Evaluation of neoadjuvant gonadotropin administration with downregulation by testosterone prior to second time microsurgical testicular sperm extraction: A prospective case–control study

Abstract

Purpose: The aim of this prospective study was to determine whether there is a beneficial role of combining gonadotropin administration with testosterone downregulation in non-obstructive azoospermia patients prior to a second time microsurgical testicular sperm extraction after a negative one. Methods: A total of 40 non-obstructive azoospermia men were recruited from a specialized IVF center from 2014 to 2016. Participants were divided equally into two groups: Group A was subjected to testosterone downregulation alone for 1 month and then combined with gonadotropin administration for 3 months prior to second time testicular sperm extraction; Group B (controls) underwent second time microsurgical testicular sperm extraction without prior hormonal therapy. Results: Mean baseline follicle-stimulating hormone levels of the controls and the cases were 26.9 ± 11.8 and 25.4 ± 8.7, respectively. One month after testosterone downregulation, follicle-stimulating hormone level of the cases was normalized and became 2.4 ± 1.2. There was no statistically significant difference between baseline follicle-stimulating hormone levels of the controls and cases (p = 0.946). Remarkably, two cases were positive after downregulation (10%) and no controls were positive at second testicular sperm extraction (0%). There was no statistically significant difference between sperm retrieval after the second microsurgical testicular sperm extraction in the controls and the cases (p = 0.072). Conclusion: Patients who underwent first time testicular sperm extraction with unfavorable outcome due to different techniques may benefit from testosterone downregulation combined with neoadjuvant gonadotropin administration as it had shown positive sperms retrieval in 2 out of the 20 cases, especially those with hypergonadotropic azoospermia.

Hormonal Treatment of Men with Nonobstructive Azoospermia: What Does the Evidence Suggest?

“…On the other hand, the two out of four studies evaluating the results of salvage micro-TESE in treated vs. untreated patients [23,59] agreed in demonstrating the beneficial effect of hormonal treatment on SRR, however, the small number of subjects (48 treated vs. 40 untreated overall) does not allow to draw firm conclusions about that.…”

“…The results of the few studies available in this field, however, are not fully able to demonstrate a beneficial effect of hormonal treatment on the SRR in men with NOA. As displayed in Table 2, five studies [34,[55][56][57][58] were carried in NOA men who underwent micro-TESE for the first time, while four [23,51,53,59] enrolled men undergoing salvage micro-TESE. The first two studies evaluated a well-selected cohort of patients, e.g., normogonadotropic men [55] and men with well-defined testis histology (MA and HYPO) [56], therefore, their results have poor generalizability, while the results of Amer and coworkers [58] are weakened by the relatively low overall SRR (32,2%), probably due to differences in skill and experience among the 15 urologists who performed micro-TESE.…”

Does hormonal therapy improve sperm retrieval rates in men with non-obstructive azoospermia: a systematic review and meta-analysis

“…There have been 11 studies ( Pavlovich et al , 2001 ; Saylam et al , 2011 ; Reifsnyder et al , 2012 ; Shiraishi et al , 2012 , 2016 ; Cavallini et al , 2013 ; Majzoub et al , 2016 ; Shoshany et al , 2017 ; Hu et al , 2018 ; Sujenthiran et al , 2019 ; Amer et al , 2020 ) investigating the use of hormone therapy in men with NOA and primary hypogonadism. The literature predominantly consisted of case series (n = 5) ( Pavlovich et al , 2001 ; Saylam et al , 2011 ; Shiraishi et al , 2016 ; Shoshany et al , 2017 ; Sujenthiran et al , 2019 ) and case-control studies (n = 5) ( Reifsnyder et al , 2012 ; Shiraishi et al , 2012 ; Majzoub et al , 2016 ; Hu et al , 2018 ; Amer et al , 2020 ) with only one RCT ( Cavallini et al , 2013 ).…”

“…There have been 11 studies ( Pavlovich et al , 2001 ; Saylam et al , 2011 ; Reifsnyder et al , 2012 ; Shiraishi et al , 2012 , 2016 ; Cavallini et al , 2013 ; Majzoub et al , 2016 ; Shoshany et al , 2017 ; Hu et al , 2018 ; Sujenthiran et al , 2019 ; Amer et al , 2020 ) investigating the use of hormone therapy in men with NOA and primary hypogonadism. The literature predominantly consisted of case series (n = 5) ( Pavlovich et al , 2001 ; Saylam et al , 2011 ; Shiraishi et al , 2016 ; Shoshany et al , 2017 ; Sujenthiran et al , 2019 ) and case-control studies (n = 5) ( Reifsnyder et al , 2012 ; Shiraishi et al , 2012 ; Majzoub et al , 2016 ; Hu et al , 2018 ; Amer et al , 2020 ) with only one RCT ( Cavallini et al , 2013 ). There were four studies solely utilizing aromatase inhibitors ( Pavlovich et al , 2001 ; Saylam et al , 2011 ; Cavallini et al , 2013 ; Shoshany et al , 2017 ), two studies investigating gonadotrophin therapy ( Shiraishi et al , 2012 , 2016 ) and three studies investigating multiple hormone agents (aromatase inhibitors, gonadotrophins, selective oestrogen receptor modulators (SERM’s) and combinations e.g.…”

“…aromatase inhibitors and hCG) ( Reifsnyder et al , 2012 ; Majzoub et al , 2016 ; Sujenthiran et al , 2019 ). Two studies investigated the use of gonadotrophins with an anti-gonadotrophin agent (either in the form of goserelin or exogenous testosterone) ( Hu et al , 2018 ; Amer et al , 2020 ). The literature included three studies analysing patients undergoing primary TESE ( Reifsnyder et al , 2012 ; Majzoub et al , 2016 ; Shoshany et al , 2017 ), four studies investigated patients undergoing secondary TESE ( Shiraishi et al , 2012 , 2016 ; Hu et al , 2018 ; Amer et al , 2020 ) and one study did not report the operation status ( Sujenthiran et al , 2019 ).…”