Impact of vitamin D supplementation as COVID-19 vaccine adjuvant on sperm parameters and sex hormones in men with idiopathic infertility: Two separate pre-post studies.

OBJECTIVE: Vitamin D deficiency is a major problem for human health worldwide. The mechanisms of vitamin D in the male reproductive system are unknown. After coronavirus disease 2019 (COVID-19) vaccines were developed, doubts were raised about their possible effects on male fertility. Based on vitamin D's function in the immune system, its potential role as an adjuvant for COVID-19 vaccines is intriguing. The aims of this study were to assess the effects of vitamin D first on sperm parameters and sex hormones, and then as an immune adjuvant on sperm parameters and sex hormones after study participants had received their second doses of COVID-19 vaccines. METHODS: Phase 1 (before the COVID-19 pandemic) included 72 men with idiopathic infertility, and phase 2 had 64 participants who received two doses of COVID-19 vaccines. Both groups were instructed to take 50,000 IU of vitamin D twice monthly for 3 months. Sperm parameters and sex hormones were assessed pre- and post-supplementation. RESULTS: Regular vitamin D intake for 3 months significantly increased the participants' vitamin D levels (p=0.0001). Both phases showed a positive correlation between vitamin D intake and sperm parameters. Vaccination had no negative effects on sperm parameters and sex hormones. Vitamin D was associated with follicle-stimulating hormone (p=0.02) and testosterone (p=0.0001) in phase 2 after treatment. CONCLUSION: Our results support vitamin D supplementation as an immune adjunct to COVID-19 vaccination for improving sperm parameters and hormone levels. COVID-19 vaccination is not harmful for male fertility potential, and vitamin D is an effective factor for male fertility.

"When," "Where," and "How" of SARS-CoV-2 Infection Affects the Human Cardiovascular System: A Narrative Review.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), reninaldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in prothrombotic effects, such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

Ovarian Endocrine Status and ART 0utcomes in Women within PCOS Based on Different Testosterone Levels.

Background: It is estimated that in women at reproductive age, the risk of polycystic ovary syndrome (PCOS) is about 5-21%. In PCOS cases with ovulation dysfunction, assisted reproductive techniques (ART) are useful for infertility treatment. Objective: This study aimed to evaluate the ART outcome in infertile PCOS women based on different testosterone levels. Finally, the relationships between testosterone in different levels and reproductive parameters including endocrine status, the response of ovaries, and pregnancy outcomes were assessed. Methods: In this retrospective study, 352 infertile PCOS women were examined. The women were categorised into five groups according to their testosterone levels: A = T < 0.4, B = 0.4 < T > 0.6, C = 0.6 < T > 0.8, D = 0.8 < T > 1.0 and E = T > 1.0 ng/dL. All study cases were in similar hyper-stimulation protocol and finally, hormonal profile and ART outcomes were compared between testosterone levels. P value ≤ 0.05 was statistically significant. Results: In testosterone levels >1.0, the levels of anti-mullerian hormone (AMH) and luteinising hormone (LH) were higher than in other testosterone level groups. AMH (P = 0.05) and LH (P = 0.001) levels showed significant differences. No correlation was present between testosterone levels and ART outcomes, including stimulation duration, endometrial thickness, oocyte numbers, numbers of matured oocytes, number of obtained embryos, fertilisation rate, implantation rate clinical pregnancy and abortion rate. Conclusions: Serum testosterone levels did not show any correlation with pregnancy outcomes in ART cycles of PCOS. However, basal testosterone levels are a good predictor for ovarian reserve and ovarian response. Consequently, we suggest that some prospective studies must be designed to approve the role of testosterone in the prediction of the outcome of pregnancy in ART cycles.

Nut consumption and urogenital and genital, gastrointestinal and women-related cancers: Assessment and review.

