Giovanna Tropeano

Non-surgical management of uterine fibroids

BACKGROUND Efforts to develop alternatives to surgery for management of symptomatic uterine fibroids have provided new techniques and new medications. This review summarizes the existing literature on uterine artery embolization (UAE) and investigational studies on four newer approaches. METHODS PubMed, Cochrane and Embase were searched up to December 2007. Studies reporting side-effects and complications and presenting numerical data on at least one outcome measure were included. RESULTS Case studies report 50-60% reduction in fibroid size and 85-95% relief of symptoms following UAE. The largest of these studies reported an in-hospital complication rate of 2.7% (90 of 3041 patients) and a post-discharge complication rate of 26% (710 of 2729 patients). Eight studies compared UAE with conventional surgery. Best evidence suggested that UAE offered shorter hospital stays (1-2 days UAE versus 5-5.8 days surgery, 3 randomized controlled trials (RCTs)) and recovery times (9.5-28 days UAE versus 36.2-63 days surgery, 3 RCTs) and similar major complication rates (2-15% UAE versus 2.7-20% surgery, 3 RCTs). Four studies analysing cost-effectiveness found UAE more cost-effective than surgery. There is insufficient evidence regarding fertility and pregnancy outcome after UAE. Five feasibility studies after transvaginal temporary uterine artery occlusion in 75 women showed a 40-50% reduction in fibroid volume and two early studies using magnetic resonance guided-focused ultrasound showed symptom relief at 6 months in 71% of 109 women. Two small RCTs assessing mifepristone and asoprisnil showed promising results. CONCLUSIONS Good quality evidence supports the safety and effectiveness of UAE for women with symptomatic fibroids. The current available data are insufficient to routinely offer UAE to women who wish to preserve or enhance their fertility. Newer treatments are still investigational.

Permanent amenorrhea associated with endometrial atrophy after uterine artery embolization for symptomatic uterine fibroids

OBJECTIVE To report a case of permanent amenorrhea associated with endometrial atrophy after uterine artery embolization for symptomatic uterine fibroids. DESIGN Case report. SETTING Gynecologic clinic of a university hospital. PATIENT(S) A 44-year-old woman with menorrhagia and anemia caused by multiple fibroids. INTERVENTION(S) Transcatheter bilateral uterine artery embolization with polyvinyl alcohol particles, with hormonal, sonographic, and hysteroscopic follow-up procedures. MAIN OUTCOME MEASURE(S) Serum follicle-stimulating hormone (FSH) and estradiol levels were measured, and sonographic appearance of the ovaries and the endometrium at baseline and 1, 3, 6, and 12 months after treatment were recorded. Hysteroscopy was performed with endometrial biopsy at baseline and 6 months after embolization. RESULT(S) The patient remained amenorrheic from the procedure. Serial posttreatment measurements of FSH and estradiol levels and repeated ovarian imaging showed no change in ovarian function as compared with baseline. A reduction in endometrial thickness (<or=5 mm), as compared with the endometrial thickness measured at baseline (7.2 mm), was sonographically documented 1, 3, 6, and 12 months after treatment. Postprocedure hysteroscopy showed an atrophic endometrium, and endometrial biopsy confirmed endometrial atrophy. CONCLUSION(S) Permanent amenorrhea associated with endometrial atrophy may occur following uterine artery embolization for fibroids and, to the best of our knowledge, this is the first time this complication has been reported. Patients should be appropriately counseled about the risk of reduced fertility after embolization.

Long-term effects of uterine fibroid embolization on ovarian reserve: a prospective cohort study.

OBJECTIVE To determine whether uterine fibroid embolization may advance ovarian follicular depletion in reproductive-aged women with apparently normal baseline ovarian function. DESIGN Prospective cohort study. SETTING University tertiary care center. PARTICIPANT(S) Thirty-six patients aged 26 to 39 years with fibroids, regular menstrual cycles, and day 3 serum FSH levels<10 mIU/mL and 36 matched control women. INTERVENTION(S) Day 3 serum FSH and E2 levels and ultrasound-based antral follicle count and ovarian volume were determined before (baseline) and at 12, 24, 36, 48, and 60 months after embolization and compared with those of the control group. Menstrual status was determined annually on the basis of prospectively recorded menstrual calendars. MAIN OUTCOME MEASURE(S) Longitudinal changes in hormone levels, ultrasound measures, and bleeding patterns. RESULT(S) Although the FSH and E2 levels increased significantly and the antral follicle count and ovarian volume values declined significantly over time within the groups, no significant differences were found between the groups. The cycle remained regular in all but two women (one in the embolization group and one in the control group), who started having cycle irregularity after 24 months and 36 months follow-up, respectively. CONCLUSION(S) This long-term follow-up study suggests that fibroid embolization does not lead to an accelerated decline in ovarian reserve in younger patients.

