Serum and intratesticular sex steroids in azoospermic men: how do they correlate?

Five intratesticular sex steroids (testosterone, dihydrotestosterone, androstenedione, estradiol and epitestosterone) along with six serum hormones (LH, FSH, prolactin, SHBG, testosterone and estradiol) were determined in 84 non-obstructive azoospermic men, in order to evaluate to what extent serum and testicular tissue as well as individual hormones in the same material mutually correlate. With exception of androstenedione, tight correlations were found among tissue content of sex steroids, while only weak correlation was recorded between serum and testicular concentrations of major sex steroids testosterone and estradiol. It points to importance of measurement of intratesticular steroids in combination with examination of sperm parameters for assessment of testicular function and spermatogenesis.

Differences in bisphenol A and estrogen levels in the plasma and seminal plasma of men with different degrees of infertility.

The general population is potentially exposed to many chemicals that can affect the endocrine system. These substances are called endocrine disruptors (EDs), and among them bisphenol A (BPA) is one of the most widely used and well studied. Nonetheless, there are still no data on simultaneous measurements of various EDs along with steroids directly in the seminal fluid, where deleterious effects of EDs on spermatogenesis and steroidogenesis are assumed. We determined levels of BPA and 3 estrogens using LC-MS/MS in the plasma and seminal plasma of 174 men with different degrees of infertility. These men were divided according their spermiogram values into 4 groups: (1) healthy men, and (2) slightly, (3) moderate, and (4) severely infertile men. Estradiol levels differed across the groups and body fluids. Slightly infertile men have significantly higher BPA plasma and seminal plasma levels in comparison with healthy men (p<0.05 and p<0.01, respectively). Furthermore, seminal BPA, but not plasma BPA, was negatively associated with sperm concentration and total sperm count (-0.27; p<0.001 and -0.24; p<0.01, respectively). These findings point to the importance of seminal plasma in BPA research. Overall, a disruption of estrogen metabolism was observed together with a weak but significant impact of BPA on sperm count and concentration.

Pericentric Inversion of Human Chromosome 9 Epidemiology Study in Czech Males and Females.

Pericentric inversion of human chromosome 9 [inv(9)] is a relatively common cytogenetic finding. It is largely considered a clinically insignificant variant of the normal human karyotype. However, numerous studies have suggested its possible association with certain pathologies, e.g., infertility, habitual abortions or schizophrenia. We analysed the incidence of inv(9) and the spectrum of clinical indications for karyotyping among inv(9) carriers in three medical genetics departments in Prague. In their cytogenetic databases, among 26,597 total records we identified 421 (1.6 %) cases of inv(9) without any concurrent cytogenetic pathology. This study represents the world's largest epidemiological study on inv(9) to date. The incidence of inv(9) calculated in this way from diagnostic laboratory data does not differ from the incidence of inv(9) in three specific populationbased samples of healthy individuals (N = 4,166) karyotyped for preventive (amniocentesis for advanced maternal age, gamete donation) or legal reasons (children awaiting adoption). The most frequent clinical indication in inv(9) carriers was "idiopathic reproductive failure" - 37.1 %. The spectra and percentages of indications in individuals with inv(9) were further statistically evaluated for one of the departments (N = 170) by comparing individuals with inv(9) to a control group of 661 individuals with normal karyotypes without this inversion. The proportion of clinical referrals for "idiopathic reproductive failure" among inv(9) cases remains higher than in controls, but the difference is not statistically significant for both genders combined. Analysis in separated genders showed that the incidence of "idiopathic reproductive failure" could differ among inv(9) female and male carriers.

Steroids pretreatment in assisted reproduction cycles.

The objective is to present an overview of trials and appreciate the relevant data on the effect of steroids pretreatment (oral contraceptives, 17ß-estradiol and estradiol valerate) in assisted reproduction cycles. The subject of the study is to evaluate the clinical characteristics during steroids pretreatment cycles focused on the prevention of ovarian cysts, the positive contraceptive effect on the onset of regular period during long gonadotropin releasing hormone agonist protocol. In gonadotropin releasing hormone antagonist protocol the review is interested in supporting ovarian stimulation in low responders, the idea of cycle scheduling and improving treatment outcomes. The method is a review from MEDLINE/Pubmed database between 1994 and July 2012. We identified 15 randomised controlled trials (n=3069 patients). One trail (n=83 patients) assessed GnRH agonist protocol with or without steroids pretreatment, 8 trials (n=1884 patients) assessed GnRH antagonist protocols with or without steroids pretreatment and 6 trials (n=1102 patients) assessed GnRH antagonist protocols versus agonist ones with steroid pretreatment. Data demonstrates that oral contraceptives offer the effective prevention of functional ovarian cysts, the predictable onset of period during desensitisation. Existing data suggest that pretreatment with oral contraceptive pills or estradiol valerate give no advantage concerning number of oocytes or pregnancy rate. Pretreatment with oral contraceptive pills aiming to avoid weekend oocytes retrievals has to be more elucidated. In low responders oral contraceptive pill pretreatment may be beneficial in improving ovarian responses by reducing the amount of gonadotropins and the number of days required for ovarian stimulation. Current research indicates that also 17ß-estradiol may be encouraging pretreatment in low responders and in cycle scheduling. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

