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Byline: Manish. Tandon, Aseem. Jindal, Sajal. Gupta, Neeraj. Goel Sir, Systemic sclerosis (SSc) affects multiple organs including the heart.[1] Abnormal electrocardiogram (ECG) is present in the majority,[2] but may be [...]

Purpose: Azoospermia is defined as the absence of spermatozoa in the pellet of a centrifuged semen sample. In fact, when a basic semen analysis fails to detect sperm in the ejaculate, there is still the possibility of detecting rare sperm after centrifugation of the sample and examination of the pellet. In this study, we assessed the role of Cytospin centrifugation in combination with the nuclear fast picroindigocarmine (NF-PIC) staining in identifying sperm in azoospermic samples. Materials and Methods: Semen samples of 251 men diagnosed as having azoospermia after standard examination were further analyzed by Cytospin centrifugation in combination with NF-PIC staining. Results: Sperm were detected in 60 men (23.9%), thus changing their diagnosis to cryptozoospermia. Conclusions: By identifying sperm in the semen of men who were thought to have total azoospermia, the Cytospin NF-PIC test can alter the diagnosis and further treatment of these men. [ABSTRACT FROM AUTHOR]

Solid pseudopapillary epithelial neoplasm (SPEN) of the pancreas is a rare neoplasm of the pancreas accounting for only 0.17-2.7% of all pancreatic neoplasms, often detected initially on imaging. Despite advances in imaging, pseudocysts and other cystic neoplasms feature in the differential diagnosis. We report a case of solid pseudopapillary epithelial neoplasm in a young female who presented with a progressively increasing abdominal lump in whom the diagnosis was considered based on imaging studies. She underwent exploratory laparotomy, pancreaticoduodenectomy, pancreaticojejunostomy, hepaticojejunostomy, gastrojejunostomy, and made an uneventful recovery in the postoperative period. Histopathological examination and immunohistochemistry confirmed the diagnosis. This case highlights the need for a high index of suspicion and timely surgical intervention for optimal outcomes. [ABSTRACT FROM AUTHOR]

Purpose The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. Materials and Methods We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic’s Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. Results Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA’s. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. Conclusions Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy. [ABSTRACT FROM AUTHOR]

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility. [ABSTRACT FROM AUTHOR]

Semen analysis is the first, and frequently, the only step in the evaluation of male fertility. Although the laboratory procedures are conducted according to the World Health Organization (WHO) guidelines, semen analysis and especially sperm morphology assessment is very difficult to standardize and obtain reproducible results. This is mainly due to the highly subjective nature of their evaluation. ICSI is the choice of treatment when sperm morphology is severely abnormal (teratozoospermic). Hence, the standardization of laboratory protocols for sperm morphology evaluation represents a fundamental step to ensure reliable, accurate and consistent laboratory results that avoid misdiagnoses and inadequate treatment of the infertile patient. This article aims to promote standardized laboratory procedures for an accurate evaluation of sperm morphology, including the establishment of quality control and quality assurance policies. Additionally, the clinical importance of sperm morphology results in assisted reproductive outcomes is discussed, along with the clinical management of teratozoospermic patients. [ABSTRACT FROM AUTHOR]

Retrograde ejaculation (RE) is a condition defined as the backward flow of the semen during ejaculation, and when present can result in male infertility. RE may be partial or complete, resulting in either low seminal volume or complete absence of the ejaculate (dry ejaculate). RE can result from anatomic, neurological or pharmacological conditions. The treatment approaches outlined are determined by the cause. Alkalinizing urinary pH with oral medications or by adding sperm wash media into the bladder prior to ejaculation may preserve the viability of the sperm. This article provides a step-by-step guide to diagnose RE and the optimal techniques to retrieve sperm. [ABSTRACT FROM AUTHOR]

The current WHO 2010 manual for human semen analysis defines leukocytospermia as the presence of peroxidase-positive leukocytes at a concentration >1×10[SUP 6] /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. [ABSTRACT FROM AUTHOR]

