Dr. Ashok Agarwal: IVF Expert of the Year 2019

American College of Embryology Names Dr. Ashok Agarwal, IVF Expert of the Year 2019 

 

           Ashok Agarwal Ph.D

Dr Ashok Agarwal is the Director of the Andrology Center at the Cleveland Clinic and the Director of Research at the American Center for Reproductive Medicine. He has held these positions for the past 26 years, since the inception of the Center. Under his visionary leadership, the Andrology Center has become a center of excellence in the United States for the advanced diagnosis of male infertility and fertility preservation of men with oncological conditions. Ashok is also a Professor of Surgery (Urology) at the Cleveland Clinic’s Lerner College of Medicine of Case Western Reserve University and a staff member in the Cleveland Clinic's Glickman Urological and Kidney Institute.
 
Throughout his distinguished career, Ashok has received over 125 research grants and published more than 735 research papers and 225 book chapters in specialized medical journals and books. Ashok is ranked in Scopus as the top-ranking author worldwide in the fields of Male Infertility/Andrology and Human Assisted Reproduction, based on his number of peer-reviewed publications, citation scores and Hirsch index (h-index). As of October 2019, his h-index was 97 on Scopus and 127 on Google Scholar, and his citation count was 32,169 on Scopus and 68,275 on Google Scholar. Based on his outstanding research in reproductive medicine, Ashok was listed by Expertscape as a top-rated world expert in male infertility.
 
Ashok and his team has presented more than 800 papers at both national and international scientific meetings. He has also been invited as a guest speaker to over 30 countries and directed more than two dozen Assisted Reproductive Technology (ART) and andrology laboratory practical workshops and symposia. Ashok serves on the editorial board of 11 peer review journals and has been a guest editor of 10 special issues, with 3 more in the pipeline. Ashok is currently an editor of 40 medical text books or manuals in the fields of reproductive medicine, fertility preservation, male infertility, fertility preservation and assisted reproduction.
 
Ashok, along with Dr. Dmitri Dozortsev and Dr. Zsolt Peter Nagy, was instrumental in the inception of the American College of Embryology in November 2009. He also served as the first Chairman of the Board of the American College of Embryology between 2009 and 2012. He currently serves on the executive committee of Alpha, an international society that promotes the advancement of the art and science of clinical embryology. Ashok is certified by the American Board of Bioanalysis as a Clinical Laboratory Director (HCLD) in Andrology. He also serves as an Inspector for the College of American Pathologists ‘Reproductive Laboratory Program’ for accreditation of Andrology and In Vitro Fertilization (IVF) Laboratories.
 
Dr. Ashok Agarwal was born in Lucknow, India. He pursued a tertiary education at the Banaras Hindu University (BHU) in Varanasi, India where he obtained his M.S. with specialization in Reproductive Physiology in 1977. Ashok continued his research work in the Reproductive Physiology Laboratory at BHU under the guidance of the late Professor CJ Dominic, a prominent researcher in mammalian reproductive pheromones, mammalian reproduction, and fertility control. Ashok was awarded a Ph.D. in Zoology with a specialization in Mammalian Reproductive Biology in 1983. His doctoral research centred on investigating the epididymal histology, histochemistry, and biochemistry of several local mammalian species from a comparative point of view. Ashok’s intense doctoral training was instrumental in shaping his career in the area of mammalian reproductive biology.
 
In 1984, Ashok moved to the United States when he was awarded a Fellowship in Reproductive Biology by the Rockefeller Foundation in New York. He spent two years as a post-doctoral researcher in Dr. Anita P. Hoffer’s laboratory in the Division of Urology at Harvard Medical School and the Brigham and Women's Hospital in Boston, Massachusetts. Early research published from his time at Harvard revolved around investigating the anti-fertility effects of gossypol in animal models and then on male contraception. This widening background strengthened his research focus on male infertility and andrology.
 
