BACKGROUND: The last decade has seen increased research on the relationship between diet and male fertility, but there are no clearly defined nutritional recommendations for men in the preconception period to support clinical fertility outcomes.
OBJECTIVE: The purpose of this scoping review is to examine the extent and range of research undertaken to evaluate the effect(s) of diet in the preconception period on male clinical fertility and reproductive outcomes.
METHODS: Four electronic databases (MEDLINE and EMBASE via Ovid, CAB Direct, and CINAHL via EBSCO) were searched from inception to July 2023 for randomized controlled trials (RCTs) and observational studies (prospective/retrospective, case-control, and cross-sectional). Intervention studies in male participants or couples aiming to achieve dietary or nutritional change, or non-intervention studies examining dietary or nutritional components (whole diets, dietary patterns, food groups or individual foods) in the preconception period were included. Controls were defined as any comparison group for RCTs, and any/no comparison for observational studies. Primary outcomes of interest included the effect(s) of male preconception diet on clinical outcomes such as conception (natural or via ART), pregnancy rates and live birth rates. Secondary outcomes included time to conception and sperm parameters.
RESULTS: A total of 37 studies were eligible, including one RCT and 36 observational studies (prospective, cross-sectional, and case-control studies; four studies in non-ART populations) published between 2008 and 2023. Eight reported clinical outcomes, 26 reported on secondary outcomes, and three reported on both. The RCT did not assess clinical outcomes but found that tomato juice may benefit sperm motility. In observational studies, some evidence suggested that increasing fish or reducing sugar-sweetened beverages, processed meat or total fat may improve fecundability. Evidence for other clinical outcomes, such as pregnancy rates or live birth rates, showed no relationship with cereals, soy and dairy, and inconsistent relationships with consuming red meat or a \'healthy diet\' pattern. For improved sperm parameters, limited evidence supported increasing fish, fats/fatty acids, carbohydrates and dairy, and reducing processed meat, while the evidence for fruits, vegetables, cereals, legumes, eggs, red meat and protein was inconsistent. Healthy diet patterns in general were shown to improve sperm health.
CONCLUSIONS: Specific dietary recommendations for improving male fertility are precluded by the lack of reporting on clinical pregnancy outcomes, heterogeneity of the available literature and the paucity of RCTs to determine causation or to rule out reverse causation. There may be some benefit from increasing fish, adopting a healthy dietary pattern, and reducing consumption of sugar-sweetened beverages and processed meat, but it is unclear whether these benefits extend beyond sperm parameters to improve clinical fertility. More studies exploring whole diets rather than singular foods or nutritional components in the context of male fertility are encouraged, particularly by means of RCTs where feasible. Further assessment of core fertility outcomes is warranted and requires careful planning in high-quality prospective studies and RCTs. These studies can lay the groundwork for targeted dietary guidelines and enhance the prospects of successful fertility outcomes for men in the preconception period. Systematic search of preconception diet suggests that increasing fish and reducing sugary drinks, processed meats and total fat may improve male fertility, while consuming healthy diets, fish, fats/fatty acids, carbohydrates and dairy and reducing processed meat can improve sperm health.

The diverse nature and high molecule concentration of seminal plasma (SP) makes this fluid a good potential source for a potential biomarker that could predict assisted reproductive technology (ART) outcomes. Currently, semen quality parameters cannot accurately predict ART outcomes. A systematic literature search was conducted to identify human SP biomarkers with potential predictive ability for the outcomes of IVF and intracytoplasmic sperm injection. Observational cohort and case-control studies describing the association between biomarkers in human SP and the outcome of infertile men attending for ART were included. Forty-three studies were selected, reporting on 89 potential SP biomarkers (grouped as oxidative stress, proteins glycoproteins, metabolites, immune system components, metals and trace elements and nucleic acids). The present review supports 32 molecules in SP as potentially relevant biomarkers for predicting ART outcomes; 23 molecules were reported once and nine molecules were reported in more than one study; IL-18 and TGF-β1-IL-18 ratio were confirmed in distinct studies. This review presents the most comprehensive overview of relevant SP biomarkers to predict ART outcomes to date, which is of clinical interest for infertility investigations and assisted reproduction; nevertheless, its potential is under-exploited. This review could serve as starting point for designing an all-encompassing study for biomarkers in SP and their predictive ability for ART outcomes, and for developing a non-invasive diagnostic tool.