Sperm vitality testing is a basic semen examination that has been described in the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen from its primary edition, 40 years ago. Several methods can be used to test sperm vitality, such as the eosin-nigrosin (E-N) stain or the hypoosmotic swelling (HOS) test. In the 6th (2021) edition of the WHO Laboratory Manual, sperm vitality assessment is mainly recommended if the total motility is less than 40%. Hence, a motile spermatozoon is considered alive, however, in certain conditions an immotile spermatozoon can also be alive. Therefore, the differentiation between asthenozoospermia (pathological decrease in sperm motility) and necrozoospermia (pathological decrease in sperm vitality) is important in directing further investigation and management of infertile patients. The causes leading to necrozoospermia are diverse and can either be local or general, testicular or extra-testicular. The andrological management of necrozoospermia depends on its etiology. However, there is no standardized treatment available presently and practice varies among clinicians. In this study, we report the results of a global survey to understand current practices regarding the physician order of sperm vitality tests as well as the management practices for necrozoospermia. Laboratory and clinical scenarios are presented to guide the reader in the management of necrozoospermia with the overall objective of establishing a benchmark ranging from the diagnosis of necrozoospermia by sperm vitality testing to its clinical management. [ABSTRACT FROM AUTHOR]

Background: Sentinel lymph node (SLN) remains one of the most important indicators of axillary lymph node status, defining the prognosis of breast cancer (BC) patients. The present study was done to map axillary SLN using dual method of intraoperative axillary ultrasound-guided (USG) and methylene blue dye, in patients receiving neoadjuvant chemotherapy (NAT) for locally advanced BC. Methods: A prospective interventional cross-sectional study was conducted on 36 core-needle biopsy-proven cases of locally advanced breast carcinoma (Stage IIb and Stage III) who received NAT. The SLNs as identified by the bluest staining node (dye method) and the node with a needle inserted in it through axillary USG method were dissected and sent for frozen section in normal saline. It was followed by complete axillary dissection and final histopathology reporting. Diagnostic test was used for calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: After NAT, 26/29 patients with pre-NAT staging of N1 and 5/7 patients with pre-NAT staging of N2 showed significant downstaging of the nodal status after NAT (P < 0.001). We found that the dual method showed similar sensitivity to the dye method and the USG method (94.74%). But, the specificity, PPV, and NPV of the dual method although similar to the dye method (76.47%, 81.82%, and 92.86%, respectively) were lower than that of the USG method (82.35%, 85.71%, and 93.33%, respectively). Conclusion: In conclusion, dual method (dye and USG) is a good attempt in increasing the SLN detection but it is not a powerful test in the application of avoiding axillary lymph node dissection. The comparable sensitivity but lower specificity in determining the SLN restricts its use, and warrants future studies with contrast-enhanced USG to decrease the false negatives. [ABSTRACT FROM AUTHOR]

Semen analysis is a basic test for evaluating male fertility potential, as it plays an essential role in driving the future management and treatment of infertility in couples. Manual semen analysis includes the evaluation of both macroscopic and microscopic parameters, whereas automated semen analysis is conducted through a computer-aided sperm analysis system and can include additional parameters that are not evaluated by manual analysis. Both quality control (QC) and quality assurance (QA) are important to ensure reproducible results for semen analysis, and represent fundamental checks and balances of all stages (pre-analytical, analytical, and post-analytical) of semen analysis. To ensure accuracy and precision, the laboratory technicians’ performance should be evaluated biannually. This narrative review aims to describe standardized laboratory procedures for an accurate assessment of semen parameters that incorporate both QC and QA practices. [ABSTRACT FROM AUTHOR]

Purpose: In response to the COVID-19 pandemic, the American Center for Reproductive Medicine (ACRM) transitioned its annual training in assisted reproductive technology (ART) from a hands-on, laboratory-based training course to a fully online training endorsed by the American College of Embryology. Here we describe our experience and assess the quality of an online training format based on participant outcomes for the first three modules of a planned series of online ART training. Materials and Methods: These modules included manual semen analysis, sperm morphology and ancillary semen tests (testing for leukocytospermia, sperm vitality, and anti-sperm antibody screening). The virtual format consisted of lecture presentations featuring laboratory protocols with corresponding video demonstrations of routine techniques and best practices. Practical scenarios, troubleshooting, and clinical interpretation of laboratory results were also discussed. At the end of each module, an optional multiple choice question test was held as a prerequisite to obtain certification on the topics presented. Course quality was assessed using participant responses collected via online surveys. Results: The digital delivery methods used were found to have largely or completely met the participants’ expectations for all questions (>85%). The majority (>87%) of the participants either strongly agreed or agreed that the course content was well-structured with appropriate depth, and that their overall expectations of the course had been met. Conclusions: This training format appears to be a realistic teaching option to freely share highly specialized expertise and technical knowledge with participants from anywhere in the world with varying levels of competency or experience. [ABSTRACT FROM AUTHOR]

