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Showing papers on "Sperm published in 2022"


Journal ArticleDOI
TL;DR: In this article , the contagiousness of sperm and its influence on fertility after recovery from COVID-19 infection was studied in one hundred twenty Belgian men who had recovered from proven CoV19 infection.

52 citations


Journal ArticleDOI
TL;DR: In this article , the authors reported a significant decrease in sperm concentration (SC) and total sperm count (TSC) among men from North America-Europe-Australia (NEA) based on studies published during 1981-2013.
Abstract: BACKGROUND Numerous studies have reported declines in semen quality and other markers of male reproductive health. Our previous meta-analysis reported a significant decrease in sperm concentration (SC) and total sperm count (TSC) among men from North America-Europe-Australia (NEA) based on studies published during 1981-2013. At that time, there were too few studies with data from South/Central America-Asia-Africa (SAA) to reliably estimate trends among men from these continents. OBJECTIVE AND RATIONALE The aim of this study was to examine trends in sperm count among men from all continents. The broader implications of a global decline in sperm count, the knowledge gaps left unfilled by our prior analysis and the controversies surrounding this issue warranted an up-to-date meta-analysis. SEARCH METHODS We searched PubMed/MEDLINE and EMBASE to identify studies of human SC and TSC published during 2014-2019. After review of 2936 abstracts and 868 full articles, 44 estimates of SC and TSC from 38 studies met the protocol criteria. Data were extracted on semen parameters (SC, TSC, semen volume), collection year and covariates. Combining these new data with data from our previous meta-analysis, the current meta-analysis includes results from 223 studies, yielding 288 estimates based on semen samples collected 1973-2018. Slopes of SC and TSC were estimated as functions of sample collection year using simple linear regression as well as weighted meta-regression. The latter models were adjusted for predetermined covariates and examined for modification by fertility status (unselected by fertility versus fertile), and by two groups of continents: NEA and SAA. These analyses were repeated for data collected post-2000. Multiple sensitivity analyses were conducted to examine assumptions, including linearity. OUTCOMES Overall, SC declined appreciably between 1973 and 2018 (slope in the simple linear model: -0.87 million/ml/year, 95% CI: -0.89 to -0.86; P < 0.001). In an adjusted meta-regression model, which included two interaction terms [time × fertility group (P = 0.012) and time × continents (P = 0.058)], declines were seen among unselected men from NEA (-1.27; -1.78 to -0.77; P < 0.001) and unselected men from SAA (-0.65; -1.29 to -0.01; P = 0.045) and fertile men from NEA (-0.50; -1.00 to -0.01; P = 0.046). Among unselected men from all continents, the mean SC declined by 51.6% between 1973 and 2018 (-1.17: -1.66 to -0.68; P < 0.001). The slope for SC among unselected men was steeper in a model restricted to post-2000 data (-1.73: -3.23 to -0.24; P = 0.024) and the percent decline per year doubled, increasing from 1.16% post-1972 to 2.64% post-2000. Results were similar for TSC, with a 62.3% overall decline among unselected men (-4.70 million/year; -6.56 to -2.83; P < 0.001) in the adjusted meta-regression model. All results changed only minimally in multiple sensitivity analyses. WIDER IMPLICATIONS This analysis is the first to report a decline in sperm count among unselected men from South/Central America-Asia-Africa, in contrast to our previous meta-analysis that was underpowered to examine those continents. Furthermore, data suggest that this world-wide decline is continuing in the 21st century at an accelerated pace. Research on the causes of this continuing decline and actions to prevent further disruption of male reproductive health are urgently needed.

47 citations


Journal ArticleDOI
TL;DR: In this paper , male and female C57BL/6 mice were exposed to saline or 0.1 mg/d polystyrene microplastics for 30 days or 44 days to determine the effects of MPs on reproductive systems, following which some of the mice were caged for 10 days to mate to test fertility.

37 citations


Journal ArticleDOI
TL;DR: In this paper , the BNT162b2 COVID-19 vaccine does not seem to affect sperm parameters, and sperm parameters showed no significant changes after vaccination among men with a normal and abnormal semen analysis.
Abstract:

Abstract

Research question

Does the BNT162b2 COVID-19 vaccine affect sperm parameters of patients with a normal or an abnormal semen analysis?

Design

Data were collected from male patients undergoing IVF treatment after completing vaccination between February 2021 and June 2021 (post-vaccine). For comparison, records of the same patients were reviewed before the vaccination (pre-vaccine) back to January 2017. Patients with azoospermia were excluded. Sperm parameters were compared between pre- and post-vaccine groups. Each patient served as self-control.

Results

Seventy-two patients were included in the study (median interquartile range [IQR] age 35.7 [33.0–43.0] years), of whom 57 had a normal semen analysis. The time between the first vaccine and the post-vaccine sperm analysis was 71.0 (40.5–104.8) days. The sperm parameters before and after the vaccination were as follows: sperm volume before 3.0 (2.0–4.0) and after 3.0 (1.6–3.9) ml, P = 0.02; sperm concentration before 26.5 (14.0–64.7) and after 31.0 (14.2–80.0) 106/ml, P = 0.35; and total motile sperm count before 33.7 (9.0–66.0) and after 29 (6.0–97.5)106, P = 0.96. Sub-group analyses were conducted for patients with male infertility and patients with a normal semen analysis. Neither of the sub-groups showed significant changes after vaccination.

