Paternal peri-conceptional physical activity and the risk of congenital heart disease in offspring: A case-control study.

BACKGROUND: Genetic and environmental factors have been shown to contribute to the development of congenital heart disease (CHD). To date, the focus of scientific articles has primarily centered on genetics and maternal environmental factors, with comparatively less attention given to paternal risk factors. OBJECTIVES: This study aims to investigate the potential association between paternal pre-conceptional physical activity levels (PA), along with paternal peri-conceptional smoking and alcohol consumption, and the risk of CHD in offspring. MATERIALS AND METHODS: An observational case-control study was conducted in Lebanon, with 279 participants, aiming to investigate potential risk factors for CHD. We included children with confirmed CHD, born between 2012 and 2022. Controls born in the same timeframe were selected randomly from the general population using online questionnaire forms. Mean age of children included was 6 years old (0-10). The pre-conceptional PA was assessed using the Global Physical Activity Questionnaire validated in Arabic. In addition, paternal smoking, alcohol consumption, and maternal risk factors were collected. RESULTS: The study included 128 CHD cases (45.9%) and their parents, as well as 151 healthy infants (54.1%) and their parents. There were no statistically significant variations in the alcohol consumption noted between the fathers in the case and control groups (p = 0.18). The paternal involvement in recreational-related PA during the peri-conception period was associated with a reduced risk of the CHD development in offspring by 46.9% (OR = 0.531, 95% CI: 0.301-0.936, p = 0.029). Additionally, increasing paternal total sitting time by 1 h above the average, which was approximately 260 min (4 h), increased the risk of CHD in offspring by 0.4% (p = 0.001). Moreover, paternal smoking exhibited an apparent association with a 56% increased risk of offspring developing CHD, notwithstanding that the confidence intervals included the null (OR = 1.56, 95% CI: 0.86-2.8, p = 0.136). DISCUSSION AND CONCLUSION: This observational study is the first to report a potential association between paternal PA, and CHD in offspring. This study aligns with previous reports, advocating for the paternal engagement in PA and the adoption of healthy lifestyle habits, especially during the critical stages of conception. Such practices are strongly recommended to enhance fertility and promote optimal health for offspring. However, due to the subjectivity in reporting PA and lack of molecular proof, additional prospective and molecular studies are required to validate these findings.

Mature oocyte dysmorphisms may be associated with progesterone levels, mitochondrial DNA content, and vitality in luteal granulosa cells.

PURPOSE: To identify whether follicular environment parameters are associated with mature oocyte quality, embryological and clinical outcomes. METHODS: This retrospective study examined 303 mature oocytes from 51 infertile women undergoing ICSI cycles between May 2018 and June 2021. Exclusion criteria consisted of advanced maternal age (> 36 years old), premature ovarian failure, obesity in women, or use of frozen gametes. Luteal granulosa cells (LGCs) were analyzed for mitochondrial DNA/genomic (g) DNA ratio and vitality. The relationships between hormone levels in the follicular fluid and oocyte features were assessed. Quantitative morphometric measurements of mature oocytes were assessed, and the association of LGC parameters and oocyte features on live birth rate after single embryo transfer was examined. RESULTS: Results indicated an inverse correlation between the mtDNA/gDNA ratio of LGCs and the size of polar body I (PBI). A 4.0% decrease in PBI size was observed with each one-unit increase in the ratio (p = 0.04). Furthermore, a 1% increase in LGC vitality was linked to a 1.3% decrease in fragmented PBI (p = 0.03), and a 1 ng/mL increase in progesterone levels was associated with a 0.1% rise in oocytes with small inclusions (p = 0.015). Associations were drawn among LGC characteristics, perivitelline space (PVS) debris, cytoplasmic inclusions, PBI integrity, and progesterone levels. Certain dysmorphisms in mature oocytes were associated with embryo morphokinetics; however, live birth rates were not associated with follicular parameters and oocyte quality characteristics. CONCLUSION: Follicular markers may be associated with mature oocyte quality features.

Identifying predictors of Day 5 blastocyst utilization rate using an artificial neural network.

