Evidence for a stimulatory role of high doses of recombinant human follicle-stimulating hormone in the treatment of male-factor infertility.

The efficacy of recombinant human follicle-stimulating hormone (rhFSH) in the treatment of normogonadotropic patients with male-factor infertility was assessed. Forty-five infertile men with moderate/severe oligoasthenozoospermia and normal FSH, luteinizing hormone (LH) and testosterone (T) levels were treated with high rhFSH dose (300 IU) on alternate days for ≥4 months. In all, the seminal parameters, endocrine profile (FSH, LH, prolactin (PRL), total and free T and estradiol) and pregnancy rate were evaluated before, during and after rhFSH treatment. Fifteen infertile men were treated with placebo and studied in the same way, as control group. rhFSH treatment induced a marked increase in sperm count and no change in sperm motility, morphology and viability. No changes in seminal parameters were observed in the placebo group. FSH levels increased during treatment with rhFSH and not with placebo. No variations in LH, PRL, free and total T and estradiol were evidenced during treatment. A significant pregnancy rate in rhFSH versus placebo patients was also highlighted. Prolonged treatment with high rhFSH doses leads to increase sperm count and improve the spontaneous pregnancy rate in normogonadotropic infertile patients with oligoasthenozoospermia. rhFSH may represent a rational and useful tool in the treatment of male-factor infertility.

Effects of long-term high dose testosterone administration on vaginal epithelium structure and estrogen receptor-α and -ß expression of young women.

To date, the effects of long-term testosterone (T) administration on the human vagina are not completely understood. Thus, the aim of this study was to investigate the effects of long-term T treatment on vaginal tissue histology, estrogen receptor alpha (ERα) and beta (ERß) expression and proliferation in female to male transsexual subjects (FtM). We compared vaginal samples from FtM subjects with those of premenopausal women (PrM) and postmenopausal women (M) not receiving any hormonal treatment for at least 2 years. Vaginal tissue samples from 16 FtM subjects treated with T (intramuscular injections of 100 mg Testoviron Depot/7-10 days for at least 1 year), undergoing sex reassignment surgery, and 16 PrM and 16 M subjects undergoing a vaginal hysterectomy for prolapse, were collected. For each sample, morphology, glycogen content, proliferation (ki-67), ERα and ERß expression were evaluated. Vaginal samples from FtM showed a loss of normal architecture of the epithelium, intermediate and superficial layers were completely lost, and glycogen content was depleted. T administration resulted in a strong proliferation reduction when compared with both M and PrM subjects. Stromal and epithelial ERα as well as ERß were significantly decreased in FtM when compared with PrM subjects. In conclusion, our data suggests that systemic T administration at supraphysiological dosage, determines profound changes in histomorphology and reduces ERs expression and proliferation of vaginal epithelium.

Androgen receptor expression in the human vagina under different physiological and treatment conditions.

Recent data report an important role of testosterone (T) in modulating female sexual responses, but little is known about the expression and distribution of androgen receptor (AR) in the human vagina. Therefore, the aims of our study were to evaluate the expression of AR in the human vagina in premenopausal (PrM) and menopausal (M) women and in T-treated women. Vaginal biopsies were obtained from PrM and postmenopausal women and from women with gender identity disorder (female to male (FtM)) receiving exogenous T. AR gene and protein expression levels in vaginal tissues were determined by real-time PCR and western blot analysis, respectively, whereas the localization of AR in vaginal mucosa and stroma was performed by immunohistochemistry. ARs were detected by immunostaining both in the mucosa and stroma. In vaginal mucosa, AR density score decreases with age but does not change with T administration. In stromal tissue, AR density score does not change with age but significantly increases with T administration (P<0.01). AR protein expression was significantly increased in FtM subjects (P<0.001). The expression of AR messenger RNA (mRNA) evaluated by Real-time PCR showed a significantly higher mRNA expression in FtM versus M patients (P<0.01) and in PrM versus M subjects (P<0.05). In conclusion, we found AR protein and mRNA expression both in the epithelium and stroma of the human vagina in all groups of women. A negative correlation exists between age and AR expression in the vaginal mucosa. T administration increases AR expression in both the mucosa and stroma.

Cryopreservation of ovarian tissue in pediatric patients.

Cancer treatments improve the survival rate of children and adolescents; however chemo- and radiotherapy result in gonadal damage leading to acute ovarian failure and sterility. Ovarian tissue cryopreservation allows long-term storage of primordial follicles and represents the only possibility of preserving the potential fertility in prepubertal girls. The aim of the present study is to describe our experience in ovarian tissue cryopreservation in 45 pediatric patients. The number of follicles per square millimeter of the overall section area and follicle quality were evaluated histologically. A strong negative correlation was found between age and follicular density in patients both prior to and after chemotherapy (P < 0.0001). Damage in follicular quality, that is, increased oocyte vacuolization and detachment of the oocyte from granulosa cells, was found after chemotherapy. Ovarian tissue cryopreservation, preferably performed before initiation of chemotherapy, should be offered to pediatric patients, including prepubertal girls, at risk of sterility.

