did not ensue, they were referred for one or more cycles of in vitro fertilization (IVF). Following ovarian electrocautery the non-insulin-resistant women more frequently achieved a regular menstrual cycle and ovulation than the insulin-resistant PCOS women. Consequently 18 (50%) of the non-insulin-resistant PCOS women achieved a pregnancy versus only five (18%) of women in the insulin-resistant PCOS group. Following treatment with both ovarian electrocautery and IVF, 27 (75%) of the non-insulin resistant PCOS women achieved a successful pregnancy, while 13 (46%) of the insulin-resistant PCOS group achieved this. In conclusion, insulin resistance may be an important marker of a poor outcome of treatment in PCOS infertility. Further studies are needed to evaluate the possible effect of treatment alternatives to alleviate the unfavorable influences of insulin resistance and hyperinsulinemia on ovulation induction in PCOS women. [ABSTRACT FROM AUTHOR]

Background: To elucidate possible differences between unexplained and minimal peritoneal endometriosis-associated infertility, we studied their outcome in natural cycle IVF (NIVF).Methods: A prospective cohort study was carried out on unexplained (33 couples), minimal peritoneal endometriosis-associated (30 couples) and tubal factor (24 couples) infertility in 223 NIVF cycles, using human chorionic gonadotrophin (HCG) for ovulation induction.Results: During the first NIVF attempt, follicular and luteal phase oestradiol, FSH, LH and progesterone concentrations, as well as endometrial thickness and follicular diameter were similar among the three groups. Periovulatory follicular growth monitored from day of HCG administration to oocyte aspiration was significantly lowered in unexplained infertility compared with minimal endometriosis-associated and tubal factor infertility. The fertilization rate, clinical pregnancy rate per initiated cycle, per successful oocyte retrieval and per embryo transfer, in minimal endometriosis (80.0, 10.4, 16.0 and 23.5% respectively) were similar to that in tubal factor infertility patients (68.6, 5.8, 11.4 and 16.0%) but significantly higher (P < 0.05) than that of the unexplained infertility group (62.2, 2.6, 5.4 and 8.7%).Conclusions: The significant reduction in follicular periovulatory growth, fertilization and pregnancy rates in unexplained infertility compared with minimal peritoneal endometriosis patients may be explained by sub-optimal follicular development with possibly reduced oocyte quality, intrinsic embryo quality factors or by impaired implantation. From a clinical point of view, NIVF is less suited to unexplained infertility treatment, but might represent an interesting treatment option for minimal peritoneal endometriosis-associated infertility. [ABSTRACT FROM AUTHOR]

The impact of insulin resistance on the outcome of IVF or intracytoplasmic sperm injection (ICSI) in women with polycystic ovarian syndrome (PCOS) was examined. Insulin sensitivity was measured by the continuous infusion of glucose with model assessment (CIGMA) test. Insulin-resistant (n = 26) and non-insulin-resistant women (n = 30) with PCOS underwent a total of 100 cycles of long-term down-regulation with buserelin acetate, stimulation with human recombinant FSH, and IVF or ICSI. Blood samples were taken throughout ovarian stimulation for hormone assays. Insulin-resistant and non-insulin-resistant women had similar concentrations of FSH, LH, testosterone and androstenedione throughout stimulation, but insulin-resistant women had hyperinsulinaemia and lower sex hormone binding globulin concentrations. Insulin-resistant women also had lower oestradiol concentrations during stimulation and required higher FSH doses, but these differences disappeared after controlling for the higher body weight in the group of insulin-resistant women. Groups had similar number of oocytes collected, similar implantation and pregnancy rates, and the incidence of ovarian hyperstimulation syndrome was also similar. Obesity, independent of hyperinsulinaemia, was related to a lower oocyte count and increased FSH requirement. It is concluded that in PCOS women receiving long-term down-regulation and stimulation with recombinant FSH, insulin resistance is neither related to hormone levels nor to IVF outcome. Obesity, independent of insulin resistance, is associated with relative gonadotrophin resistance. [ABSTRACT FROM AUTHOR]

To investigate the clinical importance of leptin's intraovarian effects, we studied the concentration of leptin and leptin binding activity in the plasma and in the follicular fluid of PCOS patients (n=20; median BMI: 27.1 kg/m2, range 19.7-36.3) undergoing controlled ovarian stimulation with long-term GnRH agonist, recombinant FSH, and in vitro fertilization. Follicular fluid and blood samples were collected during follicle aspiration for IVF. Total leptin concentration was measured by radioimmunoassay, and specific leptin binding activity was accessed by a gel filtration column assay. Follicular fluid and plasma leptin levels were similar (median 1135 pmol/l vs. 1409 pmol/l; p=0.81). Follicular fluid to plasma leptin ratio was independently associated with cumulative FSH dose (r=0.63; p=0.006) and insulin resistance index (r=-0.45; p=0.04). Specific leptin binding activity was higher in the plasma than in the follicular fluid [median 7.94% vs. 3.49%; p<0.001]. When multivariate analysis was used to predict FSH consumption, only follicular fluid leptin levels were significantly associated with cumulative FSH dose (r=0.46; p=0.04). We infer that at least in part by increased intrafollicular leptin levels, obesity directly affects ovarian function in PCOS, and may induce a relative resistance to gonadotropin stimulation. This intraovarian effect of leptin can be even more profound because of low leptin binding activity in the preovulatory follicle of obese patients. [ABSTRACT FROM AUTHOR]