RESEARCH QUESTION: Can artificial intelligence identify predictors of an increased Day 5 blastocyst utilization rate (D5BUR), which is one of the most informative key performance indicators in an IVF laboratory? DESIGN: This retrospective, multicentre study evaluated six variables for predicting D5BUR using an artificial neural network (ANN): number of metaphase II (MII) oocytes injected (intracytoplasmic sperm injection); use of autologous/donated gametes; maternal age at oocyte retrieval; sperm concentration; progressive sperm motility rate; and fertilization rate. Cycles were divided into training and testing sets through stratified random sampling. D5BUR on Day 5 was grouped into <60% and ≥60% as per the Vienna consensus benchmark values. RESULTS: The area under the receiver operating characteristic curve (AUC) to predict the D5BUR groups was 80.2%. From the ANN model, all six independent variables were found to be of significant value for the prediction of D5BUR (P<0.0001), with the most important variable being the number of MII oocytes injected. Investigation of the effect of MII oocytes injected on D5BUR indicated an inverse correlation, with injection of an increasing number of MII oocytes resulting in a decreasing D5BUR (r=-0.344, P<0.001) and injection of up to six oocytes resulting in D5BUR ≥60%. CONCLUSION: The number of MII oocytes injected is the most important predictor of D5BUR. Exploration of additional variables and further validation of models that can predict D5BUR can guide the way towards personalized treatment and increased safety.

Low E-visibility of embryologists on fertility clinic websites: a web-based cross-sectional study.

PURPOSE: This study assessed the visibility of embryologists on fertility clinic websites among Society for Assisted Reproductive Technology (SART) and the Human Fertilisation and Embryology Authority (HFEA) member clinics. METHODS: During a 1-month interval (March 2022), all Society for Assisted Reproductive Technology (SART) and the Human Fertilisation and Embryology Authority (HFEA) member fertility clinic websites were evaluated. The professional representation of the primary care team was examined including specialties, the presence of headshots, and biographies. RESULTS: A total of 446 fertility clinic websites were scanned in the search. The embryology team has the least common professional identification by their names (53.58%) compared to gynecology clinicians (96.21%, p < 0.001) and nurses (55.58%, p < 0.001). This trend also applies to other types of professional identifiers, such as headshots and biographies. Professional headshots of embryologists (50.34%) were less prominent than those of gynecology clinicians (93.51%, p < 0.001). A similar trend was observed in the biographies of the embryology team (47.20%) compared to gynecology clinicians (95.08%, p < 0.001). CONCLUSION: The present study revealed that embryologists have low professional visibility on fertility clinic websites. Fertility clinics may prioritize enhancing the online visibility of their embryology laboratory team. This approach could potentially enhance the recognition of their team, foster transparency, and provide accessible information about the skills and expertise of healthcare professionals involved in the treatment process.

Exploring behavioral systems of the reinforcement sensitivity theory in people with epilepsy: A cross-sectional study.

OBJECTIVES: Although epilepsy has previously been associated with behavioral changes, no previous study has utilized the behavioral models of the reinforcement sensitivity theory (RST) to investigate the impact of epilepsy on behavior. Therefore, the objective of this cross-sectional study is to examine the potential relationship between epilepsy and the neurobehavioral systems of the RST. METHODS: Using the Reinforcement Sensitivity Theory-Personality Questionnaire (RST-PQ), this cross-sectional study assessed the behavioral systems of the RST in a sample of 27 epilepsy patients and 27 age- and gender-matched healthy individuals. The RST-PQ was designed to assess the different behavioral systems of the RST. The behavioral approach system (BAS) is responsible of the approach behavior, in high values related to risk seeking and addictive behavior and in low values well related to depression. The behavioral inhibition system (BIS) is well related to anxiety in high levels, and the fight flight freeze system (FFFS) is responsible for the avoidance behavior. RESULTS: After adjusting for age, no significant differences were found in demographic information (gender and marital status) between the general population and epilepsy patients. Gender distribution was similar, with 55.6% females in both groups. Marital status also showed no significant difference, with 74% single in the control group and 63% in the epilepsy group. Significant differences were observed in the behavioral systems of the RST. The epilepsy group had higher scores compared with the control group in several areas. BAS reward activity had a median score of 23 in the epilepsy group and 21 in the control group (p = 0.001). BAS goal drive persistence (p = 0.04), BAS impulsivity (p = 0.014), FFFS (p = 0.002), and BIS (median score of 77 in the epilepsy group and 66 in the control group) also showed significant differences, with p = 0.001. These significant differences remained consistent before and after matching the control group, indicating their robustness. The only exception was BAS reward activity, which did not show a significant difference after matching, with p = 0.106 and p = 0.051 before and after matching, respectively. CONCLUSIONS: The study suggests a potential positive association between epilepsy and the BIS, potentially mediated by the hippocampus. The relationship between epilepsy and the BAS, as well as the FFFS, may also be influenced by the BIS. These findings have clinical implications, but further research is needed to confirm these relationships.