Abstract Oxidative stress (OS), a state characterized by an imbalance between pro-oxidant molecules including reactive oxygen and nitrogen species, and antioxidant defenses, has been identified to play a key role in the pathogenesis of subfertility in both males and females. The adverse effects of OS on sperm quality and functions have been well documented. In females, on the other hand, the impact of OS on oocytes and reproductive functions remains unclear. This imbalance between pro-oxidants and antioxidants can lead to a number of reproductive diseases such as endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility. Pregnancy complications such as spontaneous abortion, recurrent pregnancy loss, and preeclampsia, can also develop in response to OS. Studies have shown that extremes of body weight and lifestyle factors such as cigarette smoking, alcohol use, and recreational drug use can promote excess free radical production, which could affect fertility. Exposures to environmental pollutants are of increasing concern, as they too have been found to trigger oxidative states, possibly contributing to female infertility. This article will review the currently available literature on the roles of reactive species and OS in both normal and abnormal reproductive physiological processes. Antioxidant supplementation may be effective in controlling the production of ROS and continues to be explored as a potential strategy to overcome reproductive disorders associated with infertility. However, investigations conducted to date have been through animal or in vitro studies, which have produced largely conflicting results. The impact of OS on assisted reproductive techniques (ART) will be addressed, in addition to the possible benefits of antioxidant supplementation of ART culture media to increase the likelihood for ART success. Future randomized controlled clinical trials on humans are necessary to elucidate the precise mechanisms through which OS affects female reproductive abilities, and will facilitate further explorations of the possible benefits of antioxidants to treat infertility.

In 2020, the COVID‐19 pandemic led to the suspension of the annual Summer Internship at the American Center for Reproductive Medicine (ACRM). To transit it into an online format, an inaugural 6‐week 2020 ACRM Online Mentorship Program was developed focusing on five core pillars of andrology research: scientific writing, scientific methodology, plagiarism understanding, soft skills development and mentee basic andrology knowledge. This study aims to determine mentee developmental outcomes based on student surveys and discuss these within the context of the relevant teaching and learning methodology. The mentorship was structured around scientific writing projects established by the team using a student‐centred approach, with one‐on‐one expert mentorship through weekly formative assessments. Furthermore, weekly online meetings were conducted, including expert lectures, formative assessments and social engagement. Data were collected through final assessments and mentee surveys on mentorship outcomes. Results show that mentees (n = 28) reported a significant (p <.0001) improvement in all criteria related to the five core pillars. These results illustrate that the aims of the online mentorship program were achieved through a unique and adaptive online educational model and that our model has demonstrated its effectiveness as an innovative structured educational experience through the COVID‐19 crisis. [ABSTRACT FROM AUTHOR]

Purpose: Aberrant expression of seminal plasma proteins are associated with altered homeostasis that may affect the fertilizing ability of spermatozoa. However, the precise roles of seminal exosomes on sperm function remain unclear. The objective of this study was to identify the differentially expressed proteins (DEPs) associated with varicocele-mediated infertility by comparing seminal plasma protein profile of unilateral varicocele patients with proven fertile donors. Materials and Methods: Semen samples were obtained from 10 proven fertile donors with normal semen parameters and 33 infertile patients with unilateral varicocele. For proteomic analysis, 5 samples from each group were pooled and run in triplicate. Key DEPs (ANXA2, TF, CD63, KIF5B, SEMG1) associated with the exosome function were selected by bioinformatic tools and validated using Western blotting. Results: A total of 47 seminal plasma proteins were differentially expressed in unilateral varicocele patients compared to fertile donors. Validation of exosome-associated DEPs in unilateral varicocele patients (n=7) and fertile donors (n=7) revealed significant upregulation of ANXA2 (p=0.0016) and downregulation of KIF5B (p=0.009). The main upstream regulators of the DEPs in seminal plasma of unilateral varicocele group were androgen receptor, YB1 and NRF2. Conclusions: This is the first report to identify DEPs in seminal plasma of unilateral varicocele patients compared to fertile donors. Based on the detection of DEPs associated with exosomal function, Western blotting was used to validate the presence of defective exosome machinery in seminal plasma of unilateral varicocele patients. KIF5B and ANXA2 can be utilized as potential biomarkers of infertility in unilateral varicocele patients. [ABSTRACT FROM AUTHOR]

