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Sleep Apnea as a Potential Threat to Reproduction

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... However, this previous study only focused on the diagnosis of infertility and OSA and did not measure the AHI nor perform semen analysis on each patient. In another Fig. 1 Flow chart of the study in vivo study, chronic intermittent hypoxia decreased sperm quality in mice [13], although importantly the sperm samples were directly obtained from the epididymis; since the sperm did not pass through the vas deferens, vesicles, and prostate, the study samples may have differed from ejaculated semen so may not accurately reflect male fertility [20]. A recent study investigating the impact of OSA on male reproductive function only detected a higher rate of sperm abnormalities in the OSA group compared with the normal population, but the sample size was limited (n = 7 in the OSA group) [21]. ...
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Background Obstructive sleep apnea (OSA) has several notable complications such as hypertension and diabetes. Studies have also shown that OSA is associated with erectile dysfunction and reduced androgen levels. However, the effect of OSA on semen quality remains poorly studied. Methods Men attending a tertiary reproductive center for semen analysis were tested with a portable sleep breathing monitor. Patients were divided into four groups based on their apnea hypopnea index: none, mild, moderate, and severe obstructive sleep apnea. Differences between groups were assessed using χ2, and associations were tested with multiple regression analysis. Results We included a total of 175 male subjects with a mean age of 32.2 ± 3.6 years. There were significant differences between groups in progressive sperm motility (%) (43 ± 16, 42 ± 17, 36 ± 18, 29 ± 18, respectively; p = 0.002), total motility (%) (59 ± 19, 59 ± 20, 49 ± 21, 42 ± 20, respectively; p = 0.010), and vitality (%) (80 ± 10, 81 ± 11, 79 ± 8, 72 ± 19, respectively; p = 0.039). Asthenospermia (progressive motility < 35%) was significantly more common in subjects with OSA (χ2 = 5.195, p = 0.023). In multiple regression models, after adjusting for age and body mass index, apnea hypopnea index remained negatively and significantly associated with progressive motility, total motility, and vitality. Conclusions OSA is an independent risk factor for sperm motility and vitality, and further investigation is now needed to determine if continuous positive pressure ventilation or other therapies can improve semen quality in these patients.
... Potential associations between OSA and the likelihood and outcome of infertility have recently emerged, suggesting that OSA might cause male infertility or reduce fertility [7][8][9][10][11]. Torres et al. [12] discovered that intermittent hypoxia significantly increased testicular oxidative stress and consequently reduced progressive sperm motility in mice. ...
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Obstructive sleep apnea (OSA) yields intermittent hypoxia, hypercapnia, and sleep fragmentation. OSA is associated with chronic medical conditions such as cardiovascular diseases, metabolic syndrome, and neurocognitive dysfunction. However, the risk of infertility in OSA remains unclear due to limited data and lack of long-term population-based studies. The study aims to assess the risk of infertility in obstructive sleep apnea (OSA) by means of a population-based cohort study. The data was utilized from the Taiwan National Health Insurance Research Database (NHIRD) to conduct a population-based cohort study (1997–2013). Compared with the Non-OSA group, the male with OSA and surgery group has the OR (odds ratio) of infertility of 2.70 (95% CI, 1.46–4.98, p = 0.0015), but no significance exists in females with OSA. When the data was stratified according to age and gender, some associations in the specific subgroups were significant. Respectively, males aged 20–35 years old and aged 35–50 years old with a history of OSA and surgery both had a positive association with infertility. (aOR: 3.19; 95% CI, 1.18–8.66, p = 0.0227; aOR: 2.57; 95% CI, 1.18–5.62 p = 0.0176). Male patients with OSA suffer from reduced fertility, but no significant difference was noted in females with OSA. The identification of OSA as a risk factor for male infertility will aid clinicians to optimize long-term medical care. Furthermore, more studies will be encouraged to clarify the effect of OSA on female fertility.