Lactobacillus plantarum secretions may exert a cryoprotective effect on human sperm motility: A prospective in vitro study.

BACKGROUND: Semen cryopreservation is a widely used procedure for fertility preservation, despite some level of cryodamage that may occur in spermatozoa after thawing. However, there is some evidence that lactobacilli, one of the bacteria found in semen, might benefit sperm quality. OBJECTIVES: This study aims to determine whether the addition of Lactobacillus plantarum secretions to sperm freezing medium has an impact on sperm motility, morphology, and DNA fragmentation. MATERIALS AND METHODS: This is a prospective auto-controlled study. It was conducted on 30 raw semen samples from 30 infertile men attending a fertility center for semen analysis. Before freezing, all the samples were analyzed for motility, morphology, and DNA fragmentation percentages. Each sample was then divided equally into three aliquots. Cryopreservation was performed on each aliquot using one of the following three media: without Lactobacillus plantarum secretions (control group) or with 107 or 108 colony-forming units/mL Lactobacillus plantarum secretions. Sperm motility, morphology, and DNA integrity were evaluated after the cryopreservation media were added and after semen thawing. RESULTS: The results of this study indicated that after thawing, no statistically significant decrease in progressive motility and non-progressive percentages were detected in the sperm freezing medium supplemented with 108 colony-forming units/mL Lactobacillus plantarum secretions than the fresh raw semen. Moreover, multivariate linear regression model analyses showed that the progressive motility (p = 0.02), non-progressive motility (p = 0.016), and non-motile spermatozoa (p = 0.012) percentages were significantly decreased in the freezing medium (without Lactobacillus plantarum secretions) compared to the fresh raw semen. DISCUSSION AND CONCLUSION: To the best of our knowledge, this is the first study showing that Lactobacillus plantarum secretions had a cryoprotective effect on sperm motility when added to the sperm freezing medium. Furthermore, Lactobacillus plantarum secretions were found to protect sperm DNA integrity more effectively than the freezing medium without Lactobacillus plantarum secretions in non-normozoospermia group. Cryopreservation procedures must therefore be optimized to minimize any iatrogenically induced sperm DNA damage, given the correlation between sperm DNA damage and increased mutation loads in progeny.

Functional histology of human scrotal wall layers and their overlooked relation with infertility: a narrative review.

Male infertility currently contributes to nearly half of the reported infertility cases. Scrotal wall layers play a cardinal role in regulating testicular physiology. However, few studies have focused on the functional histology of these layers and their relations with infertility in humans. The objective of the present narrative review is to collate novel insights into the functional histology of the human scrotal wall layers and their relation with infertility. The data was extracted from articles published between 1946 and 2021. The study was performed between January and December 2021. 71 original studies have been included in this review. Despite the fact that few studies have presented detailed functional histology of the human scrotal wall layers, this narrative review elucidates the possible influence of scrotal histology on infertility. Scrotal wall layers-associated pathologies may induce infertility by various mechanisms. They can impose mechanical forces that may affect the testicular histology and stimulate testicular inflammation. Moreover, they may induce testicular hyperthermia. Various unanswered clinical questions have been identified in this narrative review. More clinical studies are needed to assess the effect of alterations in the components of the scrotal wall layers on fertility (e.g., due to the exposure to metabolic and/or psychological stressors). In addition, testing the effectiveness of various pharmacological/surgical interventions to treat scrotal wall layers-associated pathologies will provide more insights into infertility treatment.

