The cytokines particularly tumor necrosis factor-alpha (TNF-α) have a substantial role in the pat... more The cytokines particularly tumor necrosis factor-alpha (TNF-α) have a substantial role in the pathophysiology of rheumatoid arthritis (RA). The goal of this study was to evaluate the role of serum TNFα as a competent biomarker of disease activity in RA and to assess the correlation of serum TNF-α with DAS28-ESR (disease activity score-erythrocyte sedimentation rate in 28 joints) and other markers expressed in serum of RA patients. The study was conducted from May 2020 to October 2020 after approval from the Ethical Review Committee of Ziauddin University. This cross-sectional study included 90 diagnosed cases of RA from 30 to 65 years with the complaint of arthralgia. Patients from the rheumatology clinic were enrolled in the study by a nonprobability consecutive sampling technique. Informed consent was taken from each patient and they were assessed through a set of questions based upon disability in the performance of daily activities due to RA. Evaluation of serum levels of anti-cyclic citrullinated peptide (ACCP), rheumatoid factor (RF), erythrocyte sedimentation rate, and TNF-α were done by enzyme-linked immunosorbent assay (ELISA). Patients were segregated into groups based upon DAS28-ESR with erythrocyte sedimentation rate as an inflammatory marker. The Kruskal Wallis test was applied for the comparison of different variables in these groups. Spearman correlation was applied for the association between different variables. Multiple variable analysis was performed to assess the predictability of disease activity by serum markers included in the study. The results of our study disclosed a significant difference in ACCP, TNF-α, tender joint count of 28 joints (TJ-28), swollen joint count of 28 joints (SJ-28), and health assessment questionnaire-disability index (HAQ-DI) in disease activity groups. A significant correlation of serum TNF-α with DAS28-ESR in RA patients was observed. This study illustrated a significant correlation of serum TNF-α with DAS28-ESR in RA patients. We found that expression of serum TNF-α may intensify the inflammatory activity in early RA, therefore, RA patients must be screened for this cytokine to monitor that disease activity could be useful for patients undergoing anti-TNF therapy.
Altered protamine 1 (PRM1)/ protamine 2 (PRM2) mRNA ratio in testicular biopsy samples correlates... more Altered protamine 1 (PRM1)/ protamine 2 (PRM2) mRNA ratio in testicular biopsy samples correlates with sperm quality and its fertilising ability. This study is planned to assess PRM1/ PRM2 mRNA ratio in subgroups of azoospermia to suggest a more reliable and accurate marker for assessing sperm quality in nonobstructive azoospermia (NOA). A cross‐sectional study was done on testicular biopsy samples, taken from 106 azoospermic patients. Samples were histologically classified into subgroups: 36 obstructive azoospermia (OA), and two groups of NOA: 41 round spermatid maturation arrest (SMA) and 29 Sertoli cell‐only syndrome (SCOS). OA samples showed histologically normal spermatogenesis and serve as a positive control. mRNA expression of jumonji domain‐containing 1A (JMJD1A), PRM1, PRM2 and transition nuclear proteins (TNP1, TNP2) genes was determined, by RT‐qPCR. Significantly lower expression of JMJD1A (p < .001), PRM1 (p = .0265) and PRM2 (p = .0032) has been seen in the SCOS group of NOA. We found significant (p < .001) increase in PRM1/PRM2 mRNA ratio in testicular biopsy samples of SCOS group of NOA patients and significant negative correlation of PRM1/PRM2 mRNA ratio with JMJD1A. Hence, PRM1/PRM2 mRNA ratio may represent a more reliable and accurate marker to assess sperm quality in NOA in addition to standard semen parameters.
Cardiac endocrine Function: Heart is an endocrine organ besides a mechanical pump for circulation... more Cardiac endocrine Function: Heart is an endocrine organ besides a mechanical pump for circulation. This endocrine function was identified when atrial natriuretic peptide (ANP) was discovered as a first natriuretic peptide.1 Subsequent studies discovered two other natriuretic peptides, Brain (or B-type) natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), with the homologous sequence and structure.2,3 BNP was first detected from brain tissue , but later on was found to be mainly of cardiac origin.2,4 CNP is mainly produced by endothelial cells.3 ANP and BNP exert natriuretic, diuretic and vasodilatory effects while CNP causes smooth muscle relaxation in the peripheral vasculature.3,5 Cardiac natriuretic peptides are released into the blood in response to stretch or ischaemia of cardiac chambers. BNP is released predominantly by the cardiac ventricles and ANP by atria. 6 After being released into the interstitial space, these cardiac peptides flow either into the coronary s...
