Outcomes of Bleomycin-based electrochemotherapy in patients with repeated loco-regional recurrences of vulvar cancer.

Objective To evaluate the safety, local tumor efficacy and relief of symptoms of electrochemotherapy (ECT) treatment in patients affected by recurrence of vulvar cancer (VC), unsuitable for standard treatments. Methods Ten patients were recruited with histological diagnosis of recurrence of VC. Intravenous bleomycin was injected, after an accurate mapping of all lesions and ECT was performed. Response to therapy was evaluated and quality of life (QoL) was evaluated via questionnaires. Results Diagnosis stage of primary tumors, according to the FIGO system, was: four patients respectively at stage IB (40%), and at stage II (40%), one patient at stage IIIA (10%), one patient with Paget cancer (10%). Mean age was 76 years (SD ± 7) at time of enrollment. Eight patients (80%) were previously submitted to surgery and/or radio-chemotherapy. Mean treatment time was 20 (range 10-20) min. After a median follow-up of 12 (3-22) months, six patients (60%) were alive. Conclusions Objective responses (ORs) with local control of the tumor were obtained in 80%. After a mean follow-up of 12 (3-22) months six patients (60%) were alive. The favorable outcome of this study, indicates that ECT is a reliable treatment option that may improve their functioning, thus enhancing the care provided in the palliative setting.

Vitamin D Supplementation for Premenstrual Syndrome-Related Mood Disorders in Adolescents with Severe Hypovitaminosis D.

STUDY OBJECTIVE: Premenstrual syndrome (PMS) might become severe enough to interfere with normal interpersonal relationships. This study was planned to assess whether administration of vitamin D (200,000 IU at first, followed by 25,000 IU every 2 weeks) for a 4-month period might lessen the appearance and the intensity of mood disorders associated with PMS in young girls with severe hypovitaminosis D. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: One hundred fifty-eight young girls (15-21 years old) with PMS-related severe symptoms of the emotional and cognitive domains and low serum 25-hydroxycholecalciferol (25-OH-D) levels (≤10 ng/mL) were randomly assigned to two treatment groups and treated for 4 months with vitamin D (group 1; n = 80) or placebo (group 2; n = 78). Clinical and hormonal effects were compared between the two groups. RESULTS: In patients from group 1, levels of vitamin D reached the normal range (35-60 ng/mL) after the first month and remained stable throughout the whole study. At the end of treatment, anxiety score decreased from 51 to 20 (P < .001 vs baseline); irritability score declined from 130 to 70 (P < .001 vs baseline). Crying easily and sadness decreased by a score of 41 and 51 to a score of 30 and 31, respectively (P < .001). For disturbed relationships, the score decreased from 150 to 70 (P < .001). Conversely, no appreciable changes were noted in symptom intensity from patients of group 2. The frequency of adverse events (nausea and constipation) was not different between participants of group 1 and group 2. CONCLUSION: On the basis of the present findings, vitamin D therapy can be proposed as a safe, effective, and convenient method for improving the quality of life in young women with severe hypovitaminosis D and concomitant mood disorders associated with PMS.

Males with low serum levels of vitamin D have lower pregnancy rates when ovulation induction and timed intercourse are used as a treatment for infertile couples: results from a pilot study.

BACKGROUND: Vitamin D (Vit D) is important for the regulation of reproductive physiology. In humans, maternal Vit D deficiency has been implicated in several reproductive- and pregnancy-related disorders. Very few data are available regarding the Vit D status in male partners of couples attempting pregnancy. This observational study (IRB Prot. N. 078/13) aimed to evaluate whether low Vit D serum levels in males might decrease the rate of successful conception in couples attempting pregnancy. METHODS: Male and female partners of infertile couples (n = 102) were classified into 2 GROUPS according to normal (≥30 ng/ml) or low (below 30 ng/ml) serum Vit D levels in male partners. Semen analysis was performed in each male participant based on the WHO reference criteria. The female partners of both groups were subjected to 3 consecutive cycles of gonadotropin-induced mono-ovulation. The main outcome measures included the clinical pregnancy rate, delivery per patient and per cycle, and miscarriage rate between the 2 groups evaluated at the end of the three-month period of the study. RESULTS: In male partners of both groups, standard semen analysis did not highlight substantial differences in sperm concentration, sperm progressive motility, or typical form. The pregnancy rates per patient and per cycle and delivery rates per patient and per cycle were all significantly higher (p< 0.05) in couples with normal Vit D levels. CONCLUSIONS: These results suggest the existence of a relationship between male Vit D serum levels and semen ability to begin a pregnancy during cycles of timed vaginal intercourse.