Effects of a multilayered crisis on psychiatric hospitalizations in a university hospital in Lebanon; a retrospective study.

Lebanon is struggling with a multilayered crisis following the COVID-19 breakout, the economic crisis, and the Beirut port explosion. The aim of this article is to assess the effect of these crisis on the characteristics of patients hospitalized in psychiatry. This is a retrospective study conducted at the psychiatric ward of Hotel Dieu de France in Beirut between January 2017 and march 2022. The population was divided into three groups according to specific time events indicating the start of a certain crisis. Data regarding patients' demographics, psychiatric history and their present hospitalization was collected. A total of 1655 patient files were included in the study. Overall, the rate of hospitalized women increased following the Beirut port explosion, together with the rate of patients younger than 18 years old. Moreover, during the COVID-19 breakout and the start of the economic crisis, alcohol use decreased, as well as the length of stay in the hospital. In conclusion, in the event of a multilayered crisis children and adolescents, as well as women are the most at risk of being affected in terms of mental health.

Do follicle-stimulating hormone receptor polymorphisms in infertile men influence intracytoplasmic sperm injection outcomes? A prospective cohort study.

The follicle-stimulating hormone (FSH) and its receptor regulate the quantity and quality of spermatozoa production. Several studies have analyzed the effect of single nucleotide polymorphisms (SNPs) in exon 10 of the FSH receptor (FSHR) on basic semen parameters without yet reaching a firm consensus. The aim of this study was to evaluate the effect of p.Thr307Ala and p.Asn680Ser polymorphisms in exon 10 of the FSHR gene, in infertile men, on intracytoplasmic sperm injection (ICSI) outcomes. This study was conducted between March 2019 and February 2020 on infertile couples undergoing ICSI at Al Hadi Laboratory and Medical Center, Lebanon. Couples with severe infertility factors that may impair gametogenesis/embryogenesis (e.g. advanced maternal age, premature ovarian failure, underwent gonadotoxic treatments, etc.) were excluded from the study. Semen and blood samples were collected from infertile men on the day of oocyte collection. Infertile men (n = 173) were screened for FSHR variants using polymerase chain reaction-restriction fragment length polymorphism. Moreover, fertilization rates, embryo quality, and pregnancy outcomes were evaluated. Higher sperm concentrations were found in the p.Thr307Ala group than the p.Thr307Thr (P < 0.01) and p.Ala307Ala (P < 0.05) groups. Furthermore, fertilization rate was significantly lower in the p.Ala307Ala genotype than in the p.Thr307Thr genotype (P < 0.05). We showed that FSHR variants in infertile men undergoing ICSI could affect sperm concentration, motility, and fertilization rates. Therefore, it will be important to confirm these results in further studies using a larger sample size.

Eosinophils to Lymphocytes Ratio (ELR) as a Potential Inflammatory Biomarker in Patients with Dual Diagnosis of Bipolar and Alcohol Use Disorders: A Retrospective Cohort Study.