To access successfulness of sperm retrieval by evaluating the mRNA expression profile of JMJD1A, ... more To access successfulness of sperm retrieval by evaluating the mRNA expression profile of JMJD1A, TNP1, TNP2, PRM1 and PRM2 in patients undergoing surgical sperm retrieval procedure. Probability of sperm retrieval in azoospermia is decreased when mRNA expression profile of JMJD1A TNP2 and PRM2 in testicular tissue is decreased. Studies have been done on expression of JMJD1A in non-obstructive azoospermic patients in other part of the world with smaller sample size but this is the first study in Pakistan with larger number of patients. Study design, size, duration: Crossectional study, 100 azoospermic patients coming for purpose of sperm retrieval by TESE or micro-TESE in Australian Concept Infertility Medical Center, Karachi,from March, 2018 to December, 2019 All recruited azoospermic patients were evaluated by history, physical examination, and hormonal assessment. RNA was extracted by pureLink RNA Micro kit and mRNA expression of the JMJD1A, TNP1, TNP2, PRM1 and PRM2 genes was dete...
Assisted reproduction is the assistance provided to address infertility. All treatments of fertil... more Assisted reproduction is the assistance provided to address infertility. All treatments of fertility in which handling of both egg and embryo is done are included in “assisted reproductive techniques (ARTs).” In these techniques, eggs from woman’s ovaries are surgically removed and combined in vitro with sperm and embryo is ultimatly returned to the uterine cavity. ARTs therefore incorporate a wide range of procedures that are used to overcome natural barriers in fertilization by directly collecting and in vitro handling of human gametes and replacement of embryo into the uterus. In this chapter, the main focus will be on the steps of in vitro fertilization (IVF) and embryo transfer with normal reproductive physiology and factors predicting the success of IVF.
The difficulties encountered in surgical spermatozoa retrieval for intracytoplasmic sperm injecti... more The difficulties encountered in surgical spermatozoa retrieval for intracytoplasmic sperm injection procedure in azoospermic men have stressed the dire need for a robust biomarker for the prediction of spermatozoa retrieval. Data have highlighted the role of JMJD1A (Jumonji domain‐containing 1A), a histone H3K9 demethylase, and other nuclear proteins, protamines (PRM) and transition nuclear proteins (TNP), as biomarkers in male infertility.
JPMA. The Journal of the Pakistan Medical Association, 2019
OBJECTIVE To compare stress markers and reproductive hormones in fertile and infertile females, a... more OBJECTIVE To compare stress markers and reproductive hormones in fertile and infertile females, and to relate the markers with age, duration and cause of infertility, and body mass index.. METHODS The case-control study was conducted at Aga Khan University Hospital, Karachi, from March 2017 to February 2018. Females aged 16-50 years regardless of ethnic background were recruited from the Australian Concept Infertility Medical Centre, Karachi, and were equally divided into infertile cases group A, and fertile controls group B. Serum follicular stimulating hormone, luteinizing hormone, estradiol, glutathione reductase and cortisol were measured using enzyme-linked innmunosorbent assay. SPSS 19 was used for statistical analysis.. RESULTS There were 328 female subjects divided into two equal groups of 164(50%). Serum luteinizing hormone and cortisol was higher in the group A than in group B (p<0.001). Serum glutathione reductase was low in group A compared to group B (p<0.001). Du...
Background: Oxidative stress, an imbalance of pro-oxidants and antioxidants, is reported to be as... more Background: Oxidative stress, an imbalance of pro-oxidants and antioxidants, is reported to be associated with female infertility. This study was aimed to compare cortisol (oxidative stress marker) and vitamin E (antioxidant) levels in the fertile and infertile female population of Karachi, Pakistan. Materials and Methods: A total of 88 females, recruited from Australian Concept Infertility Medical Centre, were divided equally into infertile cases and fertile controls. Serum cortisol and vitamin E (VE) levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Statistical comparison was done by Chi-square and Mann-Whitney U-test. Correlation between two continuous variables was determined by Spearman's Correlation. The P value < 0.05 was considered significant in all cases. Results: The median age for the fertile group was 31.0 (IQR= 27.0-37.0) and for the infertile group, 32.0 (IQR= 28.0-38.0). Of the infertile females, 70.5% (n= 31) had primary infertility while 29.5% (n= 13) had secondary infertility. A significant difference in the cortisol levels was seen between the fertile and the infertile groups. (p value= 0.001). VE levels were significantly decreased in the infertile females (p value= 0.026). The levels of cortisol and VE were found to be in a weak negative correlation in the infertile women (-0.163). Conclusion: A balance between oxidants and antioxidants is required to maintain the reproductive potential in females. Decrease in the antioxidant vitamin E, and an increase in pro-oxidant cortisol, may be associated with a risk of infertility in females.
