Male Infertility Problems Research Articles

AYURVEDIC MANAGEMENT OF KSHEENA SHUKRA (OLIGOSPERMIA) LEAD-ING TO MALE INFERTILITY: A CASE STUDY

As per the World Health Organization (WHO) report in India, the overall prevalence of primary infertility ranges between 3.9 and 16.8%. A recent report on the status of infertility states that 50% of it is related to productive anomalies or disorders in males. In comparison, 90% of male infertility problems are related to Oligospermia and other abnormalities in semen analysis. As per Ayurveda, Oligospermia can be considered as Ksheena Shukra (Oligospermia). Surgery, Hormone treatments, medications and Assisted Reproductive Technology (ART) are the main lines of treatment in Conventional medicine, but these are associated with many unwanted and severe adverse effects. The present case discussion is about effectively managing a case diagnosed as Ksheena Shukra with Ayurvedic intervention. This case report aims to evaluate the effect of Ayurvedic treatment in managing Ksheena Shukra. In this case study, Shodhana (Purificatory Therapy) procedures {especially Virechana Karma (Purgation) and Vasti(Enema)} were performed before administering Rasayana (Rejuvenation) drugs; the pre- and postsemen analysis during the treatment period shows a marked increase in sperm count and motility. The outcome of this case reveals that Ayurvedic treatments can effectively manage the Oligospermia associated with male infertility.

O-134 Down regulation of Clock gene in testicle may affect energy metabolism of sertoli cell

Abstract Study question Whether decrease expression of Clock gene in the testis could affect the energy metabolism of Sertoli cells and what is the possible mechanism? Summary answer Down-regulating of Clock gene could regulate the expression of PIK3CB affect AMPK signaling pathways, significantly weakening the energy supply of sertoli cells in mouse testicular. What is known already The causes of Nonobstructive azoospermia (NOA) and other male infertility diseases are diverse and complex, including spermatogenesis and germ cell maturation at different stages of meiosis, the expression level of Clock gene maybe is one reason of which. In the testis of NOA patients, expression level of Clock gene was significantly decreased compared with Obstructive azoospermia (OA), meanwhile, the decrease of Clock gene expression can result in the decrease of male mouse fetal number. The decrease of Clock gene expression cause some kind of male infertility problem is confirmed, but the process and mechanism is not clear. Study design, size, duration Differential expression genes related to low expression of Clock and pathways related to spermatogenesis were screened out through transcriptome analysis on testicular tissue samples from patients with NOA(n = 24) and OA(n = 17). The model was established by transfecting mouse testicular Sertoli cell line (TM4 cells) with lentivirus containing Clock knock-down gene and energy metabolism effects were detected by Seahorse tests. Adifluorescein reporter gene was constructed to detect the binding of CLOCK and candidated differential expressed gene. Participants/materials, setting, methods Normal testis sequencing data were obtained from GTEX database as control. Combined with sequencing data, the differentially expressed genes were obtained as candidate gene, which expression was verified by RT-qPCR, Western-blotting. Energy metabolism were detected by Seahorse mitochondrial-stress test, glycolysis-rate test. Adifluorescein reporter gene for the promoter regions of candidate gene was constructed and transfected into TM4 cells to detect whether CLOCK could regulate candidate gene by binding to the E-box of the promoter region. Main results and the role of chance After GO(GeneOntology) and KEGG(Kyoto Encyclopedia of Genes and Genomes) enrichment analysis, PIK3CB which involved in AMPK signaling pathway was selected for further verification and molecular mechanism study. In Seahorse tests, the basal respiratory capacity, maximal respiratory capacity OCR, spare respiratory capacity and ATP-related respiratory capacity of TM4 cells were significantly decreased after Clock gene knockdown, but there were no significant differences in glycolytic rate, basal glycolysis, compensatory glycolysis level and glycolytic rate. RT-qPCR and Western-blotting confirmed that after knock down of Clock gene, the expression level of Pik3cb gene was down-regulated. That imply when Clock gene is decreased, it regulates the expression of PIK3CB affects AMPK signaling pathways, weakening the ability of mouse testicular sertoli cells to supply energy to various levels of spermatogenic cells and sperm cells, which may be one reason for the occurrence of nonobstructive azoospermia. During this process, there were significant changes in the mitochondrial energy supply of testicular supporting cells, but no significant changes in glycolysis. Finally, the dual luciferin report showed that the Clock gene could bind to the promoter regions of Pik3cb to regulate the expression of PIK3CB, and that the promoter of PIK3CB was activated by the transcription factor CLOCK. Limitations, reasons for caution Although we identified that Clock gene could bind to the promoter regions of Pik3cb to regulate the expression of PIK3CB and affect AMPK signaling pathways, weakening the ability of mouse testicular sertoli cells to supply energy, the available expression level and whether it will be work in vivo is unknown. Wider implications of the findings The results imply that the main energy changes affect the occurrence and development of spermatogonia and primary spermatocytes near the base of the seminiferous tubules are related to the influence of Clock on genes involved in regulating mitochondrial energy supply. It need more further studies. Trial registration number not applicable

