A comprehensive evaluation of cryptorchidism. epidemiology, risk factors, and clinical outcomes

Nº de DOI: 10.34896/RSI.2025.50.17.001

AUTHORS

1. Maritza Irene Calle León. General Practitioner. Attached to San Gabriel Clinic. Independent Researcher at the Matilde Hidalgo of Procel Research and Teaching Department. Graduate of the University of Guayaquil. (El Triunfo, Ecuador). https://orcid.org/0009-0000-3515-1683
2. Fabricio Josue Ruiz Procel. General Practitioner. Attached to the Urology Team. Graduate of the Catholic University of Cuenca. (⁠Machala-Ecuador). https://orcid.org/0009-0004-4725-6326
3. Jorge Andrés Zambrano Zambrano. General Practitioner. Attached to the Gustavo Domínguez Zambrano Hospital. Graduate of the University of Guayaquil. (Santo Domingo-Ecuador). https://orcid.org/0000-0001-7834-5795
4. Dhara Veruska Mendieta Díaz. General Practitioner. Attached to the Crucita Health Centre. Graduate of the University of Guayaquil. (Portoviejo-Ecuador). https://orcid.org/0009-0000-3808-3866
5. Ronie Hugo Crespo Tonato. General Practitioner. Attached to Private Clinics of Ecuador. Graduate of the Regional Autonomous University of Los Andes. (Salcedo -Ecuador). https://orcid.org/0009-0003-4070-9575

ABSTRACT

This comprehensive evaluation aims to synthesize current knowledge on the epidemiology, risk factors, and clinical outcomes of cryptorchidism, providing valuable insights into its pathogenesis, optimizing clinical management, and informing future research directions to improve patient prognosis and quality of life.

KEY WORDS

Cryptorchidism, undescended testis, epidemiology, risk factors, clinical outcomes, infertility, testicular cancer, and orchiopexy.

RESUMEN

Esta evaluación integral busca sintetizar el conocimiento actual sobre la epidemiología, los factores de riesgo y los resultados clínicos de la criptorquidia, aportando información valiosa sobre su patogénesis, optimizando el manejo clínico e informando sobre futuras líneas de investigación para mejorar el pronóstico y la calidad de vida de los pacientes.

PALABRAS CLAVE

Criptorquidia, testículo no descendido, epidemiología, factores de riesgo, resultados clínicos, infertilidad, cáncer testicular y orquidopexia.

INTRODUCTION

Cryptorchidism, commonly known as undescended testis, is among the most prevalent congenital anomalies affecting male infants worldwide, with significant implications for future reproductive health and oncological risk. Despite its widespread occurrence, the epidemiology of cryptorchidism exhibits notable variability across different regions, ethnic groups, and age cohorts, highlighting the importance of understanding its distribution and temporal trends. Over recent decades, epidemiological studies have documented fluctuations in incidence rates, raising questions about environmental, genetic, and healthcare-related factors influencing these patterns. The etiology of cryptorchidism is multifactorial, involving a complex interplay of genetic predispositions—such as familial inheritance patterns—and environmental exposures during critical periods of fetal development, including maternal health factors, endocrine disruptors, and perinatal conditions like prematurity and low birth weight. These risk factors not only contribute to the occurrence of cryptorchidism but also significantly impact the long-term clinical outcomes of affected individuals. Untreated or delayed correction of cryptorchidism has been associated with adverse consequences, notably impaired fertility due to testicular dysgenesis and an increased lifetime risk of testicular cancer, emphasizing the need for early diagnosis and intervention. Furthermore, the management strategies ranging from surgical orchiopexy to conservative monitoring have varying implications for testicular function and oncological risk mitigation.

OBJECTIVE

To synthesise current knowledge on the epidemiology, risk factors and clinical outcomes of cryptorchidism, providing valuable information on its pathogenesis, optimising clinical management and informing future research directions to improve prognosis and quality of life of patients.

METHODOLOGY

The methodology for this scientific review article, titled “A Comprehensive Evaluation of Cryptorchidism: Epidemiology, Risk Factors, and Clinical Outcomes,” adopts a structured and systematic approach to identify, evaluate, and synthesize the current body of evidence related to undescended testis. A comprehensive literature search is conducted using databases such as PubMed, Scopus, Web of Science, and Embase to retrieve peer-reviewed articles published in English over the past 20 years. The search strategy employs a combination of controlled vocabulary (e.g., MeSH terms) and free-text keywords, including “cryptorchidism”, “undescended testis”, “epidemiology”, “risk factors”, “clinical outcomes”, “infertility”, “testicular cancer” and “orchiopexy.” Boolean operators are used to refine and optimize the search.

