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Paul J Turek - One of the best experts on this subject based on the ideXlab platform.
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isolation and characterization of pluripotent human spermatogonial stem cell derived cells
Stem Cells, 2009Co-Authors: Nina Kossack, Juanito J Meneses, Shai Shefi, Ha Nam Nguyen, Shawn L Chavez, Cory R Nicholas, J Gromoll, Paul J TurekAbstract:Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells) from spermatogonial stem cells obtained from the adult mouse Testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a Testis Biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus, and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8 weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human Testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming.
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variability in Testis Biopsy interpretation implications for male infertility care in the era of intracytoplasmic sperm injection
Fertility and Sterility, 2005Co-Authors: Matthew R Cooperberg, Thomas Chi, Amir Jad, Imok Cha, Paul J TurekAbstract:Objective To determine whether center to center discrepancies in the ability to locate sperm in infertile testes with abnormal histology stems in part from inconsistencies in pathologists' readings of Testis biopsies. Design Prospective cohort study. Setting Academic male infertility practice. Patient(s) Consecutive series of azoospermic men referred with Testis Biopsy slides between 1998 and 2003. Intervention(s) Testis Biopsy histologies on azoospermic patients referred for infertility care were re-reviewed by a single pathologist blinded to the original reading. Subsequent infertility care was guided by the findings from the second histologic reading. Main Outcome Measure(s) Agreement between the outside and in-house review of Testis Biopsy readings was assessed with the kappa statistic. Pregnancy outcomes that resulted from clinical decisions informed by the second histologic readings were also assessed. Result(s) Among 113 histologic specimens, re-review was complicated by fixation artifacts in 18 cases (16%) and insufficient Biopsy sample size in 13 cases (12%). The kappa score for interobserver agreement in readings was 0.43 (95% CI 0.32–0.054). Mixed histology patterns in particular were underappreciated by outside pathologists (13% of cases on original reading, 36% of cases on review). In 27% of all cases, the differences in Biopsy readings had a significant impact on clinical management. Conclusion(s) A correlation between independent Testis histology readings in azoospermic men demonstrates frequent inconsistencies. These differences contribute to inaccurate phenotyping of male infertility and can significantly impact the direction of infertility care. These findings highlight the need for a standardized approach to Testis histologic review.
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impaired spermatogenesis in men with congenital absence of the vas deferens
Human Reproduction, 2001Co-Authors: Maxwell V Meng, Lauri D Black, Brittmarie Ljung, Renee Reijo A Pera, Paul J TurekAbstract:It is generally assumed that men with congenital bilateral absence of the vas deferens (CBAVD) have azoospermia because of obstruction and that sperm production is normal. This study examines spermatogenesis in men with CBAVD to assess the validity of this assumption. We identified all men with CBAVD who had undergone either a diagnostic or therapeutic fertility procedure. Procedures included diagnostic Biopsy, Testis fine needle aspiration (FNA) mapping, microscopic epididymal sperm aspiration (MESA), and Testis sperm extraction (TESE). Among 33 CBAVD men, 18 underwent Testis Biopsy, 27 had MESA/TESE, and 10 had FNA mapping. On evaluation of these procedures, normal spermatogenesis was present in 29 men. Four men (12%) demonstrated impaired spermatogenesis. One patient had FNA Testis cytology consistent with late maturation arrest, another demonstrated hypospermatogenesis on Biopsy and low sperm yield by MESA, and two patients had pure Sertoli cell only histology on Biopsy. Aetiologies for impaired spermatogenesis included varicocele and underlying genetic abnormalities. Although patients with CBAVD are assumed to have normal spermatogenesis and infertility due simply to obstruction, the potential for concomitant defects in sperm production exists. A clinical suspicion of Testis failure should prompt further diagnostic evaluation of spermatogenesis prior to sperm retrieval. In addition, genetic counselling should be offered and testing for genetic lesions, including cystic fibrosis gene mutations and/or variants, Y chromosome microdeletions, and karyotype abnormalities, should be considered.