Conservative Treatment of Ewing's Sarcoma of the Uterus in Young Women.

Ewing sarcoma-primitive neuroectodermal tumors (ES/PNETs) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiations. ES/PNET of the uterus is rare. There are 48 cases of ES/PNET of the uterus published in the literature as far as we know. We describe a case of Ewing sarcoma of the uterus occurring in a 17-year-old woman presenting with a two-month history of pelvic pain. After surgical excision and microscopic, immunohistochemical, and electron microscopy examination, the diagnosis of Ewing sarcoma of the uterus was suggested. This report will discuss the diagnosis and surgical and clinical management of Ewing uterine sarcoma in young women, according to the available literature. In spite of the rarity of ES/PNETs, they should be taken into account in the differential diagnosis of uterine neoplasms in young women.

Dehydroepiandrosterone decreases the age-related decline of the in vitro fertilization outcome in women younger than 40 years old.

BACKGROUND: With infertility populations rapidly aging, treatments improving pregnancy chances assume increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy rates and lower miscarriage rates in women with diminished ovarian function. This study was planned to evaluate whether pretreatment with DHEA may improve in vitro fertilization (IVF) parameters and pregnancy outcomes in infertile women with advanced reproductive age and normal ovarian reserve. METHODS: In this double-blind, randomized, placebo-controlled study, 109 infertile patients aging 36-40 years old were selected to undergo the long protocol IVF. Eight weeks before starting the IVF cycle and during treatment, patients in Group 1 received 75 mg of DHEA once a day; patients in control group (Group 2) received placebo. The primary endpoint of the study was number of clinical pregnancy, live birth and miscarriage rates; secondary endpoint was modification of standard IVF parameters, including stimulation duration (days of rhFSH administration), E2 on HCG-day, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, number of transferred embryos and score of leading embryos transferred. RESULTS: Patients in the DHEA group had a significantly higher live birth rate compared with controls (P<0.05). Conversely, miscarriage rate was higher for patients in the control group (P<0.05). CONCLUSIONS: DHEA supplementation may significantly improve IVF outcomes in infertile women with advanced reproductive age and normal ovarian reserve.

Intermittent low-dose finasteride administration is effective for treatment of hirsutism in adolescent girls: a pilot study.

STUDY OBJECTIVE: Hirsutism has negative impact on adolescent psychosocial development for both cosmetic and endocrine reasons. This study evaluated the effectiveness of a new intermittent, low-dose finasteride regimen consisting of 2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal) for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or idiopathic hirsutism (IH). DESIGN AND PARTICIPANTS: Twenty-eight girls (15-19 y old) with hirsutism were randomly assigned to 2 treatment groups and treated for 6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride; fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score (HS), clinical, and hormonal effects were compared between the 2 groups. RESULTS: In patients treated with finasteride, the HS value at 6 months was 52.9% lower than that observed at baseline in girls with IH, and 52.8% lower in girls with PCOS (P < .0001 for both). Similarly, the 3α-17 ß-androstenediol glucuronide serum levels were decreased by 34.8% in patients with IH, and by 47.5% in patients with PCOS (P < .0001, respectively). Finasteride treatment was well tolerated and did not alter values of BMI, serum levels of sexual hormones, metabolic parameters related to liver and kidney function as well as glycemic and lipidic asset. CONCLUSIONS: A low-dose of finasteride, given every 3 days, reduces the HS in young patients affected by PCOS or IH. Compared with conventional continuous finasteride administration, the intermittent low-dose regimen has similar efficacy with the advantage to be safer and less expensive.