Conclusion

Sperm parameters showed no significant changes after vaccination among men with a normal and abnormal semen analysis. Therefore, the BNT162b2 vaccine does not seem to affect sperm parameters. The preliminary results are reassuring for the entire global population, currently undergoing intense vaccination campaigns against COVID-19.

35 citations


Journal ArticleDOI
TL;DR: A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021 as mentioned in this paper , where semen samples from 75 fertile men were analyzed 1-2 months following their second dose of Pfizer's COVID-19 vaccine.
Abstract: Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters?A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1-2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology.The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 × 106/ml, with only a single participant (1.3%) with a sperm count of 12.5 × 106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO.The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

34 citations


Journal ArticleDOI
TL;DR: In this article , the authors focused on some of these environmental factors that affect semen quality and hence, can cause male infertility, including air pollution, use of pesticides and harmful chemicals, exposure to excessive heat and can lead to decreased male fertility.
Abstract: Abstract Background Worldwide rising trend in infertility has been observed in the past few years with male infertility arising as a major problem. One main reason for the rise in male infertility cases is declining semen quality. It was found that any factor that affects semen quality can affect male fertility. There are several modifiable factors affecting semen quality including air pollution, use of pesticides and harmful chemicals, exposure to excessive heat, and can lead to decreased male fertility. Main body The present review focuses on some of these environmental factors that affect semen quality and hence, can cause male infertility. The literature from 2000 till June 2021 was searched from various English peer-reviewed journals and WHO fact sheets using the USA National Library of Medicine (PubMed) database, the regional portal of Virtual Health Library, and Scientific Electronic Library Online. The search terms used were: “Air pollution and male fertility”, “Chemicals and male infertility”, “Heat exposure and infertility”, “heavy metals and male fertility”. Conclusion Adverse environmental factors have a significant impact on semen quality, leading to decreased sperm concentration, total sperm count, motility, viability, and increased abnormal sperm morphology, sperm DNA fragmentation, ultimately causing male infertility. However, all these factors are modifiable and reversible, and hence, by mere changing of lifestyle, many of these risk factors can be avoided.

27 citations


Journal ArticleDOI
TL;DR: In this article , the effects of exposure to polystyrene microplastics (MPs) on the male reproductive system of mice were investigated and it was shown that chronic exposure to MPs resulted in toxicity of male reproduction under environmental exposure levels and these potential risks may ring alarm bells of public health.
Abstract: Microplastics (MPs), which are smaller in size and difficult to degrade, can be easily ingested by marine life and enter mammals through the food chain. Our previous study demonstrated that following acute exposure to MPs, the serum testosterone content reduced and sperm quality declined, resulting in male reproductive dysfunction in mice. However, the toxic effect of long-term exposure to MPs at environmental exposure levels on the reproductive system of mammals remains unclear.In vivo, mice were given drinking water containing 100 μg/L and 1000 μg/L polystyrene MPs (PS-MPs) with particle sizes of 0.5 μm, 4 μm, and 10 μm for 180 consecutive days. We observed alterations in testicular morphology and reductions in testosterone, LH and FSH contents in serum. In addition, the viability of sperm was declined and the rate of sperm abnormality was increased following exposure to PS-MPs. The expression of steroidogenic enzymes and StAR was downregulated in testis tissues. In vitro, we used primary Leydig cells to explore the underlying mechanism of the decrease in testosterone induced by PS-MPs. First, we discovered that PS-MPs attached to and became internalized by Leydig cells. And then we found that the contents of testosterone in the supernatant declined. Meanwhile, LHR, steroidogenic enzymes and StAR were downregulated with concentration-dependent on PS-MPs. We also confirmed that PS-MPs decreased StAR expression by inhibiting activation of the AC/cAMP/PKA pathway. Moreover, the overexpression of LHR alleviated the reduction in StAR and steroidogenic enzymes levels, and finally alleviated the reduction in testosterone induced by PS-MPs.PS-MPs exposure resulted in alterations in testicular histology, abnormal spermatogenesis, and interference of serum hormone secretion in mice. PS-MPs induced a reduction in testosterone level through downregulation of the LH-mediated LHR/cAMP/PKA/StAR pathway. In summary, our study showed that chronic exposure to PS-MPs resulted in toxicity of male reproduction under environmental exposure levels, and these potential risks may ring alarm bells of public health.