... In addition, it was also found that 10-60% of OSA subjects develop erectile dysfunction, as an effect of endothelial dysfunction signal. 5 Obstructive sleep apnea also causes suppression of hypothalamogonadal axis, resulting in men hypogonadism. 6 In a study by Hammoud et al., it was recommended to screen for OSA among men with hypogonadism, erectile dysfunction, and altered sperm parameters and their reproductive potential could be improved by treating the modifiable risk factor-sleep apnea. ...
... 26 Sleep apnea is a prevalent disorder, affecting up to a third of the adult population, which has been associated with male infertility. 27 In the current issue, Chen et al. 28 report a retrospective matched cohort study in which they used the Taiwan Longitudinal Health Insurance Database to analyze the risk of infertility in men with deviated nasal septum with inferior turbinate hypertrophy, compared with a matched control group. They report that improving the nasal airway by septoturbinoplasty was associated with a 45% reduced risk of infertility in men with deviated nasal septum with inferior turbinate hypertrophy. ...
... SD are a common disease and can affect the quality of life of a normal individual [23]. Most current articles focus on the association between SD and pressure, shift work, and reproductive dysfunction as study topics [24][25][26][27] but did not perform a similar analysis on the risk of developing PPD caused by SD. This study was the first study in Taiwan relevant to this topic. ...
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Postpartum depression has become an important topic of concern in recent years. However, very few studies on the causes of postpartum depression exist, and the effects of prenatal sleep disorders on the development of postpartum depression among pregnant women have not been elucidated. This study aimed to understand the association between prenatal sleep disorders and postpartum depression. The National Health Insurance Research Database of Taiwan (between 2000 and 2010) was used to assess the effects of prenatal sleep disorder on the risk of postpartum depression using Cox regression analyses. Prenatal sleep disorder in pregnant women increased the risk of developing postpartum depression (the risk in the sleep disorder cases was 5.359-fold increased compared with control cases). In addition, regardless of postpartum week (≤ 6 weeks, 6-12 weeks, or > 12weeks), the risk of developing postpartum depression in pregnant women with prenatal sleep disorders were increased, by 5.461-fold (P < 0.001), 3.490-fold (P = 0.010), and 3.416-fold (P = 0.015), respectively, compared with pregnant women without sleep disorders. Pregnant women with prenatal sleep disorders exhibited increased risks of developing postpartum depression. For pregnant women with prenatal sleep disorder, postpartum intervention measures should be provided as early as possible to reduce the risk of developing postpartum depression.
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Co-morbidities are the presence of one or more additional conditions co-occurring with a primary condition. Several studies have reported a high prevalence of co-morbidities in OSA patients and the number of co-morbidities seen is found to be directly proportional to the severity of the OSA.
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Study objectives: Obstructive sleep apnea (OSA) is characterized by intermittent hypoxia and oxidative stress. However, it is unknown whether intermittent hypoxia mimicking OSA modifies male fertility. We tested the hypothesis that male fertility is reduced by chronic intermittent hypoxia mimicking OSA in a mouse model. Design: Case-control comparison in a murine model. Setting: University research laboratory. Participants: Eighteen F1 (C57BL/6xCBA) male mice. Interventions: Mice were subjected to a pattern of periodic hypoxia (20 sec at 5% O2 followed by 40 sec of room air) 6 h/day for 60 days or normoxia. After this period, mice performed a mating trial to determine effective fertility by assessing the number of pregnant females and fetuses. Measurements and results: After euthanasia, oxidative stress in testes was assessed by measuring the expression of glutathione peroxidase 1 (Gpx1) and superoxide dismutase-1 (Sod1) by reverse-transcription polymerase chain reaction. Sperm motility was determined by Integrated Semen Analysis System (ISAS). Intermittent hypoxia significantly increased testicular oxidative stress, showing a reduction in the expression of Gpx1 and Sod1 by 38.9% and 34.4%, respectively, as compared with normoxia (P < 0.05). Progressive sperm motility was significantly reduced from 27.0 ± 6.4% in normoxia to 12.8 ± 1.8% in the intermittent hypoxia group (P = 0.04). The proportion of pregnant females and number of fetuses per mating was significantly lower in the intermittent hypoxia group (0.33 ± 0.10 and 2.45 ± 0.73, respectively) than in normoxic controls (0.72 ± 0.16 and 5.80 ± 1.24, respectively). Conclusions: These results suggest that the intermittent hypoxia associated with obstructive sleep apnea (OSA) could induce fertility reduction in male patients with this sleep breathing disorder.