Male fertility largely depends on the ability to produce sperm that can transmit the paternal information onto the next generation. However, the factors that are critical for sperm function and the subsequent development of healthy offspring are still not completely understood in ruminants. Importantly, sperm function is not completely encoded by germ cell DNA, but rather, depends on sequential acquisition, loss, and modification of elements through interaction with secretions from the testes, epididymides, and accessory glands (collectively termed seminal plasma). In addition, these secretions can play a role in the inheritance of paternal environmental effects by progeny. This is likely achieved directly, by the regulation of sperm epigenetic effectors, and indirectly, by altering the female environment in which the individual develops. This review will provide an overview of the different organs that contribute to seminal plasma in ruminants, and summarise how their secretions shape sperm function and modulate the female reproductive tract. Finally, some consideration will be given to the potential of paternal factors to affect embryo development and offspring health in ruminants.

Infertility is a growing concerning health problem affecting around 15% of couples worldwide. Conventional semen parameters have limited accuracy for male infertility potential determination. Current advances in the understanding of male infertility indicate that environmental and occupational exposure to chemical contaminants are important etiological factors leading to infertility problems. In this context, some heavy metals (HMs) can be considered as endocrine-disrupting compounds (EDCs), thus altering the seminal quality. This systematic review aims to summarize the key points to detect and quantify HMs in human seminal plasma (SP) and the involved analytical tools. Our results showed that that for HM quantification, atomic absorption spectroscopy (AAS) and inductively coupled plasma (ICP) were the most employed techniques while Zn, Cd, Pb, and Cr were the analytes most often detected. Fast, reliable, and sensitive quantification of EDCs in SP could be important for the development of accurate diagnostic and preventive strategies to address male infertility towards providing personalized therapy.

BACKGROUND: Non-obstructive azoospermia (NOA) is considered to be the most severe form of male infertility. Before the emergence of surgical testicular sperm extraction and assisted reproductive technology, NOA patients could hardly become biological fathers of their children. However, failure of the surgery could cause physical and psychological harm to patients such as testicular damage, pain, hopeless of fertility and additional cost. Therefore, predicting the successful sperm retrieval (SSR) is so important for NOA patients to make their choice whether to do the surgery or not. Because seminal plasma is secreted by the testes and accessory gonads, it can reflect the spermatogenic environment, making it a preferential choice for SSR valuation. The purpose of this paper is to summarize the available evidence and provide the reader with a broad overview of biomarkers in seminal plasma for SSR prediction.
RESULTS: A total of 15,390 studies were searched from PUBMED, EMBASE, CENTRAL and Web of Science, but only 6615 studies were evaluated after duplications were removed. The abstracts of 6513 articles were excluded because they were irrelevant to the topic. The full texts of 102 articles were obtained, with 21 of them being included in this review. The included studies range in quality from medium to high. In the included articles, surgical sperm extraction methods included conventional testicular sperm extraction (TESE) and microdissection testicular sperm extraction (micro-TESE). Currently, the biomarkers in seminal plasma used to predict SSR are primarily RNAs, metabolites, AMH, inhibin B, leptin, survivin, clusterin, LGALS3BP, ESX1, TEX101, TNP1, DAZ, PRM1 and PRM2.
CONCLUSIONS: The evidence does not conclusively indicate that AMH and INHB in seminal plasma are valuable to predict the SSR. It is worth noting that RNAs, metabolites and other biomarkers in seminal plasma have shown great potential in predicting SSR. However, existing evidence is insufficient to provide clinicians with adequate decision support, and more prospective, large sample size, and multicenter trials are urgently needed.
RéSUMé: CONTEXTE: L’azoospermie non obstructive (ANO) est considérée comme la forme la plus grave d’infertilité masculine. Avant l’émergence de l’extraction chirurgicale de spermatozoïdes testiculaires et de la procréation médicalement assistée, les patients atteints d’ANO pouvaient difficilement devenir les pères biologiques de leurs enfants. Cependant, l’échec de la chirurgie peut causer des dommages physiques et psychologiques aux patients, tels que des lésions testiculaires, des douleurs, une fertilité impossibilité et des coûts financiers supplémentaires. Par conséquent, prédire une récupération réussie de spermatozoïdes (RRS) est très important pour les patients avec ANO, pour faire leur choix de réaliser ou non la chirurgie. Comme le plasma séminal est sécrété par les testicules et les glandes accessoires, il peut être le reflet de l’environnement de la spermatogenèse, ce qui en fait un choix préférentiel pour l’évaluation de la RRS. Le but du présent article est de résumer les preuves disponibles, et de fournir au lecteur un aperçu général des biomarqueurs du plasma séminal susceptibles de prédire la RRS. RéSULTATS: Au total, 15390 études ont été  consultées à partir de PUBMED, EMBASE, CENTRAL et Web of Science, mais seulement 6615 ont été évaluées après suppression des doublons. Les résumés de 6513 articles ont été exclus car non pertinents pour le sujet. Les textes intégraux de 102 articles ont été obtenus, dont 21 ont été inclus dans cette revue. La qualité des études incluses varie de moyenne à élevée. Dans ces articles inclus, la méthode chirurgicale d’extraction de spermatozoïdes était soit l’extraction conventionnelle de spermatozoïdes testiculaires (TESE), soit l’extraction de spermatozoïdes testiculaires par microdissection (micro-TESE). Actuellement, les biomarqueurs du plasma séminal utilisés pour prédire la RRS sont principalement les ARN, les métabolites, l’AMH, l’inhibine B, la leptine, la survivine, la clusterine, LGALS3BP, ESX1, TEX101, TNP1, DAZ, PRM1 et PRM2. CONCLUSIONS: Les preuves n’indiquent pas de façon concluante que l’AMH et l’INHB dans le plasma séminal sont utiles pour prédire la RRS. Il convient de noter que les ARN, métabolites et autres biomarqueurs du plasma séminal ont montré un potentiel élevé de prédiction de la  RRS. Cependant, les preuves existantes sont insuffisantes pour fournir aux cliniciens une aide à la décision adéquate ; des essais plus prospectifs, de grande taille, et multicentriques sont nécessaires de toute urgence.

