Klinefelter syndrome: how,what, and why?

Klinefelter syndrome is commonly encountered by the physician dealing with male infertility. Despite the success of sperm retrieval and ICSI, there remain many areas of controversy about the mechanisms and natural history of spermatogenesis, as well as the appropriate management of these patients. This collection of articles provides a state of the art review of what is known and what is unknown about this syndrome and reports a variety of management approaches to these patients.     

Effects of 17β-estradiol and trimegestone alone,and in combination,on the bone and uterus of ovariectomized rats

Trimegestone is a novel norpregnane progestin ,which is being developed ,in combination with 17β-estradiol ,for the treatment of menopausal symptoms and prevention of postmenopausal osteoporosis. A model of osteoporosis in the ovariectomized rat has been used to evaluate the effects of 17β-estradiol and trimegestone ,alone and in combination ,on bone and uterus in these animals. Two treatment protocols were investigated ,preventive with treatment starting immediately after ovariectomy and curative with treatment starting 1 or 6 months after ovariectomy. 17β-Estradiol was administered subcutaneously at a dose of 10 μg/kg/day with trimegestone or norethisterone being administered orally at a dose of 1 mg/kg/day; treatment was given 5 days per week. Treatment on both protocols was for 6 months. Given alone ,17β-estradiol maintained bone mass ,either partially or completely ,when given on the preventive protocol ,or on the curative protocol with treatment starting 1 month after ovariectomy; it did not restore bone mass when given on the curative protocol with 6 months lapsing between ovariectomy and start of treatment. Trimegestone did not block the beneficial effects of 17β-estradiol on bone. 17β-Estradiol induced uterine hypertrophy on all these protocols and this was blocked completely by trimegestone. Trimegestone administered alone had no effect on bone or uterus but ,when given in combination with 17β-estradiol ,it did not inhibit the effect of 17β-estradiol in maintaining bone mass but completely blocked its uterotropic effect. Norethisterone at a similar dose did not inhibit the effects of 17β-estradiol on bone but also did not block its uterotropic effect.     

Fertility Preservation after a Cancer Diagnosis: A Systematic Review of Adolescents', Parents', and Providers’ Perspectives,Experiences, and Preferences

Study ObjectiveSurvival into adulthood is now a reality for many adolescents facing cancer. Fertility preservation (FP) is rapidly advancing, but oncology providers and health systems struggle to incorporate the newest FP technologies into the clinical care of adolescents. Our objective was to systematically review and synthesize the available data regarding the perspectives, experiences, and preferences of adolescents, parents, and oncology providers about FP to inform clinical implementation of FP technologies.Design, Setting, Participants, Interventions, and Main Outcome MeasuresFive electronic databases (PubMed, Embase, Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature, PsychInfo) were systematically searched for studies published between January 1999 and May 2014. Adolescents were defined as 12-18 years at the time of diagnosis or designated as pubertal/postpubertal and younger than 18 years of age. Studies were assessed for methodological quality, data were extracted using a standardized form, and results were synthesized using guidelines for a narrative syntheses of quantitative and qualitative data.ResultsIn total, 1237 records were identified, with 22 articles, representing 17 unique studies that met the inclusion criteria. The following topics were consistently observed across studies and populations: (1) fertility in trust; (2) decision-making challenges; (3) provider knowledge and practices; and (4) discrepancies between desired and actual experiences.ConclusionDespite the challenges associated with a new cancer diagnosis, adolescents and parents value the opportunity to discuss fertility concerns and preservation options. Providers play an important role in addressing these topics for families and efforts should be made to incorporate FP discussions into routine cancer care for all adolescents, with attention paid to the unique needs of adolescents and their parents.     

Peculiar facies, obesity, cleft lip and palate, growth hormone deficiency and mental retardation: a new syndrome?

A female child with peculiar facies, obesity, cleft lip and palate, growth hormone deficiency and mental retardation is described. The present case does not appear to fit any of the known syndromes.     

Maternal–fetal transport and disposition of copper,iron, molybdenum,selenium and zinc in experimentally induced diabetic rats

Objective. To assess maternal–fetal status of essential trace elements such as copper, iron, molybdenum, selenium and zinc, in experimentally induced diabetic and control pregnant rats, and to correlate the findings with those observed in human diabetic pregnancies. Fetal–maternal ratios of the elements and Cu:Zn and Cu:Fe ratios were also computed in control and study groups.

Methods. Diabetes was experimentally induced in pregnant Sprague Dawley rats by injection of streptozotocin. A cocktail of essential trace elements along with antipyrine as internal reference marker were then injected intra-peritoneally to diabetic and matched control pregnant rats on the 20th day of pregnancy. Maternal and fetal blood and tissue samples were collected after sacrificing the animals at 30- and 60-minutes following cocktail injection. Concentrations of trace elements and antipyrine in various blood and tissue samples were then determined by atomic absorption spectrophotometry and colorimetry, respectively.