Isobaric laparoscopy using LaparoTenser system in surgical gynecologic oncology.

In this prospective analysis, the feasibility and outcome of isobaric laparoscopy in gynecologic oncology was evaluated. Total laparoscopic radical hysterectomy type A and B, with or without pelvic lymphadenectomy, according to the Querleu-Morrow classification was performed in 22 consecutive patients. Seven patients had early cervical cancer (adenocarcinoma stage 1B1 in 1, and squamous carcinoma stage 1B1 in 4, stage 1A2 in 1, and stage 1B2 in 1), and 15 patients had endometrial cancer (stage IA in 4, stage IB in 9, and stage IIIA in 2). Radical hysterectomy was performed using the LaparoTenser, a subcutaneous wall-lifting device. Visual analog score, duration of surgery, blood loss, complications, and postoperative course were recorded. Pathologic analysis confirmed the adequacy of the surgical specimens in type B radical hysterectomies and the number of lymph nodes removed. Low-pressure CO2 insufflation was us to improve field exposure in patients with high body mass index. Postoperatively, no patient reported substantial abdominal discomfort caused by lifting of the abdominal wall. Operative time, blood loss, and hospital stay were consistent with published data for CO2 laparoscopy. One complication related to insertion of the subcutaneous needle of the wall lifter occurred. We conclude that total laparoscopic radical hysterectomy can be successfully completed via isobaric laparoscopy using the LaparoTenser device in patients with early cervical and endometrial cancer. Gasless laparoscopy has become the first choice in our department to overcome the detrimental effects of pneumoperitoneum and represents a logical advance in the evolution of minimally invasive surgery. The LaparoTenser device is being used to perform increasingly complex procedures in high-risk patients and situations.

Possible direct influence of complement 3 in decreasing insulin sensitvity in a cohort of overweight and obese subjects.

UNLABELLED: A group of 608 apparently healthy patients, 136 men and 472 women, either overweight or obese, aged 18-69 years, were examined. BMI, waist circumference, fasting blood glucose (FBG), insulin, and complement 3 (C3) serum levels were measured; the homeostasis model assessment (HOMAIR) was used to evaluate insulin resistance; and physical activity was quantified by a questionnaire. RESULTS: HOMAIR showed a positive correlation with BMI (r: 0.478, p < 0.001), waist circumference (r: 0.487, p < 0.001), and C3 (r: 0.445, p < 0.001). Moreover, it was significantly associated with gender (F Fisher = 22.12, p < 0.001), and the mean HOMAIR levels were significantly different among the three groups of physical activity, with the lowest level of insulin resistance at the highest level of physical activity (F=7,31, p < 0.001). A multiple regression analysis was carried out with HOMAIR as the dependent variable and gender, age, BMI, waist circumference, C3 and the level of physical activity as independent variables (fitted model: F = 41.24, P<0.001, R2 = 0.328). HOMAIR maintained an independent association with C3 (ß = 0.678, P<0.001), sex (ß = 0.189, P<0.001), BMI (ß = 0.637, P<0.01), and age (ß = -0.004, P<0.05). CONCLUSIONS: This study of a cohort of overweight and obese subjects has shown that insulin resistance (dependent variable) is positively associated with C3 serum levels, independently of age, gender, anthropometric parameters and physical activity, suggesting that higher C3 serum levels may directly increase insulin resistance in obesity.

Cornual pregnancy after surgical treatment of an incarcerated fallopian tube: a case report.

BACKGROUND: Incarceration of the fallopian tube is a rare condition. Symptoms are often misleading, making proper diagnosis difficult because of nonspecific clinical presentations. We report a case of cornual pregnancy occurring 7 months after the treatment of an incarcerated fallopian tube. We believe that the abnormal cornual implantation of the gestational sac was due to myometrial reconstruction of the uterine wall. CASE: A primigravid woman treated for the incarceration of a fallopian tube was subsequently found to have a cornual pregnancy in a septate uterus. The cornual pregnancy was successfully aborted after laparoscopic myometrial reconstruction, and a metroplasty allowed a subsequent pregnancy. CONCLUSION: This hazardous type of ectopic pregnancy can be managed with systemic administration of methotrexate. If the cornual pregnancy is correctly identified at an early stage, this medical management can be attempted and offers the potential advantage of avoiding surgery and increasing the likelihood of preserving fertility.