[Laparoscopic surgery for endometrial cancer in overweight women]. / Utilizzo della laparoscopia nel trattamento chirurgico delle sovrappese affette da cancro dell' endometrio.

AIM: The aim of this study was to investigate the feasibility and safety of laparoscopic staging of overweight women with endometrial cancer and to compare the surgical outcomes among these patients with those managed by laparotomy. METHODS: This was a retrospective analysis (Canadian Task-force Classification II-3). We reviewed operative and hospital records of 70 patients with a body mass index >25 kg/m2 who underwent surgical treatment for endometrial cancer between 2001 and 2008. Thirty-five patients treated laparoscopically were compared to an equivalent group of patients treated by laparotomy. Operative and postoperative variables were afterwards assessed. RESULTS: Women in laparoscopic group had a significantly lower blood loss (median, 25th-75th percentiles: 1.2, 0.8-2.0 in laparoscopic versus 1.8, 1.0-2.8 in laparotomic group, P<0.05). No differences between both group in terms of operative time (median, 25th-75th percentiles: 165 min, 130-183 in laparoscopic versus 135 min, 110-170 in laparotomic; P>0.05) and mean number of pelvic and para-aortic lymph nodes removed (22 ± 8.4 versus 24 ± 6.2 and 9.2 ± 2.5 versus 9.3 ± 5 respectively; P>0.05). Length of urethral catheter and hospital stay were statistically higher in laparotomic group (two days versus three days; four days versus seven days respectively; P<0.05). CONCLUSION: Laparoscopic surgery in overweight women with endometrial cancer had equivalent surgical staging than women operated by laparotomy. With regard to postsurgical variables, overweight women who underwent laparoscopic surgery had better results than those treated by laparotomy.

Comparison of transvaginal sonography and double-contrast barium enema for diagnosing deep infiltrating endometriosis of the posterior compartment.

OBJECTIVES: To compare the diagnostic accuracy of transvaginal sonography (TVS) and double-contrast barium enema (DCBE) in the preoperative detection of deep infiltrating endometriosis (DIE) of the posterior compartment. METHODS: This was a prospective study of 69 consecutive patients with results of pelvic examination or symptoms suggestive of DIE of the posterior compartment. TVS and DCBE were performed before surgery by two groups of physicians specialized in endometriosis, each blinded to the results of the other technique. Imaging data were compared with histopathologic analysis of the resected specimen (gold standard). Sensitivity, specificity, positive and negative predictive values and test accuracies were calculated for both imaging modalities. RESULTS: Sixty seven of the 69 women had a nodule of DIE confirmed at laparoscopy and histopathologic examination. TVS diagnosed DIE in 57 (85%) of these patients, while DCBE revealed the presence of the lesion in 24 (36%) women. For the diagnosis of posterior DIE, TVS and DCBE had, respectively, a sensitivity of 85% and 36%, specificity of 100% and 100%, positive predictive value of 100% and 100%, negative predictive value of 17% and 4% and accuracy of 85.5% and 38%. In patients with pure bowel DIE the sensitivity was 91% and 43%, specificity was 100% and 100%, positive predictive value was 100% and 100%, negative predictive value was 29% and 6% and accuracy was 91% and 45%, respectively. CONCLUSIONS: TVS has a much higher sensitivity than does DCBE in detecting the presence of posterior DIE and should thus be regarded as the imaging modality of choice when there is clinical suspicion of the disease.

Population-based frequency assessment of HPV-induced lesions in patients with borderline Pap tests in the Emilia-Romagna Region: the PATER study.

