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Phthalic acid esters (PAEs) are recognized endocrine disruptors. Detection of PAEs in semen from idiopathic infertile males suggests possible direct mechanisms of sperm toxicity. In this study we aimed to correlate sperm function with semen levels of PAEs. Semen samples were obtained from 100 male patients attending the Unit of Andrology and Reproductive Medicine, University Hospital of Padova, (Italy), 22 of which having a recognized history of idiopathic infertility. Compared to fertile subjects, infertile patients showed reduced levels of acrosome reaction (AR), evaluated by CD46 staining upon progesterone (P4) triggering (p < 0.001). Subjects showing positive detection of PAEs in semen, evaluated by liquid chromatography-mass spectrometry (LC-MS), were significantly more represented in those reporting an history of infertility (13 out of 22), compared to fertile subjects (25 out of 78, P = 0.0266). In vitro sperm exposure to PAEs showed that lipophilic PAE representative Di-n-octyl phthalate (DNOP) had higher cell accumulation and inhibition of P4-induced AR than less lipophilic PAE representative Dibutyl phthalate (DBP). Computer-based binding analysis and fluorimetric inhibition assay, showed that both DNOP and DBP had similar Phospholipase-A2 (PLA 2 ) inhibitory activity (respectively: 3.98 nM and 5.52 nM). However, only DNOP showed a significant inhibition of PLA 2 -mediated AR, triggered by A23187 calcium ionophore. Incubation with PLA 2 -related product arachidonic acid restored AR. Our data are suggestive of a novel mechanistic model of PAEs interference on sperm function, through the inhibition of PLA 2 -mediated signaling. According to this hypothesis, the inhibitory efficacy of the specific PAE is possibly linked to the corresponding cell accumulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Telomeres are repeated DNA sequences whose main function is to preserve genome stability, protecting chromosomes ends from shortening caused by progressive loss during each cell replication or DNA damage. Telomere length regulation is normally achieved by telomerase enzyme, whose activity is progressively shut off during embryonic differentiation in somatic tissues, whereas it is maintained in germ cells, activated lymphocytes, and certain types of stem cell populations. The maintenance of telomerase activity for a longer time is necessary for germ cells to delay telomere erosion, thus avoiding chromosome segregation defects that could contribute to aneuploid or unbalanced gametes. Over the last few years, telomere biology has become an important topic in the field of human reproduction, encouraging several studies to focus on the relation between telomere length and spermatogenesis and male fertility, embryo development and quality during assisted reproductive treatment, and female pathologies as polycystic ovary, premature ovarian insufficiency, and endometriosis. This review analyzes whether telomere length in germ cells is related to reproduction fitness, whether telomere length is related to pathologies associated with male and female fertility, and whether measurement of telomere length could represent a biomarker of germ cell and embryo quality. Telomere length could be considered a molecular marker of spermatogenesis and sperm quality and is somewhat related to male fertility potential. Fewer evidence, although promising, is available for oocytes, female (in)fertility, and embryo quality. The increasing evidence for a role of telomeres and telomere length in human reproduction, indeed, has expanded the historical view of considering them just a marker of aging. Telomere length might have in the future a prognostic potential in couple infertility, especially useful to select best germ cells with the greatest potential of fertilization., (© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction.)

Context: Mutations in the androgen receptor (AR) gene might be associated with infertility mainly because they cause various degrees of androgen insensitivity. Objective: The aim of the study was to evaluate the frequency and type of AR variants in a large cohort of infertile males. Methods: A total of 8224 males of Italian idiopathic infertile couples were referred to the University Hospital of Padova. The main outcome measures were mutational screening of AR, computational, and functional analyses. Results: We found 131 patients (1.6%) harboring 45 variants in AR gene, of which 18 were novel missense AR variants. Patients with AR gene variants had lower sperm count (P= .048), higher testosterone (T) concentration (P< .0001), and higher androgen sensitivity index (ASI) (luteinizing hormone × T, P<.001) than patients without variants. Statistical analyses found T≥15.38 nmol/L and ASI ≥ 180 IU × nmol/L2 as the threshold values to discriminate with good accuracy patients with AR variants. Patients with oligozoospermia and T≥15.38 nmol/L had a 9-fold increased risk of harboring mutations compared with patients with normal sperm count and T<15.38 nmol/L (odds ratio 9.29, 95% CI 5.07-17.02). Using computational and functional approaches, we identified 2 novel variants, L595P and L791I, as potentially pathogenic. Conclusion: This is the largest study screening AR gene variants in men of idiopathic infertile couples. We found that the prevalence of variants increased to 3.4% in oligozoospermic subjects with T≥15.38 nmol/L. Conversely, more than 80% of men with AR gene variants had low sperm count and high T levels. Based on our findings, we suggest AR sequencing as a routine genetic test in cases of idiopathic oligozoospermia with T≥ 15.38 nmol/L. [ABSTRACT FROM AUTHOR]