At Harvard, Ashok’s interest in research was further stimulated by his senior colleague and close friend, Dr. Kevin R Loughlin,a well-known urologist whose inquisitive mind had a flair for simplifying complex basic science research into clinically relevant information. Their research revolved around the assessment of sperm function with a focus of utilizing basic research knowledge to investigate specific clinical problems of male infertility.
 
Upon completion of his post-doctoral training in 1986, Ashok took on the position of Director of the Clinical Andrology Laboratory and Sperm Bank at the Newton-Wellesley Hospital in Boston (Medical Director: Late Dr. Robert “Bob” Newton) where he gained valuable experience in managing a busy clinical facility for two years. In 1988, Ashok was appointed at the Harvard Medical School as the Director of the Andrology Laboratory and as an Instructor in Surgery in the Division of Urology. Along with his teaching position, Ashok also served as the Coordinator of Andrology Testing in the Reproductive Endocrinology Laboratory at the Brigham and Women's Hospital. Here he deepened his study of andrology and gained further experience in directing and conducting research in male infertility. Equipped with newer and wider research skillsets, Ashok was promoted to Assistant Professor in the Division of Urology and Director of Male Infertility Research at Harvard.
 
Ashok was recruited in 1993 to head the Clinical Andrology Center at the Cleveland Clinic in Ohio. Ashok takes immense pride in having built the Clinical Andrology Laboratory from the ground up to become one of the finest advanced diagnostic facilities of its kind in the United States. At present, this specialized clinical laboratory provides a wide variety of comprehensive testing and diagnostic modalities for infertile couples and fertility preservation services utilizing latest technological advances to meet patient needs. The laboratory’s fertility preservation services include a reliable system for the long-term preservation of human semen, epididymal aspirate and testicular tissue.
 

Ashok and co-workers at the Andrology Center designed and co-developed the novel NextGen® Home Sperm Banking kit (Agarwal, Sharma et al. 2016). This home sperm banking program allows patients to collect semen specimens in the privacy of their own homes. The specimens can then be shipped overnight in a specially designed container that preserves sperm function and fertilizing capacity. Ashok and his team were presented with Innovator Awards in 2011 and 2012 for their pioneering remote sperm banking program that provides a safe and reliable practice for storage of semen samples. The Andrology Center continues to develop new and more precise sperm function tests for diagnostic purposes.

 

In addition to these clinical services, Ashok is responsible and heavily involved in basic and translational research in the fields of male infertility and human assisted reproduction. Ashok’s research interests were centred on studies of oxidative stress and its impact on the male fertility potential. In 1999, Ashok’s team described a novel measure of oxidative stress, the ROS–TAC score, which could be used to discriminate fertile men from infertile ones (Sharma, Pasqualotto et al. 1999). Ashok and co-workers proposed the ROS–TAC score as an important measure to identify those patients with a clinical diagnosis of male infertility whose female partners were likely to become pregnant.

 
Ashok and his colleagues observed that DNA damage and ROS production were significantly higher in immature spermatozoa (with abnormal head morphology and cytoplasmic retention) than inmature ones. This led the team to propose that as sperm migrate from the seminiferous tubules to the epididymis, mature spermatozoa could be subjected to oxidative DNA damage by the presence of ROS-producing immature spermatozoa, leading to infertility in some men (Gil-Guzman, Ollero et al. 2001; Ollero, Gil-Guzman et al. 2001).
 
Ashok and his research team investigated ROS levels and their relationship with sperm quality in infertile men. They proposed that high ROS levels are an independent marker of male factor infertility, regardless of whether the normal or abnormal semen parameters in those patients (Agarwal, Sharma et al. 2006). Another study showed that sperm DNA damage is significantly increased in 1) men with idiopathic infertility, 2) men with male factor infertility and 3) men who failed to initiate a pregnancy after assisted reproductive techniques (Saleh, Agarwal et al. 2003). They also found that regardless of the clinical diagnosis and semen characteristics in infertile males, the presence of seminal oxidative stress was suggestive of its role in the pathophysiology of infertility (Pasqualotto, Sharma et al. 2000). Moreover, it was also demonstrated that infertile men with varicoceles have significantly increased sperm DNA damage that appeared to be related to elevated seminal oxidative stress levels (Saleh, Agarwal et al. 2003). In patients with male factor infertility, Ashok and colleagues have also reported a positive relationship between increased ROS-induced sperm damage and higher levels of cytochrome c and caspases 9 and 3, indicating positive apoptosis (Wang, Sharma et al. 2003).
 
