P–430 Male fertility preservation: is there a role for cancer-induced inflammation that affects semen quality in oncological patients?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Omes ◽  
V Tomasoni ◽  
R Bassani ◽  
V Amico ◽  
R E Nappi

Abstract Study question What is the cause of semen quality impairment in oncological patients during fertility preservation programs? The cancer type and stadiation or the resulting inflammatory state? Summary answer The inflammatory state seems to be related to the decrease of sperm concentration, motility, morphology and viability due to the worsening of oxidative stress microenvironment. What is known already Fertility preservation acquired a great importance in the last decades due to increase survival of oncological patients, boost of diagnosis under 40 years and postponement of paternal age. At the time of cryopreservation, only one third of these males are normozoospermic. Tumor itself or other factors, added to psychological reasons, may be involved but there is no clear evidence. An imbalance of ROS (reactive oxygen species) in semen can compromise its quality. However, the correlation between cancer-related generalized stress state and fertility is poorly investigated. Inflammatory conditions induced by infections and pathologies, including cancer, increase ROS. Study design, size, duration Retrospective observational analysis was performed on 45 patients (29.0 ± 6.9 yrs) recruited during their fertility preservation program between 2016 and 2019 with written consent on use of their clinical data for research purpose. Patients presented several oncological diagnoses. Semen samples obtained from multiple collections (N = 58) were analyzed before applying standard freezing protocol. Data on semen parameters, inflammatory indices, hematological values and type/stage of tumors were collected. No exclusion criteria were applied. Participants/materials, setting, methods Routine semen analysis was performed according to the WHO standards. Sperm concentration and motility were evaluated on Makler Chamber, whereas eosin stain and Diff-quick slides were used for viability and morphology, respectively. Lymphoma was present in 72% of cases, leukemia in 8%, seminoma in 7% and other cancers in 13%. Correlations (Pearson/Spearman tests) among principal semen parameters and hematological values (leukocytes, erythrocytes, hemoglobin, RDW, albumin, etc.) were calculated with a P-value <0.05 considered statistically significant. Main results and the role of chance The majority of semen samples showed a severe impairment, with one or more parameters under lower reference limits (WHO): 48.3% had sperm concentration under 15 millions/ml, 43.1% had a progressive motility under 32%, 41.4% had viability under 58% and 91.4% had abnormal morphology (under 4%). The role of potential inflammatory state was analyzed by correlating semen parameters and some hematological values. No correlation was found with cancer type. Negative association resulted between progressive motility (%PR) and leukocytes (p = 0.041) or RDW% (p = 0.015), but positive one with albumin (p = 0.012). Even sperm count, total motility (%PR+NP) and morphology were significantly correlated to RDW% (p = 0.003, p = 0.032, p = 0.034, respectively). These findings suggest a possible role of inflammation and ROS related generation in semen quality impairment. Indeed, albumin exerts a protective action, but leukocytes are known to cause ROS increase. Cancer-induced oxidative stress state may alter red blood cells homeostasis and vitality and increase erythrocytes turnover resulting in high RDW values. It is likely semen is worse when blood values indicate more severe cancer-induced inflammatory condition. Limitations, reasons for caution Significant correlations with type/stage of cancer were not found due to small number of each diagnosis, in spite our study considered 3 years of patients inclusion. Moreover, we lack to analyze the same patient before the cancer onset to avoid the influence of inflammatory state generated by the tumor itself. Wider implications of the findings: Understanding the influence of cancer-induced inflammatory state on semen quality could increase the awareness that clinicians should direct patient to the fertility preservation as soon as possible, even if diagnosis is still ongoing. It should be evaluated whether offering specific treatments may reduce oxidative stress conditions. Trial registration number Not applicable

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Massarotti ◽  
E Maccarini ◽  
L Loberti ◽  
C D Leo ◽  
S Stigliani ◽  
...  