BACKGROUND: The PATER study assessed the frequency of high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in HPV-induced lesions in patients with borderline cytology. METHODS: This retrospective observational cohort study was designed to evaluate ASCUS patients detected through a local cervical cancer screening programme and referred to the Department of Gynaecology and Obstetrics at the S. Orsola-Malpighi University Hospital in Bologna, in the period between January 2000 and December 2007. RESULTS: In 1047 patients aged 38.4 ± 9.6 years (range 23-65 years), 34.8% (n = 364) was positive for HR- or LR-HPV DNA. The mean age of women with HPV infection was significantly lower compared with the negative group (36.8 ± 9.4 versus 39.3 ± 9.6 years; p < 0.001). Overall, 357 (34.1%) women had cervical lesions: 279 (26.6%) had CIN1, 18 (1.7%) CIN2, and 60 (5.7%) CIN3+. HR-HPV genotype was detected in 83.3%, and 91.5% of patients with CIN2 and CIN3+ respectively. Among the 124 CIN1 HPV-positive women, 8.9% harboured LR-HPV genotypes, 80.6% HR-HPV and 10.5% a combination of HR- and LR-HPV. HPV-6 and 11 accounted for 19.4% of all HPV-positive CIN1 lesions. CONCLUSION: Our study suggest that: in ASCUS patients over 40 years there is a low risk of positivity for HPV infection; the HPV DNA testing in patients with CIN3+ and a mean age close to 40 years is highly sensitive (98.3%) and acceptably specific (75.5%); the frequency of LR-HPV (alone or in combination with HR) in ASCUS cytology is not negligible. A tetravalent-based HPV vaccination alongside the screening programme would provide considerable clinical, organizational, and economic benefits.

Doppler flow analysis of the palmaris superficial branch of the radial artery in postmenopausal women with acroparesthesia: the role of hormone therapy. A pilot study.

METHOD: Twenty-three patients with acroparesthesia were submitted to clinical evaluation and color Doppler analysis of the uterine artery and palmaris superficial branch of the radial artery. Thirteen women (Group I) were submitted to hormone treatment with drospirenone 2 mg + estradiol emidrate 1 mg. Ten patients refused the treatment and served as controls (Group II). The patients were studied at baseline and after 6 months' therapy. RESULTS: After 6 months of hormone therapy, the resistances of the uterine artery and palmaris superficial branch of the radial artery significantly decreased in Group I patients. This was associated with the complete disappearance of paresthesic symptoms in 12/13 (92%) of the treated patients. In patients belonging to Group II, the paresthesia remained unchanged. CONCLUSION: Hormone therapy with drospirenone may increase the forearm/hand blood flow, and favor the amelioration of paresthesia.

One-Step Laparoscopic Management of a Female Adnexal Tumor of Wolffian Origin.

We report a case of female adnexal tumor of Wolffian origin (FATWO), a rare neoplasm arising from the mesonephric ducts. A 48-year-old woman came first to our center for a recent discovery of a pelvic mass. Transvaginal ultrasonographic findings suggested a solid right para-ovarian mass suspected to be malignant. After thorough counseling, the patient underwent operative laparoscopy for excision of the para-ovarian mass with frozen section (FS) examination resulting in the diagnosis of a poorly differentiated adenocarcinoma. In this case, FS results allowed performing a comprehensive oncological staging, through a totally laparoscopic extrafascial hysterectomy, bilateral adnexectomy, total omentectomy, pelvic wall peritonectomy, and pelvic, parasacral and para-aortic lymphadenectomy. Final pathological and immunohistochemical results confirmed the diagnosis of FATWO. To our knowledge, this is the first case of FATWO managed entirely by a minimally invasive laparoscopic approach in a single surgical session.

Preservation of ovarian function.

In the last years, advances in diagnosis and new treatments of cancer patient have increased the life expectancy of children, adolescent and women with cancer. Unfortunately, the ovaries are very sensitive to chemio-radiotherapy that may induce the loss of ovarian function and fertility with consequent premature ovarian failure. The different cryopreservation options available for fertility preservation in cancer patients are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. The choice depends on different parameters: the type and timing of cancer treatment, the type of disease, the patient's age. The advances in reproductive technology have made fertility preservation a real possibility for patients whether they are girls or young women whose gonadal function is threatened by natural premature menopause, or by cancer therapy or surgical sterilisation.

Controversies in surgical staging of endometrial cancer.

Endometrial cancer is the most common gynaecological malignancy and its incidence is increasing. In 1998, international federation of gynaecologists and obstetricians (FIGO) required a change from clinical to surgical staging in endometrial cancer, introducing pelvic and paraaortic lymphadenectomy. This staging requirement raised controversies around the importance of determining nodal status and impact of lymphadenectomy on outcomes. There is agreement about the prognostic value of lymphadenectomy, but its extent, therapeutic value, and benefits in terms of survival are still matter of debate, especially in early stages. Accurate preoperative risk stratification can guide to the appropriate type of surgery by selecting patients who benefit of lymphadenectomy. However, available preoperative and intraoperative investigations are not highly accurate methods to detect lymph nodes and a complete surgical staging remains the most precise method to evaluate extrauterine spread of the disease. Laparotomy has always been considered the standard approach for endometrial cancer surgical staging. Traditional and robotic-assisted laparoscopic techniques seem to provide equivalent results in terms of disease-free survival and overall survival compared to laparotomy. These minimally invasive approaches demonstrated additional benefits as shorter hospital stay, less use of pain killers, lower rate of complications and improved quality of life.

