Role of Optimizing Testosterone Before Microdissection Testicular Sperm Extraction in Men with Nonobstructive Azoospermia

Reifsnyder, Jennifer; Ramasamy, Ranjith; Husseini, Jad S.; Schlegel, Peter N.

doi:10.1016/j.juro.2012.04.002

Cited by 117 publications

(98 citation statements)

References 14 publications

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“…Reifsnyder et al also reported a partial effect of testosterone optimization on micro-TESE outcomes following treatment with clomiphene citrate, hCG or aromatase inhibitors. Ramasamy et al reported that Klinefelter syndrome, men with low baseline testosterone levels who responded to medical therapy to enhance testosterone production with resultant testosterone levels greater than 250 ng/dL had a 77 % chance of sperm retrieval versus 55 % for men who did not respond [64]. These observations suggest that men who can produce increased testosterone levels may also produce increased levels of the other growth factors secreted from Leydig and Sertoli cells [48].…”

Section: Fsh Stimulation Of Sertoli Cellsmentioning

confidence: 99%

Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]

Shiraishi

Matsuyama

2017

Endocr J

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Abstract. Microdissection testicular sperm extraction and intracytoplasmic sperm injection have made it possible for men with non-obstructive azoospermia (NOA) to conceive a child. A majority of men cannot produce sperm because spermatogenesis per se is believed to be "irreversibly" disturbed. For these men, it has been thought that any hormonal therapy will be ineffective. Further understandings of endocrinological regulation of spermatogenesis are needed and LH or FSH receptor knock out (KO) mice have revealed the roles of gonadotropin separately. Spermatogenesis has been shown to shift during evolution from FSH to LH dominance because LH receptor KO causes infertility while FSH receptor KO does not. High concentrations of intratesticular testosterone secreted from Leydig cells, ranging from 100-to 1,000-fold higher than in the systemic circulation, has pivotal roles during spermatogenesis. This is especially important during spermiogenesis, a post-meiotic step for progression from round to elongating spermatids. Sertoli cells are the target of FSH and have numerous androgen receptors, indicating that Sertoli cells are regulated by FSH and the paracrine functions of testosterone. In combination with Leydig cell-derived growth factors, particularly epidermal growth factor-like growth factors, Sertoli cells support spermatogenesis, especially at proximal levels of spermatogenesis (e.g., spermatogonial proliferation). Taken together, the current knowledge from human studies indicating that testosterone optimization by clomiphene, hCG and/or aromatase inhibitors and high dose hCG/FSH treatment can, at least in part, improve spermatogenesis in NOA. Accordingly hormonal therapy may open a therapeutic window for sperm production in selected patients.Key words: Non-obstructive azoospermia, Testicular sperm extraction, Gonadotropin, Hormonal therapy FIFTEEN to twenty percent of couples are categorized as infertile. Generally, a male-related factor is involved in more than half of the cases. Among male-related factors, approximately 10 % of cases are diagnosed as non-obstructive azoospermia (NOA). NOA is the most prevalent and challenging form of azoospermia for both patients and physicians because spermatogenesis per se is believed to be "irreversibly" disturbed and it has been thought that any medical therapy, including hormonal therapy, will be ineffective. Unlike oogenesis, where there is a substantial amount of information regarding endocrine regulation, information regarding spermatogenesis, especially in humans, is very limited.Along with the development and availability of intracytoplasmic sperm injection (ICSI) since the 1990's, the goal of NOA treatment has not necessarily required many sperm in the ejaculate for assisted insemination or in-vitro fertilization. However, a single sperm is theoretically enough for ICSI to perform infertility treatment. As a result, the established surgical approach to retrieve sperm directly from the testis was called microdissection testicular sperm extraction (micro-TESE) [1]....

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Section: Fsh Stimulation Of Sertoli Cellsmentioning

confidence: 99%

Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]

Shiraishi

Matsuyama

2017

Endocr J

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“…Uncontrolled studies have reported moderate positive effects on sperm retrieval rates in patients with nonobstructive azoospermia (NOA) (78,79). However, controversy exists and a very recent study on 1054 men with NOA found that neither baseline testosterone nor the response to preoperation hormonal therapy had any effect on overall sperm retrieval, clinical pregnancy, or live birth rates (80).…”

