Salvage hormonal therapy after failed microdissection testicular sperm extraction: A multi‐institutional prospective study

Shiraishi, Koji; Ishikawa, Tomomoto; Watanabe, Noriko; Iwamoto, Teruaki; Matsuyama, Hideyasu

doi:10.1111/iju.13076

Cited by 20 publications

(19 citation statements)

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“…Furthermore, there is a distinct SRR learning curve for individual surgeons [70], affecting different results of salvage hormonal therapy among the institutions. A multi-institutional prospective study by urologists with sufficient micro-TESE experience to validate this protocol has shown a 10 % SRR from the second micro-TESE following the salvage hormonal therapy regimen [71]. The effectiveness of salvage hormonal therapy should be further validated because percentage of hyposoermatogenesis and late MA and surgeons' and embryologists' experiences may be strongly affected on sperm retrieval.…”

Section: Establishment Of Gonadotropin Therapy For Noa Menmentioning

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: Establishment Of Gonadotropin Therapy For Noa Menmentioning

confidence: 99%

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

Shiraishi

Matsuyama

2017

Endocr J

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“…As known previously, HP, MA and SCOS were the three main histological classifications of NOA [ 3 ]. SCOS is excluded here as no tubules contain germ cells in the testis specimens of the patients [ 41 ], hence the possibility of acquiring sperm was very low [ 6 ]. Spermatogenesis of MA was often arrested at the spermatogonial or primary spermatocyte stage.…”

Section: Discussionmentioning

confidence: 99%

“…Hence, we supposed that it was related with terrible testis microenvironment and improve the microenvironment via hormone may be beneficial for spermatogenesis [ 7 ]. HP were also believed to be the ideal objects for medical treatment in the previous studies [ 6 , 7 ]. Moreover, the cost of the treatment was high.…”

Section: Discussionmentioning

confidence: 99%

“…Hormone replacement therapy would improve the ability of the testis to produce spermatozoa in idiopathic NOA patients [ 6 , 7 ]. For example, the improvement of spermatogonial DNA synthesis was demonstrated by Shinjo and coworkers [ 8 ], the elevation of intra-testicular testosterone levels was demonstrated by Kato and coworkers and the hypertrophic change of leydig cells was demonstrated by Oka and coworkers, respectively [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…For example, the improvement of spermatogonial DNA synthesis was demonstrated by Shinjo and coworkers [ 8 ], the elevation of intra-testicular testosterone levels was demonstrated by Kato and coworkers and the hypertrophic change of leydig cells was demonstrated by Oka and coworkers, respectively [ 9 , 10 ]. Recently, a multi-institutional prospective study conducted by Shiraishi and coworkers provided a stronger evidence of the efficiency of hormone therapy [ 6 ]. However, the total rate of acquiring sperm was only about 10–20%.…”

Section: Introductionmentioning

confidence: 99%

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Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study

Ding

Hong

et al. 2018

Reprod Biol Endocrinol

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BackgroundElevated plasma gonadotropins were associated with desensitization of Sertoli and Leydig cells in the male testis. Testis spermatogenesis ability would be improved via inhibiting high endogenous gonadotropin in patients with severe oligozoospermia. Whether it would be beneficial for non-obstructive azoospermia (NOA) patients was still unclear.MethodsGoserelin, a gonadotropin releasing hormone agonist (GnRHα) was used to suppress endogenous gonadotropin levels (gonadotropin reset) in the NOA patients, improving the sensitization of the Sertoli and Leydig cells. Then human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) were injected to stimulate them to ameliorate the ability of testicular spermatogenesis. The main outcome measure was the existence of spermatozoa in the semen or by testicular sperm extraction (TESE). Elevation of inhibin B and/or ameliorative expression pattern of ZO-1 was the secondary objective.ResultsA total of 35 NOA men who failed to retrieve sperm via TESE were enrolled. Among these, 10 patients without treatment were selected as control group and secondary TESE was performed 6 months later. Of the 25 treated men, inhibin B was elevated in 11 patients in the first 4 weeks (Response group), while only 5 patients had constant increase in the following 20 weeks (Response group 2). Of the 5 men, 2 men acquired sperm (Response group 2B), while 3 failed (Response group 2A). Immunofluorescence of mouse vasa homologue (MVH) and ZO-1 showed that both positive MVH signals and ZO-1 expression were significantly increased in the Response group 2, but only Response group 2B showed ameliorative ZO-1 distribution.ConclusionsGonadotropin reset, a new therapeutic protocol with GnRHα, was able to improve the ability of testicular spermatogenesis in the NOA patients through restoring the sensitivity of Sertoli and Leydig cells, which were reflected by elevated inhibin B and ameliorative ZO-1 expression and distribution.Trial registrationClinicalTrials.gov identifier: NCT02544191.Electronic supplementary materialThe online version of this article (10.1186/s12958-018-0401-7) contains supplementary material, which is available to authorized users.

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Stratégies de prise en charge des azoospermies non obstructives relevant d’une atteinte testiculaire primitive

Hugues¹

2022

Bulletin de l'Académie Nationale de Médecine

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Salvage hormonal therapy after failed microdissection testicular sperm extraction: A multi‐institutional prospective study

Abstract: Effectiveness of human chorionic gonadotropin-based salvage hormonal therapy preceding a second microdissection testicular sperm extraction seems to be limited. Non-obstructive azoospermia men who have differentiated cells in their testes are likely to respond to hormonal stimulation.

Cited by 20 publications

References 27 publications

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

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

Spermatogenesis improved by suppressing the high level of endogenous gonadotropins in idiopathic non-obstructive azoospermia: a case control pilot study

Stratégies de prise en charge des azoospermies non obstructives relevant d’une atteinte testiculaire primitive

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