Joint Analysis of Genome-wide DNA Methylation and Transcription Sequencing Identifies the Role of BAX Gene in Heat Stress-Induced-Sertoli Cells Apoptosis.

The problem of male infertility is a global health crisis and poses a serious threat to the well-being of families. Under heat stress (HS), the reduction of Sertoli cells (SCs) inhibits energy transport and nutrient supply to germ cells, leading to spermatogenesis failure. DNA methylation of genes is a central epigenetic regulatory mechanism in mammalian reproduction. However, it remains unclear how DNA methylation regulates gene expression in heat-stressed SCs. In this study, we investigated whether the decrease in SC levels during HS could be related to epigenetic DNA modifications. The cells exposed to HS showed changes in differential methylation cytosines and regions (DMCs/DMRs) and differential expression genes (DEGs), but not in global DNA methylations. One of the most important biological processes affected by HS is cell apoptosis induced by the intrinsic apoptotic signaling pathway (GO: 2,001,244, P < 0.05) by enrichment in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The joint analysis showed that several gene expressions in RNA-seq and WGBS overlapped and the shortlisted genes BAX, HSPH1, HSF1B, and BAG were strongly correlated with stress response and apoptosis. Methylation-specific PCR (MSP) and flow cytometry (FCM) analyzes showed that reduced promoter methylation and enhanced gene expression of BAX with a consequence of apoptosis. The activity of BAX, as well as an increase in its expression, is likely to result in a reduction of SCs population which could further impair ATP supply and adversely affect membrane integrity. These findings provide novel insights into the molecular mechanisms through which stressors cause male reproductive dysfunction and a new molecular etiology of male infertility.

Non-thermal plasma promotes boar sperm quality through increasing AMPK methylation

Boar sperm quality, as an important indicator of reproductive efficiency, directly affects the efficiency of livestock production. Here, this study was conducted to improve the boar sperm quality by using a non-thermal dielectric barrier discharge (DBD) plasma. Our results showed that DBD plasma exposure at 2.1 W for 15 s could improve boar sperm quality by increasing exon methylation level of adenosine monophosphate-activated protein kinase (AMPK) and thus improving the glycolytic flux, mitochondrial function, and antioxidant capacity without damaging the integrity of sperm DNA and acrosome. In addition, DBD plasma could rescue DNA methyltransferase inhibitor decitabine-caused low sperm quality through reducing the oxidative stress and mitochondrial damage. Therefore, the application of non-thermal plasma provides a new strategy for reducing sperm oxidative damage and improving sperm quality, which shows a great potential in assisted reproduction to solve the problem of male infertility.

Antioxidant activity of Flemingia praecox and Mucuna pruriens and their implications for male fertility improvement