26 citations


Journal ArticleDOI
TL;DR: In this article , the authors evaluated the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters, and showed that the use of mRNA CoV-19 vaccines does not affect sperm quality.
Abstract: The short- and long-term andrological effects of coronavirus disease 2019 (COVID-19) have not been clarified. Our aim is to evaluate the available evidence regarding possible andrological consequences of COVID-19 either on seminal or hormonal parameters. The safety of the COVID-19 vaccines in terms of sperm quality was also investigated.All prospective and retrospective observational studies reporting information on severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) mRNA semen and male genitalia tract detection (n = 19), as well as those reporting data on semen analysis (n = 5) and hormonal parameters (n = 11) in infected/recovered patients without any arbitrary restriction were included.Out of 204 retrieved articles, 35 were considered, including 2092 patients and 1138 controls with a mean age of 44.1 ± 12.6 years, and mean follow-up 24.3 ± 18.9 days. SARS-CoV-2 mRNA can be localized in male genitalia tracts during the acute phase of the disease. COVID-19 can result in short-term impaired sperm and T production. Available data cannot clarify long-term andrological effects. Low T observed in the acute phase of the disease is associated with an increased risk of being admitted to the Intensive Care Unit or death. The two available studies showed that the use of mRNA COVID-19 vaccines does not affect sperm quality.The results of our analysis clearly suggest that each patient recovering from COVID-19 should be monitored to rule out sperm and T abnormalities. The specific contribution of reduced T levels during the acute phase of the infection needs to be better clarified.

25 citations


Journal ArticleDOI
TL;DR: In this article , the effects of exposure to polystyrene microplastic microplastics (MPs) on the male reproductive system of mice were investigated. And the results showed that chronic exposure to MPs resulted in toxicity of male reproduction under environmental exposure levels, which may ring alarm bells of public health.
Abstract: Microplastics (MPs), which are smaller in size and difficult to degrade, can be easily ingested by marine life and enter mammals through the food chain. Our previous study demonstrated that following acute exposure to MPs, the serum testosterone content reduced and sperm quality declined, resulting in male reproductive dysfunction in mice. However, the toxic effect of long-term exposure to MPs at environmental exposure levels on the reproductive system of mammals remains unclear.In vivo, mice were given drinking water containing 100 μg/L and 1000 μg/L polystyrene MPs (PS-MPs) with particle sizes of 0.5 μm, 4 μm, and 10 μm for 180 consecutive days. We observed alterations in testicular morphology and reductions in testosterone, LH and FSH contents in serum. In addition, the viability of sperm was declined and the rate of sperm abnormality was increased following exposure to PS-MPs. The expression of steroidogenic enzymes and StAR was downregulated in testis tissues. In vitro, we used primary Leydig cells to explore the underlying mechanism of the decrease in testosterone induced by PS-MPs. First, we discovered that PS-MPs attached to and became internalized by Leydig cells. And then we found that the contents of testosterone in the supernatant declined. Meanwhile, LHR, steroidogenic enzymes and StAR were downregulated with concentration-dependent on PS-MPs. We also confirmed that PS-MPs decreased StAR expression by inhibiting activation of the AC/cAMP/PKA pathway. Moreover, the overexpression of LHR alleviated the reduction in StAR and steroidogenic enzymes levels, and finally alleviated the reduction in testosterone induced by PS-MPs.PS-MPs exposure resulted in alterations in testicular histology, abnormal spermatogenesis, and interference of serum hormone secretion in mice. PS-MPs induced a reduction in testosterone level through downregulation of the LH-mediated LHR/cAMP/PKA/StAR pathway. In summary, our study showed that chronic exposure to PS-MPs resulted in toxicity of male reproduction under environmental exposure levels, and these potential risks may ring alarm bells of public health.

24 citations


Journal ArticleDOI
TL;DR: Systemic immune response after BNT162b2 vaccine is a reasonable cause for transient semen concentration and TMC decline and long-term prognosis remains good.
Abstract: The development of covid‐19 vaccinations represents a notable scientific achievement. Nevertheless, concerns have been raised regarding their possible detrimental impact on male fertility

24 citations


Book ChapterDOI
28 Feb 2022
TL;DR: This chapter follows the development of cryopreservation for mammalian sperm and expands upon the earlier review of indications and protocols.
Abstract: Introduction Sperm cryopreservation, more commonly referred to as sperm banking, has long been a fertility preservation technique for men but had been limited to those men whose post-thaw specimen after cryopreservation yielded sufficient motile sperm for intrauterine insemination. With the advances in assisted reproductive techniques (ART), and in particular intracytoplasmic sperm injection (ICSI), cryopreservation has become an essential component of fertility treatment for men with oligozoospermia, cryptozoospermia, and even azoospermia. It has also become standard practice to cryopreserve at the time of testis biopsy for azoospermia as well as when semen quality declines in the face of standard treatment paradigms. Over the past decade, sperm banking has become an essential component of the treatment of the subfertile couple. Impairment in male fertility can result from several causes. These include disease, anatomic, and/or functional issues (e.g., absence of the vas deferens, retrograde ejaculation or anejaculation), primary or secondary hormonal insufficiency, and frequently, from damage or depletion of the germinal stem cells resulting in impaired spermatogenesis. There are many potential threats to spermatogenesis with disease treatment, often resulting in compromised sperm number, motility, morphology, as well as DNA integrity. Chemotherapy and radiotherapy for various cancers easily disrupt biochemical processes that occur during spermatogenesis [1]. In addition, non-chemotherapeutic drugs and herbal as well as non-herbal supplements can and do affect sperm quantity, quality, and fertility potential. The popularity of sperm cryopreservation has been a direct result of patient demand. The majority of men who bank sperm have been afflicted by cancer at a young age and wish to preserve their future fertility. Although cancer survivors can become parents through adoption and gamete donation (using an anonymous or directed donor) most prefer to have biologic offspring [2]. In one study 48% reported that having children was an important issue to them after completing their treatment [3]. Similar results were reported by Schover et al. noting that over 50% of male cancer survivors in the reproductive age group desire to preserve their future fertility climbing to a rate of 77% in men who are childless at the time of cancer diagnosis [4,5]. Many of these men have concerns that their cancer or cancer treatment may result in birth defects or other health issues for their potential offspring [6]. Importantly, aside from inherited genetic syndromes, large registry studies have revealed no increased risk of genetic abnormalities, birth defects, or cancers in the children of cancer survivors [7,8,9,10,11,12]. This chapter follows the development of cryopreservation for mammalian sperm. It expands upon our earlier review of indications and protocols [13]. We also provide evidenced based answers to some of the questions our patients ask when seeking advice regarding sperm banking.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated whether GLY-induced gut microbiota dysbiosis contributed to male reproductive toxicity, showing that male reproductive dysfunction exhibited impaired testis architectural structure, reduced sperm motility, together with increased sperm malformation ratio.