Silent information Regulators (SIRT1) gene stimulates antioxidants' expression, repairs cells dam... more Silent information Regulators (SIRT1) gene stimulates antioxidants' expression, repairs cells damaged by oxidative stress (OS), and prevents the cells' dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS in GCs by targeting a transcription factor vital for ovarian functions and maintenance. ROS-mediated damage to spermatozoa's motility and morphology is responsible for 30-80% of men's infertility cases. High levels of ROS can cause damage to deoxyribo nucleic acid (DNA) in the nucleus and mitochondria, lipid peroxidation, apoptosis, inactivation of enzymes, and oxidation of proteins in spermatozoa. SIRT 1 is a cardioprotective molecule that prevents atherosclerosis by modulating various mechanisms such as endothelial injury due to impaired nitric oxide (NO) production, inflammation, OS, and regulation of autophagy. SIRT 1 is abundantly expressed in tubular cells and podocytes. It is also found to be highly expressed in aquaporin 2 positive cells in the distal nephron suggesting its involvement in sodium and water handling. SIRT1 improves insulin resistance by reducing OS and regulating mitochondrial biogenesis and function. It also decreases adiposity and lipogenesis and increases fatty acid oxidation. So, its involvement in the multiple pathways ensures its unique role in reproductive and metabolic derangement mechanisms.
The correlation of subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) is a sti... more The correlation of subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) is a still insufficiently explored entity. The aim of this study was to determine the correlation between SCH and PCOS along with the impact of SCH on metabolic and hormonal parameters in women with PCOS. This cross-sectional study was conducted at the Gynecology Outpatient Department of Ziauddin Hospital Kemari, Karachi, Pakistan, from June 2019 to December 2019. A total of 90 diagnosed cases of PCOS were enrolled in the study. A non-probability consecutive sampling technique was used. After taking informed consent, participants were evaluated through clinical interviews, a questionnaire, and anthropometric measurements. The participants underwent the following assessments, i.e., transabdominal ultrasonography, hormonal profile (free testosterone, follicle-stimulating hormone, luteinizing hormone), and fasting blood sugar. Participants were divided into two groups based on thyroid-stimulating hormone (TSH) into the euthyroid group and subclinical hypothyroid (SCH) group. The Mann-Whitney test was used for comparing the two groups. Our results showed a significant difference in weight, body mass index (BMI), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and TSH were found in the SCH group as compared to the euthyroid group. A significant correlation of TSH with waist-hip ratio (WHR), weight, body mass index (BMI), insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR) in PCOS patients. This study showed a significant correlation of subclinical hypothyroidism with polycystic ovary syndrome. We found subclinical hypothyroidism may aggravate the insulin resistance; therefore, PCOS patients must be screened with a thyroid profile.
Objective: To compare stress markers and antioxidants in fertile and infertile males, and to expl... more Objective: To compare stress markers and antioxidants in fertile and infertile males, and to explore their effects on reproductive hormones and fertility. Methods: The cross-sectional case-control study was conducted from July 2017 to July 2018 at the Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, and comprised male subjects aged 25-55 years. Infertile subjects were the cases, while healthy fertile males acted as the controls. Stress hormones cortisol and adrenaline and antioxidants glutathione peroxidase and superoxide dismutase were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. Results: Of the 376 subjects, 241(64%) were cases and 135(36%) were controls. Median cortisol, adrenaline, superoxide dismutase and glutathione levels were significantly higher among the cases compared to te controls (p<0.05). Follicle stimulating hormone and luteinizing hormone levels were higher in cases compared to the controls (p=0.05). Mean testosterone level was higher among the controls than the cases (p<0.001). After adjusting for other covariates, every increase of 7 units in cortisol increased the prevalence of infertility by 3% (p=0.001). There was significant interaction between luteinizing hormone and testosterone in the final model (p<0.05). Conclusion: Stress together with decrease in antioxidants was found to play a significant role in reducing the fertilising potential of male infertile subjects.