The prevalence of cancer, especially in industrial countries, is a major problem for health and treatment systems. Cancer can affect the quality of life of all family members and has many negative effects on the community. Despite many advances in cancer treatment, this disease is still a major worldwide problem. There is strong evidence that dietary habits are effective in protecting against cancer and even helping in the disease treatment progress. Nuts with various biologically-active compounds, such as vitamins, phytosterols, isoflavones, flavonoids, and polyphenols have been reported to possess anticarcinogenic properties. Accordingly, this review provides an insight into the association between nut consumption and the prevention of some cancers. We considered the cancers related to the urogenital and genital tract, gastrointestinal tract, as well as women-related cancers. Both cell culture examinations and experimental animal studies alongside observational epidemiological studies demonstrated that regular consumption of a nut-enriched diet is able to reduce the risk of these cancers.

Evaluation of the Effect of Vitamin E on Reproductive Parameters in Morphine-Treated Male Mice.

Background: Morphine is a narcotic pain reliever that is prescribed to reduce postoperative pain and can produce reactive oxygen species (ROS). Therefore, it can have negative effects on spermatogenesis and male fertility. Vitamin E is an effective antioxidant which plays an important role in membrane lipid peroxidation due to increased ROS. The present study aimed to evaluate the effects of vitamin E and morphine on sperm parameters, level of malondialdehyde (MDA), and diameter of seminiferous tubules in morphine-treated mice. Methods: In this experimental study, 80 mice were divided into ten groups (n=8) including control, normal saline, vehicle, morphine, various doses of vitamin E (100, 200, 300 mg/kg), and morphine plus vitamin E (100, 200, 300 mg/kg) groups. The groups were followed up for 30 consecutive days. Sperm parameters, testis weight, the diameter of seminiferous tubules, and the level of MDA were analyzed and compared. Findings: Data analysis showed seminal parameters decreased significantly (excluding sperm count) and there was an increase in the level of MDA in morphine-treated mice compared with the normal saline group (P<0.05). Administration of E100 to morphinetreated mice did not show a significant difference in the evaluated parameters compared with the morphine group. However, E200 and E300 significantly reduced MDA and improved sperm parameters (P≤0.05). Conclusion: The results showed co-administration of vitamin E in high doses (200 & 300) could prevent the deleterious effects of morphine on some reproductive parameters and decrease the level of MDA in morphine-treated mice.

Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.

The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review.

Earlier research has suggested that the male reproductive system could be particularly vulnerable to SARS-CoV-2 (COVID-19) infection, and infections involving this novel disease not only pose serious health threats but could also cause male infertility. Data from multi-organ research during the recent outbreak indicate that male infertility might not be diagnosed as a possible consequence of COVID-19 infection. Several review papers have summarized the etiology factors on male fertility, but to date no review paper has been published defining the effect of COVID-19 infection on male fertility. Therefore, the aim of this study is to review the published scientific evidence regarding male fertility potential, the risk of infertility during the COVID-19 pandemic, and the impact of COVID-19 vaccination on the male reproductive system. The effects of COVID-19 infection and the subsequent vaccination on seminal fluid, sperm count, sperm motility, sperm morphology, sperm viability, testes and sex hormones are particularly reviewed.

Male factor testing in recurrent pregnancy loss cases: A narrative review.

Recurrent pregnancy loss is a distinct disorder defined as the loss of at least 2 pregnancies before the 20 th wk of gestation. With half of the genome of the embryo belonging to the father, the integrity of the sperm genome is crucial for a successful pregnancy. Semen analysis is recommended for men in such cases to evaluate sperm concentration, morphology, vitality and motility. However, other important sperm parameters such as sperm epigenetics, aneuploidy, Y chromosome microdeletion and chromatin integrity also correlate with successful pregnancy and delivery rate. This article examines the use of different sperm tests and their importance in male partners of women suffering from recurrent pregnancy loss.

The Effect of Phytosterols and Fatty Acids of Pistachio (Pistacia vera) Oil on Spermatogenesis and Histological Testis Changes in Wistar Adult Male Rats.