Globally, 15–24% couples are unable to conceive naturally and 50% of cases of this problem are due to infertility in males. Of this, about 50% of male infertility problems are developed due to unknown reasons called as idiopathic infertility. It is well established that, reactive oxygen species (ROS) have negative impact on male fertility and are involved in 80% of total idiopathic male infertility cases. Medicinal plants are considered as an alternative approach for mitigating the health problems. The plants with good antioxidant capacity can improve the male infertility symptoms generated by ROS. Such medicinal plants can be used to alleviate the symptoms of male infertility with their diverse phytoconstituents. Mucuna pruriens is a well-accepted herb, with its seeds being used to improve the male fertility in various ways and one of the ways is by eliminating the ROS. In our field survey, another plant, Flemingia praecox, although less known, its roots are used in all problems related to the male fertility by tribal people of the Gadchiroli district of Maharashtra, India. The study was conducted to determine in vitro antioxidant potential of F. praecox and compared the results with the well-established male fertility improving plant M. pruriens with special emphasis on medicinally important roots of F. praecox and seeds of M. pruriens. The objective of the study was investigated by studying their total phenol (TPC) and flavonoid (TFC) content, antioxidant parameters (DPPH, FRAP, ABTS, DMPD, β-carotene bleaching and TAA) and finally DNA damage protection capacity of the plant extracts was studied. The plant parts used for the medicinal purposes have been investigated along with other major parts (leaves, stem and roots of both the plants) and compared with synthetic antioxidants, BHA, BHT and ascorbic acid. Moreover, the inhibition of two male infertility enzyme markers, PDE5 and arginase by F. praecox root and M. pruriens seed extract was also studied in vitro. The results showed that F. praecox possesses higher antioxidant activity than M. pruriens in the majority of studies as observed in TFC, DPPH, TAA, ABTS and DMPD assays. However, M. pruriens seeds showed best results in TPC, FRAP and DNA damage protection assay. F. praecox root extract also gave better PDE5 inhibition value than M. pruriens seeds. This study will help to establish the authenticity of F. praecox used by tribal people and will encourage its further use in managing the male infertility problems.

SAT446 Association of Polychlorinated Biphenyls With the Hormonal Parameters of the Normal Menstrual Cycle May Contribute to Unexplained Infertility

Abstract Disclosure: A.E. Butler: None. E. Brennan: None. T. Sathyapalan: None. S.L. Atkin: None. Introduction: Polychlorinated biphenyls (PCBs) are organic lipophilic pollutants that accumulate through the diet and increase with age and obesity. Previous research has linked PCBs with menstrual function; therefore, this study was undertaken to look at the association of PCBs with parameters of menstrual function at day 21 of the menstrual cycle in a group of women who were undergoing in vitro fertilization (IVF). Methods: 29 Caucasian women from a UK academic center aged 32.9±4.4 years, with body mass index BMI 25.4±3.6 kg/m2, who were undergoing in vitro fertilization were recruited. Five of the women had unexplained infertility and the remainder (n=24) had male factor infertility or tubal problems. Blood was withdrawn at day 21 of their menstrual cycle, at the time of mock embryo transfer. PCBs were measured using high resolution gas chromatography. Results: Only PCB118, PCB153, PCB138 and PCB180 were detected. PCB153, PCB138, PCB180 inversely correlated with estradiol (p&amp;lt;0.05). PCB 118 and PCB138 inversely correlated with FSH (p&amp;lt;0.05). PCB118, PCB153, PCB138 and PCB180 inversely correlated with LH (p&amp;lt;0.05, p&amp;lt;0.01, p&amp;lt;0.01 and p&amp;lt;0.01, respectively). No correlation was seen between PCBs and progesterone. Women with unexplained infertility showed higher levels of PCB118, PCB153, PCB138 and PCB180 (p&amp;lt;0.05) compared to those with male factor infertility though other hormonal parameters did not differ other than FSH that was lower in the unexplained group (p=0.01). Conclusion: These data are in accord with an effect of PCBs on the menstrual cycle in normal women and may be involved in the mechanism of unexplained infertility. Presentation Date: Saturday, June 17, 2023

Exploration of the correlation of serum polychlorinated biphenyl levels with luteal phase hormonal parameters and infertility in women with or without polycystic ovary syndrome.