Infertility is an important health problem that affects up to 16% of couples worldwide. Male infertility is responsible for about 50% of the cases, and the various causes of male infertility may be classified in pre-testicular (for example hypothalamic diseases), testicular, and post-testicular (for example obstructive pathologies of seminal ducts) causes. Sexually transmitted infections (STI) are increasingly widely accepted by researchers and clinicians as etiological factors of male infertility. In particular, several recent reports have documented the presence of HPV in seminal fluid and observed that sperm infection can also be present in sexually active asymptomatic male and infertile patients. In this review, we aimed to perform a systematic review of the whole body of literature exploring the impact of HPV infection in natural and assisted fertility outcomes, from both an experimental and a clinical point of view. Starting from in-vitro studies in animals up to in-vivo studies in humans, we aimed to study and evaluate the weight of this infection as a possible cause of idiopathic infertility in males with any known cause of conception failure. [ABSTRACT FROM AUTHOR]

Capsule: This expert opinion summarizes current knowledge on risk factors for infertility and identifies a practical clinical and diagnostic approach for the male and female partners of an infertile couple aimed to improve the investigation and management of fertility problems. Background: Infertility represents an important and growing health problem affecting up to 16% of couples worldwide. In most cases, male, female, or combined factor can be identified, and different causes or risk factors have been related to this condition. However, there are no standardized guidelines on the clinical-diagnostic approach of infertile couples and the recommendations concerning infertility are sometimes lacking, incomplete, or problematic to apply. Objective: The aim of this work is to provide an appropriate clinical and diagnostic pathway for infertile couples designed by a multidisciplinary-team of experts. The rationale is based on the history and physical examination and then oriented on the basis of initial investigations. This approach could be applied in order to reduce variation in practice and to improve the investigation and management of fertility problems. Methods: Prominent Italian experts of the main specialties committed in the ART procedures, including gynecologists, andrologists, embryologists, biologists, geneticists, oncologists, and microbiologists, called "InfertilItaly group", used available evidence to develop this expert position. Outcomes: Starting from the individuation of the principal risk factors that may influence the fertility of females and males and both genders, the work group identified most appropriate procedures using a gradual approach to both partners aimed to obtain a precise diagnosis and the most effective therapeutic option, reducing invasive and occasionally redundant procedures. Conclusions: This expert position provides current knowledge on risk factors and suggests a diagnostic workflow of infertile couples. By using this step-by-step approach, health care workers involved in ART, may individuate a practical clinical management of infertile couples shared by experts. [ABSTRACT FROM AUTHOR]

Objective: To evaluate sperm parameters and sexual hormones in young males affected with spondyloarthritis (SpA) before and after 1 year of anti–tumor necrosis factor (TNF) α treatment. Design: Prospective case-control study. Setting: Rheumatology and human reproduction pathology units at a university hospital. Patients: Ten SpA outpatients attending the rheumatology clinic; 20 healthy control subjects attending the unit of human reproduction pathology within an infertility prevention program. Interventions: At baseline and after a 12-month treatment, disease activity was assessed and an andrologic evaluation made. Main Outcome Measure(s): Rheumatologists assessed anamnestic, clinical, functional, and biomarker data. Andrologists evaluated semen analysis, fluorescence in situ hybridization for chromosomes X, Y, 13, 18, and 21, FSH, LH, and T plasma levels, and testicular color Doppler ultrasound. Results: At baseline, SpA patients showed reduced sperm motility, higher plasma LH and FSH, and lower T levels compared with control subjects; a significant correlation between disease activity and sperm quality was found. After treatment, a statistically significant decrease in sperm aneuploidies and normal hormone levels were observed. Conclusions: Although inflammation in SpA appears to be related to impaired testicular function, anti–TNF-α agents seem to be safe on testicular function and fertility. [Copyright &y& Elsevier]