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Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS) are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2), which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM) in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity.
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Several studies have found an association between sleep duration and morbidity and mortality, but no previous studies have examined the association between sleep disturbances and semen quality. We conducted a cross-sectional study among 953 young Danish men from the general population who were recruited in Copenhagen at the time of determination of fitness for military service between January 2008 and June 2011. All of the men delivered a semen sample, had a blood sample drawn, underwent a physical examination, and answered a questionnaire including information about sleep disturbances. Sleep disturbances were assessed on the basis of a modified 4-item version of the Karolinska Sleep Questionnaire, which includes questions on sleep patterns during the past 4 weeks. Sleep disturbances showed an inverse U-shaped association with sperm concentration, total sperm count, percent motile and percent morphologically normal spermatozoa, and testis size. Men with a high level of sleep disturbance (score >50) had a 29% (95% confidence interval: 2, 48) lower adjusted sperm concentration and 1.6 (95% confidence interval: 0.3, 3.0) percentage points' fewer morphologically normal spermatozoa than men with a sleep score of 11-20. This appears to be the first study to find associations between sleep disturbances and semen quality. In future studies, investigators should attempt to elucidate mechanistic explanations and prospectively assess whether semen quality improves after interventions restoring a normal sleeping pattern.
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Several reports have suggested a high incidence of erectile dysfunction (ED) among patients with obstructive sleep apnea syndrome (OSAS). The aim of this study was to investigate the correlation between OSAS and ED, or disease-specific quality of life (QOL) in patients with OSAS. In addition, we analyzed specific polysomnographic (PSG) parameters in predicting ED in OSAS patients. In total, 32 patients with OSAS and 27 normal controls were asked to complete the Korean versions of the International Index of Erectile Function questionnaire (KIIEF-5) and the Calgary Sleep Apnea Quality of Life Index (SAQLI). All patients then underwent a full-night in-laboratory PSG examination. Patients were diagnosed with OSAS if they had clinical symptoms suggestive of OSAS for at least 1 year and an apnea-hypopnea index (AHI) of more than 10 in PSG. Nineteen patients (59.3%) in the OSAS group showed ED, which was significantly higher than in the control group (8 patients, 29.6%, P=0.012). In addition, SAQLI scores worsened as AHI increased (r=0.327, P=0.011) and as the lowest oxygen saturation level decreased (r=0.420, P=0.001). ED was not significantly correlated with AHI (r=0.061, P=0.649); however, it was significantly correlated with the lowest oxygen saturation decreased (r=0.338, P=0.009). When the cutoff value for the lowest oxygen saturation level to predict ED was set at 77%, its positive predictive value was 88.9% (sensitivity=0.70, specificity=0.62). Thus, all male patients with OSAS should be screened for erectile dysfunction and more comprehensive consultation is needed, especially, if their lowest oxygen saturation levels are below 77%.