Ashok and his team also showed that supplementing embryo culture media with L-carnitine improved the blastocyst development rate and reduced the level of DNA damage in developing embryos, which could lead to a higher yield of good-quality embryos. This approach had the potential for significant clinical applications in the setting of ART, particularly in terms of improving fertility outcomes and cost (Abdelrazik, Sharma et al. 2009). For these useful research findings, Ashok received an Innovation Award from Cleveland Clinic in 2007.
 
In the past eight years, Ashok and his collaborators have focused on studies relating to sperm and seminal plasma proteomics and bioinformatics in the search for biomarkers of various conditions in infertility, including varicocele and cancer. Using the high-throughput LC-MS/MS technique, Ashok’s research team successfully profiled sperm and seminal plasma proteins in males diagnosed with oxidative stress induced infertility - a first in the field of sperm proteomics. The study outcomes were published in 2013 as two research articles: 1) Proteomic analysis of human spermatozoa proteins with oxidative stress (Sharma, Agarwal et al. 2013) and 2) Proteomic analysis of seminal fluid from men exhibiting oxidative stress (Sharma, Agarwal et al. 2013). These findings were a breakthrough in the scientific community to further identify the molecular factors that are dysfunctional in infertile men with oxidative stress-related infertility.
 
Ashok and his research team have extended their expertise in the area of proteomics to demonstrate the prognostic and diagnostic protein biomarkers in varicocele-mediated male infertility. Ashok’s laboratory applied proteomics and functional bioinformatics analyses to examine the effect of varicocele on the onset of infertility and to identify the underlying alteration in the protein profile. A 2018 study with his international collaborators on Proteomic signatures of sperm mitochondria in varicocele (Samanta, Agarwal et al. 2018) reported that impaired mitochondrial structure and function in varicocele may lead to oxidative stress and sperm dysfunction. They predicted that mitochondrial electron-transport chain (ETC) proteins (NDFSU1, UQCRC2 and COX5B) may serve as non-invasive biomarkers of sperm function in patients with varicocele and may assist in the development of mitochondria targeted antioxidant-based approaches. These findings are considered an important landmark in varicocele proteomics research. Recently, Agarwal and his team have proposed a novel pathway showing aberrant redox homeostasis against chronic hypoxic insult in varicocele leading to sperm dysfunction (Swain, Samanta, Agarwal et al. 2019).
 
At present, Ashok’s research team is focused on the study of male cancer patients facing infertility issues. Under his guidance, Ashok’s laboratory has conducted sperm proteomic studies to investigate the molecular pathways associated with altered reproductive functions in men with testicular cancer and Hodgkin’s lymphoma. In the future, the team is planning to develop proteomic-based novel diagnostic tests for male infertility and sperm function to achieve better pregnancy outcomes with semen samples from cancer patients.
 
Ashok maintains successful research collaborations with more than a hundred prominent researchers in the field of andrology and male infertility, both locally and internationally. Among his most active collaborators are Professor Ralf Henkel (University of the Western Cape, Belville, South Africa), Professor Luna Samanta (Ravenshaw University, Odisha, India), Dr. Sandro Esteves (Medical Director, ANDROFERT Center, Campinas, Brazil), Drs. Mohamed Mostafa Arafa and Ahmad Majzoub (Specialists in Male Infertility, Hamad Medical Corporation, Doha, Qatar), Associate Professor Dr. Damayanthi Durairajanayagam (Universiti Teknologi MARA, Sungai Buloh, Malaysia), Dr. Saradha Baskaran (New Jersey, USA) and Dr. Cho Chak Lam (Specialist in Male Infertility, Kwong Wah Hospital, Hong Kong). Ashok’s exceptional research productivity and outstanding research collaboration were recognized with an award by Hamad Medical Corporation in 2018.
 
