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Unraveling the origin of azoospermia in male cystinosis patients

Reda, Ahmed, Veys, Koenraad, Kadam, Prashant, Camps, Carlo, Taranta, Anna, Rega, Laura R, Cyr, Daniel G. ORCID: https://orcid.org/0000-0002-6566-783X, Emma, Francesco, Van den Heuvel, Lambert P, Goossens, Ellen et Levtchenko, Elena (2019). Unraveling the origin of azoospermia in male cystinosis patients In: 35th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), 23-26 June 2019, Vienne, Austria.

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Résumé

Study question:Is azoospermia in male cystinosis patients obstructive or nonobstructive in origin?

Summary answer: Azoospermia in male cystinosis patients is obstructive in origin.

What is known already: Cystinosis is a rare autosomal recessive metabolic disorder caused by mutations in the lysosomal membrane protein cystinosin (CTNS), which leads to intracellular lysosomal cystine accumulation. Depending on the disease severity, three forms are distinguished: infantile (most severe), juvenile (intermediate), and ocular (benign) form. The main clinical presentation in infantile cystinosis is the renal Fanconi syndrome, leading to end stage renal disease (ESRD) by the age of ten, if the patient is left untreated. Cysteamine, a cystine-depleting agent, beside renal replacement therapy, has improved the life expectancy of cystinosis patients. In contrast to females, male infantile cystinosis patients suffer from infertility.

Study design, size, duration: Three groups were included in a prospective case control study; adult cystinosis patients (three infantile, two juvenile, and one ocular male patients), control group (seven adult fertile male subjects), and a positive control group for obstructive azoospermia (ten adult vasectomized males who underwent vasectomy 4-8 weeks prior to enrollment). In addition, clinical data and testicular sections for five adult infantile male cystinosis patients were retrospectively included in the study (in total, eight infantile cystinosis patients).

Participants/materials, setting,methods:Scrotal ultrasound for screening for soft biomarkers of obstruction and semen analysis were performed in all prospectively included subjects, while sexual hormonal levels were evaluated only in the cystinosis patients. In addition, clinical data, semen analysis results, percutaneous epididymal sperm aspiration (PESA) results, sexual hormonal profile, and testicular sections from the retrospectively included cystinosis patients were analyzed. For the testicular sections, morphological evaluation and immunohistochemistry were performed.

Main results and the role of chance:All testicular sections taken from three infantile cystinosis patients (3/3) showed the presence of testicular sperm and normal spermatogenesis, with a Johnsen’s score of 7 to 9. Besides, epididymal sperm was present in two other infantile cystinosis patients (2/2), obtained by PESA procedure, which was only performed in those two patients. Hence, all of the five investigated infantile cystinosis patients showed either testicular or epididymal sperm (5/5 or 100%), indicating that testicular function was preserved in those patients. In contrast, seven out of the total eight infantile cystinosis patients underwent semen analysis, and they all presented with azoospermia (7/7 or 100%), including four out of the five patients that showed testicular or epididymal sperm, while a semen sample from one infantile patient, who underwent testicular biopsy, could not be retrieved. Meanwhile, the two juvenile cystinosis patients (2/2) showed a reduced sperm count (15.9 and 6.4 million/ml), and the ocular cystinosis patient (1/1) showed normal sperm count (71.6 million/ml). Remarkably, the scrotal ultrasound results revealed a significant higher epididymis caput diameter (normalized to the testis volume) in infantile cystinosis group compared with healthy controls (1.63±0.66 mm/cm3 for infantile cystinosis vs 0.50±0.18 mm/cm3 for controls, p<0.001).

Limitations, reasons for caution: The study is performed in a small group of patients; however, the rarity of the disease makes it challenging to recruit more male cystinosis patients. Moreover, we could not investigate the presence of testicular or epididymal sperm in all included cystinosis patients due to ethical reasons. Wider implications of the findings: The results obtained in the study further unravel the origin of the observed azoospermia in male infantile-type cystinosis patient by suggesting an obstructive cause. In addition, our research might provide a better age-dependent treatment to circumvent infertility in these patients.

Trial registration number:Not applicable

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Human Reproduction 34 (suppl1): 174-174 https://doi.org/10.1093/humrep/34.Supplement_1.1 Affiche scientifique
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 22 juill. 2021 21:54
Dernière modification: 15 févr. 2022 14:48
URI: https://espace.inrs.ca/id/eprint/11735

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