Jaron Rabinovici

Sustained Relief of Leiomyoma Symptoms by Using Focused Ultrasound Surgery

OBJECTIVE: To assess several measures of the long-term outcome of magnetic resonance–guided focused ultrasound surgery for symptomatic uterine leiomyomata. METHODS: Data on 359 women completing 24-month follow-up in all clinical trials of magnetic resonance–guided focused ultrasound surgery for uterine leiomyomata were analyzed. Quality of life outcomes, measured by the symptom severity score of the Uterine Fibroid Symptoms Quality Of Life Questionnaire were assessed for 24 months after treatment. Clinical endpoints, including uterine shrinkage, the need for additional leiomyoma treatment, and the time to additional leiomyoma treatment, were all assessed. The nonperfused volume ratio after treatment, calculated from the gadolinium-enhanced magnetic resonance imaging after treatment and the best measure of tissue necrosis after treatment, was used to assess outcome based on completeness of leiomyoma ablation. RESULTS: Women undergoing magnetic resonance–guided focused ultrasound surgery for symptomatic uterine leiomyomata have durable symptom relief, as measured by the symptom severity score at 24 months, with significantly greater improvement with more complete ablation (P<.001). Survival analysis demonstrates a significant reduction in the percentage of women undergoing additional leiomyoma treatment (P=.001) in women in the high nonperfused volume group. The mean shrinkage and mean residual nonperfused volume ratio are both significantly above zero at 6 months in the high nonperfused volume group (P<.001). The incidence of adverse events is low. However, for women with minimal treatment, the risk of additional procedures is high. CONCLUSION: Magnetic resonance–guided focused ultrasound surgery is an effective treatment for uterine leiomyomata and results in sustained symptomatic relief. LEVEL OF EVIDENCE: III

Pregnancy outcome after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for conservative treatment of uterine fibroids

OBJECTIVE To report all pregnancies to date after magnetic resonance-guided focused ultrasound surgery (MRgFUS) for the conservative treatment of clinically significant uterine fibroids. DESIGN Prospective registry of all known pregnancies occurring after MRgFUS maintained by the device manufacturer and reported to the Food and Drug Administration. SETTING World experience of pregnancies after treatment with reports from 13 sites in seven countries. PATIENT(S) Fifty-one reproductive-age women with uterine leiomyomas. INTERVENTION(S) Women underwent MRgFUS treatment for symptomatic uterine leiomyomas before this report. MAIN OUTCOME MEASURE(S) Pregnancy outcomes and complications. RESULT(S) Fifty-four pregnancies in 51 women have occurred after MRgFUS treatment of uterine leiomyomas. The mean time to conception was 8 months after treatment. Live births occurred in 41% of pregnancies, with a 28% spontaneous abortion rate, an 11% rate of elective pregnancy termination, and 11 (20%) ongoing pregnancies beyond 20 gestational weeks. The mean birth weight was 3.3 kg, and the vaginal delivery rate was 64%. CONCLUSION(S) Preliminary pregnancy experience after MRgFUS is encouraging, with a high rate of delivered and ongoing pregnancies.

Ovarian hyperstimulation syndrome: prediction by number and size of preovulatory ovarian follicles *

Monitoring of human menopausal gonadotropin (hMG) treatment for induction of ovulation according to either preovulatory estrogen levels or the presence of a dominant ovarian follicle was found insufficient to prevent ovarian hyperstimulation syndrome (OHS). In 65 infertile patients treated with hMG and human chorionic gonadotropin (hCG), a possible correlation between the number and size of all ovarian follicles on the day of assumed ovulation and the occurrence of OHS was evaluated in order to assess the value of ultrasonography in predicting OHS. It was found that patients with OHS had significantly more follicles at the time of hCG than patients without OHS. Mild OHS was characterized by the presence of eight to nine follicles, 68.7% of which were of intermediate size (9 to 15 mm). In moderate to severe OHS 95% of the preovulatory follicles were less than 16 mm, most of them (54.7%) less than 9 mm in diameter. It can be concluded that a specific preovulatory follicular configuration characterizes mild and severe hyperstimulation. This is important information before hCG administration and emphasizes the value of ovarian ultrasonography in predicting OHS.

