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Male infertility caused by anejaculation is common after spinal cord injury (SCI) and following retroperitoneal lymph node dissection (RPLND) for testicular cancer. Other conditions sometimes associated with neurogenic ejaculation loss are diabetes mellitus, multiple sclerosis, extensive pelvic surgery and adult myelodysplasia. Primary absence of ejaculation also has been described. Few treatment options exist for these patients, if they wish to father a child. With electroejaculation (EEJ), or the low-current stimulation of the ejaculatory organs via a rectal probe, emission of semen can be initiated in these men. In non-SCI-patients EEJ requires general anaesthesia. The collected semen is washed and the motile sperm fraction isolated before artificial insemination (AI) of the partner. At the University of Michigan 198 men have been treated between 1986 and December 1991. An ejaculate could be obtained from nearly all patients. A major obstacle to success is the severe asthenozoospermia and the poor functional quality of the obtained sperm samples. This can be caused by the EEJ-technique itself, as well as by the long anejaculatory status. A semen sample with at least 10 million progressively motile sperm cells, useful for AI, was obtained in 75% of the SCI men and in 87% of the men following RPLND. In the couples wishing insemination, 49 pregnancies were induced, accounting for an overall pregnancy rate of 35% per couple. Thirty five healthy babies have been born. Only three complications were encountered. At Hannover Medical School only few patients have been stimulated to date. We could obtain an adequate sperm sample for AI from all of them. No complications were seen. As the first couple has just entered the phase of AI with husband sperm, an analysis of these results would be premature. Electroejaculation combined with artificial insemination is an efficient and safe treatment of male infertility due to neurogenic anejaculation.
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PMID:Treatment of anejaculation with electroejaculation. 149 31

Viagra and in vitro fertilization (IVF) with intraovocyte injection of spermatozoa (ICSI) have revolutionized the treatments of impotence and male sterility. They are able to treat successfully most of the cases whatever is the cause of the problem. The andrologist is tempted to renounce to look for an etiological factor and to treat directly his patient. The risk is to miss a diagnosis such as genital tract obstruction, testicular cancer, gonadotropin deficiency, sperm autoimmunity, coital disorders, or reversible toxin exposures, which could benefit from a specific treatment. Moreover IVF can endanger the woman's health and genetic consequences must not be overlooked if ICSI is performed. Concerning impotence a diagnosis of prolactinoma, diabetes or ischemic cardiopathy must not be missed because Viagra can also have cardio-vascular side-effects. This article reviews some etiological factors responsible for male infertility or impotence. The importance of a global appraisal of the patient is underlined in order not to limit his role to the one of a sperm producer.
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PMID:[Do viagra and fertilization in vitro announce the end of etiologic treatments in andrology?]. 1084 22