Ashok and his collaborators worldwide are strong advocates of sperm DNA fragmentation testing as an adjunct to routine semen analysis. They have developed practice recommendations based on clinical scenarios describing the clinical utility and value of sperm DNA fragmentation testing in infertile men (Agarwal, Majzoub et al. 2016). The Andrology Center is also a keen supporter of the TUNEL assay using flow cytometry to measure sperm DNA fragmentation. Ashok and his team have described a step-by-step protocol for most precise measurement of sperm DNA fragmentation using the TUNEL assay as well as the inter-laboratory and intra-laboratory standardization of the TUNEL assay using a bench-top flow cytometer (Gupta, Sharma et al. 2017).
 
Ashok’s collaborative efforts (with 90 experts from 26 countries) have resulted in the proposal of the oxidation-reduction potential (ORP, measured using the MiOXSYS™ analyzer) as a suitable clinical biomarker for males with abnormal semen parameters and oxidative stress. This alternative method of assessing oxidative stress is quick, easy, reliable and cost-effective. Ashok’s team has also suggested a standardised method of reliably measuring ORP levels in semen and seminal plasma using the MiOXSYS analyzer in a clinical setting (Agarwal, Sharma et al. 2016).
 
Most recently, Ashok and collaborators introduced the term Male Oxidative Stress Infertility (MOSI) as a novel descriptor of a distinct male infertility diagnosis for infertile men with abnormal semen characteristics and oxidative stress, including patients previously classified as having idiopathic male infertility. They have also have suggested that ORP is a useful clinical biomarker for the classification of MOSI that could then offer a more targeted and reliable approach for managing antioxidant therapy (Agarwal, Parekh et al. 2019).
 
Over the years, Ashok’s laboratory has trained more than 500 clinicians, scientists, and researchers from over 55 countries. In addition, over 500 medical, undergraduate, and highschool students have gained exposure into the field by working in his laboratory. During the program’s developmental years, Ashok received firm support from the late Professor Andrew Novick (former Chair of Urology, Cleveland Clinic) and constant advice and encouragement from his senior colleague and close friend, the late Dr Anthony Thomas (former, Head of Male Infertility at Cleveland Clinic) and in more recent years, from Professors Edmund Sabanegh (President, Cleveland Clinic, Main Hospital) and Eric Klein (Institute Chair, Glickman Urology and Kidney Institute, Cleveland Clinic).
 
Ashok is the Director of the highly successful annual Summer Internship Course in Reproductive Medicine. The one-of-a-kind program is Ashok’s brain-child and just completed its twelfth year. Solid emphasis is placed on the six pillars of the course, i.e. building knowledge in reproductive medicine/andrology, hands-on laboratory research training, training in applied biostatistics, scientific writing and public speaking, as well as soft skill development during the four weeks of the program. Not only do students and young researchers gain valuable experience in research, scientific presentation and writing, they gain exposure to cutting-edge research topics and the opportunity to be mentored by renowned figures in reproductive medicine and biology.
 
In the last decade, more than 270 local and international pre-med and medical students have graduated from this unique program. Ashok’s innovative course has been thrice-recognized in the form of a prestigious Scholarship in Teaching Award by the Case Western Reserve University Medical School in 2011, 2013, and 2014.  In addition, Ashok’s laboratory offers a unique ART course that includes comprehensive, hands-on training in human assisted reproduction (Embryology and Andrology techniques). To date, the American Center for Reproductive Medicine has provided hands-on training in ART techniques to more than 200 candidates from 44 countries. This program is the only one of its kind across the USA and is held annually in September and October. It offers multiple comprehensive training modules, which are fully customizable by the candidate. Over the years, the program has garnered excellent satisfaction rates by the trainees. The local and international training faculty include clinical embryologists, IVF and male infertility specialists. The Training Program in Advanced Reproductive Techniques also achieved repeated recognition by the Case Western Reserve University Medical School with a prestigious Scholarship in Teaching Award in 2013 and 2014.
 