Polychlorinated biphenyls (PCBs) are organic lipophilic pollutants that accumulate in the body. Previous research has linked PCBs with menstrual function; therefore, this study was undertaken to investigate the correlation of PCBs with luteal phase hormonal parameters of menstrual function at day 21 in a group of non-obese women prior to in vitro fertilization (IVF). Fifty-eight non-obese Caucasian women from a UK academic center, 29 with polycystic ovary syndrome (PCOS) and 29 without, were recruited. PCOS women all had anovulatory infertility. Non-PCOS women: five with unexplained infertility, the remainder with male factor infertility (n=14) or tubal problems (n=10). Blood was withdrawn at day 21 of the menstrual cycle for non-PCOS women, at the time of mock embryo transfer. PCBs were measured using high resolution gas chromatography. Only PCB118, PCB153, PCB138 and PCB180 were detected in all samples, and levels did not differ between PCOS and non-PCOS subjects. In non-PCOS subjects, PCB153, PCB138 and PCB180 inversely correlated with estradiol (p<0.05); PCB118 and PCB138 inversely correlated with follicle stimulating hormone (FSH) (p<0.05); PCB118 (p<0.05), PCB153, PCB138 and PCB180 (all p<0.01) inversely correlated with luteinizing hormone (LH). Control women without PCOS with unexplained infertility showed higher levels of PCB118, PCB153, PCB138 and PCB180 (p<0.05) compared to those control women without PCOS with tubal or male factor infertility, though other hormonal parameters did not differ other than that FSH that was lower in the unexplained group (p=0.01). The only correlation observed in PCOS women with anovulatory infertility was that between PCB180 and progesterone (p<0.05). PCBs correlated with luteal phase menstrual cycle hormones in control women without PCOS and may contribute to the mechanism of unexplained infertility; in PCOS women, no correlations of the PCBs were seen for estradiol, LH or FSH.

Risk for Congenital Anomalies in Children Conceived With Medically Assisted Fertility Treatment : A Population-Based Cohort Study.

More than 2 million children are conceived annually using assisted reproductive technologies (ARTs), with a similar number conceived using ovulation induction and intrauterine insemination (OI/IUI). Previous studies suggest that ART-conceived children are at increased risk for congenital anomalies (CAs). However, the role of underlying infertility in this risk remains unclear, and ART clinical and laboratory practices have changed drastically over time, particularly there has been an increase in intracytoplasmic sperm injection (ICSI) and cryopreservation. To investigate the role of underlying infertility and fertility treatment on CA risks in the first 2 years of life. Propensity score-weighted population-based cohort study. New South Wales, Australia. 851 984 infants (828099 singletons and 23885 plural children) delivered between 2009 and 2017. Adjusted risk difference (aRD) in CAs of infants conceived through fertility treatment compared with 2 naturally conceived (NC) control groups-those with and without a parental history of infertility (NC-infertile and NC-fertile). The overall incidence of CAs was 459 per 10 000 singleton births and 757 per 10 000 plural births. Compared with NC-fertile singleton control infants (n= 747 018), ART-conceived singleton infants (n= 31256) had an elevated risk for major genitourinary abnormalities (aRD, 19.0 cases per 10 000 births [95% CI, 2.3 to 35.6]); the risk remained unchanged (aRD, 22 cases per 10 000 births [CI, 4.6 to 39.4]) when compared with NC-infertile singleton control infants (n= 36251) (that is, after accounting for parental infertility), indicating that ART remained an independent risk. After accounting for parental infertility, ICSI in couples without male infertility was associated with an increased risk for major genitourinary abnormalities (aRD, 47.8 cases per 10 000 singleton births [CI, 12.6 to 83.1]). There was some suggestion of increased risk for CAs after fresh embryo transfer, although estimates were imprecise and inconsistent. There were no increased risks for CAs among OI/IUI-conceived infants (n= 13574). This study measured the risk for CAs only in those children who were born at or after 20 weeks' gestation. Observational study design precludes causal inference. Many estimates were imprecise. Patients should be counseled on the small increased risk for genitourinary abnormalities after ART, particularly after ICSI, which should be avoided in couples without problems of male infertility. Australian National Health and Medical Research Council.

Herbal remedies for male infertility and spermatogenic activity in animals: A review

Male infertility is becoming an important untouched area that needs immediate attention due to the increasing demand for breeding strategies, keeping in view the production and increasing per animal productivity. Many additives and antioxidants have been tried for enhancing the seminal quality, but still there is no evidence of full- proof effect on the conception rates in female animals. However, herbal preparations which promise multi-factorial effect in the breeding male animals can be explored, and in turn could prove to be a better tool to encounter the problem of male infertility holistically. The herbal preparations and its effect at the cellular, molecular and metabolic level still needs to be understood. However, the advantage of using the herbal ingredients could be, use of available local herbal ingredients which are more economical, affordable, can reduce the use of hormonal therapy, have less side effects on long term usage, and have greater acceptability by the farmers. These herbal ingredients will be useful in breeding programmes for improvement of germplasm in terms of productivity. The current review covers how the herbs can be utilized in improving the semen quality and quantity, enhancing function of sertoli and leydig cells, mating behaviour, fecundity, seminal antioxidant status, hypophyseal adrenal gonadal axis cum endocrine regulation, microcirculation of testes, as well as in semen cryopreservation and post thaw quality of different species.