Recent advances in human cryobiology have been substantially greater than the first slow step from freezing spermatozoa in animals in Italy, published in 1776 to observing motility in frozen-thawed human sperm in 1938(1). Reports on cryopreservation of rabbit oocytes (1947)(1) and births from fertilised frozen-thawed mice oocytes in 1977(1) were soon followed by the first human pregnancy (1983)(1) and birth (1984)1 following transfer of frozen-thawed embryos after in-vitro fertilisation (IVF). Whereas cryopreservation of human sperm and embryos in tertiary level fertility centres is now commonplace, the full clinical, scientific and sociological consequences of progress in this rapidly moving field are to be determined. These include pregnancy with frozen-thawed human mature, oocytes after conventional IVF (1986)4, intracytoplasmic sperm injection (ICSI)(5) (1996), pregnancies following use of frozen-thawed mature (1995)(5,6) and immature oocytes (1999)(7), ovarian tissue banking (8) and possible autografting (1999)(9) as well as repeated freeze-thawing of male gametes and of embryos (10,11). Cryopreservation of female and male gametes instead of embryos offer solutions of obvious religious, ethical, legal and clinical problems. In addition, there may be benefits in reducing the cost of infertility treatment, improving the safety of fertility treatment with respect to ovarian hyperstimulation syndrome and repeated treatment with controlled ovarian hyperstimulation, prevention of diseases such as sexually transmitted diseases and hereditary disorders and preventing infertility by possible long-term storage of gametes, gonadal tissue and even embryos. The benefits of cryopreservation of sperm, oocytes and embryos in the management of subfertile couples, many being self-evident to some, bear emphasis. Cryopreservation of sperm offers substantial organisational, cost and social advantages in IVF/ICSI treatment, in that it is no longer necessary for both partners to be present at the time of oocyte retrieval, or to have the sperm retrieval done simultaneously, as frozen-thawed sperm (ejaculatory, epididymal or testicular) can be used. This strategy permits men in the latter two categories to be able to support their partners at the time of oocyte retrieval, with the knowledge that their sperm surgically obtained some time previously, is available. It is now clear that, in men with obstructive azoospermia, the use of fresh or frozen-thawed sperm will yield equivalent fertilisation rates following ICSI. In men with non-obstructive azoospermia, with a 60% chance only of obtaining sperm from the testicular aspiration or biopsy, the option could be cryopreservation of the sperm harvested first and later controlled ovarian hyperstimulation of the female partner, to use thawed sperm which will lead to equivalent fertilisation rates using fresh sperm. Thus, one may avoid cost of treatment of the female in those couples who do not wish to use donor sperm as a back-up in the 40% of men from whom sperm is not obtained. Important consequences of cryopreservation of gametes and gonadal tissue are likely to be in the area of prevention of hereditary and familial diseases, as cryopreservation of oocytes, sperm, embryos and blastocysts is exploited fully in pre-implantation genetic diagnosis (PGD) strategies12. Embryo biopsy now permits screening to identify normal embryos from couples who are carriers of known single gene defects and hereditary disorders and the list of these conditions is expanding rapidly. PGD is feasible on frozen-thawed blastomeres even if cells have lysed after thawing, providing information relevant for surviving blastomeres or blastocysts. But what of the gene probes which will soon deluge us on the completion of the Human Genome Project? Can we anticipate benefits and consider proposing that couples with familial disorders, whether degenerative e.g. Type 2 Diabetes, or malignant conditions such as cancer of the ovary, breast and colon? Should we cryopreserve oocytes/sperm/embryos for the purposes of PGD once the markers are available? Cryobiology indeed provides hope now for women and men with neoplastic diseases, who are about to receive oncotherapy for malignancies which inevitably will render them sterile. Men may now freeze epididymal, testicular as well as ejaculatory sperm as ICSI has revolutionalised the treatment of male infertility. It might be likely that testicular tissue from prepubertal boys can be cryopreserved with a reasonable expectation that techniques will soon be developed to effect maturation of spermatogonia in-vivo or in-vitro13. The greatest advance is likely to be for women suffering from reproductive cancer, who may now consider mature and immature oocytes being frozen or vitrified with a reasonable chance of fertilisation by ICSI later, as well as the cryopreservation and storage of ovarian cortex tissue biopsies. Work is proceeding still to refine techniques of in-vitro maturation of frozen-thawed immature oocytes, and the frozen-thawed ovarian cortex tissue slices. The potential benefits will not only be to female fertility for the latter conditions but endocrine disorders as well as by autotransplantation (1999)9. Currently, ovarian tissue banking8 is being considered by women undergoing procedures or treatment which could destroy ovarian function with quite realistic but cautious expectations of preserving ovarian function, but tomorrow women may consider banking ovarian tissue as insurance against childlessness because of the risk of disorders in the reproductive tract (endometriosis, simple recurrent ovarian cysts) and even advancing years. For those who have conceived with surplus oocytes cryopreserved, anonymous oocyte donation is a possibility for the solution of ethical and legal problems. All over Europe, the age of women having their first child is dramatically increasing now being in their late twenties, with likely significant implications in the need to fertility treatment in the Millennium. Society has always been excited but understandably cautious about the prospect of whole body cryopreservation. Hippocrates would have argued that Society could separate medicine and its advances from religious views, dogma and prejudice and, on the present evidence, would probably have looked upon human cryobiology favourably. Human cryobiology is here to stay and society as well as the profession is addressing its relevance. There are clear signs that this technology can and will alleviate suffering by preventing genetic and familial diseases, infections and infertility as well as lowering the cost and social consequences of the treatment. For these reasons, further research in this field should be welcomed and supported.
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PMID:Cryobiology in human assisted reproductive technology. Would Hippocrates approve? 1175 34

Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations of the CFTR gene. The number of adult CF patients increased dramatically, since life expectancy is now around thirty years. CF is usually a pediatric disease. In adult patients the disease associate a diffuse bronchectasia with chronic colonisation of sputum with Pseudomonas aeruginosa, and pancreatic insufficiency. Mortality is usually related to respiratory insufficiency. One third of adult patients develop diabetes mellitus. A diagnosis of CF can be made in adult patients particularly when it exists male infertility with congenital absence of vas deferens, chronic sinusitis or diffuse bronchectasia or chronic pancreatitis, acute and recurrent pancreatitis, allergic bronchopulmonary aspergillosis. The diagnosis is established with positive sweat chloride concentration, or double CFTR mutations and/or other suggestive organ involvement.
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PMID:[Cystic fibrosis in adulthood]. 1179 81

Bardet-Biedl syndrome (BBS) is a heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, hypogenitalism, and an increased incidence of diabetes and hypertension. No information is available regarding the specific function of BBS2. We show that mice lacking Bbs2 gene expression have major components of the human phenotype, including obesity and retinopathy. In addition, these mice have phenotypes associated with cilia dysfunction, including retinopathy, renal cysts, male infertility, and a deficit in olfaction. With the exception of male infertility, these phenotypes are not caused by a complete absence of cilia. We demonstrate that BBS2 retinopathy involves normal retina development followed by apoptotic death of photoreceptors, the primary ciliated cells of the retina. Photoreceptor cell death is preceded by mislocalization of rhodopsin, indicating a defect in transport. We also demonstrate that Bbs2(-/-) mice and a second BBS mouse model, Bbs4(-/-), have a defect in social function. The evaluation of Bbs2(-/-) mice indicates additional phenotypes that should be evaluated in human patients, including deficits in social interaction and infertility.
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PMID:Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. 1553 63

Oxidative stress is now recognized as an important etiological factor in the causation of several chronic diseases including cancer, cardiovascular diseases, osteoporosis, and diabetes. Antioxidants play an important role in mitigating the damaging effects of oxidative stress on cells. Lycopene, a carotenoid antioxidant, has received considerable scientific interest in recent years. Epidemiological, tissue culture, and animal studies provide convincing evidence supporting the role of lycopene in the prevention of chronic diseases. Human intervention studies are now being conducted to validate epidemiological observations and to understand the mechanisms of action of lycopene in disease prevention. To obtain a better understanding of the role of lycopene in human health, this chapter reviews the most recent information pertaining to its chemistry, bioavailability, metabolism, role in the prevention of prostate cancer and cancer of other target organs, its role in cardiovascular diseases, osteoporosis, hypertension, and male infertility. A discussion of the most relevant molecular markers of cancer is also included as a guide to future researchers in this area. The chapter concludes by reviewing global intake levels of lycopene, suggested levels of intake, and future research directions.
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PMID:Lycopene. 1701 75

The ejaculate specimen represents an output derived from the efficiency of three essential biological events: testicular production of sperm, progression and maturation of testicular sperm through epididymides, neurophysiological integrity of the mechanisms leading to the final process of ejaculation. All three events can negatively be affected by temporary conditions in the three months up to seminal analysis (temperature, temporary/seasonal exposure to chemical substances; extended use of medicines), and so it will be negatively influenced by chronic internal conditions (diabetes, chronic liver or kidney diseases, colopathy, etc.) that will be appropriate to call again in the patient's history (anamnesis). In a diagnostic, level-based model of care, a standard semen analysis is a first level procedure (including clinical history, physical general and focused examination, semen analysis) to be performed only when male infertility is suspected, with few or without initial specific clinical indications. Beyond the limits of semen analysis, the test may be useful for the specialist (and also to the patient!) and reliable. The reliability of the semen analysis is linked to whether it is done according to the recommendations and the codified techniques of the World Health Organization (WHO) standard manual (fourth revised edition 1999). A standard semen analysis includes three operative stages: preanalytic phase; analytic phase; postanalytic phase.
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PMID:Spermiogram: techniques, interpretation, and prognostic value of results. 1755 37