Pregnancy in a woman with premature ovarian insufficiency undergoing intracytoplasmic sperm injection after pretreatment with estrogens followed by therapy with estrogens associated with ovarian stimulation with gonadotropins: remarks about oocyte and embryo quality.

OBJECTIVE: The aim of this study was to achieve pregnancy in a woman with premature ovarian insufficiency (POI) by means of estrogen pretreatment, a combination of estrogen therapy and gonadotropin ovarian stimulation, and intracytoplasmic sperm injection (ICSI). METHODS: A 34-year-old woman with POI who failed to achieve follicular growth in two previous ovarian stimulation protocols using high doses of gonadotropins alone underwent an ICSI trial after estrogen pretreatment (ethinyl estradiol 0.05 mg three times a day for 10 d) followed by estrogens (at the same dose) and recombinant ß-follicle-stimulating hormone (250 IU/d for 12 d). RESULTS: Delivery of a healthy female baby was achieved. CONCLUSIONS: Stimulation with gonadotropins plus estrogens after pretreatment with estrogen can be considered a useful intervention in women with POI trying to conceive.

Intussusception and incarceration of a fallopian tube: report of 2 atypical cases, with differential considerations, clinical evaluation, and current management strategies.

Herein are presented 2 cases from the last 5 years. In case 1, a fallopian tube intussusception without perforation, misdiagnosed as a myoma, was observed at hysteroscopy of the uterine cavity 18 months after last vacuum aspiration. In case 2, a fallopian tube incarceration, misdiagnosed as a placental polyp, was observed 3 months after last suction curettage. Although uterine perforation caused by suction curettage after abortion or of afterbirth occurs rarely, it is a complication that must be taken into account because after this procedure there may be painful symptoms such as the typical triad of abdominal pain, vaginal discharge, and dyspareunia. In some situations, as in case 2, amenorrhea occurs alone, without other distressing symptoms. In both cases, a hysteroscopic approach was used; laparoscopy was necessary only in case 2.

Predictive value of ovarian stroma measurement for cardiovascular risk in polycyctic ovary syndrome: a case control study.

BACKGROUND: To verify the feasibility of ovarian stromal evaluation and correlate ovarian parameteres (echogenicity and volume) with hyperandrogenism, and both cardiovascular and metabolic risk factors in PCOS. METHODS: Twenty four young PCOS patients and twelve age-matched control women were enrolled. Diagnosis of PCOS was based on the Rotterdam criteria. Ultrasound ovarian study included ovarian volume, stromal volume, stromal area and stromal area/total ovarian area ratio (S/A). Concerning hormones, insulin, LH, FSH, estradiol, androstenedione, testosterone, DHEAS, 17-hydroxy-progesterone, and SHBG were measured during the early follicular phase (days 2-5). Cardiovascular risk factors were represented by fasting plasma levels of glucose, lipids (total and HDL-cholesterol), plasminogen activator inhibitor 1 (PAI-1), von-Willebrand factor (vWF), and adiponectin. Carotid intima-media thickness (C-IMT) was measured as a parameter of cardiovascular risk. RESULTS: A positive correlation between the S/A ratio and plasma levels of testosterone (p < 0.05) and androstenedione (p < 0.05) was found. The stromal volume, stromal area and S/A ratio were also significantly and positively correlated with PAI-1, and vWF levels, and with IMT in PCOS women (P < 0.05). CONCLUSIONS: This study shows that the ultrasound measurement of ovarian stroma is a predicting factor of hyperandrogenism degree, prothrombotic factors and cardiovascular risk in patients with PCOS.

Effect of finasteride on ovulation induction in nonresponder (hyperandrogenic) polycystic ovary syndrome (PCOS) women.