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Erectile dysfunction (ED) is frequent in obstructive sleep apnea syndrome (OSAS). Chronic intermittent hypoxia (CIH), one of the hallmarks of OSAS, could mediate ED. To determine whether intermittent hypoxia during sleep affects erectile dysfunction in mice. Three groups of C57BL/6 mice were exposed to CIH for 5 or 24 weeks. Sexual function was evaluated by in vivo telemetry of corpus spongiosum pressure. Spontaneous erections, sexual activity during mating, and noncontact tests were assessed after 5 weeks of CIH and after treatment with tadalafil. Plasma testosterone was measured after 8 and 24 weeks of CIH, and the expression of nitric oxide synthase (NOS) isoforms was examined in penile tissue. Noncontact, spontaneous, and contact sexual activity in the mice was suppressed after CIH. Spontaneous erection counts decreased after the first week of CIH by 55% (P < 0.001) and remained unchanged thereafter. Recovery of erectile activity during normoxia for 6 weeks was incomplete. Compared with control mice, latencies for mounts and intromissions increased by 60- and 40-fold, respectively (P < 0.001), and the sexual activity index decreased sixfold. Tadalafil treatment significantly attenuated these effects. Immunoblot analyses of NOS proteins in the erectile tissue showed decreased expression of endothelial NOS after CIH (P < 0.01), with no changes in plasma testosterone levels after 8 and 24 weeks of CIH. CIH during sleep is associated with decreased libido in mice. The decreased expression of endothelial NOS protein in erectile tissue and the favorable response to tadalafil suggest that altered nitric oxide mechanisms underlie CIH-mediated ED. No changes in testosterone emerge after intermittent hypoxia.
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Rationale: Erectile dysfunction (ED) is a frequent occurrence in male patients with obstructive sleep apnea syndrome (OSAS). Long-term intermittent hypoxia (LTIH), one of the hallmarks of OSAS, could mediate ED. Objectives: To test the hypothesis that increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity contributes to ED in rats responses to the LTIH. Methods: Healthy male Sprague-Dawley (SD) rats were randomly distributed into four groups: a LTIH group, an apocynin (a selective NADPH oxidase inhibitor)-treated LTIH group, a sham LTIH group, an apocynin-treated sham group. Erectile function was examined by measuring the mean arterial blood pressure (MAP) and intracavernosal pressure (ICP) upon electrical stimulation of the cavernous nerve. Real-time quantitavite-PCR and Western blot were used to examine mRNA and protein expression of NADPH oxidase subunit in corpus cavernosa (CC). The level of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric method. Nitric oxide synthase (NOS) isoforms in corpus cavernosa were also investigated. Results: LTIH markedly attenuated the erectile responses (ICP/MAP) and these were partially prevented by apocynin treatment. Promoted oxidative stress associated NADPH oxidase subunit activation was found in CC form LTIH rats. Decreased expression and activity of constitutive NOS (cNOS), including endothelial NOS (eNOS) and neuronal NOS (nNOS), associated with enhanced inducible NOS (iNOS) expression and activity were observed in LTIH rats. Apocynin prevented the decrease in cNOS activity and inhibited iNOS expression and activity in LTIH rats. Conclusions: These results indicate that NADPH oxidase activation plays an important role in the pathogenesis of LTIH-mediated ED.
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It has been documented that copulatory experience can alter or improve sexual performance in male rats. However, the hormonal basis and the number of sexual encounters needed for a rat to acquire sufficient performance remains unclear. The aim of this study was to examine whether levels of testosterone and progesterone are associated with sexual performance in male rats. Adult male Wistar Hannover rats were exposed to a receptive female for 15 minutes every other day for 9 days for acquiring sexual experience. After training protocol, rats were scored as low or high sexual performers. Hormonal levels (testosterone and progesterone) were evaluated in both trained and non-trained control groups. Our results showed that a 9-day training period was not sufficient for some male rats to acquire a good level of sexual performance. While 42.5% of the rats displayed excellent sexual performance during the training sessions, 17.5% showed adequate performance, 7.5% had low sexual activity, and 32.5% of the rats did not display any sexual behaviors whatsoever. Additionally, after 4 days of training, rats with excellent/adequate performance showed a significant decrease in ejaculation latency relative to the first day of training. The rats with low or no sexual activity had lower progesterone levels relative to those displaying the highest sexual performance after 9 days of training. Testosterone, in turn, was also significantly reduced in animals with low/no sexual performance compared with excellent/adequate rats. In conclusion, progesterone may be a limiting factor to promoting sexual performance in male rats.
