6p21 rearrangements in uterine leiomyomas targeting HMGA1.

To quantify the expression of HMGA1 mRNA in uterine leiomyomas, the expression of HMGA1 was analyzed in a series including tumors with aberrations of chromosome 6 (n = 7) and cytogenetically normal tumors (n = 8) as a control group by quantitative reverse transcriptase-polymerase chain reaction. The average expression level in the 6p21 group was found to be 5.6 times higher than that in the control group, and with one exception, all cases with 6p21 alteration revealed a high expression of HMGA1 mRNA than cytogenetically normal tumors. Nevertheless, compared to fibroids with a normal karyotype, the upregulation of the HMGA1 mRNA in these cases was much less strong than that of HMGA2 mRNA in case of 12q14∼15 aberrations identified in previous studies.

Overexpression of HMGA2 in uterine leiomyomas points to its general role for the pathogenesis of the disease.

An overexpression of HMGA2 is supposed to be a key event in the genesis of leiomyoma with chromosomal rearrangements affecting the region 12q14-15 targeting the HMGA2 gene, but gene expression data regarding differences between uterine leiomyomas with and those without 12q14-15 aberrations are insufficient. To address the question whether HMGA2 is only upregulated in the 12q14-15 subgroup, the expression of HMGA2 was analyzed in a comprehensive set of leiomyomas (n = 180) including tumors with 12q14-15 chromosomal aberrations (n = 13) and matching myometrial tissues (n = 51) by quantitative RT-PCR. The highest expression levels for HMGA2 were observed in tumors with rearrangements affecting the region 12q14-15, but although HMGA2 is expressed at lower levels in leiomyomas without such aberrations, the comparison between the expression in myomas and matching myometrial tissues indicates a general upregulation of HMGA2 regardless of the presence or absence of such chromosomal abnormalities. The significant (P < 0.05) overexpression of HMGA2 also in the group of fibroids without chromosomal aberrations of the 12q14-15 region suggests a general role of HMGA2 in the development of the disease.

A double-blind, randomized, placebo-controlled study to assess the efficacy of ketoconazole for reducing the risk of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the role of ketoconazole in prevention of ovarian hyperstimulation syndrome (OHSS) in women with the polycystic ovary syndrome (PCOS) undergoing ovarian stimulation with gonadotropins. DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: University hospitals. One hundred nine women with PCOS who were referred for treatment with gonadotropins. INTERVENTION(S): Fifty patients were randomly assigned to receive 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. Fifty-one patients received the same amount of hMG plus one tablet of placebo every 48 hours. MAIN OUTCOME MEASURE(S): Follicular development, E(2) level, and pregnancy rate. RESULT(S): The total number of hMG ampoules and duration of treatment to attain ovarian stimulation were higher among ketoconazole recipients. The serum E(2) level and number of patients with dominant follicles on day 9 of the cycle were greater in placebo recipients. Serum E(2) level and total number of follicles at the time of hCG administration did not differ between the two groups. The cancellation rate and OHSS rate were similar in the two groups. CONCLUSION(S): Ketoconazole does not prevent OHSS in patients with PCOS who are undergoing ovarian stimulation. It may reduce the rate of folliculogenesis and steroidogenesis.

Comparative, double-blind, randomized, placebo-controlled trial of intraperitoneal of bupivacaine and lidocaine for pain control after diagnostic laparoscopy.

STUDY OBJECTIVE: To compare the effect of intraperitoneal bupivacaine and lidocaine on reducing pain after diagnostic laparoscopy. DESIGN: Randomized, double-blind, placebo-controlled study (Canadian Task Force classification I). SETTING: University teaching hospital. PATIENTS: One hundred thirty-four women with unexplained infertility. INTERVENTION: Diagnostic laparoscopy with intraperitoneal administration of bupivacaine or lidocaine. MEASUREMENTS AND MAIN RESULTS: Patients were randomized into one of four groups. In group A, at the end of laparoscopy 0.125% bupivacaine 30 ml was instilled into the pelvic cavity and the same dose was instilled over the diaphragmatic vault. Groups B and C received the same volume of 5% lidocaine and normal saline, respectively. Group D received no intraperitoneal agent. The verbal pain scale questionnaire was used to assess postoperative pain. Pain scores 2 and 24 hours postoperatively were significantly lower for group A than for groups B and C (p = 0.0001). Scores in group B were also significantly lower than those in groups C and D (p = 0.0001). Women in group A required less additional analgesia than those in the other groups. CONCLUSION: Compared with lidocaine and placebo, intraperitoneal bupivacaine significantly decreased postoperative pain, and this effect was long lasting.

Ovarian stromal blood flow changes after laparoscopic ovarian cauterization in women with polycystic ovary syndrome.

BACKGROUND: Women with PCOS have significant differences in intra-ovarian and uterine artery haemodynamics. The aims of this study were to compare the ovarian stromal blood flow before and after laparoscopic ovarian diathermy, and to evaluate the value of these parameters in predicting the outcome of treatment in women with polycystic ovaries. METHODS: Colour Doppler blood flow within the ovarian stroma was recorded and serum concentrations of FSH, LH and testosterone were measured in 52 women with polycystic ovaries before and after laparoscopic ovarian diathermy. Ovulation was evaluated by folliculometry and progesterone assay in the first menstrual cycle after operation. RESULTS: Six to 10 weeks after the diathermy, serum concentrations of LH and testosterone decreased significantly (P = 0.001). The mean +/- SD peak systolic velocity decreased from 14.04 +/- 6.28 to 12.49 +/- 6.32 cm/s (P = 0.001), pulsatility index increased from 0.98 +/- 0.36 to 1.78 +/- 0.72 (P = 0.001), and resistance index increased from 0.55 +/- 0.16 to 0.71 +/- 19 (P = 0.001). A total of 73% of the women ovulated. There were significant negative correlations between pulsatility index and LH (r = -0.43, P = 0.001), pulsatility index and testosterone (r = -0.40, P = 0.003) and pulsatility index and LH/FSH ratio (r = -0.53, P = 0.001). CONCLUSIONS: Laparoscopic ovarian diathermy in women with polycystic ovary syndrome may result in a decrease in ovarian stromal blood flow velocity. There was a significant correlation between hormonal and ovarian stromal blood-flow changes. Changes in the Doppler parameters were significantly higher in women who ovulated. The measurement of ovarian stromal blood flow by colour Doppler may be of value in predicting the outcome of treatment.