Objective: It is well-established that Bipolar Disorder (BD) has comorbidity with Alcohol Use Disorder (AUD) and could present the same symptoms of an underlying diagnosis of BD, therefore delaying the proper relevant treatment. Recent studies show the occurrence of alterations in the circulating levels of inflammatory mediators in patients dealing with AUD as well as those with BD. The objective of this study is to get an assessment of whether patients with AUD and BD comorbidity [BD(+)] would present different ratios of the Complete Blood Count (CBC) in comparison with patients with AUD but without a BD comorbidity [BD(-)]. Methods: This is a retrospective study, conducted through a selection of patients files who were admitted to the psychiatric department at Hôtel-Dieu de France University Hospital in Beirut, Lebanon, between January of the year 2016 and May of the year 2021. Overall, 83 files of patients dealing with AUD were included in this study. Results: Patients with BD(+) showed a higher Eosinophils to Lymphocytes Ratio (ELR) in comparison to those with BD(-). The Receiver Operation Characteristic (ROC) analysis had an area under the curve at 0.719 with a p = .001. The cutoff value of ELR that best differentiates BD(-) from BD(+) was 0.087 (Sensitivity = 81.3%; Specificity = 63.6%). The logistic regression analysis showed that an ELR superior to 0.087 presented a statistically significant difference, exposing patients belonging to the BD(+) group (OR = 11.66; p < .001). Conclusions: Our data suggest that ELR may be a valuable, reproducible, easily accessible, and cost-effective inflammatory marker, pointing at the presence of a BD comorbidity with AUD.

Differential impact of four sperm preparation techniques on sperm motility, morphology, DNA fragmentation, acrosome status, oxidative stress, and mitochondrial activity: A prospective study.

BACKGROUND: Suboptimal human semen handling in vitro may induce sperm damage. However, the effects of semen swim-up, pellet swim-up, density gradient, and density gradient followed by SU on sperm motility, morphology, DNA fragmentation, acrosome reaction, intracellular reactive oxygen species, and mitochondrial activity were not fully understood. OBJECTIVES: To study the impact of four sperm preparation techniques on sperm functional parameters. MATERIALS AND METHODS: This study was conducted on 60 infertile men with a minimum sperm concentration of 20 × 106 /ml and total sperm motility of ≥30%. Each raw semen sample was divided into four aliquots. Each aliquot was prepared by one of the tested techniques. Various sperm characteristics were assessed before and after sperm preparation. RESULTS: Density gradient and density gradient followed by SU resulted in significantly higher DNA fragmentation percentages compared with semen swim-up (p < 0.001 and p < 0.001, respectively) and pellet swim-up (p < 0.001 and p < 0.001, respectively). Significantly higher percentages of spermatozoa with intact acrosome were detected in semen swim-up (p < 0.001) and pellet swim-up (p < 0.001) compared with raw semen. The percentage of reactive oxygen species-positive spermatozoa was significantly higher after pellet swim-up (p < 0.001), density gradient (p < 0.001), and density gradient followed by SU (p < 0.001) than raw semen. In addition, the percentages of 100% stained midpiece (active mitochondria) were significantly higher in semen swim-up (p < 0.001) and pellet swim-up (p < 0.001) compared with raw semen. DISCUSSION AND CONCLUSION: To the best of our knowledge, this is the first report comparing the impact of these techniques on various sperm functional parameters. Semen swim-up was more effective than density gradient in selecting better spermatozoa in terms of DNA integrity, reactive oxygen species levels, acrosome status, and mitochondrial activity. Randomized clinical trials comparing these four techniques are required to test their impact on embryo development and pregnancy outcomes.

Paternal multigenerational exposure to an obesogenic diet drives epigenetic predisposition to metabolic diseases in mice.

Obesity is a growing societal scourge. Recent studies have uncovered that paternal excessive weight induced by an unbalanced diet affects the metabolic health of offspring. These reports mainly employed single-generation male exposure. However, the consequences of multigenerational unbalanced diet feeding on the metabolic health of progeny remain largely unknown. Here, we show that maintaining paternal Western diet feeding for five consecutive generations in mice induces an enhancement in fat mass and related metabolic diseases over generations. Strikingly, chow-diet-fed progenies from these multigenerational Western-diet-fed males develop a 'healthy' overweight phenotype characterized by normal glucose metabolism and without fatty liver that persists for four subsequent generations. Mechanistically, sperm RNA microinjection experiments into zygotes suggest that sperm RNAs are sufficient for establishment but not for long-term maintenance of epigenetic inheritance of metabolic pathologies. Progressive and permanent metabolic deregulation induced by successive paternal Western-diet-fed generations may contribute to the worldwide epidemic of metabolic diseases.