Abstract Study question Does ejaculatory frequency during the three months preceding semen collection influence semen parameters in oligospermic men? Summary answer A frequency of 2–3 ejaculations/week during the three months preceding semen collection significantly optimizes sperm motility, without any reduction in sperm concentration. What is known already Male gametes undergo crucial physiological and biochemical changes during epididymal transit, but a longer storage is known to have negative effects on semen quality, especially on motility. Previous studies focused on abstinence prior to semen collection, while few data are available on the effect of ejaculation frequency. On one hand, a longer storage could increase exposure to reactive oxygen species and a pro-inflammatory environment, with a reduction in vitality and motility. On the other, an increased ejaculation frequency could cause a reduction in sperm volume and concentration. The effects of ejaculatory frequency are particularly understudied in men with oligospermia. Study design, size, duration This is a retrospective study performed at a tertiary level public infertility center. We included all semen samples, collected both for diagnostic purposes and ART cycles between September 2019 and September 2020, with a sperm concentration of 15 million/ml or less, and an abstinence of 3- 5 days. Exclusion criteria were surgically collected or collected for fertility preservation semen samples. Participants/materials, setting, methods Standard demographic and clinical data were recorded, as well as semen parameters. Ejaculation frequency was considered “optimal” (at least 2–3/week) or “reduced” (<1/week). The potential predictive role of ejaculation frequency, age, BMI, smoking habits, previous cryptorchidism, varicocele, days of abstinence on semen parameters was evaluated by univariate and then by multivariate analysis for all factors significant in the univariate models. P < 0.05 was considered statistically significant. Main results and the role of chance: Out of 738 men, 491 reported an optimal ejaculation frequency, 247 had <1 ejaculation/week, no one reported everyday ejaculations. Total sperm mobility (35.91±22.84% vs. 32.28±16.91%, p = 0.02) and sperm rapid progressive motility (5.56±6.09% vs. 4.20±6.1%, p = 0.006) were significantly higher in the group with optimal ejaculation frequency. Ejaculation frequency remained predictive of total mobility (p = 0.04) and rapid progressive mobility (p = 0.03) in a multivariate linear regression model with age and sperm concentration. Sperm volume (2.92±1.56 ml vs. 2.91±1.54 ml, p=NS) and concentration (5.74±5.05 mil/ml vs. 6.05±4.78 mil/ml, p=NS) did not significantly differ depending on the declared ejaculation frequency. Limitations, reasons for caution The study is retrospective and ejaculatory frequency was self-reported as an estimate of the mean of the number of ejaculations per week. Wider implications of the findings: Optimizing ejaculatory frequency may improve ART outcomes as well as success of spontaneous conceptions. There is no reason to limit ejaculatory frequency in oligospermic men for a hypothesized benefic in sperm concentration. Trial registration number Not applicable


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Michał Dobrakowski ◽  
Zbigniew Kaletka ◽  
Anna Machoń-Grecka ◽  
Sławomir Kasperczyk ◽  
Stanisław Horak ◽  
...  

The aim of the study was to investigate the associations between standard semen parameters and the parameters reflecting oxidative stress intensity, antioxidant defense functions, levels of selected macro and trace elements, and parameters characterizing immune system function. The study group consisted of 103 fertile males. Based on semen volume, sperm concentration, total sperm count, and percentage of motile sperm at 1 hour postcollection, the individuals were divided into two equal groups—those with excellent (EX) semen quality and those with mediocre (ME) semen quality. The remaining measured parameters characterizing motility and the percentage of normal morphology were higher in the EX group than in the ME group; however, the seminal plasma pH did not differ between the examined groups. The phosphate level was 31% lower in the EX group than in the ME group, whereas there was a tendency toward a 25% lower level of Fe in the EX group than in the ME group (p=0.064). The activities of enzymes involved in antioxidant defense, CuZn-SOD, CAT, and G6PD, were 14%, 63%, and 39%, respectively, higher in the EX group than in the ME group. However, the level of alpha-tocopherol was 32% lower in the EX group than in the ME group. The other measured parameters characterizing antioxidant defense and the parameters of oxidative stress intensity and immune system function were not significantly different. The value of seminal plasma pH is not related to the semen quality of fertile males. Higher fertility potential estimated based on standard semen parameters in fertile males is associated with lower levels of Fe and higher activities of some antioxidant enzymes.