Results. Concentrations of Cu, Fe, Mo, Se, Zn, and antipyrine averaged 2907.0 ± 212.0 μg/L, 3950.0 ± 766.0 μg/L, 15.8 ± 1.7 μg/L, 74.8 ± 6.5 μg/L, 726.4 ± 67.4 μg/L, and 170.5 ± 8.2 mg/L, respectively, in maternal blood in control pregnant rats (n = 5) at day 20 in the 30-minute study phase, while in the diabetic group (n = 5) the values of the various trace element concentrations and antipyrine averaged 2875.0 ± 225.0 μg/L, 5875.0 ± 688.0 μg/L, 21.2 ± 2.1 μg/L, 116.0 ± 3.6 μg/L, 753.0 ± 71.3 μg/L, and 171.7 ± 4.2 mg/L, respectively. Unpaired student's t-test showed that Fe and Se levels were significantly higher (p < 0.05) in the diabetic pregnant rats compared to controls. Cu, Mo and Zn values, however, were not significantly different (p > 0.05) between the two groups. Cu:Zn and Cu:Fe ratios showed varying differences between maternal and fetal samples in the control and study groups.

Conclusions. Considering the disparity of results in pregnant diabetic rats and pregnant diabetic women, we urge exercising caution when comparing data from animal studies to human situations.     

Conceptus implantation and placentation: molecules related to epithelial–mesenchymal transition,lymphocyte homing,endogenous retroviruses,and exosomes

Processes of conceptus implantation and placentation, unique to mammalian reproduction, have been extensively studied. It was once thought that processes of these events varied greatly, notably between invasive and noninvasive modes of implantation and/or placentation. Regardless of the mode of implantation, however, physiological and biochemical processes in conceptus implantation to the maternal endometrium including the kinds of gene expression and their products are now considered not to differ so much. Recent progress has identified that in addition to the hormones, cytokines, proteases and cell adhesion molecules classically characterized, epithelial–mesenchymal transition, molecules related to lymphocyte homing, the expression of endogenous retroviruses and possibly exosomes are all required for the progression of conceptus implantation to placentation. In this review, therefore, new findings related to these events are integrated into the context of conceptus implantation to the maternal endometrium.     

Inhibins, activins and anti-Müllerian hormone: structure, signalling pathways, roles and predictive value in reproductive medicine

Anti-Müllerian hormone (AMH), inhibins and activins are members of the transforming growth factor (TGFbeta) superfamily and are known to have a variety of actions concerning reproduction, hormonogenesis, development processes and differentiation. Inhibins and activins are dimeric glycoproteins that are defined by their actions on the pituitary gonadotroph cells. AMH, inhibins and activins have a vast array of actions usually exerted through paracrine and endocrine mechanisms. The recent availability of specific inhibin assays has demonstrated that inhibin B is the relevant circulating inhibin form in the human male. Inhibin B seems to be a useful marker of spermatogenesis, but serum and seminal inhibin B levels are not predictive parameters for the selection of azoospermic men as candidates for testicular sperm extraction (TESE). AMH in seminal plasma may be important for sperm production, and is a good marker for sertoli cell development. It might be the only one seminal marker of spermatogenesis in non-obstructive azoospermia. Nevertheless, many of these studies were carried out with small patient numbers, and consequently must be interpreted with caution. In women ongoing assisted reproductive therapy (ART), day 3 inhibin B and AMH levels predict the number of oocytes retrieved, but cannot predict likelihood of pregnancy. Further studies are needed to determine if AMH and inhibin predict ART outcomes better than classical parameters (age, FSH levels and follicular ultrasonography). AMH and inhibin are also specific markers of Sertoli- and granulosa-cell origin in gonadal tumors.     

Association Study of ERβ, AR,and CYP19A1 Genes and MtF Transsexualism

IntroductionThe etiology of male-to-female (MtF) transsexualism is unknown. Both genetic and neurological factors may play an important role.AimTo investigate the possible influence of the genetic factor on the etiology of MtF transsexualism.MethodsWe carried out a cytogenetic and molecular analysis in 442 MtFs and 473 healthy, age- and geographical origin-matched XY control males. The karyotype was investigated by G-banding and by high-density array in the transsexual group. The molecular analysis involved three tandem variable regions of genes estrogen receptor β (ERβ) (CA tandem repeats in intron 5), androgen receptor (AR) (CAG tandem repeats in exon 1), and CYP19A1 (TTTA tandem repeats in intron 4). The allele and genotype frequencies, after division into short and long alleles, were obtained.Main Outcome MeasuresWe investigated the association between genotype and transsexualism by performing a molecular analysis of three variable regions of genes ERβ, AR, and CYP19A1 in 915 individuals (442 MtFs and 473 control males).ResultsMost MtFs showed an unremarkable 46,XY karyotype (97.96%). No specific chromosome aberration was associated with MtF transsexualism, and prevalence of aneuploidy (2.04%) was slightly higher than in the general population. Molecular analyses showed no significant difference in allelic or genotypic distribution of the genes examined between MtFs and controls. Moreover, molecular findings presented no evidence of an association between the sex hormone-related genes (ERβ, AR, and CYP19A1) and MtF transsexualism.ConclusionsThe study suggests that the analysis of karyotype provides limited information in these subjects. Variable regions analyzed from ERβ, AR, and CYP19A1 are not associated with MtF transsexualism. Nevertheless, this does not exclude other polymorphic regions not analyzed. Fernández R, Esteva I, Gómez-Gil E, Rumbo T, Almaraz MC, Roda E, Haro-Mora J-J, Guillamón A, and Pásaro E. Association study of ERβ, AR, and CYP19A1 genes and MtF transsexualism. J Sex Med 2014;11:2986–2994.