The inclusion criteria encompass original research studies, systematic reviews, meta-analyses, and clinical guidelines that specifically address the incidence, prevalence, contributing risk factors (genetic, environmental, and perinatal), and long-term outcomes associated with cryptorchidism. Studies focusing on both unilateral and bilateral presentations are considered. Articles are excluded if they are case reports, editorials, animal-only studies, or if they lack relevance to the primary themes of the review.

The extracted data are synthesized thematically and analyzed to identify patterns, discrepancies, and knowledge gaps. Particular emphasis is placed on global variations in epidemiology, the interplay of genetic and environmental risk factors, and the implications of early versus delayed surgical intervention. Where applicable, statistical outcomes from meta-analyses are discussed to provide quantitative insight into risks and benefits.

RESULTS

Epidemiology of Cryptorchidism:

What are the global and regional prevalence rates of cryptorchidism?

The global and regional prevalence rates of cryptorchidism demonstrate striking variability, shaped by both biological factors and geographic influences. Globally, approximately 3% to 5% of full-term male infants are born with undescended testes, but this rate is not uniform across regions or populations¹. For instance, studies have documented that the prevalence among full-term newborns ranges from as low as 1% to as high as 9% depending on the country, with notable differences observed even among neighboring nationsq². For example, a comparative study found that Danish newborns had a fourfold higher risk of cryptorchidism (9.0%) compared to Finnish newborns (2.4%), highlighting sharp intra-regional contrasts that may reflect variations in diagnostic criteria, genetic backgrounds, or environmental exposures^2,3. Outside of Europe, prevalence rates also vary; in the United States, the rate for full-term boys is reported at 2.1%, while Malaysian data indicate a rate of 3.3%³. These differences are further complicated by the inclusion of both term and preterm infants in some analyses, as the prevalence among premature male neonates is substantially higher, reaching up to 30%¹. Regardless of region, the prevalence generally declines after birth as spontaneous testicular descent occurs, with global rates decreasing to about 1% to 2.5% by nine months of age¹. Such regional and temporal variations in prevalence emphasize the need for standardized diagnostic protocols and robust epidemiological surveillance to better understand the underlying causes and to guide public health interventions targeting at-risk populations.

How do age and ethnic background influence the incidence of cryptorchidism?

Age and ethnic background are intricately linked to the incidence and management of cryptorchidism, with significant implications for patient outcomes. Epidemiological studies indicate that certain ethnic groups, such as Asians, experience a higher prevalence of cryptorchidism, while delayed testicular descent is more commonly observed among Hispanic and Black populations⁴. These disparities in incidence are paralleled by differences in access to timely surgical intervention: racial and ethnic minorities are more likely to undergo orchiopexy at older ages, which increases their risks for subsequent subfertility and testicular malignancy due to delayed correction⁵. Moreover, Black and Hispanic children are disproportionately represented among those who receive surgery later than the recommended age, underscoring the influence of ethnic background not only on disease incidence but also on the timing of intervention⁵. Compounding these disparities, access to care, quality of surgical treatment, and postoperative outcomes also differ along racial and ethnic lines, with factors such as insurance status further contributing to delays in care⁵. These interconnected domains—disease prevalence, healthcare access, and treatment timing—highlight the urgent need for targeted interventions to ensure equitable and timely management of cryptorchidism across all demographic groups.

What trends have been observed in the epidemiology of cryptorchidism over recent decades?

Recent epidemiological data from Korea reveal a marked increase in the incidence of cryptorchidism, rising from 5.01 to 17.43 per 10,000 persons between 2000 and 2005, which aligns with broader global observations of rising prevalence in both Asian and Western populations over recent decades⁶. This upward trend is not uniformly distributed; for example, regions with significant petrochemical activity, such as Yeocheon and Ulsan, consistently reported higher incidence rates compared to the national average, whereas Chuncheon and the CC region exhibited notably lower rates during the same period⁶. Such regional disparities highlight the potential role of environmental exposures, particularly to endocrine disrupting chemicals (EDCs), which animal studies have shown can induce cryptorchidism when exposure occurs in utero⁷. The heightened incidence in youth children compared to both national and regional rates, as well as temporal spikes in the upper-limb and youth child regions, further supports the hypothesis that sensitive developmental windows, possibly influenced by environmental or lifestyle factors, may underlie these trends^6,7. These intertwined patterns suggest that a combination of industrial, geographic, and possibly sociocultural determinants contributes to the rising burden of cryptorchidism, emphasizing the urgent need for targeted research into regional differences and environmental risk factors to inform public health interventions and preventive strategies⁶.

