Poor Sperm Research Articles

The impact of fresh and frozen testicular tissue quality on embryological and clinical outcomes.

Our ability to predict the potential of testicular spermatozoa to support embryonic development is still limited. Although motility of testicular spermatozoa is associated with embryo development, the impact of morphology and the presence of spermatozoa in the testicular sample has not been previously researched. Moreover, while the majority of data indicate no effect of cryopreservation, there are studies reporting impaired clinical outcomes due to testicular cryopreservation. In a retrospective study, 118 ICSI-TESE cycles were analysed to study the impact of (a) total quality of testicular tissue, (b) testicular tissue cryopreservation and (c) presence/motility/morphology of testicular spermatozoa in fertilisation rate, embryonic development, clinical pregnancy (CPR), ongoing pregnancy (OPR) and live birth rate (LBR). Results showed that fertilisation rate was significantly affected by both total quality of testicular tissue (p<.05) and rare presence of spermatozoa (p<.01). Moreover, total tissue quality (p<.01), cryopreservation of low-quality samples (p<.01), absence of motile testicular spermatozoa (p<.01) and poor spermatozoa morphology (p<.05) had a negative impact on the number of good quality day 3 embryos. CPR, OPR or LBR was not affected by any parameters examined. Our data suggest that the quality of testicular tissue influences both fertilisation rate and embryo development. Moreover, cryopreservation of low-quality testicular samples has a negative impact on the number of available embryos for transfer.

Effect of Butylated Hydroxytoluene and Tocopherol Supplementation on In vitro Sperm Characters during Cryopreservation of Black Bengal Buck Semen

Background: Black Bengal goat is one of the important goat breeds of India. Cryopreservation of semen and artificial insemination are effective techniques for improving goat breeding programs. Various biochemical and functional changes that occur during freezing-thawing process results in poor post thaw sperm recovery. Supplementation of antioxidants to the extender has been reported to have positive effects on semen cryopreservation in various species. The present study was undertaken to assess the effect of antioxidants butylated hydroxyl toluene (BHT), α tocopherol on post thaw in vitro sperm characters, lipid peroxide level and superoxide dismutase (SOD) activity during cryo­preservation of Black Bengal buck semen. Methods: Semen was collected from bucks by artificial vagina, antioxidant BHT was added to the Tris egg yolk extender @ 0, 1 and 2 mM/ml in control group (BHTC), treatment group 1 (BHTT1) and treatment group 2 (BHTT2), respectively. Similarly, tocopherol was added @ 0, 1 and 2 mg/ml in control group (TFC), in treatment group 1 (TFT1) and treatment group 2 (TFT2), respectively. Each antioxidant was tested with 20 semen ejaculates. Semen samples were frozen in liquid nitrogen and post freeze-thaw in vitro sperm characters, malondialdehyde (MDA) concentration and SOD activity were measured. Result: Post thaw sperm motility, functional membrane integrity and viable count were significantly (P less than 0.05) higher in the BHT and α tocopherol supplemented groups than control groups. Significantly (P less than 0.05) higher acrosome intact cells were recovered in BHTT1, BHTT2 and TFT2 groups than the control and TFT1 groups. Further, BHT supplemented groups had significantly lower level of MDA than the control, while the supplementation of α tocopherol could not control the generation of MDA. Post thaw SOD activity was found significantly lower in the antioxidant treated groups than their respective controls. It is concluded that supplementation of BHT and α tocopherol were found to be more promising in conserving in vitro sperm characters from cryo-damages during freezing of Black Bengal bucks semen.

Low sperm to egg ratio required for successful in vitro fertilization in a pair-spawning teleost, Senegalese sole (Solea senegalensis).

