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INNOVATIONS IN MALE INFERTILITY RESEARCH

Cleveland Clinic's American Center for Reproductive Medicine
1993 - 2008

Clinical Infertility Research

 

We are conducting a variety of studies with immediate clinical implications in male infertility. Some of the areas that our clinical research encompasses include: reasons for rejecting potential donors from a sperm bank program; the relationship between semen quality and tobacco chewing in men undergoing infertility evaluation; significance of sperm characteristics in male infertility evaluation; assessing sperm structure and function; developing a model to predict whether vasoepididymostomy will be required for vasectomy reversal; relationship of adolescent gynecomastia with varicocele and somatometric parameters; and a retrospective study that examines the effect of patient and semen characteristics on live birth rates following intrauterine insemination.

  • PDF File (agradoc036.pdf 1168 Kb)
    Sidhu RS, Sharma RK, Kachoria S, Curtis C, Agarwal A (1997):
    Reasons for rejecting potential donors from a sperm bank program.
    J Assist Reprod Genet 14:354-359.
     
  • PDF File (agradoc049.pdf 920 Kb)
    Carbone DJ Jr, Shah A, Thomas AJ Jr, Agarwal A (1998):
    Partial obstruction, not antisperm antibodies, causing infertility after vasovasostomy.
    J Urol 159:827-830.
     
  • PDF File (ladoc23.pdf 24 Kb)
    Agarwal A (1999):
    Your genome - just another credit card to carry around [letter].
    Fertil Steril 72:378-9.
     
  • PDF File (agradoc73.pdf 20 Kb)
    Agarwal A (1999):
    Do herbal supplements impair male fertility? An expert responds to the Loma Linda studies.
    Healthnotes 6:74-75.
     
  • PDF File (agradoc75.pdf 41 Kb)
    Pasqualotto F, Agarwal A, Srivastava M, Nelson D, Thomas AJ Jr (1999):
    Fertility outcome after repeat vasoepididymostomy.
    J Urol 162:1626-1628.
     
  • PDF File (agradoc79.pdf 420 Kb)
    Hendin B, Falcone T, Hallak J, Nelson D, Vemulapalli S, Goldberg J, Thomas AJ Jr, Agarwal A (2000):
    The effect of patient and semen characteristics on live birth rates following intrauterine insemination: a retrospective study.
    J Assist Reprod Genet 17:245-252.
     
  • PDF File (agradoc80.pdf 101 Kb)
    Hendin BN, Falcone T, Hallak J, Goldberg J, Thomas AJ Jr, Nelson D, Agarwal A (2000):
    Effect of clinical and semen characteristics on efficacy of ovulatory stimulation in patients undergoing intrauterine insemination.
    J Assist Reprod Genet 17:189-193.
     
  • PDF File (agradoc101.pdf 50 Kb)
    Singh M, Goldberg J, Falcone T, Nelson DR, Pasqualotto E, Attaran M, Agarwal A (2001):
    Superovulation and intrauterine insemination in cases of treated mild pelvic disease.
    J Assist Reprod Genet 18:26-29.
     
  • PDF File (agradoc137.pdf 65 Kb)
    Pasqualotto FF, Pasqualotto EB, Agarwal A, Thomas AJ Jr (2003):
    Results of microsurgical anastomosis in men with seminal tract obstruction due to inguinal herniorrhaphy.
    Rev Hosp Clin Fac Med S Paulo 58:305-309.
     
  • PDF File (agradoc115.pdf 63 Kb)
    Saleh RA, Ranga GM, Raina R, Nelson DR, Agarwal A (2003):
    Sexual dysfunction in men undergoing infertility evaluation: a cohort observational study.
    Fertil Steril 79:909-912.
     
  • PDF File (cirdoc012.pdf 79 Kb)
    Agarwal A (2003):
    Sexual dysfunction in men undergoing infertility evaluation: a cohort observational study. Letter to the Editor.
    Fertil Steril 80:1542-1543.
     
  • PDF File (agradoc171.pdf 718 Kb)
    Kumanov P, Nandipati KC, Tomova A, Robeva R, and Agarwal A (2005):
    The significance of inhibin in reproductive pathophysiology and current clinical applications. Review article.
    Reprod Biomed Online 10:786-96.
     
