Novel insights on testicular volume and testosterone replacement therapy in Klinefelter patients undergoing testicular sperm extraction. A retrospective clinical study

Garolla, Andrea; Selice, Riccardo; Menegazzo, Massimo; Valente, Umberto; Zattoni, Filiberto; Iafrate, Massimo; Prayer-Galetti, Tommaso; Gardiman, Marina Paola; Ferlin, Alberto; Nisio, Andrea Di; Foresta, Carlo

doi:10.1111/cen.13572

Cited by 27 publications

(23 citation statements)

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“…Madgar et al, 36 for example, showed that testicular volume was significantly higher in men with positive SRR. However, there are several studies reporting that testicular atrophy does not affect the success of SR. 9,[27][28][29]32,37 Garolla et al, 28 indeed, observed a 23% SRR even in KS patients with testicles < 1 mL. Our results support these findings as we failed to find any relationship between testicular volume and SRR in NOA patients with KS.…”

Section: Discussionsupporting

confidence: 87%

“…9 So far, there is a lack of reliable clinical and biological predictors for sperm retrieval success in NOA patients with KS. [27][28][29] Advanced paternal age has been considered a negative predictive factor for SR in Klinefelter men undergoing TESE. 30,31 Ozer at al.…”

Section: Discussionmentioning

confidence: 99%

“…Our findings are in line with previous studies that did not show any impact of testosterone treatment on spermatogenesis in adolescents and adults Klinefelter men. 9,27,28,34 Therefore, some authors did not recommend postponing androgen treatment in adolescent boys with KS for fear of impairing their TESE results. 27 Lastly, the superiority of mTESE as compared to cTESE in NOA men has been extensively investigated in the previous literature but with conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…Figure 1shows the distribution of patients among the five centers. Median (IQR) patient's age was 32(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) years. Baseline serum FSH and total testosterone levels were 29.5 (19.9-40.9) mUI/mLand 3.8 (2.5-11.0) ng/mL, respectively.…”

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confidence: 99%

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Sperm retrieval rates in non‐mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real‐life setting?

et al. 2020

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Background: A recent meta-analysis (Human Reproduction Update 23, 2017 and 265) reported positive sperm retrieval rates (SRR) in 50% of patients with Klinefelter syndrome (KS) undergoing testicular sperm extraction (TESE). However, these results do not reflect the rates of SR that we observe in clinical practice. We assessed the rate and potential predictors of SR in Klinefelter patients in the real-life setting. Materials and Methods:We reviewed clinical data of 103 KS men who underwent TESE between 08/2008 and 03/2019 at five tertiary referral Andrology centers. Patients underwent testis ultrasound, hormonal evaluation, and genetic testing. All patients were azoospermic based on the 2010 WHO reference criteria. Conventional TESE (cTESE) or microsurgical TESE (mTESE) was performed based on the surgeon's preference. We used descriptive statistics and logistic regression models to describe the whole cohort.Results: Median (IQR) patient's age was 32 (24-37) years. Baseline serum FSH and total testosterone levels were 29.5 (19.9-40.9) mUI/mL and 3.8 (2.5-11.0) ng/mL, respectively. Conventional TESE and mTESE were performed in 38 (36.5%) and 65 (63.5%) men, respectively. The sperm retrieval rate was 21.4% (22/103 men). Fifteen patients used spermatozoa for ICSI and five ended in live birth children. Patients with positive SR were similar to those with a negative TESE in terms of clinical, hormonal, and procedural parameters (all P > .05). Logistic regression analyses confirmed the lack of association between clinical, hormonal, and procedural parameters with SR outcome. Discussion: Given the conflicting results in the literature regarding SRR in KS, patients should be carefully counseled regarding TESE outcomes based on data from published literature and local results.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Sperm retrieval rates in non‐mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real‐life setting?

