Subfertile Men Research Articles

Finasteride use in the male infertility population: effects on semen and hormonal parameters

ObjectiveThere are reports of infertile men on finasteride (F) with improved fertility after cessation. It is unknown how often subfertile men are on F, and the degree of semen improvement after cessation.DesignMen presenting for fertility evaluation from 2008-2012 on F, identified via prospective database.Materials and MethodsSemen & hormonal parameters were analyzed before & after F cessation; Student's t-test was used, P<0.05 indicative of significant differences.ResultsTabled 1Sperm counts while on finasteride and after discontinuationSperm Counts million/mLSperm Counts million/mLSperm Counts million/mLSperm Counts million/mL% Motile% Normal MorphologyInitial count < 5Initial count 5-15Initial count > 15All menNumber of men725141414Mean ± SD on Finasteride1.48 ± 1.1510.98 ± 0.5584.14 ± 42.7432.34 ± 46.6716.84 ± 11.2113.28 ± 17.63Mean ± SD after Finasteride discontinued23.54 ± 12.26149.85 ± 16.12264.43 ± 137.47127.62 ± 137.825.91 ± 23.4811.0 ± 9.3P value0.002 *0.05 *0.024 *0.002 *0.1830.844 Open table in a new tab ConclusionF, even at low doses used to treat hair loss, is associated with oligospermia in subfertile men. In this group, counts improved dramatically after F cessation. Hormones, sperm motility & morphology were unchanged. F should be discontinued in subfertile men with oligospermia, & used with caution in men interested in having children. ObjectiveThere are reports of infertile men on finasteride (F) with improved fertility after cessation. It is unknown how often subfertile men are on F, and the degree of semen improvement after cessation. There are reports of infertile men on finasteride (F) with improved fertility after cessation. It is unknown how often subfertile men are on F, and the degree of semen improvement after cessation. DesignMen presenting for fertility evaluation from 2008-2012 on F, identified via prospective database. Men presenting for fertility evaluation from 2008-2012 on F, identified via prospective database. Materials and MethodsSemen & hormonal parameters were analyzed before & after F cessation; Student's t-test was used, P<0.05 indicative of significant differences. Semen & hormonal parameters were analyzed before & after F cessation; Student's t-test was used, P<0.05 indicative of significant differences. ResultsTabled 1Sperm counts while on finasteride and after discontinuationSperm Counts million/mLSperm Counts million/mLSperm Counts million/mLSperm Counts million/mL% Motile% Normal MorphologyInitial count < 5Initial count 5-15Initial count > 15All menNumber of men725141414Mean ± SD on Finasteride1.48 ± 1.1510.98 ± 0.5584.14 ± 42.7432.34 ± 46.6716.84 ± 11.2113.28 ± 17.63Mean ± SD after Finasteride discontinued23.54 ± 12.26149.85 ± 16.12264.43 ± 137.47127.62 ± 137.825.91 ± 23.4811.0 ± 9.3P value0.002 *0.05 *0.024 *0.002 *0.1830.844 Open table in a new tab ConclusionF, even at low doses used to treat hair loss, is associated with oligospermia in subfertile men. In this group, counts improved dramatically after F cessation. Hormones, sperm motility & morphology were unchanged. F should be discontinued in subfertile men with oligospermia, & used with caution in men interested in having children. F, even at low doses used to treat hair loss, is associated with oligospermia in subfertile men. In this group, counts improved dramatically after F cessation. Hormones, sperm motility & morphology were unchanged. F should be discontinued in subfertile men with oligospermia, & used with caution in men interested in having children.

The effects of pyospermia and ureaplasma urealyticum culture positivity on semen quality in subfertile men

