The effect of plasmapheresis on clinical outcome, interleukin-6 and D-dimer in COVID-19 patients

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Data may be preliminary. 31 December 2025 V1 Latest version Share on The effect of plasmapheresis on clinical outcome, interleukin-6 and D-dimer in COVID-19 patients Authors : Zahra Sadin 0000-0003-3014-7954 [email protected] , Fateme Salemi 0000-0003-4297-7154 , Mohammadreza Mirjalili , Mehdi Raadabadi , Ali Dehghani , Hossein Fallahzadeh , Mohammad Hossein Jarahzadeh , and Fatemeh Aghaeimeybodi Authors Info & Affiliations https://doi.org/10.22541/au.176718075.53874610/v1 221 views 96 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Acute respiratory distress syndrome (ARDS) is characterized by severe hypoxemia with severe lung inflammation. Inflammatory mediators such as colony stimulating factors, tumour necrosis factors, IL-1, IL-6, and IFNs pass through the alveolar membrane and cause a process known as cytokine storm (hypercytokinemia). It occurs commonly in viral infections such as COVID-19. Recent attention has been focused on extracorporeal adjustment of intravascular cytokine levels in COVID-19 patients experiencing severe inflammatory response. Therefore, plasmapheresis has been suggested to reduce the load of plasma cytokines and coagulation factors. The effects of plasmapheresis and its frequency on clinical manifestations, inflammatory markers, specific laboratory values, and their correlation were the main subjects of this study. The length of hospital stays and fatality rates were also evaluated. The participants were COVID-19 cases receiving either invasive mechanical ventilation (IMV) or non-invasive positive pressure ventilation (NIPPV), who were admitted to Shahid Sadoughi Hospital, Yazd, Iran. from March 2020 to May 2021. We evaluated 108 COVID-19 patients with positive PCR test results. A higher admission to plasmapheresis time significantly increased the mortality rate, while presence of chronic illnesses had no effect on survival. The dead cases had a longer admission to plasmapheresis period and hypoxemia upon arrival, whereas d-dimer and length of stay did not show any significant elevation in this group. In conclusion, our study showed that the therapeutic plasmapheresis blood purification technology is safe, effective, and enhances tissue oxygenation by removing inflammatory cytokines and acute phase proteins. Introduction The respiratory tract is one of the main targets of corona viruses, a member of the Coronaviridae family. Respiratory involvement ranges from a minor upper respiratory tract infection to severe pneumonia with a wide range of pulmonary complications, including acute respiratory distress syndrome (ARDS). A process known as cytokine storm (hypercytokinemia) occurs in viral infections such as COVID-19 when pro-inflammatory cytokines such as colony stimulating factors, tumour necrosis factors, IL-1, IL-6, and IFNs are uncontrollably produced due to the activation of innate immune system receptors such as MDA-5 and RIG-1. Immune cells infiltrate the lungs and destroy the pulmonary al-veolar epithelium, causing respiratory distress, septic shock, and multiple organ failure. Furthermore, the resulting uncontrolled severe immune response impairs T-cells function, and decreases their life span and production which exacerbates the disease outcome (1, 2). Therefore, the main concern of the global medical profession is to choose effective approaches to reduce systemic inflammation, viral load, and subsequently mortality rates, especially in critical cases. In the early stages of the cytokine storm, Covid-19 patients are managed primarily by immunosuppressives such as corticosteroids and cytokine antagonist inhibitors to impede disproportionate production of cytokines. Other anti-inflammatory medications, such as intravenous immunoglobulins and Janus kinase (JAKs) inhibitors, have directly improved the survival rate. Eliminating inflammatory mediators, which prevents the immune system from overreacting, is considered a promising strategy to minimize COVID-19-induced injury. The extracorporeal adjustment of intravascular cytokine levels in COVID-19 patients experiencing severe inflammatory responses has recently received attention. (3, 4). Therefore, plasmapheresis has been suggested as a method of reducing the load of plasma cytokines and coagulation factors. In this procedure, specific particles are filtered out or extracted using a centrifuge. Studies have shown positive impacts of plasmapheresis on a variety of disorders, including COVID-19, influenza, and sepsis (5). In this study, the