PURPOSE: Oilseeds and their related products are known to have various bioactive and health-promoting ingredients. In this research, we investigated the effects of phytosterols and fatty acids of Pistacia vera on spermatogenesis process and testis histological changes in Wistar male rats for the first time. MATERIALS AND METHODS: A total number of 64 adult male Wistar rats were divided randomly into eight groups including one control group, and seven test groups. Test groups received phytosterols, fatty acids, and pistachio oil orally for 30 days. Then, LH, FSH, and serum testosterone levels were determined. Also, the spermatogenesis process and changes in testicular tissue in rats were investigated. RESULTS: The results of this research suggest that phytosterols in doses of 10 and 50 mg/kg reduce the spermatogenesis process. Fatty acid in a low dose of 10 mg/kg increases spermatogenesis, but when a high dose of 50 mg/kg was used, it harmed the spermatogenesis process. When low levels of phytosterols and fatty acids are used simultaneously in dose 5 mg/kg, improvement in spermatogenesis process is observed but when these were used together in the dose of 25 mg/kg, the spermatogenesis process was disrupted. Using pistachio oil alone also improved spermatogenesis process. CONCLUSION: It seems that phytosterols reduce spermatogenesis at high and low doses, while fatty acids increase spermatogenesis when used in low doses and reduce this process when used in high doses. The use of fatty acids extracted from pistachios to treat infertility in men seems hopeful.

Effect of Selenium and Vitamin E on the Level of Sperm HSPA2+, Intracellular Superoxide Anion and Chromatin Integrity in Idiopathic Asthenoteratozoospermia: A Double-Blind, Randomized, Placebo- Controlled Trial.

PURPOSE: Male infertility accounts for about half of all infertility cases. Asthenoteratozoospermia is a severe form of male infertility. Free radicals play an important role in infertility. In a study we found that asthenoteratozoospermic men had a lower mean percentage of sperm HSPA2+ and higher intracellular anion superoxide than normozoospermia. Antioxidants are thought to be able to counteract the negative effects of free radicals. We explored the efficacy of vitamin E in combination with Se on the level of sperm HSPA2+, intracellular anion superoxide and chromatin integrity in these patients. MATERIALS AND METHODS: 60 patients entered the study. They were randomized to treatment group of oral Se (200 µg) in combination with vitamin E (400 units) for 3 months (n= 30) or placebo (n= 30). Semen samples were obtained and assessed for sperm parameters, intracellular O2-, protamine deficiency, sperm HSPA2+ and apoptotic spermatozoa at baseline and after treatment phase. RESULTS: There were no significant differences in baseline semen parameters, intracellular O2- protamine deficiency, sperm HSPA2+ and apoptotic spermatozoa between the treatment and placebo groups. There was a statistically significant decrease in sperm apoptosis and the level of anion superoxide (P=.001) and an increase in sperm motility and viability (P=.001) in the treated group, but no significant difference was found in the percentage of sperm HSPA2+ and sperm protamine deficiency compared with baseline. Moreover, no significant change was found in these parameters in placebo group after 3 months. CONCLUSION: Our results showed that administration of vitamin E and selenium for three months may improve sperm motility and viability by decreasing intracellular anion superoxide and sperm apoptosis in asthenoteratozoospermic infertile men. We suggest that consuming these supplements before assisted reproductive technology (ART) may improve outcomes in these patients.

Correction to "Platelet-rich plasma in the management of Asherman's syndrome: An RCT" [Int J Reprod BioMed 2020; 18: 113-12].

[This corrects the article DOI: 10.18502/ijrm.v18i2.6423.].

The effect of low-dose aspirin on the pregnancy rate in frozen-thawed embryo transfer cycles: A randomized clinical trial.