OBJECTIVE: To evaluate whether the addition of finasteride (a 5-reductase inhibitor) to conventional protocol of ovarian stimulation with gonadotropin can improve ovarian follicular growth in polycystic ovary syndrome (PCOS) women who did not respond to previous stimulation with gonadotropin alone. DESIGN: Double-blind randomized study. SETTING: Outpatient in an academic research environment. PATIENT(S): Thirty-six PCOS patients in whom the previous multifollicular stimulation protocols with gonadotropin failed. INTERVENTION(S): The patients were randomly assigned to two treatment groups: group 1 underwent ovarian stimulation with recombinant FSH (rFSH) plus finasteride, and group 2 received rFSH alone. When the dominant follicle reached a mean diameter of 18 mm, hCG was administered and finasteride withdrawn. MAIN OUTCOME MEASURE(S): Ovulation rate in women with PCOS. RESULT(S): Follicular growth and ovulation occurred in eight patients in group 1, whereas no cases were detected in group 2. CONCLUSION(S): This study confirms that hyperandrogenism interferes with follicular growth and suggests that administration of finasteride during ovarian stimulation with rFSH improves ovulation rate in selected hyperandrogenic anovulatory women.

Effects of pretreatment with estrogens on ovarian stimulation with gonadotropins in women with premature ovarian failure: a randomized, placebo-controlled trial.

OBJECTIVE: To evaluate the hypothesis that pretreatment with estrogens in women affected by premature ovarian failure (POF) may improve the results of ovarian stimulation. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: Outpatient department in an academic research environment. PATIENT(S): Fifty women with POF seeking pregnancy. INTERVENTION(S): Before starting ovarian stimulation, group 1 received 0.05 mg ethinyl-E(2) (EE) three times a day for 2 weeks, while group 2 received placebo. Ovarian stimulation was carried out with recombinant FSH (r-betaFSH), 200 IU/day/SC. Both EE and placebo were administered during ovarian stimulation. Human chorionic gonadotropin (10,000 IU/IM) was added when the follicle exceeded a mean diameter of 18 mm. MAIN OUTCOME MEASURE: Rate of ovulation in women with POF. RESULT(S): Levels of FSH before stimulation were significantly lower in group 1 than in group 2. The rate of ovulation in group 1 (8/25; 32%) was significantly higher than in group 2 (0/25; 0%). Notably, induction of ovulation was successful only in patients whose FSH levels after EE treatment were < or =15 mIU/mL. CONCLUSION(S): Our data suggest that pretreatment with EE improves the success of rate of ovulation induction with exogenous gonadotropins in patients with POF. A threshold of FSH < or =15 mIU/mL should be achieved before starting ovarian stimulation.

Inhibitory effect of obesity on gonadotropin, estradiol, and inhibin B levels in fertile women.

OBJECTIVE: To examine whether obesity and insulin resistance have an independent effect on the gonadotropin, estradiol, and inhibin B serum levels and follicle count in the early follicular phase of fertile women with a wide range of BMI and without signs of hyperandrogenism. RESEARCH METHODS AND PROCEDURES: Twenty-two overweight and obese (BMI > or =25.0 kg/m(2)) women and 10 normal-weight (BMI <25.0 kg/m(2)) women, all having apparently normal fertility, were studied. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, inhibin B, and insulin, level of insulin resistance (estimated by homeostasis model assessment for insulin resistance), and follicle count were measured during the early follicular phase (Days 2 to 5 of the menstrual cycle). RESULTS: Overweight women showed lower FSH (p < 0.001), LH (p < 0.001), and inhibin B (p < 0.05) levels compared with normal-weight women, whereas estradiol concentrations and follicle count were not significantly different between the two groups. When normal-weight and overweight women were examined as a group and multiple regression analyses were performed, estradiol showed a negative association with BMI (or waist circumference) (p < 0.05) and a positive correlation with LH (p < 0.05) and FSH (p < 0.05); inhibin B maintained a positive association only with estradiol (p < 0.05); and FSH and LH showed a negative correlation with BMI (or waist circumference) (p < 0.001 and p < 0.01, respectively). DISCUSSION: Overweight and obese fertile women have lower FSH, LH, inhibin B, and estradiol levels in the early follicular phase, with a possible direct inhibitory effect of body mass on gonadotropin and estradiol production, independently of age, insulin (concentrations and sensitivity), and other hormones. By contrast, the number of ovary follicles does not seem to be influenced by insulin and body mass in these patients.