Stress Management during the Intracytoplasmic Sperm Injection Cycle May Slow Down First Embryo Cleavage and Accelerate Embryo Compaction: A Pilot Randomized Controlled Trial.

INTRODUCTION: A firm consensus on the effectiveness of psychological interventions during infertility treatment has not been reached yet in terms of mental health and pregnancy rates. Moreover, the influence of these interventions on embryo cleavage kinetics has not been investigated. OBJECTIVE: The aim of this work was to study whether stress management in couples undergoing an intracytoplasmic sperm injection (ICSI) cycle influences stress levels, mitochondrial DNA (mtDNA) levels in granulosa cells, and cleavage-stage embryos. METHODS: Infertile couples were randomized into a treatment as usual (TAU) group (n = 30) and stress management program (SMP) group (n = 29) at the beginning of an ICSI cycle. Couples in the SMP group attended education and relaxation sessions at each visit to the clinic for folliculometry. The perceived stress scale (PSS) was used to assess stress levels at the beginning and end of the cycle. Moreover, mtDNA levels of granulosa cells and embryo morphokinetics were evaluated. RESULTS: Post-intervention, women in the SMP group had significantly lower PSS scores than their initial PSS (p < 0.001; effect size, ES = 0.5) and than the final PSS of the TAU group (p = 0.02; ES = 0.09). Additionally, mtDNA levels were significantly lower in luteal granulosa cells of the SMP group than the TAU group (p = 0.02). An earlier time of pronuclei appearance (p = 0.03) and time to 2 cells (p = 0.015) and a faster time to full compaction (p = 0.045) were detected in the embryos of the SMP group compared with the TAU group. CONCLUSION(S): The implemented program may reduce stress levels, retard first embryo cleavage, and accelerate embryo compaction. Further studies with an active control group are needed to confirm these results.

Neurophysiology of cognitive behavioural therapy, deep breathing and progressive muscle relaxation used in conjunction with ART treatments: a narrative review.

BACKGROUND: Infertility is defined as the failure to achieve clinical pregnancy after 12 months of regular unprotected intercourse. It could be due to male or female factors, each requiring different treatment options. ART treatment exposes couples to numerous psychological stressors. Therefore, it has been recommended by the ESHRE Psychology and Counselling Guideline Development Group recently that psychosocial support should be offered as a complementary therapy during infertility treatments. In this context, the efficiency of different psychological interventions, such as cognitive behaviour therapy (CBT), deep breathing (DB), and progressive muscle relaxation (PMR), was evaluated in several clinical trials in terms of couples' mental health and pregnancy outcomes. OBJECTIVE AND RATIONALE: The neurophysiology of CBT, DB and PMR, which are used in interventional studies, in both men and women undergoing ART, has not yet been fully elucidated. This review represents a comprehensive report, aiming to collate novel insights into the neurobiological processes and physiological mechanisms that occur during the practice of CBT, DB and PMR. SEARCH METHODS: PubMed, Google Scholar and Cochrane Library were interrogated to conduct this comprehensive literature review. The search was carried out using combinations of MeSH terms and keywords: infertility, assisted reproductive techniques, IVF, ICSI, emotions, psychological stress, cognitive behavioural therapy, mind-body therapies and relaxation. Relevant information related to the mechanism of action of stress management techniques were obtained from original articles and reviews published in English without taking into consideration the time of publication. Moreover, as it was not the major focus of the review, only recent systematic reviews (2015-2019) pinpointing the effects of psychological interventions on infertility treatment outcomes were also retrieved from the above-mentioned databases. OUTCOMES: CBT, DB and PMR may modify the activity of stress-related brain regions such as the prefrontal cortex, amygdala, hypothalamus and hippocampus, as demonstrated by functional MRI and electroencephalogram studies. Furthermore, applying these techniques was associated with mood improvements and a decline in stress biomarkers, and, hypothetically, reducing stress biomarkers attenuates the stress-induced effects on ART outcomes. WIDER IMPLICATIONS: Increasing the knowledge of fertility staff, researchers and physicians regarding the mechanisms of action of these stress management techniques has several advantages. For instance, understanding the underlying neurophysiological pathways would assist practitioners to engage ART couples in the practice of these techniques. Also, it may enhance the quality of the support programmes and psychological research. Accordingly, this will ensure that these interventions reach their full potential and therefore improve clinical outcomes.