Cultured Senegalese sole (Solea senegalensis) breeders fail to spawn fertilized eggs. The implantation of large-scale in vitro fertilization protocols, to solve this problem, has been frustrated by low production of poor quality sperm. Cultured females were induced to ovulate with a 5 µg kg−1 single injection of gonadotropin-releasing hormone agonist (GnRHa) and viable eggs (82.6 ± 9.2% fertilization) were stripped 41:57 ± 1:46 h after the injection. Sperm was collected from cultured males, diluted in modified Leibovitz and used fresh to fertilize the eggs. Males were not treated with hormones. A nonlinear regression, an exponential rise to a maximum (R = 0.93, p < 0.0001) described the number of motile spermatozoa required to fertilize a viable egg and 1617 motile spermatozoa were sufficient to fertilize 99 ± 12% (±95% CI) of viable eggs. Similar, spermatozoa egg−1 ratios of 592 ± 611 motile spermatozoa egg−1 were used in large-scale in vitro fertilizations (190 512 ± 38 471 eggs). The sperm from a single male (145 ± 50 µl or 8.0 ± 6.8 × 108 spermatozoa) was used to fertilize the eggs. The mean hatching rate was 70 ± 14% to provide 131 540 ± 34 448 larvae per fertilization. The viability of unfertilized eggs stored at room temperature decreased gradually, and the sooner eggs were fertilized after stripping, the higher the viability of the eggs. The collection of sperm directly into a syringe containing modified Leibovitz significantly increased the percentage of motile spermatozoa (33.4 ± 12.2%) compared with other collection methods. The spz egg−1 ratios for Senegalese sole were at the lower end of ratios required for fish. Senegalese sole have a pair-spawning reproductive behaviour characterized by gamete fertilization in close proximity with no sperm competition. The provision of a large-scale in vitro fertilization protocol (200 µl of sperm per 100 ml of eggs) will enable the industry to operate sustainably and implement breeding programmes to improve production.

Heat stress response of somatic cells in the testis

The testis is a temperature-sensitive organ that needs to be maintained 2–7 °C below core body temperature to ensure the production of normal sperm. Failure to maintain testicular temperature in mammals impairs spermatogenesis and leads to low sperm counts, poor sperm motility and abnormal sperm morphology in the ejaculate. This review discusses the recent knowledge on the response of testicular somatic cells to heat stress and, specifically, regarding the relevant contributions of heat, germ cell depletion and inflammatory reactions on the functions of Sertoli and Leydig cells. It also outlines mechanisms of testicular thermoregulation, as well as the thermogenic factors that impact testicular function.

High mRNA expression of GABA receptors in human sperm with oligoasthenoteratozoospermia and teratozoospermia and its association with sperm parameters and intracytoplasmic sperm injection outcomes.

ObjectiveThis study investigated the mRNA expression of gamma-aminobutyric acid (GABA) receptors in the sperm of oligoasthenoteratozoospermic (OAT) and teratozoospermic (TER) men compared to normozoospermic (NOR) men, as well as the relationships between GABA receptor expression and sperm parameters, fertilization rate, and embryo quality.MethodsThe mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm was examined using reverse transcription–polymerase chain reaction in three groups of patients: NOR (n=32), OAT (n=22), and TER (n=45). The fertilization rate and embryo quality were assessed in 35 patients undergoing intracytoplasmic sperm injection (ICSI; 10 NOR, 10 OAT, and 15 TER men). ResultsOAT men had significantly higher mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm than NOR men; however, the difference between TER and NOR men was not significant. High levels of these receptors were significantly correlated with low sperm concentration, motility, and morphology, as well as the rate of good-quality embryos (GQEs) at the cleavage stage after ICSI. Patients whose female partners had a >50% GQE rate at the cleavage stage had significantly lower levels of GABA A-α1 receptor expression than those whose partners had a ≤50% GQE rate.ConclusionOur findings indicate that mRNA levels of GABA receptors in human sperm are correlated with poor sperm quality and associated with embryo development after ICSI treatment. The GABA A-α1 receptor in sperm has a stronger relationship with embryo quality at the cleavage stage than the GABA B-R2 receptor.

The Relationship between Antithyroid Antibody and Pregnancy Outcome in Invitro Fertilization and Embryo Transfer

Background of the study: One type of assisted reproductive technique is intracytoplasmic sperm injection(ICSI) Despite use ofintracytoplasmic sperm injectionICSI it remain has low birth rate due to failurerate there are many markers associated with poor predict the outcome one of these factor effect outcomeinintracytoplasmic sperm injection ICSI presence of antithyroid antibody ineuthyroid patientAim of study: To examine the effect of antithyroid antibody on pregnancy results following the in vitrofertilization and fetus transmitMethods and patients : Cross section study conducted at AL-Sader infertility center atotal of eighty oneIraqi women were enrolled in this study of them 22positive antithyroid antibody,59 negative antithyroidantibody were undergone intra-cytoplasmic sperm injection ICSI in Al-Sader infertility center. The group ofthe study involved onlyeuthyroid women outwardly any clinically showed autoimmune illness.Result:there was higher significant difference p value&lt;0.004 in fertilization rate number of availableembryos p value&lt;0.003 and number of transfer embryos p value&lt; 0.001among study group which washigher in group of women with antithyroid negative followed by,group with antithyroid positive in infertileeuthyroid women Conclusion:patients with antithyroid antibody associated with poor pregnancy outcomein infertile euthyroid women undergoingintracytoplasmic sperm injection ICSI

The overview of current evidence on the reproductive toxicity of dibutyl phthalate.