No valid method is currently available to analyze the entire genome of sperm, including aneuploidies and structural chromosomal alterations. Here we describe the optimization and application of array-Comparative Genomic Hybridization (aCGH) on single human sperm. The aCGH procedure involves screening of the entire chromosome complement by DNA microarray allowing having a molecular karyotype, and it is currently used in research and in diagnostic clinical practice (prenatal diagnosis, pre-implantation genetic diagnosis), but it has never been applied on sperm. DNA from single human sperm isolated by micromanipulator was extracted, decondensed and amplified by whole-genome amplification (WGA) and then labeled, hybridized to BAC array, and scanned by microarray scanner. Application of this protocol to 129 single sperm from normozoospermic donors identified 7.8% of sperm with different genetic anomalies, including aneuploidies and gains and losses in different chromosomes (unbalanced sperm). On the contrary, of 130 single sperm from men affected by Hodgkin lymphoma at the end of three months of chemotherapy cycles 23.8% were unbalanced. Validation of the method also included analysis of 43 sperm from a man with a balanced translocation [46,XY,t(2;12)(p11.2;q24.31)], which showed gains and losses corresponding to the regions involved in the translocation in 18.6% of sperm and alterations in other chromosomes in 16.3% of sperm. Future application of this method might give important information on the biology and pathophysiology of spermatogenesis and sperm chromosome aberrations in normal subjects and in patients at higher risk of producing unbalanced sperm, such as infertile men, carriers of karyotype anomalies, men with advanced age, subjects treated with chemotherapy, and partners of couples with repeated miscarriage and repeated failure during assisted reproduction techniques. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of three sperm washing protocols for removing human papillomavirus (HPV)-infected cells from semen samples of infertile patients. Design: Cross-sectional clinical study. Setting: Andrology and microbiology sections at a university hospital. Patient(s): A group of 32 infertile patients positive for semen HPV, detected with polymerase chain reaction (PCR) and in-situ hybridization in sperm and exfoliated cells. Intervention(s): Semen analysis and in-situ hybridization for HPV detection were performed before and after sperm washing, discontinuous Ficoll gradients, and swim-up protocols. Statistical analysis was performed with a two-tailed Student’s t-test. Main Outcome Measure(s): Evaluation of sperm parameters and presence of HPV, performed in semen samples before and after procedures of sperm selection. Result(s): All native samples showed the presence of infected sperm with a mean percentage of positivity (24.7% ± 8.9%) higher than exfoliated cells (13.8% ± 4.3%). Fifteen samples had HPV DNA on sperm and exfoliated cells. Sperm washing centrifugation showed no changes in the number of infected samples and in the percentage of infected cells. Ficoll and swim-up protocols induced a slight reduction in the number of infected samples (30 and 26, respectively). Conclusion(s): This study demonstrated that conventional sperm selection rarely eliminates HPV sperm infection. More attention should be paid to the reproductive health of infected patients because, not only can HPV be transmitted, but it may also have a negative effect on development of the fetus. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of treatment with recombinant human FSH (r-hFSH) on seminal parameters and seminiferous epithelium in idiopathic patients with oligozoospermia with normal FSH plasma levels.Design: Randomized single-blind study.Setting: Academic setting.Patient(s): Forty-five subjects with idiopathic oligozoospermia (sperm count <10 x 10(6)/mL) and normal FSH and inhibin B plasma levels.Intervention(s): Three months of treatment with r-hFSH 50 IU (15 patients) or with r-hFSH 100 IU on alternate days (15 patients) or no treatment (15 patients); bilateral testicular fine-needle aspiration (FNA) performed before and after therapy; FSH and inhibin B plasma levels evaluated during treatment.Main Outcome Measure(s): Seminal parameters; testicular cytological features evaluated by FNA; plasma levels of FSH, LH, T, and inhibin B.Result(s): Treatment with r-hFSH at a dose of 50 IU induced no increase in sperm concentration, while treatment with r-hFSH at a dose of 100 IU induced a significant increase in sperm concentration. In particular, in 11/15 patients a doubling of the pretreatment sperm concentration was observed. No significant increase in sperm parameters was observed in the control group. In both groups of patients treated with r-hFSH, the cytological analysis before treatment showed hypospermatogenesis. An increase in the percentage of spermatogonia and spermatocytes was observed only after the treatment with r-hFSH at a dose of 100 IU.Conclusion(s): The findings of this study demonstrate that r-hFSH at a dose of 100 IU, as previously seen with highly purified FSH, increases the spermatogonial population and sperm production in idiopathic patients with oligozoospermia with normal FSH and inhibin B plasma levels and a cytological picture of hypospermatogenesis. [ABSTRACT FROM AUTHOR]

