Association of leptin and insulin resistance in PCOS: a case-controlled study

Background: Endocrine abnormalities related to polycystic ovary Syndrome [PCOS] are important problems

Objective: To compare serum leptin levels between infertile women with and without PCOS. To rank sensitivity of six indirect methods for detection of insulin resistance [IR] and to evaluate the association between leptin and IR in PCOS group

Materials and methods: This Case-controlled study performed on 189 infertile women referred to Shiraz Mother and Child Hospital during 2012-2015. Ninety-nine PCOS cases according to Rotterdam criteria were compared to 90 cases without PCOS. Serum leptin, body mass index [BMI], several hormones, and their correlation coefficients with leptin were compared. IR in PCOS women was measured by indirect methods, including fasting blood sugar [FBS], fasting insulin [FI], glucose/insulin, homeostatic model assessment of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], and MacAuley index. Association between IR and leptin was evaluated. Independent sample t-test and Pearson's test were used

Results: Infertile women with PCOS had higher BMI [26.47 +/- 3.62 vs. 24.82 +/- 5.18 kg/m[2]] and serum leptin levels [41.79 +/- 187.89 vs. 19.38 +/- 12.57 ng/mL]. Leptin showed significant association with weight and BMI in both groups [p<0.001] and to age in non-PCOS group. HOMA-IR showed the highest rate of IR followed by FI and QUICKI methods. The mean leptin levels had positive association with IR assessed by HOMA-IR [p<0.001], QUICKI [p<0.001], FI [p=.002], and FBS [p=0.02]

Conclusion: BMI and IR have positive association with serum leptin in PCOS infertile women. HOMA-IR followed by FI and QUICKI is the most sensitive test for detection of IR

Absence of Correlation between Changes in the Number of Endothelial Progenitor Cell Subsets

BACKGROUND AND OBJECTIVES: Previously, various methodologies were used to enumerate the endothelial progenitor cells (EPCs). We now know that these methodologies enumerate at least three different EPC subsets: circulating angiogenic cells (CACs), colony-forming unit endothelial cells (CFU-ECs), and endothelial colony-forming cells (ECFCs). It is not clear whether there is a correlation between changes in the number of these subsets. The aim of the current study is to find an answer to this question. MATERIALS AND METHODS: The number of all EPC subsets was quantified in the peripheral blood of nine pregnant women in their first and third trimesters of pregnancy. We enumerated 14 cell populations by quantitative flow-cytometry using various combinations of the markers, CD34, CD133, CD309, and CD45, to cover most of the reported phenotypes of CACs and ECFCs. Culturing technique was used to enumerate the CFU-ECs. Changes in the number of cells were calculated by subtracting the number of cells in the first trimester peripheral blood from the number of cells in the third trimester peripheral blood, and correlations between these changes were analyzed. RESULTS: The number of CFU-ECs did not correlate with the number of ECFCs and CACs. Also, CACs and ECFCs showed independent behaviors. However, the number of CACs showed a strong correlation with the number of CD133+CD309+ cells (p=0.001) and a moderate correlation with the number of CD34+CD309+ cells (p=0.042). Also, the number of ECFCs was correlated with the number of CD309+CD45- cells (p=0.029) and CD34+CD45- cells (p=0.03). CONCLUSION: Our study showed that the three commonly used methods for quantifying EPC subsets represent different cells with independent behaviors. Also, any study that measured the number of EPCs using the flow cytometry method with a marker combination that lacks CD309 may be inaccurate.

Intrauterine administration of recombinant human chorionic gonadotropin before embryo transfer on outcome of in vitro fertilization/ intracytoplasmic sperm injection: a randomized clinical trial

The direct effect of hCG on the human endometrium was studied several times. The objectives of this study were to evaluate the effectiveness of intrauterine injection of recombinant human chorionic gonadotropin [rhCG] before embryo transfer [ET]. In this randomized placebo-controlled clinical trial, a total number of 182 infertile patients undergoing their first in vitro fertilization/ intracytoplasmic sperm injection [IVF-ICSI] cycles were randomly assigned to receive 250 micro g intrauterine rhCG [n=84] or placebo [n=98] before ET. The implantation and pregnancy rates were compared between groups. Patients who received intrauterine rhCG before ET had significantly higher implantation [36.9% vs. 22.4%; p=0.035], clinical pregnancy rates [34.5% vs. 20.4%; p=0.044] and ongoing pregnancy rate [32.1% vs. 18.4%; p=0.032] when compared to those who received placebo. The abortion [2.4% vs. 2.0%; p=0.929] and ectopic pregnancy rates [1.2% vs. 1.0%; p=0.976] were comparable between groups of rhCG and placebo, respectively. Intrauterine injection of 250 micro g of rhCG before ET significantly improves the implantation and pregnancy rates in IVF/ICSI cycles.