Over the past years, many legitimate concerns have been raised about the effects of dibutyl phthalate (DBP) as an endocrine disruptor, especially on reproduction. The aim of this publication is to critically review the literature related to the developmental and reproductive toxicity of DBP in animals. Several electronic databases were systematically searched until 2019. Studies were qualified for the review if they: linked exposure to DPB with reproduction, were published in English after 1990, and were conducted on animals. In the studies of the testicular effects of DBP on experimental animals, the most common effects of exposure included reduced fertility, atrophic changes in male gonads, degenerative changes in the epididymis, as well as a reduction in sperm count and motility, cryptorchidism, hypospadias, poor sperm quality and other genital defects (decreased testicular weight, delayed spermatogenesis, Leydig cell aggregation, impaired Sertoli cell maturation, and significant inhibitions of testicular enzymes). The embryotoxic effects of DBP on laboratory animals included mainly an increase in fetal resorption and a decrease in live births. The teratogenic effects of DBP also manifest as skeletal malformations in fetuses, malformations of male gonads and other genital effects. On the basis of the literature data, it is clearly demonstrated that DBP shows anti-androgenic effects; however, there are also reports confirming its weak estrogenic effect. Additionally, lower doses cause more adverse effects than the highest dose, which is an important fact because of the widespread environmental exposure to DBP. The studies clearly confirm that DBP is an endocrine disruptor. Int J Occup Med Environ Health. 2021;34(1):15-37.

The effect of a novel LRRC6 mutation on the flagellar ultrastructure in a primary ciliary dyskinesia patient

There are limited genes known to cause primary ciliary dyskinesia (PCD)-associated asthenozoospermia. In the present study, we aimed to expand the spectrum of mutations in PCD and to provide new information for genetic counseling diagnoses and the treatment of male infertility in PCD. One sterile patient with typical situs inversus was recruited to our center, and semen sample was collected. We performed whole-exome sequencing (WES) on the patient to identify the pathogenic mutations associated with PCD and used transmission electron microscopy to investigate spermatozoal ultrastructure. In addition, western blotting and immunofluorescence staining were used to confirm the untoward impact of the variant on the expression of LRRC6, as well as on the dynein arm proteins in the patient's spermatozoa. We identified a homozygous nonsense variant c.749G>A (p.W250*) of LRRC6 in the PCD patient. This variant severely impaired LRRC6 expression and further led to negative effects on dynein arm protein expression in the spermatozoa of the affected individual, which eventually caused defects in sperm ultrastructure and motility. Moreover, we are the first to report a positive prognosis using intracytoplasmic sperm injection (ICSI) for LRRC6-associated male infertility. Our findings strongly implicated the homozygous mutation of c.749G>A (p.W250*) in LRRC6 as a new genetic cause of PCD, uncovering its involvement in defective sperm flagella and poor sperm motility. Furthermore, we posit that patients with LRRC6 mutations may have good outcomes with ICSI treatment. These findings add to the literature on the genetic diagnoses and treatment of male infertility associated with PCD.

HAART and anti‐Koch’s impair sexual competence, sperm quality and offspring quality when used singly and in combination in male Wistar rats

This study investigated the impact of the administration of HAART and anti-Koch's, singly and in combination, on sexual competence and birth statistics. Adult male Wistar rats were randomised into distilled water-treated control, HAART-treated, anti-Koch's-treated and HAART+anti-Koch's-treated groups. The 56-day oral treatment led to impaired sexual competence evident by significantly reduced motivation to mate, prolonged latencies of mount, intromissions, ejaculations and post-ejaculatory interval, as well as reduced frequencies of mount, intromissions and ejaculations. This was accompanied by significant reductions in penile erection reflex and penile grooming. HAART and anti-Koch's, when administered singly or in combination, also led to significant reductions in the circulatory follicle-stimulating hormone, luteinizing hormone, testosterone and intratesticular testosterone, but a significant rise in prolactin. Also, HAART and/or anti-Koch's significantly reduced sperm count, sperm motility, sperm viability and spermatozoa with normal morphology. Furthermore, HAART and anti-Koch's, separately or in combination, significantly lowered fertility capacity, litter size and litter weight and offspring survival. The deleterious effects of these drugs were more pronounced when combined. Findings of the present study revealed that HAART and/or anti-Koch's impair sexual competence via a testosterone-dependent hyperprolactinemia-mediated mechanism. These events are associated with reduced fertility capacity, poor sperm quality and lowered offspring survival.

