Bulent Tiras

The effects of rosiglitazone and metformin on insulin resistance and serum androgen levels in obese and lean patients with polycystic ovary syndrome

Aim: The aim of this study was to assess the effects of metformin and rosiglitazone on insulin resistance and serum androgen levelsin both obese and lean patients with polycystic ovary syndrome (PCOS). Materials and methods: Forty lean [body mass index (BMI) <25 kg/m2] and 40 overweight and obese (BMI>²5 kg/m2) patients were included in the study. Waist and hip measurements, serum sex steroid levels, insulin response to 75-g oral glucose tolerance test, fasting insulin, fasting C-peptide levels and homeostasis modelassessment of insulin resistance (HOMA-IR) were determined in all patients. The degree of hirsutism was determined by the Ferriman-Gallwey scoring system. Patients were divided into two groups, with 40 (20 overweight and obese; 20 non-obese) patients each. One group was treated with metformin (MET group) 850 mg bid while the other received rosiglitazone (ROSI group) 4 mg/day for 12 weeks. All measurements were repeated at the end of this period. Results: After the 12-week treatment period, HOMA-IR, area under the curve of insulin, fasting insulin and C-peptide levels were observed to have be decreased significantly in all groups. The decrease in the parameters mentioned above was similar in the four groups. The serum levels of free testosterone, androstenedione and DHEA-S decreased in all groups, but the decrease was statistically significant only in the ROSI groups. Within the lean MET group one patient became pregnant and was hence excluded from the final data analysis. Menstruations became regular after metformin therapy in 41.6% of lean and 35.7% of obese patients who had menstrual disturbance prior to the study. Rosiglitazone therapy improved menstrual disturbance in 61.5 % of lean and 53.8% of obese patients. Conclusions: Our data showed that both metformin and rosiglitazone increased insulin sensitivity in obese patients with PCOS as expected, and in lean patients as well. Rosiglitazone seemed to be more effective in decreasing the androgen levels and in achieving slightly greater improvement in menstrual disturbance than metformin.

The effects of rosiglitazone and metformin on menstrual cyclicity and hirsutism in polycystic ovary syndrome.

Objective. The aim of the present study was to assess the effects of metformin and rosiglitazone on menstrual cyclicity and hirsutism in patients with polycystic ovary syndrome (PCOS). Materials and methods. Ninety-six patients were included in the study. Serum sex steroids, serum fasting glucose and insulin levels, and insulin response to a 75-g oral glucose tolerance test were assessed in all patients. Menstrual cyclicity, with recording of menses in the 6-month periods before the study and during treatment, was evaluated in each patient. Patients were divided into two groups: one was treated with metformin (MET group, n = 48), while the other received rosiglitazone (ROSI group, n = 48). At baseline and after 24 weeks of treatment all patients underwent hormonal and clinical assessments, including body mass index (BMI), waist and hip measurements and Ferriman – Gallwey (FG) scores. Results. Of the 96 patients included in the study, 88 (91.7%) were able to complete it and yielded data for analyses. After the 24-week treatment period, fasting insulin levels and area under the curve for serum insulin decreased significantly, while the glucose/insulin ratio increased in both groups. The degree of reduction in serum free testosterone and androstenedione levels was similar in the two groups. The decreases in luteinizing hormone/follicle-stimulating hormone ratio and serum dehydroepiandrosterone sulfate levels were significantly greater in the ROSI group compared with the MET group. BMI increased in the ROSI group, while it decreased in the MET group. In patients with menstrual disturbance treated with rosiglitazone, menstrual cycles became regular in 87.8%, while improvement occurred in 79.3% of the patients treated with metformin. FG score decreased in both ROSI and MET groups, but the degree of decrease was significantly greater in the ROSI group than in the MET group. Conclusion. Our data show that both metformin and rosiglitazone improve ovarian function and hirsutism in patients with PCOS. Rosiglitazone appears better than metformin in the treatment of hirsutism and has better patient tolerance.

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.

TESE-ICSI in patients with non-mosaic Klinefelter syndrome: a comparative study.