Efficacy of Shrungatak Modak and Jatifal Oil in Ksheenshukrata w.s.r. to Oligospermia – A Single Case Study

Infertility is defined as the failure of a couple to achieve a pregnancy with regular unprotected sexual intercourse after 12 months or more. A recent study status on Infertility states that, 50% is related to reproductive anomalies or disorders in the male, in which 90% of male infertility problems are related to Oligospermia and other abnormalities in semen analysis. However, there are number of treatments like hormonal therapies, intrauterine Insemination and test tube baby. Available but it is cost effective and not surety is there. That is the reason today to explore Ayuerveda are mediator to treat this type of condition. As per Ayurveda, Oligospermia can be considered as Ksheenashukra. In Ksheenashukra there is diminished level of Shukra in the infertile couples. In Auervedic texts many herbal preparations mentioned in management of Ksheenashukra. Here a Single case were taken to evaluate the effectiveness of Shrungatak Modak to treat a Ksheenashukra.

Investigación del efecto de la coenzima Q10 sobre el daño testicular inducido por ciclofosfamida en ratas macho

Cyclophosphamide (CP) is one of the frequently preferred chemotherapeutic agents Worldwide. CP has negative effects on the testes, spermatogenesis, and reproductive hormones. The aim of this study was to determine the protective effect of Coenzyme Q10 (CoQ10) on the damage caused by CP. CoQ10 is use in the treatment of infertility problems and is naturally found in the testes and seminal fluid. Thirty–six Albino Wistar male rats were divided into six groups (Control, Sham, Cyclophosphamide (CP), Coenzyme Q10 (CoQ10), CP + CoQ10 I, CP + CoQ10 II), with six animals in each group. Semen analysis included investigations of sperm DNA damage, motility, abnormal sperm ratio, and density. Histopathological examination and assessment of oxidative stress parameters in the testes were conducted. Additionally, serum levels of FSH, LH, and Testosterone were measured. CoQ10 administration increased the motility rate, density, and Testosterone levels in testicular damage caused by CP (P&lt;0.05). Furthermore, it was observed that the abnormal sperm ratio, sperm DNA damage, and oxidative stress were reduced (P&lt;0.05). Based on the results of this study, the use of CoQ10 in conjunction with CP has the potential to alleviate male infertility problems that may arise from CP administration.

Morphological structure of testicles under conditions of experimental gonadopathy and after the administration of cholecalciferol in comprehensive correction schemes