Background: This study aimed to estimate stress markers, oxidative stress (OS), reproductive horm... more Background: This study aimed to estimate stress markers, oxidative stress (OS), reproductive hormones and sperm parameters in male smokers and non-smokers and observe the impact of oxidative stress markers and smoking on sperm count, motility and morphology in a selected population of Karachi, Pakistan. Methods: This cross-sectional study was conducted from July 2017 to July 2018 at Aga Khan University (AKU), in Karachi, Pakistan. The subjects were recruited from the Sindh Institute of Reproductive Medicine (SIRM), Karachi based on defined inclusion criteria. The subjects were categorized into fertile and infertile based on cut off values of sperm parameters as recommended by the WHO i.e., sperm count/ejaculate of 39 × 10 6 /ml, sperm motility 40% and normal morphology 4%. Two hundred eleven fertile and 165 infertile male subjects were included in the study. Serum cortisol, adrenaline, superoxide dismutase (SOD), and glutathione peroxidase (GPX) were analyzed by ELISA kits. Data was analyzed on SPSS-22. A p-value of <0.05 was considered statistically significant. Results: Age, Body Mass Index (BMI), and body fat were similar among smokers and non-smokers. Age was significantly lower, while mean BMI and body fat were significantly higher among infertile smokers vs. fertile smokers (p-value < 0.05). The testosterone levels were significantly reduced among smokers as compared to nonsmokers (p-value < 0.05). The median cortisol levels were increased as well as GPX, and steroid hormone-binding globulin (SHBG) were significantly reduced among smokers as compared to non-smokers. Additionally, the same findings with a significant difference have also been observed among infertile smokers as compared to fertile smokers (p-value < 0.05). This study has shown that the semen parameters (total count, motility, and morphology) are decreased in infertile smokers as compared to infertile non-smokers. Furthermore, the multivariate analysis showed that smoking causes a significant decrease in sperm count and morphology but it did not have any significant effect on motility. Smoking has a significant effect on fertility, specifically sperm count and normal morphology of sperm. This might be due to OS produced by smoking, which has
Infertility is a global problem which has an impact on the physical as well as social well-being ... more Infertility is a global problem which has an impact on the physical as well as social well-being of infertile couples (Alam, Khan, & Rehman, 2018). The male factors account for 20%-70% of infertility problems (Agarwal, Mulgund, Hamada, & Chyatte, 2015). Obesity is an important issue worldwide that influences fertility as well (Katib, 2015), and the incidence of obesity and infertility has been increasing globally. Various metabolic changes associated with obesity are glucose intolerance, insulin resistance (hyperinsulinemia), hyperleptinemia, chronic inflammation and male hypogonadism (Leisegang, Bouic, Menkveld, & Henkel, 2014). Leptin, an adipocyte-secreted protein hormone composed of 167 amino acids, plays multiple functions in the human body, such as regulation of appetite, energy homeostasis and neuroendocrine function (Dalamaga et al., 2013; Park & Ahima, 2015). Leptin is also an important regulator of male reproduction by modulating the hypothalamus-pituitary-testes (HPT) axis (Leisegang et al., 2014). It has both direct and indirect effects on the HPT axis (Aquila et al., 2005). It acts indirectly via the central neuroendocrine system on the gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It also has a direct local effect on leydig and sertoli cell function (Lampiao, Agarwal, & du Plessis, 2009). Serum leptin levels have been found to be high in most obese
Background: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produ... more Background: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produced by the heart, is elevated in patients with left ventricular dysfunction. The purpose of this study was to compare the abilities of serum and pericardial fluid levels of amino-terminal pro-B-type natriuretic peptide to detect the left ventricular systolic dysfunction determined by echocardiography. Methods: 50 patients undergoing coronary artery bypass grafting were included in this study. Left ventricular systolic function was assessed using echocardiography before coronary artery bypass grafting. The samples of serum and pericardial fluid were collected during surgery, and amino-terminal pro-B-type natriuretic peptide levels were assessed by an electrochemiluminescence immunoassay. The log value of amino-terminal pro-B-type natriuretic peptide concentrations was calculated. Results: the pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide were significantly ...
JPMA. The Journal of the Pakistan Medical Association, 2019
OBJECTIVE This review aimed to determine the impact of exercise protocol among peripheral artery ... more OBJECTIVE This review aimed to determine the impact of exercise protocol among peripheral artery disease patients. Literature search was done from 2005 to 2018. METHODS Databases such as Google Scholar, Medline and PubMed was reconnoitred for the purpose of research articles by using key words like exercise training, peripheral artery disease, ankle brachial index, haemodynamic and atherosclerosis. Studies fulfilling the inclusion criteria were retrieved and encompassed in the present study. RESULTS The heterogeneity of the studies included in the analysis and the impact of exercise programmes on outcome measures were assessed by using hedge gstatistical model.Of the54 studies found, 9(16.6%) were analysed that suggest supervised and structured exercises programmes significantly improved (p<0.05) outcome variables. CONCLUSIONS Future randomized controlled trials related to the duration of exercises regimes are required in order to tailor the training programmes according to the n...