Relevance of Leukocytospermia and Semen Culture and Its True Place in Diagnosing and Treating Male Infertility.

The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×106/mL of semen. Granular leukocytes when activated are capable of generating high levels of reactive oxygen species in semen resulting in oxidative stress. Oxidative stress has been correlated with poor sperm quality, increased level of sperm DNA fragmentation and low fertility potential. The presence of leukocytes and pathogens in the semen may be a sign of infection and/or localized inflammatory response in the male genital tract and the accessory glands. Common uro-pathogens including Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrhoeae, Mycoplasma hominis, and Escherichia coli can cause epididymitis, epididymo-orchitis, or prostatitis. The relationship between leukocytospermia and infection is unclear. Therefore, we describe the pathogens responsible for male genital tract infections and their association with leukocytospermia. The review also examines the diagnostic tests available to identify seminal leukocytes. The role of leukocytospermia in male infertility and its management is also discussed.

Towards Post-Meiotic Sperm Production: Genetic Insight into Human Infertility from Mouse Models

Declined quality and quantity of sperm is currently the major cause of patients suffering from infertility. Male germ cell development is spatiotemporally regulated throughout the whole developmental process. While it has been known that exogenous factors, such as environmental exposure, diet and lifestyle, et al, play causative roles in male infertility, recent progress has revealed abundant genetic mutations tightly associated with defective male germline development. In mammals, male germ cells undergo dramatic morphological change (i.e., nuclear condensation) and chromatin remodeling during post-meiotic haploid germline development, a process termed spermiogenesis; However, the molecular machinery players and functional mechanisms have yet to be identified. To date, accumulated evidence suggests that disruption in any step of haploid germline development is likely manifested as fertility issues with low sperm count, poor sperm motility, aberrant sperm morphology or combined. With the continually declined cost of next-generation sequencing and recent progress of CRISPR/Cas9 technology, growing studies have revealed a vast number of disease-causing genetic variants associated with spermiogenic defects in both mice and humans, along with mechanistic insights partially attained and validated through genetically engineered mouse models (GEMMs). In this review, we mainly summarize genes that are functional at post-meiotic stage. Identification and characterization of deleterious genetic variants should aid in our understanding of germline development, and thereby further improve the diagnosis and treatment of male infertility.

Oligoasthenoteratospermia and sperm tail bending in PPP4C-deficient mice.

Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and '9 + 2' flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.

Seminal oxidation-reduction potential as a possible indicator of impaired sperm parameters in Turkish population.

Oxidative stress (OS) has been shown to have a key role in male infertility. Recently, a new measurement method has been developed to measure the overall oxidation-reduction potential (ORP) in a semen sample known as the MiOXSYS system. The aim of this study was to investigate the correlation of sperm parameters with oxidative stress levels determined by ORP and to evaluate whether the current limit is able to distinguish abnormal sperm parameters from normal ones in Turkish population. Semen samples of 121 patients who applied for infertility investigation were divided into two groups as (OS +; n:39) and (OS -; n:82). Semen parameters were compared between groups. Sperm concentration, total motility and progressive motility were found to be significantly lower in OS (+) patients compared to those OS (-), while immotile sperm count was significantly higher in OS (+) patients. Oxidative stress determined by MiOXSYS system was found to be related to reduced sperm parameters in Turkish population, which may be used as an indicator of poor sperm parameters and a support to routine semen analysis. In addition, recommended reference value was found to be reliable in distinguishing normal from impaired semen parameters.

Study of semen quality by SQA (QwikCheck Gold)

Introduction: Infertility is defined as failure of a couple to conceive after twelve months of regular intercourse without the use of contraception in women 15 million/ml.34% men had less than 4% normal morphology of sperms. 39.5% patients had >40% motility. Teratospermia was observed in 60.5%patients. Poor sperm motility (asthenospemia) was observed in 61.5% patients. Conclusion: Semen analysis remains the main fool for evaluating male infertility. SQA (QwikCheck Gold) is a unique, compact desktop instrument which is rapid, runs on low cost, is easy to use and provides standardized quantitation of semen parameters. It can be used as a screening tool for semen quality determination and management of male infertility. Keywords: Semen, SQA (QwikCheck Gold), Azoospermia, Teratospermia.