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systematic fine needle aspiration of the Testis correlation to Biopsy and results of organ mapping for mature sperm in azoospermic men
Urology, 1997Co-Authors: Paul J Turek, Imok Cha, Brittmarie LjungAbstract:Abstract Objectives This study compares fine-needle aspiration (FNA) and Testis Biopsy for the ability to detect mature sperm in the testes of azoospermic men. In addition, we introduce the concept of Testis “mapping” with FNA and apply it to detect sperm in men with severe Testis failure. Methods Sixteen patients were evaluated for azoospermia in a university-based infertility clinic. All men had Testis biopsies and FNAs from matched testicular sites to assess for the presence of spermatozoa. Adequacy criteria for FNA specimens were strictly defined, and correlative analysis of the two techniques was performed. In addition, a subset of 12 men with nonobstructive azoospermia (NOA) had systematic FNA mapping (more than four FNA sites per Testis) to detect mature sperm for potential clinical use. Results Adequate FNA specimens were obtained in 115 (91.3%) of 126 FNA attempts. Of 34 paired Biopsy FNA sites, FNA was seen to be more sensitive than, and equally specific as, Testis Biopsy for sperm detection. When compared with the Biopsy touch imprint, FNA was equally as sensitive and specific. Among men with NOA who underwent FNA mapping, 4 (33%) of 12 had localized “patches” of sperm detected in areas distant from sperm-negative Biopsy sites. In 1 case, a pregnancy was achieved with later Biopsy and sperm extraction “directed” by previous FNA. Conclusions For sperm detection, Testis FNA provides equivalent or better information than a Testis Biopsy. FNA can localize areas of sperm production within the Testis and accurately guide sperm extraction procedures in men with NOA.
Mohammad Mehdi Akhondi - One of the best experts on this subject based on the ideXlab platform.
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Testis Biopsy in absolute head teratospermia is it a logical option
Urologia Journal, 2020Co-Authors: Nasser Shakhssalim, Mohamad Reza Sadeghi, Mohammad Mehdi Akhondi, Hamed AkhavizadeganAbstract:Introduction:Absolute head teratospermia (100% abnormal head morphology) is associated with poor fertility and assisted reproductive techniques results. We aimed to find if it is possible to bypass...
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molecular analysis of Testis Biopsy and semen pellet as complementary methods with histopathological analysis of Testis in non obstructive azoospermia
Journal of Assisted Reproduction and Genetics, 2014Co-Authors: Maryam Eghbali, Mohammad Mehdi Akhondi, Mohammad Reza Sadeghi, Niknam Lakpour, Hale Edalatkhah, Hojjat Zeraati, Haleh Soltanghoraee, Behnam S Hashemi, Mohammad Hossein ModarressiAbstract:Purpose Non-obstructive azoospermia (NOA) is one the many causes of male infertility (10 %) resulting from testicular failure. Multiple testicular biopsies fail to find mature sperm in at least 50 % of cases Therefore; hunting for sensitive and specific biomarkers of spermatogenesis that could better determine the fertility status in NOA can lead to improved management of male infertility. Therefore, we evaluated sperm production through analyses of germ cell-specific transcripts (DAZ, TSPY1, SPTRX3 and SPTRX1) in semen and testicular biopsies of men with azoospermia.
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Isolation and Culture of Human Spermatogonial Stem cells Derived from Testis Biopsy
Avicenna journal of medical biotechnology, 2013Co-Authors: Leila Goharbakhsh, Kazem Parivar, Arash Mohazzab, Sheida Salehkhou, Mahnaz Heidari, Amir-hassan Zarnani, Mohammad Mehdi AkhondiAbstract:BACKGROUND In cancer patients, chemo and radiotherapy can cause infertility by damaging spermatogenesis process. This process is based on self-renewal and differentiation of a rare population of the testicular cells called Spermatogonial Stem Cells (SSCs). Scientists have tried to isolate, enrich and culture Human spermatogonial stem cells, hoping to resolve infertility problems in cancer recovered patients in the future. METHODS Spermatogonial stem cells were isolated and purified from human testicular biopsies sample consisting of at least 500,000 and at most 2,000,000 cells. Two enzymatic digestion steps were performed. Enriching methods, differential plating, and specific culture in serum-free medium with added growth factors: human GDNF, bFGF, EGF and LIF was performed on coated dishes. RESULTS Human spermatogonial stem cell clusters were observed after 7 to 10 days in specific culture, then after several passages and successful expanding duration of 52 days, the cells were evaluated by three layer immunocytochemistry test (LSAB) to stain GPR125 protein as a surface marker in human spermatogonial stem cells. CONCLUSION In current study human spermatogonial stem cell were isolated and expanded with the least manipulations in comparison with the other usual isolation methods like florescent or magnetic activated cell sorting. In contrast to the other SSCs isolation and culture methods, this system is based on the testicular biopsies against large samples, thus suggested method in this study is closer to clinical usage in the future.