participants were COVID-19 cases receiving either invasive mechanical ventilation (IMV) or non-invasive positive pressure ventilation (NIPPV), who were admitted to Shahid Sadoughi Hospital, Yazd, Iran, from March 2020 to May 2021. We compared the effects of plasmapheresis and its frequency on clinical manifestations, inflammatory markers, specific laboratory values, and their correlation. we also assessed length of hospital stay and mortality rate in both groups. Methods This case series study was conducted at the internal medicine department, Shahid Sadoughi Hospital, Yazd, Iran, from March 29, 2020 to May 26, 2021. The deadline for follow-up was June 15, 2021. This study was conducted in accordance with the principles outlined in the Declaration of Helsinki and approved by the Shahid Sadoughi Ethics Committee in March 2020, with reference number IR.SSU.MEDICINE.REC.1399.001. All participants were provided with detailed information regarding the study, and informed consent was obtained prior to their participation. Where applicable, collection and use of human tissue or data were performed with adherence to relevant ethical guidelines. In unconscious patients, consent was obtained from legal guardians. Study Population and Sampling We included all consecutive COVID-19 patients admitted during the study period who met the following criteria: laboratory-confirmed COVID-19 using quantitative Real-Time polymerase chain reaction (qRT-PCR), oxygen saturation (SpO₂) <94% on room air at sea level (in those with normal baseline SpO₂ at rest), arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO₂/FiO₂) 30 breaths/min, and viral involvement in more than half of the lungs. During the study period, 142 patients met these criteria; 34 were excluded due to inability to tolerate central line placement (n=18), unstable hemodynamics (n=12), or heparin allergies/heparin-induced thrombocytopenia (n=4), resulting in a final cohort of 108 patients who received plasmapheresis. This represents consecutive sampling of all eligible patients during the specified period. Therapeutic Approach All patients received standard antiviral treatment with remdesivir 100 mg, dexamethasone (10 mg for ICU patients and 4 mg for non-ICU patients), aspirin 80 mg, atorvastatin 10 mg, and 5000 units of subcutaneous heparin daily for five days. Remdesivir dose was adjusted based on creatinine clearance and liver function. Plasmapheresis Protocol To suppress cytokine storm, patients were treated with plasmapheresis aimed at separating patients’ plasma to reduce inflammatory factor load. The plasmapheresis protocol consisted of 2 liters of filtration daily (approximately 1-1.5 plasma volumes based on patient body weight and calculated plasma volume), compensated with four units of fresh frozen plasma, five vials of albumin, and one or two 10-20 mL calcium gluconate (20%), depending on patient serum calcium level. The remaining volume was replaced with normal saline according to patient volume status. Plasmapheresis was performed for a median of 3 sessions (range: 1-5 sessions) over consecutive days. Treatment was discontinued when patients showed clinical improvement (improved oxygenation, reduced inflammatory markers) or if adverse effects occurred. Patients were closely monitored during plasmapheresis to avoid potential side effects (6). Plasmapheresis would have been discontinued if any change in patient condition or red flags (dyspnea, seizures, chest pain, hypotension unresponsive to 1 or 2 fluid boluses) had been noticed. During apheresis, patients’ vital signs were monitored every 10 to 15 minutes. No adverse effects occurred in any patients due to close monitoring. Data Gathering This case series included all COVID-19 patients with positive qRT-PCR for SARS-CoV-2. Clinical information was obtained from review of the hospital’s electronic system and included: demographic data, days of admission from symptom onset, presenting symptoms, date of plasmapheresis, requirement of mechanical ventilation, presence of chronic diseases, number of days from admission to plasmapheresis, and length of hospital stay. Laboratory values, including IL-6 and D-dimer, were also assessed. Pulse oximeter was used to record SpO₂ in survived participants at admission and discharge. Statistical Analysis Statistical analysis was performed using SPSS 26.0 software (IBM Corporation, Armonk, NY, USA). Given the exploratory nature of this case series and the need to assess multiple potential prognostic factors, we performed both bivariate and multivariate analyses without adjustment for multiple comparisons, acknowledging this as