Author(s):  
Nasim Bidram ◽  
Amir Nili-Ahmadabadi ◽  
Iraj Javadi ◽  
Seyedmahdi Tabatabaei

Background and Aims: Smoking has an influence on different semen parameters. It is regarded as a risk factor for infertility. This study aims to evaluate the effect of smoking cigarettes on the expression of nuclear factor erythroid 2-related factor 2 (NRF2) and glutathione S-transferase Mu 1 (GSTM1) genes and biomarkers of oxidative stress in sperm. Materials and Methods: A case-control study was conducted on 15 men smoker (case) and 15 men nonsmokers (control) who had referred to infertility clinics in Isfahan, Iran. After sampling and analysis of semen quality parameters, gene expression of NRF2 and GSTM1 was determined using a Real time-polymerase chain reaction instrument. The lipid peroxidation and total antioxidant capacity (TAC) were evaluated by colorimetric methods. Results: Sperm concentration and their progressive motility in smokers were significantly lower than the nonsmoker population (p<0.001). In addition, the lipid peroxidation level increased and TAC level (p<0.01) as well as gene expression of NRF2 (p<0.05) and GSTM1 (p<0.01) decreased compared to control groups. Conclusions: Our data demonstrated that the NRF2 and GSMT1 expressions are significantly lower in human males with low sperm motility and correlated with specific sperm quality parameters.


2021 ◽  
Author(s):  
Ning Wang ◽  
Fang Lv ◽  
Ge Yu ◽  
Cuige Shi ◽  
Shangming Wang ◽  
...  

Abstract Background: Iodine is an essential element for hormones synthesized by the human thyroid gland. Thyroid hormone deficiency affects all body tissues, including multiple endocrine changes that alter growth hormones, corticotrophin, glucocorticoids, and gonadal function. In many countries, subfertility is an important problem affecting about 10–15% of all couples trying to conceive. Male subfertile factors have accounted for 25–30% of all cases in their studies. The aim of this study was to study the correlation between urinary iodine concentration (UIC) and semen quality of fertile male in China.Methods: semen and urine samples were collected from males who attended a survey for the reproductive physiological constants of male and female in China. All participants were fertile and they should be free from diseases of male reproductive system and thyroid related diseases. We studied the correlation between UIC and semen quality parameters in fertile males and the effect of iodine concentration on male reproduction. Participants were divided into six groups based on UIC. We measured semen parameters and UIC. Semen parameters or time-to-pregnancy (TTP) were analyzed by Spearman correlation, linear regression and multivariable logistic regression. Results: 1089 men were recruited in the study. The mean and median age of participants were 27.46±0.12 and 27±3.88 years, respectively. UIC of 274 (25.16%) men was lower than the UIC of WHO recommended. UIC of 405 men located in the region of WHO recommended. 62.35% of them were not located in the optimal region. Semen concentration and total sperm count were found to decrease when UIC increases when the UIC≥100 ug/L. Conclusions: A male with deficient UIC or excessive UIC has more risk of lower semen quality such as sperm concentration and total sperm count. In addition, if a male with deficient UIC or excessive UIC, his wife has longer TTP than the males who had normal UIC. Deficient UIC associated with lower semen quality and TTP than excessive UIC.


Author(s):  
W. N. Li ◽  
M. M. Jia ◽  
Y. Q. Peng ◽  
R. Ding ◽  
L. Q. Fan ◽  
...  