The problem of male infertility is relevant and calls for a solution. The use of the D3 vitamin in infertility treatment schemes has a potentially positive effect on reproductive health in male individuals. The present study aims to examine the effect of vitamin D3, administered alone or in combination with a preparation containing the extract of Tribulus terrestris on the changes in the histological picture of testicular morphology in rats with experimental gonadopathy. Male rats with modeled reproductive function pathology (Serotonin-induced gonadopathy) were divided into groups receiving correction using cholecalciferol alone or in combination with the reference drug Tribestan (Tr), which contains an extract of Tribulus terrestris. In addition to observational microscopy, morphometric evaluation of spermatogenesis was performed on sections of the testicles stained with hematoxylin and eosin. The statistical analysis was performed using the standard software package “Statistica 6.0” with the utilization of the Student’s t-test and its nonparametric counterpart, the Kruskal-Wallis test for one-way analysis of variance, followed by the Mann-Whitney test. It was found that the seminiferous tubules of rats with Serotonin-induced gonadopathy are significantly reduced in size, and their tunica propria is thickened. Sertoli cells are often destructively altered, and the uniformity of their arrangement is disrupted. A decrease in the weight of the gonads, epididymis, prostate gland, and hypoandrogenization was observed as well as a decline in spermatogenesis indicators. An improvement in the morphological characteristics of the gonads was noted following the administration of vitamin D3 in the presence of pathology. The seminiferous tubules had a normal histological structure. The germ cells were arranged in concentric rows according to their developmental stages, and the Sertoli cells appeared visually unchanged. The population of Leydig cells appeared visually more heterogeneous than in the control animals. However, occasionally seminiferous tubules with focal necrobiosis of germ cells and dystrophy of Sertoli cells, as well as a reduction in rows of germ cells, were observed. Overall, the quantitative indicators of spermatogenesis improved after the administration of vitamin D3 compared to rats with experimental gonadopathy, although they did not reach the levels of the intact control. The administration of a combination of vitamin D3 and Tribestan in the presence of gonadopathy resulted in a greater positive effect compared to their individual use. The microscopic condition of the testicular tissue in rats was fully recovered. The combined use of vitamin D3 with Tribestan normalized the weight of the gonads and their appendages, significantly reduced the manifestations in the histological sections of degeneration and damage in the reproductive cells during the period of growth and differentiation, improved the relative level of androgen status in the organism and had a positive effect on spermatogenesis in the gonads. Thus, we have established that the combined use of Сholecalciferol and Tribestan for correcting experimental gonadopathy was more effective than either of the mentioned components alone.

Biochemical indicators of sperm plasma and morphofunctional features of spermatozoa in HIV-infected men

BACKGROUND: The problem of male infertility particularly affects men with HIV infections, as semen volume and sperm motility are reduced by highly active antiretroviral therapy.&#x0D; AIM: To analyze the metabolic parameters of spermatozoa, spermograms and spermatozoa morphology in HIV-infected men.&#x0D; MATERIALS AND METODS: The study included 47 patients (aged 2546 years) who were under observation at the clinic of Professor M.A. Florova (Samara). 2 groups were formed: main (n=22) HIV-infected patients who want to have children (with an undetectable viral load (4050 copies/ml) and taking antiretroviral therapy); control (n=25) clinically healthy men with one child. The material was taken and the ejaculate was examined according to standardized methods proposed by WHO experts.&#x0D; RESULTS: In HIV-infected men, spermatozoa motility was low (the number of progressively motile spermatozoa was 28.503.72%), the spermatozoa concentration was two times lower compared to the control group of men, the morphological characteristics of spermatozoa were significantly worse than in the control group: most often pathology of the head (21.751.10%) and neck of the spermatozoon (22.301.18%) was detected, which negatively affects the fertilizing ability.&#x0D; In HIV-infected men, changes in metabolic metabolism were noted: the activity of creatine phosphokinase in both sperm plasma (661.951.08 U/l) and blood plasma (76.901.09 U/l) was lower, than in the control group (844.250.13 and 79.501.37 U/l, respectively), the glucose concentration (8.071.14 mmol/l) was 2 times higher than in the control group (3.061.09 mmol/l), the concentration of calcium 6.530.01 and sodium (119.201.23 mol/l) slightly exceeded those in the group of healthy patients (5.550.08 and 116.850.01 mol/l, respectively). Electron microscopic analysis revealed fragmentation of sperm DNA: the highest percentage of sperm with fragmented DNA was found in men with HIV infection (more than 23%).&#x0D; CONCLUSION: It was revealed that in vivo fertilization in HIV-infected men is impossible in most cases. The study forms the basis for a future comprehensive assessment of the state of reproductive function in HIV-infected men to assess their fertility and the need for assisted reproductive technologies.

Women of reproductive age living in the North of the Netherlands: Lifelines Reproductive Origins of Adult Health and Disease (Lifelines-ROAHD) cohort

PurposeThe Lifelines Reproductive Origins of Adult Health and Disease (Lifelines-ROAHD) cohort provides a uniquely detailed dataset allowing investigations of determinants of reproductive health as well as the influence of reproductive...

Role of sphingolipid metabolites in the homeostasis of steroid hormones and the maintenance of testicular functions.