Optimization of The Cell Aggregates Method for Isolation and Purification of Human Granulosa Cells from Follicular Fluid.

BACKGROUND: Aspirated ovarian follicular fluids (FF) contain luteal granulosa cells (LGCs) and other contaminating cell types. Several strategies, such as the antibody binding methods, the flask method, the cell strainer and positive selection of granulosa aggregates after density gradient (DG) centrifugation, were tested as LGC purification methods. Each of these strategies has its own advantages and disadvantages. Positive selection of granulosa aggregates after DG centrifugation is simple, rapid and efficient in terms of LGC recovery. However, it results in a low purity. Here, we aimed to test whether modifying the traditional protocol by collecting the aggregates from the FF, before the DG centrifugation could decrease the percentage of contaminating cells. MATERIALS AND METHODS: In the present prospective study, 32 FF, from 32 women,were randomly assigned into one of the two purification techniques: positive selection of granulosa aggregates from the FF, after DG centrifugation (DG/ Agg, n=16) or positive selection of granulosa aggregates from the FF, before DG centrifugation (Agg/DG, n=16). At the end of each procedure cell count, vitality, morphology and purity of the cell suspension were evaluated. RESULTS: No significant difference was detected in the total number of GCs between DG/Agg and Agg/DG (P>0.05). However, higher percentage of GCs with normal morphology was detected in Agg/DG compared to DG/Agg (P<0.001). Moreover, lower percentages of white blood cells (P<0.01), red blood cells (P<0.001) and epithelial cells (P<0.01) were identified in Agg/DG compared to DG/Agg. CONCLUSION: Here we showed that positive selection of granulosa aggregates from the FF prior to DG technique had a higher purity compared to the traditional protocol. Thus, it could be a method of choice to prepare GCs for research purposes in clinical in vitro fertilization settings.

What are the effects of vitamin C on sperm functional properties during direct swim-up procedure?

SummaryDirect swim-up procedure is widely used to separate the motile competent spermatozoa from the antioxidant-rich semen. Subsequently, spermatozoa become more vulnerable to reactive oxygen species (ROS) due to their cytological characteristics. The effect of vitamin C, a highly concentrated antioxidant in the semen, on direct swim-up-enriched sperm population is not fully investigated. Therefore, the aim of the present study was to assess the effect of vitamin C on sperm functional properties during direct swim-up procedure. Semen samples were collected from 22 participants. Each semen sample was divided into several aliquots. The first portion was overlaid with sperm medium without ascorbic acid (0 µM AA). The second and third fractions were overlaid with sperm medium supplemented with 300 µM and 600 µM AA; respectively. After 1 h of incubation, basic sperm parameters, intracellular ROS levels, acrosome reaction, chromatin integrity, and glucose uptake were assessed. Swim-up without AA significantly increased the percentage of ROS(+) spermatozoa compared with the raw semen (P<0.01). Interestingly, swim-up with 300 µM AA did not increase the percentage of ROS(+) sperm compared with the raw semen. In parallel, the percentage of sperm with altered chromatin integrity was significantly lower in the 300 µM AA group compared with that in the raw semen (P<0.05). These findings suggest that supplementation of vitamin C to sperm medium could be beneficial for direct swim-up-derived spermatozoa.

Adverse effects of paternal obesity on the motile spermatozoa quality.