Marc Goldstein - One of the best experts on this subject based on the ideXlab platform.
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detection of sperm in men with y chromosome microdeletions of the azfa azfb and azfc regions
Human Reproduction, 2003Co-Authors: Carin V Hopps, Marc Goldstein, Anna Mielnik, G D Palermo, Z Rosenwaks, Peter N SchlegelAbstract:BACKGROUND: Y chromosome microdeletions are associated with severe male factor infertility. In this study, the success rate of testicular sperm retrieval was determined for men with deletions of AZF regions a, b or c. METHODS: AZF deletions were detected by PCR of 30 sequence-tagged sites within Yq emphasizing the AZFa, b and c regions. Semen analysis and diagnostic Testis Biopsy or testicular sperm extraction (TESE) findings were correlated with the specific AZF region deleted. RESULTS: A total of 78 men with AZF deletions included three with AZFa deletion, 11 with AZFb, 42 with AZFc, 16 with AZFb+c and six with Yq (AZFa+b+c). All men with AZFa, AZFb, AZFb+c and Yq deletions were azoospermic and no sperm were found with TESE or Biopsy. Of men with isolated AZFc deletion, sperm were found in 75% (9/12) by TESE and 45% (9/20) on Biopsy (56% overall); 62% (26/42) were azoospermic and 38% (16/42) severely oligozoospermic. A total of 7 patients with deletion patterns that included the complete AZFa region and 23 that included the complete AZFb region who underwent TESE or Biopsy did not have sperm detected by these surgical measures. CONCLUSIONS: Microdeletion of the entire AZFa or AZFb regions of the Y chromosome portends an exceptionally poor prognosis for sperm retrieval, whereas the majority of men with AZFc deletion have sperm within the semen or testes available for use in IVF/ICSI.
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microsurgical Testis Biopsy a novel technique for retrieval of testicular tissue
The Journal of Urology, 2000Co-Authors: Kambiz Dardashti, Russel H Williams, Marc GoldsteinAbstract:Purpose: In vitro fertilization with intracytoplasmic sperm injection has resulted in a dramatic increase in the need for diagnostic and therapeutic Testis biopsies. We developed a microsurgical Testis Biopsy technique which allows identification of testicular vessels and individual seminiferous tubules. We compare the results of this technique to our prior series of nonmicroscopic biopsies. Materials and Methods: A retrospective study of 226 consecutive patients who had undergone open testes Biopsy with or without an operating microscope was performed. Between 1988 and 1994 standard open Testis Biopsy was performed without a microscope in 119 patients and a single sample of testicular tissue was taken. After 1994 microsurgical Biopsy was performed under 6 to 25× magnification in 107 patients, nearly half of whom had multiple biopsies of each Testis. The complication rates of the 2 procedures were compared. Results: Scrotal hematoma required surgical drainage in 3 of the 119 standard Testis Biopsy cases and Testis atrophy was noted in 1, for a total complication rate of 3.4%. There were no episodes of clinically detectable testicular atrophy or scrotal hematoma requiring surgical drainage in the 107 microsurgical Biopsy cases (p Conclusions: Use of the operating microscope for testicular Biopsy allows identification and avoidance of testicular vessels, minimizing complications. It also may allow selection of seminiferous tubules more likely to contain sperm.