The cytokines particularly tumor necrosis factor-alpha (TNF-α) have a substantial role in the pat... more The cytokines particularly tumor necrosis factor-alpha (TNF-α) have a substantial role in the pathophysiology of rheumatoid arthritis (RA). The goal of this study was to evaluate the role of serum TNFα as a competent biomarker of disease activity in RA and to assess the correlation of serum TNF-α with DAS28-ESR (disease activity score-erythrocyte sedimentation rate in 28 joints) and other markers expressed in serum of RA patients. The study was conducted from May 2020 to October 2020 after approval from the Ethical Review Committee of Ziauddin University. This cross-sectional study included 90 diagnosed cases of RA from 30 to 65 years with the complaint of arthralgia. Patients from the rheumatology clinic were enrolled in the study by a nonprobability consecutive sampling technique. Informed consent was taken from each patient and they were assessed through a set of questions based upon disability in the performance of daily activities due to RA. Evaluation of serum levels of anti-cyclic citrullinated peptide (ACCP), rheumatoid factor (RF), erythrocyte sedimentation rate, and TNF-α were done by enzyme-linked immunosorbent assay (ELISA). Patients were segregated into groups based upon DAS28-ESR with erythrocyte sedimentation rate as an inflammatory marker. The Kruskal Wallis test was applied for the comparison of different variables in these groups. Spearman correlation was applied for the association between different variables. Multiple variable analysis was performed to assess the predictability of disease activity by serum markers included in the study. The results of our study disclosed a significant difference in ACCP, TNF-α, tender joint count of 28 joints (TJ-28), swollen joint count of 28 joints (SJ-28), and health assessment questionnaire-disability index (HAQ-DI) in disease activity groups. A significant correlation of serum TNF-α with DAS28-ESR in RA patients was observed. This study illustrated a significant correlation of serum TNF-α with DAS28-ESR in RA patients. We found that expression of serum TNF-α may intensify the inflammatory activity in early RA, therefore, RA patients must be screened for this cytokine to monitor that disease activity could be useful for patients undergoing anti-TNF therapy.
Altered protamine 1 (PRM1)/ protamine 2 (PRM2) mRNA ratio in testicular biopsy samples correlates... more Altered protamine 1 (PRM1)/ protamine 2 (PRM2) mRNA ratio in testicular biopsy samples correlates with sperm quality and its fertilising ability. This study is planned to assess PRM1/ PRM2 mRNA ratio in subgroups of azoospermia to suggest a more reliable and accurate marker for assessing sperm quality in nonobstructive azoospermia (NOA). A cross‐sectional study was done on testicular biopsy samples, taken from 106 azoospermic patients. Samples were histologically classified into subgroups: 36 obstructive azoospermia (OA), and two groups of NOA: 41 round spermatid maturation arrest (SMA) and 29 Sertoli cell‐only syndrome (SCOS). OA samples showed histologically normal spermatogenesis and serve as a positive control. mRNA expression of jumonji domain‐containing 1A (JMJD1A), PRM1, PRM2 and transition nuclear proteins (TNP1, TNP2) genes was determined, by RT‐qPCR. Significantly lower expression of JMJD1A (p < .001), PRM1 (p = .0265) and PRM2 (p = .0032) has been seen in the SCOS group of NOA. We found significant (p < .001) increase in PRM1/PRM2 mRNA ratio in testicular biopsy samples of SCOS group of NOA patients and significant negative correlation of PRM1/PRM2 mRNA ratio with JMJD1A. Hence, PRM1/PRM2 mRNA ratio may represent a more reliable and accurate marker to assess sperm quality in NOA in addition to standard semen parameters.
Cardiac endocrine Function: Heart is an endocrine organ besides a mechanical pump for circulation... more Cardiac endocrine Function: Heart is an endocrine organ besides a mechanical pump for circulation. This endocrine function was identified when atrial natriuretic peptide (ANP) was discovered as a first natriuretic peptide.1 Subsequent studies discovered two other natriuretic peptides, Brain (or B-type) natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), with the homologous sequence and structure.2,3 BNP was first detected from brain tissue , but later on was found to be mainly of cardiac origin.2,4 CNP is mainly produced by endothelial cells.3 ANP and BNP exert natriuretic, diuretic and vasodilatory effects while CNP causes smooth muscle relaxation in the peripheral vasculature.3,5 Cardiac natriuretic peptides are released into the blood in response to stretch or ischaemia of cardiac chambers. BNP is released predominantly by the cardiac ventricles and ANP by atria. 6 After being released into the interstitial space, these cardiac peptides flow either into the coronary s...