ObjectiveTo analyze the relationship between pyospermia, semen quality and the results of Ureaplasma urealyticum testing in subfertile men.DesignRetrospective Cohort Study.Materials and MethodsThis is a retrospective cohort study of subfertile men (n=122) visiting a single institution over a 5 year period with pyospermia and reflexive urine culture for Ureaplasma urealyticum. Study subjects had follow up semen analyses (SAs) no less than 28 days after Ureaplasma testing. The Wilcoxon rank-sum test was used to compare mean SAs before doxycycline treatment and to compare the change in mean SAs in pyospermic patients with positive (n=9) vs. negative (n=113) Ureaplasma cultures.ResultsComparison of pyospermic men after antibiotic treatment with positive vs. negative. Ureaplasma cultures revealed no statistical difference in incident semen leukocyte levels (3.73 vs. 2.59 x 106 WBC/mL, p = 0.92), volume (2.0 vs. 2.79 mL, p = 0.15), concentration (39.43 vs. 49.27 M/mL, p = 0.95), motility (44.89% vs. 50.73, p = 0.31), or strict morphology (5.0 vs. 4.97%, p = 0.40). Comparison of the change between incident and follow up semen analyses after antibiotic treatment in positive vs. negative Ureaplasma cultures did not reveal a statistically significant difference in change in semen leukocyte levels (-0.2 vs. -1.66 x 106 WBC/mL, p = 0.50), volume (-0.17 vs. -0.05 mL, p = 0.55), concentration (6.88 vs. -0.56 M/mL, p = 0.85), motility (8.56 vs. -0.11%, p = 0.16), or strict morphology (0.67 vs. -1.12%, p = 0.18).ConclusionUreaplasma culture positivity does not influence semen parameters and reflexive Ureaplasma testing in the setting of pyospermia may be of limited utility. ObjectiveTo analyze the relationship between pyospermia, semen quality and the results of Ureaplasma urealyticum testing in subfertile men. To analyze the relationship between pyospermia, semen quality and the results of Ureaplasma urealyticum testing in subfertile men. DesignRetrospective Cohort Study. Retrospective Cohort Study. Materials and MethodsThis is a retrospective cohort study of subfertile men (n=122) visiting a single institution over a 5 year period with pyospermia and reflexive urine culture for Ureaplasma urealyticum. Study subjects had follow up semen analyses (SAs) no less than 28 days after Ureaplasma testing. The Wilcoxon rank-sum test was used to compare mean SAs before doxycycline treatment and to compare the change in mean SAs in pyospermic patients with positive (n=9) vs. negative (n=113) Ureaplasma cultures. This is a retrospective cohort study of subfertile men (n=122) visiting a single institution over a 5 year period with pyospermia and reflexive urine culture for Ureaplasma urealyticum. Study subjects had follow up semen analyses (SAs) no less than 28 days after Ureaplasma testing. The Wilcoxon rank-sum test was used to compare mean SAs before doxycycline treatment and to compare the change in mean SAs in pyospermic patients with positive (n=9) vs. negative (n=113) Ureaplasma cultures. ResultsComparison of pyospermic men after antibiotic treatment with positive vs. negative. Ureaplasma cultures revealed no statistical difference in incident semen leukocyte levels (3.73 vs. 2.59 x 106 WBC/mL, p = 0.92), volume (2.0 vs. 2.79 mL, p = 0.15), concentration (39.43 vs. 49.27 M/mL, p = 0.95), motility (44.89% vs. 50.73, p = 0.31), or strict morphology (5.0 vs. 4.97%, p = 0.40). Comparison of the change between incident and follow up semen analyses after antibiotic treatment in positive vs. negative Ureaplasma cultures did not reveal a statistically significant difference in change in semen leukocyte levels (-0.2 vs. -1.66 x 106 WBC/mL, p = 0.50), volume (-0.17 vs. -0.05 mL, p = 0.55), concentration (6.88 vs. -0.56 M/mL, p = 0.85), motility (8.56 vs. -0.11%, p = 0.16), or strict morphology (0.67 vs. -1.12%, p = 0.18). Comparison of pyospermic men after antibiotic treatment with positive vs. negative. Ureaplasma cultures revealed no statistical difference in incident semen leukocyte levels (3.73 vs. 2.59 x 106 WBC/mL, p = 0.92), volume (2.0 vs. 2.79 mL, p = 0.15), concentration (39.43 vs. 49.27 M/mL, p = 0.95), motility (44.89% vs. 50.73, p = 0.31), or strict morphology (5.0 vs. 4.97%, p = 0.40). Comparison of the change between incident and follow up semen analyses after antibiotic treatment in positive vs. negative Ureaplasma cultures did not reveal a statistically significant difference in change in semen leukocyte levels (-0.2 vs. -1.66 x 106 WBC/mL, p = 0.50), volume (-0.17 vs. -0.05 mL, p = 0.55), concentration (6.88 vs. -0.56 M/mL, p = 0.85), motility (8.56 vs. -0.11%, p = 0.16), or strict morphology (0.67 vs. -1.12%, p = 0.18). ConclusionUreaplasma culture positivity does not influence semen parameters and reflexive Ureaplasma testing in the setting of pyospermia may be of limited utility. Ureaplasma culture positivity does not influence semen parameters and reflexive Ureaplasma testing in the setting of pyospermia may be of limited utility.

