Impaired Sperm Motility Research Articles

Genetic Association in the Maintenance of the Mitochondrial Microenvironment and Sperm Capacity.

Sperm motility is one of the major determinants of male fertility. Since sperm need a great deal of energy to support their fast movement by active metabolism, they are thus extremely vulnerable to oxidative damage by the reactive oxygen species (ROS) and other free radicals generated as byproducts in the electron transport chain. The present study is aimed at understanding the impact of a mitochondrial oxidizing/reducing microenvironment in the etiopathology of male infertility. We detected the mitochondrial DNA (mtDNA) 4,977 bp deletion in human sperm. We examined the gene mutation of ATP synthase 6 (ATPase6 m.T8993G) in ATP generation, the gene polymorphisms of uncoupling protein 2 (UCP2, G-866A) in the uncoupling of oxidative phosphorylation, the role of genes such as manganese superoxide dismutase (MnSOD, C47T) and catalase (CAT, C-262T) in the scavenging system in neutralizing reactive oxygen species, and the role of human 8-oxoguanine DNA glycosylase (hOGG1, C1245G) in 8-hydroxy-2′-deoxyguanosine (8-OHdG) repair. We found that the sperm with higher motility were found to have a higher mitochondrial membrane potential and mitochondrial bioenergetics. The genotype frequencies of UCP2 G-866A, MnSOD C47T, and CAT C-262T were found to be significantly different among the fertile subjects, the infertile subjects with more than 50% motility, and the infertile subjects with less than 50% motility. A higher prevalence of the mtDNA 4,977 bp deletion was found in the subjects with impaired sperm motility and fertility. Furthermore, we found that there were significant differences between the occurrences of the mtDNA 4,977 bp deletion and MnSOD (C47T) and hOGG1 (C1245G). In conclusion, the maintenance of the mitochondrial redox microenvironment and genome integrity is an important issue in sperm motility and fertility.

Ejaculate quality and testosterone levels in men vaccinated with Gam-Covid-Vac (Sputnik-V)

Background. COVID-19 disease is often severe, and therefore it is rational to use vaccination. But many men have concerns about its effect on fertility, which requires clarification. Aim. Evaluation of the quality of the ejaculate and the levels of total testosterone during the use of the Gam-Covid-Vac vaccine (Sput-nik-V). Material and methods. The pilot observational prospective study included 30 men with normozoospermia and 30 with pathozoosper-mia, who have been vaccinated with Gam-Covid-Vac. The study period was from March 2021 to June 2021. The total blood testosterone level and parameters of ejaculate quality were determined. The comparisons were carried out in dynamics, the differences were considered statistically significant at p<0.05. Results. The effect of vaccination on total testosterone levels was not revealed. The effect of vaccination on the parameters of the ejaculate quality in patients with pathozoospermia was not revealed. In the group of patients with normozoospermia among patients with impaired sperm motility, which was –5[–7;–3]% and had no clinical significance, an increase in temperature after vaccination was statistically significantly more frequent. Conclusion. There was no negative effect of the vaccine on total testosterone levels and ejaculate quality. © 2021, Media Sphera Publishing Group. All rights reserved.

Is serum vitamin D level a risk factor for idiopathic male fertility?