Randomized management of the second nonvertex twin: Vaginal delivery or cesarean section

Sixty twin deliveries after the thirty-fifth gestational week with vertex-breech and vertex-transverse presentations were managed according to a randomization protocol. Thirty-three parturient women (21 vertex-breech and 12 vertex-transverse presentations) were allocated for vaginal delivery and 27 for cesarean section (18 vertex-breech and nine vertex-transverse). Six pairs of twins in the vaginal delivery group were delivered in a different mode than requested by the protocol (two women underwent cesarean section; in four cases the second twin spontaneously changed to vertex presentation). There were no significant differences between 1- and 5-minute Apgar scores and incidence of neonatal morbidity between the second-born twins in both study groups. Firstborn twins had higher 1-minute Apgar scores than the second-born infants irrespective of route of delivery (p less than 0.05). No case of birth trauma or neonatal death was recorded. Maternal febrile morbidity was significantly higher in the cesarean section group than in the vaginal delivery group (40.7% versus 11.1%, p less than 0.05). These results suggest that in twins with vertex-breech or vertex-transverse presentations after the thirty-fifth week of gestational age the neonatal outcome of the second twin was not significantly influenced by the route of delivery.

Cancer incidence in a cohort of infertile women who underwent in vitro fertilization

OBJECTIVE To assess whether ovarian hyperstimulation and IVF increase the risk for cancer. DESIGN Historical cohort analysis. SETTING; IVF units of two medical centers in Israel. PATIENT(S) Five thousand twenty-six women who underwent IVF between 1981 and 1992. INTERVENTION(S); Cancer incidence rates were determined through linkage to the National Cancer Registry and were compared with expected rates with respect to age, sex, and place of birth. MAIN OUTCOME MEASURE(S) Development of cancer. RESULT(S) Twenty-seven cases of cancer were observed, and 35.6 were expected (standardized incidence ratio, 0.76 [95% CI, 0.50-1.10]). Eleven cases of breast cancer were observed, whereas 15.86 were expected (standardized incidence ratio, 0.69 [95% CI, 0.46-1.66]). One case of ovarian cancer and 1 case of cervical cancer were observed, compared with 1.74 and 1.73 cases expected, respectively. The type of infertility, number of IVF cycles, and treatment outcome did not significantly affect risk for cancer. CONCLUSION(S) In a cohort of women treated with IVF, no excess risk for cancer was noted.

Activin and inhibin in the human adrenal gland. Regulation and differential effects in fetal and adult cells.

Recent experimental data have revealed that activins and inhibins exert pivotal effects on development. As part of our studies on growth and differentiation of the human fetal adrenal gland, we examined the subunit localization, as well as the mitogenic and steroidogenic actions of activin and inhibin in human fetal and adult adrenals. All three activin and inhibin subunit proteins (alpha, beta A, and beta B) were detected in the fetal and adult adrenal cortex. Immunoreactive activin-A dimer was demonstrated in midgestation fetal and neonatal adrenals. ACTH1-24-stimulated fetal adrenal cell expression of alpha and beta A subunit messenger RNA. In addition, ACTH elicited a rise in levels of immunoreactive alpha subunit secreted by fetal and adult adrenal cells. Human recombinant activin-A inhibited mitogenesis and enhanced ACTH-stimulated cortisol secretion by cultured fetal zone cells, but not definitive zone or adult adrenal cells. Recombinant inhibin-A had no apparent mitogenic or steroidogenic effects. Thus, activin selectively suppressed fetal zone proliferation and enhanced the ACTH-induced shift in the cortisol/dehydroepiandrosterone sulfate ratio of fetal zone steroid production. These data indicate that activin-A may be an autocrine or paracrine factor regulated by ACTH, involved in modulating growth and differentiated function of the human fetal adrenal gland.