Sperm chromatin dispersion (SCD) test identifies more spermatozoa with DNA damage than the TUNEL assay in men with unexplained infertility

Sperm chromatin dispersion (SCD) test identifies more spermatozoa with DNA damage than the TUNEL assay in men with unexplained infertility

Spectral Doppler Sonography

Sonography is a noninvasive, office-based diagnostic tool often used for evaluation of subfertile men. Previous studies have suggested that a resistive index (RI) greater than 0.6 is associated with impaired spermatogenesis. We sought to validate this threshold in a urologic patient population presenting for infertility evaluation. We retrospectively reviewed 99 consecutive patients seen for nonobstructive male infertility at our institution. Patient demographics, semen analysis parameters, hormone profiles, lipid profiles, and penile and scrotal sonographic measurements were recorded. The RI was calculated from measurements of the peak systolic velocity and end-diastolic velocity. Ninety-one patients fit the inclusion criteria and were subsequently divided into 2 groups based on RI: group 1 with RI values of 0.6 or less (n = 49) and group 2 with RI values greater than 0.6 (n = 42). Variables that were significantly different between the groups included age, total sperm count, percent motile sperm, total motile sperm, follicle-stimulating hormone, high-density lipoprotein, and testis volume. On the other hand, body mass index, forward progression, World Health Organization score, total testosterone, free testosterone, estradiol, total cholesterol, low-density lipoprotein, and triglycerides were not significantly different between the groups. A receiver operating characteristic curve revealed an area under the curve of 0.64 (confidence interval, 0.52-0.75; P = .025). At the threshold of greater than 0.6, the RI had specificity of 63.27% and a 1.56 likelihood ratio to predict total motile sperm less than 20 × 10(6) at spermatogenesis. An intratesticular RI greater than 0.6 is associated with impaired spermatogenesis. This finding supports the use of testicular spectral Doppler sonography as a noninvasive tool for evaluation of testicular function.

Telling sperm to sort themselves out

Telling sperm to sort themselves out

Testicular microlithiasis in Japanese male infertility patients: Clinical implications for predicting future testicular malignancy.

e15579 Background: Testicular microlithiasis (TM) is commonly diagnosed by scrotal ultrasonography (US) in which it appears as multiple, small, uniform, echogenic foci without shadowing, scattered randomly throughout the testicular parenchyma. It is also prevalent in several urologic diseases including subfertility and testicular germ cell tumor. TM has been reported to be associated with carcinoma in situ (CIS) and the development of second testicular germ cell tumor (TGCT) after contralateral orchiectomy treatment for primary TGCT; however, no prospective studies have investigated the relationship between the detection of TM in patients without TGCT and future development of TGCT. In the present study, therefore, we investigated the prevalence of TM in the testes of male infertility patients and unilateral TGCT patients to determine if TM could be a predictor of future germ cell tumor in such patients. Methods: A total of 1,139 subfertile patients (296 with nonobstructive azoospermia, 58 with obstructive azoospermia, and 785 with oligozoospermia) and 22 unilateral testicular germ cell tumor patients were enrolled in the study. Prevalence of testicular microlithiasis according to testicular ultrasonography was compared between patients, and development of testicular germ cell tumors was monitored for at least 3 years. All patients were fully informed about the study, and their prior consent was obtained according to the recommendation of the institutional ethics committee. Results: The prevalence of TM was significantly higher in unilateral TGCT patients (40.9%) than in subfertile men (8.6%). No infertile patients without TM developed TGCT but one infertile patient with TM developed TGCT (seminoma) during follow up. One seminoma patient with TM in his remaining testis went on to developed testicular seminoma 3years after primary surgery. Conclusions: Testicular microlithiasis is more common in testicular germ cell tumor patients than in subfertile men. Since TM could be a surrogate marker for future TGCT in both patient populations, TM patients are recommended to perform careful self-checking of the testes and periodical testicular ultrasonography.

Is thioredoxin reductase involved in the defense against DNA fragmentation in varicocele?