Background: Idiopathic male infertility is a health problem that is increasingly common worldwide. Aetiology of idiopathic male infertility is still controversial. In this cross-sectional retrospective study, we aimed to investigate the relationship between serum vitamin D level and sperm quality in patients with idiopathic male infertility.Methods: Between June 2018 and June 2020, 297 patients including 147 men with idiopathic infertility (as a study group) and 150 fertile men (as a control group) were retrospectively enrolled into the study. Blood samples were collected, and these samples included serum sex steroids, serum vitamin D levels, glucose tests, lipid profiles, liver function tests and kidney function tests. At least two sperm analyses, scrotal doppler ultrasonography and karyotype analysis were performed on each of the patients. Demographic, laboratory and radiological features were also recorded. The Mann Whitney-U test was used to compare groups and quantitative independent data. The Chi-square test was used for qualitative independent data. Spearman's correlation analysis was applied for correlation. Significant results were investigated and analysed further using the logistic regression test.Results: The mean age of the patients was 31.98 ± 6.97 years. The mean serum vitamin D level of the patients was 23.16 ± 10.40 ng/dL and the mean infertility duration of patients with idiopathic infertility was 29.88 ± 28.86 months. We observed statistical significance in terms of serum vitamin D levels, impaired total sperm motility, progressive sperm motility and sperm morphology in idiopathic infertile men when compared to fertile men. There were no statistically significant between idiopathic infertile men and fertile men in terms of serum testosterone levels.Conclusions: We observed a positive correlation between serum vitamin D levels and impaired sperm parameters, specifically in terms of sperm morphology, total sperm motility and progressive sperm motility. Vitamin D supplementation may be a beneficial contribution to achieving high paternity rates in men with idiopathic male infertility.

High doses of Uvaria chamae root extract impair sperm motility and viability

Uvaria chamae is a tropical medicinal plant with documented antimicrobial and antimalarial activities. Agents with these activities are known to impair fertility. This study investigated the antifertility effects of ethanolic extract of U. chamae on male albino Wistar rats. Two different oral doses; 56.6 mg/kg body weight and 113.2 mg/kg body weight of the extracts were administered to low dose and high dose group, respectively. A third group served as control and received 2 mL of distilled water. There were five animals in each group. Administration lasted six weeks after which animals were sacrificed and samples collected. Results showed that sperm count, sperm morphology and semen pH were not affected (P&gt;0.05) by the extract. Sperm motility (55.65 %) and viability (64.38 %) were however decreased (P&lt;0.05) by high doses of the extract. Histopathology of testicular tissues also showed no difference across the groups. U. chamae thus impair fertility in vivo especially at high doses.

Expression of PPP3CC and not PPP3R2 is associated with asthenozoospermia

Background and objective: Protein phosphatase 3 catalytic subunit gamma (PPP3CC) and protein phosphatase 3 regulatory subunit B, beta (PPP3R2) are respectively the catalytic and regulatory subunits of calcineurin in sperm. Deficiency in either protein causes impaired sperm motility leading to male infertility. Many cases of sterility are attributed to asthenozoospermia (AZS); however, it remains unknown whether PPP3CC and PPP3R2 are related to AZS. Material and methods: Quantitative PCR and Western blotting were used to investigate the expression levels of PPP3CC and PPP3R2 in the spermatozoa of patients with AZS and to explore the clinical significance. Results: Two calcineurin inhibitors cyclosporine A (CsA) and tacrolimus (FK506) markedly impaired the total motility and progressive motility of human sperm, indicating that PPP3CC or PPP3R2 might be involved in AZS. PPP3CC mRNA and protein expression was lower in the ejaculated spermatozoa of patients with AZS than in normal sperm (NS). Correlation analysis showed that PPP3CC protein expression correlated positively with progressive motility (r = 0.2592, P &lt; 0.05); however, there were no significant differences in PPP3R2 mRNA and protein levels between AZS and NS. Conclusion: These findings suggest that the abnormal expression of PPP3CC rather than PPP3R2 might be a pathological factor or indicator in AZS. Thus, PPP3CC may be a potential therapeutic or diagnostic target for some cases of male infertility.

