The case presented herein highlights the potential association between polyorchidism and male infertility, specifically severe asthenozoospermia and teratozoospermia. Furthermore, transmission electron microscopy provided additional evidence of ultrastructural defects and mitochondrial damage within spermatozoa. Despite medical treatment and failed ART attempts, the lack of significant improvement underscores the challenges in managing polyorchidism with severely impaired spermatogenesis. Consequently, although polyorchidism is a rare condition, its potential impact on male fertility should not be overlooked, as evidenced by this case.
This intricate case thus sets the stage for a deeper investigation into the underlying causes and contributing factors of male infertility in the context of polyorchidism. The etiology of male infertility in patients with polyorchidism remains poorly understood, with various factors potentially contributing to impaired spermatogenesis or sperm quality. Although evidence definitively linking polyorchidism to specific sperm abnormalities has been limited, prior reports have documented associations between polyorchidism and impaired semen parameters, suggesting a predisposition to male infertility in some individuals [7, 8]. To this end, the complexity of factors involved underscores the necessity for extensive research to unravel the multifaceted relationship between polyorchidism and impaired semen parameters.
Among the myriad factors influencing male fertility, mitochondrial function emerges as a critical element. Mitochondria play an indispensable role in sperm motility, providing energy through oxidative phosphorylation [14]. Consequently, mitochondrial dysfunction or damage can lead to impaired sperm motility and additional sperm defects [15, 16]. In this specific case, the patient exhibited mitochondrial damage in sperm, potentially contributing to the observed severe asthenozoospermia. The mechanism underlying these mitochondrial abnormalities remains unclear but is speculated to relate to the potential impact of polyorchidism on the testicular microenvironment and spermatogenesis. This rare finding suggests a potential pathophysiological mechanism, indicating that the presence of additional testes may impair sperm motility through mitochondrial damage, energy depletion, or related apoptotic pathways [17,18,19,20]. However, it is important to note that the relationship between polyorchidism and mitochondrial dysfunction cannot be conclusively established based on a single case. Accordingly, further studies are imperative to elucidate whether mitochondrial dysfunction and impaired sperm motility represent common manifestations of polyorchidism.
In addition to mitochondrial damage, the patient’s high sperm DFI of 53.6% is noteworthy. While the exact cause of the elevated DFI remains uncertain, the patient’s bilateral varicocele may have contributed to the increased DNA fragmentation, as varicocele has been independently associated with higher DFI [21]. This finding underscores the importance of considering concomitant factors, such as varicocele, when evaluating the impact of polyorchidism on male fertility.
Genetic factors also demand attention for their potential role in the development of polyorchidism and subsequent infertility challenges. While no known pathogenic gene variations or Y chromosome AZF microdeletions were identified in this case, other genetic abnormalities have been documented in polyorchidism patients. Notably, a study by Fiorella Shabtai et al. highlighted a case of a neonate with polyorchidism, revealing the novel discovery of ipsilateral intra-abdominal testes along with a chromosome 21 long arm deletion [22]. Furthermore, cases of polyorchidism associated with chromosomal syndromes [23], and several instances of disorders of sexual differentiation, specifically in individuals with karyotypes of 46,XX [24] and 46,XY DSD [25], have been documented. These findings indicate that genetic factors may contribute to the development of polyorchidism and associated reproductive abnormalities in certain patients.
Understanding the intricate interplay of mitochondrial and genetic factors in polyorchidism lays the groundwork for addressing the significant challenges inherent in its management, particularly in the realm of male infertility. The management of polyorchidism, particularly in the context of male infertility, presents significant challenges. The recommended approaches for managing symptomatic polyorchidism are still a subject of controversy. Some experts advocate for surgical interventions such as orchiopexy or orchiectomy for supernumerary testes with abnormal characteristics, to minimize risks such as torsion, malignancy, or infertility [26]. However, it is important to note that surgical removal can also entail risks, including testosterone deficiency, anti-sperm antibody formation, and ischemic atrophy of the remaining testicular tissue. It is crucial to consider the potential impact of polyorchidism on hormonal regulation and spermatogenesis feedback mechanisms. In this case, the patient’s hormonal profiles were within normal ranges, and clomiphene therapy may not have been essential. Considering the patient’s fertility aspirations, we recommended a trial of conservative medical therapy. Despite pursuing conservative management and ART, these interventions failed to significantly improve sperm motility, thus not achieving successful conception for this patient. In cases resistant to initial treatments, a more definitive surgical approach, involving the removal of abnormal testicular tissue, may become necessary to achieve pregnancy. Careful patient counseling and the management of expectations play a crucial role in the management of polyorchidism, particularly when semen parameters are profoundly impaired.
While repeated testosterone measurements would have provided a more comprehensive hormonal profile, the patient’s decision to pursue assisted reproductive treatment precluded additional testing. Although polyorchidism has been associated with an increased risk of testicular cancer [1], the patient chose to prioritize assisted reproductive treatment. We will advise the patient to undergo oncological marker testing in the future. Reactive oxygen species measurement was not performed on the patient’s semen. The lack of improvement with antioxidant therapy suggests that significant oxidative stress may not have been the primary cause of the patient’s infertility.
This rare case of polyorchidism, characterized by severe asthenozoospermia, teratozoospermia, and mitochondrial damage in sperm, clearly illustrates the significant impact of this congenital anomaly on male fertility. This necessity for comprehensive evaluation and personalized management strategies in such cases is underscored, emphasizing a tailored approach to treatment. Consequently, further research is crucial to elucidate the mechanisms underlying polyorchidism and its impact on male fertility, and to develop targeted therapeutic strategies aimed at enhancing reproductive outcomes in affected individuals.
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