Polarisation of Tumor-Associated Macrophages toward M2 Phenotype Correlates with Poor Response to Chemoradiation and Reduced Survival in Patients with Locally Advanced Cervical Cancer.

Objective we investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with chemoradiation (CT/RT). Methods 84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2) was finally calculated. Results At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001). Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor) to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029). At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037) emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019), and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037) survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis. Conclusions polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC.

Ovarian vein incompetence: a potential cause of chronic pelvic pain in women

OBJECTIVE(S) To evaluate whether ovarian vein incompetence may be a source of chronic pelvic pain (CPP) in women. STUDY DESIGN Twenty-two women, aged 19-50 years, with chronic pelvic pain, no laparoscopically detected pelvic pathology, and evidence of reflux in dilated pelvic veins on transvaginal color Doppler ultrasound underwent retrograde ovarian venography and sclerotherapy of the ovarian vein(s) if incompetent. The primary outcome was symptom change as assessed by a symptom questionnaire and visual analog pain scales (VAS) at 3, 6, and 12 months of follow-up. Changes in pelvic circulations after sclerotherapy procedure were also evaluated by serial ultrasound examinations. Differences between baseline and post-procedural VAS scores were analysed using the Wilcoxon signed-rank test. RESULTS Twenty (91%) of the 22 women had venographic evidence of incompetent ovarian vein(s) and received sclerotherapy. There were no immediate or late complications. Variable symptom relief was observed in 17 (85%) of the 20 treated women, with follow-up at 12 months showing marked-to-complete relief in 15 patients and mild-to-moderate relief in the remaining 2 patients. Three (15%) women had no improvement in symptoms. Median VAS scores at 3 (2.0), 6 (2.5), and 12 months (3.0) were significantly lower than at baseline (8.0) (P<.001). Follow-up ultrasound examinations showed absence of pelvic venous reflux in all but 3 patients, in whom recurrence of reflux was seen at 3 months. CONCLUSION(S) Ovarian vein sclerotherapy provided symptomatic relief and improved pelvic circulation in most patients. These findings suggest that ovarian vein incompetence was the likely source of chronic pain in these women, and that sclerotherapy was a safe and effective treatment for this condition. CONDENSATION Ovarian vein incompetence leading to pelvic circulatory changes may be a cause of chronic pelvic pain in women.

Incidence and risk factors for clinical failure of uterine leiomyoma embolization.

OBJECTIVE: To estimate the incidence of clinical failure after uterine leiomyoma embolization and identify possible risk factors. METHODS: One hundred seventy-six consecutive women undergoing uterine leiomyoma embolization were followed prospectively for a median of 48 months (range 12–84 months) to estimate the occurrence of clinical failure, defined as persistence or recurrence of leiomyoma symptoms, and any subsequent invasive treatment. Cumulative failure and reintervention rates were estimated by survival analysis and log-rank tests according to baseline patient characteristics. Multivariable Cox proportional hazards analysis was performed to adjust for confounders. RESULTS: Overall, there were 18 failures at a median of 36 months (range 3–84 months). The cumulative failure rate increased steadily over time, 3% at 1 year, 7% at 3 years, 14% at 5 years, and 18% at 7 years. Of the 18 failures, 11 had reintervention, including six hysterectomies, four myomectomies, and one repeat uterine leiomyoma embolization, at a median of 56 months (range 15–84 months). The cumulative reintervention rate was 0 at 1 year, 3% at 3 years, 7% at 5 years, and 15% at 7 years. Women aged 40 years or younger had a higher failure risk (hazard ratio [HR] 5.89, 95% confidence interval [CI] 2.50–20.02, P=.023) compared with older women. A history of previous myomectomy was also associated with an increased failure risk (HR 3.79, 95% CI 2.07–13.23, P=.037). CONCLUSION: The 7-year cumulative rates of clinical failure and reintervention after uterine leiomyoma embolization were 18% (95% CI 8.2–27.8) and 15% (95% CI 5.2–24.8), respectively. The failure risk was higher for younger patients and for those with a prior myomectomy. LEVEL OF EVIDENCE: III

Selective arterial embolization as a first-line treatment for postpartum hematomas.

BACKGROUND: Postpartum hematomas are a potentially serious obstetric complication for which management options are not standardized. We report successful treatment of a large postpartum hematoma using arterial embolization as primary approach. CASE: A 29-year-old woman at term gestation underwent vacuum-assisted vaginal delivery. Two hours later, marked rectal pain developed. Examination revealed a large left vaginal hematoma and no obvious bleeding sites. Computed tomography demonstrated a 10-cm supralevator hematoma and extrauterine arterial bleeding. Angiography revealed contrast extravasation from a branch of the left internal pudendal artery. Selective embolization of this branch stopped the bleeding. The patient was discharged on the third postpartum day. Eight weeks after delivery, there was no evidence of the hematoma. CONCLUSION: Arterial embolization can be used as a first-line treatment for large postpartum hematomas.

