Akanksha Mehta

Emory University, Atlanta, Georgia, United States

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Publications (26)81.61 Total impact

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    ABSTRACT: To assess the concordance of sperm chromatin structure assay (SCSA) results, epifluorescence TUNEL assay results, and standard semen parameters. Prospective, observational study. Tertiary referral andrology clinic. A total of 212 men evaluated for subfertility by a single physician. Clinical history, physical examination, semen analysis, SCSA, and TUNEL assay. Spearman's rank correlation coefficients (r) between SCSA DNA fragmentation index (DFI), percentage TUNEL-positive sperm, and semen analysis parameters. There was a positive correlation between SCSA DFI and TUNEL (r = 0.31), but the strength of this correlation was weaker than has previously been reported. The discordance rate between SCSA and TUNEL in classifying patients as normal or abnormal was 86 of 212 (40.6%). The SCSA DFI was moderately negatively correlated with sperm concentration and motility. The TUNEL results were unrelated to standard semen parameters. The SCSA DFI and percentage TUNEL-positive sperm are moderately correlated measures of sperm DNA integrity but yield different results in a large percentage of patients. The DFI is well-correlated with semen analysis parameters, whereas TUNEL is not. These data indicate that the SCSA and TUNEL assay measure different aspects of sperm DNA integrity and should not be used interchangeably. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
    Fertility and sterility 05/2015; 104(1). DOI:10.1016/j.fertnstert.2015.04.023 · 4.59 Impact Factor
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    ABSTRACT: The aim of this study was to design a molecular assay for the diagnosis of Klinefelter syndrome (KS), based on the detection of supernumerary X-chromosomes (X-chs). DNA was extracted from peripheral blood samples of twenty-six 47,XXY males; two 46,XY/47,XXY males; twenty-two 46,XY males; and 15 females; and deaminated. Methylation-specific quantitative polymerase chain reaction (MS-qPCR) was performed using primers for unmethylated and methylated copies of the X-ch inactive-specific transcript (XIST-U and XIST-M) gene. X-ch disomy was determined on the basis of XIST methylation status. Degree of mosaicism in the 46,XY/47,XXY males was compared with karyotype and fluorescent in situhybridization (FISH) results. Data analysis was performed using the Roche; LightCycler software V. 3.5.3., including determination of crossing points (CPs) by fit-point analysis and melting curve analysis. X-ch disomy was detected in all female controls and KS patients; male controls expressed XIST-M only. CPs ranged from 29.5 to 32.5 (standard deviation (s.d.) 0.8) for XIST-U and from 29 to 31 (s.d. 0.6) for XIST-M. Limit of detection of mosaicism was 1%. Based on XIST-U/XIST-M ratios for the two 47,XXY/46,XY patients, the calculated degree of mosaicism (1.8% and 17.8%) was comparable to FISH results (2.3% and 15%, respectively). Turnaround time from DNA deamination to final data analysis was under 9 h. We conclude that MS-qPCR is a sensitive, specific and rapid test for the detection of X-ch disomy, with applicability for the screening and diagnosis of KS, even in the setting of low grade 47,XXY/46,XY mosaicism.
    Asian Journal of Andrology 05/2014; 16(5). DOI:10.4103/1008-682X.125914 · 2.53 Impact Factor
  • Akanksha Mehta · Theresa Clearman · Darius A. Paduch
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    ABSTRACT: Purpose We investigated the safety and tolerability of testosterone replacement therapy in adolescents with Klinefelter syndrome. Materials and Methods We reviewed the medical records of all consecutive adolescents with Klinefelter syndrome evaluated between 2007 and 2012. Patients receiving testosterone replacement and aromatase inhibitor therapy were identified. Data on demographics, physical characteristics, medical history and serum hormone concentrations were collected for each patient. We evaluated longitudinal changes in serum testosterone, luteinizing hormone and follicle-stimulating hormone as well as changes in body mass index after the initiation of testosterone replacement therapy. Results We identified 151 adolescents with Klinefelter syndrome. Mean age at presentation was 11.6 years. Testosterone replacement therapy and aromatase inhibitors were initiated in 110 and 75 patients, respectively, at an average age of 13 to 14 years. Topical testosterone replacement therapy was used in 95% of patients with good clinical efficacy and compliance based on serial serum testosterone values. After the