A very early and acute renal impairment due to polyomavirus allograft nephropathy.

Polyomavirus-associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant.

Diagnostic accuracy and potential limitations of transvaginal sonography for bladder endometriosis.

OBJECTIVES: To evaluate the accuracy and the potential limitations of transvaginal sonography (TVS) in the preoperative evaluation of women with clinically suspected bladder endometriosis and to describe the sonographic features of the pathological condition in cases in which it was confirmed. METHODS: In the period between 2001 and 2006, we operated on 490 patients with clinically/sonographically suspected endometriosis. In 41 cases, bladder endometriosis was diagnosed at surgery and confirmed at histopathological examination. All patients underwent TVS in a standardized manner not more than 1 month before surgery. Findings at preoperative TVS were described and compared with those at laparoscopy in order to evaluate the sensitivity, specificity, and positive and negative predictive values of TVS. RESULTS: Bladder endometriosis was correctly identified at TVS in 18/41 cases (43.9%) while 23/41 (56.1%) patients had a negative preoperative sonogram. The sensitivity, specificity and positive and negative predictive values of TVS for bladder endometriosis were 44% (18/41), 100% (449/449), 100% (18/18) and 95% (449/472), respectively, and the total accuracy was 95% (467/490). The detection rate was strongly related to mean lesion diameter as measured by the pathologist (mean +/- SD, 42.5 +/- 22.1 mm in the nodules detected vs. 28.9 +/- 14.8 mm in the nodules missed; P = 0.029) and to a history of previous surgery for endometriosis (70.6% vs. 25.0%; P = 0.005). At TVS, the nodule was hypoechogenic, its morphology was either elongated ('comma-shaped': 12/18, 66.7%) or spherical (6/18, 33.3%), and the site involved was the dome (11/18, 61.1%) or the base (7/18, 38.9%) of the bladder. Small anechogenic cystic areas within the nodule were seen in five of the 18 patients (27.8%) and a bright hyperechogenic rim was seen in 10 (55.6%). CONCLUSIONS: The detection rate of bladder endometriosis by TVS depends on the size of the endometriotic nodules, with detected nodules being larger than those that were missed. A history of previous surgery for endometriosis increases the likelihood of bladder endometriosis being detected on ultrasound examination.

Post-operative use of oral contraceptive pills for prevention of anatomical relapse or symptom-recurrence after conservative surgery for endometriosis.

BACKGROUND: Endometriosis recurrence after conservative surgery is not infrequent. Variable regimens of hormonal therapy have been proposed as adjuvant post-operative measures for prophylaxis against recurrence. Among these, the combined oral contraceptive pills (OCP), represents a valuable option in terms of safety and tolerability for long-term use. The objective of this review is to evaluate the effect of post-operative use of OCP in preventing symptom recurrence, and/or anatomical relapse of endometriosis. METHODS: A systematic search of Medline identified seven studies evaluating post-operative OCP treatment on prevention of endometriosis recurrence. RESULTS: A reduction in anatomical relapse rate was observed when oral contraceptive therapy was administered for more than 1 year after conservative surgery. Post-operative use of OCP was associated with a reduction in frequency and intensity of dysmenorrhoea recurrence. No association was found between OCP therapy and dyspareunia prevention, although the effect of OCP on chronic pelvic pain was conflicting. CONCLUSION: Long-term OCP therapy can be a reliable adjuvant post-operative measure to prevent or reduce frequency/severity of recurrent dysmenorrhoea and anatomical relapse of endometriosis. Since both continuous and cyclic OCP administration regimens seem to have comparable effects, the choice of regimen can be modulated according to patient preferences. The protective effect seems to be related to the duration of treatment.

Effects of indoor air purification by an air cleaning system (Koala technology) on semen parameters in male factor infertility: results of a pilot study.

A number of studies indicated a clear decline in semen quality in the past 30-50 years and there is accumulating evidence that this decline might result from exposure to high levels of air pollution. To examine the impact of environment on male reproductive ability, we undertook for the first time a pilot study on semen quality of infertile men exposed to purification of indoor air. Ten subjects with a history of unexplained male infertility and poor semen quality were exposed for at least 1 year to a cleaning indoor air system (Koala technology). The key feature of this air purifier is the unique innovative multiple filtering system. The treatment of total purification of indoor air showed neither improvements in semen parameters nor variation in reproductive hormones (P = N.S.), but induced an evident increase (P < 0.03 and more) in seminal leucocytic concentrations. Within the limits due to the small sample of subjects recruited, the sole purification of indoor air does not seem enough to improve semen quality, although the increase in leucocytic concentrations could indicate an activation of the role of immunosurveillance in a purified indoor air environment.