Hakan Yarali

Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria

STUDY QUESTION What is the prevalence, phenotype and metabolic features of polycystic ovary syndrome (PCOS) in the same population according to three different diagnostic criteria? SUMMARY ANSWER The prevalence of PCOS under National Institutes of Health (NIH), Rotterdam and Androgen Excess and PCOS (AE-PCOS) Society criteria was 6.1, 19.9 and 15.3%, respectively. PCOS carried a 2-fold increased risk of metabolic syndrome regardless of the diagnostic criteria used. WHAT IS KNOWN AND WHAT THIS PAPER ADDS The prevalence rates of PCOS differ depending on the diagnostic criteria used to define the syndrome. The current paper gives the prevalence rates of the component and composite phenotypes of PCOS in the same population and reports similar rates of metabolic syndrome in women with PCOS under contrasting diagnostic criteria. DESIGN In this cross-sectional study, 392 women between the ages of 18 and 45 years were analyzed. PARTICIPANTS AND SETTING When the prevalence of PCOS according to NIH was set to 8% with a precision of 2.2% and confidence interval of 95%, the sample size required for a prevalence survey was found to be 400 subjects. The study was carried out in the General Directorate of Mineral Research and Exploration, a government-based institute, in which the largest number of female staff (n = 527) are employed within a single institute in Ankara, Turkey. The study was performed between 7 December 2009 and 30 April 2010. All female subjects between the ages of 18 and 45 years were invited to participate. Women older than 45 or younger than 18 years, post-menopausal women, women with a history of hysterectomy or bilateral oopherectomy and pregnant women were excluded. Totally, 392 of the employees were recruited for the final analyses. MAIN RESULTS AND THE ROLE OF CHANCE The prevalence of PCOS under NIH, Rotterdam and AE-PCOS Society criteria were 6.1, 19.9 and 15.3%, respectively. While the prevalence of metabolic syndrome was 6.1% in the whole study group, within the patients diagnosed as PCOS according to NIH, Rotterdam and AE-PCOS Society criteria, it was 12.5, 10.3 and 10.0%, respectively. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION Even though we have included women working at a single institution with a high response rate for the participation, we cannot exclude potential selection bias due to undetermined differences between our sample and background community. We might have underestimated actual prevalence of metabolic syndrome in PCOS due to lack of oral glucose tolerance test 2 h glucose data. GENERALIZABILITY TO OTHER POPULATIONS Current results can be generalized to Caucasian populations and may present variations in other populations according to race and ethnicity. STUDY FUNDING/COMPETING INTEREST(S) This work was, in part, sponsored by Merck Serono. TRIAL REGISTRATION NUMBER Not applicable.

Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome

OBJECTIVE To assess cardiac flow parameters in patients with polycystic ovary syndrome (PCOS). DESIGN A prospective case-control study. SETTING University-based hospital. PATIENT(S) Thirty consecutive patients with PCOS were enrolled. Thirty women with regular menstrual cycles served as the controls. INTERVENTION(S) Systolic and diastolic function parameters were assessed by standard two-dimensional and M-mode echocardiography. Insulin sensitivity was evaluated by a standard 75-g oral glucose tolerance test and area-under-curve insulin analysis. Serum hormones, lipid profile, homocysteine, vitamin B(12), folate, fibrinogen, uric acid, and plasminogen activator inhibitor-I concentrations were measured. MAIN OUTCOME MEASURE(S) Systolic and diastolic function parameters, insulin sensitivity and serum homocysteine levels. RESULT(S) The mean serum homocysteine and uric acid concentrations were significantly higher in the PCOS group. Patients with PCOS had significant hyperinsulinemia. All systolic function parameters were comparable between the two groups. However, patients with PCOS had significantly lower peak mitral flow velocity in early diastole and significantly lower ratio between the early and late peak mitral flow velocities and also had significantly longer isovolumic relaxation time, reflecting a trend for nonrestrictive-type diastolic dysfunction. The area-under-curve insulin correlated positively with peak mitral flow velocity in late diastole (r = 0.375). The mean cholesterol/high-density lipoprotein ratio correlated negatively with mean mitral flow velocity in early diastole (E) peak (r = -0.474). The mean fasting insulin level correlated negatively with mean E/A ratio (r = -0.387). CONCLUSION(S) Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular disease risk in patients with PCOS.

Evaluation of adhesion formation after laparoscopic treatment of polycystic ovarian disease.

The incidence and fertility effects of postoperative adhesion formation after laparoscopic ovarian electrocautery or laser photocoagulation of polycystic ovaries has not been adequately analyzed. Short-interval second-look laparoscopy appears to be a useful method for addressing this issue. Employing short-interval second-look laparoscopy 3 to 4 weeks after the initial laparoscopic intervention, we were able to demonstrate adhesions in 6 of 7 patients (85%) treated with ovarian electrocautery and 8 of 10 patients (80%) submitted to laser therapy. The adhesions were amenable to laparoscopic lysis in 12 of 14 patients (85%). The subsequent conception rates within 6 months of second-look laparoscopy that were 57% and 40% in the electrocautery and the Nd:YAG laser groups, respectively, may in part be attributed to the restoration of normal pelvic anatomy during this procedure.

Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG

STUDY QUESTION Is severe early ovarian hyperstimulation syndrome (OHSS) completely prevented with the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol? SUMMARY ANSWER Severe early OHSS can occur even after the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol. WHAT IS KNOWN ALREADY Prior studies including over 200 women who received the GnRH agonist trigger and 1500 hCG luteal rescue protocol have reported complete prevention of severe early OHSS. Only a few late OHSS cases have been reported and it has been suggested that this protocol can be safely applied to any women under risk. STUDY DESIGN, SIZE, DURATION This retrospective cohort study included all women who were at high risk of OHSS and were given the GnRH agonist trigger plus hCG luteal rescue protocol between December 2008 and August 2012 in the two participating centers. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 23 women with a mean estradiol level of 4891 ± 2214 pg/ml and a mean number of >12 mm follicles of 20 ± 6 on the day of ovulation triggering. OHSS was categorized according to the Golan criteria. MAIN RESULTS AND THE ROLE OF CHANCE Overall 6 of the 23 (26%) women developed severe OHSS. Five women had severe early OHSS requiring ascites drainage and hospitalization and three of these women did not undergo embryo transfer. The number of follicles measuring 10-14 mm on the day of triggering was significantly different between women who developed severe early OHSS and those who did not. LIMITATIONS, REASONS FOR CAUTION The small number of women with severe early OHSS may have prevented identification of other significant risk factors. WIDER IMPLICATIONS OF THE FINDINGS Although the GnRH agonist plus 1500 IU hCG luteal rescue protocol significantly decreases the risk of severe OHSS, this life threatening complication can still occur in high-risk patients. It would be prudent to avoid hCG luteal rescue and freeze all embryos for future transfer in such women particularly when there are ≥18 follicles with 10-14 mm diameters even with few larger follicles.

Impact of isolated obesity on ICSI outcome

The aim of this study was to assess the impact of isolated obesity on the outcome of intracytoplasmic sperm injection (ICSI). A total of 775 patients undergoing 1113 ICSI cycles were categorized on the basis of body mass index (BMI): group 1 (BMI 18.5-24.9 kg/m(2); normal weight; n = 627 cycles), group 2 (BMI 25.0-29.9 kg/m m(2); overweight; n = 339 cycles) and group 3 (BMI >or=30 kg/m(2); obese; n = 147 cycles). Sixty-three (10.0%) cycles in group 1, 53 (15.6%) cycles in group 2 and 26 cycles (17.7%) in group 3 were cancelled (P < 0.05 for group 1 versus groups 2 and 3). Despite the significantly higher total gonadotrophin consumption in groups 2 and 3 compared with group 1, the mean serum oestradiol level on the day of human chorionic gonadotrophin administration was significantly higher in group 1 (P < 0.05). The number of cumulus-oocyte complexes, metaphase II oocytes, and two-pronucleated oocytes were significantly lower in group 3 compared with group 1 (P < 0.05). However, fertilization rate, the mean number of embryos transferred, the mean number of grade 1 embryos transferred, clinical pregnancy, implantation, multiple pregnancy and miscarriage rates were comparable among the three groups. The rate of cycles with cryopreservable embryos was significantly lower in groups 2 and 3 compared with group 1 (P < 0.05).

Intracytoplasmic sperm injection versus in vitro fertilization for patients with a tubal factor as their sole cause of infertility: a prospective, randomized trial

OBJECTIVE To compare the efficacy of intracytoplasmic sperm injection and IVF in women with a tuboperitoneal factor as their sole cause of infertility. DESIGN Prospective, randomized study. SETTING Hacettepe University Assisted Reproduction Unit, Ankara, Turkey. PATIENT(S) Seventy-six consecutively seen patients with tuboperitoneal factor infertility were randomized on an alternate basis to undergo either intracytoplasmic sperm injection (38 patients and cycles) or IVF (38 patients and cycles). INTERVENTION(S) Intracytoplasmic sperm injection and IVF. MAIN OUTCOME MEASURE(S) Fertilization, implantation, and clinical pregnancy rates. RESULT(S) A comparable number of oocytes and embryos were obtained with intracytoplasmic sperm injection and IVF. The two-pronuclei fertilization rates per metaphase II oocyte or mature cumulus-oocyte complex were similar in the two groups. The numbers of total and grade I embryos transferred also were similar. Comparisons of intracytoplasmic sperm injection and IVF did not reveal any statistically significant differences in individual implantation rates (38.75% +/- 24.46% and 34.58% +/- 16.97%, respectively) clinical pregnancy rates per cycle (21.05% and 21.05%, respectively), or take-home infant rates (18.42% and 15.79%, respectively). The type of procedure performed was not a significant predictor of clinical pregnancy. CONCLUSION(S) When a decision is made to proceed with an assisted reproductive technique in patients with a tubal factor as their sole cause of infertility, IVF should be the initial treatment of choice.