Clinical improvement and shrinkage of uterine fibroids after thermal ablation by magnetic resonance‐guided focused ultrasound surgery

Hysterectomy or myomectomy are the accepted treatments for symptomatic uterine fibroids. Heat ablation of uterine fibroids has been shown to be an effective alternative treatment. The aim of this study was to determine the clinical efficacy of non‐invasive thermal ablation by transcutaneous magnetic resonance‐guided high‐intensity focused ultrasound (MRgFUS) for the treatment of symptomatic uterine fibroids.

Outcome of hysteroscopic resection of submucous myomas for infertility

OBJECTIVE To examine the reproductive outcome after operative hysteroscopic resection of submucous myomas in women for whom no other infertility factor was identified. DESIGN Fifteen infertile women with submucous myomas underwent an intensive workup to exclude other causes of infertility. Operative hysteroscopy for resection of the submucous myomas was performed using a rigid 26 French resectoscope (Karl Storz GmbH & Co., Tuttlingen, Germany). SETTING Academic tertiary referral center. RESULTS The mean +/- SD duration of the procedure was 25.5 +/- 5.6 minutes. No operative or postoperative complications occurred and all patients were discharged within 6 hours. The follow-up period was 12.0 +/- 4.2 months (mean +/- SD). Seven women conceived (pregnancy rate of 47%) and six of them subsequently delivered at term. CONCLUSION The results of this study indicate that operative hysteroscopy achieved a pregnancy rate comparable to myomectomy via laparotomy. These results suggest that operative hysteroscopy is the procedure of choice for the resection of submucous myomas in infertile women.

Increased prevalence of thrombophilia among women with severe ovarian hyperstimulation syndrome

OBJECTIVE To determine the prevalence of markers of thrombophilia in women hospitalized for severe OHSS. DESIGN Prospective study. SETTING Academic research center. PATIENT(S) Women undergoing induction of ovulation complicated by severe OHSS (n = 20) and women undergoing induction of ovulation without development of severe OHSS (n = 41). INTERVENTION(S) Blood samples to test for markers of thrombophilia were obtained during the luteal phase of the treatment cycle. MAIN OUTCOME MEASURE(S) Blood samples were analyzed for markers of thrombophilia, such as plasma levels of antithrombin, protein S and protein C, antiphospholipid antibodies, the factor V Leiden mutation, and 677T polymorphism in the 5,10 methyltetrahydrofolate reductase (MTHFR 677T) gene. RESULT(S) Seventeen of 20 patients with severe OHSS (85%) and 11 of 41 controls (26.8%) had one or more positive markers of thrombophilia. Of the women with severe OHSS, 6 had a decreased antithrombin level, 8 had decreased levels of protein S, 7 were homozygous for the MTHFR 677T mutation, 1 was heterozygous for the factor V Leiden mutation, and 5 had antiphospholipid antibodies. Eight women with OHSS and no controls had more than one positive marker of thrombophilia. CONCLUSION(S) The prevalence of thrombophilia is increased in women with severe OHSS. These findings suggest that prophylactic screening for this disorder and possible use of heparin prophylaxis for thromboembolic phenomena should be considered in these patients.

Insulin-like growth factor I (IGF-I) levels in follicular fluid from human preovulatory follicles: correlation with serum IGF-I levels *

Insulin-like growth factor I (IGF-I) levels were measured in both serum and fluid of preovulatory follicles (n = 156) in 43 women undergoing in vitro fertilization (IVF). The mean IGF-I level in follicular fluid (FF) was significantly lower than in serum (0.52 +/- 0.02 IU/L versus 0.66 +/- 0.23 IU/L), and FF levels were significantly correlated with individual serum IGF-I levels as well as with follicular size and FF volume but not with oocyte maturity, granulosa cell appearance, or IVF. This suggests that FF IGF-I levels cannot serve as a clinical indicator for the degree of oocyte/granulosa cell differentiation or a predictor for IVF. Serum IGF-I levels were inversely correlated with the number of human menopausal gonadotropin ampules administered during treatment, suggesting that IGF-I might enhance ovarian gonadotropic stimulation.