Dynamics of fertility in patients on waiting list for kidney transplantation.

OBJECTIVES: To evaluate the presence of hormonal abnormalities and fertility disorders in patients with chronic kidney disease (CKD) awaiting renal transplantation. METHODS: From September 2009 to April 2011 all male patients with CKD awaiting kidney transplantation were investigated. The following tests were performed: semen analysis, serum concentration of testosterone, SHBG, LH, FSH and prolactin. Differences in hormone levels and sperm count parameters were statistically evaluated between the control group and the patient group. RESULTS: The group of patients consisted of 74 and the control group of 41 men. Average testosterone levels were lower in patients compared to control group. In patients significantly higher levels of SHBG, LH, FSH and PRL were found, and statistically significantly lower ejaculate volume, total sperm count, sperm concentration, total and progressive sperm motility and sperm morphology than in the control group. Within the group of patients a negative correlation between testosterone and PRL was found and a positive correlation between testosterone and total sperm motility and morphology. A negative correlation was detected between the duration of haemodialysis and testosterone, sperm concentration, total and progressive motility and sperm morphology. CONCLUSION: Significant changes in hormone levels and impaired fertility are found in haemodialyzed patients on a waiting list for kidney transplantation. The dynamics of these changes are dependent on the duration of haemodialysis (Tab. 4, Fig. 2, Ref. 15). Text in PDF www.elis.sk.

Hormones and endocrine disruptors in human seminal plasma.

Seminal plasma represents a unique environment for maturation, nutrition, and protection of male germ cells from damaging agents. It contains an array of organic as well as inorganic chemicals, encompassing a number of biologically and immunologically active compounds, including hormones. Seminal plasma contains also various pollutants transferred from outer environment known as endocrine disruptors. They interfere with hormones at the receptor level, act as inhibitors of their biosynthesis, and affect hormone regulation.In this minireview, the main groups of hormones detected in seminal plasma are summarized. Seminal gonadal steroids were investigated mostly with aim to use them as biomarkers of impaired spermatogenesis (sperm count, motility, morphology). Concentrations of hormones in the seminal plasma often differ considerably from the blood plasma levels in dependence on their origin. In some instances (dihydrotestosterone, estradiol), their informative value is higher than determination in blood.Out of peptide hormones detected in seminal plasma, peptides of transforming growth factor beta family, especially antimullerian hormone, and oligopeptides related to thyrotropin releasing hormone have the high informative value, while assessment of seminal gonadotropins and prolactin does not bring advantage over determination in blood.Though there is a large body of information about the endocrine disruptors' impact on male reproduction, especially with their potential role in decline of male reproductive functions within the last decades, there are only scarce reports on their presence in seminal plasma. Herein, the main groups of endocrine disruptors found in seminal plasma are reviewed, and the use of their determination for investigation of fertility disorders is discussed.

[Obesity and male infertility]. / Obezita a muzská neplodnost.

The authors present a review on the effects of obesity on male fertility. Current scientific findings suggest an elevated risk of infertility among couples in which the male partner is obese. In obese men can be found reduced serum levels of androgens and SHBG and increased estrogen levels without compensatory increase in FSH. Among other impacts of male obesity that may contribute to increased risk of infertility are altered retention and metabolism of environmental toxins, lifestyle, sexual dysfunction, genetic factors, excessive secretion of hormones derived from adipose tissue, oxidative stress, sperm specific proteomic changes or elevated levels of cytokines. The increasing prevalence of obesity calls for greater clinical awareness of its impact on male fertility.

Testicular sperm aneuploidy in non-obstructive azoospermic patients.