a limitation. Measurement data with normal distribution are expressed as mean ± standard deviation (mean ± SD). Chi-squared test was used to compare associations between patients’ data (age, gender, occupation, admission-to-plasmapheresis period, mechanical ventilation, chronic disease) and vital status as final outcome. Mann-Whitney U test was used to compare differences between survivors and non-survivors in terms of age, length of stay, SpO₂ at admission, D-dimer, and IL-6. Univariate logistic regression analysis was executed to compute odds ratio (OR) estimates to assess associations between vital status and clinical and laboratory variables. Due to the limited sample size and exploratory nature of this study, multivariate analysis was not performed. P-value formal sample size calculation was performed as this was a consecutive case series of all eligible patients during the study period. Results We evaluated 108 COVID-19 patients with positive PCR test results; their demographic information is shown in Table 1. The study consisted of 60 (55.6%) males and 48 (44.4%) females. Seventy-eight (72.2%) patients required respiratory support via mechanical ventilation, and 73 participants had one or more chronic disorders. As the final outcome, only 41 (38.0%) survived. Chi-square test showed significant associations between vital status and admission-to-plasmapheresis period [X² (df: 2) = 9.35, p=0.009], occupation [X² (df: 3) = 9.34, p=0.025], and mechanical ventilation [X² (df: 1) = 54.07, p<0.001]. However, presence of underlying disease [X² (df: 1) = 2.47, p=0.116] and sex [X² (df: 1) = 1.22, p=0.182] were not significantly related to patient final outcome. According to Mann-Whitney U test results, IL-6 (U=125.0, p=0.008), oxygen level at admission (SpO₂ in survivors: 87%, SpO₂ in non-survivors: 80%) (U=882.0, p=0.002), admission-to-plasmapheresis period (U=888.0, p=0.002), and age (U=926.5, p=0.005) in non-survivors were statistically significantly higher than in survivors. D-dimer levels were numerically higher in non-survivors (1629.46 vs. 1104.80 mg/L), though this 47% difference did not reach statistical significance (U=250.5, p=0.230), possibly due to high variability and limited sample size. Length of stay (U=1355.0, p=0.907) also showed no significant difference between groups (Table 1a and 1b). Variable Survived (N = 41) Non-survived (N = 67) Total (N = 108) P value* N (%) N (%) N (%) Sex Male 20 (18.6) 40 (37) 60 (55.6) 0.182 Female 21 (19.4) 27 (25) 48 (44.4) Occupation Self-employed 11 (10.2) 20(18.5) 31 (28.7) 0.025 Employee 5 (4.7) 1(0.9) 6 (5.6) Housewife 20 (18.5) 26(24.1) 46 (42.6) Retired 5 (4.6) 20(18.5) 25 (23.1) Mechanical Ventilation Yes 13 (12) 65(60.2) 78 (72.2) <0.001 No 28 (25.9) 2(1.9) 30 (27.8) Underlying disease Yes 24 (22.2) 49 (45.4) 73 (67.6) 0.116 * No 17 (15.7) 18 (16.7) 35 (32.4) chi-square test Survived (N = 41) Non survived (N = 67) Total (N = 108) P value (Mean ± SD) (Mean ± SD) (Mean ± SD) APP (day) categorize 0-2 18 (16.7) 14(13) 32 (29.7) 0.009 * 3-6 16 (14.8) 25(23.1) 41 (37.9) >7 7 (6.5) 28(25.9) 35 (32.4) Age (year) 51.95 ± 14.57 60.28 ± 13.10 57.12 ± 14.20 0.005 ** LOS (day) 16.80 ± 15.40 15.14 ± 8.31 15.77 ± 11.49 0.907 ** APP (day) 4.10 ± 3.71 7.21 ± 5.85 6.03 ± 5.34 0.002 ** IL-6 (pg/ml) 30.40 ± 41.18 185.28 ± 315.50 118.40 ± 249.58 0.008 ** D-dimer (DDU) mg/L 1104.80 ± 2403.89 1629.46 ± 2244.76 1377.62 ± 249.58 0.230 ** Spo2 a (%) 87.41 ± 6.80 80.04 ± 13.15 82.84 ± 11.70 0.002 ** Spo2 b (%) 95.29 ± 2.30 - 95.29 ± 2.30 - * chi-square test, **Mann-Whitney Test a at the time of admission, b at the time of discharge Abbreviations: SD: standard deviation, LOS: length of stay, APP: admission to plasmapheresis period, IL-6: interleukin -6, SpO2: oxygen saturation. According to univariate logistic regression analysis, each year of age increased the risk of death by 4% (OR=1.04, 95% CI: 1.01-1.07, p=0.004). Increasing oxygen saturation by 1% reduced the risk of death by 7% (OR=0.93, 95% CI: 0.88-0.97, p=0.003). A one-day delay in plasmapheresis increased the risk of death by 16% (OR=1.16, 95% CI: 1.04-1.28, p=0.006). When categorizing patients by admission-to-plasmapheresis period, we found increased mortality among patients with more than 7 days delay (OR=5.14, 95% CI: 1.75-15.11, p=0.003). Patients who required mechanical ventilation had 99% lower chance of survival (OR=0.01, 95% CI: 0.00-0.06, p<0.001). Length of stay, occupation, laboratory values, and presence of underlying disorders did not significantly affect patient survival (Table 2). P-value OR (95% CI) Wald B Demographic data 0.269 0.64 (0.30-1.38) 1.223 -0.442 Gender 