To access successfulness of sperm retrieval by evaluating the mRNA expression profile of JMJD1A, ... more To access successfulness of sperm retrieval by evaluating the mRNA expression profile of JMJD1A, TNP1, TNP2, PRM1 and PRM2 in patients undergoing surgical sperm retrieval procedure. Probability of sperm retrieval in azoospermia is decreased when mRNA expression profile of JMJD1A TNP2 and PRM2 in testicular tissue is decreased. Studies have been done on expression of JMJD1A in non-obstructive azoospermic patients in other part of the world with smaller sample size but this is the first study in Pakistan with larger number of patients. Study design, size, duration: Crossectional study, 100 azoospermic patients coming for purpose of sperm retrieval by TESE or micro-TESE in Australian Concept Infertility Medical Center, Karachi,from March, 2018 to December, 2019 All recruited azoospermic patients were evaluated by history, physical examination, and hormonal assessment. RNA was extracted by pureLink RNA Micro kit and mRNA expression of the JMJD1A, TNP1, TNP2, PRM1 and PRM2 genes was dete...
Assisted reproduction is the assistance provided to address infertility. All treatments of fertil... more Assisted reproduction is the assistance provided to address infertility. All treatments of fertility in which handling of both egg and embryo is done are included in “assisted reproductive techniques (ARTs).” In these techniques, eggs from woman’s ovaries are surgically removed and combined in vitro with sperm and embryo is ultimatly returned to the uterine cavity. ARTs therefore incorporate a wide range of procedures that are used to overcome natural barriers in fertilization by directly collecting and in vitro handling of human gametes and replacement of embryo into the uterus. In this chapter, the main focus will be on the steps of in vitro fertilization (IVF) and embryo transfer with normal reproductive physiology and factors predicting the success of IVF.
The difficulties encountered in surgical spermatozoa retrieval for intracytoplasmic sperm injecti... more The difficulties encountered in surgical spermatozoa retrieval for intracytoplasmic sperm injection procedure in azoospermic men have stressed the dire need for a robust biomarker for the prediction of spermatozoa retrieval. Data have highlighted the role of JMJD1A (Jumonji domain‐containing 1A), a histone H3K9 demethylase, and other nuclear proteins, protamines (PRM) and transition nuclear proteins (TNP), as biomarkers in male infertility.
JPMA. The Journal of the Pakistan Medical Association, 2019
OBJECTIVE To compare stress markers and reproductive hormones in fertile and infertile females, a... more OBJECTIVE To compare stress markers and reproductive hormones in fertile and infertile females, and to relate the markers with age, duration and cause of infertility, and body mass index.. METHODS The case-control study was conducted at Aga Khan University Hospital, Karachi, from March 2017 to February 2018. Females aged 16-50 years regardless of ethnic background were recruited from the Australian Concept Infertility Medical Centre, Karachi, and were equally divided into infertile cases group A, and fertile controls group B. Serum follicular stimulating hormone, luteinizing hormone, estradiol, glutathione reductase and cortisol were measured using enzyme-linked innmunosorbent assay. SPSS 19 was used for statistical analysis.. RESULTS There were 328 female subjects divided into two equal groups of 164(50%). Serum luteinizing hormone and cortisol was higher in the group A than in group B (p<0.001). Serum glutathione reductase was low in group A compared to group B (p<0.001). Du...
Background: Oxidative stress, an imbalance of pro-oxidants and antioxidants, is reported to be as... more Background: Oxidative stress, an imbalance of pro-oxidants and antioxidants, is reported to be associated with female infertility. This study was aimed to compare cortisol (oxidative stress marker) and vitamin E (antioxidant) levels in the fertile and infertile female population of Karachi, Pakistan. Materials and Methods: A total of 88 females, recruited from Australian Concept Infertility Medical Centre, were divided equally into infertile cases and fertile controls. Serum cortisol and vitamin E (VE) levels were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. Statistical comparison was done by Chi-square and Mann-Whitney U-test. Correlation between two continuous variables was determined by Spearman's Correlation. The P value < 0.05 was considered significant in all cases. Results: The median age for the fertile group was 31.0 (IQR= 27.0-37.0) and for the infertile group, 32.0 (IQR= 28.0-38.0). Of the infertile females, 70.5% (n= 31) had primary infertility while 29.5% (n= 13) had secondary infertility. A significant difference in the cortisol levels was seen between the fertile and the infertile groups. (p value= 0.001). VE levels were significantly decreased in the infertile females (p value= 0.026). The levels of cortisol and VE were found to be in a weak negative correlation in the infertile women (-0.163). Conclusion: A balance between oxidants and antioxidants is required to maintain the reproductive potential in females. Decrease in the antioxidant vitamin E, and an increase in pro-oxidant cortisol, may be associated with a risk of infertility in females.