There are limited data in the literature on the performance of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) treatment in patients with Klinefelter syndrome. The current study compared TESE-ICSI treatment in patients with non-mosaic Klinefelter syndrome with controls having non-obstructive azoospermia and normal karyotype. Thirty-three consecutive patients (39 TESE-ICSI cycles) with Klinefelter syndrome (study group) and 113 consecutive patients (130 TESE-ICSI cycles) with non-obstructive azoospermia and normal karyotype (control group) were recruited in a private IVF setting. In the two groups, the mean ages of the men at the time of TESE were 32.0 +/- 6.4 and 34.3 +/- 5.8 years respectively (P < 0.05) and the successful sperm recovery rates per total TESE attempts were 56 (22/39) and 44% (57/130) respectively. Similarly, fertilization rates were comparable between the two groups. In the Klinefelter syndrome group, following biopsy and fluorescence in-situ hybridization, a normal karyotype was obtained in 42 of the 71 embryos (59%). The clinical pregnancy and implantation rates in the study and control groups were similar (39, 23 and 33, 26% respectively). In conclusion, patients with non-mosaic Klinefelter syndrome have sperm recovery and pregnancy rates comparable with patients having non-obstructive azoospermia and normal karyotype.

Comparison of diagnostic accuracy of saline infusion sonohysterography, transvaginal sonography and hysteroscopy

We aimed to compare the accuracy of transvaginal sonography (TVS), saline infusion sonohysterography (SIS) and hysteroscopy (HS) for uterine pathologies among infertile women. A total of 346 patients were selected for operative hysteroscopy, following SIS after TVS. SİS was performed with a Cook Soft 500 IVF catheter. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated to compare the accuracy of TVS, SIS and hysteroscopy for uterine abnormalities. SIS showed a sensitivity of 87%, specificity of 100% and PPV of 100% for endometrial hyperplasia, and a sensitivity and NPV of 100% for polypoid lesions. For submucosal myoma SIS showed a sensitivity of 99% with PPV of 96%. Hysteroscopy had a sensitivity, specificity, PPV and NPV of 98%, 83%, 96% and 91%, respectively for overall uterine pathologies. Finally, SIS seems to be superior to TVS, for uterine pathologies, with respect to hysteroscopy as the gold standard.

Impact of embryo replacement depth on in vitro fertilization and embryo transfer outcomes.

OBJECTIVE To investigate the impact of embryo replacement depth on IVF and embryo transfer outcomes. DESIGN Retrospective analysis (May 2005 to November 2008) of 5,055 ultrasound-guided embryo transfers belonging to 3,930 infertile couples. The distance between the fundal endometrial surface and the catheter tip was measured and accordingly, patients were divided into five groups. SETTING Anatolia IVF Center, Ankara, Turkey. PATIENT(S) All patients enrolled in the IVF program undergoing embryo transfer. INTERVENTION(S) No patient received any additional procedure or intervention. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate (PR) and ongoing PR. RESULT(S) Mean total number of embryos transferred in groups 4 and 5 were significantly higher than in groups 2 and 3. Analysis of PRs and outcome of gestations in the five groups studied yielded similar PRs in all groups except for group 1. CONCLUSION(S) Pregnancy rates and ongoing PRs are higher if the embryos are replaced at a distance >10 mm from the fundal endometrial surface. In addition because significantly more embryos were replaced in cycles where the transfers occurred at a distance of >20 mm, a distance>10 mm to <20 mm seems to be the best site for embryo transfer to achieve higher PRs.

Assisted reproduction in the treatment of polycystic ovarian syndrome.