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testicular sperm extraction with intracytoplasmic sperm injection for nonobstructive azoospermia
Urology, 1997Co-Authors: Gianpiero D Palermo, N Zaninovic, Marc Goldstein, Silvia MenendezAbstract:Abstract Objectives To provide fertility for men with nonobstructive azoospermia. Methods A retrospective review of treatment results at a university infertility center was undertaken. Sixteen couples entered an attempted in vitro fertilization (IVF)-intracytoplasmic sperm injection (ICSI) cycle for treatment of nonobstructive azoospermia. Each man was azoospermic, and the male factor diagnosis of nonobstructive azoospermia was made on Testis Biopsy for 14 men and on clinical grounds for 2 men. Sperm were retrieved by testicular Biopsy on the day of oocyte retrieval. Results of testicular examinations, serum follicle-stimulating hormone levels, and testicular histology as well as evaluation of the success rates of sperm retrieval, fertilizations, and pregnancies were made. Results Sperm were extracted from Testis biopsies in 10 of 16 (62%) testicular sperm extraction (TESE) attempts. For cycles in which sperm were retrieved, normal fertilizations were achieved for 51 of 98 (52%) mature oocytes injected with testicular sperm in 10 couples. Biochemical pregnancies were achieved for 6 of 16 (38%) couples, with clinical pregnancies during 5 of 16 (31 %) attempts at sperm retrieval, and ongoing pregnancy and subsequent live delivery for 4 of 16 (25%) attempts. Conclusions Pretreatment clinical parameters are unable to predict which men with nonobstructive azoospermia will have spermatozoa retrieved by TESE. When sperm are found, clinical pregnancies can occur for half (5/10) of these couples using TESE with ICSI, with ongoing pregnancy and delivery for 4 of 10 (40%). Many men with nonobstructive azoospermia will have retrievable sperm with Testis Biopsy that are suitable for ICSI; however, 6 of 16 (38%) couples will not have sperm retrieved with TESE and may undergo an unnecessary IVF procedure.
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motile sperm in human Testis Biopsy specimens
Journal of Andrology, 1993Co-Authors: William W Jow, Joph Steckel, Peter N Schlegel, Margret S Magid, Marc GoldsteinAbstract:We prospectively studied 62 consecutive infertile men who underwent 100 intraoperative wet prep cytological examinations of Testis Biopsy material obtained simultaneously with permanently fixed specimens. Wet preps were performed by placing a small sample of fresh testicular tissue on a slide, adding a drop of Ringer's lactate, and compressing the specimen under a glass coverslip. Among these 100 wet preps, complete sperm with tails were identified in 62 specimens, of which 44 contained nonmotile sperm and 18 contained motile sperm. Reproductive tract obstruction was documented in 65 testes (65%) on subsequent reconstructive surgery and/or inferred from histological evaluation, including mean mature spermatid counts on the permanent sections fixed in Bouin's solution. Obstruction was absent in the remaining testes (35%). All 18 testes with motile sperm found on wet prep were obstructed. These testes were also found to have complete spermatogenesis, a category selected to include normal spermatogenesis and slight hypospermatogenesis, determined by examination of the permanently fixed sections. The finding of motile vs. nonmotile sperm on a wet prep has positive predictive values of 100% vs. 81% for the presence of reproductive tract obstruction and 94% vs. 86% for complete spermatogenesis, respectively. The presence of motile sperm in human Testis Biopsy specimens is a novel finding. When any complete sperm with tail is found in a Testis Biopsy wet prep, obstruction is likely. When motile sperm are present, obstruction is almost certain, and immediate exploration and reconstructive surgery can be justified.(ABSTRACT TRUNCATED AT 250 WORDS)
Nina Kossack - One of the best experts on this subject based on the ideXlab platform.
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isolation and characterization of pluripotent human spermatogonial stem cell derived cells
Stem Cells, 2009Co-Authors: Nina Kossack, Juanito J Meneses, Shai Shefi, Ha Nam Nguyen, Shawn L Chavez, Cory R Nicholas, J Gromoll, Paul J TurekAbstract:Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells) from spermatogonial stem cells obtained from the adult mouse Testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a Testis Biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus, and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8 weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human Testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming.
Sherman J Silber - One of the best experts on this subject based on the ideXlab platform.
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Testis Biopsy and the infertile male
2005Co-Authors: Sherman J SilberAbstract:This chapter begins with the use of diagnostic Testis Biopsy to evaluate azoospermia. It then describes the basics of spermatogenesis in oligospermic and normospermic men, and the use of therapeutic Testis Biopsy for sperm retrieval and intracytoplasmic sperm injection (ICSI). Finally, it discusses the differences in embryo quality, chromosomal abnormalities, and pregnancy rates with Testis sperm versus ejaculated sperm.