BACKGROUND: Non-obstructive azoospermic (NOA) men can father children after testicular sperm extraction (TESE). Previous studies suggest that they may be at risk of producing chromosomally abnormal spermatozoa, but the number of sperm analysed per patient was usually very low. METHODS: Multicolour fluorescence in situ hybridization was used for detection of chromosome 13, 15, 16, 18, 21, 22, X and Y disomy and diploidy in sperm obtained from NOA men (n = 17) and control donors (n = 10). At least 500 testicular sperm were scored in each patient to increase the precision of our study. RESULTS: The mean frequency of overall disomy (2.32%) and diploidy (0.80%) found in 13 689 testicular spermatozoa of NOA patients was significantly higher than in the ejaculated sperm of normospermic control donors, disomy (0.62%) and diploidy (0.29%). A highly significant increase in frequencies of chromosome 15, Y and overall disomy (P < 0.001), and a significant increase in disomy of chromosome 13 (P = 0.002), 16 (P = 0.031) and 21 (P = 0.018), overall diploidy (P = 0.031) and diploidy caused by errors in meiosis I (P = 0.011) were observed in the NOA group. CONCLUSIONS: Testicular sperm samples of NOA patients show a higher incidence of numerical chromosomal abnormalities compared with ejaculated sperm of control donors. Appropriate genetic counselling is necessary in NOA men undergoing TESE.

The content of five sex steroids in human testis.

In order to assess whether intratesticular hormone content may be helpful for prediction of successful conception in men with fertility problems, five sex steroids, testosterone, dihydrotestosterone, androstenedione, estradiol and, for the first time epitestosterone, were measured in testicular tissue obtained by surgical retrieval from total 84 men. The group consisted of non-obstructive azoospermic men, aged 21-67 years who attended the centre for in vitro fertilization. Steroids after ether extraction and solvent partition were separated by high performance liquid chromatography and then measured by specific radioimmunoassays. The values varied considerably with means ± S.D. 2.43±2.47, 0.27±0.24, 0.080±0.13, 0.071±0.089 and 0.31±0.27 for testosterone, dihydrotestosterone, androstenedione, estradiol and epitestosterone, respectively.

[Preimplantation genetic diagnosis (PGD) in carriers of chromosomal translocations: possibilities and results]. / Moznosti a výsledky preimplantacní genetické diagnostiky (PGD) u páru s chromozomální translokací.

AIM OF THE STUDY: To assess the PGD results in couples with robertsonian and reciprocal translocations. DESIGN: Retrospective study. SETTING: Sanatorium Pronatal, Prague, accredited IVF unit. METHODS: 94 infertile couples with translocation (44 couples with robertsonian and 50 couples with reciprocal translocations) were included in the study. The mean woman's age was not different: 33 +/- 4,4 in robertsonian vers. 33 +/- 3.9 in reciprocal translocations. The performance of FISH probes in specific cases was tested on patient's lymfocytes before the treatment was started. After ovarian stimulation (recombinant FSH or hMG + GnRH agonist, "long" protocol) and transvaginal oocyte pick-up, embryo biopsy of a single cell was performed 72 hours after fertilization. After blastomere fixation, translocated chromosomes + chromosomes 13, 18, 21, X and Y were tested using FISH. The maximum of two embryos euploid for detected chromosomes were transferred, supernumerary euploid embryos were frozen. RESULTS: From the total number of 629 embryos, 126 embryos (21.9%) were detected as normal or with balanced translocation--25.2% (68/270) in couples with robertsonian and 16.4% (59/359) with reciprocal translocation. Embryotransfer was performed in 30 cycles (68.2%) in robertsonian and 27 (54%) in reciprocal translocations. 24 pregnancies were achieved--15 (39% per cycle and 50% per ET) for robertsonian and 9 (19% per cycle and 33% per ET) for reciprocal translocation--this difference was statistically significant (p = 0.033). Only one pregnancy in each group ended as abortion. SUMMARY: IVF is a valuable option for couples with infertility problems and translocation. This technique allows in short-term a conception and delivery of a healthy baby with general better prognosis for couples with robertsonian translocation.

[Clinical effects of recombinant versus urinary gonadotropins in ovulation induction]. / Prokázané klinické ucinky rekombinantních gonadotropinu v porovnání s urinárními v indukci ovulace.