Seminal plasma contains numerous extracellular vesicles (sEVs). Since sEVs are apparently involved in male (in)fertility, this systematic review focused on studies specifically investigating such relationship. Embase, PubMed, and Scopus databases were searched up to 31 December 2022, primarily identifying a total of 1440 articles. After processing for screening and eligibility, 305 studies were selected as they focused on sEVs, and 42 of them were considered eligible because they included the word fertility or a related word such as infertility, subfertility, fertilization, and recurrent pregnancy loss in the title, objective(s), and/or keywords. Only nine of them met the inclusion criteria, namely (a) conducting experiments aimed at associating sEVs with fertility concerns and (b) isolating and adequately characterizing sEVs. Six studies were conducted on humans, two on laboratory animals, and one on livestock. The studies highlighted some sEV molecules, specifically proteins and small non-coding RNAs, that showed differences between fertile and subfertile or infertile males. The content of sEVs was also related to sperm fertilizing capacity, embryo development, and implantation. Bioinformatic analysis revealed that several of the highlighted sEV fertility-related proteins would be cross-linked to each other and involved in biological pathways related to (i) EV release and loading and (ii) plasma membrane organization.

Seminal plasma cytokines are associated with fertility and reproductive health, but progressing their clinical utility is hampered by absence of reference data on concentration ranges of relevant cytokines in healthy men. We employed a systematic approach to assemble current evidence on the concentrations of immune regulatory cytokines present in seminal plasma (SP) of normozoospermic and/or fertile men and evaluated the impact of different platform methodologies for cytokine quantification.
A systematic literature search was performed utilising PubMed, Web of Science and Scopus. Databases were searched from inception until 30th June 2022 inclusive, using combinations of keywords pertaining to seminal fluid and cytokines, and was restricted to human participants. Original data with values reported as concentration of specific cytokines in SP of men clearly defined as fertile or normozoospermic were extracted from studies written in English.
A total of 3769 publications were initially identified, of which 118 fulfilled the eligibility criteria for inclusion. A total of 51 individual cytokines are detectable in SP of healthy men. The number of studies reporting on each cytokine range from 1 to >20. The reported concentrations for many cytokines linked with fertility status, including IL6, CXCL8/IL8, and TNFA, are highly variable between published studies. This is associated with the different immunoassay methodologies utilised and may be exacerbated by a lack of validation of assays to ensure suitability for SP assessment. Due to the large variation between studies, accurate reference ranges for healthy men cannot be determined from the published data.
The concentrations of cytokines and chemokines detected in SP is inconsistent and highly variable between studies and cohorts, limiting current capacity to define reference ranges for cytokine concentrations in fertile men. The lack of standardisation in methods used to process and store SP, and variation in platforms used to evaluate cytokine abundance, are factors contributing to the observed heterogeneity. To progress the clinical utility of SP cytokine analysis will require standardisation and validation of methodologies so that reference ranges for healthy fertile men can be defined.