initiation of testosterone replacement therapy average serum testosterone improved from 240 to 650 ng/ml. Serum luteinizing hormone and follicle-stimulating hormone increased with the progression of puberty from 2.6 to 16.6 and 7 to 42 mIU/ml, respectively. No adverse outcomes related to testosterone replacement therapy were reported. Conclusions Hormone supplementation with testosterone and aromatase inhibitors in adolescents with Klinefelter syndrome appears to be safe and effective for maintaining serum testosterone within the normal range. Compliance with topical formulations is high. Topical testosterone replacement therapy is not associated with the suppression of endogenous serum luteinizing hormone or follicle-stimulating hormone.
    The Journal of urology 05/2014; DOI:10.1016/j.juro.2013.09.015 · 3.75 Impact Factor
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    ABSTRACT: Estradiol (E2) modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30), a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. Isolated Leydig cells (LC) from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH) -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist), and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.
    PLoS ONE 04/2014; 9(4):e92425. DOI:10.1371/journal.pone.0092425 · 3.23 Impact Factor
  • The Journal of Urology 04/2014; 191(4):e803-e804. DOI:10.1016/j.juro.2014.02.2194 · 3.75 Impact Factor
  • Akanksha Mehta · Darius A Paduch · Peter N Schlegel
    Fertility and sterility 08/2013; DOI:10.1016/j.fertnstert.2013.08.001 · 4.59 Impact Factor
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    ABSTRACT: To evaluate surgical sperm retrieval rates in adolescents with Klinefelter syndrome and testosterone replacement therapy (TRT). Case series. Academic medical center. Ten patients with Klinefelter syndrome, aged 14-22 years, treated with testosterone replacement and aromatase inhibitor therapy for a period of 1-5 years before surgical sperm retrieval. Microsurgical testis sperm extraction with cryopreservation of harvested tissue. Presence of spermatozoa within testis tissue. Successful sperm retrieval in 7/10 patients (70%). Use of topical TRT did not appear to suppress spermatogenesis in adolescents with KS. It is uncertain whether sperm retrieval rates would be higher or lower without testosterone replacement in these young males. Sperm cryopreservation should be discussed in all KS adolescents who are either receiving or considering initiating TRT.
    Fertility and sterility 07/2013; 100(4). DOI:10.1016/j.fertnstert.2013.06.010 · 4.59 Impact Factor
  • Akanksha Mehta · Wayland Hsiao · Peggy King · Peter N Schlegel
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    ABSTRACT: PURPOSE:: To evaluate the effect of daily peri-operative celecoxib on patient-reported pain control and opioid use following testicular surgery. MATERIALS AND METHODS:: Men scheduled to undergo elective, outpatient microsurgical testicular sperm extraction were prospectively randomized to receive 200 mg of celecoxib or placebo b.i.d., initiated the night prior to surgery, and continued for six days thereafter. Using an 11-point visual analog scale, participants self-reported their post-operative pain level, and use of acetaminophen/hydrocodone for supplemental pain control. Differences in pain scores and opioid use between the two groups of patients were compared using Student's t-test. A p-value <0.05 was considered significant. RESULTS:: At one-year interim analysis, 35/78 (45%) of eligible participants had returned study questionnaires; 34 were included in the final analysis. Patients given celecoxib (16/34) had a significantly lower post-operative opioid use compared to patients given placebo (6 vs. 16 pills, p=0.02). A statistically significant difference in POD #1 and #2 patient-reported pain scores (4 vs. 6, p<0.05 and 3 vs. 5, p=0.03) and opioid use (1 vs. 5 pills, p<0.01 and 2 vs. 4 pills, p=0.02), was seen between the celecoxib and placebo groups, respectively. No study complications were identified. The trial was terminated early based the results of the interim analysis. CONCLUSIONS:: Twice daily celecoxib use, started pre-operatively, significantly reduces patient-reported post-operative pain and opioid use, especially in the early post-operative period. A short course of celecoxib is well-tolerated, and may be effectively used as part of a multimodal post-operative analgesia in patients undergoing testicular surgery for sperm retrieval.
    The Journal of urology 04/2013; 190(5). DOI:10.1016/j.juro.2013.04.058 · 3.75 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e940. DOI:10.1016/j.juro.2013.02.2235 · 3.75 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e836-e837. DOI:10.1016/j.juro.2013.02.2456 · 3.75 Impact Factor