Effects of anesthetic MS-222 on stress and reproduction of South American silver catfish (Rhamdia quelen) males

Anesthesia is a common practice used in fish research and aquaculture. It is important to understand anesthetic effects on the animal and tissues of interest to ensure validity of data and to improve animal welfare in research and fish production endeavors. The production of some captive fish species is only possible by imposing artificial reproduction procedures, and manipulation of fish for these purposes is a stressor. The purpose of this study, therefore, was to evaluate effects of different concentrations (100, 200, and 300 mg/L) of the anesthetic MS-222 (tricaine methanesulfonate) on cortisol concentrations and effects on sperm quality in Rhamdia quelen. After hormonal induction of gamete production, 28 sexually mature males were randomly assigned to treatments, and milt and blood samples were collected. Anesthesia induction time, motility rate, sperm concentration and morphology, plasma cortisol concentrations, and reproductive hormone concentrations (testosterone, 17-α-hydroxyprogesterone, and estradiol) were evaluated. Sperm motility was greater in the control than 300 mg/L treatment group but did not differ among the control, 100, and 200 mg/L groups. The estradiol concentration was greater in non- anesthetized than anesthetized Rhamdia quelen, but plasma cortisol concentrations did not differ among treatment groups (182.50 ± 42.03 ng/mL). The anesthetic MS-222 at concentrations of 100, 200, and 300 mg/L did not inhibit the stress response due to handling of Rhamdia quelen males. In addition, treatment with MS-222 was not effective in inhibiting detrimental effects on sperm quality because this treatment was associated with impaired sperm motility and lesser concentrations of plasma estradiol.

Impaired sperm quantity and motility in adult rats following gestational and lactational exposure to environmentally relevant levels of PBDE-47: A potential role of thyroid hormones disruption.

Polybrominated diphenyl ethers (PBDEs) are flame retardants and the congener 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) is capable of inducing thyroid endocrine disruption and developmental toxicity. However, little is known about whether developmental PBDE-47 exposure-elicited alterations in semen quality is associated with thyroid hormones (THs) perturbation. In this research, we sought to explore the impacts of gestational and lactational PBDE-47 exposure on adult sperm quantity and motility, and its link with THs levels. For this purpose, female Sprague-Dawley rats were administered environmentally relevant PBDE-47 levels (0.1, 1.0, 10mg/kg/day) by oral gavage from prepregnancy through lactation cessation to achieve early-life exposure of offspring and to mimic the actual exposure. Sperm quantity and motility together with serum THs levels from male offspring were determined on postnatal day 88. In utero and lactational exposure to PBDE-47 boosted the weight gain while reduced the relative testis weight in adult male offspring. These were accompanied with the reductions in sperm counts (total and living sperm counts), the percentage of progressive sperm motility, sperm velocities (curvilinear velocity, straight-line velocity and average path velocity), motion path (beat cross frequency, linearity and wobble) and linear motile sperm parameters (count, motility and concentration). Further studies identified that the levels of serum triiodothyronine (T3) were increased by PBDE-47 exposure and negatively associated with those differential semen parameters on quantity and motility. Collectively, our results indicate that exposure to low-level PBDE-47 during early-life development impairs semen quality in adult rats, which could be mediated partially by abnormal T3 levels.

Evaluation of the role of reflux pattern in Color Doppler Ultrasound on spermogram improvement after varicocelectomy.

Many attempts are being made to find an association between varicocele characteristics and sperm parameters. In this study, we investigated the association between a newly introduced varicocele reflux grading pattern and sperm parameters, as well as its effect on spermogram improvement after varicocelectomy. In a prospective study, 73 patients with a clinical single-sided varicocele who underwent corrective varicocelectomy were included. Reflux pattern was determined on Color Doppler Ultrasound (CDUS) and categorized into four grades: grade 1 (retrograde), grade 2 (augmentation), grade 3 (enhancement), and grade 4 (stasis). The association of pre- and postoperative spermogram with the patients' reflux pattern was evaluated. A significant positive association was found between the venous diameter and reflux pattern. Higher grades of the reflux pattern were associated with the more severe hemodynamic pattern of the reflux (shunt type). A significant association was found between the reflux pattern and preoperative semen characteristics, and this association was more prominent in constant venous diameter. In this respect, the enhancing reflux type was associated with the most impaired preoperative sperm count, motility, and morphology. The enhancing type also revealed the most improvement in spermogram after varicocelectomy. Patients with a higher reflex grade, particularly enhancing pattern, will most benefit from the surgical correction of varicocele. These findings suggest reflux pattern as a promising prognostic factor for a favorable outcome after varicocelectomy.

