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Blood Biomarkers Predict Risk of Future Infertility in Children With Undescended Testis

The ratios of sex hormones in serum can help predict the extent of impaired germ cells and risk of infertility, eliminating the need for a testicular biopsy.

Normal testis development involves the progressive migration of the developing testes to reach the scrotum. This development cascade is an incredibly complex process that begins even before birth and involves various physiological processes and interactions of different cell types. Any abnormality in the cascade could easily compromise sex development and ultimately lead to male infertility.

In cryptorchidism, the most common genital problem encountered in paediatric urology, one or both testicles fail to descend into the proper scrotal position by the time of birth. Later in life, cryptorchid individuals face a high risk of infertility. Therefore, predicting the link between cryptorchidism and the chance of infertility may be useful to treat the condition and bring new insights into male infertility. However, the lack of appropriate biomarkers has impeded research efforts in developing a robust prediction method.

In a novel study by a research group from Japan, including Dr. Taiki Kato of Nagoya City University East Medical Center; and Dr. Kentaro Mizuno, Dr. Hidenori Nishio, and Dr. Yutaro Hayashi of Nagoya City University Graduate School of Medical Sciences, scientists have successfully uncovered the ratio of several sex hormones in serum that can provide valuable clues to predict future infertility in cryptorchid boys.

Normally, diagnosing male infertility requires a testicular biopsy. This involves analysing germ cells, which are the source of sperm cells, in males and therefore, linked to fertility. However, some cryptorchid individuals have a fewer number of germ cells in their testes. Therefore, scientists use the mean number of germ cells per tubular transverse section (G/T) that is found in the small portion of the testis to predict future infertility in cryptorchid boys. This small segment is usually removed during “orchidopexy”, which moves the undescended testicle into the scrotum. However, surgical biopsies introduce risks such as injury, infection, or hypogonadism, hence the need for a safer diagnostic method.

Hoping to solve this problem, the scientists embarked on a search for suitable biomarkers that can be easily detected in the serum.

“The state of testes dramatically changes during puberty. Therefore, we identified 145 prepubertal boys, aged between 7-91 months, who underwent orchidopexy due to unilateral or bilateral cryptorchidism between 2014 and 2019, at our hospital. From the available clinical records, we evaluated the pre-treatment testicular position and size; serum hormone levels; and the mean number of germ cells per tubule transverse section (G/T) of these boys,” explained senior author Dr. Kato regarding their investigation.

While it is known that inhibin B and anti-Mullerian hormone (AMH) can act as direct markers of spermatogenesis and the function of Sertoli cells, the latter of which are important for proper testicular development, the researchers took a step further to identify biomarkers based on the pre-treatment testicular positions.

Their results showed that serum inhibin B levels and G/T were significantly lower in boys suffering from bilateral cryptorchidism than those with unilateral cryptorchidism. In bilateral cryptorchid boys less than or equal to 2 years old, it was also observed that the inhibin B/follicle-stimulation hormone (FSH) ratio and AMH/FSH ratio positively correlated with G/T, the standard infertility marker. In contrast, the levels of serum hormones and G/T did not differ in boys with unilateral undescended testis.

“Based on the ratios of sex hormones in serum, we can now predict the extent of impaired germ cells and the high risk of infertility without performing a testicular biopsy. Further, the hormonal assessment may guide decisions regarding additional hormonal therapy after orchiopexy for a closer and longer follow-up of patients after the surgery,” said Dr. Kato.

From a patient care perspective, these findings may greatly change clinical practice scenarios for patients with cryptorchidism by initiating changes in clinical guidelines and even counselling strategies of families of children with bilateral undescended testes based on their preoperative hormonal evaluation. In future, the researchers believe that it may be useful to prioritise the order of patients who require orchidopexy based on their predicted chance of infertility. [APBN]

Source: Kato et al. (2021). Low Serum Inhibin B/Follicle-Stimulating Hormones and Anti-Müllerian Hormone/Follicle-Stimulating Hormones Ratios as Markers of Decreased Germ Cells in Infants with Bilateral Cryptorchidism. Journal of Urology.