Risk Factors Associated with Cryptorchidism:

What genetic factors contribute to the development of cryptorchidism?

Genetic factors play a central role in the etiology of cryptorchidism, as evidenced by both familial aggregation and the identification of multiple genetic loci associated with the condition. Familial clustering—such as the increased prevalence observed among first-degree relatives and the notably higher rates in fathers, brothers, and siblings of affected individuals—strongly supports a hereditary component and suggests a multilocus model of genetic susceptibility⁸. Despite this, the genetic architecture underlying cryptorchidism remains complex and heterogeneous, with no single genetic marker reliably replicated as a definitive risk factor for non-syndromic cases, highlighting the intricate interplay between various genes and potential environmental modifiers⁹. Among the candidate genes implicated, mutations in INSL3 and its receptor LGR8 have been shown to disrupt the hormonal and anatomical processes necessary for testicular descent, while elongated CAG and GGN repeats within the androgen receptor (AR) gene have been associated with bilateral forms of cryptorchidism, illustrating that both endocrine regulation and cytoskeletal mechanisms are intertwined in the pathogenesis⁹. Genome-wide association studies further reinforce this complexity, identifying numerous loci involved in cytoskeletal function and androgen receptor signaling pathways, and animal models corroborate the importance of these genetic factors in testicular development^8,9. The overlapping domains of protein-coding genes, chromosomal mutations, and copy number variations reflect the multifactorial and interconnected landscape of genetic risk, necessitating continued research to unravel the precise genetic networks involved and to inform targeted interventions for at-risk populations¹⁰.

How do environmental exposures and maternal health affect the risk of cryptorchidism?

The interplay between environmental exposures and maternal health reveals a multifaceted risk profile for cryptorchidism, implicating both paternal and maternal factors as well as the broader context of environmental contaminants. Notably, paternal occupational exposure to pesticides has been consistently associated with a heightened risk of cryptorchidism, with some estimates indicating an odds ratio as high as 3.8, underscoring the influence of paternal environmental contact on fetal development¹¹. In contrast, maternal occupational, dietary, and lifestyle exposures have not demonstrated a significant association with cryptorchidism, suggesting that the maternal route of exposure might be less critical, or that current assessment methods do not capture relevant risk vectors as effectively¹¹. Nonetheless, suboptimal maternal health, encompassing conditions such as preterm delivery, low maternal education, and possible maternal age and country of origin interactions, emerges as a crucial determinant of increased cryptorchidism risk, highlighting the central role of maternal health status and sociodemographic context in shaping outcomes¹¹. These findings indicate that while direct maternal environmental exposures may not independently raise the risk, the intersection of parental health, environmental factors, and social determinants collectively modulates the likelihood of cryptorchidism. To address this complex etiology, comprehensive interventions targeting both the reduction of paternal occupational exposures and the improvement of maternal health—especially in vulnerable subgroups—are essential for mitigating risk and promoting better reproductive health outcomes.

What perinatal and neonatal conditions are linked to an increased risk of cryptorchidism?

Multiple perinatal and neonatal conditions have been identified as contributing factors to the increased risk of cryptorchidism, highlighting the complex interplay of genetic predisposition, fetal development, and maternal influences. Prematurity stands out as a significant risk factor, with premature infants exhibiting a notably higher incidence of undescended testes compared to their full-term counterparts^12,13. This association is closely linked to the fact that testicular descent typically occurs during the final trimester of gestation, and interruption of this process due to early birth can result in incomplete descent. Similarly, low birth weight—both as an absolute measure and when assessed relative to gestational age—has been repeatedly associated with a greater likelihood of cryptorchidism, suggesting that intrauterine growth restriction and suboptimal fetal environments play a critical role in testicular development and positioning^12,14,15. Maternal factors further exacerbate these risks; for instance, maternal tobacco smoking, exposure to certain environmental toxins, and prepregnancy overweight or obesity have all been implicated in disrupting the hormonal milieu necessary for normal testicular descent¹³. The intrauterine environment, shaped by such maternal behaviors and exposures, likely exerts a stronger influence on the risk of cryptorchidism than paternal or purely genetic factors, underscoring the need for targeted interventions during pregnancy to mitigate these modifiable risks¹³. This interconnection between neonatal health, fetal growth parameters, and maternal well-being emphasizes the importance of comprehensive perinatal care, with a particular focus on optimizing maternal health and minimizing environmental exposures to reduce the burden of cryptorchidism in at-risk populations.