Oxidative stress is pre‐empted by an adequate level of antioxidants, which scavenge oxidants when they are produced in excess by different sources, including leukocytes and immature spermatozoa. Enzymatic antioxidants, such as superoxide dismutase, catalase and glutathione peroxidase, and several non‐enzymatic antioxidants (proteins, vitamins and minerals), working as oxidant scavengers and cofactors of enzymatic antioxidants have been identified in seminal plasma. The total antioxidant capacity (TAC) is a diagnostic test that can be utilised in the male infertility workup. TAC measures the amount of total antioxidants in seminal plasma. Therefore, it provides an assessment of the reductive potential in seminal plasma. Several studies have investigated the diagnostic application of TAC in various andrology conditions. There is substantial evidence in the literature to show that infertile patients have lower seminal TAC in comparison with fertile men. Moreover, there is a positive correlation between TAC and seminal parameters, such as sperm concentration, motility and morphology. Evaluation of TAC together with reactive oxygen species (ROS) and sperm DNA fragmentation index (DFI) may be beneficial in the diagnosis of male infertility. [ABSTRACT FROM AUTHOR]

Although the lack of information on the costs and pricing of healthcare services prevails throughout the medical industry, empiric observations have demonstrated that pricing information is even more obscured in the sperm cryopreservation market. Thus, the objectives of our study are to assess and compare online price transparency and the price of sperm cryopreservation across various healthcare settings in the United States. This study examined online pricing published by facilities that have an active registration to store spermatozoa with the Food and Drug Administration. Less than one‐fifth of registered facilities display any pricing information online. Price transparency also varies among census regions and facility types. Nationally, the median initial bank fee and annual price of storage are $350 and $385 respectively. Although there were no differences in the initial fee by facility type and census region, the annual price of storing spermatozoa is highest in the Northeast, which could be attributed to laboratory techniques, demographic patterns or insurance coverage. Guidelines from professional societies or different legislation and regulatory requirements across different US states can increase price transparency, which can promote consumer decision‐making and decrease the barrier for men seeking fertility preservation. [ABSTRACT FROM AUTHOR]

