5th International Andrology Symposium
5th International Andrology Symposium
Beata Vincel (Vilnius)
Children’s Surgery Centre, Clinic of Gastroenterology, Nephrourology and Surgery, Institute of Clinical Medicine, Vilnius, Lithuania
Correspondence; Dr med PhD Beta Vincel Institute of Clinical Medicine, Vilnius, Lithuania
International guidance on cryptorchidism has been shaped by three reference documents: the Nordic consensus (2007), the American Urological Association (AUA) guideline (2014), and the periodically updated European Association of Urology/European Society for Paediatric Urology (EAU/ESPU) guidelines, which were most recently revised in 2024. These statements agree regarding early orchidopexy (generally before 12–18 months of age), avoidance of routine imaging before specialist referral, and laparoscopy for non-palpable testicles. Clinical studies demonstrate that surgery alone—even early and expertly performed surgery—does not fully restore male reproductive potential in 50% of cryptorchid boys belonging to the high infertility risk (HIR) group. This patient group suffers hypogonadotropic hypogonadism, such that the logical treatment approach includes hormonal replacement.
Since the drafting of the main reference guidelines, emerging translational evidence has refined our understanding of the biology of mini-puberty, the prognostic value of Ad spermatogonia, and the molecular/epigenetic landscape that underpins impaired germ-cell maturation in cryptorchidism. The present review appraises which aspects of contemporary guidance remain robust, which recommendations lag behind new data, and where pragmatic multidisciplinary updates are likely warranted. It concludes with targeted proposals aimed at aligning future guidance with the latest science, while preserving the feasibility of implementation across varied health systems.
Key words. Cryptorchidism, treatment, surgery, Rey
Les recommandations internationales concernant la cryptorchidie reposent sur trois documents de référence : le consensus nordique (2007), les recommandations de l’Association américaine d’urologie (AUA) (2014) et les recommandations périodiquement mises à jour de l’Association européenne d’urologie/Société européenne d’urologie pédiatrique (EAU/ESPU), dont la dernière révision date de 2024. Ces recommandations s’accordent sur l’orchidopexie précoce (généralement avant l’âge de 12 à 18 mois), l’absence de recours systématique à l’imagerie avant consultation spécialisée et la laparoscopie en cas de testicule non palpable. Des études cliniques démontrent que la chirurgie seule, même précoce et réalisée par un expert, ne permet pas de rétablir pleinement la fertilité masculine chez 50 % des garçons cryptorchides appartenant au groupe à haut risque d’infertilité (HRI). Ces patients souffrent d’hypogonadisme hypogonadotrope, ce qui justifie l’instauration d’un traitement hormonal substitutif. Depuis l’élaboration des principales recommandations de référence, les données translationnelles émergentes ont affiné notre compréhension de la biologie de la mini-puberté, de la valeur pronostique des spermatogonies Ad et du paysage moléculaire/épigénétique sous-jacent à l’altération de la maturation des cellules germinales dans la cryptorchidie. La présente revue évalue quels aspects des recommandations actuelles restent pertinents, quelles recommandations sont en retard par rapport aux nouvelles données et où Des mises à jour pragmatiques et multidisciplinaires sont probablement nécessaires. Le document se conclut par des propositions ciblées visant à aligner les futures recommandations sur les données scientifiques les plus récentes, tout en préservant la faisabilité de leur mise en œuvre dans divers systèmes de santé.
Mots clés : cryptorchidie, traitement, chirurgie, hormones
In pediatric urology, guidelines have the power to shape referrals, parental expectations, intervention timing, and how success is measured [1–3]. While the “gold-standard” surgery, orchidopexy, is standardized and safe, it is not curative in cases where cryptorchidism is more than a positional problem. Even with appropriate surgery, long-term outcomes, including adult fertility and paternity, remain suboptimal for men with previously undescended testicles [4–10]. New data regarding the biology of mini-puberty and germ-cell transformation challenge the notion that testicular repositioning alone is sufficient to ensure future reproductive potential in a substantial subset of patients [11–14].
This review examines whether current guidance is fully aligned with the most recent evidence. The three most influential guidance documents are summarized. Next, specific domains are reviewed—including diagnosis, imaging, timing, surgical technique, and the potentially crucial role of hormonal therapy—using recent studies and translational work presented at The 5th International Andrology Symposium — Cryptorchidism: Molecular Biology meets Endocrinology and Surgery. Finally, areas where the current recommendations should be refined are identified and denoted.
The Nordic statement was seminal in consolidating early surgery (ideally before 1 year of age), deemphasizing imaging, and recommending laparoscopy for non-palpable testicles [1]. It reflects skepticism towards the use of hormonal therapy to induce testicular descent. Many of its surgical and diagnostic positions have aged well; however, some of its recommendations are now outdated. Notably, it has not been updated to reflect the latest results regarding restoration of fertility potential, i.e. spermiograms.
The AUA reinforces early orchidopexy, and discourages routine imaging before specialist evaluation, since ultrasonography has poor sensitivity for non-palpable testicles and rarely changes management strategy [2]. Critically, the AUA advises against administering hormonal therapy to induce descent, due to low response and lack of durable efficacy [2, 15, 16]. However, this position is contradicted by the results of long-term follow-up studies, with Höcht et al. reporting that 52% of testicles remain descended at 10 years after hormonal treatment [17], and Waldschmidt et al. showing that 50.5–67% of testicle remain descended at 5–7 years after treatment [18].