Deeply passionate about his work, Ashok remains fully active in basic and clinical research. His research interests include molecular markers of oxidative stress, DNA integrity, apoptosis in the pathophysiology of male and female reproduction, cryopreservation of spermatozoa in patients with cancer, epididymal physiology, and the effects of radio frequency radiation on fertility and fertility preservation in patients with cancer. In recent years, his laboratory has channelled its focus on the use of proteomics and bioinformatics tools in discovering the biological processes and pathways underlying oxidative stress-induced infertility. A new study published in Antioxidants journal by Ashok and his group showed for the first time that antioxidant supplementation (FH RRO) in idiopathic infertile men improves sperm function at the molecular level by modulating proteins involved in CREM signaling, mitochondrial function and protein oxidation (Agarwal, Panner Selvam et al 2019). According to Scopus, Ashok’s Lab is the current world leader in Sperm Proteomics research based on the number of peer reviewed original articles published in high impact journals.
 
Ashok and his wife, Meenu, have two sons, Rishi an investment banker at Cleveland and Neil Yogi who is a senior at the Washington University in St. Louis. The family lives in Moreland Hills, an eastern suburb of Cleveland with their Beagle-Corgi mix puppy, Chotoo.
 
 
 
Relevant publications:
 
Abdelrazik, H., R. Sharma, R. Mahfouz and A. Agarwal (2009). "L-Carnitine decreases DNA damage and improves the in vitro blastocyst development rate in mouse embryos." Fertility and Sterility 91(2): 589-596.
Agarwal, A., A. Majzoub, S. C. Esteves, E. Ko, R. Ramasamy and A. Zini (2016). "Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios." TranslAndrolUrol 5(6): 935-950.
Agarwal, A., M.K. PannerSelvam, L. Samanta, S.C. Vij, N. Parekh, E. Sabanegh, N.N. Tadros, M. Arafa and R. Sharma.(2019). “Effect of antioxidant supplementation on the sperm proteome of idiopathic infertile men.” Antioxidants (Basel) 8(10).
Agarwal, A., N. Parekh, M. K. PannerSelvam, R. Henkel, R. Shah, S. T. Homa, R. Ramasamy, E. Ko, K. Tremellen, S. Esteves, A. Majzoub, J. G. Alvarez, D. K. Gardner, C. N. Jayasena, J. W. Ramsay, C.-L. Cho, R. Saleh, D. Sakkas, J. M. Hotaling, S. D. Lundy, S. Vij, J. Marmar, J. Gosalvez, E. Sabanegh, H. J. Park, A. Zini, P. Kavoussi, S. Micic, R. Smith, G. M. Busetto, M. E. Bakırcıoğlu, G. Haidl, G. Balercia, N. G. Puchalt, M. Ben-Khalifa, N. Tadros, J. Kirkman-Browne, S. Moskovtsev, X. Huang, E. Borges, D. Franken, N. Bar-Chama, Y. Morimoto, K. Tomita, V. S. Srini, W. Ombelet, E. Baldi, M. Muratori, Y. Yumura, S. La Vignera, R. Kosgi, M. P. Martinez, D. P. Evenson, D. S. Zylbersztejn, M. Roque, M. Cocuzza, M. Vieira, A. Ben-Meir, R. Orvieto, E. Levitas, A. Wiser, M. Arafa, V. Malhotra, S. J. Parekattil, H. Elbardisi, L. Carvalho, R. Dada, C. Sifer, P. Talwar, A. Gudeloglu, A. M. A. Mahmoud, K. Terras, C. Yazbeck, B. Nebojsa, D. Durairajanayagam, A. Mounir, L. G. Kahn, S. Baskaran, R. D. Pai, D. Paoli, K. Leisegang, M.-R. Moein, S. Malik, O. Yaman, L. Samanta, F. Bayane, S. K. Jindal, M. Kendirci, B. Altay, D. Perovic and A. Harlev (2019). "Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility." World J Mens Health 37.