With the acceleration of life pace and the increase of work pressure, the problem of male infertility has become a social problem of general concern. Sphingolipids are important regulators of many cellular processes like cell differentiation and apoptosis, which are ubiquitously expressed in all mammalian cells. Various sphingolipid catabolic enzymes can generate multiple sphingolipids like sphingosine-1-phosphate and sphingomyelin. Present studies have already demonstrated the role of steroid hormones in the physiological processes of reproduction and development through hypothalamus-pituitary-gonad axis, while recent researches also found not only sphingolipids can modulate steroid hormone secretion, but also steroid hormones can control sphingolipid metabolites, indicating the role of sphingolipid metabolites in the homeostasis of steroid hormones. Furthermore, sphingolipid metabolites not only contribute to the regulation of gametogenesis, but also mediate damage-induced germ apoptosis, implying the role of sphingolipid metabolites in the maintenance of testicular functions. Together, sphingolipid metabolites are involved in impaired gonadal function and infertility in males, and further understanding of these bioactive sphingolipids will help us develop new therapeutics for male infertility in the future.

Reprotoxic Effect of Tris(2,3-Dibromopropyl) Isocyanurate (TBC) on Spermatogenic Cells In Vitro

Tris(2,3-dibromopropyl) isocyanurate (TBC) belongs to the class of novel brominated flame retardants (NFBRs) that are widely used in industry. It has commonly been found in the environment, and its presence has been discovered in living organisms as well. TBC is also described as an endocrine disruptor that is able to affect male reproductive processes through the estrogen receptors (ERs) engaged in the male reproductive processes. With the worsening problem of male infertility in humans, a mechanism is being sought to explain such reproductive difficulties. However, so far, little is known about the mechanism of action of TBC in male reproductive models in vitro. Therefore, the aim of the study was to evaluate the effect of TBC alone and in cotreatment with BHPI (estrogen receptor antagonist), 17β-estradiol (E2), and letrozole on the basic metabolic parameters in mouse spermatogenic cells (GC-1 spg) in vitro, as well as the effect of TBC on mRNA expression (Ki67, p53, Pparγ, Ahr, and Esr1). The presented results show the cytotoxic and apoptotic effects of high micromolar concentrations of TBC on mouse spermatogenic cells. Moreover, an increase in Pparγ mRNA levels and a decrease in Ahr and Esr1 gene expression were observed in GS-1spg cells cotreated with E2. These results suggest the significant involvement of TBC in the dysregulation of the steroid-based pathway in the male reproductive cell models in vitro and may be the cause of the currently observed deterioration of male fertility. However, more research is needed to reveal the full mechanism of TBC engagement in this phenomenon.

Dietary patterns and fertility status in men: Mediterranean diet does make a difference in ameliorating the rise in male infertility problems due to changing lifestyle

Dietary patterns and fertility status in men: Mediterranean diet does make a difference in ameliorating the rise in male infertility problems due to changing lifestyle

Effect of calcium ionophore (A23187) on embryo development and its safety in PGT cycles.

Intracytoplasmic sperm injection (ICSI) has tremendous advantages for resolving the problem of male infertility. However, ICSI fertilization can fail in some patients because of various reasons, primarily because of the failure of oocyte activation. Oocytes have been activated using calcium ionophore (A23187) in previous clinical cases of ICSI fertilization failure. However, studies on the efficiency of calcium ionophore (A23187) activation, its effects on the developmental potential of embryos, and its effects on pregnancy outcomes after embryo transfer are relatively limited. In this study, we investigated the safety and long-term efficacy of calcium ionophore (A23187) by analyzing its effects on fertilization, embryonic development, aneuploidy, and pregnancy outcomes in patients undergoing preimplantation genetic testing (PGT) cycles. Comparative analyses of the activation followed by PGT (A-PGT) and PGT groups revealed no significant differences between the oocyte cleavage rate and high-quality embryo rate (98.19% vs. 98.63% and 63.13% vs. 68.39%, respectively, p > 0.05). Although the blastocyst formation rate was significantly lower in the A-PGT group than that in the PGT group (52.22% vs. 59.90%, p < 0.05), no significant difference was observed in the blastocyst aneuploidy rates of the two groups (24.49% vs. 24.55%, p > 0.05). Furthermore, no significant differences were observed between the two groups in terms of the live birth rate (43.75% vs. 52.99%), week of delivery, and birth weight of the infants after transfer of euploid blastocysts (p > 0.05). Furthermore, the 2PN rate, oocyte cleavage rate, blastocyst formation rate, and live birth rate were found to be significantly lower in the A-ICSI group than those in the ICSI group (p < 0.01), but there was no significant difference between the two groups in the week of delivery and birth weight of live births (p > 0.05). These results suggest that the use of calcium ionophore (A23187) activation as an option in cases of ICSI fertilization failure does not affect the ploidy of developing blastocysts and has no significant effects on the week of delivery or birth weight after transfer. Thus, we provide a scientific basis for the clinical safety of oocyte activation using calcium ionophore (A23187).