Heart Rate Variability in Young Women with Polycystic Ovary Syndrome

Background: Limited data are available related to the effects of sex hormones on cardiac autonomic function. Few studies investigated the heart rate variability (HRV) parameters during regular menstrual cycle or in postmenopausal women using hormone replacement therapy, but the results were contradictory. The aim of the study was to compare the characteristics of the autonomic innervation of the heart in polycystic ovary syndrome (PCOS) patients with regularly cycling controls.

What is the role of office hysteroscopy in women with failed IVF cycles

Recurrent implantation failure (RlF) may be due to unrecognized uterine pathology. Hysterosalpingography, transvaginal ultrasonography, saline infusion sonography and hysteroscopy are the tools to assess the inner architecture of the uterus. Hysteroscopy is considered to be the gold standard; however, the validity of hysteroscopy may be limited in the diagnosis of endometritis and endometrial hyperplasia. The frequencies of unrecognized uterine pathology revealed by hysteroscopy are 18-50% and 40-43% in patients undergoing IVF with or without RlF, respectively. Endometrial polyps may be associated with increased miscarriage rates. Implantation rates are decreased in patients with submucous or intramural fibroids with distorted uterine cavity. There is controversy on the impact of uterine septum less than 1 cm length on pregnancy outcome in IVF cycles. There is paucity of data on the role of hysteroscopy in failed IVF cycles. In the available two randomized controlled trials, pregnancy rates appear to be increased when hysteroscopy is performed; however within the hysteroscopy group, pregnancy rates are comparable among the normal or surgically corrected subgroups. Further studies are warranted to delineate the role of hysteroscopy in patients with failed IVF cycle(s). This review aims to evaluate the validity of office hysteroscopy in failed IVF cycles.

Antagonist/letrozole protocol in poor ovarian responders for intracytoplasmic sperm injection: a comparative study with the microdose flare-up protocol

OBJECTIVE To compare the effect of the GnRH antagonist/letrozole protocol (AL) with the microdose GnRH agonist flare-up (MF) protocol in poor ovarian responders for intracytoplasmic sperm injection (ICSI). DESIGN Retrospective, case-control study. SETTING Anatolia Women and IVF Center. PATIENT(S) Eight hundred eighty-five consecutive patients (1383 cycles) predicted to have or with a history of poor ovarian response who were undergoing ICSI were enrolled. The MF protocol was used in 673 patients (1026 cycles), and the AL protocol was used in the remaining 212 patients (357 cycles). INTERVENTION(S) Controlled ovarian hyperstimulation and ICSI. MAIN OUTCOME MEASUREMENT(S) Cycle cancellation rate, number of oocytes retrieved, fertilization rate, embryo quality, clinical pregnancy, and implantation rates. RESULT(S) The total gonadotropin consumption, duration of stimulation, E(2) level on the day of hCG administration, and number of oocytes retrieved were significantly lower with the AL protocol compared with the MF protocol. However, the fertilization rate and the rate of at least one top-quality embryo transferred were higher with the AL compared with the MF protocol. The clinical pregnancy rates were comparable between the two groups. The implantation rates with the MF and AL protocols were 9.8% and 14.5%, respectively. CONCLUSION(S) The GnRH AL protocol is an effective protocol that may be used in poor ovarian responders for ICSI.

Urinary follicle-stimulating hormone (FSH) versus recombinant FSH in clomiphene citrate–resistant, normogonadotropic, chronic anovulation: a prospective randomized study

OBJECTIVE To compare the efficacy and safety of urinary FSH and recombinant FSH for ovulation induction in patients with clomiphene citrate-resistant, normogonadotropic, chronic anovulation. DESIGN Prospective, randomized trial. SETTING University-based infertility clinic. PATIENT(S) Fifty-one women. INTERVENTION(S) Subjects were randomized to receive either urinary FSH (35 patients, 64 cycles) or recombinant FSH (16 patients, 32 cycles). A maximum of three cycles using the low-dose step-up protocol with the same gonadotropin were undertaken. MAIN OUTCOME MEASURE(S) Cumulative ovulation and pregnancy rates after three cycles, total gonadotropin dose, duration of stimulation, and single follicle development rate. RESULT(S) Cumulative ovulation rates were 89.3% and 93.1% for the urinary FSH and recombinant FSH groups, respectively. The threshold and total doses of FSH and the duration of stimulation were similar between the two groups. Significantly more single follicle development was noted in the recombinant FSH group. The respective clinical pregnancy rates per noncanceled cycles in the urinary FSH and recombinant FSH groups were 23.2% and 27.6%. There were three sets of twins in the urinary FSH group. No case of ovarian hyperstimulation syndrome was encountered. CONCLUSION(S) Urinary FSH and recombinant FSH are both efficient and safe for inducing ovulation with the low-dose step-up protocol.