Journal ArticleDOI
TL;DR: In this article , the authors investigated whether GLY-induced gut microbiota dysbiosis contributed to male reproductive toxicity, showing that male reproductive dysfunction exhibited impaired testis architectural structure, reduced sperm motility, together with increased sperm malformation ratio.

Journal ArticleDOI
TL;DR: In conclusion, supplementation of the summer diet with ZnF improved the whole reproductive functions such as testicular hemodynamics and semen quality of rams housed in heat stress conditions.
Abstract: This study was aimed to investigate the combined effect of zinc sulfate and folic acid (ZnF) dietary supplementation on testicular hemodynamics (TH), testicular volume (TV), serum testosterone levels (T) and semen quality of rams under heat stress conditions. Fifteen Ossimi rams were allocated to three groups: (1) G0 (n=5) received only basic diet; (2) G1 (n=5) received basic diet + ZnF (Zn, 0.4 mg/kg bw; F, 0.02 mg/kg bw) and (3) G2 (n=5) received basic diet + ZnF (Zn, 0.8 mg/kg bw; F, 0.04 mg/kg bw) daily for 60 days. TH was evaluated using color (testicular coloration, TC) and spectral modes [resistive index (RI) and pulsatility index (PI)] Doppler of the supra testicular arteries (proximal and distal parts, STA). Semen traits including progressive motility (PM), alive sperm % (AS), sperm viability (SV), sperm abnormalities (SA) and acrosome integrity (AI) were also assessed. The examinations were carried out one month before (D -30), the beginning of ZnF inclusion in the diet (D 0), and continued for the successive two months (D 30 and D 60). TH was significantly (P < 0.05) improved at D 30 and D 60, evidenced by lowering both RI and PI and increasing of TC in G1 compared to G0 and G2. In addition, both TV and serum T levels were elevated (P < 0.05) at D 30 and D 60 in G1 compared to other groups. Semen quality parameters (PM, AS, SV and AI) were significantly (P < 0.05) augmented in the same trend as TH, TV and T in G1 versus G0 and G2. A marked decrease (P < 0.05) in SA % was noticed at Days 30 and 60 after ZnF inclusion in G1 compared to G0 and G2. In conclusion, supplementation of the summer diet with ZnF improved the whole reproductive functions such as testicular hemodynamics and semen quality of rams housed in heat stress conditions.

Journal ArticleDOI
TL;DR: Findings indicate that the indigenous yogurt-isolated/cultured probiotics had a high potential antioxidant activity and the ameliorative effect against reprotoxicity and blood biochemical alterations induced by the NAFLD model.

Journal ArticleDOI
TL;DR: In this paper , the authors reviewed the evidence supporting the use of sperm DNA fragmentation testing in the assessment of male infertility and testicular sperm extraction in non-azoospermic men.
Abstract: Accumulating evidence has highlighted the contribution of oxidative stress and sperm DNA fragmentation (SDF) in the pathophysiology of male infertility. SDF has emerged as a novel biomarker of risk stratification for patients undergoing assisted reproductive technologies. Studies have also supported the use of testicular over ejaculated sperm at the time of intracytoplasmic sperm injection, as testicular sperm may have lower SDF than ejaculated samples. The European Association of Urology Working Panel on Male Sexual and Reproductive Health provides an evidence-based consultation guide on the indications for SDF testing in male infertility and also for testicular sperm extraction (TESE) in nonazoospermic men. We present the limitations and advantages of SDF testing and a framework to ensure that it is appropriately utilised in clinical practice. Furthermore, we critically appraise the current literature advocating the use of TESE in nonazoospermic men. PATIENT SUMMARY: This article reviews the evidence supporting the use of sperm DNA fragmentation testing in the assessment of male infertility and testicular sperm extraction in nonazoospermic men.