Silent information Regulators (SIRT1) gene stimulates antioxidants' expression, repairs cells dam... more Silent information Regulators (SIRT1) gene stimulates antioxidants' expression, repairs cells damaged by oxidative stress (OS), and prevents the cells' dysfunction. In particular, the role of different Sirtuins, particularly SIRT1 in reproduction, has been widely studied over the past decade. Decreased SIRT 1 causes mitochondrial dysfunction by increasing Reactive Oxygen Species (ROS), lipid peroxidation, and DNA damage in both male and female gametes (Sperms and Oocytes), leading to infertility. In the female reproductive system, SIRT1 regulates proliferation and apoptosis in granulosa cells (GCs), and its down-regulation is associated with a reduced ovarian reserve. SIRT1 also modulates the stress response to OS in GCs by targeting a transcription factor vital for ovarian functions and maintenance. ROS-mediated damage to spermatozoa's motility and morphology is responsible for 30-80% of men's infertility cases. High levels of ROS can cause damage to deoxyribo nucleic acid (DNA) in the nucleus and mitochondria, lipid peroxidation, apoptosis, inactivation of enzymes, and oxidation of proteins in spermatozoa. SIRT 1 is a cardioprotective molecule that prevents atherosclerosis by modulating various mechanisms such as endothelial injury due to impaired nitric oxide (NO) production, inflammation, OS, and regulation of autophagy. SIRT 1 is abundantly expressed in tubular cells and podocytes. It is also found to be highly expressed in aquaporin 2 positive cells in the distal nephron suggesting its involvement in sodium and water handling. SIRT1 improves insulin resistance by reducing OS and regulating mitochondrial biogenesis and function. It also decreases adiposity and lipogenesis and increases fatty acid oxidation. So, its involvement in the multiple pathways ensures its unique role in reproductive and metabolic derangement mechanisms.
The correlation of subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) is a sti... more The correlation of subclinical hypothyroidism (SCH) and polycystic ovary syndrome (PCOS) is a still insufficiently explored entity. The aim of this study was to determine the correlation between SCH and PCOS along with the impact of SCH on metabolic and hormonal parameters in women with PCOS. This cross-sectional study was conducted at the Gynecology Outpatient Department of Ziauddin Hospital Kemari, Karachi, Pakistan, from June 2019 to December 2019. A total of 90 diagnosed cases of PCOS were enrolled in the study. A non-probability consecutive sampling technique was used. After taking informed consent, participants were evaluated through clinical interviews, a questionnaire, and anthropometric measurements. The participants underwent the following assessments, i.e., transabdominal ultrasonography, hormonal profile (free testosterone, follicle-stimulating hormone, luteinizing hormone), and fasting blood sugar. Participants were divided into two groups based on thyroid-stimulating hormone (TSH) into the euthyroid group and subclinical hypothyroid (SCH) group. The Mann-Whitney test was used for comparing the two groups. Our results showed a significant difference in weight, body mass index (BMI), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and TSH were found in the SCH group as compared to the euthyroid group. A significant correlation of TSH with waist-hip ratio (WHR), weight, body mass index (BMI), insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR) in PCOS patients. This study showed a significant correlation of subclinical hypothyroidism with polycystic ovary syndrome. We found subclinical hypothyroidism may aggravate the insulin resistance; therefore, PCOS patients must be screened with a thyroid profile.
Objective: To compare stress markers and antioxidants in fertile and infertile males, and to expl... more Objective: To compare stress markers and antioxidants in fertile and infertile males, and to explore their effects on reproductive hormones and fertility. Methods: The cross-sectional case-control study was conducted from July 2017 to July 2018 at the Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, and comprised male subjects aged 25-55 years. Infertile subjects were the cases, while healthy fertile males acted as the controls. Stress hormones cortisol and adrenaline and antioxidants glutathione peroxidase and superoxide dismutase were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. Results: Of the 376 subjects, 241(64%) were cases and 135(36%) were controls. Median cortisol, adrenaline, superoxide dismutase and glutathione levels were significantly higher among the cases compared to te controls (p<0.05). Follicle stimulating hormone and luteinizing hormone levels were higher in cases compared to the controls (p=0.05). Mean testosterone level was higher among the controls than the cases (p<0.001). After adjusting for other covariates, every increase of 7 units in cortisol increased the prevalence of infertility by 3% (p=0.001). There was significant interaction between luteinizing hormone and testosterone in the final model (p<0.05). Conclusion: Stress together with decrease in antioxidants was found to play a significant role in reducing the fertilising potential of male infertile subjects.