We aimed to investigate the role of thioredoxin reductase (TR) and inducible heat shock protein 70 (iHsp70) and their relationship with sperm quality in varicocele (VAR) patients. Semen samples were obtained from 16 subfertile men diagnosed as VAR and 10 fertile men who applied to the Andrology Laboratory of Istanbul Medical Faculty of Istanbul University. The sperm TR and iHsp 70 expression levels were determined using Western blot analysis. The TR activity of the sperm was assayed spectrophometrically. The sperm quality was evaluated both by conventional sperm analysis and by a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique that assayed DNA-fragmented spermatozoa in semen samples. The percentage of TUNEL-positive spermatozoa in the VAR group (16.3%± 5.6%) was higher than that in the fertile group (5.5%± 1.9%). Significant inverse correlations were detected between the percentage of TUNEL-positive cells and both the concentration (r=-0.609; P=0.001) and motility (r=-0.550; P=0.004) of spermatozoa. Both the TR expression and activity were increased significantly in the VAR group (U=22.0; P=0.001 and U=33.5; P=0.012, respectively) as analyzed using the Mann-Whitney U Wilcoxon rank sum W test. Furthermore, significant positive correlations were found between TR expression and activity (r=0.406; P=0.040) and between TR expression and the percentage of TUNEL-positive cells (r=0.665; P=0.001). Sperm iHsp70 expression did not differ between the VAR and fertile groups. In conclusion, increased sperm TR expression might be a defense mechanism against apoptosis in the spermatozoa of men with VAR.

2029 SPERM PROTAMINE MRNA RATIO AS A CLINICAL PARAMETER TO ESTIMATE THE FERTILIZING POTENTIAL OF MEN TAKING PART IN AN IVF/ICSI PROGRAM

You have accessJournal of UrologyInfertility: Basic Research, Physiology, Pathophysiology1 Apr 20132029 SPERM PROTAMINE MRNA RATIO AS A CLINICAL PARAMETER TO ESTIMATE THE FERTILIZING POTENTIAL OF MEN TAKING PART IN AN IVF/ICSI PROGRAM Nina Rogenhofer, Temuujin Dansranjavin, Martin Schorsch, Andrej Spiess, Hongxiang Wang, von Schönfeldt Viktoria, Heike Cappallo-Obermann, Vera Baukloh, Hao Yang, Agnieszka Paradowska, Bin Chen, Christian Thaler, Wolfgang Weidner, Hans-Christian Schuppe, and Klaus Steger Nina RogenhoferNina Rogenhofer Munich, Germany More articles by this author , Temuujin DansranjavinTemuujin Dansranjavin Giessen, Germany More articles by this author , Martin SchorschMartin Schorsch Wiesbaden, Germany More articles by this author , Andrej SpiessAndrej Spiess Hamburg, Germany More articles by this author , Hongxiang WangHongxiang Wang Shanghai, China, People's Republic of More articles by this author , von Schönfeldt Viktoriavon Schönfeldt Viktoria Munich, Germany More articles by this author , Heike Cappallo-ObermannHeike Cappallo-Obermann Hamburg, Germany More articles by this author , Vera BauklohVera Baukloh Hamburg, Germany More articles by this author , Hao YangHao Yang Shanghai, China, People's Republic of More articles by this author , Agnieszka ParadowskaAgnieszka Paradowska Giessen, Germany More articles by this author , Bin ChenBin Chen Shanghai, China, People's Republic of More articles by this author , Christian ThalerChristian Thaler Munich, Germany More articles by this author , Wolfgang WeidnerWolfgang Weidner Giessen, Germany More articles by this author , Hans-Christian SchuppeHans-Christian Schuppe Giessen, Germany More articles by this author , and Klaus StegerKlaus Steger Giessen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2448AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Production of competent sperm requires replacement of DNA-binding histones by protamines. In man, the relative proportion of protamine-1 to protamine-2 is regulated at approximately an 1:1 ratio. Numerous studies reported a correlation between an aberrant protamine ratio and male infertility. We performed a multicentre study to analyse prognostic value and clinical utility of the protamine ratio in ejaculated spermatozoa for the discrimination between fertile and subfertile men. Furthermore, it should be investigated whether the protamine ratio correlates with fertilization and pregnancy rates of infertile couples undergoing IVF or ICSI. METHODS Semen was obtained from 306 patients, whose female partners took part in an IVF (n=76, Hamburg, Shanghai) or an ICSI (n=230, Munich, Wiesbaden) program. 32 healthy volunteers revealing normozoospermia served as control. The protamine ratio was determined applying real-time quantitative RT-PCR. RESULTS 1. The protamine ratio discriminates between fertile and subfertile men. While the protamine ratio in IVF patients is similar to that of normozoospermic healthy volunteers (0.98±0.3), it is significantly different from that of ICSI patients (Munich 0.81±0.1, Wiesbaden 0.78±0.2; p<0.001). (2) Normal protamine ratio was associated with a significantly higher total motile sperm count (TMSC) compared to semen samples with an aberrant protamine mRNA ratio (IVF, p=0.004; ICSI, p=0.027). Analysing single read-out parameters reflecting sperm quality in ejaculates from IVF patients, 58%±16% of sperm with a normal protamine ratio were progressive motile, while the respective proportion of sperm with an aberrant protamine ratio was only 33%±19% (p<0.001). (3) Sperm with normal protamine ratio reveal higher fertilization capacity in both IVF and ICSI. 53.6% of IVF patients with a normal protamine mRNA ratio exhibited a fertilizing capacity of ≥80%, while 78.9% with an aberrant protamine ratio displayed a fertilizing capacity of <80% (p=0.017). In ICSI patients, 65.1% with a normal protamine ratio reveal a fertilizing capacity of ≥70%, whereas 56.0% with an aberrant protamine ratio display a fertilizing capacity of <70% (p=0.028). CONCLUSIONS The protamine mRNA ratio clearly discriminates between fertile and subfertile men and therefore represents an excellent prognostic marker to estimate the sperm fertilizing potential in patients with an infertile relationship in addition to standard semen parameters. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e833 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nina Rogenhofer Munich, Germany More articles by this author Temuujin Dansranjavin Giessen, Germany More articles by this author Martin Schorsch Wiesbaden, Germany More articles by this author Andrej Spiess Hamburg, Germany More articles by this author Hongxiang Wang Shanghai, China, People's Republic of More articles by this author von Schönfeldt Viktoria Munich, Germany More articles by this author Heike Cappallo-Obermann Hamburg, Germany More articles by this author Vera Baukloh Hamburg, Germany More articles by this author Hao Yang Shanghai, China, People's Republic of More articles by this author Agnieszka Paradowska Giessen, Germany More articles by this author Bin Chen Shanghai, China, People's Republic of More articles by this author Christian Thaler Munich, Germany More articles by this author Wolfgang Weidner Giessen, Germany More articles by this author Hans-Christian Schuppe Giessen, Germany More articles by this author Klaus Steger Giessen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