Journal ArticleDOI
TL;DR: It is suggested that control measures to reduce exposure to ambient particulate matter may help increase male fertility and reduce the risk of asthenozoospermia.
Abstract: Key Points Question Is exposure to different fractions of particulate matter (<2.5, 2.5-10, and ≤10 μm in diameter) associated with poor semen quality? Findings In this cohort study of 33 876 Chinese men, decreased total and progressive sperm motility and increased risk of asthenozoospermia were associated with exposure to particulate matter of less than 2.5 μm and 10.0 μm or less. Meaning These findings suggest that control measures to reduce exposure to ambient particulate matter may help increase male fertility and reduce the risk of asthenozoospermia.

Journal ArticleDOI
TL;DR: In this paper , the main detrimental effects of sperm cryopreservation are described, including the negative repercussion on reproductive performance, and the potential use of molecular biomarkers to predict sperm cryotolerance is discussed, as well as the added substances that can mitigate the harmful impact of freezing and thawing on sperm.

Journal ArticleDOI
TL;DR: The phase 2 MANTA and MANTA-RAy studies were developed in consultation with global regulatory authorities to investigate potential impacts of filgotinib, a Janus kinase 1 preferential inhibitor, on semen parameters in men with active inflammatory diseases as discussed by the authors .
Abstract: The phase 2 MANTA and MANTA-RAy studies were developed in consultation with global regulatory authorities to investigate potential impacts of filgotinib, a Janus kinase 1 preferential inhibitor, on semen parameters in men with active inflammatory diseases. Here we describe the methods and rationale for these studies. The MANTA and MANTA-RAy studies included men (aged 21–65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases, respectively. Participants had no history of reproductive health issues, and the following semen parameter values (≥ 5th percentile of World Health Organization reference values) at baseline: semen volume ≥ 1.5 mL, total sperm/ejaculate ≥ 39 million, sperm concentration ≥ 15 million/mL, sperm total motility ≥ 40% and normal sperm morphology ≥ 30%. Each trial included a 13-week, randomized, double-blind, placebo-controlled period (filgotinib 200 mg vs placebo, up to N = 125 per arm), for pooled analysis of the week-13 primary endpoint (proportion of participants with ≥ 50% decrease from baseline in sperm concentration). All semen assessments were based on two samples (≤ 14 days apart) to minimize effects of physiological variation; stringent standardization processes were applied across assessment sites. From week 13, MANTA and MANTA-RAy study designs deviated owing to disease-specific considerations. All subjects with a ≥ 50% decrease in sperm parameters continued the study in the monitoring phase until reversibility, or up to a maximum of 52 weeks, with standard of care as treatment. Overall conclusions from MANTA and MANTA-RAy will be based on the totality of the data, including secondary/exploratory measures (e.g. sperm motility/morphology, sex hormones, reversibility of any effects on semen parameters). Despite the complexities, the MANTA and MANTA-RAy studies form a robust trial programme that is the first large-scale, placebo-controlled evaluation of potential impacts of an advanced IBD and rheumatic disease therapy on semen parameters. EudraCT numbers 2017-000402-38 and 2018-003933-14; ClinicalTrials.gov identifiers NCT03201445 and NCT03926195. Filgotinib is a treatment for patients with ulcerative colitis and rheumatoid arthritis, and is being studied in other inflammatory diseases. Filgotinib works by blocking Janus kinase 1, an intracellular protein involved in inflammatory signalling processes. We designed the MANTA and MANTA-RAy trials with global health agencies to find out if filgotinib decreases the quality of semen in men with active inflammatory bowel disease (ulcerative colitis or Crohn’s disease) (MANTA) or rheumatic disease (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or non-radiographic axial spondylitis) (MANTA-RAy). This paper describes the design of the two trials. Patients had normal sperm measurements and could not have had previous reproductive health issues. Nearly 250 patients were included in each trial. In both MANTA and MANTA-RAy, half of the patients were treated with 200 mg of filgotinib once a day for 13 weeks, and the other half with placebo. We determined if any patients had a decrease in number of sperm cells per millilitre (sperm concentration) by at least half after 13 weeks of treatment. We then monitored any patients who had such a decrease in sperm concentration for up to 52 weeks (while they received standard of care treatment) or until the decrease was reversed. The conclusions from the trials will be in a different paper and will be based on all the final data, including changes in sex hormones. This is the first large-scale clinical trial programme to measure the effect of a treatment on sperm in men with inflammatory bowel disease or rheumatic diseases.

Journal ArticleDOI
TL;DR: In this paper , a systematic review used the Navigation Guide to evaluate the current body of evidence examining sperm quality and pesticide exposure in epidemiological studies and found consistent associations between pesticide exposure and diminished sperm parameters, particularly sperm motility and sperm DNA integrity.

Journal ArticleDOI
TL;DR: To examine the effect of the BNT162b, mRNA, SARS‐CoV‐2 virus vaccine on sperm quality, a large number of sperm samples were collected from men and women infected with SARS.