BACKGROUND: The results of previous studies on the effect of low-dose aspirin in frozen-thawed embryo transfer (FET) cycles are limited and controversial. OBJECTIVE: To evaluate the effect of low-dose aspirin on the clinical pregnancy in the FET cycles. MATERIALS AND METHODS: This study was performed as a randomized clinical trial from May 2018 to February 2019; 128 women who were candidates for the FET were randomly assigned to two groups receiving either 80 mg oral aspirin (n = 64) or no treatment. The primary outcome was clinical pregnancy rate and secondary outcome measures were the implantation rate, miscarriage rate, and endometrial thickness. RESULTS: The endometrial thickness was lower in patients who received aspirin in comparison to the control group. There were statistically significant differences between the two groups (p = 0.018). Chemical and clinical pregnancy rates and abortion rate was similar in the two groups and there was no statistically significant difference. CONCLUSION: The administration of aspirin in FET cycles had no positive effect on the implantation and the chemical and clinical pregnancy rates, which is in accordance with current Cochrane review that does not recommend aspirin administration as a routine in assisted reproductive technology cycles.

Comparison between sperm parameters and chromatin in recurrent pregnancy loss couples after antioxidant therapy.

BACKGROUND AND AIMS: Recurrent Pregnancy loss (RPL) is a heterogeneous disease. The role of maternal factor is clear but the relationship between the paternal factors remains uncertain. It has been shown that increase the level of Reactive Oxygen Species (ROS) and decrease the antioxidant levels in men can lead to RPL. New researches show treatment with antioxidant can improved sperm parameter. The aim of the present study was to assess the effect of vitamin E plus Zinc therapy on sperm parameters and chromatin quality in couples with RPL. METHODS: In this clinical trial study, 60 RPL patients were selected from RPL clinic. Standard sperm parameters were analyzed and then male partners were intake vitamin E and Zinc in antioxidant therapy plan for 90 days. After that, sperm parameters were analyzed again. Sperm chromatin assay was reviewed before and after vitamin E and Zinc therapy by cytochemical assay including aniline blue (AB), chromomycin A3 (CMA3), toluidine blue (TB). To assess DNA fragmentation index, TUNEL test was used. Data were analyzed and compared before and after treatment. RESULTS: data analysis showed all sperm parameters significantly improved after treatment (P < 0.001). The number of AB+ and TB+ sperms were decreased significantly after vitamin E and Zinc therapy (P = 0.0001). Decrease in DNA fragmentation in post treatment group in comparison to pre-treatment was statistically significant. CONCLUSION: Supplemental of vitamin E plus Zinc may improve sperm parameters chromatin quality and decrease sperm DNA fragmentation in RPL patients.

Platelet-rich plasma in the management of Asherman's syndrome: An RCT.

BACKGROUND: Asherman's syndrome (AS) is a rare reproductive abnormality, resulting in endometrial collapse due to aggressive or recurrent endometritis and/or curettage. OBJECTIVE: We aimed to assess the effectiveness of using platelet-rich plasma (PRP) to lower the recurrence rate of intrauterine adhesions (IUAs) following hysteroscopy. MATERIALS AND METHODS: In this non-randomized clinical trial, women aged 20-45 years with AS diagnosed by sonohysterography, 3D sonography, hysteroscopy, or uterosalpingography between May 2018 and September 2018 were included. Participants (n = 30) were divided into case and control groups. Following hysteroscopic adhesiolysis, a Foley catheter was placed into the uterine cavity in all women. After two days, the catheter was removed, and 1-mL PRP was injected into the uterine cavity of women in the PRP (case) group, while the control received no PRP. All controls and subjects underwent diagnostic hysteroscopy 8-10 weeks following the intervention to assess the IUAs according to the American Society for Reproductive Medicine scoring system. RESULTS: Our results did not reveal any significant difference in the menstrual pattern of either the control or test groups before or after treatment (p = 0.2). Moreover, the IUA stage in both studied groups before and after treatment was similar (p = 0.2). The duration of menstrual bleeding in both studied groups before and after treatment was also similar. CONCLUSION: PRP cannot change the menstrual pattern or development of postsurgical AS, as evaluated by follow-up hysteroscopy.

