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.

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.

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.

[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.

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.

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.

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.

Multiplex chemiluminescence microscope imaging of P16(INK4A) and HPV DNA as biomarker of cervical neoplasia.

Classification of cervical intraepithelial neoplasia (CIN) lesions in low-grade (CIN1) or high-grade (CIN2-3) ones is crucial for optimal patient management, but current histological diagnosis on bioptic samples is often hampered by inter-observer variability. To allow objective classification, we have exploited the peculiar characteristics of chemiluminescence detection, such as high sensitivity and easy quantification of the luminescence signal, to perform sequentially in the same tissue section both an immunohistochemical quantitative detection of p16(INK4A) (a protein marker of high-grade CIN lesions) and an in situ hybridization for human papillomavirus (generally accepted as a necessary but insufficient cause of cervical carcinoma). Different label enzymes (alkaline phosphatase and horseradish peroxidase) were employed in order to avoid any interference between the two assays, and quantitative chemiluminescence image analysis was used to obtain objective evaluation of sample positivity. The multiplexed method allowed detection of two complementary biomarkers and provided discrimination between different lesions (non-neoplastic, low-grade and high-grade CIN). This assay might thus represent an accurate and objective diagnostic test providing important information for counseling, selection of therapy and follow up after surgical treatment.

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.

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.

Healthy twins delivered after oocyte cryopreservation and bilateral ovariectomy for ovarian cancer.

Anti-neoplastic treatments have significantly increased the survival of cancer patients, but female patients risk premature menopause. Oocyte cryopreservation has been proposed as a fertility-saving option. This report describes the first live birth achieved with autologous cryopreserved oocytes in an ovariectomized borderline cancer patient. A patient with a borderline ovarian tumour asked for oocyte cryopreservation after a right adnexectomy. Ovulation induction resulted in the retrieval and cryopreservation of seven mature oocytes. Thirty-nine months after a left ovariectomy, the patient asked for oocyte thawing and embryo transfer. Endometrial growth was induced using hormone replacement treatment. Three of the seven cryopreserved oocytes were thawed; they survived and, after insemination, normal fertilization took place. Three embryos were transferred into the patient's uterus. A twin pregnancy was achieved with the birth of two healthy females. Oocyte cryopreservation may be a reliable option for preserving fertility in young cancer patients who risk premature menopause due to surgery, chemotherapy or radiotherapy.

High concentrations of catecholamines in human hypothalamic-hypophysial blood.

While the hypothalamic-hypophysial portal system has been extensively studied in laboratory animals, equivalent studies have not been performed in humans. Here, we present an experimental procedure for collecting suprapituitary blood in man. To solve the question on the origin of such blood we investigated specific markers of hypothalamic secretory activity: the catecholamines (CAs). We found (a) norepinephrine (NE), dopamine (DA), and epinephrine (E) concentrations from approximately 1.5 to 2.5, 3.5 to 4.5, and 6- to 10-fold higher, respectively, in suprapituitary than peripheral blood, (b) different NE/DA and NE/E ratios in favor of DA and E in suprapituitary blood, and (c), a complete (100%) group separation (suprapituitary vs. peripheral) when discriminant analysis included only DA and E. These data indicate that suprapituitary blood composition is different from that of the peripheral blood, and is particularly rich in CAs and claimed differences between DA and E release on one hand and NE release on the other in suprapituitary blood also are observed. We advance the hypothesis of a hypothalamic source of such amines draining via median eminence into portal vasculature, and name this blood "hypothalamic-hypophysial blood." Besides serving as "classical" neurotransmitters, CAs may also have a direct neurohormonal role in the regulation of the human hypothalamic-hypophysial function.

Surgical outcome and long-term follow up after laparoscopic rectosigmoid resection in women with deep infiltrating endometriosis.

The aim of this study was to assess the long-term outcome of treating severely symptomatic women with deep infiltrating intestinal endometriosis by laparoscopic segmental rectosigmoid resection. Detailed intraoperative and postoperative records and questionnaires (preoperatively, 1 month postoperatively and every 6 months for 3 years) were collected from 22 women. The estimated blood loss during surgery was 290 +/- 162 ml (range 180-600), and average hospital stay was 8 days (range 6-19). One woman required blood transfusion after surgery. Two cases were converted to laparotomy. One woman had early dehiscence of the anastomosis. Six months after surgery, there was a significant reduction of symptom scores (greater than 50% for most types of pain) related to intestinal localisation of endometriosis (P < 0.05). Score improvements were maintained during the whole period of follow up. Noncyclic pelvic pain scores showed significant reductions (P < 0.05) after 6 and 12 months, but there was a high recurrence rate later. Dysmenorrhoea and dyspareunia improved in 18/21 and 14/18 women with preoperative symptoms, respectively. Constipation, diarrhoea and rectal bleeding improved in all affected women for the whole period of follow up. Laparoscopic segmental rectosigmoid resection seems safe and effective in women with deep infiltrating colorectal endometriosis resulting in significant reductions in painful and dysfunctional symptoms associated with deep bowel involvement.

Fetal calf serum versus human serum: ultrastructural evaluation of protein support influence on human ovarian tissue cryopreservation.