0.004 1.04 (1.01-1.07) 8.247 0.043 Age 0.473 0.99 (0.95-1.03) 0.515 -0.012 LOS Occupation 0.056 1.00 7.555 - Self-employed 0.057 0.11 (0.01-1.02) 3.633 -2.207 employee 0.484 0.72 (0.29-1.77) 0.491 -0.335 housewife 0.207 2.20 (0.65-7.43) 1.590 0.788 Retired Clinical data 0.118 0.52 (0.23-1.17) 2.443 -0.657 Chronic disease 0.003 0.93 (0.88-0.97) 8.607 -0.077 SpO2 at admission 0.006 1.16 (1.04-1.28) 7.649 0.146 APP (day) APP (day) categorize 0.012 1.00 8.778 - 0-2 0.145 2.01 (0.79-5.11) 2.121 0.698 3-6 0.003 5.14 (1.75-15.11) 8.777 1.638 >7 <0.001 0.01 (0.00-0.06) 28.741 -4.248 Mechanical ventilation Laboratory data 0.126 1.01 (1.00-1.03) 2.346 0.012 IL-6 0.423 1.00 (1.00-1.00) 0.641 0.000 D-dimer Abbreviations: B, regression coefficient; OR, odds ratio; CI, confidence interval; SpO₂, oxygen saturation; APP, admission-to-plasmapheresis period; IL-6, interleukin-6. Discussion Corona viruses are identified in human and animal infections, but the World Health Organization (WHO) has identified a new form of corona virus, established as severe acute respiratory syndrome corona virus 2 (SARSCoV2). This unique variety has caused a pandemic around the world, with pneumonia being the leading cause of death especially in patients receiving intensive care (7, 8). This publication suggested that, despite being an unidentified technique, plasmapheresis may be a valuable way for reducing viral load and treating cytokine outburst. COVID-19 pneumonia causes a gradual hypoxemia and inflammatory response that can lead to severe pulmonary fibrosis and multiorgan failures, and subsequent death (9). When compared to the mortality rate reported in extreme ARDS caused by other disorders, individuals with high COVID-19 ARDS have a greater mortality rate (10, 11). Though there are no COVID-19-specific pharmaceuticals on the market, COVID-19 ARDS therapy has remained palliative and relies on a number of repurposed medications. As a result, severe COVID-19 patients have been treated with a variety of drugs including corticosteroids, antimicrobials, antimalarials, antivirals, and other medications with variable degrees of success (12, 13). Clinical studies demonstrate that circulating leukocyte subsets and cytokine production, particularly IL-6, IL-1, IL-10, TNF, GM-CSF, IP-10 (IFN-induced protein 10), and IL-17, are altered in both moderate and severe illness states (5). Individuals who have severe critical manifestations of COVID-19 disease frequently experience a cytokine storm, accompanied by a dramatic decrease in the number of lymphocytes and NK cells as well as increased levels of D-dimer, CRP, ferritin, and procalcitonin. Extensive alveolar damages caused by a deadly cytokine storm is characterized by the production of hyaline membranes and the infiltration of interstitial lymphocytes (14, 15). Higher IL-6 plasma concentrations and IL-8 levels in bronchoalveolar lavage fluid, on the other hand, increase mortality rate in ARDS patients. IL6 and TNF-α levels are elevated in COVID-19 individuals with ARDS, especially those who require ICU admission, indicating that the cytokine storm may contribute to serious illness. A potential for antiinflammatory cytokines like IL-10 and IL-4 has also been proposed in COVID-19, in conjunction to such proinflammatory mediators (16, 17). Plasma replacement technique has been proven to be effective in eliminating immune complexes, inflammatory mediators, and managing the cytokine storm in a variety of illnesses, particularly severely ill COVID-19 individuals. Furthermore, plasmapheresis reduces IL-6 and TNF-α level in the blood after transplant. IL-1β is significantly higher in the early stages of ARDS and is linked to subsequent chemokine synthesis and edema, hence it is used clinically to reduce IL-1β levels (2, 18-20). This research investigated the effects of plasmapheresis and its frequency on cytokine levels, clinical manifestations, inflammatory markers, specific laboratory values, and their correlation in COVID-19 patients with ARDS. Plasmapheresis depressed excessive pro-inflammatory cytokines, liver enzymes, and concentration of acute phase proteins in severely ill COVID-19 patients, improving organ function. Plasmapheresis also enhanced oxygenation, lymphocyte count. Furthermore, all NIPPV patients who had plasmapheresis were recovered. These findings highlight the importance of conducting controlled investigations of plasmapheresis in patients with severe COVID-19 and ARDS. Only few investigations of plasmapheresis in COVID-19 patients have examined the biochemical and molecular pathways that underpin the treatment’s efficacy. Align with our