Anti-nuclear antibodies in patients with polycystic ovary syndrome before and after laparoscopic electrocauterization

Polycystic ovary syndrome [PCOS] has been suggested to be linked with autoimmune processes. Laparoscopic ovarian electrocauterization has the potency to stimulate more autoimmune reactions in PCOS patients. In the present study, we considered anti-nuclear antibodies [ANAs] as the hallmark of autoimmune reactions, and investigated the serum level of these antibodies in 35 patients with PCOS [21-38 years old] pre and one-month after electrocauterization, and in 35 fertile healthy women [25-35 years old] as the control group. Serum levels of ANAs, as well as ANA subtyping, were investigated using the Enzyme-Linked Immunosorbent Assay [ELISA]. While 3 out of the 35 patients [8.6%] were positive for ANAs before electrocauterization, none of the controls was positive. The number of ANA-positive cases increased following electrocauterization [3 out of 35 [8.6%] before vs. 10 out of 35 [28.6%] after the procedure]. The main ANA subtype in the positive samples was SS-A. The higher ANA level among the PCOS patients suggests association of the disease with autoimmune reactions. Laparoscopic ovarian electrocauterization seems to increase the number of positiveANA patients

Pregnancy rate after endometrial injury in couples with unexplained infertility: a randomized clinical trial

Unexplained infertility is still a challenging issue as to its causes, appropriate management and treatment. Evidence implicates early embryopathy or implantation failure as likely causes. This study aims to investigate the effect of local endometrial injury on pregnancy rate in selected unexplained infertile patients. This was a randomized clinical trial conducted in Shiraz University Infertility Clinic of Ghadir Hospital. A total of 217 women with unexplained infertility aged 23-35 years old were randomly divided into two study groups through block randomization. After superovulation by clomiphene-citrate and gonadotropins and when the dominant follicles reached 18-20 mm, patients were randomly assigned to undergo endometrial local injury at posterior uterine wall by piplle endometrial sampling [n=114] or mock pipette biopsy [n=103] during pre-ovulatory days [when spontaneous urinary LH surge was detected]. Then all the patients were instructed to follow a regularly timed intercourse. The pregnancy rate was significantly higher in the endometrial injury group compared to the control group [17/114 [14.9%] vs. 6/103 [5.8%] [OR: 2.83 95% CI: 1.07-7.49, p=0.03]. The abortion rate was comparable between two groups [17.64% vs. 14.28%; p=0.701]. Local mechanical injury of the endometrium can enhance the uterine receptivity and facilitates the embryo implantation. This simple, easy, and cost effective procedure is worth considering in selective unexplained infertility patients who implantation failure is the likely causes of infertility before complex treatments. This procedure may help reduce psychological tensions and high expenses imposed through such interventions

Metformin versus chromium picolinate in clomiphene citrate-resistant patients with PCOs: a double-blind randomized clinical trial

Chromium picolinate could be effective in clomiphen citrate resistant PCOS patients. To compare the effects of chromium picolinate vs. metformin in clomiphen citrate resistant PCOS patients. The present randomized clinical trial was performed on 92 women with clomiphen citrate-resistant PCOS at the clinics which were affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. The subjects were randomly assigned to two groups receiving either chromium picolinate [200micro g daily] or metformin [1500mg daily] for 3 months. Anthropometric and hormonal profile were measured and compared both before and after the treatment. Ovulation and pregnancy rate was measured in the two study groups, as well. Chromium picolinate significantly decreased fasting blood sugar [FBS] after 3 months of treatment [p=0.042]. In the same way, the serum levels of fasting insulin had significantly decreased leading to an increase in insulin sensitivity as measured by QUICKI index [p=0.014]. In comparison to the patients who received chromium picolinate, those who received metformin had significantly lower levels of testosterone [p=0.001] and free testosterone [p=0.001] after 3 months of treatment. Nevertheless, no significant difference was found between the two study groups regarding ovulation [p=0.417] and pregnancy rates [p=0.500]. Chromium picolinate decreased FBS and insulin levels and, thus, increased insulin sensitivity in clomiphene citrate-resistance PCOS women. These effects were comparable with metformin; however, metformin treatment was associated with decreased hyperandrogenism. Overall, chromium picolinate was better tolerated compared to metformin; nonetheless, the two study groups were not significantly different regarding ovulation and pregnancy rates