Growing evidence suggests that paternal obesity may decrease male fertility potential. During infertility treatment with intra-cytoplasmic sperm injection (ICSI), a morphologically normal motile spermatozoon is injected into a mature egg, when possible. However, sperm motility and morphology per se do not reflect the sperm molecular composition. In this study, we aimed to assess the quality of motile spermatozoa in the context of obesity by analysing their conventional and molecular characteristics as well as their ability to promote early embryonic development. A prospective study was conducted on 128 infertile men divided into three groups: 40 lean, 42 overweight, and 46 obese men. Conventional sperm parameters (concentration, motility and morphology) and sperm molecular status (chromatin composition and integrity, 5-methycytosine (5-mC) and 5-hydroxycytosine (5-hmC) contents and oxidative stress level) were analysed on raw semen and/or on motile spermatozoa selected by density gradient or swim-up techniques. Morphokinetic analysis of the embryos derived from ICSI was performed using the Embryoviewer software. Our results showed that the motile sperm-enriched fraction from obese men exhibited higher levels of retained histones (p<0.001), elevated percentage of altered chromatin integrity (p<0.001), and decreased contents of 5-hmC (p<0.001), and 5-mC (p<0.05) levels as compared to that from lean men. Importantly, there were no statistically significant correlations between these molecular parameters and the percentages of morphologically normal motile spermatozoa. Regarding embryo morphokinetics, the CC1 (p<0.05) and CC3 (p<0.05) embryonic cell cycles were significantly delayed in the cleavage embryos of the obese group as compared to the embryos of the lean group. Our data is of particular interest because, besides demonstrating the negative impacts of obesity on motile spermatozoa molecular composition, it also highlights the possible risk of disturbing early embryonic cell cycles kinetics in the context of paternal obesity.

Paternal obesity: how bad is it for sperm quality and progeny health?

There is substantial evidence that paternal obesity is associated not only with an increased incidence of infertility, but also with an increased risk of metabolic disturbance in adult offspring. Apparently, several mechanisms may contribute to the sperm quality alterations associated with paternal obesity, such as physiological/hormonal alterations, oxidative stress, and epigenetic alterations. Along these lines, modifications of hormonal profiles namely reduced androgen levels and elevated estrogen levels, were found associated with lower sperm concentration and seminal volume. Additionally, oxidative stress in testis may induce an increase of the percentage of sperm with DNA fragmentation. The latter, relate to other peculiarities such as alteration of the embryonic development, increased risk of miscarriage, and development of chronic morbidity in the offspring, including childhood cancers. Undoubtedly, epigenetic alterations (ie, DNA methylation, chromatin modifications, and small RNA deregulation) of sperm related to paternal obesity and their consequences on the progeny are poorly understood determinants of paternal obesity-induced transmission. In this review, we summarize and discuss the data available in the literature regarding the biological, physiological, and molecular consequences of paternal obesity on male fertility potential and ultimately progeny health.

De plus en plus de données tendent à montrer que l'obésité paternelle a non seulement des effets néfastes sur la santé métabolique et reproductive de l'individu mais également sur celle de sa descendance. Les mécanismes mis en jeu dans ce processus incluraient des altérations physiologiques et hormonales des fonctions reproductives de l'homme obèse ainsi que des altérations épigénétiques au niveau du génome spermatique. Les modifications hormonales associées à l'obésité et qui se caractérisent principalement par une réduction du taux d'androgènes et une augmentation du niveau d'estrogène induiraient une altération des paramètres spermatiques, une diminution de la concentration ou de la numération totale en spermatozoïde et du volume séminal. Le stress oxydatif dans le testicule induirait une augmentation de la fragmentation de l'ADN spermatique et pourrait rendre compte de l'augmentation des risques de fausses-couches, des problèmes de développement embryonnaire ainsi que de l'augmentation des risques de mortalité chez la descendance, problèmes fréquemment rencontrés lorsque le père est. obèse. Les modifications épigénétiques (altérations des profils de méthylation de l'ADN, de la structure de la chromatine ou/et des profils d'expression des ARN spermatiques) induites par l'obésité sont, quant à elles, loin d'être comprises, même si elles sont, surement, les vecteurs clés de la transmission épigénétique paternelle des maladies métaboliques. L'objet de cette revue est. de résumer puis de discuter les différentes études expérimentales et épidémiologiques publiés à ce jour sur les conséquences physiologiques et moléculaire de l'obésité paternelle sur la santé de l'individu et sur celle de sa descendance.