FIGO statement: Fertility preservation.

Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach.

Top 10 priorities for future infertility research: an international consensus development study.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/ COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Not applicable.

Top 10 priorities for future infertility research: an international consensus development study† ‡.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand and Maurice and Phyllis Paykel Trust. G.D.A. reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. A.W.H. reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research and Wellbeing of Women and consultancy fees from AbbVie, Ferring, Nordic Pharma and Roche Diagnostics. M.L.H. reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. N.P.J. reports research sponsorship from AbbVie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics and Vifor Pharma. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from AbbVie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. E.H.Y.N. reports research sponsorship from Merck. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring and retains a financial interest in NexHand. J.S. reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring and being a clinical subeditor of Human Fertility. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: N/A.

Surgical sperm retrieval for assisted reproduction.

Intra-cytoplasmic sperm injection (ICSI) has revolutionized the treatment of male infertility by requiring only a single sperm to allow men whose infertility was previously considered to be uncorrectable to father a biological offspring. As a result, surgical sperm retrieval for assisted reproduction has developed to support this therapy. Microsurgical techniques have been applied to either identify areas of active spermatogenesis within the testis or to aspirate sperm-containing fluid or tissue. The combination of these techniques with in vitro fertilization (IVF)/ICSI has been shown to be a powerful approach to the treatment of azoospermic men. The availability of sperm cryopreservation offers an additional advantage, negating the need for synchronization of sperm retrieval and ovulation. Thus, the advanced methods for sperm retrieval discussed in this review also provide therapeutic options, as compared the traditional diagnostic testicular biopsy.

Microsatellite instability and defects in mismatch repair proteins: a new aetiology for Sertoli cell-only syndrome.

Microsatellite instability is characteristic of certain types of cancer, and is present in rodents lacking specific DNA mismatch repair proteins. These azoospermic mice exhibit spermatogenic defects similar to some human testicular failure patients. Therefore, we hypothesized that microsatellite instability due to deficiencies in mismatch repair genes might be an unrecognized aetiology of human testicular failure. Because these azoospermic patients are candidates for testicular sperm extraction and ICSI, transmission of mismatch repair defects to the offspring is possible. Seven microsatellite loci were analysed for instability in specimens from 41 testicular failure patients and 20 controls. Blood and testicular DNA were extracted from patient and control specimens, and amplified by PCR targeting seven microsatellite loci. DNA fragment length was analysed with an ABI Prism 310 Genotyping Machine and GeneScan software. Immunohistochemistry was performed on paraffinized testis biopsy sections and cultured testicular fibroblasts from each patient to determine if expression of the mismatch repair proteins hMSH2 and hMLH1 was normal in both somatic and germline cells. Results demonstrate that microsatellite instability and DNA mismatch repair protein defects are present in some azoospermic men, predominantly in Sertoli cell-only patients (P < 0.01 and P < 0.05 respectively). This provides evidence of a previously unrecognized aetiology of testicular failure that may be associated with cancer predisposition.

Human chorionic gonadotropin free beta-subunit in the human seminal plasma: a new marker for spermatogenesis?

UNLABELLED: In the past 20 years, several factors were detected in the human seminal plasma and proposed as markers for spermatogenesis. Human chorionic gonadotropin (hCG) and its beta-subunit were therefore investigated, and their seminal levels were found to be higher than those detected in the serum and to correlate with sperm parameters. OBJECTIVE: We designed a retrospective study to determine the suitability of hCG free beta-subunit concentration in the seminal plasma of fertile and infertile male patients as marker of spermatogenesis. STUDY DESIGN: A total of 79 infertile male patients were divided into four groups by their semen analysis results (group 1 [n=8]: azoospermia; group 2 [n=21]: severe oligozoospermia; group 3 [n=40]: oligoasthenospermia (OAS); group 4 [n=10]: asthenospermia) and 10 healthy volunteers of proven fertility were evaluated. RESULTS: The hCG free beta-subunit levels in the seminal plasma were found to be significantly higher (P<0.0001) in the control group in respect to those assayed in the infertile patients and showed a correlation with sperm count (r=0.5) and total motile sperm density (r=0.5). Twenty-five patients were on treatment with oral Mesterolone (100mg daily) plus Tamoxifen (20mg daily) for 3-6 months. Apart from a significant improvement (P<0.05) in sperm morphology, no significant changes in sperm count and motility were observed after the treatment in all the patients. In the seminal plasma of 10 patients who showed a significant increase in sperm count, hCG free beta-subunit levels were found to be significantly higher compared to those detected in the remaining patients (P<0.01). In all patients, these levels remained unchanged after the treatment. CONCLUSIONS: The evidence regarding the positive correlation between hCG free beta-subunit levels in the seminal plasma and sperm concentration is consistent with the previous results regarding hCG levels. A previous study demonstrated that testosterone levels in seminal plasma correlated with sperm concentrations; from the same evidence regarding hCG we hypothesize that seminal plasma testosterone and hCG levels are correlated. Thus, hCG may play a paracrine role in the intratesticular regulation of testosterone secretion.