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“…Consequently, although the endocrine feedback regulation is definitely disturbed, impaired T production cannot be the reason for the lowered peripheral serum T levels. Testes of KS patients are phenotypically described as small and firm with volume of approximately 2-2.5 mL vs. the healthy normal range above 12 mL per testis 19,20 which is due to a dramatically altered testicular architecture caused by germ cell loss and Leydig cell hyperplasia. We reported previously that the vascularization of testes in 30 weeks old mice was altered mainly due to a changed blood vessel composition 18 .…”

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Testicular blood supply is altered in the 41,XXY* Klinefelter syndrome mouse model

Wistuba

Beumer

Warmeling

et al. 2020

Sci Rep

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Hypergonadotropic hypogonadism is a major feature of Klinefelter syndrome (KS), assumed to be caused by testicular hormone resistance. It was previously shown that intratesticular testosterone levels in vivo and Leydig cell function in vitro seem to be normal indicating other functional constraints. We hypothesized that impaired testicular vascularization/blood flow could be a co-factor to the observed hypergonadotropic hypogonadism. We evaluated the testicular vascular system by measuring blood vessel sizes during postnatal development and testis blood flow in adult 41,XX Y * mice. Proportional distribution and size of blood vessels were analyzed during testicular development (1, 3, 5, 7, 10, 21 dpp, 15 wpp). While ratios of the vessel/testis area were different at 15 wpp only, a lower number of smaller and mid-sized blood vessels were detected in adult KS mice. For testicular blood flow determination we applied contrast enhanced ultrasound. Floating and reperfusion time for testicular blood flow was increased in 41,XX Y * mice (floating: XY* 28.8 ± 1.69 s vs XX Y * 44.6 ± 5.6 s, p = 0.0192; reperfusion XY* 19.7 ± 2.8 s vs XX Y *: 29.9 ± 6.2 s, p = 0.0134), indicating a diminished blood supply. Our data strengthen the concept that an impaired vascularization either in conjunction or as a result of altered KS testicular architecture contributes to hormone resistance. The presence of one or more supernumerary X-chromosomes causes Klinefelter syndrome (KS, 47,XXY) in men. This chromosomal aneuploidy occurs at a high incidence of 1-2 in 1,000 male births and is the most frequent genetic cause for male infertility. Characteristic for KS is the hypergonadotropic hypogonadism characterized by highly elevated gonadotropins and low to very-low testosterone (T) levels resulting from testicular hormone resistance. Germ cell loss prevails, generally leading to azoospermia in nearly all KS patients 1-5. During the last years, co-morbidities have been associated with KS such as cardiovascular disease (shortened QTc times), increased risk for pulmonary embolism and peripheral vascular diseases 6-11. As for vascular problems, reduced diameters of brachial, common carotid and femoral as well as of the abdominal arteries have been reported. Low T levels in KS patients have numerous effects on health and are likely contributing to the majority of symptoms but can be clinically treated by T substitution positively influencing some but not all of the symptoms 4,12,13. However, and more problematic, androgen replacement interferes with the endocrine feedback by down-regulating Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH). This negatively impacts the sperm retrieval success in KS patients with remaining focal spermatogenesis 14-16. Consequently, it is of crucial importance to elucidate the underlying mechanisms causing hypergonadotropic hypogonadism to potentially develop novel therapeutic options for the treatment of KS patients. Previously, disturbed Leydig cell function was thought to be causative for serum T def...

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Morbidity in Klinefelter syndrome and the effect of testosterone treatment

Chang

Skakkebæk

Davis

et al. 2020

American J of Med Genetics Pt C

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Novel insights on testicular volume and testosterone replacement therapy in Klinefelter patients undergoing testicular sperm extraction. A retrospective clinical study

Abstract: Age at TESE, anthropometric measures, testis volume, sex hormones levels and semen parameters are not predictive parameters of SRR. Among TRT patients, reduced gonadotropin is related to failure in sperm retrieval.

Cited by 27 publications

References 49 publications

Sperm retrieval rates in non‐mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real‐life setting?

Sperm retrieval rates in non‐mosaic Klinefelter patients undergoing testicular sperm extraction: What expectations do we have in the real‐life setting?

Testicular blood supply is altered in the 41,XXY* Klinefelter syndrome mouse model

Morbidity in Klinefelter syndrome and the effect of testosterone treatment

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