Journal ArticleDOI
TL;DR: In this article , the authors examined the selective forces that drive changes in sperm structure and physiology to understand the adaptive values of this variation and impact on male reproductive success and examined cellular and molecular mechanisms of sperm formation in the testis.
Abstract: The spermatozoon is a highly differentiated and polarized cell, with two main structures: the head, containing a haploid nucleus and the acrosomal exocytotic granule, and the flagellum, which generates energy and propels the cell; both structures are connected by the neck. The sperm’s main aim is to participate in fertilization, thus activating development. Despite this common bauplan and function, there is an enormous diversity in structure and performance of sperm cells. For example, mammalian spermatozoa may exhibit several head patterns and overall sperm lengths ranging from ∼30 to 350 µm. Mechanisms of transport in the female tract, preparation for fertilization, and recognition of and interaction with the oocyte also show considerable variation. There has been much interest in understanding the origin of this diversity, both in evolutionary terms and in relation to mechanisms underlying sperm differentiation in the testis. Here, relationships between sperm bauplan and function are examined at two levels: first, by analyzing the selective forces that drive changes in sperm structure and physiology to understand the adaptive values of this variation and impact on male reproductive success and second, by examining cellular and molecular mechanisms of sperm formation in the testis that may explain how differentiation can give rise to such a wide array of sperm forms and functions.

Journal ArticleDOI
TL;DR: The data reveal a molecular “hand-off” from males to females, which is postulate to be an important component of sperm–female interactions.
Abstract: Significance In species with internal fertilization, sperm spend an important part of their lives within the female. To examine the life history of the sperm during this time, we used semiquantitative proteomics and sex-specific isotopic labeling in fruit flies to determine the extent of molecular continuity between male and female reproductive tracts and provide a global catalog of sperm-associated proteins. Multiple seminal fluid proteins and female proteins associate with sperm immediately after mating. Few seminal fluid proteins remain after long-term sperm storage, whereas female-derived proteins constitute one-fifth of the postmating sperm proteome by then. Our data reveal a molecular “hand-off” from males to females, which we postulate to be an important component of sperm–female interactions.

Journal ArticleDOI
TL;DR: In this paper, a systematic review of epidemiologic studies published between 1991 through 2013 has reported associations between environmental and occupational pesticide exposure and reduced sperm quality, particularly associations with reduced sperm concentration.

Journal ArticleDOI
TL;DR: This paper introduces a novel automatic SMA based on a neural architecture search algorithm termed GeNAS, built specifically for noisy, low quality, and imbalanced datasets which are common in the field of medical imaging.
Abstract: Male infertility is a disease that affects approximately 7% of men. Sperm morphology analysis (SMA) is one of the main diagnosis methods for this problem. However, manual SMA is an inexact, subjective, non-reproducible, and hard to teach process. Therefore, in this paper, we introduce a novel automatic SMA technique that is based on the neural architecture search algorithm, named Genetic Neural Architecture Search (GeNAS). For this purpose, we used a collection of images termed MHSMA dataset, which contains 1540 sperm images that have been collected from 235 patients with infertility problems. In detail, GeNAS consists of a special genetic algorithm that acts as a meta-controller which explores the constrained search space of plain convolutional neural network architectures. Every individual of this genetic algorithm is a convolutional neural network trained to predict morphological deformities in different segments of human sperm (head, vacuole, and acrosome). The fitness of each individual is calculated by a novel proposed method, named GeNAS Weighting Factor (GeNAS-WF). This technique is specially designed to evaluate the fitness of neural networks which, during their learning process, validation accuracy highly fluctuates. To speed up the algorithm, a hashing method is practiced to save each trained neural architecture fitness, so we could reuse them during fitness evaluation. In terms of running time and computational power, our proposed architecture search method is far more efficient than most of the other existing neural architecture search algorithms. Moreover, whereas most of the existing neural architecture search algorithms are designed to work well with well-prepared benchmark datasets, the overall paradigm of GeNAS is specially designed to address the challenges of real-world datasets, particularly shortage of data and class imbalance. In our experiments, the best neural architecture found by GeNAS has reached an accuracy of 91.66%, 77.33%, and 77.66% in the vacuole, head, and acrosome abnormality detection, respectively. In comparison to other proposed algorithms for MHSMA dataset, GeNAS achieved state-of-the-art results.