Potency preservation following conformal radiotherapy for localized prostate cancer: impact of neoadjuvant androgen blockade, treatment technique, and patient-related factors.

PURPOSE: Impotence is a familiar sequela of both definitive external-beam radiotherapy (EBRT) and radical prostatectomy for localized prostate cancer. Among surgical options, nerve-sparing radical prostatectomy (NSRP) offers the highest potency preservation rate of 70%. We report the change in potency over time in an EBRT-treated population, determine the significantly predisposing health and treatment factors affecting post-EBRT potency, and compare age- and stage-matched potency rates with those of NSRP-treated patients. PATIENTS AND METHODS: Our results are from a retrospective study of 287 patients diagnosed with prostate cancer in clinical stages A to C and treated with conformal techniques to 6200 to 7380 cGy. Information regarding preradiotherapy potency, medical and surgical history, neoadjuvant antiandrogen use, and post-EBRT potency was documented for each patient. The median follow-up time was 34 months. RESULTS: At months 1, 20, 40, and 60, actuarial potency rates were 96%, 75%, 59%, and 53%, respectively. Factors identified as significant predictors of post-EBRT impotence include pre-EBRT partial potency, diabetes, coronary artery disease, and anti-androgen medication usage. Among treatment factors, a trend toward potency preservation was noted for the six-field versus the four-field technique. Finally, age- and stage-matched comparisons of potency rates for our population and NSRP-treated patients were performed. For patients older than 70 years, 60.9% of EBRT patients and 32.9% of NSRP patients remained potent after treatment. Overall, EBRT patient potency preservation was 71.3%, versus 66.2% for NSRP patients. DISCUSSION: Pre-EBRT partial potency, diabetes, coronary artery disease, and anti-androgen medication usage are significant predispositions to impotence in EBRT-treated prostate cancer patients. In comparing EBRT with NSRP for various age and stage groups, EBRT offers notably higher potency preservation rates than NSRP for patients older than 70 years.

Quality of cryopreserved testicular sperm in patients with obstructive and nonobstructive azoospermia.

PURPOSE: Sperm retrieved by testicular sperm extraction is routinely used to attempt pregnancy by in vitro fertilization-intracytoplasmic sperm injection. We evaluated the efficacy of cryopreserving testicular sperm collected by testicular sperm extraction at diagnostic biopsy. MATERIALS AND METHODS: A total of 73 men with obstructive and 42 with nonobstructive azoospermia underwent testicular sperm extraction at diagnostic biopsy. Sperm was retrieved and cryopreserved in all cases of obstruction and in 15 of nonobstructive azoospermia cases. Before freezing we determined sperm count, motility, morphology and viability, and after thawing we assessed sperm motility and viability. In 17 couples a total of 20 cycles of in vitro fertilization-intracytoplasmic sperm injection were performed and fertilization, cleavage and pregnancy rates were determined in cases of obstruction and nonobstruction. RESULTS: Sperm count and morphology were lower in the testicular biopsies of men with nonobstructive versus obstructive azoospermia. Motility was low or absent in all testicular sperm extraction specimens. Importantly, pre-freeze (63%) and post-thaw (31%) viability was the same in both patient groups. After in vitro fertilization-intracytoplasmic sperm injection using frozen and thawed testicular sperm the fertilization, cleavage, implantation and clinical pregnancy rates were 60, 86, 16 and 50%, respectively. Using cryopreserved sperm we observed no differences in outcome of any in vitro fertilization-intracytoplasmic sperm injection procedure in patients with obstructive versus nonobstructive azoospermia. CONCLUSIONS: Cryopreservation of testicular sperm provides enough good quality sperm after thawing to result in excellent in vitro fertilization-intracytoplasmic sperm injection outcomes. Cryopreservation does not adversely affect intracytoplasmic sperm injection outcomes, including pregnancy rate. Therefore, we recommend routine testicular sperm extraction and cryopreservation of sperm at testicular biopsy.

Expression of the ErbB family of receptors in ovarian cancer.