2028 ROLE OF EPIGENETICALLY MODIFIED HISTONE H4 (H4K12AC) FOR HUMAN SPERM TRANSCRIPTS AND MURINE PRONUCLEUS FORMATION

INTRODUCTION AND OBJECTIVES: Histone H4 acetylated at lysine K12 (H4K12ac) represents an activating epigenetic mark, which is present within sperm and prior to full decondensation of sperm chromatin during early embryogenesis. Together with silent sperm mRNAs, it may represent an epigenetic fingerprint monitoring past events of spermatogenesis with possible impact also on early embryo development. We therefore aimed to analyze whether association of H4K12ac with specific gene promoters is correlated with silent sperm mRNAs. Furthermore, the role of paternally derived H4K12ac for early embryo development should be clarified in the mouse model. METHODS: Sperm from fertile and subfertile men were subjected to ChIP-on-chip using anti-H4K12ac antibody. Data set was compared with genome-wide expression profiling of sperm mRNA. Functional studies comprized IVF in mice. RESULTS: In sperm from fertile men, H4K12ac-associated gene promoters expressed high levels of mRNAs. Many of these transcripts are coding testis-specific proteins, such as PHD finger protein 7 (PHF7) or testis development protein (NYD-SP6). Aberrant mRNA levels of these testis-specific genes were observed in subfertile patients. Immunofluorescence analysis of mouse preimplantation embryos revealed a strong signal for H4K12ac in the male pronuclus and a weaker signal in the female pronucleus. During pronuclei migration and at pronuclei fusion, an increasing H4K12ac signal could be observed in the female pronucleus, while the male pronucleus remained strongly labelled. CONCLUSIONS: Aberrant acetylation of H4K12ac within developmentally important gene promoters may reflect insufficient sperm chromatin compaction in subfertile men followed by inappropriate transfer of epigenetic information to the oocyte.