About one-fifth of couples has fertility problems in Western countries. Male factors are present in about half of them, either alone or in combination with female causes. Therefore, both partners should be evaluated simultaneously. The fertility status and/or specific conditions of each partner influence the clinical and treatment approach. This article summarizes in a practical way when, how, and why the male partner of an infertile couple should be investigated. The available evidence and international guidelines were used, interpreting, discussing, and expanding them from personal decades-long experience in this field. The aim is to delineate the most appropriate clinical approach for the male partner of infertile couples, considering traditional and emerging technologies and laboratory analyses in the context of their clinical significance. Components of the initial evaluation in men without known risk factors for infertility should include at minimum medical history, physical examination, and semen analysis. Semen microbiological examination, endocrine assessment, scrotal ultrasound, and transrectal ultrasound are suggested in most men and are mandatory when specific risk factors for male infertility are known to be present or when the initial screening demonstrated abnormalities. Full examination, including genetic tests, testicular histology, or additional tests on sperm, is clinically oriented and/or suggested after the results of initial investigations. [ABSTRACT FROM AUTHOR]

Over the past two decades, public health has focused on the identification of environmental chemical factors that are able to adversely affect hormonal function, known as endocrine disruptors (EDs). EDs mimic naturally occurring hormones like estrogens and androgens which can in turn interfere with the endocrine system. As a consequence, EDs affect human reproduction as well as post and pre-natal development. In fact, infants can be affected already at prenatal level due to maternal exposure to EDs. In particular, great attention has been given to those chemicals, or their metabolites, that have estrogenic properties or antagonistic effects on the activity of androgen or even inhibiting their production. These compounds have therefore the potential of interfering with important physiological processes, such as masculinization, morphological development of the urogenital system and secondary sexual traits. Animal and in vitro studies have supported the conclusion that endocrine-disrupting chemicals affect the hormone-dependent pathways responsible for male gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, epidemiological studies have reported an overall decline of male fertility and an increased incidence of diseases or congenital malformations of the male reproductive system. The majority of studies point towards an association between exposure to EDs and male and/or female reproductive system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants has yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Despite the lack of consistency in the results of so many studies investigating endocrine-disrupting properties of many different classes of chemicals, the overall conclusion points toward a positive association between exposure to EDs and reproductive system. Future studies should focus on a uniform systems to examine human populations with regard to the exposure to specific EDs and the direct effect on the reproductive system. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor discussing the results of the diagnostic evaluation for infertility of female patients with inflammatory bowel disease citing the normalcy of all measures except for the presence of antisperm antibodies in the serum speculating the role of the autoimmune process in its development.

Abstract: Genetic causes account for 10–15% of severe male infertility, including chromosomal aberrations and single gene mutations. Natural selection prevents the transmission of mutations causing infertility, while this protective mechanism may be overcome by assisted reproduction techniques. Consequently the identification of genetic factors has become good practice for appropriate management of the infertile couple. Furthermore, patients affected by some forms of genetic alterations produce a higher frequency of sperm with aneuploidies. Sperm aneuploidies are the direct result of the constitutional genetic abnormality or are caused by meiotic errors induced by the altered testicular environment that these men present. In this review we will report and discuss the genetic causes of male infertility known up to date and we will analyse genetic polymorphisms possibly associated with male infertility. [Copyright &y& Elsevier]