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y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction
Human Reproduction, 1998Co-Authors: Sherman J Silber, Raaji Alagappan, L G Brown, David C PageAbstract:Y chromosome deletions encompassing the AZFc region have been reported in 13% of azoospermic men and 7% of severely oligozoospermic men. We examined the impact of these Y deletions on the severity of testicular defects in 51 azoospermic men undergoing intracytoplasmic sperm injection (ICSI) after testicular sperm extraction (TESE) and 30 men with severe oligozoospermia undergoing ICSI after ejaculation of spermatozoa. In addition, five azoospermic patients shown previously to have Y chromosome deletions underwent histological evaluation of their previously obtained Testis Biopsy specimens. A further 27 azoospermic men underwent TESE-ICSI, but not Y chromosome DNA testing. Ten of 51 azoospermic men (20%) who underwent TESE-ICSI and Y-DNA testing were found to be deleted for portions of the Y chromosome AZFc region. Of these 10, five had spermatozoa retrievable from the Testis, and in two cases the wives became pregnant. Of the 41 azoospermic men with no Y chromosome deletion, 22 (54%) had spermatozoa retrievable from the Testis, and in 12 cases (29%) the wives became pregnant. Four of 30 (13%) severely oligozoospermic patients were found to be deleted for AZFc and in three (75%) of these pregnancy was achieved. The other 26 severely oligozoospermic couples who had no AZFc deletions underwent ICSI, and 12 (46%) have an ongoing or delivered pregnancy. The embryo implantation rate was not significantly different for azoospermic (22%), oligozoospermic (16%), Y-deleted (14%) or Y-intact (18%) men. Of the total of 19 infertile men who had Y chromosome deletions, 14 had deletions within Y chromosome intervals 6D-6F, in the AZFc region. Twelve of those 14 had some spermatozoa (however few in number) in the ejaculate or Testis. Five of the Y-deleted men had deletions that extended more proximally on the Y chromosome, and in none of these could any spermatozoa be observed in either ejaculate or Testis. These results support the concept that, in azoospermic or oligozoospermic men with Y chromosome deletions limited to intervals 6D-6F (AZFc), there are generally very small numbers of testicular or ejaculated spermatozoa. Larger Y deletions, including and extending beyond the AZFc region and encompassing more Y genes, tend to be associated with a total absence of testicular spermatozoa. In those cases where spermatozoa were retrieved, the presence of Y deletions had no obvious impact on fertilization or pregnancy rate.
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are spermatid injections of any clinical value rosni and rosi revisited round spermatid nucleus injection and round spermatid injection
Human Reproduction, 1998Co-Authors: Sherman J Silber, L JohnsonAbstract:Tiny numbers of spermatozoa can be extracted from an extensive Testis Biopsy and be used successfully for intracytoplasmic sperm injection (ICSI) in ∼60% of cases of non-obstructive azoospermia caused by testicular failure (e.g. maturation arrest, Sertoli cell only, cryptorchid atrophy, post-chemotherapy, or even Klinefelter's syndrome). However, no sperm are recoverable in 40% of cases even after a very extensive testicular sperm extraction (TESE)-ICSI attempt. Round spermatid nucleus injection (ROSNI) and round spermatid injection (ROSI) would be an appropriate alternative if no elongated spermatozoa, or elongated spermatids were recoverable. Round cells are abundant in morselated testicular tissue of almost all azoospermic men, but difficulties arise in distinguishing under Hoffman or Nomarski optics whether they are haploid round spermatids, diploid spermatocytes or spermatogonia, or even somatic cells like Sertoli cell nuclei or Leydig cells. This paper attempts to clarify such confusion by reviewing data on 143 consecutive Testis biopsies of men with non-obstructive azoospermia due to germinal failure, and 62 controls with obstructive azoospermia and normal spermatogenesis. In no cases were round spermatids found in the absence of elongated spermatozoa, and maturation arrest was found always to be a failure of progression beyond meiosis (not at maturation from round spermatid to mature elongated spermatid). Errors arising after injecting somatic or other round cells could result in an appearance resembling fertilization and cleavage, and explain reports of finding 'round spermatids' in azoospermic men where no 'spermatozoa' were retrievable. The use of TESE-ICSI to achieve pregnancies in azoospermic men with deficient spermatogenesis is more concerned with finding tiny foci of spermatozoa, rather than searching for 'round spermatids', which are recoverable only if elongated forms are also available.