Abstract Background The aim of this study was to provide information on the semen quality pattern of infertile men and age thresholds for semen parameters in China. Methods This was a retrospective cross-sectional study investigating 71,623 infertile men from the Reproductive and Genetic Hospital of CITIC Xiangya in Hunan, China, from 2011 to 2017. The Kruskal-Wallis test, Mann-Kendall test, linear regression model and joinpoint regression were used. Results Although erratic changes were observed in the median semen parameters (sperm concentration 40.1–52.1 × 106/ml, total sperm count 117.8–153.1 × 106, sperm progressive motility 33.4–38.1%) during the 7 years of observation, no significant decrease in semen quality was found, and 47.88% of infertile men showed normal semen parameters according to the World Health Organization (WHO) criteria. According to the joinpoint regression analysis, sperm progressive motility appeared to decrease earlier than the sperm concentration and total sperm count (at 28, 58, and 42 years of age, respectively). Conclusions There is no evidence of a deterioration in semen quality among infertile men in Hunan, China. Semen parameters decreased with increasing age, with turning points noted at different ages. Semen parameters are not absolute evidence for the assessment of male fertility potential. Therefore, we believe that, among semen parameters, the sperm concentration is the best predictor of fertility for ART, followed by motility. Decreased sperm motility may affect natural pregnancy, but it is not necessary for successful IVF.


2019 ◽  
Vol 02 (02) ◽  
pp. 49-57
Author(s):  
Wenli Cao ◽  
Xinyao Pan ◽  
Feijun Ye ◽  
Jing Zhou ◽  
Zengshu Huang ◽  
...  

Objective: This study aimed to evaluate the semen quality of male adults whose spouses suffer from recurrent spontaneous abortion (RSA) in the island area, and to explore the association between RSA and occupational exposures. Methods: A total of 131 male patients were recruited and divided into two groups: spouse with recurrent spontaneous abortion group (RSA group, [Formula: see text]) and the normal fertility group (control group, [Formula: see text]). Information such as height, weight and occupational exposure history of 131 men were obtained. Semen samples were collected and analyzed. Differences in semen parameters and DNA fragmentation index (DFI) between the two groups were compared. Odds ratios (ORs) and their corresponding 95% confidence intervals were calculated to evaluate the association between occupational exposures and RSA status. Results: Overall, no significant difference was found in sperm concentration, progressive motility and normal morphology rate between RSA and control groups. Only DFI was observed to be significantly higher in the RSA group. Evaluation of the receiver operating characteristic (ROC) curve showed DFI (AUC: 0.623, [Formula: see text]) could discriminate between males from the couples with RSA and without RSA. Conclusion: The analysis of conventional semen parameters could not directly reflect their influence on embryonic development, and test of integrity of the sperm DNA is of paramount importance to fully understand male fertility. It is crucial to conduct studies regarding occupational exposures and pregnancy loss and/or RSA risk, since it will provide population-level data to aid in the identification of important risk factors that warrant further mechanistic investigation, and eventually lead to effective prevention and treatment strategies.


2020 ◽  
Vol 35 (9) ◽  
pp. 2149-2162
Author(s):  
F Belva ◽  
M Bonduelle ◽  
A Buysse ◽  
A Van den Bogaert ◽  
F Hes ◽  
...  