Abstract In a healthy body, ROS (reactive oxygen species) and antioxidants remain in balance. When the balance is disrupted towards an overabundance of ROS, oxidative stress (OS) occurs. OS influences the entire reproductive lifespan of a woman and even thereafter (i.e. menopause). OS results from an imbalance between prooxidants (free radical species) and the body's scavenging ability (antioxidants). ROS are a double-edged sword – they serve as key signal molecules in physiological processes but also have a role in pathological processes involving the female reproductive tract. ROS affect multiple physiological processes from oocyte maturation to fertilization, embryo development and pregnancy. It has been suggested that OS modulates the age-related decline in fertility. It plays a role during pregnancy and normal parturition and in initiation of preterm labor. Most ovarian cancers appear in the surface epithelium, and repetitive ovulation has been thought to be a causative factor. Ovulation-induced oxidative base damage and damage to DNA of the ovarian epithelium can be prevented by antioxidants. There is growing literature on the effects of OS in female reproduction with involvement in the pathophsiology of preeclampsia, hydatidiform mole, free radical-induced birth defects and other situations such as abortions. Numerous studies have shown that OS plays a role in the pathoysiology of infertility and assisted fertility. There is some evidence of its role in endometriosis, tubal and peritoneal factor infertility and unexplained infertility. This article reviews the role OS plays in normal cycling ovaries, follicular development and cyclical endometrial changes. It also discusses OS-related female infertility and how it influences the outcomes of assisted reproductive techniques. The review comprehensively explores the literature for evidence of the role of oxidative stress in conditions such as abortions, preeclampsia, hydatidiform mole, fetal embryopathies, preterm labour and preeclampsia and gestational diabetes. The review also addresses the growing literature on the role of nitric oxide species in female reproduction. The involvement of nitric oxide species in regulation of endometrial and ovarian function, etiopathogenesis of endometriosis, and maintenance of uterine quiescence, initiation of labour and ripening of cervix at parturition is discussed. Complex interplay between cytokines and oxidative stress in the etiology of female reproductive disorders is discussed. Oxidant status of the cell modulates angiogenesis, which is critical for follicular growth, corpus luteum formation endometrial differentiation and embryonic growth is also highlighted in the review. Strategies to overcome oxidative stress and enhance fertility, both natural and assisted are delineated. Early interventions being investigated for prevention of preeclampsia are enumerated. Trials investigating combination intervention strategy of vitamin E and vitamin C supplementation in preventing preeclampsia are highlighted. Antioxidants are powerful and there are few trials investigating antioxidant supplementation in female reproduction. However, before clinicians recommend antioxidants, randomized controlled trials with sufficient power are necessary to prove the efficacy of antioxidant supplementation in disorders of female reproduction. Serial measurement of oxidative stress biomarkers in longitudinal studies may help delineate the etiology of some of the diosorders in female reproduction such as preeclampsia.

Lack of standardized, reproducible protocols and reference values is among the challenges faced when using new or upgraded versions of instruments in reproductive laboratories and flow cytometry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay combined with flow cytometry routinely used for diagnostic measurement of sperm DNA fragmentation (SDF) is a unique example. Any change in the setting of the standard instrument, including upgrades of hardware or software, can lead to different results and may affect clinicians' decision for treatment. Therefore, we compared TUNEL results of SDF obtained from a standard (C6) flow cytometer with a newer version of the same instrument (C6 Plus) and examined the cutoff, sensitivity, and specificity without calibration (adjustment) and after adjustment. Identical sperm preparation and matched acquisition settings were used to examine the performance of two flow cytometers. The strength of agreement of the results between the two observers was also assessed. After adjustment of the settings, overall concordance became high and the two cytometers showed 100% positive and negative predictive value with 100% area under the curve. The overall correlation coefficient observed between C6 and C6 Plus was highly significant (P < 0.0001; r = 0.992; 95% confidence interval [CI]: 0.982--0.997). After adjustment, the two cytometers showed very high precision of 98% and accuracy of >99%. The interobserver agreement on C6 flow cytometer for the two observers was 0.801 ± 0.062 and 0.746 ± 0.044 for C6 Plus. We demonstrated a strong agreement between the samples tested on the two flow cytometers after calibration and established the robustness of both instruments. [ABSTRACT FROM AUTHOR]

This work looks at some definitive signatures of magnetars, in particular of period closures accompanied by a decline of X-ray radiation in two models. We review some of the previous works which are based on the well-known dynamo model in which the star is born with a period of a few milliseconds at high temperatures. In such a convection regime, the dynamo mechanism can amplify the magnetic fields to the magnetar value. This is in contrast to a screened core model which posits that a high-density phase transition occurs in the inner core of magnetars that dynamically aligns all the neutron magnetic moments producing a large magnetic field in the core. The accompanying change of flux gives rise to shielding or screening currents in the surrounding high conductivity plasma that do not permit the field to exit to the surface. Ambipolar diffusion then transports the field to the crust dissipating energy in neutrinos and X-rays. The upwelling field cleaves the crust resulting in flares and X-ray radiation from Ohmic dissipation in the crust till the screening currents are damped and the surface polar field attains its final value. In the dynamo model, the polar magnetic field decreases with time, whereas in our screened model it increases to its final value. One consequence of this is that in the latter model, as a function of time and period, the ratio of the dipole radiation loss, |$\dot{E}$| to the X-ray luminosity, L X, is a 'U' curve, indicating that it is the exponential decline in L X that brings closure to the spin periods that are observed for magnetars. [ABSTRACT FROM AUTHOR]