Treatment of patients with polycystic ovary syndrome (PCOS) with assisted reproductive techniques is a great challenge for the infertility specialist. Patients with PCOS demonstrate many problems, such as excessive body weight and hyperinsulinaemia, that render management more complex. Prior to treatment with IVF, the PCOS patient should be thoroughly evaluated for disclosure of endometrial neoplasia, hyperinsulinaemia, and other general health related problems. Ovarian stimulation for IVF carries the risks of overstimulation and severe hyperstimulation, which should be avoidable in most cases with preventive measures. The outcome in terms of pregnancy and implantation rates is similar for patients with PCOS when compared with patients undergoing IVF for other indications. There are some questions regarding oocyte and embryo quality in women with PCOS. This manifests itself in lower fertilization rate and decreased embryo quality in some studies. However, increased numbers of oocytes available for insemination or ICSI compensate for decreased fertilization rates and embryo quality. More recent studies suggest higher cumulative conception rates in women with PCOS when compared with controls. In-vitro maturation (IVM) of oocytes retrieved from non-stimulated or minimally stimulated cycles represents a viable option that should be considered seriously when assisted conception is attempted. Results of IVM, however, should be improved further and generalized before the technique can be advocated as the initial treatment approach in these patients.

Intravenous leiomyomatosis treated with aromatase inhibitor therapy

[1]. The gonads of these patients develop into ovaries in utero, but then degenerate into streaks owing to the lack of a second X chromosome [1]. Cesarean is the usual mode of delivery in these patients [3], but in the present case the patient had a spontaneous vaginal delivery. Gonadal neoplasm can occur in up to 30% of cases and gonadoblastoma accounts for the majority of tumors [2]. Gonadoblastoma may synthesize estrogens or testosterone and is associated with dysgerminoma in 50% of cases [4]. In one case report 5 different histological subtypes of germ cell malignancies were described [4]. Early diagnosis is important and immediate gonadectomy is strongly recommended, as these tumors may even develop in infancy. A multidisciplinary approach with psychological support is important for the management of patients with pure gonadal dysgenesis. Normal uterine function including vaginal delivery is possible in these patients. References

Management of endometrial polyps diagnosed before or during ICSI cycles

This retrospective study aimed to shed light on the management options of endometrial polyps diagnosed before or during intracytoplasmic sperm injection (ICSI) treatment. The study included all fresh ICSI cycles performed in the Anatolia IVF Center between July 2005 and January 2009. Group 1 consisted of 47 patients who were diagnosed with an endometrial polyp before their ICSI cycle. All patients diagnosed with an endometrial polyp by transvaginal ultrasonography before the ICSI cycle underwent hysteroscopic polyp resection. Group 1 was compared with 47 matched control patients without endometrial polyps who underwent standard ICSI cycles (group 2). Group 3 included 128 patients diagnosed with an endometrial polyp during stimulation in their ICSI cycles. Group 3 was compared with 128 matched control patients without endometrial polyps who underwent standard ICSI cycles (group 4). Patients diagnosed with an endometrial polyp before ICSI cycles were similar to their controls with regard to clinical pregnancy (29.8% versus 38.3%) and live-birth (25.5% versus 31.9%) rates per transfer, as were patients diagnosed with an endometrial polyp during ovarian stimulation (clinical pregnancy rates 45.3% versus 46.9%; live-birth rates 40.6% versus 39.8%). In conclusion, further studies are required to identify the most appropriate management of endometrial polyps.

Effect of air bubble localization after transfer on embryo transfer outcomes

OBJECTIVES Our study aimed to provide information about the effects of air bubble localization after transfer on embryo transfer outcomes. STUDY DESIGN Retrospective analysis of 7489 ultrasound-guided embryo transfers. Group 1 included 6631 embryo transfers in which no movement of the air bubbles was observed after transfer. Group 2 consisted of 407 embryo transfers in which the air bubbles moved towards the uterine fundus spontaneously, a little time after transfer. Group 3 included 370 embryo transfers in which the air bubbles moved towards the uterine fundus with ejection, immediately after transfer. Group 4 consisted of 81 embryo transfers in which the air bubbles moved towards the cervical canal. RESULTS The four patient groups were different from one another with respect to positive pregnancy tests. Post hoc test revealed that this difference was between group 4 and other groups. CONCLUSIONS An initial finding of our study was significantly decreased positive pregnancy test rates and clinical pregnancy rates with air bubbles moving towards the cervical canal after transfer. Although air bubbles moving towards the uterine fundus with ejection were associated with higher pregnancy rates, higher miscarriage rates and similar live birth rates were observed compared to air bubbles remaining stable after transfer.