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To estimate the prevalence of Obstructive Sleep Apnea Syndrome (OSAS), using current clinical and epidemiological techniques, among the adult population of Sao Paulo, Brazil. This population-based survey used a probabilistic three-stage cluster sample of Sao Paulo inhabitants to represent the population according to gender, age (20-80 years), and socio-economic status. Face-to-face interviews and in-lab full-night polysomnographies using a nasal cannula were performed. The prevalence of OSAS was determined according to the criteria of the most recent International Classification of Sleep Disorders (ICDS-2) from American Academy of Sleep Medicine (2005). A total of 1042 volunteers underwent polysomnography (refusal rate=5.4%). The mean age+/-SD was 42+/-14 years; 55% were women and 60% had a body mass index>25 kg/m(2). OSAS was observed in 32.8% of the participants (95% CI, 29.6-36.3). A multivariate logistic regression model identified several independent and strong associations for the presence of OSAS: men had greater association than women (OR=4.1; 95% CI, 2.9-5.8; P<0.001) and obese individuals (OR=10.5; 95% CI, 7.1-15.7; P<0.001) than individuals of normal weight. The adjusted association factor increased with age, reaching OR=34.5 (95% CI, 18.5-64.2; P<0.001) for 60-80 year olds when compared to the 20-29 year old group. Low socio-economic status was a protective factor for men (OR=0.4), but was an associated factor for women (OR=2.4). Self-reported menopause explained this increased association (age adjusted OR=2.1; 95% CI, 1.4-3.9; P<0.001), and it was more frequent in the lowest class (43.1%) than either middle class (26.1%) or upper class (27.8%) women. This study is the first apnea survey of a large metropolitan area in South America identifying a higher prevalence of OSAS than found in other epidemiological studies. This can be explained by the use of the probabilistic sampling process achieving a very low polysomnography refusal rate, the use of current techniques and clinical criteria, inclusion of older groups, and the higher prevalence of obesity in the studied population.
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Obstructive sleep apnea (OSA) has been linked with erectile dysfunction (ED), but it is unknown whether this association is maintained in the presence of other risk factors for ED. The aim of this study was to evaluate the relationship between ED/sexual dysfunction and polysomnographic measures of sleep apnea in patients with known risk factors for ED. Prospective cross-sectional analysis of 401 male patients undergoing in-lab polysomnography for suspected OSA. Erectile (EF) and sexual function were assessed by the 15-item International Index of Erectile Function (IIEF-15) questionnaire. Severity of OSA via apnea-hypopnea index (AHI) and mean/lowest nocturnal oxygen saturation (SaO(2)). The IIEF-15 including the sexual domains: EF, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction. OSA (AHI > 5/h) was diagnosed in 92% of patients. ED (EF subdomain < or = 25) was present in 69% of patients with, and 34% of patients without OSA (P < 0.001). Multivariate stepwise regression analyses including known risk factors for ED, such as age, obesity, coronary heart disease, peripheral occlusive disease, hypertension, diabetes, prostate surgery, and beta-blocker treatment, and measures of sleep apnea identified mean nocturnal SaO(2) as independently associated with ED (P = 0.002; mean [95% CI] normalized slope 0.126 [0.047; 0.205]). Age (P < 0.001), peripheral occlusive disease (P = 0.001), prostate surgery (P = 0.018), and hypertension (P = 0.021) were confirmed as risk factors for ED, but did not abolish the sleep apnea-associated risk. Similar results were obtained for sexual dysfunction. Logistic regression analysis using the diagnosis of ED (EF subdomain < or = 25) as binary dependent variable confirmed that mean nocturnal SaO(2) (P = 0.012), as well as age (P < 0.001) were independently associated with ED. ED and overall sexual dysfunction were highly prevalent in patients with suspected OSA. Irrespective of known risk factors, mean nocturnal SaO(2) was an additional, independent correlate of these dysfunctions, suggesting that OSA-related intermittent nocturnal hypoxemia specifically contributes to their development.
Male fertility is reduced by chronic intermittent hypoxia mimicking sleep apnea in mice
  • M Torres
  • R Laguna-Barraza
  • M Dalmases