OBJECTIVE: To characterize the relative levels of the ErbB family of receptors and their relationship to one another in ovarian cancer. METHODS: A total of 17 serous cystadenocarcinomas were analyzed for epidermal growth factor receptor (EGF-R or ErbB-1) and ErbB-2, ErbB-3, and ErbB-4 receptor expression by Western blot analysis. Receptor levels were quantified by densitometry and expressed as relative densitometry units normalized to the level of alpha-tubulin. Linear regression analysis was used to analyze receptor group differences. A value of P < or = .05 was considered statistically significant. RESULTS: All 17 tumors expressed detectable levels of EGF-R, ErbB-2, and ErbB-3, but ErbB-4 expression was not detected. EGF-R levels correlated with ErbB-2 (r = .70, P < .01) and ErbB-3 (r = .52, P < .05) levels. The highest correlation was obtained between the levels of ErbB-2 and ErbB-3 (r = 0.81, P < .001). CONCLUSION: This study indicates an association between the levels of ErbB receptor family members in ovarian cancer. This association suggests that one or more coordinated regulatory mechanisms may be involved in determining their relative expression levels to one another.

Exogenous inositol and genes responsible for inositol transport are required for mating and sporulation in Shizosaccharomyces pombe.

Fission yeast, Schizosaccharomyces pombe, is a natural inositol auxotroph. We show here that the amount of exogenous inositol added to the medium is critical for the control of its life cycle. Above growth-limiting concentrations inositol stimulates mating and sporulation in minimal medium. The effect of inositol is also observed on yeast-extract-medium plates. We selected a mutant, IM49, which mates and sporulates only poorly and show that it is defective in inositol transport. Its defect is in a gene (itr2) coding for a putative 12 membrane-spanning protein. The polypeptide contains the two sugar-transport motifs typical for hexose transporters and shows good homology to the two Saccharomyces cerevisiae inositol transporters. The itr2 gene is essential for cell growth and its mRNA level is repressed by glucose. Mutant IM49 is also complemented by a multicopy suppressor gene (itr1) which codes for a putative hexose transporter with unknown substrate specifity.

Expression of epidermal growth factor and androgen receptors in ovarian cancer.

Ovarian cancer is the second most common malignancy of the female reproductive tract. Approximately 50% of ovarian cancers have elevated levels of epidermal growth factor receptor (EGFR). This overexpression is correlated with a poor prognosis for patient survival. Ovarian cancers also express a number of sex steroid receptors. The androgen receptor (AR) is the predominant sex steroid receptor and is expressed in over 80% of ovarian cancers. We investigated whether a relationship exists between EGFR and AR in ovarian cancer. Sixty serous cystadenocarcinomas were analyzed for their relative levels of EGFR and AR by Western blot analysis. Data were analyzed by Student's t test and linear regression analysis for statistical significance. More than 98% of the tumors expressed detectable levels of EGFR, while 65% of the tumors expressed detectable levels of AR. The levels of EGFR (mean +/- SEM) were found to be significantly (P < 0.01) higher in AR+ (516 +/- 15) than in AR- (304 +/- 57) tumors. EGFR levels significantly correlated to AR levels (r = 0.49, P < 0.001). These results demonstrate an association between EGFR and AR levels in ovarian cancer. Whether this association represents a causal or a casual relationship remains to be determined.

Expression of a truncated epidermal growth factor receptor-like protein (TEGFR) in ovarian cancer.

The epidermal growth factor receptor (EGFR) system has been implicated in the etiology of numerous cancers, including that of ovarian cancer. Elevated levels of EGFR are associated with poor patient prognosis. Moreover, a significant number of ovarian cancers express both the receptor and one of its ligands, suggesting an autocrine mechanism for autonomous tumor growth. Because of the implicated role of the EGFR system in neoplasia, a greater understanding of the factors involved in this system is necessary. We have recently characterized a truncated EGFR-like protein (TEGFR) in human placenta, and we now extend this investigation to ovarian cancer. We report that TEGFR is expressed in ovarian cancer and its level correlates to that of EGFR. Moreover, the level of TEGFR is reduced in metastatic compared to primary tumors. These results suggest that TEGFR may play a role in the EGFR system.

Predictors of general quality of life in patients with benign prostate hyperplasia or prostate cancer.