Section: Preoperation Hormonal Therapymentioning

confidence: 99%

Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review

Aksglæde

Juul

2013

European Journal of Endocrinology

175

114

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Klinefelter syndrome, 47,XXY (KS), is the most frequent sex chromosome aberration in males, affecting 1 in 660 newborn boys. The syndrome is characterized by testicular destruction with extensive fibrosis and hyalinization of the seminiferous tubules resulting in small testes, hypergonadotropic hypogonadism, and azoospermia in the majority of cases. Until recently, infertility was considered an untreatable condition in KS. However, with the development of new advanced assisted reproductive techniques such as testicular sperm extraction (TESE) combined with ICSI it seems that KS patients should no longer be labelled as infertile. Especially, microdissection (micro)-TESE has proved to be an advantageous procedure for the identification of testicular spermatozoa in KS. The aim of this review was to describe current knowledge on the testicular changes occurring in KS, the associated changes in reproductive hormones and spermatogenesis, and the existing possibilities of biological fatherhood in 47,XXY patients. European Journal of Endocrinology 168 R67-R76

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“…However, the lack of useful predictive biomarkers suggestive for successful sperm retrieval at microTESE in NOA men still represents a relevant gap with a very negative return for the patient. Indeed, no significant association has been found between microTESE sperm retrieval outcomes and (i) preoperative testicular volume, (ii) baseline follicular stimulating hormone (FSH) levels, (iii) basal level of Testosterone (T) or increased T level following treatments with aromatase inhibitors, clomiphene citrate or human chorionic gonadotropin 13,14 . Thereof, we sought to identify novel and user-friendly prognostic factors reliably predicting surgical outcomes in iNOA men in the real-life setting.…”

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confidence: 99%

Anti-Mullerian hormone-to-testosterone ratio is predictive of positive sperm retrieval in men with idiopathic non-obstructive azoospermia

Alfano¹,

Ventimiglia²,

Locatelli³

et al. 2018

European Urology Supplements

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The lack of clinically-reliable biomarkers makes impossible to predict sperm retrieval outcomes at testicular sperm extraction (TESE) in men with non-obstructive azoospermia (NOA), resulting in up to 50% of unnecessary surgical interventions. Clinical data, hormonal profile and histological classification of testis parenchyma from 47 white-Caucasian idiopathic NOA (iNOA) men submitted to microdissection TESE (microTESE) were analyzed. Logistic regression analyses tested potential clinical predictors of positive sperm retrieval. The predictive accuracy of all variables was evaluated using the receiver operating characteristic-derived area under the curve, and the clinical net benefit estimated by a decision-curve analysis (DCA). Overall, 23 (49%) and 24 (51%) patients were classified as positive and negative sperm retrievals at microTESE. While circulating hormones associated to a condition of primary hypogonadism did not predict sperm retrieval, levels of anti-Mullerian hormone (AMH) and the ratio AMH-to-total Testosterone (AMH/tT) achieved independent predictor status for sperm retrieval at microTESE, with a predictive accuracy of 93% and 95%. Using cutoff values of <4.62 ng/ml for AMH and <1.02 for AMH/tT, positive sperm retrieval was predicted in all individuals, with 19 men out of 47 potentially spared from surgery. DCA findings demonstrated clinical net benefit using AMH and AMH/tT for patient selection at microTESE.The relevance of male infertility has progressively grown in Western societies, with significant medical, psychological, and socio-economic implications. Seven out of 100 men are infertile, with up to 40% of infertile conditions still of unexplained or idiopathic origin [1][2][3] . Azoospermia affects about 1% among all men and 10-15% of infertile men 4,5 . With no sperm found at multiple semen analyses, non-obstructive azoospermia (NOA) is the most severe form of infertility 1,5 . Despite genetic causes have been associated with male infertility 3,6,7 , genetic defects are found only in 17-20% of NOA individuals [7][8][9][10] . Except for a portion of patients with central endocrine disorders, the remaining 80% of NOA men having negative results on genetic testing are classified as idiopathic NOA (iNOA) 11 .In patients with clinical evidence of NOA, testicular sperm extraction (TESE) is the technique of choice, which rationally has to be planned as a part of in vitro fertilization programs; in this context, microdissection TESE (microTESE) has been advocated as the gold-standard technique to improve sperm yield with minimal

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Role of Optimizing Testosterone Before Microdissection Testicular Sperm Extraction in Men with Nonobstructive Azoospermia

Abstract: Men with nonobstructive azoospermia and hypogonadism often respond to hormonal therapy with an increase in testosterone levels, but neither baseline testosterone level nor response to hormonal therapy appears to affect overall sperm retrieval, clinical pregnancy or live birth rates.

Cited by 117 publications

References 14 publications

Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]

Gonadotoropin actions on spermatogenesis and hormonal therapies for spermatogenic disorders [Review]

Therapy of endocrine disease: Testicular function and fertility in men with Klinefelter syndrome: a review

Anti-Mullerian hormone-to-testosterone ratio is predictive of positive sperm retrieval in men with idiopathic non-obstructive azoospermia

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