Journal ArticleDOI
TL;DR: Older women randomized to the trial’s experimental arm (selection of sperm bound to immobilized (solid-state) HA) had the same live birth rates as younger women, most likely a result of better avoidance of sperm with damaged DNA.
Abstract: Abstract STUDY QUESTION What effects did treatment using hyaluronic acid (HA) binding/selection prior to ICSI have on clinical outcomes in the Hyaluronic Acid Binding sperm Selection (HABSelect) clinical trial? SUMMARY ANSWER Older women randomized to the trial’s experimental arm (selection of sperm bound to immobilized (solid-state) HA) had the same live birth rates as younger women, most likely a result of better avoidance of sperm with damaged DNA. WHAT IS KNOWN ALREADY Recent randomized controlled trials (RCTs) investigating the efficacy of HA-based sperm selection prior to ICSI, including HABSelect, have consistently reported reductions in the numbers of miscarriages among couples randomized to the intervention, suggesting a pathological sperm-mediated factor mitigated by prior HA-binding/selection. The mechanism of that protection is unknown. STUDY DESIGN, SIZE, DURATION The original HABSelect Phase 3 RCT ran from 2014 to 2017 and included 2752 couples from whom sperm samples used in control (ICSI) and intervention (Physiological IntraCytoplasmic Sperm Injection; PICSI) arms of the trial were stored frozen for later assessment of DNA quality (DNAq). The trial overlapped with its mechanistic arm, running from 2016 to 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS As miscarriage reduction was a significant secondary outcome of the trial, samples (n = 1247) selected for the mechanistic analysis were deliberately enriched for miscarriage outcomes (n = 92 or 7.4%) from a total of 154 miscarriages (5.6%) among all (n = 2752) couples randomized by stratified random sampling. Values from fresh semen samples for sperm concentration (mml), percentage forward progressive motility and percentage HA-binding score (HBS) were obtained before being processed by differential density gradient centrifugation or (rarely) by swim-up on the day of treatment. Surplus sperm pellets were recovered, aliquoted and cryopreserved for later analysis of DNAq using slide-based Comet, TUNEL, acridine orange (AO) and the sperm chromatin dispersion (SCD) assays. Following their classification into normal and abnormal sample subcategories based on reference values for sperm concentration and motility, relationships with HBS and DNAq were examined by Spearman correlation, Student’s t-tests, Mann Whitney U tests, and logistic regression (univariable and multivariable). Parsimonious selection enabled the development of models for exploring and explaining data trends. Potential differences in future cumulative pregnancy rates relating to embryo quality were also explored. MAIN RESULTS AND THE ROLE OF CHANCE Results from the 1247 sperm samples assayed for HBS and/or DNAq, generated data that were considered in relation to standard physiological measures of (sperm) vitality and to treatment outcomes. All measures of HBS and DNAq discriminated normal from abnormal sperm samples (P < 0.001). SCD correlated negatively with the Comet (r = −0.165; P < 0.001) and TUNEL assays (r = −0.200; P < 0.001). HBS correlated negatively with AO (r = −0.211; P < 0.001), Comet (r = −0.127; P < 0.001) and TUNEL (r = −0.214; P < 0.001) and positively with SCD (r = 0.255; P < 0.001). A model for predicting live birth (and miscarriage) rates included treatment allocation (odds ratio: OR 2.167, 95% CI 1.084–4.464, P = 0.031), female age (OR 0.301, 95% CI 0.133–0.761, P = 0.013, per decade) and the AO assay (OR 0.79, 95% CI 0.60–1. 02.761, P = 0.073, per 10 points rise). A model predicting the expected rate of biochemical pregnancy included male age (OR 0.464, 95% CI 0.314–0.674, P < 0.001, per decade) and the SCD assay (OR 1.04, 95% CI 1.007–1.075, P = 0.018, per 10 point rise). A model for conversion from biochemical to clinical pregnancy did not retain any significant patient or assay variables. A model for post-injection fertilization rates included treatment allocation (OR 0.83, 95% CI 0.75–0.91, P < 0.001) and the Comet assay (OR 0.950, 95% CI 0.91–1.00, P = 0.041). LIMITATIONS, REASONS FOR CAUTION HABSelect was a prospective RCT and the mechanistic study group was drawn from its recruitment cohort for retrospective analysis, without the full benefit of randomization. The clinical and mechanistic aspects of the study were mutually exclusive in that measures of DNAq were obtained from residual samples and not from HA-selected versus unselected sperm. Models for fitting mechanistic with baseline and other clinical data were developed to compensate for variable DNAq data quality. HABSelect used a solid-state version of PICSI and we did not assess the efficacy of any liquid-state alternatives. PICSI reduced fertilization rates and did not improve the outlook for cumulative pregnancy rates. WIDER IMPLICATIONS OF THE FINDINGS Notwithstanding the interventional effect on fertilization rates and possibly blastocyst formation (neither of which influenced pregnancy rates), poor sperm DNAq, reflected by lower HBS, probably contributed to the depression of all gestational outcomes including live births, in the HABSelect trial. The interventional avoidance of defective sperm is the best explanation for the equalization in live birth rates among older couples randomized to the trial’s PICSI arm. As patients going forward for assisted conception cycles globally in future are likely to be dominated by an older demographic, HA-based selection of sperm for ICSI could be considered as part of their treatment plan. STUDY FUNDING/COMPETING INTEREST(S) The study was supported by the National Institute for Health Research (NIHR) EME (Efficacy and Mechanism Evaluation)-11-14-34. National Research Ethics Service approval 11/06/2013: 13/YH/0162. S.L. is CEO of ExamenLab Ltd (company number NI605309). TRIAL REGISTRATION NUMBER ISRCTN99214271.