Multifunctional 4D-Printed Sperm-Hybrid Microcarriers for Assisted Reproduction.

Remotely controllable microrobots are appealing for various biomedical in vivo applications. In particular, in recent years, ourgroup has focused on developing sperm-microcarriers to assist sperm cells with motion deficiencies or low sperm count (two of the most prominent male infertility problems) to reach the oocyte toward in-vivo-assisted fertilization. Different sperm carriers, considering their motion in realistic media and confined environments, have been optimized. However, the already-reported sperm carriers have been mainly designed to transport single sperm cell, with limited functionality. Thus, to take a step forward, here, the development of a 4D-printed multifunctional microcarrier containing soft and smart materials is reported. These microcarriers can not only transport and deliver multiple motile sperm cells, but also release heparin and mediate local enzymatic reactions by hyaluronidase-loaded polymersomes (HYAL-Psomes). These multifunctional facets enable in situ sperm capacitation/hyperactivation, and the local degradation of the cumulus complex that surrounds the oocyte, both to facilitate the sperm-oocyte interaction for the ultimate goal of in vivo assisted fertilization.

O-170 A blessing or a curse? A bit of both

Abstract My name is Katarina Turković Gulin, now I am 46 years old, and I have 11 IVF procedures behind. I will go back to the beginning, when my husband and I first thought we would need help. We got married and we did not plan to have children right away, there seemed to be time. When we decided it was time, the pregnancy was by no means able to happen. I will not lie. We could and should have sought help earlier. We both studied, we struggled with resolving the housing issue, waited for permanent or at least safer employment, and all of that delayed the start of our medical treatment. All off this influenced by the opinion of my gynecologist in primary health care, who for years assured us that everything was fine, that we were young, that, there was time. Mistake! After years of trying without any results, in 2010 we resolutely set out to seek help. We lost another year in cycle monitoring and targeted intercourse, and when there were no results, we insisted that doctor send us to human reproduction specialists. The first findings pointed to the problem of male infertility. We both graduated from medical school and were able to understand what was going on, what that diagnosis meant, and what the treatment options were. I think, one of the problems that most patients face it in their treatments is the inability to understand the words of medical specialist. We have been fortunate to have our medical education help us understand everything that is happening to us and around us. I have had the opportunity to connect with many couples who are going through IVF and provide support through various groups. Many of them are looking for additional information and it is difficult to understand something so professionally said, all those professional terms and names. We started the treatment in our city, but already at the first conversation with medical specialist, we learned how unsuccessful the clinic was, how bad the conditions and materials used were, how outdated methods they use.Many methods and procedures that we could read about were not available in Croatia. Especially in the field of diagnostics. Something in that field is changing today, but slowly, insufficiently. At that time, the percentage of success of the clinic was barely 3%, so all of this rejected us. We set out to seek help further. I was a full 35 and we knew there was no time for waiting. We were by experts in the Netherlands, Slovenia and Italy. In Maribor we met a top expert, who received and treated us in Zagreb, in a private clinic he cooperated. Already in the first procedure, we succeeded. The first positive home test, the first positive beta hCG! But it didn’t take long. In the 8th week of pregnancy, we lost the battle.In that period we tried to look for answers, we asked for additional tests. Then tried again, at the private clinic of a doctor who is a pioneer of IVF in this area. We followed the condition through several cycles, it seemed like everything was still working even though I was approaching 43 at the time. The approach was a bit different, better preparation, better diagnostics. After 11 IVF procedures, we stopped. At some point, it is important to stop and say enough. Then, in that moment, it is a blessing to know that we have done everything possible. Only in that way can calmly accept this ‘’failure’’ and continue to live happily with what we have instead of despairing over what we does not have.