  • The Journal of Urology 04/2013; 189(4):e654. DOI:10.1016/j.juro.2013.02.3143 · 3.75 Impact Factor
  • Akanksha Mehta · Wayland Hsiao · Peggy King · Peter Schlegel
    The Journal of Urology 04/2013; 189(4):e773-e774. DOI:10.1016/j.juro.2013.02.2305 · 3.75 Impact Factor
  • Akanksha Mehta · Doron S Stember · Keith O'Brien · John P Mulhall
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    ABSTRACT: Men presenting with chronic pelvic pain syndrome (CPPS) frequently report concomitant erectile dysfunction (ED), but the underlying cause of ED in this patient population has not been previously studied. This study prospectively investigated the aetiology of ED in men with CPPS. The study population comprised 46 men with penile pain or dysorgasmia, and concomitant ED. All participants completed the NIH-CPSI and international index of erectile function- erectile function domain (IIEF-EFD) questionnaires, and underwent penile duplex Doppler ultrasonography (DUS), following intracavernosal trimix injection, to evaluate erectile hemodynamic parameters. Pearson's correlation between NIH-CPSI and IIEF-EFD scores, and between NIH-CPSI score and the erectile response to trimix injections was investigated. The prevalence of mild, moderate and severe CPPS symptoms was 26, 48 and 26% respectively. The severity of ED was mild, moderate or severe in 15, 61 and 24% of men respectively. NIH-CPSI and IIEF-EFD scores were negatively correlated (r = -0.32, p = 0.002). Peak systolic velocity (PSV) and end-diastolic velocity (EDV) were normal in 96 and 100% of men respectively. The majority of men (78%) required ≥2 trimix injections to attain an adequate erection for DUS. NIH-CPSI scores and the number of trimix injections needed were positively correlated (r = 0.22, p = 0.035). The aetiology of erectile dysfunction in men who present with CPPS and concomitant ED is almost always psychogenic. Penile DUS in this population of men is fraught with the potential for error, and frequently necessitates more than one dose of a vasoactive agent.
    Andrology 02/2013; 1(3). DOI:10.1111/j.2047-2927.2013.00066.x · 3.37 Impact Factor
  • Akanksha Mehta · Darius A. Paduch
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    ABSTRACT: The diagnosis of testosterone deficiency requires the presence of symptoms and low serum testosterone levels. Significant intra-individual fluctuations in serum testosterone levels, the wide range of testosterone levels in human serum samples, and technical limitations of currently available assays have led to poor reliability of testosterone measurements in the clinical laboratory setting. Although there is no universally accepted threshold of testosterone concentration that distinguishes eugonadal from hypogonadal men, a testosterone concentration below 300 ng/dL is suggestive of testosterone deficiency in the appropriate clinical setting. The laboratory evaluation of testosterone deficiency should begin with the measurement of total testosterone using a sensitive and reproducible method, and may include free or bioavailable testosterone if the total testosterone is close to the lower limit of the normal range or discordant with the clinical presentation, or when altered levels of sex-hormone binding globulin are suspected. This chapter reviews the multitude of biological and technical factors that affect serum testosterone measurements. It also discusses the currently used assays for testosterone measurement, their utility and limitations, and implications for clinical practice.
    Androgen Deficiency and Testosterone Replacement, 01/2013: pages 15-31; , ISBN: 978-1-62703-178-3
  • Akanksha Mehta · Darius A. Paduch · Marc Goldstein
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    ABSTRACT: The goal of testosterone replacement therapy (TRT) is to alleviate the symptoms of hypogonadism while minimizing potential adverse affects associated with testosterone replacement. There are several approved options available for the treatment of androgen deficiency, including oral, transdermal, injectable, and implantable formulations of testosterone, as well as emerging therapies such as selective androgen receptor modulators (SARMs), each associated with specific advantages, disadvantages, and side effects. In men with an identifiable etiology of hypogonadism, the underlying pathology should be addressed first. For men interested in fertility, androgen deficiency may be treated with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropin therapy using human chorionic gonadotropin (hCG), purified or recombinant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) preparations. The empiric use of selective estrogen receptor modulators (SERMs) and aromatase inhibitors for the treatment of men with primary hypogonadism is associated with variable outcomes, depending on the severity of the underlying defect. The choice of therapy should be guided by consideration of the formulation-specific pharmacokinetics and adverse effects, cost, and patient preference. All patients on any form of TRT should be evaluated on a regular basis.