Human X chromosome exome sequencing identifies BCORL1 as contributor to spermatogenesis

BackgroundInfertility affects approximately 15% of couples worldwide with male infertility being responsible for approximately 50% of cases. Although accumulating evidence demonstrates the critical role of the X chromosome in spermatogenesis...

Evaluation of human papilloma virus in semen as a risk factor for low sperm quality and poor in vitro fertilization outcomes: a systematic review and meta-analysis

To analyze the effect of human papilloma virus (HPV) sperm infection on sperm parameters and invitro fertilization (IVF) outcomes. Systematic review and meta-analysis. Not applicable. Men with HPV sperm infection and couples undergoing IVF. Searches were conducted in the following databases: Medline(R), PubMed, Embase, Web of Science, Scopos, and the Cochrane Library. We included studies examining sperm parameters and IVF results in patients with and without HPV sperm infection. Sperm analysis (concertation, count, volume, motility, morphology), according to the World Health Organization manual, pregnancy rate (PR), and miscarriage rate (MR). Sixteen studies were included in this meta-analysis. The presence of HPV had a significant association with impaired sperm parameters in terms of concentration (mean difference [MD] -4.48, 95% confidence interval [CI] - 6.12 to -2.83), motility (MD -11.71, 95% CI - 16.15 to -7.26), and morphology (MD -2.44, 95% CI - 4.08 to -0.79. A review of the literature regarding ART outcomes showed an association between HPV infection and decreased PR, and an even stronger association between HPV infection and increased MR. Our meta-analysis shows a negative effect of HPV on sperm concentration, motility, and morphology. Further subgroup and categorical analysis confirmed the clinical significance of impaired sperm motility in HPV-infected sperm, although the sperm count and morphology must be carefully analyzed. The studies reviewed reported lower PR and increased MR in couples with HPV-infected sperm. As most studies had a moderate risk of bias, these observations warrant further large, well-designed studies before introducing clinical management recommendations. CRD42019127419.

Long-term storage of boar seminal doses contaminated with Proteus vulgaris: A dose-dependent effect on sperm motility and sperm-bacteria interaction

This study evaluated how Proteus vulgaris affects sperm quality and sperm-bacteria interaction in stored semen samples. A strain of P. vulgaris resistant to streptomycin, penicillin, lincomycin and spectinomycin was added to boar semen in doses of 103, 105, 106, 107 and 108 CFU/mL. A sample in which there was no addition of P. vulgaris was the negative control. Sperm quality was determined by evaluating sperm motility and morphology using the computer-assisted sperm analysis (CASA) system, and plasma membrane and acrosome integrity using flow cytometry at 0, 1, 2, 4, 6, 8 and 10 days of liquid-storage at 17 °C. At the same time points, pH, sperm agglutination, sperm-bacteria interaction and bacterial growth were also assessed. There was impaired sperm motility when the infective doses of P. vulgaris were equal to or greater than 105 CFU/mL with the effect being dose-dependent (P < 0.05). When infective doses of P. vulgaris were of 106 to 108 CFU/mL there were impairments of plasma membrane and acrosome integrity by Day 1 of storage (P < 0.05), and alkalinisation of the storing medium by Day 4 (P < 0.05). Bacterial adhesion increased when infective dose of P. vulgaris was greater and as duration of storage increased. P. vulgaris had a high affinity for the mid- and principal pieces of sperm cells. It is concluded there were alterations in sperm motility in samples infected with P. vulgaris that were associated with bacterial adhesion and medium alkalinisation.

Discovery of the First Human Arylsulfatase A Reversible Inhibitor Impairing Mouse Oocyte Fertilization.