Clinical Outcomes of Cryptorchidism:

How does cryptorchidism impact fertility and testicular function later in life?

Cryptorchidism, a condition characterized by the failure of one or both testes to descend into the scrotum, significantly affects fertility and testicular function later in life through a complex interplay of anatomical, hormonal, and developmental disruptions. The distinction between unilateral and bilateral cryptorchidism is crucial, as bilateral cases—where both testicles are undescended—are more often associated with severe abnormalities in semen quality, including azoospermia, or the complete absence of spermatozoa in the ejaculate¹⁶. In contrast, unilateral cryptorchidism, which involves only one testicle, generally has a less pronounced effect on fertility, though it still poses risks for compromised testicular health¹⁶. At the physiological level, untreated cryptorchidism can impair both hormone production and spermatogenesis, leading to decreased testicular hormone concentrations and potential dysfunction of Leydig and Sertoli cells, which are essential for normal testicular development and fertility^17,18. These disruptions in testicular function are further reflected in smaller testicular volumes among subfertile men with a history of cryptorchidism compared to their non-cryptorchid or fertile counterparts, with bilateral cases demonstrating even greater reductions in testicular size¹⁸. The interconnection between impaired testicular function, altered testicular architecture, and compromised reproductive outcomes highlights the necessity for early intervention. Timely diagnosis and management, including consideration of surgical and hormonal therapies, are vital for mitigating long-term adverse effects, emphasizing the need for proactive clinical strategies to preserve fertility and optimize testicular health in affected individuals^16,17,19.

What is the relationship between cryptorchidism and the risk of testicular cancer?

The relationship between cryptorchidism and the risk of testicular cancer has been firmly established through numerous epidemiological and clinical studies, demonstrating that males with a history of cryptorchidism are several times more likely to develop testicular cancer than those with normally descended testes²⁰. This increased risk extends beyond the anatomical abnormality itself, as cryptorchidism is now recognized as a core component of testicular dysgenesis syndrome, suggesting that the underlying developmental and genetic factors contribute to both the failure of testicular descent and malignant transformation²¹. Notably, the risk is most pronounced in the undescended testicle, with research showing a four- to sixfold increase in cancer incidence, but even the contralateral, normally descended testicle in unilateral cryptorchidism carries an elevated risk, albeit to a lesser degree²². The interconnections between the abnormal testicular environment—characterized by increased temperature and hormonal dysregulation—and somatic cell mutations in cryptorchid testes play a pivotal role in this carcinogenic process, potentially leading to both morphological breakdown and the misexpression of growth factors that drive tumorigenesis²³. Furthermore, while early surgical intervention (orchiopexy) is advocated to mitigate cancer risk, it does not completely abrogate the long-term risk, pointing to the persistent impact of early developmental insults and the need for ongoing surveillance in affected individuals^23,24. These findings underscore the importance of timely diagnosis, individualized management, and long-term monitoring for patients with cryptorchidism to address the multifaceted risks associated with this condition and to intervene early in the event of malignant transformation.

What are the long-term outcomes following surgical and non-surgical management of cryptorchidism?

The long-term outcomes of cryptorchidism management are intricately tied to the timing and modality of intervention, with significant implications across reproductive, endocrine, and oncological domains. Early surgical correction, particularly orchidopexy performed between 6 and 12 months of age, has been shown to improve testicular volume, increase the number of spermatogonia per tubule, and thereby enhance fertility potential in adulthood²⁵. Furthermore, prompt intervention reduces the risk of neoplastic transformation, which is a critical consideration given the persistent, albeit slight, increase in testicular cancer risk among individuals with a history of cryptorchidism¹. Both congenital and acquired forms of the condition carry similar threats to future fertility, underscoring the necessity for strategic treatment planning to mitigate adverse reproductive outcomes^14,25. Advances in laparoscopic surgical techniques have broadened management options for non-palpable testes, yielding comparable success rates and long-term testicular health outcomes when contrasted with traditional approaches²⁵. However, despite surgical and, in some cases, hormonal interventions, men with prior cryptorchidism remain susceptible to testicular hypofunction—manifested by diminished testis volume, lower sperm concentration, and impaired Leydig cell function—pointing to lingering physiological consequences that necessitate ongoing surveillance and patient counseling¹. Collectively, these interconnections between early diagnosis, timely surgical or hormonal management, and long-term endocrine-reproductive health highlight the need for proactive, multidisciplinary interventions to optimize outcomes and minimize lifelong complications in affected individuals.