Eruca sativa action on the male reproductive system and fertility has not been precisely defined. In this study, the aim was to investigate the ameliorative activity of E. sativa aqueous extracts (ESAE) on reproductive toxicity associated with oxidative stress induced by bisphenol A (BPA). Wistar rats were used and divided into six groups of animals each; control (0.4 mL of corn oil/rat), ESAE at the higher dose (200 mg/kg), BPA [100 mg/kg, body weight (b.w.), perorally (p.o.)] alone, or in combination with varied doses of ESAE (50, 100, and 200 mg/kg, b.w, p.o.). The diverse doses were administrated orally for 30 consecutive days. The results showed that BPA-treatment produced a diminution of density, motility, and viability of sperm with disruption of spermatozoa morphology and fertilizing potential as well as testosterone, luteinizing hormone, and follicle stimulating hormone levels. These results were accompanied by testis and epididymis histological damages, which were shown by an induction of testicular dysfunction as seen with a lower number of Leydig-cells and spermatocytes as well as a reproductive stress which was modeled. The oxidative stress was measured by malondialdehyde production, thiol group (-SH) decline and antioxidant enzyme activities disturbance, in particular superoxide dismutase, catalase, and glutathione peroxidase in reproductive tissues. ESAE coadministration at the two lower doses improved all histological and biochemical parameter injuries. These finding suggested the ESAE ability to prevent the testicular damages in rats, which might be linked to functional-bioactive substances such as phenolic compounds with higher antioxidant capacity. [ABSTRACT FROM AUTHOR]

Objective: To quantify the amount of AR messenger RNA (mRNA) and to analyze the presence and functionality of the AR protein in X- and Y-carrier human spermatozoa. Design: A molecular and cellular research study. Setting: Academic research clinic and laboratories. Patient(s): Ten normozoospermic volunteers. Intervention(s): Sperm were analyzed for expression of AR mRNA and protein. The functionality of AR protein was assessed after incubation with 1 nM of synthetic androgen. Main Outcome Measure(s): Reverse-transcription polymerase chain reaction (PCR), real-time PCR, Western immunoblotting, confocal immunofluorescence, and fluorescence in situ hybridization analysis were performed. Result(s): A significant amount of AR mRNA (around 30% of that found in the testis) was found in sperm. Androgen receptor protein was found in both X- and Y-carrier spermatozoa and translocates into the nucleus in the presence of synthetic androgen. Conclusion(s): A functional AR is expressed in human sperm. In view of the fact that AR protein is found in both X- and Y-carrier spermatozoa, it most probably is translated in earlier steps of spermatogenesis and moves to Y-carrier spermatids through the cytoplasmic bridges. [Copyright &y& Elsevier]

Male infertility represents one of the clearest examples of a complex disease with a substantial genetic basis. Numerous male mouse models, mutation screening and association studies reported over the last few years reveal the high prevalence of genetic causes of spermatogenic impairment, accounting for 10-15% of severe male infertility, including chromosomal aberrations and single gene mutations. Natural selection prevents the transmission of mutations causing infertility, but this protective mechanism may be overcome by assisted reproduction techniques. Consequently, the identification of genetic factors is important for appropriate management of the infertile couple. However, a large proportion of infertile males are diagnosed as idiopathic, reflecting poor understanding of the basic mechanisms regulating spermatogenesis and sperm function. Furthermore, the molecular mechanisms underlying spermatogenic damage in cases of genetic infertility (for example Yq microdeletions) are not known. These problems can be addressed only by large scale association studies and testicular or spermatozoal expression studies in well-defined alterations of spermatogenesis. It is conceivable that these studies will have important diagnostic and therapeutic implications in the future. This review discusses the genetic causes of male infertility known to date, the genetic polymorphisms possibly associated with male infertility, and reports novel results of global gene expression profiling of normal human testis by microarray technology. [ABSTRACT FROM AUTHOR]