Effects of ovary suppression by a long-acting GnRH-agonist on circulating GH, insulin-like growth factor I and insulin levels in women with polycystic ovary syndrome

Our aim was to investigate the effect of GnRH-agonist (GnRH-a) induced suppression of plasma sex steroids on serum GH, insulin like growth factor-l (IGF-I) and insulin levels after an oral glucose load (OGTT) in women with polycystic ovary syndrome (PCOS). Serum insulin, GH and IGF-I levels during a 75-g 4-h OGTT were measured in 3 nonobese and 7 obese hyperandrogenic women with PCOS and normal glucose tolerance before and after 10 weeks of treatment with the GnRH-a triptorelin (3, 75 mg im every 28 days). Basal estrogen and androgen levels were also measured at time 0 of the first and the second OGTT. After the therapy serum estrogens and androgens were significantly suppressed. Body weight remained unchanged. Basal GH significantly increased after the treatment while fasting IGF-I and insulin levels decreased from (mean±SE) 349.3±31.8 to 278.7±33.2 ng/mL and from 22.4±4.1 to 18.8±4.4 µU/mL, respectively. The insulin response to OGTT (area under curve) was also reduced (from 16017±2598 to 11736±2317 µU/mL/240 min). Our results suggest that the GnRH-a induced suppression of ovary secretion may modify the serum GH and IGF-I levels and the insulin response to an OGTT in women with PCOS.

Gonadotropin levels in women with polycystic ovary syndrome: Their relationship to body weight and insulin levels

The purpose of this work was to investigate the relationship of gonadotropin levels to body weight and insulin levels in women with polycystic ovary syndrome (PCOS). Specifically, we wished to test the hypothesis that circulating luteinizing hormone (LH) and insulin levels are different in obese and normal weight patients with PCOS. The basal plasma levels of gonadotropins, estrogens, androgens and sex hormone-binding globulin, the gonadotropin responses to gonadotropin releasing hormone (GnRH) and the insulin and C-peptide responses to a 3-hour oral glucose tolerance test (OGTT) were measured in 19 obese and 19 normal weight patients with PCOS and 7 obese and 8 normal weight ovulatory controls. Data of the patients were evaluated according to body weight (obese vs normal weight) and basal LH (high vs normal). There was no significant difference in basal LH and androgen levels and in the insulin response to oral glucose between obese and normal weight patients with PCOS. Compared to the weight matched controls, both obese and non obese patients showed significantly higher LH responses to GnRH and C-peptide responses to OGTT. When the high LH patients (no=18) were compared those with normal LH (no=20), the high LH subjects exhibited significantly higher androstenedione levels. Both obese (no=10) and normal weight (no=8) patients with high LH showed significantly greater C-peptide responses to OGTT than obese (no=9) and non obese (no=11) patients with normal LH. However, as compared with the weight matched controls, both the high LH and normal LH patients had significantly greater C-peptide responses to OGTT. We conclude that obese and non obese patients with PCOS do not seem to differ in the prevalence of elevated LH levels or in the LH secretory pattern. Insulin resistance, expressed by an enhanced pancreatic sensitivity to oral glucose, is present in both the high LH and the normal LH subjects, even though the PCOS patients with elevated LH tend to be more insulin resistant and hyperandrogenic than the normal LH patients.

The timing of natural menopause after uterine fibroid embolization: a prospective cohort study

OBJECTIVE To determine whether uterine fibroid embolization before the age of 45 years advances the timing of natural menopause. DESIGN Prospective cohort study. SETTING University tertiary-care center. PARTICIPANT(S) Forty-three regularly cycling women aged 35-44 years who underwent embolization and 43 age-matched control subjects. INTERVENTION(S) Annual assessments of menopausal status using prospectively recorded menstrual diaries and hormonal (serum FSH and E(2)) and ultrasound measures (ovarian volume and antral follicle count). Women were followed for 7 years or until they reached menopause. MAIN OUTCOME MEASURE(S) Age at menopause as computed by subtracting the date of birth from the exact date of the last menstrual period. RESULT(S) Over the study period, 9 patients (25%) and 12 control subjects (33%) became menopausal, 19 patients (53%) and 18 control subjects (50%) entered the menopausal transition (irregular cycles), and 8 patients (22%) and 6 control subjects (17%) continued to menstruate regularly. Mean menopausal age in the embolization group (48.94 ± 2.48 years) was not significantly different from that in the control group (49.52 ± 1.25 years). There was no significant difference of menopause occurrence between the groups. Longitudinal changes in hormonal and ultrasound measures were similar for the two groups. CONCLUSION(S) This long-term follow-up study found no evidence for fibroid embolization advancing the timing of menopause in women before the age of 45 years.