  • PDF File (agradoc176.pdf 360 Kb)
    Hussein MR, Abou-Deif ES, Bedaiwy MA, Said TM, Mustafa MG, Nada E, Ezat A, Agarwal A (2005):
    Phenotypic characterization of the immune and mast cell infiltrates in the human testis showing normal and abnormal spermatogenesis.
    Fertil Steril 83:1447-53.
     
  • PDF File (agradoc178.pdf 99 Kb)
    Parekattil SJ, Kuang W, Agarwal A, Thomas, AJ Jr(2005):
    Model to predict if a vasoepididymostomy will be required for vasectomy reversal.
    J Urol 173:1681-4.
     
  • PDF File (agradoc187.pdf 141 Kb)
    Said TM, Ranga G, and Agarwal A (2005):
    Relationship between semen quality and tobacco chewing in men undergoing infertility evaluation.
    Fertil Steril 84:649-53.
     
  • PDF File (agradoc201.pdf 450 Kb)
    Aziz N, Agarwal A, Nallella KP, Thomas AJ Jr (2006):
    Relationship between epidemiological features and aetiology of male infertility as diagnosed by a comprehensive infertility service provider.
    Reprod Biomed Online 12:209-14.
     
  • PDF File (agradoc205.pdf 102 Kb)
    Nallella KP, Sharma RK, Aziz NF, Agarwal A (2006):
    Significance of sperm characteristics in male infertility evaluation.
    Fertil Steril 85:629-34.
     
  • PDF File (agradoc242.pdf 424 Kb)
    Fnu D, Chowdary H, Agarwal A (2007):
    Role of metabolomic analysis biomarkers in the management of male infertility.
    Expert Review of Molecular Diagnostics 7:351-58.
     
  • PDF File (agradoc244.pdf 378 Kb)
    Kumanov P, Deepinder F, Robeva R, Tomova A, Li J, Agarwal A (2007):
    Relationship of adolescent gynecomastia with varicocele and somatometric parameters: A cross-sectional study in 6200 healthy boys.
    Journal of Adolescent Health 41:126-31.
     
  • PDF File (agradoc250.pdf 388 Kb)
    Fnu D, Makker K, Agarwal A (2007):
    Cell phone and male infertility: Dissecting the relationship. Review Article.
    RBM Online 15:266-70.
     
  • PDF File (agradoc239.pdf 174 Kb)
    Agarwal A, Deepinder F, Rakesh S, Ranga G, Li J (2007):
    Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study.
    Fertil Steril. January 2008; 124-128.
     
  • PDF File (agradoc256.pdf 470 Kb)
    Varghese AC, Goldberg E, Bhattacharyya AK, Agarwal A (2007):
    Emerging technologies for the molecular study of infertility and potential clinical applications. Review Article.
    RBM Online 15: 451-56.
     
  • PDF File (agradoc260.pdf 55 Kb)
    Aziz N, Agarwal A (2007):
    Evaluation of sperm damage: Beyond the WHO criteria. Commentary. Review article.
    Fertil Steril. 2007 Oct 20; [Epub ahead of print].
     
  • PDF File (agradoc262.pdf 948 Kb)
    Varghese AC, Goldberg E, Agarwal A (2007):
    Current and future perspectives on intracytoplasmic sperm injection: a critical commentary. Review Article.
    RBM Online Vol 15 No 6. 2007: 719-727.
     
  • PDF File (agradoc264.pdf 310 Kb)
    Coccuzza M, Agarwal A (2007):
    Nonsurgical treatment of Male infertility: Specific and empiric Therapy. Review Article.
    Biologics: Targets & Therapy 2007:1(3) 259-269.
     
  • Tomova T, Makker M, Kirilov G, Agarwal A, Kumanov P (2007):
    Disturbances in gonadal axis in women with anorexia nervosa.
    Eating and Weight Disorders (In Press).
     
  • Agarwal A, Bragais F, Makker K. (2007):
    Laboratory assessment of male infertility: A guide for the urologist.
    Business Briefing - US Genitourinary Disease (In Press).
     
  • Agarwal A, Bragais FM, Sabanegh E. (2007):
    Assessing sperm structure and function: Current status: Review Article.
    Urological Clinics of North America (In Press).
     