OBJECTIVE: To present an overview of trials and discussion focused on the clinical characteristics of recombinant gonadotropins compared with urinary ones in ovulation induction. SUBJECT: Review article. SETTING: Sanatorium Pronatal, Prague. SUBJECT AND METHOD: The subject of the study is to compare the clinical characteristics of recombinant gonadotropins versus urinary ones focused on the daily dose of FSH achieving FSH threshold and the risk of multifollicular development in ovulation induction before intrauterine insemination, number of follicles and oocytes, the risk of ovarian hyperstimulation syndrome (OHSS), total consumption of FSH, cost effectiveness and expected pregnancy rate during in vitro fertilization technique. The method is a MEDLINE research of articles from 1994 to 2010. CONCLUSIONS: Data demonstrates that recombinant FSH (rFSH) offers higher ovarian response, less consumption of gonadotropins, lower risk of complications (multiple pregnancy and OHSS) compared with urinary FSH (uFSH). Expected pregnancy rate is probably comparable.

[Comparison of human chorionic gonadotropin (Pregnyl 10 000 IU i.m.) versus GnRH agonist (triptorelin 0,2 mg s.c.) for final oocytes maturation in the same egg donors--clinical and embryological characteristics]. / Srovnání lidského choriového gonadotropinu (Pregnyl 10 000 IU i.m.) s GnRH agonistou (triptorelin 0.2 mg s.c.) pro maturaci oocytu u stejných dárkyn vajícek--klinické a embryologické charakteristiky.

OBJECTIVE: To compare clinical and embryological characteristics in donor cycles triggered for final oocytes maturation with Pregnyl 10 000 IU i.m. versus triptorelin 0.2 mg s.c. in the same patients in two sequential stimulation cycles. The aim of the study is to decrease the risk of the development of ovarian hyperstimulation syndrome (OHSS) at high response donors by the replacement of Pregnyl 10 000 IU i.m. vs. triptorelin 0.2 mg s.c. The administration of a single dose of gonadotropin-releasing hormone agonist (triptorelin 0.2 mg s.c.) induces release of LH from the pituitary gland similarly to a spontaneous LH surge. SUBJECT: Prospective cross-over trial. SETTING: Sanatorium Pronatal, Praha. SUBJECT AND METHOD: From August 2009 to July 2010 we analysed 24 stimulation cycles in 12 egg donors treated with GnRH antagonist protocol with recombinant FSH (follitropin beta). We identified patients with more than 15 follicles during examination by transvaginal ultrasound. When at least 3 leading follicles reached 17 mm in diameter we administrated Pregnyl 10 000 IU i.m. for final oocytes maturation and triptorelin 0.2 mg s.c in the subsequent treatment cycle. RESULTS: The primary outcome measure was number of oocytes, proportion mature oocytes and fertilized oocytes. The secondary outcome were duration of FSH stimulation, total dose of gonadotropins and mean daily dose of gonadotropins. Data was analysed by paired t-test. We retrieved 17.2 +/- 8.6 vs. 15.8 +/- 5.3 (ns) oocytes, 12.6 +/- 7.3 vs. 13.0 +/- 5.4 (ns) metaphase II oocytes, proportion of metaphase II oocytes (%) was 73 vs. 83 (ns), number of fertilized oocytes 11.5 +/- 6.7 vs. 11.7 +/- 4.5 (ns), fertilization rate (%) 91 vs. 90 (ns) in Pregnyl's vs. triptorelin's group, resp. Duration of FSH stimulation (days) 12.2 +/- 0.8 vs. 12.4 +/- 0.7 (ns), total dose of gonadotropins (IU) 1744 +/- 277 vs. 1740 +/- 276 (ns), mean daily dose of gonadotropins (IU) 238 +/- 43 vs. 221 +/- 36 (ns), were not statistically different in both groups. CONCLUSIONS: Number of mature oocytes and subsequent embryonic cleavage is comparable to standard hCG treatment. There are no differences in clinical and embryological characteristics in both groups. Only one patient with administration of Pregnyl 10 000 IU i.m. was treated for OHSS grade II by vaginal paracentesis. Administration of triptorelin 0.2 mg s.c. is a safe and effective approach to achieve mature oocytes in egg donation programme, where we do not take care of implantation, which has got some limitations based on several studies.

[Long GnRH agonist vs. GnRH antagonist protocol in randomized controlled trial in unselected patients--hormonal and cycle characteristics--pilot study]. / Randomizované srovnání dlouhého GnRH agonistického cs 0ynek7 vs. GnRH antagonistického protokolu--hormonální parametry a charakteristiky cyklui--pilotní studie.