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TL;DR: In the Hyaluronic acid binding sperm selection (HABSelect) clinical trial as mentioned in this paper , the authors found that older women randomized to the trial's experimental arm had the same live birth rates as younger women, most likely a result of better avoidance of sperm with damaged DNA.
Abstract: What effects did treatment using hyaluronic acid (HA) binding/selection prior to ICSI have on clinical outcomes in the Hyaluronic Acid Binding sperm Selection (HABSelect) clinical trial?Older women randomized to the trial's experimental arm (selection of sperm bound to immobilized (solid-state) HA) had the same live birth rates as younger women, most likely a result of better avoidance of sperm with damaged DNA.Recent randomized controlled trials (RCTs) investigating the efficacy of HA-based sperm selection prior to ICSI, including HABSelect, have consistently reported reductions in the numbers of miscarriages among couples randomized to the intervention, suggesting a pathological sperm-mediated factor mitigated by prior HA-binding/selection. The mechanism of that protection is unknown.The original HABSelect Phase 3 RCT ran from 2014 to 2017 and included 2752 couples from whom sperm samples used in control (ICSI) and intervention (Physiological IntraCytoplasmic Sperm Injection; PICSI) arms of the trial were stored frozen for later assessment of DNA quality (DNAq). The trial overlapped with its mechanistic arm, running from 2016 to 2018.As miscarriage reduction was a significant secondary outcome of the trial, samples (n = 1247) selected for the mechanistic analysis were deliberately enriched for miscarriage outcomes (n = 92 or 7.4%) from a total of 154 miscarriages (5.6%) among all (n = 2752) couples randomized by stratified random sampling. Values from fresh semen samples for sperm concentration (mml), percentage forward progressive motility and percentage HA-binding score (HBS) were obtained before being processed by differential density gradient centrifugation or (rarely) by swim-up on the day of treatment. Surplus sperm pellets were recovered, aliquoted and cryopreserved for later analysis of DNAq using slide-based Comet, TUNEL, acridine orange (AO) and the sperm chromatin dispersion (SCD) assays. Following their classification into normal and abnormal sample subcategories based on reference values for sperm concentration and motility, relationships with HBS and DNAq were examined by Spearman correlation, Student's t-tests, Mann Whitney U tests, and logistic regression (univariable and multivariable). Parsimonious selection enabled the development of models for exploring and explaining data trends. Potential differences in future cumulative pregnancy rates relating to embryo quality were also explored.Results from the 1247 sperm samples assayed for HBS and/or DNAq, generated data that were considered in relation to standard physiological measures of (sperm) vitality and to treatment outcomes. All measures of HBS and DNAq discriminated normal from abnormal sperm samples (P < 0.001). SCD correlated negatively with the Comet (r = -0.165; P < 0.001) and TUNEL assays (r = -0.200; P < 0.001). HBS correlated negatively with AO (r = -0.211; P < 0.001), Comet (r = -0.127; P < 0.001) and TUNEL (r = -0.214; P < 0.001) and positively with SCD (r = 0.255; P < 0.001). A model for predicting live birth (and miscarriage) rates included treatment allocation (odds ratio: OR 2.167, 95% CI 1.084-4.464, P = 0.031), female age (OR 0.301, 95% CI 0.133-0.761, P = 0.013, per decade) and the AO assay (OR 0.79, 95% CI 0.60-1. 02.761, P = 0.073, per 10 points rise). A model predicting the expected rate of biochemical pregnancy included male age (OR 0.464, 95% CI 0.314-0.674, P < 0.001, per decade) and the SCD assay (OR 1.04, 95% CI 1.007-1.075, P = 0.018, per 10 point rise). A model for conversion from biochemical to clinical pregnancy did not retain any significant patient or assay variables. A model for post-injection fertilization rates included treatment allocation (OR 0.83, 95% CI 0.75-0.91, P < 0.001) and the Comet assay (OR 0.950, 95% CI 0.91-1.00, P = 0.041).HABSelect was a prospective RCT and the mechanistic study group was drawn from its recruitment cohort for retrospective analysis, without the full benefit of randomization. The clinical and mechanistic aspects of the study were mutually exclusive in that measures of DNAq were obtained from residual samples and not from HA-selected versus unselected sperm. Models for fitting mechanistic with baseline and other clinical data were developed to compensate for variable DNAq data quality. HABSelect used a solid-state version of PICSI and we did not assess the efficacy of any liquid-state alternatives. PICSI reduced fertilization rates and did not improve the outlook for cumulative pregnancy rates.Notwithstanding the interventional effect on fertilization rates and possibly blastocyst formation (neither of which influenced pregnancy rates), poor sperm DNAq, reflected by lower HBS, probably contributed to the depression of all gestational outcomes including live births, in the HABSelect trial. The interventional avoidance of defective sperm is the best explanation for the equalization in live birth rates among older couples randomized to the trial's PICSI arm. As patients going forward for assisted conception cycles globally in future are likely to be dominated by an older demographic, HA-based selection of sperm for ICSI could be considered as part of their treatment plan.The study was supported by the National Institute for Health Research (NIHR) EME (Efficacy and Mechanism Evaluation)-11-14-34. National Research Ethics Service approval 11/06/2013: 13/YH/0162. S.L. is CEO of ExamenLab Ltd (company number NI605309).ISRCTN99214271.