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Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial.

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method.Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Background: Currently, there is some evidence that adenomyosis patients using gonadotropin-releasing hormone (GnRH) agonist long downregulation (LDR) prior to embryo transfer may improve in vitro fertilization (IVF) success rate, but not to the baseline expected success where there is no adenomyosis. Given the association between adenomyosis and an aberrant endometrial immune environment, many physicians also use prednisolone or Intralipid adjuvant treatments in combination with GnRH agonist therapy, despite neither being of proven benefit. Objective: The purpose of this study was to investigate whether the addition of prednisolone or Intralipid immune therapy to GnRH agonist LDR improves fertility outcomes in patients with adenomyosis. Methods: This is a retrospective cohort study of 116 consecutive adenomyosis patients who underwent their first transfer of a genetically screened euploid embryo between January 2019 and December 2020 at a private IVF clinic. Results: There was no difference in maternal age, body mass index, number of embryo’s transferred and gravidity or parity among the three treatment groups. Patients who received Intralipid had a poorer prognosis with a longer duration of infertility (4 years) and a higher number of previous embryo transfers (ETs, 5 previous ETs) compared to the comparison groups. Logistic regression analysis adjustment for all covariates revealed that LDR plus Intralipid therapy produced significantly higher live birth rates (LBRs; 60%) compared to LDR alone (40% LBR); yet, the addition of prednisolone to GnRH agonist LDR (30% LBR) provided no additional live birth benefit. Conclusion: In this retrospective analysis, we showed Intralipid adjuvant treatment in combination with GnRH agonist therapy in adenomyosis patients undergoing IVF resulted in a LBR expected in women without adenomyosis using preimplantation genetic testing screened embryos. This benefit was not seen when using prednisolone as an adjuvant to GnRH agonist LDR. Future randomized clinical trials will be required to confirm the therapeutic benefit of Intralipid in combination with GnRH agonist therapy.

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 im-mune 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 relation-ship 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 ar-ticle, 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 as-sessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are pre-sented 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.

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.

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.

Purpose: The use of antioxidants is common practice in the management of infertile patients. However, there are no estab-lished guidelines by professional societies on antioxidant use for male infertility. Materials and Materials and Methods:Methods: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. Results:Results: Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3?? months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician?셲 age, geographic origin, experience or training in male infertility. Conclusions:Conclusions: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide under-standing of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage. Since sperm DNA damage may reduce embryo quality and increase miscarriage rates, it is possible that untreated sperm oxidative stress may impair in vitro fertilization (IVF) live birth rates. Given that the antioxidant Menevit is reported to reduce sperm DNA damage, it was hypothesized that men's consumption of this supplement may alter IVF outcomes. Therefore, a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer. Men were classified as controls if they were taking no supplements, health conscious controls if taking “general health” supplements, or Menevit users. Men with karyotype abnormalities, or cycles using donated, frozen and surgically extracted sperm were excluded. Among the final study cohort of 657 men, live birth rates were significantly higher in Menevit users than controls (multivariate adjusted odds ratio [OR]: 1.57, 95% confidence interval [CI]: 1.01–2.45, P= 0.046), but not between controls taking no supplements and those using general health supplements, thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users. Interestingly, in a post hoc sensitivity analysis, live birth rates among Menevit users were statistically superior to controls for lean men (OR: 2.73, 95% CI: 1.18–6.28; P= 0.019), not their overweight/obese counterparts (OR: 1.29, 95% CI: 0.75–2.22, P = 0.37). The results of this large cohort study therefore support a positive association between men's use of the Menevit antioxidant during IVF treatment and live birth rates, especially in lean individuals.