Abstract: Despite the continuous improvement of cancer treatment protocols, altered testicular function and infertility frequently represent major adverse effects of oncologic treatments. Thus, strong efforts are needed to avoid or at least to reduce these complications that are particularly relevant in young men without offspring. Furthermore in the last years, concerns have been raised about the possible mutagenic effect of chemotherapy on sperm. Alkylating agents are frequently and successfully used in the treatment of paediatric tumors despite their well-known gonadotoxic effect. While gonadal toxicity of cyclophosphamide has been well demonstrated, little and conflicting data are reported about the effects on testicular function of ifosfamide. The aim of this study was to compare long-term effects of ifosfamide versus cyclophosphamide based therapies, on testicular function, fertility and sperm aneuploidies in a group of 33 young males survivors of childhood cancer. Patients who had received cyclophosphamide showed a severe gonadal failure characterized by reduced testicular size, very low sperm count and some degree of Leydig cell impairment. On the contrary, in subjects who had received ifosfamide all parameters of testicular function including sperm aneuploidies were in the normal range, despite of different dose, protocol of infusion and pubertal stage at treatment. In conclusion, our results confirm data of literature reporting the high gonadal toxicity of cyclophosphamide and suggest that ifosfamide treatment seems to be safer for testicular function and fertility. [Copyright &y& Elsevier]

Abstract: A mosaic ring chromosome 22 (mos 46,XY,r(22)[93]/45,XY,-22[7]) was found in an euploid azoospermic otherwise phenotypically normal individual. Testicular cytological analysis showed hypospermatogenesis with a complete spermatogonial arrest. The majority of subjects with constitutional r(22) are dysmorphic and mentally retarded due to deletion of a sizable segment of the chromosome 22q. Only a few cases of r(22) chromosome are known in which deletion of the very distal telomeric regions is associated with unremarkable phenotype and fertility, both in males and females. The present patient is the first example of male infertility associated with this cytogenetic anomaly. It is likely that infertility arose from a mechanical block of meiosis, resulting from pairing failure of chromosomes 22, similarly to azoospermia occurring in few known males with r(21) chromosomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of the male factor on the outcomes of intracytoplasmic sperm injection (ICSI) cycles combined with preimplantation genetic testing for aneuploidies (PGT-A).Design: Observational longitudinal cohort study.Setting: Private in vitro fertilization (IVF) center.Patient(s): A total of 1,219 oocyte retrievals divided into five study groups according to sperm parameters: normozoospermia (N), moderate male factor (MMF), severe oligoasthenoteratozoospermia (OAT-S), obstructive azoospermia (OA), and nonobstructive azoospermia (NOA).Intervention(s): ICSI with ejaculated/surgically retrieved sperm, blastocyst culture, trophectoderm-based quantitative polymerase chain reaction PGT-A, and frozen-warmed euploid embryo transfer (ET).Main Outcomes Measure(s): The primary outcome measures were fertilization, blastocyst development, and euploidy rates; the secondary outcome measures were live birth and miscarriage rates. Perinatal and obstetrical outcomes were monitored as well.Result(s): A total of 9,042 metaphase II oocytes were inseminated. The fertilization rate was significantly reduced in MMF, OAT-S, OA, and NOA compared with N (74.8%, 68.7%, 67.3%, and 53.1% vs. 77.2%). The blastocyst rate per fertilized oocyte was significantly reduced in MMF and NOA compared with N (48.6% and 40.6% vs. 49.3%). The timing of blastocyst development also was affected in OA and NOA. Logistic regression analysis adjusted for confounders highlighted NOA as a negative predictor of obtaining an euploid blastocyst per OPU (odds ratio 0.5). When the analysis was performed per obtained blastocyst, however, no correlation between male factor and euploidy rate was observed. Embryo transfers also resulted in similar live birth and miscarriage rates. No impact of sperm factor on obstetrical/perinatal outcomes was observed.Conclusion(s): Severe male factor impairs early embryonic competence in terms of fertilization rate and developmental potential. However, the euploidy rate and implantation potential of the obtained blastocysts are independent from sperm quality. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the reproductive outcome of infertile couples undergoing assisted reproduction techniques (ART) with or without human papillomavirus (HPV) semen infection.Design: Cross-sectional clinical study.Setting: Units of andrology, reproductive medicine, and gynecology.Patient(s): A total of 226 infertile couples.Intervention(s): Male partners were evaluated by means of fluorescence in situ hybridization (FISH) for HPV on semen. After a diagnostic period, female partners underwent intrauterine insemination (IUI) or intracytoplasmic sperm injection (ICSI).Main Outcome Measure(s): Seminal parameters and FISH analysis for HPV in sperm head. Spontaneous or assisted pregnancies, live births, and miscarriages were recorded. Statistical analysis included unpaired Student t test and chi-square test.Result(s): Fifty-four male partners (23.9%) had HPV semen infection confined to sperm, confined to exfoliated cells, or in both cells. During the diagnostic period, noninfected couples showed spontaneous pregnancies. IUI and ICSI treatments were performed in, respectively, 60 and 98 noninfected and in 21 and 33 infected couples, with 38.4% and 14.2% cumulative pregnancy rates, respectively. The follow-up of pregnancies showed a higher miscarriage rate in infected couples (62.5% vs. 16.7%). Ongoing pregnancies of the latter group were characterized by HPV infection confined to exfoliated cells.Conclusion(s): A reduction in natural and assisted cumulative pregnancy rate and an increase in miscarriage rate are related to the presence of HPV at sperm level. Although the exact mechanism by which sperm infection is able to impair fertility remains unclear, this aspect is worthy of further investigations. If confirmed, these results could change the clinical and diagnostic approach to infertile couples. [ABSTRACT FROM AUTHOR]