Arylsulfatase A (ARSA) plays a crucial role in the reproduction of mammals due to its involvement in the specific gamete interaction preceding sperm and egg fusion leading to fertilization. Recently, it has been shown that zona pellucida (ZP) sperm binding and in vivo fertilization in mice are markedly hampered by using a specific anti-ARSA antibody. Herein, the design and discovery of the first ARSA small molecule inhibitor based on a coumarin-containing polycycle are presented. Through a structure-based approach applied on our in-house library, compound 1r was identified as an ARSA reversible inhibitor (ARSAi); then its activity was validated through both surface plasmon resonance and biochemical inhibition experiments, the first providing a KD value of 21 μM and the latter an IC50 value of 13.2 μM. Further investigations highlighted that compound 1r induced 20% sperm death at 25 μM and also impaired sperm motility; nevertheless both the effects were mediated by ROS production, since they were rescued by the cotreatment of 1r and N-acetyl cysteine (NAC). Interestingly, while 1r was not able to hamper the ZP/sperm binding, it markedly decreased the in vitro oocyte fertilization by mouse sperm up to 60%. Notably, this effect was not hampered by 1r/NAC coadministration, hence allowing the ruling out of an ROS-dependent mechanism. In conclusion, herein is reported the first ever hit of ARSAi as a chemical tool that will enable better exploration of ARSA's biological role in fertilization as well as provide a starting point for developing 1r structure optimization aimed at increasing enzyme inhibition potency but also providing a deeper understanding of the involvement of ARSA in the fertilization pathway mechanism.

Testis-enriched kinesin KIF9 is important for progressive motility in mouse spermatozoa.

Kinesin is a molecular motor that moves along microtubules. Kinesin family member 9 (KIF9) is evolutionarily conserved and expressed strongly in mouse testis. In the unicellular flagellate Chlamydomonas, KLP1 (ortholog of KIF9) is localized to the central pair microtubules of the axoneme and regulates flagellar motility. In contrast, the function of KIF9 remains unclear in mammals. Here, we mutated KIF9 in mice using the CRISPR/Cas9 system. Kif9 mutated mice exhibit impaired sperm motility and subfertility. Further analysis reveals that the flagella lacking KIF9 showed an asymmetric waveform pattern, which leads to a circular motion of spermatozoa. In spermatozoa that lack the central pair protein HYDIN, KIF9 was not detected by immunofluorescence and immunoblot analysis. These results suggest that KIF9 is associated with the central pair microtubules and regulates flagellar motility in mice.

Absence of murine CFAP61 causes male infertility due to multiple morphological abnormalities of the flagella

Impaired flagellar development and impaired motility of sperm is a cause of infertility in males. Several genes, including those of the AKAP, CCDC, CFAP, and DNAH families, among others, are involved in the “multiple morphological abnormalities of the flagella” (MMAF) phenotype; these are the most common causes of male infertility. The Cilia-and flagella-associated protein (CFAP) family includes six members reported to cause MMAF phenotypes: CFAP43, CFAP44, CFAP69, CFAP65, CFAP70, and CFAP251. Here, we found that cilia-and flagella-associated protein 61 (Cfap61) is highly expressed specifically in murine testes and show that the Cfap61-knockout male mice demonstrate MMAF phenotype, including sperm with short, coiled, and irregular flagella. Deletion of Cfap61 resulted in severe morphological and behavior abnormalities in sperm, reduced total sperm counts, impaired sperm motility, and led to male infertility. Notably, absence of Cfap61 impaired sperm flagella ultrastructural abnormalities on account of numerous distortions in multiple flagellum components. Immunostaining experiments in wild-type mice and healthy adult humans indicated that Cfap61 is initially localized at the neck of sperm, where it potentially functions in flagellum formation, and is later localized to the midpiece of the sperm. Thus, our study provides compelling evidence that dysregulation of Cfap61 affects sperm flagellum development and induces male infertility in mice. Further investigations of the CFAP61 gene in humans alongside clinical evidence showing MMAF phenotype in humans should contribute to our understanding of developmental processes underlying sperm flagellum formation and the pathogenic mechanisms that cause male infertility.