Increased numbers of DNA-damaged spermatozoa in samples presenting an elevated rate of numerical chromosome abnormalities

Is there a relationship between DNA damage and numerical chromosome abnormalities in the sperm of infertile patients? A strong link between DNA fragmentation and the presence of numerical chromosome abnormalities was detected in human sperm. Chromosomally abnormal spermatozoa were more likely to be affected by DNA fragmentation than those that were chromosomally normal. Several studies have described the presence of elevated levels of DNA damage or chromosome defects in the sperm of infertile or subfertile men. However, the nature of the relationship between sperm DNA damage and chromosome abnormalities is poorly understood. The fact that some assisted reproductive techniques have the potential to allow abnormal spermatozoa to achieve oocyte fertilization has led to concerns that pregnancies achieved using such methods may be at elevated risk of genetic anomalies. For this prospective study, semen samples were collected from 45 infertile men. Samples were assessed for DNA fragmentation using the Sperm Chromatin Dispersion Test (SCDt) and for chromosome abnormalities using multi-colour fluorescence in situ hybridization (FISH) with probes specific to chromosomes 13, 16, 18, 21, 22, X and Y. Additionally, both parameters were assessed simultaneously in 10 of the samples using a protocol combining SCDt and FISH. A significant correlation between the proportion of sperm with a numerical chromosome abnormality and the level of DNA fragmentation was observed (P < 0.05). Data from individual spermatozoa subjected to combined chromosome and DNA fragmentation analysis indicated that chromosomally abnormal sperm cells were more likely to display DNA damage than those that were normal for the chromosomes tested (P < 0.05). Not only was this association detected in samples with elevated levels of numerical chromosome abnormalities, but it was also evident in samples with chromosome abnormality rates in the normal range. The inability to assess the entire chromosome complement is the main limitation of all studies aimed at assessing numerical chromosome abnormalities in sperm samples. As a result, some of the sperm classified as 'chromosomally normal' may be aneuploid for chromosomes that were not tested. During spermatogenesis, apoptosis (a process that involves active DNA degradation) acts to eliminate abnormal sperm. Failure to complete apoptosis may explain the coincident detection of aneuploidy and DNA fragmentation in some spermatozoa. In addition to shedding light on the biological mechanisms involved in the processing of defective sperm, this finding may also be of clinical relevance for the identification of patients at increased risk of miscarriage or chromosomally abnormal pregnancy. In some instances, detection of elevated sperm DNA fragmentation may indicate the presence of chromosomal abnormalities. It may be worth considering preimplantation genetic screening (PGS) of embryos produced using such samples in order to minimize the risk of aneuploidy.

32 The depletion of H4K12ac within developmentally relevant promoters is not accompanied by alteration of DNA methylation in sperm of subfertile men.

32 The depletion of H4K12ac within developmentally relevant promoters is not accompanied by alteration of DNA methylation in sperm of subfertile men.

The sperm protamine mRNA ratio as a clinical parameter to estimate the fertilizing potential of men taking part in an ART programme

Could the protamine-1 to protamine-2 mRNA ratio serve as a biomarker to estimate the fertilizing capacity of sperm from men taking part in an IVF/ICSI programme? The protamine mRNA ratio clearly discriminates between fertile and subfertile men and sperm with a normal protamine mRNA ratio exhibit a higher fertilizing capacity in IVF/ICSI. Aberrant sperm protamine ratios are associated with male factor infertility and mRNA ratio is comparable with protein ratio (due to transcriptional stop in elongating spermatids). The study population was drawn from subfertile men, whose female partners participated in IVF or ICSI programmes between September 2010 and February 2012. Normozoospermic healthy volunteers served as controls. Sperm cells were lysed, mRNA extracted, reverse transcribed and subjected to real-time quantitative PCR using specific primer pairs for protamine-1 and protamine-2. Relative protamine-1 and protamine-2 mRNA levels were analysed with the Mann-Whitney U-test (two-tailed). Quantitative RT-PCR for protamines 1 and 2 has been performed in ejaculates from 32 normozoospermic volunteers (control, University Clinic Giessen, Germany) and 306 patients, whose female partners took part in an IVF (n = 76; University Clinic Hamburg, Germany and Shanghai Jiaotong University, China) or an ICSI (n = 230; University Clinic Munich, Germany and Kinderwunschzentrum Wiesbaden, Germany) programme. The sperm protamine mRNA ratio in normozoospermic men (0.98 ± 0.3) differed significantly from that of ICSI patients (Munich 0.81 ± 0.1; Wiesbaden 0.78 ± 0.2; P < 0.001), while processed samples obtained from IVF patients revealed a normal protamine mRNA ratio (Hamburg 1.0 ± 0.07; Shanghai 1.0 ± 0.54). Normal protamine mRNA ratios were associated with a significantly higher total motile sperm count and a significantly higher percentage of progressively motile sperm. Sperm with a normal protamine mRNA ratio revealed a higher fertilization capacity (fc) in both IVF (53.6% of patients with fc > 80%; P = 0.017) and ICSI (65.1% of patients with fc > 70%; P = 0.028). The protamine mRNA ratio in an individual sperm cell used for ICSI may be different from the overall value obtained from a semen aliquot. Data are in line with current literature and suggest the protamine mRNA ratio as a diagnostic marker to estimate the fertilizing capacity of sperm. The German Research Foundation (DFG) to K.S., W.W. and A.P. (STE 892/9-2), as well as to A.S. and H.C.O. (SP721/1-3). None.