Abstract STUDY QUESTION Is there a relationship between karyotype abnormalities in fetuses and children conceived by ICSI and their father’s semen parameters? SUMMARY ANSWER The de novo chromosomal abnormality rate in pre- and postnatal karyotypes of ICSI offspring was higher than in the general population and related to fathers’ sperm parameters. WHAT IS KNOWN ALREADY Several studies have reported a higher rate of de novo chromosomal anomalies in ICSI fetuses but recent data from large cohorts are limited. Overall, reported prevalences of non-inherited karyotype aberrations are increased in fetuses conceived after ICSI and vary between 1.6% and 4.2%. Only a few studies focus on the relation between karyotype anomalies in ICSI offspring and semen parameters of their fathers. Furthermore, an increased incidence of abnormal karyotypes in ICSI neonates has been described, but the rates vary widely across studies. STUDY DESIGN, SIZE, DURATION We report on karyotype results from prenatal testing by means of chorionic villus sampling and amniocentesis and results from postnatal blood sampling in offspring conceived by ICSI in a single center. Ongoing pregnancies resulting from an oocyte retrieval between January 2004 and December 2012 and after transfer of fresh ICSI embryos obtained using ejaculated or non-ejaculated sperm (fresh or frozen-thawed) were considered. Pregnancies following frozen embryo transfer, oocyte or sperm donation, IVF, preimplantation genetic testing and IVM were excluded. All abnormal prenatal results after sampling are reported irrespective of the outcome of the pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS From the 4816 ongoing ICSI pregnancies, information on pregnancy outcome was available for 4267 pregnancies. Prenatal testing was performed in 22.3% of the pregnancies, resulting in a diagnosis in 1114 fetuses. A postnatal karyotype was obtained in 29.4% of the pregnancies in which no invasive prenatal diagnosis was performed, resulting in a total of 1391 neonates sampled. The prevalence of chromosomal anomalies according to maternal age and semen quality was analyzed with logistic regression. For definitions of normal semen quality, the World Health Organization reference values for human semen characteristics were adopted. MAIN RESULTS AND THE ROLE OF CHANCE An abnormal fetal karyotype was found in 29 singletons and 12 multiples (41/1114; 3.7%; 95% CI 2.7–4.9%): 36 anomalies were de novo (3.2%; 95% CI 2.3–4.4), either numerical (n = 25), sex (n = 6) or structural (n = 5), and five were inherited. Logistic regression analysis did not show a significant association between maternal age and a de novo chromosomal fetal abnormality (odds ratio (OR) 1.05; 95% CI 0.96–1.15; P = 0.24). In all but one case, fetuses with an abnormal karyotype were conceived by ICSI using ejaculated sperm. Abnormal karyotypes were found in 14 (1.0%; 95% CI 0.6–1.7) out of 1391 postnatal samples of children born after ICSI who were not tested prenatally: 12 were de novo anomalies and two were inherited balanced karyotypes. The 14 abnormal karyotypes were all found in children born after ICSI using ejaculated sperm. The odds of a de novo karyotype aberration increased with maternal age when combining pre- and postnatal data (OR 1.11; 95% CI 1.04–1.19). A higher rate of de novo chromosomal abnormalities was found in fetuses and children of couples with men having a sperm concentration &lt;15 million/ml (adjusted OR (AOR) 2.10; 95% CI 1.14–3.78), sperm concentration &lt;5 million/ml (AOR 1.9; 95% CI 1.05–3.45) and total sperm count &lt;10 million (AOR 1.97; 95% CI 1.04–3.74). LIMITATIONS, REASONS FOR CAUTION We cannot exclude that the observation of a higher prevalence of karyotype anomalies in ICSI offspring compared to literature data in the general population is due to enhanced surveillance after ART given the lack of a control group. Although we did not find more chromosomal anomalies after ICSI with non-ejaculated sperm, the small numbers do not allow firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS The observed increased risk of a de novo karyotype anomaly after ICSI conception in couples with poor sperm warrants continued counseling toward prenatal testing. The current and widespread use of innovative non-invasive prenatal testing will result in larger datasets, adding to a balanced estimation of the prevalence of karyotype anomalies in ICSI offspring. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the Methusalem grants issued by the Vrije Universiteit Brussel. All authors declared no conflict of interest related to this study. TRIAL REGISTRATION NUMBER N/A


2020 ◽  
Vol 32 (2) ◽  
pp. 137
Author(s):  
Y. Pirosanto ◽  
M. Valera ◽  
A. Molina ◽  
J. Dorado ◽  
S. Demyda-Peyrás