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distribution of spermatogenesis in the testicles of azoospermic men the presence or absence of spermatids in the testes of men with germinal failure
Human Reproduction, 1997Co-Authors: Sherman J Silber, H Tournaye, Z Nagy, P Devroey, Andre Van SteirteghemAbstract:Abstract The aim of the study was to determine whether a prior diagnostic testicle Biopsy can predict success or failure of testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI) in patients with non-obstructive azoospermia caused by testicular failure, and what is the minimum threshold of sperm production in the Testis which must be surpassed for spermatozoa to reach the ejaculate. Forty-five patients with non-obstructive azoospermia caused by testicular failure underwent diagnostic testicle Biopsy prior to a planned future TESE-ICSI procedure. The diagnostic testicle Biopsy was analysed quantitatively, and correlated with the quantitative findings of spermatogenesis in patients with normal spermatogenesis, as well as with the results of subsequent attempts at TESE-ICSI. Men with non-obstructive azoospermia caused by germinal failure had a mean of 0-6 mature spermatids/seminiferous tubule seen on a diagnostic testicle Biopsy, compared to 17-35 mature spermatids/tubule in men with normal spermatogenesis and obstructive azoospermia. These findings were the same for all types of testicular failure whether Sertoli cell only, maturation arrest, cryptorchidism, or post-chemotherapy azoospermia. Twenty-two of 26 men with mature spermatids found in the prior Testis Biopsy had successful retrieval of spermatozoa for ICSI, 12 of their partners became pregnant, and are either ongoing or delivered. The study suggests that 4-6 mature spermatids/tubule must be present in the Testis Biopsy for any spermatozoa to reach the ejaculate. More than half of azoospermic patients with germinal failure have minute foci of spermatogenesis which are insufficient to produce spermatozoa in the ejaculate. Prior diagnostic testicle Biopsy analysed quantitatively (for the presence of mature spermatids) can predict subsequent success or failure with TESE-ICSI. Incomplete testicular failure may involve a sparse multi-focal distribution of spermatogenesis throughout the entire testicle, rather than a regional distribution. Therefore, it is possible that massive testicular sampling from many different regions of the testes may not be necessary for successful TESE-ICSI.
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normal pregnancies resulting from testicular sperm extraction and intracytoplasmic sperm injection for azoospermia due to maturation arrest
Fertility and Sterility, 1996Co-Authors: Sherman J Silber, Andre Van Steirteghem, Zsolt Nagy, Jiaen Liu, H TournayeAbstract:Objective To see whether testicular sperm extraction could be used to perform intracytoplasmic sperm injection (ICSI) for men with nonobstructive azoospermia caused by maturation arrest. Design Uncontrolled prospective trial of an attempt to find occasional elongated spermatids or spermatozoa in testes of azoospermic patients with maturation arrest and to use these haploid cells for ICSI. Setting European university-based center for reproductive medicine and private American community hospital. Patients Thirty-eight azoospermic males without obstruction and with Biopsy-documented maturation arrest, seven of whom elected, with their wives, to undergo scrotal exploration and testicular sperm extraction with ICSI in an attempt to become pregnant. Interventions Histologic evaluation of spermatid development in 38 patients with azoospermic maturation arrest. Testicular sperm extraction with ICSI in seven random volunteers from this group. Main Outcome Measures Presence or absence of mature spermatids in the Testis Biopsy specimen of patients with azoospermic maturation arrest. Fertilization, cleavage, and pregnancy after testicular sperm extraction and ICSI in patients with azoospermic maturation arrest. Results All seven patients with azoospermic maturation arrest had occasional sperm found with testicular sperm extraction. Five had sufficient numbers (between 6 and 30) for ICSI, and those five had ETs. In four, the partners became pregnant. In all 38 patients examined, the maturation defect was in meiosis rather than in spermiogenesis. Conclusion Nonobstructive azoospermia caused by maturation arrest may be treated with testicular sperm extraction with ICSI apparently as successfully as Sertoli cell only.