results, Hashemian et al. that assessed 15 COVID-19 cases in a randomized controlled trial, found out that plasmapheresis reduced inflammatory markers including TNF-, IL-6, hepatic enzymes, ferritin and CRP levels while improving oxygen levels in these patients (21). Furthermore, another study demonstrated a meaningful association between older age and male sex and the dismal outcome and higher mortality rate in COVID patients. Similar to our findings, acute phase reactants and inflammatory mediators such as ferritin, D-dimer, IL-6 and CRP were significantly higher in severe COVID-19 cases (22). Hassaniazad et al. found out that plasmapheresis dramatically relieved clinical and analytical markers like cough, weakness, fever, blood oxygen saturation, and CRP levels in a trial involving patients with severe COVID-19. After plasmapheresis treatments, serum levels of IL-1, IL-6, IFN- and IL-17 significantly decreased in the plasmapheresis group, while Only the IL-6 level significantly diminished between the first and fourteenth day of the sickness in the control group. Additionally, serum levels of IL-1, IL-6, IFN-, and IL-17 were found to be inversely related to blood oxygen saturation before and after plasmapheresis (23). Following the infusion of convalescent plasma containing neutralizing antibodies, the clinical condition of \RL5 critically ill patients with COVID-19 and ARDS improved in a preliminary uncontrolled case series. These findings need to be tested in clinical trials because of the small sample size and study methodology, which prevent a conclusive conclusion on the treatment’s potential efficacy (24). This retrospective single-center case series is limited by the absence of a control group, small sample size, potential selection bias, and residual confounding. The lack of randomization, multiple unadjusted statistical comparisons, and absence of a huger sample size calculation further limit causal inference. Plasmapheresis appeared more beneficial in NIPPV than IMV patients. it suggests reduced efficacy in advanced inflammatory states and needs more controlled studies. Despite the promising results of plasma exchange in improving the PaO2/FiO2 ratio of critically ill COVID-19 patients, more data are required to implicate this method in improving oxygenation and overall survival on a daily basis (21, 25). Furthermore, by assessing the impact of delay in plasmapheresis on the mortality of COVID-19 patients specifically in this research, we found a significant positive association between increased APP and a higher risk of death. In critically ill COVID-19 patients, prompt plasmapheresis treatment accompanied by intravenous immune globulin (IVIG) administration may prevent disease progression and enhance the patients’ clinical outcomes by decreasing the need for mechanical ventilation and intense supportive care. However, randomized controlled trials are required to demonstrate the benefits of plasmapheresis and IVIG combination in critically ill COVID-19 patients (2). Yamakova et al. used nanomembrane \RL based plasmapheresis as the final management of ARDS in a myasthenia gravis patient infected with COVID-19 to eliminate plasma inflammatory mediators. The patient’s condition improved after three plasmapheresis procedures, and he was effectively weaned off of artificial ventilation. Aligned with our findings, using plasmapheresis as a beneficial supplement to protective mechanical ventilation considerably decreased inflammation in COVID-19 patients with ARDS (26). In this study, plasmapheresis reduced IL-6 blood levels and enhanced clinical outcome in severe COVID-19 patients on NIPPV. Therefore, its clinical application can be an effective and safe blood purifying technique to remove acute phase proteins and inflammatory cytokines and boost tissue oxygenation. There were some limitations to this investigation. Chronic diseases (diabetes, hypertension, and hyperlipidemia) had no effect on the patient’s outcome. However, this is likely due to the fact that each illness is not evaluated separately. Assessment of high blood pressure separately might reveal mortality risks. Although the decrease in Pao2/Fio2 was positive, this was a caseseries study that assessed the effect of plasmapheresis as an observational therapeutic method. So, clinical trials are needed to compare ”before treatment” and ”after treatment” only in survived patients and make a survival study to establish the improvement of survival rates with plasmapheresis. Unlike individuals who underwent IMV, plasmapheresis had promising results in eliminating inflammatory cytokines and lowering mortality in