BACKGROUND: Human life without sperm is not possible. Therefore, it is alarming that the fertilizing ability of human spermatozoa is continuously decreasing. The reasons for that are widely unknown, but there is hope that metabolomics-based investigations may be able to contribute to overcoming this problem. This review summarizes the attempts made so far.
METHODS: We will discuss liquid chromatography-mass spectrometry (LC-MS), gas chromatography (GC), infrared (IR) and Raman as well as nuclear magnetic resonance (NMR) spectroscopy. Almost all available studies apply one of these methods.
RESULTS: Depending on the methodology used, different compounds can be detected, which is (in combination with sophisticated methods of bioinformatics) helpful to estimate the state of the sperm. Often, but not in all cases, there is a correlation with clinical parameters such as the sperm mobility.
CONCLUSIONS: LC-MS detects the highest number of metabolites and can be considered as the method of choice. Unfortunately, the reproducibility of some studies is poor, and, thus, further improvements of the study designs are needed to overcome this problem. Additionally, a stronger focus on the biochemical consequences of the altered metabolite concentrations is also required.

To identify the most robust molecular biomarkers in sperm and seminal plasma for the diagnosis of male infertility, and to evaluate their clinical use.
Systematic review.
Not applicable.
Accessible studies reporting well-defined (in)fertile populations and semen molecular biomarkers were included in this review.
A systematic search of the literature published in MEDLINE-PubMed and EMBASE databases was performed, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
The primary outcome was the content, expression, or activity of molecular biomarkers in human semen samples. Only studies reporting a receiver-operating characteristic (ROC) analysis values were included.
Eighty-nine studies were included. Direct evaluation of sperm DNA damage has high potential as a diagnostic biomarker of fertility and assisted reproductive technology outcomes (area under the curve [AUCs] median = 0.67). Regarding strand break-associated chromatin modifications, γH2AX levels show good predictive value for the diagnosis of male infertility (AUCs median = 0.93). Some noncoding ribonucleic acid (RNA) exhibit excellent predictive values; miR-34c-5p in semen is the most well-characterized and robust transcriptomic biomarker (AUCs median = 0.78). While many proteins in semen show fair diagnostic value for sperm quality and fertilizing capacity, the levels of some, such as TEX101, in seminal plasma have an excellent diagnostic potential (AUCs median = 0.69). Although individual metabolites and metabolomic profiles in seminal plasma present good predictive value, the latter seem to be better than the former when inferring sperm quality and fertilizing capacity.
The current review supports that some Omics (e.g., DNA structure and integrity, genomics and epigenomics, transcriptomics, metabolomics, and proteomics) could be considered relevant molecular biomarkers that may help identify infertility etiologies and fertilization prognosis with cost-effective, simple, and accurate diagnosis.

Human male infertility affects approximately 1/10 couples worldwide, and its prevalence is found more in developed countries. Along with sperm cells, the secretions of the prostate, seminal vesicle and epididymis plays a major role in proper fertilization. Many studies have proven the functions of seminal vesicle secretions, especially semenogelin protein, as an optimiser for fertilization. Semenogelin provides the structural components for coagulum formation after ejaculation. It binds with eppin and is found to have major functions like motility of sperm, transporting the sperm safely in the immune rich female reproductive tract until the sperm cells reach the egg intact. The capacitation process is essential for proper fertilization and semenogelin involved in mediating capacitation in time. Also, it has control of events towards the first step in the fertilization process. It is a Zn ions binding protein, and Zn ions act as a cofactor that helps in the proper motility of sperm cells. Therefore, any imbalance in protein that automatically affect sperm physiology and fertility status. This review sheds a comprehensive and critical view on the significant functions of semenogelin in fertilization. This review can open up advanced proteomics research on semenogelin towards unravelling molecular mechanisms in fertilization.