Cryobiology of Human Spermatozoa

 

Various methods of cryopreservation have been evaluated for their effects on sperm motility; optimal dose and duration of exposure to artificial stimulants in cryopreserved human spermatozoa; suitability of the hypoosmotic swelling test for assessing the viability of cryopreserved sperm; sperm quality improvement in cryopreserved human semen; influence of artificial stimulation on unprocessed and Percoll-washed cryopreserved sperm; effect of centrifuge speed, refrigeration medium, and sperm washing medium on cryopreserved spermatozoa quality after thawing; effect of in vitro incubation on spontaneous acrosome reaction in fresh and cryopreserved human spermatozoa; improvement in motion characteristics and acrosome status in cryopreserved human spermatozoa by swim-up processing before freezing.

During cryopreservation, spermatozoa are exposed to physical and chemical stress, changes in lipid composition of sperm plasma membrane, reduced head size, and externalization of phosphatidylserine residues Factors contributing to these changes include temperature, maturity of the cell, cryoprotectant used, and cooling rate. Ejaculated human spermatozoa show evidence of DNA fragmentation and plasma membrane translocation of phosphatidyl serine. Recently, caspase activation also has been demonstrated. These characteristics are typical of programmed cell death in somatic cells. We have demonstrated that selection of annexin V-negative mature spermatozoa might be of clinical relevance for fertility preservation, as this sperm fraction shows no activated apoptosis during the cryopreservation process.

Furthermore, using super-paramagnetic annexin V-conjugated microbeads, we have shown that we are able to eliminate spermatozoa with externalized phosphatidylserine, a membrane feature of apoptotic cells, as well as spermatozoa with deteriorated plasma membrane. We have evaluated the effects of annexin V magnetic-activated cell sorting (MACS) in cryopreservation-thawing protocols and on integrity of sperm mitochondrial transmembrane potential and mitochondrial integrity survival rate (MSR). MACS using annexin V microbeads enhances the percentage of spermatozoa with intact transmembrane mitochondrial potential and mitochondrial integrity survival rates following cryopreservation.

  • PDF File (agradoc27.pdf 444 Kb)
    Sharma RK, Tolentino MV Jr, Agarwal A. (1996):
    Sperm kinematics of cryopreserved normozoospermic specimens following artificial stimulation.
    Urology 47:77-81.
     
  • PDF File (agradoc030.pdf 1321 Kb)
    Esteves SC, Sharma RK, Thomas AJ Jr, Agarwal A. (1996):
    Suitability of the hypo-osmotic swelling test for assessing the viability of cryopreserved sperm.
    Fertil Steril 66:798-804.
     
  • PDF File (agradoc026.pdf 1085 Kb)
    Sharma RK, Tolentino MV Jr, Thomas AJ Jr, Agarwal A (1996):
    Optimal dose and duration of exposure to artificial stimulants in cryopreserved human spermatozoa.
    J Urol 155:568-573.
     
  • PDF File (agradoc028.pdf 1235 Kb)
    Sharma RK and Agarwal A (1996):
    Sperm quality improvement in cryopreserved human semen.
    J Urol 156:1008-1012.
     
  • PDF File (agradoc033.pdf 848 Kb)
    Sharma RK and Agarwal A (1997):
    Influence of artificial stimulation on unprocessed and Percoll-washed cryopreserved sperm.
    Arch Androl 38:173-179.
     
  • PDF File (agradoc034.pdf 1212 Kb)
    Sharma RK, Padron OF, Agarwal A (1997):
    Usefulness of the acrobead test in evaluating human acrosome function in fresh and cryopreserved sperm.
    J Urol 157:1692-1696.
     
  • PDF File (agradoc037.pdf 704 Kb)
    Sharma RK, Vemulapalli S, Kohn S, Agarwal A. (1997):
    Effect of centrifuge speed, refrigeration medium, and sperm washing medium on cryopreserved spermatozoa quality after thawing.
    Arch Androl 39:33-38.
     
  • PDF File (agradoc041.pdf 3321 Kb)
    Sharma RK and Agarwal A (1997):
    Artificial stimulation of cryopreserved human spermatozoa by sodium nitroprusside, 2-chloroadenosine and 2-deoxyadenosoine.
    Eur Urol 32:344-352.
     