Novel Proteomic Profiling of Epididymal Extracellular Vesicles in the Domestic Cat Reveals Proteins Related to Sequential Sperm Maturation with Differences Observed between Normospermic and Teratospermic Individuals

Extracellular vesicles (EVs) secreted by the epididymal epithelium transfer to spermatozoa key proteins that are essential in promoting motility and subsequent fertilization success. Using the domestic cat model, the objectives were to (1) characterize and compare protein content of EVs between segments of the epididymis, and (2) compare EV protein compositions between normo- and teratospermic individuals (producing >60% of abnormal spermatozoa). Epididymal EVs from adult cats were isolated and assessed via liquid chromatography tandem MS. Both male types shared 3008 proteins in total, with 98 and 20 EV proteins unique to normospermic and teratospermic males, respectively. Expression levels of several proteins changed between epididymal segments in both male types. Several proteins in both groups were related to sperm motility (e.g. hexokinase 1, adenylate kinase isoenzyme) and zona pellucida or oolemma binding (e.g. disintegrin and metalloproteinase domain proteins, zona binding proteins 1 and 2). Interestingly, seven cauda-derived EV proteins trended downward in teratospermic compared with normospermic males, which may relate to poor sperm quality. Collective results revealed, for the first time, EV proteins related to sequential sperm maturation with differences observed between normospermic and teratospermic individuals.

Assessing the impact of semen quality on embryo development in an egg donation model

ObjectiveTo investigate if any of the World Health Organization semen parameters and/or male age are associated with embryo development.DesignRetrospective chart review between January 2008 and May 2015.SettingAcademic fertility practice.PatientsAnonymous egg donors aged ≤30 years.InterventionsChart review.Main Outcome MeasuresSperm parameters were evaluated on a continuum and were dichotomized to determine if low values (strict morphology < 4%, concentration < 15 × 106, low motility < 40%) or older age (>50 years) are associated with embryo morphology. Repeated linear regression measures to determine the associations and multivariate testing to determine independent effects for each predictor were performed.ResultsThree hundred eighty-four donors with 574 egg donation cycles were identified, and 205 subjects with 275 cycles were included in the final analysis. The mean donor age was 25.31 ± 2.81 years, with a mean antral follicle count of 28.09 ± 10.5. The mean male age was 43.25 ± 6.65 years. The mean World Health Organization semen parameters at fertilization were 55.8 × 106 ± 44.3 × 106/mL concentration, 44.8% ± 20.2% motility, and 6.9% ± 5.3% strict morphology. Neither male age nor sperm morphology was associated with embryo morphology. A low total motile count was significantly associated with a higher cell number in day-3 embryos and a 1.56-times higher chance of poor day-3 cell symmetry. There was no statistically significant difference in blastocyst formation, clinical pregnancy, or live-birth rates.ConclusionsAlthough statistically significant, the effect of the low total motile count on day-3 cell number and cell symmetry are likely clinically insignificant. Male age, race, or poor sperm morphology were not associated with a poor cycle outcome or impaired embryo development. The use of intracytoplasmic sperm injection likely alleviates the negative effect of diminished semen quality on treatment outcome.

In vivo exposure to codeine induces reproductive toxicity: role of HER2 and p53/Bcl-2 signaling pathway

Several studies have implicated codeine use in the aetiopathogenesis of male infertility. The purpose of this study was to investigate the role of HER2, Ki67, oestrogen and p53/Bcl-2 signaling pathways and the possible outcome of codeine cessation on codeine-induced reproductive toxicity. Thirty adult male Wistar rats of comparable ages and weights were randomly allocated into 5 groups. The control animals received distilled water per os (p.o), while animals in the low-dose (LDC) and high dose (HDC) codeine-treated groups received 2 and 5 mg/kg/day of codeine respectively p.o for 6 weeks. The animals in the low-dose codeine recovery (LDC-R) and high-dose codeine recovery (HDC-R) groups received treatment as LDC and HDC respectively followed by another drug-free six weeks, recovery period. Cessation of codeine exposure led to a partial reversal of codeine-induced poor sperm quality, reduced litter size and weight, increased oxidative testicular injury, testicular apoptosis, and testicular DNA damage caused by codeine administration. Codeine-induced gonado-spermotoxicity was associated with a reduction of circulatory testosterone, suppression of testicular HER2, Ki67, and Bcl-2 expression, down-regulation of oestrogen signaling, and upregulation of testicular caspase 3 activities and p53 signaling pathway. Conclusion: Upregulation of oestrogen signaling associated with enhanced testicular HER2 and Ki67 expression during the recovery period is seemingly beneficial in protecting against codeine-related testicular injury and infertility.