Forty-four infertile patients with the polycystic ovarian syndrome (PCOS) resistant to other treatment modalities were treated in 58 cycles of IVF after accomplishment of pituitary gonadotroph suppression with a GnRH-agonist. Four cycles were cancelled before oocyte retrieval while embryo transfer was deferred for 10 cycles due to imminent ovarian hyperstimulation syndrome (OHSS). Follicle aspiration yielded 18.8±9 oocytes per cycle. The cleavage rate was 68%. There was no cleavage in five cycles. The pregnancy rate was 33.3% per embryo transfer. In 32 cycles 9.0±5 suitable supernumerary embryos were cryopreserved. Transfer of cryopreserved embryos gave three additional pregnancies. The accumulated pregnancy rate per patient was 36%. In clomiphene citrate resistant patients, transfer of cryopreserved embryos was accomplished after secretory transformation of the endometrium by oestradiollprogester one substitution. Although seven pregnancies ended in a miscarriage, the ‘take-home’ baby rate was 20%. OHSS ensued in 28(46.7%) cycles. In PCOS, in-vitro fertilization following pituitary gonadotroph suppression seems a treatment alternative with pregnancy rates comparable to normo-ovulatory women with tubal factor infertility. However, the incidence of OHSS is high and constitutes the major problem of cycle control. [ABSTRACT FROM PUBLISHER]

Forty-three patients who responded poorly to previous stimulation with clomiphene citrate (CC)/human menopausal gonadotrophin (HMG) for IVF were followed during 70 further cycles. Eighteen patients had a normal FSH response to CC in the previous cycle, while 25 had an abnormal FSH response. Three stimulation protocols were used: buserelin/HMG, CC/HMG and HMG only. No difference between the two groups was observed in the dose of HMG used for any stimulation protocol. More cycles were cancelled due to a poor response in the abnormal response group compared to the normal response group. In the completed cycles, the maximum oestradiol level and number of oocytes retrieved were lower in the abnormal response group compared to the normal response group. The total pregnancy rate per patient, including spontaneous conceptions during the study period, was lower in the abnormal response group compared to the normal response group, 4 versus 33%. We conclude that poor responders with an abnormal FSH response to CC have a latent ovarian failure with a low chance of success in further IVF attempts. [ABSTRACT FROM AUTHOR]

A comparison of the relative efficacy of in-vitro fertilization with uterine embryo transfer (IVF), tubal embryo stage transfer (TEST) and gamete intra-Fallopian transfer (GIFT) was performed in infertile patients with patent Fallopian tubes. A total of 150 couples with unexplained infertility, peritoneal endometriosis or reduced semen quality were included in the study. The three groups were comparable with regard to age distribution, indications, semen parameters, stimulation regimens, response to stimulation and numbers of oocytes retrieved. In the IVF and TEST groups there was no cleavage in 24% and a cleavage rate of only 47.6%. The highest cleavage rate was obtained in the endometriosis patients. The pregnancy rate was highest in the two groups in which in-vitro fertilization was performed, IVF = 45.7%, TEST = 37.9%, GIFT = 26.2%. To obtain one live intrauterine fetus, more oocytes had to be transferred in the GIFT group compared to the number of embryos in the IVF group, 14.4 versus 6.2, P less than 0.05. Due to a high success rate of IVF but at the same time a high frequency of no cleavage in cases of unexplained infertility or male subfertility, we recommend IVF as the primary procedure in infertile couples with patent Fallopian tubes. [ABSTRACT FROM AUTHOR]

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and prolactin levels were studied in a sequential clomiphene citrate/human menopausal gonadotrophin (CC/HMG) regimen for in-vitro fertilization. At completion of CC administration, the median FSH level in 44 cancelled cycles was elevated compared to a control group of 65 completed cycles, 29 IU/l versus 15 IU/l, P less than 0.01. Also the median FSH/LH ratio was higher in the cancelled cycles than in the control group, 1.08 versus 0.71, P less than 0.05. Conversely, the median oestradiol level was lower in the cancelled cycles than in the completed cycles, 0.27 nmol/l versus 0.59 nmol/l, P less than 0.01. No difference was seen in the median LH and prolactin levels. An FSH value above the 95% confidence limit was found in 24 of the cancelled cycles, but in only two of the completed cycles. Based on this study, an elevated FSH value following CC administration predicts a poor response to further stimulation with an accuracy of 92.3% and should result in cancellation of the cycle. [ABSTRACT FROM AUTHOR]