Detection of chronic endometritis at fluid hysteroscopy.

STUDY OBJECTIVE: Chronic endometritis is a subtle condition that is difficult to detect; however, it may cause abnormal uterine bleeding and infertility. Few data exist about the appearance of chronic endometritis at fluid hysteroscopy and about the value of diagnostic fluid hysteroscopy in the detection of this condition. In our experience, at fluid hysteroscopy chronic endometritis is characterized by consistent association of stromal edema and either focal or diffuse hyperemia; in some cases, this finding is associated with endometrial micropolyps (less than 1 mm in size). This study attempted to describe diagnostic criteria for chronic endometritis at fluid hysteroscopy and assess the diagnostic accuracy of fluid hysteroscopy in the detection of this condition. DESIGN: Retrospective Study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Nine hundred-ten women in whom hysteroscopy was indicated. INTERVENTIONS: Fluid hysteroscopy followed by endometrial biopsy. MEASUREMENTS AND MAIN RESULTS: Sensitivity, specificity, positive and negative predictive values, and accuracy of fluid hysteroscopy in the detection of chronic endometritis, based on the association of edema; hyperemia; and, if present, micropolyps were calculated. Based on the presence of hyperemia and edema, chronic endometritis was diagnosed in 158 patients (17.4%); in 61 patients (6.7%), micropolyps also were present. Histology confirmed the diagnosis in 101 patients (63.9% of positive cases at hysteroscopy) and was positive in 9 additional cases not detected by hysteroscopy. Chronic endometritis at histology was found in approximately 30% of infertile women and 35% of cases related to abnormal uterine bleeding. The sensitivity, specificity, and positive and negative predictive values of hysteroscopy for chronic endometritis based on detection of only hyperemia and edema were 91.8%, 92.9%, 63.9%, and 98.8%, respectively; the diagnostic accuracy was 92.7 %. The combination of hyperemia, edema, and micropolyps had sensitivity, specificity, and positive and negative predictive values of 55.4%, 99.9%, 98.4%, 94.5%, respectively, with a diagnostic accuracy of 93.4%. CONCLUSIONS: Fluid hysteroscopy is very reliable in diagnosing no inflammation, while detection of micropolyps is a very reliable sign of inflammation. When performing hysteroscopy for abnormal uterine bleeding or infertility, signs of chronic endometritis should always be sought.

Endometrial micropolyps at fluid hysteroscopy suggest the existence of chronic endometritis.

BACKGROUND: At fluid hysteroscopy the presence of endometrial micropolyps (less than 1 mm of size) is a frequent finding. Although their origin is still unknown, in our experience they are associated with stromal edema, endometrial thickening and periglandular hyperhaemia that suggest the existence of chronic endometritis. This study will aim to describe these lesions and evaluate their inflammatory significance by comparing hysteroscopic and histological findings. METHODS: 820 women underwent hysteroscopy and endometrial biopsy. Sensitivity, specificity, positive and negative predictive values and accuracy of the micropolyps presence for the diagnosis of chronic endometritis were calculated. RESULTS: Micropolyps were found in 96 cases (11.7% of all hysteroscopies); in 90 (93.7%) of these cases histology confirmed the presence of chronic endometritis. In women without micropolyps, chronic endometritis was significantly less frequent (78 cases, 10.8%) (P < 0.000001). The likelihood of chronic endometritis for women with micropolyps was very high (odds ratio 124.2, confidence interval 50.3-205.4). The sensitivity, specificity, positive and negative predictive values were 54%, 99%, 94% and 89%, respectively; the diagnostic accuracy was 90%. CONCLUSIONS: The presence of endometrial micropolyps at fluid hysteroscopy is significantly associated with endometrial inflammation and can be considered a reliable diagnostic sign for this pathology.