Schistosoma haematobium ova in human semen: a case report

ObjectiveTo report a rare case of schistosomiasis observed during semen evaluation.DesignCase report.SettingUniversity hospital.Patient(s)A 30-year-old man referred for semen analysis.Interventions(s)None.Main Outcome Measures(s)Poor sperm motility and viability.Result(s)The patient produced 9.8 mL of brown colored semen with a bad odor. Total and progressive sperm motility were 9% and 2%, respectively. Sperm concentration was 112 million/mL. Microscopic semen evaluation showed slight sperm agglutination, a large number of Schistosoma haematobium ova, extensive debris, and a large numberot of amorphous cells. Approximately 20 million/mL of neutrophils were observed in the ejaculate. The sperm viability was extremely low (13%). Sperm morphology was 6% normal, and most abnormal sperm had coiled tails in addition to other abnormalities.Conclusion(s)A microscopic examination of semen from suspected Schistosoma haematobium–infected patients may not only help in confirming diagnosis but may also highlight the underlying infertility due to this infestation. Such cases are rarely observed in andrology laboratories; therefore, it is important to train all testing staff on rare semen samples.

Baseline levels of seminal reactive oxygen species predict improvements in sperm function following antioxidant therapy in men with infertility.

Poor sperm function is a major cause of infertility. There is no drug therapy to improve sperm function. Semen oxidative stress is a recently identified pathway for sperm damage. Commercial antioxidants such as L-carnitine and acetyl-L-carnitine (LAL) are commonly self-administered by infertile men. However, concerns have been raised whether inappropriate LAL therapy causes reductive stress-mediated sperm damage. It is imperative to investigate whether: (1) LAL improves sperm function by reducing reactive oxidative species (ROS); (2) LAL has differential effects on sperm function between men with normal and elevated ROS. A prospective cohort study of routine clinical practice was performed in infertile men with abnormal sperm quality. Changes in sperm function and semen ROS levels following three months of oral LAL therapy were compared between participants with baseline seminal normal ROS (≤10RLU/SEC/106 sperm; n=29) and High ROS (>10 RLU/SEC/106 sperm; n=15) levels measured using an established colorimetric-luminol method. In normal ROS group, sperm function did not change following LAL therapy. In high ROS group, LAL therapy reduced semen ROS fivefold, increased sperm count by 50% (mean count in mill/ml: 21.5+7.2, baseline; 32.6+9.5, post-treatment, P=.0005), and total and progressive sperm motility each by 30% (mean total sperm motility in % 29.8+5.0, baseline: 39.4+6.2, post-treatment, P=.004; mean progressive sperm motility in % 23.1+4.6, baseline: 30.0+5.5, post-treatment, P=.014 vs. baseline). We report for the first time that LAL only improves sperm quality in infertile men who have baseline high-ROS levels prior to treatment. These data have important potential implications for couples with male infertility and their clinicians.

Novel dynein axonemal assembly factor 1 mutations identified using whole‑exome sequencing in patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder caused by dysfunction of the cilia and flagella; however, causative genetic defects have not been detected in all patients with PCD. Seven Chinese Han patients with Kartagener syndrome were enrolled onto the present study. Transmission electron microscopy (TEM) was performed to evaluate the cilial defects and whole-exome sequencing was used to analyze relevant genetic variations in all patients. In two of the seven patients with PCD, four novel dynein axonemal assembly factor 1 (DNAAF1) mutations were identified (NM_178452.6:c.3G>A, c.124+1G>C, c.509delG and c.943A>T) in three alleles. Both of these patients had long-standing infertility. Their chest computed tomography results showed bronchiectasis, lung infections and situs inversus, and paranasal computed tomography revealed sinusitis. Semen analysis of the male patient showed poor sperm motility. TEM showed defects in the inner and outer dynein arms in both patients. The DNAAF1 sequences of family members were then analyzed. Bioinformatics analysis indicated that these mutations may be the cause of the cilial defects in these two probands. Thus, the present study identified novel PCD-causing mutations in DNAAF1 in two patients with PCD. These genetic variations were predicted to alter DNAAF1 amino acid residues and lead to loss of function, thereby inhibiting cilia-mediated motility. Accordingly, the two probands had PCD symptoms, and one of them died due to PCD-associated complications.