Biallelic mutations in CFAP65 cause male infertility with multiple morphological abnormalities of the sperm flagella in humans and mice

BackgroundMale infertility is a prevalent issue worldwide, mostly due to the impaired sperm motility. Multiple morphological abnormalities of the sperm flagella (MMAF) present aberrant spermatozoa with absent, short, coiled, bent...

Taurine effects on Bisphenol A-induced oxidative stress in the mouse testicular mitochondria and sperm motility.

Objectives:This study was performed to investigate the protective effects of taurine (2-aminoethanesulfonic acid, TAU) on oxidative stress in the isolated mouse testicular mitochondria, mitochondrial membrane potential (MMP), viability and motility of the exposed sperms to the BPA.Methods:We treated epididymal spermatozoa obtained from mice and isolated mouse testicular mitochondria with BPA (0.8 mmol/mL) and various doses of TAU (5, 10, 30 and 50 µmol/L). We used the MTT assay and Rhodamine 123 uptake to assess sperm viability and MMP. We assessed the oxidative stress through measuring ROS (reactive oxygen species), MDA (malondialdehyde), GSH (glutathione), and SOD (super-oxide dismutase) levels in the testicular mitochondrial tissue.Results:BPA significantly elevated ROS, MDA and MMP levels, and markedly reduced SOD and GSH levels in the isolated mitochondria. BPA also considerably impaired spermatozoa viability and motility. Pretreatment with 30 and 50 µmol/L of TAU could considerably suppressed mitochondrial oxidative stress, enhanced MMP, and improved sperm motility and viability.Conclusion:TAU may attenuate the BPA-induced mitochondrial toxicity and impaired sperm motility via decreasing oxidative stress.

Association of tension-free inguinal hernia repair and pathospermia in fertile men

To reveal the association of tension-free inguinal hernia repair and pathospermia in fertile men. We have retrospectively analyzed medical records of 512 men who appealed to andrologist with complaints of the absence of pregnancy in wife in 2018. We evaluated duration and features of infertility, presence/absence of previous inguinal hernia repair, spermogram data (according to WHO criteria, 2010) in all patients. Duration of infertility in men after inguinal hernia repair persists for 4.2±2.1 years. Right-sided hernia repair was performed in 36 (48.6%) patients, left-side - 23 (31%), bilateral repair - 15 (20.2%) patients. Men with impaired sperm motility prevailed among patients after right-sided inguinal hernia repair (17 (47.2%) people). Left-sided hernia repair was followed by asthenozoospermia in 8 (34.7%) cases, bilateral hernia repair - in 3 (20%) cases. The most severe abnormalities in semen analysis (azoospemia) develop after bilateral hernia repair. Inguinal tension-free hernia repair is a risk factor for male infertility in 14.4% of cases. It is very important to examine a man in case of infertile marriage. Previous surgical interventions including inguinal hernia repair should be considered.

Roles of glycogen synthase kinase 3 alpha and calcineurin in regulating the ability of sperm to fertilize eggs

Glycogen synthase kinase 3 (GSK3) was identified as an enzyme regulating sperm protein phosphatase. The GSK3α paralog, but not GSK3β, is essential for sperm function. Sperm lacking GSK3α display altered motility and are unable to undergo hyperactivation, which is essential for fertilization. Male mice lacking sperm-specific calcineurin (PP2B), a calcium regulated phosphatase, in testis and sperm, are also infertile. Loss of PP2B results in impaired epididymal sperm maturation and motility. The phenotypes of GSK3α and PP2B knockout mice are similar, prompting us to examine the interrelationship between these two enzymes in sperm. High calcium levels must exist to permit catalytically active calcineurin to function during epididymal sperm maturation. Total and free calcium levels are high in immotile compared to motile epididymal sperm. Inhibition of calcineurin by FK506 results in an increase in the net phosphorylation and a consequent decrease in catalytic activity of sperm GSK3. The inhibitor FK506 and an isoform-selective inhibitor of GSK3α, BRD0705, also inhibited fertilization of eggs in vitro. Interrelated functions of GSK3α and sperm PP2B are essential during epididymal sperm maturation and during fertilization. Our results should enable the development of male contraceptives targeting one or both enzymes.