  • PDF File (agradoc42.pdf 603 Kb)
    Sharma RK, Padron OF, Thomas AJ Jr, Agarwal A (1997):
    Factors associated with the quality before freezing and after thawing of sperm obtained by microsurgical epididymal aspiration.
    Fertil Steril 68:626-631.
     
  • PDF File (agradoc46.pdf 449 Kb)
    Sidhu RS, Sharma RK, Agarwal A (1997):
    Effects of cryopreserved semen quality and timed intrauterine insemination on pregnancy rate and gender of offspring in a donor insemination program.
    J Assist Reprod Genet 14:531-537.
     
  • PDF File (agradoc48.pdf 546 Kb)
    Sidhu RS, Sharma RK, Lee J-C, Agarwal A (1998):
    Accuracy of computer-assisted semen analysis in pre-freeze and post-thaw specimens with high and low sperm counts and motility.
    Urology 51:306-312.
     
  • PDF File (agradoc57.pdf 81 Kb)
    Esteves SC, Sharma RK, Thomas AJ Jr, Agarwal A (1998):
    Cryopreservation of human spermatozoa with pentoxifylline improves the post-thaw agonist-induced acrosome reaction rate.
    Hum Reprod 13:3384-3389.
     
  • PDF File (agradoc58.pdf 38 Kb)
    Esteves SC, Sharma RK, Thomas AJ Jr, Agarwal A (1998):
    Effect of in vitro incubation on spontaneous acrosome reaction in fresh and cryopreserved human spermatozoa.
    Int J Fertil Womens Med 43:235-242.
     
  • PDF File (ladoc22.pdf 22 Kb)
    Esteves SC, Sharma RK, Thomas A.J Jr, Agarwal A (1999):
    Sperm viability assays - a matter of life and death [letter; comment].
    Fertil Steril 72:184-185.
     
  • PDF File (agradoc77.pdf 36 Kb)
    Hallak J, Sharma RK, Wellstead C, Thomas AJ Jr, Agarwal A. (2000):
    Cryopreservation of human spermatozoa: comparison of TEST-yolk buffer and glycerol.
    Int J Fertil Womens Med 45:38-42.
     
  • PDF File (agradoc85.pdf 121 Kb)
    Esteves SC, Sharma RK, Thomas AJ Jr, Agarwal A. (2000):
    Improvement in motion characteristics and acrosome status in cryopreserved human spermatozoa by swim-up processing before freezing.
    Hum Reprod 15:2173-2179.
     
  • PDF File (agradoc154.pdf 216 Kb)
    Nallella KP, Sharma RK, Allamaneni SSR, Aziz N, Agarwal A (2004):
    Cryopreservation of human spermatozoa: comparison of two cryopreservation methods and three cryoprotectants.
    Fertil Steril 82:913-8.
     
  • PDF File (agradoc158.pdf 517 Kb)
    Paasch U, Sharma RK, Gupta AK, Grunewald S, Mascha E, Thomas AJ Jr, Glander H-J, Agarwal A (2004):
    Cryopreservation and thawing is associated with varying extent of activation of apoptotic machinery in subsets of ejaculated human spermatozoa.
    Biol Reprod 71:1828-37.
     
  • PDF File (agradoc177.pdf 149 Kb)
    Said TM, Grunewald S, Paasch U, Rasch M, Agarwal A, Glander, H-J (2005):
    Effects of magnetic-activated cell sorting on sperm motility and cryosurvival rates.
    Fertil Steril 83:1442-6.
     
  • PDF File (agradoc208.pdf 191 Kb)
    Grunewald S, Paasch U, Said TM, Rasch M, Agarwal A, Glander H-J (2006):
    Magnetic-activated cell sorting before cryopreservation preserves mitochondrial integrity in human spermatozoa.
    Cell Tissue Bank 7:99-104.
     
  • PDF File (agradoc233.pdf 68 Kb)
    Prabakaran S, Agarwal A, Sundaram A, Thomas AJ Jr, Sikka S (2006):
    Cryosurvival of testicular spermatozoa from obstructive azoospermic patients: The Cleveland Clinic experience.
    Fertil Steril 86:1789-91.
     

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Last Update : December 11, 2008
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American Center for Reproductive Medicine
The Cleveland Clinic
10681 Carnegie Avenue, X11
Cleveland, OH 44195 USA
Tel: (216) 444-9485
Fax: (216) 445-6049
E-mail: CRM@ccf.org