DISCUSSION

The comprehensive evaluation of cryptorchidism presented in this study underscores its complexity as a multifactorial condition influenced by a confluence of genetic, environmental, and socio-economic factors. The marked variability in prevalence across different regions and ethnic groups highlights the necessity for standardized diagnostic criteria and robust surveillance systems to facilitate more accurate epidemiological assessments. The observed associations between environmental exposures—particularly endocrine-disrupting chemicals and paternal occupational contact with pesticides—and increased risk emphasize the critical need for further research into the environmental determinants of cryptorchidism. Additionally, the influence of maternal health factors such as preterm birth, low birth weight, and smoking suggests that prenatal care and maternal health optimization could serve as pivotal intervention points. The disparities in healthcare access and treatment timing among different populations reveal systemic inequities that may contribute to poorer long-term outcomes, including subfertility and increased testicular cancer risk. While advancements in minimally invasive surgical techniques have improved management, the persistent elevated risk of testicular malignancy and hypofunction in affected individuals indicates that current interventions may not fully mitigate the long-term sequelae. This underscores the importance of ongoing surveillance and long-term follow-up, especially for bilateral cases, to facilitate early detection of malignancy and preserve reproductive function. However, the study’s reliance on observational data and regional variations introduces limitations, such as potential selection bias and underreporting, which warrant cautious interpretation of the findings. Future research should aim to elucidate the genetic and molecular pathways underlying testicular maldescent and carcinogenesis, as well as evaluate the efficacy of early intervention strategies in diverse populations. Addressing the identified disparities and environmental risk factors will be crucial in developing targeted public health policies and preventive measures. Overall, this study reinforces the imperative for a multidisciplinary approach that integrates genetic research, environmental health, and healthcare equity to improve outcomes for individuals with cryptorchidism worldwide.

CONCLUSIONS

1. Cryptorchidism, or undescended testis, represents one of the most common congenital anomalies in male infants and continues to pose significant challenges in pediatric urology and reproductive health. This comprehensive review underscores the multifactorial nature of the condition, with contributions from genetic, hormonal, environmental, and maternal factors influencing its development.
2. The global variation in incidence—particularly higher rates in preterm infants and certain geographic regions—suggests that both biological susceptibility and environmental exposures play crucial roles. Furthermore, the review highlights the importance of early detection and timely surgical correction, typically recommended before 18 months of age, to optimize outcomes.
3. From a clinical perspective, cryptorchidism is associated with notable long-term risks, including subfertility, increased likelihood of testicular malignancy, testicular torsion, and psychological effects related to body image and masculinity. While early orchiopexy improves fertility potential and facilitates surveillance for malignancy, the risk is not entirely eliminated, especially in cases where treatment is delayed. Despite advances in surgical techniques and a better understanding of hormonal regulation, controversies remain regarding the efficacy of hormonal therapy and the ideal timing for intervention in certain borderline cases.

FUTURE DIRECTIONS

1. Future research should prioritize the identification of precise genetic markers and prenatal exposures that predispose to cryptorchidism, which would enhance early diagnosis and prevention strategies. Large-scale, prospective cohort studies are needed to establish more accurate risk prediction models and to evaluate the long-term reproductive and oncologic outcomes of different treatment modalities. Additionally, studies exploring the psychosocial impacts of undescended testis and its treatment are limited and warrant greater attention.
2. There is also a need to refine surgical guidelines, particularly regarding management of non-palpable or intra-abdominal testes, and to evaluate the long-term efficacy of laparoscopic versus open approaches. Advancements in imaging and minimally invasive techniques may further improve diagnostic precision and outcomes. On a broader scale, public health initiatives aimed at educating healthcare providers and caregivers about the importance of early intervention, especially in underserved regions, will be critical to improving global health outcomes related to cryptorchidism. By integrating genetic research, clinical innovation, and public health awareness, future strategies can offer more personalized, timely, and effective care for individuals affected by this condition.

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