Agarwal, A., R. Sharma, S. Roychoudhury, S. Du Plessis and E. Sabanegh (2016). "MiOXSYS: a novel method of measuring oxidation reduction potential in semen and seminal plasma." Fertility and Sterility 106(3): 566-573.e510.
Agarwal, A., R. Sharma, A. Singh, S. Gupta and R. Sharma (2016). "Standardisation of a novel sperm banking kit – NextGen® – to preserve sperm parameters during shipment." Andrologia 48(6): 662-669.
Agarwal, A., R. K. Sharma, K. P. Nallella, A. J. Thomas, Jr., J. G. Alvarez and S. C. Sikka (2006). "Reactive oxygen species as an independent marker of male factor infertility." Fertility and Sterility 86(4): 878-885.
Gil-Guzman, E., M. Ollero, M. C. Lopez, R. K. Sharma, J. G. Alvarez, A. J. Thomas, Jr and A. Agarwal (2001). "Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation." Human Reproduction 16(9): 1922-1930.
Gupta, S., R. Sharma and A. Agarwal (2017). "Inter-and Intra-Laboratory Standardization of TUNEL Assay for Assessment of Sperm DNA Fragmentation." Current Protocols in Toxicology 74(1): 16.11.11-16.11.22.
Ollero, M., E. Gil-Guzman, M. C. Lopez, R. K. Sharma, A. Agarwal, K. Larson, D. Evenson, A. J. Thomas, Jr and J. G. Alvarez (2001). "Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility." Human Reproduction 16(9): 1912-1921.
Pasqualotto, F. F., R. K. Sharma, D. R. Nelson, A. J. Thomas, Jr. and A. Agarwal (2000). "Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation." Fertility and Sterility 73(3): 459-464.
Saleh, R. A., A. Agarwal, E. A. Nada, M. H. El-Tonsy, R. K. Sharma, A. Meyer, D. R. Nelson and A. J. Thomas, Jr. (2003). "Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility." Fertility and Sterility 79: 1597-1605.
Saleh, R. A., A. Agarwal, R. K. Sharma, T. M. Said, S. C. Sikka and A. J. Thomas, Jr. (2003). "Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele." Fertility and Sterility 80(6): 1431-1436.
Samanta, L., A. Agarwal, N. Swain, R. Sharma, B. Gopalan, S. C. Esteves, D. Durairajanayagam and E. Sabanegh (2018). "Proteomic Signatures of Sperm Mitochondria in Varicocele: Clinical Use as Biomarkers of Varicocele Associated Infertility." Journal of Urology 200(2): 414-422.
Sharma, R., A. Agarwal, G. Mohanty, S. S. Du Plessis, B. Gopalan, B. Willard, S. P. Yadav and E. Sabanegh (2013). "Proteomic analysis of seminal fluid from men exhibiting oxidative stress." ReprodBiolEndocrinol 11: 85.
Sharma, R., A. Agarwal, G. Mohanty, A. J. Hamada, B. Gopalan, B. Willard, S. Yadav and S. du Plessis (2013). "Proteomic analysis of human spermatozoa proteins with oxidative stress." ReprodBiolEndocrinol 11: 48.
Sharma, R. K., F. F. Pasqualotto, D. R. Nelson, A. J. Thomas, Jr and A. Agarwal (1999). "The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility." Human Reproduction 14(11): 2801-2807.
Swain, N., L.S. Samanta, A. Agarwal, S. Kumar, A. Dixit A, B. Gopalan B, D. Durairajanayagam, R. Sharma R, P.N. Pushparaj andS. Baskaran.(2019). “Aberrant upregulation of compensatory redox molecular machines may contribute to sperm dysfunction in infertile men with unilateral varicocele: A proteomic insight.” Antioxid Redox Signal. doi: 10.1089/ars.2019.7828.
Wang, X., R. K. Sharma, S. C. Sikka, A. J. Thomas, Jr., T. Falcone and A. Agarwal (2003). "Oxidative stress is associated with increased apoptosis leading to spermatozoa DNA damage in patients with male factor infertility." Fertility and Sterility 80(3): 531-535.