Selection of a blastocyst for transfer is based on day5/6 morphology with day3 morphology only used if two blastocysts are equal in quality. Day3 assessments are based on cell number and fragmentation with embryos that are developmentally advanced ([Formula: see text]10 cells) being downgraded. After extended development, if [Formula: see text]10 cell embryos are the best quality they are selected for transfer. Thus, the aim of this study was to determine if cell number on day3 has an impact on embryo fate, euploidy rates and pregnancy rates. Data was retrospectively analysed from 269 women (average age 35.7) undergoing stimulated IVF treatment. Embryos were allocated to one of four categories based on day3 morphological score [Formula: see text]6 cells, 7-9 cells, 10-12 cells and [Formula: see text]13 cells. Results were correlated with embryo fate (vitrification/transfer) and pregnancy rates. After extended culture embryos with [Formula: see text]13 cells on day 3 were mostly likely to have undergone a fresh transfer (28.1%, p[Formula: see text]0.05) compared with embryos with 7-9 cells and 10-12 cells (13.7% and 14.0%, respectively). Embryos with [Formula: see text]6 cells were least likely to be transferred (5.2%) and vitrified (7.1%). Further, embryos with [Formula: see text]6 cells had the lowest pregnancy rate (12.5%) compared with all other groups (p[Formula: see text]0.05). No differences were observed for embryos with 7-9 cells, 10-12 cells and [Formula: see text]13 cells for vitrification rates (42.3%, 40.5% and 35.1%, respectively) or pregnancy rates (33.5%, 43.5% and 45.8%, respectively). Interestingly, the incidence of euploid embryos was increased in [Formula: see text]13 cell embryos (70.0%, p[Formula: see text]0.05) compared with [Formula: see text]6 cells, 7-9 cells and 10-12 cells (52.0%, 42.6% and 52.5%, respectively). Results from this study provide evidence that a review on cleavage stage embryo grading protocols which currently downgrades developmentally advanced embryos [Formula: see text]10 cells is warranted as these embryos do not appear to have a negative impact on pregnancy rates and can result in some of the best clinical outcomes.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

The dual-sugar intestinal permeability test is a commonly used test to assess changes in gut barrier function. However, it does not identify functional changes and the exact mechanism of damage caused by the increased intestinal permeability. This study aims to explore the application of untargeted metabolomics and lipidomics to identify markers of increased intestinal permeability. Fifty fasting male participants (18–50 years) attended a single visit to conduct the following procedures: assessment of anthropometric measures, assessment of gastrointestinal symptoms, intestinal permeability test, and assessment of blood samples 90 min post-administration of the intestinal permeability test. Rhamnose and lactulose were analysed using gas chromatography-mass spectrometry (GC-MS). Untargeted polar metabolites and lipidomics were assessed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF MS). There was an elevated lactulose/rhamnose ratio in 27 subjects, indicating increased permeability compared to the remaining 23 control subjects. There were no significant differences between groups in characteristics such as age, body mass index (BMI), weight, height, and waist conference. Fourteen metabolites from the targeted metabolomics data were identified as statistically significant in the plasma samples from intestinal permeability subjects. The untargeted metabolomics and lipidomics analyses yielded fifteen and fifty-one statistically significant features, respectively. Individuals with slightly elevated intestinal permeability had altered energy, nucleotide, and amino acid metabolism, in addition to increased glutamine levels. Whether these biomarkers may be used to predict the early onset of leaky gut warrants further investigation.

The Limulus amebocyte assay (LAL) is increasingly used to quantify metabolic endotoxemia (ME), particularly in feeding studies. However, the assay was not intended to assess plasma at levels typically seen in ME. We aimed to optimize and validate the LAL assay under a range of pre-treatment conditions against the well-established lipopolysaccharide binding protein assay (LBP). Fifteen healthy overweight and obese males aged 28.8 ± 9.1years provided plasma. The LAL assay employed a range of pre-treatments; 70 °C for 15 and 30 min and 80 °C for 15 and 30 min, ultrasonication (70 °C for 10 min and then 40 °C for 10 min), and dilution (1:50, 1:75, 1:100, and 1:200 parts) or diluted using 0.5% pyrosperse. Seventeen different plasma pre-treatment methods employed prior to the use of the LAL analytical technique failed to show any relationships with either LBP, or body mass index (BMI; obesity), the biological trigger for ME (p > 0.05 for all). As expected, BMI positively correlated with LBP (r = 0.523, p = 0.052. No relationships were observed between LAL with any of the sample pre-treatments and LBP or BMI. In its current form, the LAL assay is unsuitable for detecting levels of endotoxin typically seen in ME.