Inbreeding depression, a genetic condition produced by the mating of close-related individuals, has been associated with a reduction of fertility in several species. However, a loss in sperm quality was also associated with age. In horses, the few existing reports have described a tendency of both parameters to produce a negative effect on sperm quality. However, those reports were performed using a subjective evaluation of sperm motility. In the present study, a total of 692 ejaculates from 86 Pure Spanish stallions (PRE), aged between 3 and 22 years, were evaluated using a computer-assisted methodology to determine the effect of inbreeding in four semen parameters: free-gel volume (V), sperm concentration (C, by haemocytometer), and total (TM) and progressive (PM) sperm motility (by Spermvision sperm class analyser; Minitube). The inbreeding coefficient (F) was estimated using 300 000 PRE pedigree records approximately (minimum pedigree depth, eight equivalent complete generations; range, between 1 and 30.1%). Stallion, age, ejaculate, and season of semen collection were the variables included in the statistical model (general linear model), with ejaculate and season being the variables with a major effect (by variance components analysis). Our results showed that sperm concentration (r=−0.18; P&lt;0.0001) and volume (to a lesser extent) were reduced with advancing age, both showing a major decline after 15 years of age. To the contrary, sperm motility was not affected by age of the stallion. We also found a negative correlation between the inbreeding coefficient and ejaculate volume (r=−0.14; P&lt;0.001), with a marked decrease seen when F was between 7 and 20%. Also, a negative correlation was observed in PM (r=−0.08; P&lt;0.05), although to a lower extent. Conversely, C and TM were not affected by inbreeding depression (P&gt;0.05). In conclusion, our results demonstrated that high levels of inbreeding can compromise severely the sperm quality of the PRE stallion, which, subsequently, may have a negative influence on fertility. Ongoing studies using genomic data will help to detect genetic variants associated with stallion semen quality and how it is influenced by inbreeding in specific genomic regions.


2020 ◽  
Vol 112 (3) ◽  
pp. 707-719 ◽  
Author(s):  
Ghazaleh Eslamian ◽  
Naser Amirjannati ◽  
Nazanin Noori ◽  
Mohammad-Reza Sadeghi ◽  
Azita Hekmatdoost

ABSTRACT Background It is unknown which compounds in spermatozoa or seminal plasma may be involved in the regulation of sperm motility. Objectives The aim of this study was to investigate the effects of DHA (22:6n–3), vitamin E, and their probable interactions in men with asthenozoospermia. Methods A factorial, randomized, double-blind, placebo-controlled trial was conducted in infertility clinics in Tehran, Iran. The participants were idiopathic asthenozoospermic men aged 20–45 y, with normal endocrine function. Their concentration of spermatozoa and percentage of morphologically normal spermatozoa were equal to or above the lower reference limits, according to the fifth edition of the WHO guideline. Out of 717 men referred to the infertility clinics, 180 asthenozoospermic men were randomly assigned to 1 of 4 groups according to stratified blocked randomization by age and sperm concentration. Participants took daily 465 mg DHA plus 600 IU vitamin E (DE), 465 mg DHA plus placebo (DP), 600 IU vitamin E plus placebo (EP), or both placebo capsules (PP) for 12 wk. Sperm characteristics, oxidative stress of seminal plasma, serum and sperm membrane fatty acids, dietary intakes, anthropometric measurements, and physical activity were measured at baseline and after 12 wk. Results After the intervention, mean ± SD sperm progressive motility was greater in the DE group (27.9 ± 2.8) than in the DP (25.7 ± 3.4), EP (26.1 ± 2.8), and PP (25.8 ± 2.6) groups (P &lt; 0.05). Sperm count (P = 0.001) and concentration (P = 0.044) increased significantly in the DE group compared with the other 3 groups, whereas other semen parameters were not significantly different between the groups after the intervention. Serum concentrations of n–3 PUFAs were significantly higher in the DE and DP groups than in the EP and PP groups. Conclusions Combined DHA and vitamin E supplements led to increased sperm motility; however, no significant changes occurred in sperm morphology and vitality in asthenozoospermic men. This trial was registered at clinicaltrials.gov as NCT01846325.


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