New understandings of the genetic basis of isolated diopathic central hypogonadism

Idiopathic hypogonadotropic hypogonadism is a rare disease that is characterized by delayed/absent puberty and/or infertility due to an insufficient stimulation of an otherwise normal pituitary-gonadal axis by gonadotrophin-releasing hormone （GnRH） action. Because reduced or normal luteinizing hormone （LH）/follicle-stimulating hormone （FSH） levels may be observed in the affected patients, the term idiopathic central hypogonadism （ICH） appears to be more appropriate. This disease should be distinguished from central hypogonadism that is combined with other pituitary deficiencies. Isolated ICH has a complex pathogenesis and ~s fivefold more prevalent in males. ICH frequently appears in a sporadic form, but several familial cases have also been reported. This finding, in conjunction with the description of numerous pathogenetic gene variants and the generation of several knockout models, supports the existence of a strong genetic component. ICH may be associated with several morphogenetic abnormalities, which include osmic defects that, with ICH, constitute the cardinal manifestations of Kallmann syndrome （KS）. KS accounts for approximately 40% of the total ICH cases and has been generally considered to be a distinct subgroup. However, the description of several pedigrees, which include relatives who are affected either with isolated osmic defects, KS, or normo-osmic ICH （nlCH）, justifies the emerging idea that ICH is a complex genetic disease that is characterized by variable expressivity and penetrance. In this context, either multiple gene variants or environmental factors and epigenetic modifications may contribute to the variable disease manifestations. We review the genetic mechanisms that are presently known to be involved in ICH pathogenesis and provide a clinical overview of the 227 cases that have been collected by the collaborating centres of the Italian ICH Network.

The number of spermatozoa collected with testicular sperm extraction is a novel predictor of intracytoplasmic sperm injection outcome in non-obstructive azoospermic patients

The purpose of this study was to determine the relationships between monitors of spermatogenesis and predictors of the intracytoplasmic sperm injection （ICSI） outcome in patients with non-obstructive azoospermia （NOA） undergoing testicular sperm extraction （TESE）. Seventy-nine patients with NOA （mean age： 43.6±5.2 years）, each of whom yielded （97 000±3040） spermatozoa with conventional TESE, were considered in our analysis. Their partners （mean age： 35.8±5.1 years） underwent a total of 184 ICSI cycles; 632 oocytes were collected, 221 oocytes were injected, 141 oocytes were fertilized, 121 embryos were obtained, 110 embryos were transferred, 14 clinical pregnancies were achieved and only one miscarriage occurred. Multivariate regression analysis indicated relationships between the percentage of fertilized oocytes, transferred embryos and clinical pregnancies with the following variable values： female partner＇s age, number of spermatozoa collected, testicular volume, male partner＇s levels of follicle stimulating hormone （FSH）, number of oocytes collected, number of oocytes injected and number of ICSI cycles. A significant inverse relationship was found between female partner＇s age or male partner＇s FSH levels and biochemical pregnancies. A significant direct relationship emerged between the number of ICS! cycles and the percentage of oocytes fertilized, embryos transferred and biochemical pregnancies, and between the number of spermatozoa collected per testicular biopsy and biochemical pregnancies. The number of spermatozoa was positively linked to the number of clinical pregnancies, independent of the number of ICSI cycles and the number of oocytes collected/injected. The number of spermatozoa collected, FSH level and testicular volume are monitors of spermatogenesis linked to ICSI success.

Effects of oncological treatments on semen quality in patients with testicular neoplasia or lymphoproliferative disorders

Pretherapy sperm cryopreservation in young men is currently included in good clinical practice guidelines for cancer patients. The aim of this paper is to outline the effects of different oncological treatments on semen quality in patients with testicular neoplasia or lymphoprol iferative disorders, based on an 8-year experience of the Cryopreservation Centre of a large public hospital. Two hundred and sixty-one patients with testicular neoplasia and 219 patients with lymphoproliferative disorders who underwent chemotherapy and/or radiotherapy and pretherapy semen cryopreservation were evaluated. Sperm and hormonal parameters （follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone, inhibin B levels） were assessed prior to and 6, 12, 18, 24 and 36 months after the end of cancer treatment. At the time of sperm collection, baseline FSH level and sperm concentration were impaired to a greater extent in patients with malignant testicular neoplasias than in patients with lymphoproliferative disorders. Toxic effects on spermatogenesis were still evident at 6 and 12 months after the end of cancer therapies, while an improvement of seminal parameters was observed after 18 months. In conclusion, an overall increase in sperm concentration was recorded about 18 months after the end of cancer treatments in the majority of patients, even if it was not possible to predict the evolution of each single case ＇a priori＇. For this reason, pretherapy semen cryopreservation should be considered in all young cancer patients.

Male idiopathic oligoasthenoteratozoospermia

Idiopathic oligoasthenoteratozoospermia （iOAT） affects approximately 30% of all infertile men. This mini-review discussed recent data in this field. Age, non-inflammatory functional alterations in post-testicular organs, infective agents （Chlamydia trachomatis, herpes virus and adeno-associated viruses）, alterations in gamete genome, mitochondrial alterations, environmental pollutants and ＂subde＂ hormonal alterations are all considered possible causes of iOAT. Increase of reactive oxygen species in tubules and in seminal plasma and of apoptosis are reputed to affect sperm concentration, motility and morphology, iOAT is commonly diagnosed by exclusion, nevertheless spectral traces of the main testicular artery may be used as a diagnostic tool for iOAT. The following can be considered therapies for iOAT： 1） tamoxifen citrate （20 mg/d） ＋ testosterone undecanoate （120 mg/d） （pregnancy rate per couple/month [prcm]： 3.8%）; 2） folic acid （66 mg/d） ＋ zinc sulfate （5 mg/d）; 3） L-carnitine （2 g/d） alone or in combination with acetyl-L- canitine （1 g/d） （prcm： 2.3%）; and 4） both camitines ＋ one 30 mg cinnoxicam suppository every 4 days （prcm： 8.5%）. Alpha-blocking drugs improved sperm concentration but not morphology, motility or pregnancy rate. Tranilast （300 mg/d） increased sperm parameters and pregnancy rates in an initial uncontrolled study. Its efficacy on sperm concentration （but not on sperm motility, morphology or prcm） was confirmed in subsequent published reports. The efficacy of tamoxifen ＋ testosterone undecanoate, tamoxifen alone, and recombinant follicle-stimulating hormone is still a matter for discussion. （Asian J Andro12006 Mar; 8： 143-157）