OBJECTIVE: To evaluate hormonal and cycle characteristics (estradiol and LH level on day 5 and on the day of hCG administration) comparing long GnRH agonist vs. GnRH antagonist protocol for unselected patients. SUBJECT: Randomized prospective pilot study. SETTING: Sanatorium Pronatal, Praha. SUBJECT AND METHOD: From January 2006 to June 2006 we randomized 40 unselected patients into GnRH agonist (triptorelin 0.1 mg) and GnRH antagonist (cetrorelix 0.25 mg) group. We recommended starting dose from 150 to 225 IU of rFSH or hMG based on the response to clomifencitrate treatment. We examined follicular growth on day 5 and on day 8 by transvaginal ultrasound and estradiol (E2) level on day 5 and on the day of hCG administration. RESULTS: We randomized 21 patients in GnRH agonist and 19 patients in GnRH antagonist group. We proved E2 on day 5 (pg/ml) 269 +/- 243 vs. 385 +/- 293, LH on day 5 (IU/l) 1.7 +/- 1.2 vs. 2.8 +/- 1.4, E2 on the day of hCG administration (pg/ml) 1548 +/- 1167 vs. 1397 +/- 1076 (p < 0.05) and LH on the day of hCG administration (IU/l) 2.2 +/- 1.9 vs. 1.4 +/- 1.1 (ns), endometrial thickness (mm) 10.6 +/- 1.8 vs. 9.2 +/- 0.9 (ns), total dose of FSH (IU) 1865 +/- 517 vs. 1513 +/- 357 (p < 0.001), duration of FSH stimulation (days) 9.3 +/- 1.6 vs. 7.8 +/- 1.2 (p < 0.001) in GnRH agonist vs. GnRH antagonist group, resp. CONCLUSIONS: There are significant differences in hormonal characteristics and cycle characteristics comparing both protocols (longer duration of treatment and higher consumption of gonadotropins, higher E2 levels on the day of hCG administration in GnRH agonist compared to GnRH antagonist group).

Circulating neuroactive C21- and C19-steroids in young men before and after ejaculation.

Twelve neuroactive and neuroprotective steroids, androgens and androgen precursors i.e. 3alpha,17beta-dihydroxy-5alpha-androstane, 3alpha-hydroxy-5alpha-androstan-17-one, 3alpha-hydroxy-5beta-androstan-17-one, androst-5-ene-3beta,17beta-diol, 3beta,17alpha-dihydroxy-pregn-5-en-20-one (17alpha-hydroxy-pregnenolone), 3beta-hydroxy-androst-5-en-17-one (dehydroepiandrosterone, DHEA), testosterone, androst-4-ene-3,17-dione (androstenedione), 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), 3beta-hydroxy-pregn-5-en-20-one (pregnenolone), 7alpha-hydroxy-DHEA, and 7beta-hydroxy-DHEA were measured using the GC-MS system in young men before and after ejaculation provoked by masturbation. The circulating level of 17alpha-hydroxypregnenolone increased significantly, whereas the other circulating steroids were not changed at all. This fact speaks against the hypothesis that a drop in the level of neuroactive steroids, e.g. allopregnanolone may trigger the orgasm-related increase of oxytocin, reported by other authors.

[Reproductive medicine from childhood to adulthood]. / Reprodukcní medicína od detství po dospelost.

Modern era brought new diagnostic and therapeutic methods to endocrinology and changed the approach to many diseases and developmental disorders. Explosion of new findings brought about the possibility of examinations on subcellular level. Possibility to study structure and function of various genes is not any more the futurology. However, still in medicine romain a roas which are considered as less important. It is usually assumed that questions of fertility will be dealt by the specialist for adults. We suppose that the given problems should be well advised by an interdisciplinary co-operating team in the paediatric patients already. However, it should be recognised that some reproduction disorders have their origin in the early age. The aim of this paper is to give an overview on endocrine disorders in relation to reproduction impairments and to outline possibilities of co-operation between different specialist treating patients from childhood trough adulthood.

[Intracytoplasmic injections (ICSI) with epididymal and testicular spermatozoa]. / Intracytoplazmatická injekce (ICSI) s epididymálními a testikulárními spermiemi.

Azoospermia is no longer a clear indication for using donor sperm. Aspiration of epididymal sperm or extraction of testicular sperm offers the same hope of pregnancy as ICSI using ejaculated sperm. Not even the high effectiveness of ICSI should be the reason for less intensive efforts to assess the exact cause of azoospermia, in particular with regard to genetic aspects.