Background: This study aimed to estimate stress markers, oxidative stress (OS), reproductive horm... more Background: This study aimed to estimate stress markers, oxidative stress (OS), reproductive hormones and sperm parameters in male smokers and non-smokers and observe the impact of oxidative stress markers and smoking on sperm count, motility and morphology in a selected population of Karachi, Pakistan. Methods: This cross-sectional study was conducted from July 2017 to July 2018 at Aga Khan University (AKU), in Karachi, Pakistan. The subjects were recruited from the Sindh Institute of Reproductive Medicine (SIRM), Karachi based on defined inclusion criteria. The subjects were categorized into fertile and infertile based on cut off values of sperm parameters as recommended by the WHO i.e., sperm count/ejaculate of 39 × 10 6 /ml, sperm motility 40% and normal morphology 4%. Two hundred eleven fertile and 165 infertile male subjects were included in the study. Serum cortisol, adrenaline, superoxide dismutase (SOD), and glutathione peroxidase (GPX) were analyzed by ELISA kits. Data was analyzed on SPSS-22. A p-value of <0.05 was considered statistically significant. Results: Age, Body Mass Index (BMI), and body fat were similar among smokers and non-smokers. Age was significantly lower, while mean BMI and body fat were significantly higher among infertile smokers vs. fertile smokers (p-value < 0.05). The testosterone levels were significantly reduced among smokers as compared to nonsmokers (p-value < 0.05). The median cortisol levels were increased as well as GPX, and steroid hormone-binding globulin (SHBG) were significantly reduced among smokers as compared to non-smokers. Additionally, the same findings with a significant difference have also been observed among infertile smokers as compared to fertile smokers (p-value < 0.05). This study has shown that the semen parameters (total count, motility, and morphology) are decreased in infertile smokers as compared to infertile non-smokers. Furthermore, the multivariate analysis showed that smoking causes a significant decrease in sperm count and morphology but it did not have any significant effect on motility. Smoking has a significant effect on fertility, specifically sperm count and normal morphology of sperm. This might be due to OS produced by smoking, which has
Infertility is a global problem which has an impact on the physical as well as social well-being ... more Infertility is a global problem which has an impact on the physical as well as social well-being of infertile couples (Alam, Khan, & Rehman, 2018). The male factors account for 20%-70% of infertility problems (Agarwal, Mulgund, Hamada, & Chyatte, 2015). Obesity is an important issue worldwide that influences fertility as well (Katib, 2015), and the incidence of obesity and infertility has been increasing globally. Various metabolic changes associated with obesity are glucose intolerance, insulin resistance (hyperinsulinemia), hyperleptinemia, chronic inflammation and male hypogonadism (Leisegang, Bouic, Menkveld, & Henkel, 2014). Leptin, an adipocyte-secreted protein hormone composed of 167 amino acids, plays multiple functions in the human body, such as regulation of appetite, energy homeostasis and neuroendocrine function (Dalamaga et al., 2013; Park & Ahima, 2015). Leptin is also an important regulator of male reproduction by modulating the hypothalamus-pituitary-testes (HPT) axis (Leisegang et al., 2014). It has both direct and indirect effects on the HPT axis (Aquila et al., 2005). It acts indirectly via the central neuroendocrine system on the gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It also has a direct local effect on leydig and sertoli cell function (Lampiao, Agarwal, & du Plessis, 2009). Serum leptin levels have been found to be high in most obese
Background: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produ... more Background: serum level of amino-terminal pro-B-type natriuretic peptide, a cardiac hormone produced by the heart, is elevated in patients with left ventricular dysfunction. The purpose of this study was to compare the abilities of serum and pericardial fluid levels of amino-terminal pro-B-type natriuretic peptide to detect the left ventricular systolic dysfunction determined by echocardiography. Methods: 50 patients undergoing coronary artery bypass grafting were included in this study. Left ventricular systolic function was assessed using echocardiography before coronary artery bypass grafting. The samples of serum and pericardial fluid were collected during surgery, and amino-terminal pro-B-type natriuretic peptide levels were assessed by an electrochemiluminescence immunoassay. The log value of amino-terminal pro-B-type natriuretic peptide concentrations was calculated. Results: the pericardial fluid levels of log amino-terminal pro-B-type natriuretic peptide were significantly ...
JPMA. The Journal of the Pakistan Medical Association, 2019
OBJECTIVE This review aimed to determine the impact of exercise protocol among peripheral artery ... more OBJECTIVE This review aimed to determine the impact of exercise protocol among peripheral artery disease patients. Literature search was done from 2005 to 2018. METHODS Databases such as Google Scholar, Medline and PubMed was reconnoitred for the purpose of research articles by using key words like exercise training, peripheral artery disease, ankle brachial index, haemodynamic and atherosclerosis. Studies fulfilling the inclusion criteria were retrieved and encompassed in the present study. RESULTS The heterogeneity of the studies included in the analysis and the impact of exercise programmes on outcome measures were assessed by using hedge gstatistical model.Of the54 studies found, 9(16.6%) were analysed that suggest supervised and structured exercises programmes significantly improved (p<0.05) outcome variables. CONCLUSIONS Future randomized controlled trials related to the duration of exercises regimes are required in order to tailor the training programmes according to the n...
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Papers by Sofia Amjad