NIPPV patients. This finding could indicate that the intensity of inflammation in IMV patients is too severe for plasma exchange to improve their prognosis; therefore, brings up a controversy that should be addressed by future research. We only assessed IL-6 as an inflammatory cytokine and D-dimer as an acute phase reactant due to limited financial support, therefore measuring additional cytokines (IL-1, IL-4 TNF-α, and INF) and acute phase proteins (CRP, ferritin) in therapeutic plasmapheresis in the clinical care of COVID-19 patients should be considered in future studies. It might be better to divide acute phase reactants into mild, moderate, and severe levels. Since mild and severe forms may require different plasmapheresis protocols. However, the research was conducted during the advent of COVID-19 when hospital admissions were limited to clinically ill patients due to a widespread pandemic and insufficient healthcare facilities. Since most of these patients had high levels of IL-6 and D-dimer, we focused on the variations in these inflammatory cytokines after plasmapheresis and did not categorize the patient according to their acute phase reactant levels. Future studies may, however, follow this approach. Also, more controlled trials are required to reach a definitive protocol in clinical implication of plasmapheresis. Conclusion Our findings indicated a significant association between the survival and longer period of admission to plasmapheresis, and use of mechanical ventilation. IL-6, O2 level at the time of admission, admission to plasmapheresis period and the age in the dead patients were statistically significantly higher than the alive group. Plasmapheresis reduces IL-6 levels in the blood quickly, and it is linked to better clinical consequences in severe COVID-19 patients on NIPPV. The postulated mechanism suggested that therapeutic plasmapheresis blood purification technology enhances tissue oxygenation by removing inflammatory cytokines and acute phase proteins. Plasmapheresis acts as a beneficial supplement to protective mechanical ventilation as it considerably decreased inflammation in COVID-19 patients with ARDS. Acknowledgements None. Funding source None. Authors’ contributions Z.S and F.S and M.M wrote the main manuscript text and H.K and W.A. prepared Tables. Z.S, F.S, M.M, M.R, M.J, and F.A revised the main manuscript text. A.D and M.F performed data analysis. All authors reviewed the manuscript. Availability of data and materials The data that support the findings of this study are available on request from the corresponding author. 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Nanomembrane-based therapeutic plasmapheresis after non-invasive ventilation failure for treatment of a patient with acute respiratory distress syndrome and myasthenia gravis: a case report. Blood Purification. 2019;48(4):382-4. Supplementary Material File (table 1.docx) Download 17.44 KB File (table 2.docx) Download 15.60 KB Information & Authors Information Version history V1 Version 1 31 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords coronavirus cytokine/chemokine immune responses pathogenesis respiratory tract virus classification Authors Affiliations Zahra Sadin 0000-0003-3014-7954 [email protected] Shahid Sadoughi University of Medical Sciences Yazd Reproductive Sciences Institute View all articles by this author Fateme Salemi 0000-0003-4297-7154 Tehran University of Medical Sciences Hematology Oncology and BMT Research Center View all articles by this author Mohammadreza Mirjalili Shahid Sadoughi University of Medical Sciences Yazd Reproductive Sciences Institute View all articles by this author Mehdi Raadabadi Shahid Sadoughi University of Medical Sciences and Health Services Yazd Research and Clinical Centre for Infertility View all articles by this author Ali Dehghani Shahid Sadoughi University of Medical Sciences Yazd Reproductive Sciences Institute View all articles by this author Hossein Fallahzadeh Shahid Sadoughi University of Medical Sciences and Health Services Yazd Research and Clinical Centre for Infertility View all articles by this author Mohammad Hossein Jarahzadeh Shahid Sadoughi University of Medical Sciences Yazd Reproductive Sciences Institute View all articles by this author Fatemeh Aghaeimeybodi Shahid Sadoughi University of Medical Sciences Yazd Reproductive Sciences Institute View all articles by this author Metrics & Citations Metrics Article Usage 221 views 96 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Zahra Sadin, Fateme Salemi, Mohammadreza Mirjalili, et al. 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