The aim of this study was to examine the effect of the different protein supports in the cryopreservation solution on improving human ovarian tissue preservation after frozen-thawed procedures. Biopsies of ovarian cortical tissue were obtained from 14 subjects. All specimens were cryopreserved using a slow freezing/rapid thawing method in a solution consisting of propanediol and sucrose in different proportions of 3 protein supports: 30% human serum (HS) (solution A), 20% HS (solution B), or 20% fetal calf serum (solution C). After thawing, 191 follicles and a total of 70 samples were analyzed using transmission electron microscopy (TEM). The post-thaw preservation rate of the follicles in solution A was significantly higher with respect to solution C (p < 0.05). Unlike the follicles, the stromal cell morphology was not affected by any of the solutions investigated. By comparing stromal morphology and the patient age, it was found that HS better preserved the tissue in patients over 20 years of age with respect to younger ones, which showed a wider variability in ovarian preservation. TEM evaluation showed that 30% HS is more suitable for human ovarian tissue cryopreservation, and research should be focused on defining cryopreservation protocols specific to young patients.

[Laparoscopic hysterectomy in the management of endometrial cancer]. / Isterectomia laparoscopica nel trattamento del carcinoma endometriale.

Endometrial carcinoma is the most commonly reported gynaecologic malignancy in industrialized countries. Traditionally the surgical treatment of endometrial cancer is total abdominal hysterectomy, bilateral salpingo-oophorectomy, and peritoneal washing cytology. Alternative surgical procedures have been proposed compared to abdominal hysterectomy: increased number of issues about laparoscopy shows the common trend to use this technique. Literature largely described advantages of the laparoscopic procedure compared to abdominal and vaginal surgery. Long-term follow-up series are not available; further investigation into survival and recurrence rates is indicated.

Different gonadotropin pulsatile fashions in anovulatory cycles of young girls indicate different maturational pathways in adolescence.

To characterize the spectrum of pulsatile gonadotropin secretion during the postmenarchal period, we studied 24 adolescents whose gynecological age was 1-4 yr. Six women with ovulatory cycles formed a control group. Eighteen women with anovulatory cycles were grouped on the basis of mean plasma LH values: group 1 (n = 8) with high LH values and group 2 (n = 10) with normal LH values. In all women, plasma gonadotropin concentrations were measured at 10-min intervals for 8 h on day 4 of the cycle. Pulsatile gonadotropin secretion was also studied a second time in 7 women from group 1 and 7 from group 2 after 5 days of progesterone (P) in oil treatment to assess the role of P in regulating gonadotropin secretion in the postmenarchal period. Group 1 had more frequent and greater LH pulses than the other two groups (which were very similar) and had the highest plasma 17 beta-estradiol, testosterone (T), androstenedione (A), and 17-hydroxyprogesterone concentrations. In all anovulatory women, basal LH values were correlated with the LH interpulse interval (r = -0.65; P less than 0.01) and pulse amplitude (r = 0.86; P less than 0.001). LH pulse amplitude was correlated with basal 17 beta-estradiol values (r = 0.74; P less than 0.001), and LH interpulse interval with basal T (r = -0.83; P less than 0.001), A (r = -0.51; P less than 0.05), and 17-hydroxyprogesterone (r = -0.79; P less than 0.001) values. P administration decreased LH pulse frequency and increased LH pulse amplitude more in group 2 than in group 1 with high LH values; a clear reduction was also found in A, T, and 5 alpha-dihydrotestosterone values. These results indicate that 1) anovulatory young women with high plasma LH values have an alternative maturational pathway, different from that of anovulatory women with normal plasma LH values, who are similar to ovulatory adolescents; 2) the pulsatile pattern of gonadotropin secretion has specific roles linked separately to amplitude and frequency in controlling ovarian steroidogenesis, which accounts for the endocrine differences between groups; and 3) in the postmenarchal period, by modulating LH and FSH pulsatility and thus reducing androgen levels and their atretic action on follicles, P may be a basic regulatory factor in enhancing functional cyclicity.

Adeno-pituitary hormones in human hypothalamic hypophysial blood.

An in vivo technique for collecting blood from the pituitary stalk using transphenoidal microsurgery has recently been developed in men with nonfunctioning pituitary disease. To determine the origin of this blood and the direction of the stream, we measured contemporaneously the levels of LH, FSH, PRL, GH, TSH, and ACTH in hypothalamic-hypophysial blood (HHB) and peripheral blood (PB). Eleven patients with nonfunctioning pituitary adenomas entered the study. The surgical procedure used for collecting HHB consisted of periodically aspirating small amounts of blood using a microsuction apparatus, just after tumor removal, kept in the postero-superior corner of the sella turcica at the junction of the diaphragm with the dursum sellae. The data show clearly the existence of a dramatic concentration gap in HHB vs. PB in all adeno-pituitary hormones (P = 0.003). The HHB/PB ratio varied from 50-600 in the different hormones. The secretion of adeno-pituitary hormones in blood drawn at the pituitary stalk level in man was reported for the first time. The dramatic HHB/PB ratio of the hormone levels has been emphasized. The most likely explanation for the markedly elevated hormone concentration gradient between central and peripheral blood was sampling of peri- and/or suprapituitary blood. To consider the origin and direction of the HHB stream, two hypotheses have been further advanced: 1) a retrograde bloodflow from the pituitary, and 2) a central-hypothalamic secretion.