Is there any association between vitamin D levels and polycystic ovary syndrome (PCOS) phenotypes?

ABSTRACT Objective The aim of this study was to assess the serum vitamin D level in a retrospective study in women with polycystic ovary syndrome (PCOS), according to the different phenotypes of the disease. Subjects and methods In this retrospective study, the records of 351 infertile women who were diagnosed with PCOS were examined, and 200 of them were enrolled in the study randomly in 4 PCOS phenotypes. Fifty normal ovulatory women with the history of male factor were selected as the control group. Parameters, including age, infertility duration, body mass index (BMI), hormone profile, as well as the serum vitamin D level were compared among the 4 phenotypes, with the P-value ≤ 0.05 considered statistically significant. Results The findings showed a higher serum vitamin D level in the control group than in PCOS patients, which was statistically significant (P < 0.001). In addition, there was no significant difference in the serum vitamin D level among the four phenotypes of PCOS. Conclusions No significant difference was found in the serum vitamin D level of the different phenotypes of PCOS. Further studies with larger sample sizes are recommended to be done to establish the role of the serum vitamin D level in PCOS patients.

Is there any association between vitamin D levels and polycystic ovary syndrome (PCOS) phenotypes?

Objective The aim of this study was to assess the serum vitamin D level in a retrospective study in women with polycystic ovary syndrome (PCOS), according to the different phenotypes of the disease. Subjects and methods In this retrospective study, the records of 351 infertile women who were diagnosed with PCOS were examined, and 200 of them were enrolled in the study randomly in 4 PCOS phenotypes. Fifty normal ovulatory women with the history of male factor were selected as the control group. Parameters, including age, infertility duration, body mass index (BMI), hormone profile, as well as the serum vitamin D level were compared among the 4 phenotypes, with the P-value ≤ 0.05 considered statistically significant. Results The findings showed a higher serum vitamin D level in the control group than in PCOS patients, which was statistically significant (P < 0.001). In addition, there was no significant difference in the serum vitamin D level among the four phenotypes of PCOS. Conclusions No significant difference was found in the serum vitamin D level of the different phenotypes of PCOS. Further studies with larger sample sizes are recommended to be done to establish the role of the serum vitamin D level in PCOS patients.

Cytochemical tests to investigate sperm DNA damage: Assessment and review.

Male factor infertility has been diagnosed as the cause of infertility in about 20% of infertile couples. Sperm analysis is the most common method for diagnosing infertility in a laboratory. However, approximately 15% of infertile men have a normal sperm analysis. Therefore, the result of a routine sperm analysis often cannot be a definitive diagnosis for male factor infertility. Also, approximately 8% of infertile men with normal sperm parameters have high levels of abnormal sperm DNA. This indicates the role of the integrity of sperm DNA in male infertility. Here, we review the current tests available to evaluate the sperm DNA integrity along with their benefits and limitations.

Evaluation of Sperm Chromatin Integrity Using Aniline Blue and Toluidine Blue Staining in Infertile and Normozoospermic Men.

BACKGROUND: Male infertility is defined as a man lost his ability to fertilize a fertile female naturally. Diagnosis of male infertility cannot be made just according to basic semen analysis. It is necessity to have specific tests for evaluation of chromatin integrity. In this study, an attempt was made to evaluate the sperm chromatin quality in fertile men and infertile subgroup. METHODS: Among 1386 couples, 342 men were categorized into normospermia and 1044 were infertile and they were referred to Yazd Research and Clinical Center for infertility treatment. Standard semen analysis and sperm nuclear maturity tests including aniline blue (AB) and toluidine blue (TB) staining were done. Data were analyzed by SPSS software. The p≤0.05 was considered statistically significant. RESULTS: The mean value of TB staining was significantly higher in infertile group compared to normospermic group (p=0.005). Mean of sperm normal morphology was lower in idiopathic infertile men in comparison with normozoospermic men (p= 0.001). The highest negative correlation was obtained between sperm count and AB staining. Progressive motility was negatively correlated with AB and TB staining in both groups but there was no significant difference between AB staining and progressive motility in men normospermia group. CONCLUSION: Sperm chromatin staining using AB and TB showed a negative association between sperm chromatin condensation with sperm count, normal morphology and progressive motility. It seems that the AB and TB test may be useful for the assessment of male fertility potential.