[Prevalence of metabolic syndrome in fathers of patients with polycystic ovarian syndrome]

Women with polycystic ovarian syndrome [PCOS] have twice the risk for metabolic syndrome as compared to women from the general population. Mothers and sisters of affected women also have an increased prevalence of metabolic syndrome. The aim of the study was to determine the prevalence of metabolic syndrome in fathers of patient with PCOS. 34 fathers of PCOS patients were evaluated. The control group was 34 fathers of normal women. The data were obtained from the clinical history and personal interview with the patients, the controls and their fathers at Shiraz University of Medical Sciences in 2009. Prevalence of metabolic syndrome was determined according to Adult Treatment Panel index III [ATPIII] and International Diabetes Federation [IDF] criteria. Also incidence of hypertension and impaired glucose tolerance test, insulin resistance and diabetes type II were considered in both groups. According to ATOIII and IDF criteria, the prevalence of metabolic disorders was 29.35% and 41.17 in the fathers of the PCOS patients and 8.85% and 11.76% in the fathers of the control group respectively [p<0.008 and p<0.007, respectively]. Also incidence of hypertension and impaired glucose tolerance test was significantly higher in fathers of the PCOS patients that control groups [p<0.05]. Our findings indicate that the fathers of women with PCOS have higher prevalence of metabolic syndrome and higher risk of developing hypertension and impaired glucose tolerance and diabetes

Comparison of the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome

For more than four decades clomiphene citrate has been the first line of the treatment for ovulatory disorders. The aim of this study was to compare the effects of letrozole and clomiphene citrate on ovulation and pregnancy rate in patients with polycystic ovary syndrome. In this prospective double-blind study, 100 patients with polycystic ovary syndrome were randomized into two equal groups. The first group received letrozole, 5mg daily [per oral] and the second group received clomiphene, 100mg daily during the 3rd-7th days of the menstrual cycles. Intramuscular human chorionic gonadotropin [hCG] [10,000 IU] was administered to trigger ovulation when at least one mature follicle [>/= 18mm] was developed. Ovulation occurred in 30 patients [60%] of the letrozole group and in 16 patients [32%] of the clomiphene group, which showed a statistically significant difference [P=0.009]. The mean number of follicles with diameter >/= 14 mm on the day of administration of hCG was 1.06 +/- 0.95 in the letrozole group and 1.14 +/- 1.17 in the clomiphene group, which showed non-significant difference [P=0.962]. No difference was found in the endometrial thickness between the two groups. A non-significant increase in pregnancy rate was observed in the letrozole group [26% v 14% P=0.21]. Ovulation rate was higher in letrozole group and administration of letrozole was associated with a non-significant increase in pregnancy rate

double blind, randomized, placebo controlled study to assess the efficacy of ketoconazole for reducing the riskof ovarian hyperstimulation syndrome

In order to evaluate the role of ketoconazole in the prevention of ovarian hyperstimulation syndrome [OHSS] in women with polycystic ovary syndrome [PCOS] undergoing ovarian stimulation with gonadotropins, a prospective, random-ized, double-blind, placebo controlled study was done on one-hundred and nine PCOS women that had been referred to be treated by gonadotropins.All 109 women were assigned for random allocation. Group A [50 patients] received two ampoules of hMG beginning on day 2 or 3 of the cycle and ketoconazole [50 mg/every 48 hours] starting on the first day of hMG treatment. Group B [51 patients] received the same protocol of hMG combined with one tablet of placebo every 48 hours. Main outcome measures were follicular development, E2 levels, and pregnancy rate.The total number of hMG ampoules and duration of treatment to attain ovarian stimulation was higher in group A [p<0.0001]. Serum E2 level and number of patients with dominant follicles on day 9 of the cycle were higher in group B [p<0.0001]. There was no significant difference between serum E2 level and total number of follicles at the time of hCG administration in the two groups. The cancellation rate and OHSS rate were similar in the two groups.Ketoconazole has no effect in prevention of OHSS in PCOS patients undergoing ovarian stimulation. It may however reduce the rate of folliculogenesis and steroidogenesis