PURPOSE: Studies in disease specific populations have emphasized disease specific quality of life with little study of general quality of life. Furthermore, studies of general quality of life in disease specific populations have mostly examined the importance of disease specific variables, and have generally yielded poor correlations of such variables and general quality of life. We attempted to model the emotional component of general quality of life in patients with prostate disease. MATERIALS AND METHODS: We integrated prospectively collected disease specific and nonspecific clinical and self-reported patient data. We also applied neural network and more conventional statistical tools to examine the relative use of various available analytical methodologies in modeling general quality of life. RESULTS: Neural networks created reasonably good models of the emotional component of general quality of life. Logistic regression analysis also created reasonably good models and, given current computational schemes, allowed for identification of significant inputs in the models more readily than did the feed-forward, back propagation neural networks. All models of general quality of life relied primarily on disease nonspecific inputs, including social support, activities of daily living and coping. CONCLUSIONS: Our observations suggested that efforts to optimize general quality of life in patients with prostate disease must integrate disease nonspecific variables.

Microsurgical epididymovasostomy: predictors of success.

The results of microsurgical epididymovasostomy for congenital and acquired vasoepididymal obstruction were retrospectively reviewed in 22 patients in an attempt to determine what preoperative or intraoperative factors might predict surgical success. The overall success rate, defined as sperm on postoperative semen analysis, was 48%. The presence of sperm on an intraoperative touch preparation from the epididymis was significantly correlated with response (chi-square 3.24, p < 0.10) and no patient without sperm on touch preparation had sperm on subsequent semen analyses. Testicular biopsy positive for spermatogenesis and presence of motile sperm on intraoperative touch preparation were not statistically significant predictors of response. These results suggest that presence or absence of sperm on intraoperative touch preparation is the only significant prognosticator of successful microsurgical epididymovasostomy.

Primary malignant melanoma of urinary bladder.

We report a case of primary malignant melanoma of the urinary bladder. Exclusion of other sites of melanoma confirmed the primary character of the tumor, and careful histologic examination proved it to be malignant melanoma. Six previously reported cases of bladder melanoma are reviewed. Therapy and prognosis are discussed.

Paracrine factors and the regulation of spermatogenesis.

MAIN PROBLEM: Although the gonadotropins and testosterone are required for normal spermatogenesis, it is believed that local control factors regulate spermatogenesis. For many years these regulatory factors had not been identified. Over the past five years, a number of growth factors have been identified in testis or isolated testicular cell types or secretions. Growth factors are key regulatory molecules which affect cell proliferation, meiosis, and differentiated function. These factors usually act in an autocrine (acting upon the cell which secreted it) or paracine (affecting another cell) manner and thus are involved in intercellular communications. METHODS: Growth factor secretion by testicular cell types or testis tissue has been analyzed using a variety of assays measuring cell proliferation in vitro, as well as assays using immunocytochemicals. Growth factor gene expression in testis has been analyzed by Northern blot analysis and in situ hybridization, which gives information concerning the stage and cell specific expression of the gene. Inbred strains of mice with mutations of deletions in a growth factor gene has been used to suggest the function of two specific factors in testicular development and growth. RESULTS: Among the growth factors expressed or secreted by testicular cell types, most are common to some other cell types in the body, such as transforming growth factors alpha and beta, epidermal growth factor, fibroblast-like growth factors, insulin-like growth factors, interleukins, endorphins, inhibin and activin, while others may be more testis specific such as mullerian inhibiting substance (anti-mullerian hormone) and Sertoli cell secreted growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)

A local direct effect of pituitary graft on growth of the lateral prostate in rats.

Prolactin and testosterone are synergistic in stimulating growth of the rat prostate. The lateral lobe is more sensitive to this synergism than the ventral and dorsal lobes. To investigate whether prolactin acts directly in the rat prostate or indirectly through another systemic mediator, anterior pituitary grafts (1 mm3) were implanted in the lateral prostate of castrated Sprague-Dawley rats in whom a 0.5 cm or 1.0 cm testosterone-filled silastic tubing was implanted subcutaneously at the same time. Rats were randomly assigned to receive either the pituitary or a muscle chip of similar size grafted beneath the fascia lateral to the lateral prostate. Twenty-one days later, serum prolactin levels were not elevated in pituitary-grafted animals and were not significantly different from those in muscle-grafted rats. The mean lateral prostate weight on the grafted side in pituitary-implanted rats with 1.0 cm testosterone tubing was 43% heavier than either that of the contralateral side or the corresponding weights in muscle-implanted rats. In pituitary-implanted rats with 0.5 cm testosterone tubing, the mean lateral prostate weight on the grafted side was 60% heavier than either that of the contralateral side or that of the corresponding weights in muscle-implanted rats. The weight of the ventral and dorsal lobes of the prostate was not significantly affected by the presence of pituitary grafts in one of the lateral lobes. The local effect of prolactin on the lateral prostate was further demonstrated by an overall decline in tissue concentrations of dihydrotestosterone in the grafted side. These results provided evidence to indicate that there was a direct effect of prolactin on growth of the lateral prostate in rats.