The etiologies of DNA abnormalities in male infertility: An assessment and review.

The sperm DNA damage may occur in testis, genital ducts, and also after ejaculation. Mechanisms altering chromatin remodeling are abortive apoptosis and oxidative stress resulting from reactive oxygen species. Three classifications of intratesticular, post-testicular, and external factors have been correlated with increased levels of human sperm DNA damage which can affect the potential of fertility. Lifestyle, environment, medical, and iatrogenic factors might be considered to cause dysmetabolism to make distracting interactions and endocrine disrupting compounds. As a result, these may induce chromatin/DNA alteration in germ cells, which may be transmitted across generations with phenotypic consequences. Alcohol consumption may not increase the rate of sperm residual histones and protamine deficiency; however, it causes an increase in the percentage of spermatozoa with DNA fragmentation and apoptosis. In a medical problem as spinal cord injury, poor semen parameters and sperm DNA damage were reported. Infection induces reactive oxygen species production, decreases the total antioxidant capacity and sperm DNA fragmentation or antigen production that lead to sperm dysfunctions and DNA fragmentation. While reactive oxygen species generation increases with age, oxidative stress may be responsible for the age-dependent sperm DNA damage. The exposing of reproductive organs in older men to oxidative stress for a long time may produce more DNA-damaged spermatozoa than youngers. Examining the sperm chromatin quality in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy demonstrated the high incidence of DNA damage and low compaction in spermatozoa at the time of the diagnosis. In chemotherapy cycle with genotoxic agents in cancer patients, an increase in sperm DNA damage was shown after treatment. In overall, those factors occurring during the prenatal or the adult life alter the distribution of proteins associated with sperm chromatin induce changes in germ cells which can be detected in infertile patients.

Evaluation of intracellular anion superoxide level, heat shock protein A2 and protamine positive spermatozoa percentages in teratoasthenozoospermia.

BACKGROUND: Teratoasthenozoospermia (TA) is a severe form of male infertility with no clear etiology. OBJECTIVE: To compare the level of intracellular anion superoxide (O2-), heat shock protein A2 (HSPA2) and protamine deficiencies in ejaculated spermatozoa between teratoasthenozoospermic and normozoospermic men. MATERIALS AND METHODS: In this case- control study, semen samples of 20 infertile men, with TA (with normal morphology lower than 4%_ and total motility lower than 40% ) as the case group and 20 normozoospermic fertile men as the control group were evaluated for intracellular O2- and HSPA2 by flow cytometry and protamine deficiency by Chromomycin A3 (CMA3) test. RESULTS: The rate of CMA3+ spermatozoa in the case group was higher than controls (p=0.001). The percentages of HSPA2+ spermatozoa in the cases were significantly lower than controls (p=0.001). Also, intracellular O2- levels in the case group were significantly higher than controls (p=0.001) and had positive correlations with sperm apoptosis (r=0.79, p=0.01) and CMA3 positive sperm (r=0.76, p=0.01), but negative correlations with normal morphology (r=-0.81, p=0.01) and motility (r=-0.81, p=0.01). There was no significant correlation between intracellular O2- and HSPA2 in the case group (r=0.041, p=0.79). CONCLUSION: We suggest that the increase in intracellular O2-, decrease in spermatozoa HSPA2+, and high percentages of spermatozoa with immature chromatin might be considered as etiologies of infertility in TA patients.