    Clinical Urologic Endocrinology, 01/2013: pages 59-87; , ISBN: 978-1-4471-4404-5
  • Open Journal of Urology 01/2013; 03(04):173-178. DOI:10.4236/oju.2013.34032
  • Akanksha Mehta · Philip S Li
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    ABSTRACT: Microsurgical training is imperative for urologists and clinical andrologists specializing in male infertility. Success in male infertility microsurgery is heavily dependent on the surgeon's microsurgical skills. Laboratory-based practice to enhance microsurgical skills improves the surgeon's confidence, and reduces stress and operating time, benefiting both the patient and the surgeon. This review provides guidelines for setting up a microsurgical laboratory to develop and enhance microsurgical skills using synthetic and animal models. The role of emerging techniques, such as robotic-assisted microsurgery, is also discussed.Asian Journal of Andrology advance online publication, 19 November 2012; doi:10.1038/aja.2012.86.
    Asian Journal of Andrology 11/2012; DOI:10.1038/aja.2012.86 · 2.53 Impact Factor
  • Akanksha Mehta · Marc Goldstein
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    ABSTRACT: Varicocelectomy is the most commonly performed surgical procedure for the treatment of male infertility. Although several different techniques for varicocele repair have been described in the literature, microsurgical varicocelectomy performed through a subinguinal or inguinal incision is recognized as the gold-standard approach for varicocelectomy, due to high success rates with minimal complications. Standard indications for varicocelectomy include palpable varicocele(s), with one or more abnormal semen parameters, and, for the couple trying to conceive, in the setting of normal or correctable female infertility. However, varicocele repair is often recommended and undertaken for reasons other than infertility, including low serum testosterone, testicular pain, testicular hypotrophy and poor sperm DNA quality. This article reviews the technical aspects of microsurgical varicocelectomy, and its indications in adults and adolescents.Asian Journal of Andrology advance online publication, 12 November 2012; doi:10.1038/aja.2012.98.
    Asian Journal of Andrology 11/2012; 15(1). DOI:10.1038/aja.2012.98 · 2.53 Impact Factor
  • Akanksha Mehta · Darius A Paduch
    Fertility and sterility 09/2012; 98(5):e26. DOI:10.1016/j.fertnstert.2012.08.032 · 4.59 Impact Factor
  • Akanksha Mehta · Marc Goldstein
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    ABSTRACT: To evaluate the role of varicocelectomy in the management of patients with varicoceles and nonobstructive azoospermia and to review predictors of successful outcomes. Several small, retrospective, noncontrolled studies have documented return of sperm to the ejaculate in up to 56% of men with nonobstructive azoospermia (NOA) following varicocele repair. Additionally, a recent meta-analysis has reported a 6% spontaneous pregnancy rate in amongst NOA patients who underwent varicocele repair, regardless of surgical technique. Although these observations are promising, evidence for whether or not varicocele repair significantly improves spermatogenesis within an impaired testicle is conflicting. No clear predictors of success following varicocele repair have been identified, but a certain level of spermatogenesis on testicular biopsy appears to be necessary for a desirable outcome after varicocele repair. The role of varicocelectomy for the treatment on NOA is controversial. Prospective, controlled studies are needed in order to define the true benefit of varicocele repair in men with NOA, in terms of improvement in semen parameters, testicular sperm retrieval rates, and pregnancy outcomes.
    Current opinion in urology 08/2012; 22(6):507-12. DOI:10.1097/MOU.0b013e328358e27b · 2.12 Impact Factor

Publication Stats

63 Citations
81.61 Total Impact Points

Institutions

  • 2014–2015
    • Emory University
      • Department of Urology
      Atlanta, Georgia, United States
  • 2012–2014
    • Weill Cornell Medical College
      • Department of Urology
      New York City, New York, United States
  • 2013
    • Cornell University
      Итак, New York, United States