Light microscopic studies comparing sperm parameters show little association between diabetes and male fertility. However, with the introduction of new analytical techniques, evidence is now emerging of previously undetectable effects of diabetes on sperm function. Specifically, a recent study has found a significantly higher sperm nuclear DNA fragmentation in diabetic men. As advanced glycation end products (AGEs) are important instigators of oxidative stress and cell dysfunction in numerous diabetic complications, we hypothesized that these compounds could also be present in the male reproductive tract. The presence and localization of the most prominent AGE, carboxymethyl-lysine (CML), in the human testis, epididymis and sperm was determined by immunohistochemistry. Parallel ELISA and Western blot analyses were performed to ascertain the amount of CML in seminal plasma and sperm from 13 diabetic and nine non-diabetic subjects. CML immunoreactivity was found throughout the seminiferous epithelium, the nuclei of spermatogonia and spermatocytes, in the basal and principle cells cytoplasm and nuclei of the caput epididymis and on most sperm tails, mid pieces and all cytoplasmic droplets. The acrosomal cap, especially the equatorial band, was prominently stained in diabetic samples only. The amount of CML was significantly higher (p = 0.004) in sperm from non-diabetic men. Considering the known detrimental actions of AGEs in other organs, the presence, location and quantity of CML, particularly the increased expression found in diabetic men, suggest that these compounds may play a hitherto unrecognized role in male infertility.
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PMID:Advanced glycation end products accumulate in the reproductive tract of men with diabetes. 1821 85

The pomegranate, Punica granatum L., is an ancient, mystical, unique fruit borne on a small, long-living tree cultivated throughout the Mediterranean region, as far north as the Himalayas, in Southeast Asia, and in California and Arizona in the United States. In addition to its ancient historical uses, pomegranate is used in several systems of medicine for a variety of ailments. The synergistic action of the pomegranate constituents appears to be superior to that of single constituents. In the past decade, numerous studies on the antioxidant, anticarcinogenic, and anti-inflammatory properties of pomegranate constituents have been published, focusing on treatment and prevention of cancer, cardiovascular disease, diabetes, dental conditions, erectile dysfunction, bacterial infections and antibiotic resistance, and ultraviolet radiation-induced skin damage. Other potential applications include infant brain ischemia, male infertility, Alzheimer's disease, arthritis, and obesity.
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PMID:Therapeutic applications of pomegranate (Punica granatum L.): a review. 1859 Mar 49

The primary goal of this study was to determine the 5'region of the Insl3 gene that specifically targets the expression of human insulin to Leydig cells, and to explore whether the testicular proinsulin is efficiently processed to insulin that is able to rescue the diabetes in different mouse models of diabetes. We show here that the sequence between nucleotides -690 and +4 of mouse Insl3 promoter is sufficient to direct the Leydig cell-specific expression of the human insulin transgene (Insl3-hIns). We also found that the 3'untranslated region (3'UTR) of Insl3 was effective in enhancing transgene expression of the insulin in vivo. Expression analysis revealed that the temporal expression pattern of the hIns transgene in Leydig cells of transgenic testes is roughly the same as that of the endogenous Insl3. Despite the Leydig cells translate human proinsulin and secrete a significant level of free C-peptide into the serum, the Leydig cell-derived insulin is not able to overcome the diabetes in different mouse models of diabetes, suggesting a lack of glucose sensing mechanisms in the Leydig cells. A consequence of overexpression of the human proinsulin in Leydig cells was the decrease of fertility of transgenic males at older ages. Germ cells in transgenic males were able to initiate and complete spermatogenesis. However, there was a progressive and age-dependent degeneration of the germ cells that lead to male infertility with increasing age.
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PMID:Directed overexpression of insulin in Leydig cells causes a progressive loss of germ cells. 1869 15


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