Objective To study the role of NR5A1 in cryptorchidism and male factor infertility. Mutations in NR5A1 have been initially associated with primary adrenal insufficiency and 46,XY gonadal dysgenesis and more recently with less severe phenotypes, including preliminary descriptions in severe forms of male factor infertility. Far less clear is the possible involvement of NR5A1 mutations in cryptorchidism. Design Retrospective cross-sectional cohort study and functional analysis of mutant proteins. Setting University department. Patient(s) Nine hundred fifty-nine subjects, including children with cryptorchidism and adults with different semen phenotypes associated or not associated with a history of cryptorchidism. Intervention(s) None. Main Outcome Measure(s) Mutation screening of NR5A1 by sequencing all exons. Functional analysis of mutant proteins by transactivation assays of CYP11A1 and CYP17A1 promoters. Result(s) We identified seven undescribed and one previously described missense mutation in subjects with severe spermatogenic impairment, without (4/236, 1.7%) and with (3/85, 3.5%) a history of cryptorchidism. Newborns with cryptorchidism carry NR5A1 mutations at low frequency (0.7%), whereas no mutations were found in milder forms of infertility and normozoospermia, irrespective of the presence of cryptorchidism. The mutant proteins showed impaired transactivation of gonadal promoters. A single nucleotide polymorphism (rs1110061; c.437 G→C; p.Gly146Ala) was also associated with more severe forms of spermatogenic impairment with cryptorchidism. Conclusion(s) This study, combined with what is already known about NR5A1-associated phenotypes, suggests considering mutations in this gene as a novel genetic cause of more severe forms of male factor infertility, especially when associated with a history of cryptorchidism. [ABSTRACT FROM AUTHOR]

Objective: To evaluate prevalence, association, and clearance of human papillomavirus (HPV) and antisperm antibodies (ASAs) in infected semen samples from infertile patients. Design: Cross-sectional clinical study. Setting: Andrology and microbiology sections at a university hospital. Patient(s): Three groups of subjects: 61 infertile patients with HPV semen infection, 104 noninfected infertile subjects, and 92 control subjects. Intervention(s): Semen analysis, spermMar test, fluorescence in situ hybridization for sperm aneuploidy and for HPV, and immunofluorescence for HPV 16-L1 and immunoglobulins (IgA, IgG, and IgM) determination. Main Outcome Measure(s): Association of sperm procedures, HPV sperm infection, sperm aneuploidies, and sperm ASAs. Result(s): Infertile patients with HPV semen infection showed high percentages of ASAs. In these patients HPV sperm infection was associated with lower sperm motility, which was worse in subjects with ASAs. No alterations of sperm chromosomes were observed. To obtain a significant clearance of both HPV sperm infection and ASAs at least 24 months of follow-up were needed. Conclusion(s): Human papillomavirus has been recently suggested to have an important role in male infertility. This study demonstrated that HPV sperm infection can be long lasting and frequently associated with ASAs that may further reduce male fertility. Infertile patients with positive spermMar test results should be considered for investigation for HPV, especially if they are candidates for assisted reproduction. [ABSTRACT FROM AUTHOR]