The apoptotic pathway in fertile and subfertile men: a case-control and prospective study to examine the impact of merocyanine 540 bodies on ejaculated spermatozoa

To evaluate the presence of merocyanine 540 (M540) bodies and their impact on the measurement of apoptotic biomarkers in human spermatozoa. Case-control, prospective study. Academic centers. Fertile and subfertile subjects. Semen samples from subfertile and fertile men, 11 per group, were analyzed for basic semen parameters and early (annexin-V binding) and late (terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) sperm apoptotic biomarkers by flow cytometry. Samples were also stained with M540 to assess the presence of M540 apoptotic bodies. Presence of M540 apoptotic bodies. Groups differed significantly in the expression of early and late apoptosis biomarkers. The percentage of M540 bodies between groups was not different. The exclusion of M540 bodies from TUNEL results did not have a significant impact on measurement in either fertile or subfertile groups. This study confirmed the occurrence of M540 bodies in semen and that male factor infertility is associated with an increased expression of apoptosis biomarkers. Moreover, we demonstrated that the presence of M540 bodies did not affect the quantification of apoptotic biomarkers in either group.

Impact of Surgical Varicocele Repair on Pregnancy Rate in Subfertile Men With Clinical Varicocele and Impaired Semen Quality: A Meta-Analysis of Randomized Clinical Trials

PurposeTo elucidate the impact of surgical varicocele repair on the pregnancy rate through new meta-analyses of randomized clinical trials that compared surgical varicocele repair and observation.Materials and MethodsThe PubMed and Embase online databases were searched for studies released before December 2012. References were manually reviewed, and two researchers independently extracted the data. To assess the quality of the studies, the Cochrane risk of bias as a quality assessment tool for randomized controlled trials was applied.ResultsSeven randomized clinical trials were included in our meta-analyses, all of which compared pregnancy outcomes between surgical varicocele repair and control. There were differences in enrollment criteria among the studies. Four studies included patients with clinical varicocele, but three studies enrolled patients with subclinical varicocele. Meanwhile, four trials enrolled patients with impaired semen quality only, but the other three trials did not. In a meta-analysis of all seven trials, a forest plot using the random-effects model showed an odds ratio (OR) of 1.90 (95% confidence interval [CI], 0.77 to 4.66; p=0.1621). However, for subanalysis of three studies that included patients with clinical varicocele and abnormal semen parameters, the fixed-effects pooled OR was significant (OR, 4.15; 95% CI, 2.31 to 7.45; p<0.001), favoring varicocelectomy.ConclusionsVaricocelectomy for male subfertility is proven effective in men with clinical varicocele and impaired semen quality. Therefore, surgical repair should be offered as the first-line treatment of clinical varicocele in subfertile men.

Folic acid does not improve semen parametrs in subfertile men: A double-blin, randomized, placebo-controlled study

Folic acid does not improve semen parametrs in subfertile men: A double-blin, randomized, placebo-controlled study

The Key Role of Zinc in Enhancement of Total Antioxidant Levels in Spermatozoa of Patients with Asthenozoospermia