Perfluoro-octanoic acid impairs sperm motility through the alteration of plasma membrane.

Perfluoroalkyl-substances (PFAS) are chemical additives considered harmful for humans. We recently showed that accumulation of perfluoro-octanoic acid (PFOA) in human semen of exposed subjects was associated with altered motility parameters of sperm cells, suggesting direct toxicity. To determine whether direct exposure of human spermatozoa to PFOA was associated to impairment of cell function. Spermatozoa isolated from semen samples of ten normozoospermic healthy donors were exposed up to 2h to PFOA, at concentrations from 0.1 to 10ng/mL. Viability and motility parameters were evaluated by Sperm Class Analyser. Cell respiratory function was assessed by both mitochondrial probe JC-1 and respiratory control ratio (RCR) determination. Sperm accumulation of PFOA was quantified by liquid chromatography-mass spectrometry. Expression of organic ion-transporters OATP1 and SLCO1B2 was assessed by immunofluorescence and respective role in PFOA accumulation was evaluated by either blockade with probenecid or membrane scavenging through β-cyclodextrin (β-CD). Plasma membrane fluidity and electrochemical potential (ΔΨp) were evaluated, respectively, with Merocyanine-540 and Di-3-ANEPPDHQ fluorescent probes. Compared to untreated controls, a threefold increase of the percentage of non-motile sperms was observed after 2h of exposure to PFOA regardless of the concentration of PFOA, whilst RCR was significantly reduced. Only scavenging with β-CD was effective in reducing PFOA accumulation, suggesting membrane involvement. Altered membrane fluidity, reduced ΔΨp and sperm motility loss associated with exposure to PFOA were reverted by β-CD treatment. PFOA alters human sperm motility through plasma-membrane disruption, an effect recovered by incubation with β-CD.

What do we know about the genetic background of primary ciliary dyskinesia (PCD) and the reproductive approach?

Introduction: Primary ciliary dyskinesia (PCD; MIM 244400) is a heterogeneous autosomal recessive genetic disorder associated with infertility due to impaired sperm motility in men. We describe two such cases and give a literature review on the genetic background and reproductive outcome. Materials and methods: Two primary infertile couples were referred to our clinic. Native semen, analyzed according to the WHO manual (2010), showed that male partners have completely immotile sperm with a negative pentoxifylline test. Sample vitality was compared according to different semen preparation methods (gradient density and washing method only). Genetic testing was done by Whole Exome next-generation Sequencing (WES) analysis. For the IVF/ICSI procedure, semen was prepared using the gradient density method, and prior to the ICSI procedure itself, a hypo-osmotic swelling test (HOST) was done. Results: Semen analysis showed oligoasthenozoospermia in Patient 1 and oligoasthenoteratozoospermia in Patient 2. Blood draw for hormones and karyotype showed no irregularities in either case. Patient 1 was previously diagnosed with PCD, while Patient 2 was not. Parallel vitality testing did not show any differences between the two semen preparation methods in either of the two cases. Genetic testing in Patient 2 showed a pathogenic apparently homozygous CCDC40:c.2440C&amp;gt;T variant in exon 14 of the CCDC40 gene (MIM 613799). Fertilization rate after HOST/ICSI in both patients was 100%, and the final outcome for both patients was the birth of a healthy child. Conclusion: Although PCD has diverse etiology, assisted reproduction techniques such as HOST give these couples a good chance for parenthood. Advances in testing and strict adherence to advised procedures are to be credited for such outcome improvement. Additionally, our recommendation for PCD patients and patients with immotile sperm is to do genetic testing and counselling prior to the IVF/ICSI procedure.