The recommendations of the EAU/ESPU mirror those of the AUA with regards to diagnostic and surgical fundamentals, imaging, and timelines, with surgery ideally performed between 6–12 months of age, and not later than 18 months of age [3]. The distinctive position of the EAU/ESPU guidelines is to consider low-dose GnRH analogues as an adjunct for fertility preservation in bilateral cases, after successful orchidopexy, with acknowledgement of the evidence showing improved markers of germ-cell maturation (e.g. Ad spermatogonia) in carefully phenotyped cohorts [3, 17–22].
In all statements, the hands-on exam is rightfully placed at the center of diagnosis and triage. Distinguishing a retractile testicle from a truly undescended testicle carries profound consequences: the former requires only observation, not surgery or hormones; while the latter benefits from timely surgery to correct its positioning [2, 3, 23–26]. Patience, proper positioning (e.g. cross-legged “frog” position), and allowing the cremaster to fatigue are pragmatic and evidence-concordant practices that reduce misclassification.
The AUA and EAU/ESPU guidelines discourage the use of ultrasound for initial evaluation, since this method exhibits poor sensitivity and specificity for non-palpable testicles, and recommend that these patients should be referred for examination by an experienced pediatric surgeon or urologist [2, 3, 27, 28]. Data from the Choosing Wisely® initiative suggest that inappropriate imaging remains common despite guidance, underscoring the need for education and system-level reminders [29].
Diagnostic laparoscopy is the gold standard, offering immediate therapeutic paths—including orchidopexy, one- vs two-stage Fowler–Stephens, or confirmation of testicular absence [2, 3, 23, 30–32]. No new data have overturned this approach.
Although surgery cannot guarantee a positive final fertility outcome, all major guidelines recommend that orchidopexy be performed within the first year of life (ideally 6–12 months of age), and certainly before 18 months of age, with the aim of minimizing acquired histological damage [1–3, 16, 33].
Mini-puberty, during the first 3–6 months of life, is characterized by transient rises of GnRH/LH/FSH and testosterone, which drive the critical transition of gonocytes to type A dark (Ad) spermatogonia—i.e. the human spermatogonial stem-cell pool [5, 11–14]. Failure of this transition predicts severe oligospermia/azoospermia later in life, despite technically successful orchidopexy; azoospermia development is observed in 32% of patients with bilateral undescended testicles, and 10% with unilateral undescended testicles [5–11, 13, 34]. Studies in multiple cohorts demonstrate that an absence or paucity of Ad spermatogonia in early biopsies is linked to poor adult sperm counts in cases of cryptorchidism [5, 6, 10–13, 34]. In other words, a correct position of the testicle is necessary, but biology determines fertility potential.
Some guidance states that hormonal therapy to induce testicular descent is ineffective, or not durably effective, and should not be used as primary treatment [1–3, 15, 16]. However, the EAU/ESPU guidelines include a carefully worded allowance to consider low-dose intermittent treatment with GnRH analogues after successful orchidopexy in selected boys, with bilateral disease and histologic signs of impaired germ-cell maturation. This recommendation is aligned with translational and clinical signals showing improved markers (e.g. increased Ad spermatogonia and biomarkers of Sertoli cell function) and possibly better long-term semen parameters in some cohorts [3, 17–22]. In one study, early surgery showed no positive impact on these parameters, as the sperm quality of the surgical group did not differ from the sperm results of untreated boys, and these authors concluded that hormonal therapy is advisable for all patients with cryptorchidism, independently from the surgical option to promote testicular descent to the scrotum [22]. A recent narrative synthesis and small prospective series consistently demonstrate these benefits, while emphasizing the need for careful selection and standardized protocols [17–22]. Best results were obtained with Pergoveris,( LH/FSH 75/150 IU) therapy; all 20 bilateral intraabdominal cryptorchid testes descended to the scrotal position [35].
Routine biopsy of all cryptorchid testes should be performed at the time of orchidopexy to identify patients who require subsequent hormonal treatment. Biopsy analysis by a trained pathologist can provide powerful prognostic information, e.g., Ad spermatogonia counts [5, 6, 10–14, 36]. Notably, there are real-world barriers to routine biopsy—including inconsistent pathology expertise, lack of standardized reporting, and system incentives that discourage the practice. However, none of these barriers constitute a scientific reason to avoid biopsy where it can improve case management.
It is increasingly indefensible to treat every boy with cryptorchidism as if surgery alone will normalize risk. Guidance must be updated to acknowledge the prognostic role of Ad spermatogonia in cryptorchidism, regardless of whether it is unilateral or bilateral; as well as to describe structured pathways for centers with the capability to phenotype risk (biopsy and expert histology) and to offer adjuvant time-limited GnRH analogue therapy after orchidopexy for the patients at highest risk [3, 5–14].
The current guidance regarding cryptorchidism remains strong in terms of its surgical core—which includes early expert orchidopexy, minimal pre-referral imaging, and laparoscopy for non-palpable testicles. However, it lags in translating a decade of progress in developmental and molecular andrology into actionable and equitable recommendations for fertility preservation in HIR cryptorchid boys. The EAU/ESPU guidelines include a cautious allowance for post-orchidopexy treatment with GnRH analogues in such cases, which is congruent with the best available translational signal. The AUA could converge with this narrow risk-stratified use, while continuing to discourage hormone therapy for inducing testicular descent. An interdisciplinary update—co-authored by experts in pediatric surgery/urology and pediatric endocrinology—would harmonize global practice, reduce unwarranted imaging and operations and, most importantly, give families evidence-based and realistic paths to parenthood. Overall, the next edition of guidance should retain its surgical backbone, while adding a measured endocrine “limb”, which will constitute a potentially decisive addition for boys whose risk is determined by biology, rather than just anatomy.
I thank colleagues across Europe and the Americas for candid discussions that informed the practical emphasis herein, and the organizers for the opportunity to align surgical craft with endocrine science. Funding No financial conflicts.
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