Semen samples were obtained from 60 fertile (age 31.6 ± 3.3 years) and 60 subfertile (age 32.5 ± 3.23 years) men with asthenozoospermia between July 2011 to July 2012, from couples who had consulted the infertility clinic of Babil Hospital of Maternity (Hilla city/ IRAQ). The subfertile group was treated with zinc sulfate, with every participant taking two capsules of zinc sulfate per day for three months (each one 220mg). Semen samples were obtained (before and after zinc sulfate supplementation). After liquefaction, seminal fluid at room temperature, routine semen analyses were performed. Total antioxidant capacity (TAC) and various sperm parameters were compared among fertile controls and infertile patients (before and after treatment with zinc sulfate). The mean antioxidant capacity of fertile controls (1.557 mmol/L in seminal plasma & 0.605 mmol/10 6 spermatozoa in spermatozoa) was significantly higher than that of the infertile patient group (1.157 mmol/L in seminal plasma & 0.528 mmol/106 spermatozoa in spermatozoa) (p<0.05). Furthermore, TAC levels were significantly higher in the infertile group which treated with zinc sulfate (1.585 mmol/L in seminal plasma & 0.573 mmol/10 6 spermatozoa in spermatozoa) (p<0.05). On the other hand, antioxidant capacity is positively correlated with sperm motility. Decreased antioxidant capacity was associated with impaired sperm function as a result of either increased ROS production or inadequate antioxidant capacity. Volume of semen, progressive sperm motility percentage, and total normal sperm count were increased after zinc sulfate supplementation.

Assessment of the infertile male

Key content Male factors alone account for up to 30% of subfertile couples undergoing in vitro fertilisation. Male infertility may be due to problems with sperm production or transport and also sexual dysfunction. The underlying cause in most cases is idiopathic. Modifiable lifestyle factors can have an impact on male fertility, but medical treatments have a limited value in enhancing semen quality. Most treatments are based on assisted fertilisation techniques, rather than treatment of the underlying cause. The number and quality of sperm that can be recovered, either from the ejaculate or surgically, determines the available options for assisted conception. Intracytoplasmic sperm injection (ICSI) is considered relatively safe; however, because of the ability to bypass natural barriers to conception, there are concerns regarding its potential to transmit genetic defects. Learning objectives To review appropriate practice in the assessment and investigation of the infertile male. To critically appraise the currently available investigations for male fertility. To summarise the treatment options for subfertile men. Ethical issues Does ICSI propagate genetic causes of male infertility? Could there ever be a role for the use of artificial sperm in assisted reproduction?

Clinical value of sperm DNA damage should be assessed in motile sperm fraction rather than whole ejaculated sperm

To determine differences and frequency of excessive (≥50%) sperm DNA damage between ejaculated and motile sperm. Sperm DNA damage was assessed by acridine orange fluorescence and the results of ejaculated and motile sperm were compared. Public and private clinical assisted reproduction centers. A total of 272 subfertile men were studied. None. Semen analysis and sperm DNA damage. Sperm DNA damage was negatively correlated with sperm motility and normal morphology. Overall, 39.7% (108 of 272) of semen samples had excessive sperm DNA damage. In contrast, only 15% (41 of 272) of motile sperm fractions had excessive DNA damage. Based on DNA results of motile sperm and semen characteristics, the proportion of men with excessive sperm DNA damage was 26% in severe teratozoospermia, 17.5% in oligozoospermia, 12.5% in moderate teratozoospermia, and 4.6% in normozoospermia. Severe teratozoospermia had five times more frequent excessive DNA damage than normozoospermia. Abnormal sperm morphology is highly associated with sperm DNA damage. Results of DNA damage of ejaculated sperm do not accurately reflect DNA status of motile sperm. Therefore, sperm DNA damage should be assessed in motile sperm fraction rather than whole ejaculated sperm.

The value of chromosomal analysis in oligozoospermic men

To determine the prevalence of chromosomal abnormalities in relation to sperm concentration in subfertile oligozoospermic men. Retrospective cohort study. Two teaching hospitals. We retrospectively studied all men who received chromosomal analysis prior to intracytoplasmic sperm injection (ICSI) treatment from 2000 to 2010 in two teaching hospitals. None. The results of chromosomal analysis and semen analysis were recorded. The frequency of abnormal karyotypes was analyzed in relation to the sperm concentration, categorized as extreme oligozoospermia (>0 to ≤1 million/mL), severe oligozoospermia (>1 to ≤5 million/mL), moderate oligozoospermia (>5 to ≤20 million/mL), or normospermia (>20 million/mL). Among 582 male ICSI candidates, the rates of abnormal karyotypes were 1.2% (2/162), 2.2% (5/227), and 1.5% (2/130) for men with extreme, severe, and moderate oligozoospermia, respectively. No abnormalities were present in normospermic men. The risk of conceiving a viable child with unbalanced structural chromosomal abnormalities in men with oligozoospermia may not justify karyotyping.

The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

Is there an association between high levels of sperm DNA damage and miscarriage? Miscarriage rates are positively correlated with sperm DNA damage levels. Most ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates. A systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012. We used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment. We identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P < 0.00001). There is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss. The use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy. None.