Pediatric cryptorchidism and male infertility

After birth, a testicle that has not descended to its normal anatomical position, i.e., is not palpable in the scrotum, is called cryptorchid. The position of the testis can be anywhere on the way down or it may be ectopic elsewhere. The temperature in the scrotum is 1.5-2.0°C lower than in the abdominal cavity, and this temperature difference is sufficient to affect the process of spermatogenesis. I. Occurrence and classification of cryptorchidism 1. Embryology of descending testes In women, the undifferentiated gonads differentiate into fetal testes under the influence of SRY proteins during the 7th week of pregnancy. In male embryos at week 8, the fetal testes begin to secrete two hormones, testosterone and mullerian inhibitory factor. Testosterone is secreted by fetal Leydig cells and is regulated by maternal hCG. Mullerian inhibitory factor secreted by fetal Sertoli cells causes degeneration of the Mullerian duct, leaving only the testicular appendages remaining. At the same time as the testicular sheath emerges, the levator ani muscle differentiates from the internal abdominal oblique muscle. At this time the testis is located at the upper end of the testicular lead. Between 12 weeks and 7 months of embryonic life, the testis descends in response to dihydrotestosterone. The testicular sheath “herniates” out of the weak deltoid region below the abdominal wall and into the scrotum. Gonadotropins and testosterone play a major role in the descent of the testis. Tests have shown that gonadotropins cause the testes to descend in preterm animals, while blocking dihydrotestosterone synthesis in animals causes cryptorchidism in newborns. In patients with Kallman syndrome who are deficient in GnRH, cryptorchidism can be one of the typical presentations. Other factors that determine testicular descent are (1) the pull of the testicular lead and the levator muscle, (2) the development of the abdominal wall at a certain rate while the lead is relatively static, resulting in a spatial discrepancy, (3) the passage of the testis through the inguinal canal by abdominal pressure, (4) the role of the epididymis in development, and (5) the role of the genitofemoral nerve. Abnormalities in all of the above factors can lead to cryptorchidism. 2, Incidence of cryptorchidism Cryptorchidism is common, but should be distinguished from the sliding testicle (retractiletestis). The incidence of cryptorchidism is 30.3% in preterm infants and 3.4% in full-term newborns. The incidence of cryptorchidism in one-year-old boys is 0.8-1.5%. The incidence of cryptorchidism in adults is about 1%. This means that 75% of full-term infants and 95% of preterm infants will have a cryptorchid testis that descends into the scrotum within the first year of life, actually within three months. If the cryptorchid testis does not descend into the scrotum within the first year of life, it will not descend thereafter. Surgical exploration in cryptorchidism reveals an absent testicle in 3-5% of cases. 10% of cryptorchid patients are bilateral, and 3% of them have one or both testes missing. 3.Classification of cryptorchid testis Undescended testis can be classified into four types: (1) abdominal type, which is located above the inner ring; (2) inguinal canal type, which is located between the inner and outer rings; (3) ectopic type, which is far away from the normal path of descending testis, and the five common ectopic sites are perineum, foramen ovale, inguinal hypodermis, suprapubic region, and contralateral scrotal sac, and the inguinal hypodermis is the most common one; (4) glide type, which is a fully descended testis can be found at the bottom of the scrotum and in the inguinal hypodermis. freely between the base of the scrotum and the groin. There are also various possibilities to classify the location of testis into two categories: palpable and nonpalpable. 2. Cryptorchidism and male infertility Cryptorchidism can occur as a comorbidity of infertility, testicular tumor and testicular torsion, etc. In the first three months of embryonic life, the testes can be found in the first two weeks of life. During the first 3 months of the embryo, the number of Sertoli cells grows until it remains stable until puberty, and spermatogonia are transformed into spermatogonia during the first 6 months. At birth, germ cells may be reduced in the undescended testis. The undescended testis may have congenital abnormalities. The number of germ cells may be normal before birth, but studies have shown that the number of germ cells in the seminiferous tubules of cryptorchid testes, as well as the total number of germ cells, decreases before birth. The size and weight of the testes also decrease. Studies have shown a decrease in the number of germ cells in the ductus deferens in undescended testes in children aged 0-1 yr. Seventy-five percent of children aged 1-2 yr who have undergone testicular immobilization have a decrease in the number of germ cells. If the testis is not immobilized in the scrotum, the number of germ cells may be further reduced, and infertility in adulthood is more likely.Germ cell reduction occurs in more than 90% of children between the ages of 3 and puberty. Undescended testes will delay the process of spermatogenesis. Patients with bilateral cryptorchidism have a low likelihood of fertility if left untreated. The higher the position of the testicle, the greater the damage to the varicocele. The sooner the testicle enters the scrotum, the greater the likelihood of recovery of the spermatogenic process. Unilateral cryptorchidism with descending fixation has a lower sperm density than normal, suggesting that unilateral cryptorchidism may be associated with bilateral testicular development. more than 80% of untreated bilateral cryptorchidism patients have no spermatozoa in the semen, and the remainder have a markedly reduced sperm density. 20% of patients with descending fixation of bilateral cryptorchidism have sperm densities that can be brought up to the low limit of normal. Some authors found that 16% of patients who underwent bilateral cryptorchid descent fixation at the age of 10-15 years could achieve a sperm count of 20´106/ml. Unilateral cryptorchid testes undergoing descent fixation have a higher likelihood of fertility than unilateral cryptorchid testes untreated if the testes are not atrophied. Semen analysis results in untreated unilateral cryptorchidism are more variable, ranging from 29% to 89% above the low limit of normal, and from 0-27% in azoospermia. After surgery, 69% of patients can reach a sperm count of 20´106/ml. more than 70% of patients undergoing descending testicular fixation at the age of 2-11 years can reach a semen analysis above the low limit of normal. 65% of patients undergoing descending cryptorchid testicular fixation at the age of 1-8 years have a normal semen analysis in adulthood, and for those who have undergone surgery at the age of 9-12 years, the semen analysis of those who have a normal semen analysis in adulthood is about 50%. Diagnosis and treatment of cryptorchidism 1. Diagnosis When the testicle is not palpable in the scrotum, the recoverable testicle should be identified according to the history and physical examination, such as the history of birth and within one year of age records that there is a testicle in the scrotum or the physical examination finds that the testicle can be pulled into the scrotum straight to the bottom, the diagnosis of recoverable testicle can be made. When both testes are not palpable, the possibility of bilateral anorchiasis should be thought of.The diagnosis can be made in boys under 9 years of age if FSH is elevated on further examination. If FSH is normal, hCG stimulation test, i.e., intramuscular injection of hCG 2000U once daily for 3 days, is required to detect testosterone level, if elevated, it indicates the presence of Leydig cell component of testis, and if there is no response, it indicates the absence of testis. When the testis is located in the inguinal subcutis or in the inguinal canal, ultrasound can easily detect it, probing for testes located in the abdominal cavity requires more experience, in which case CT or MRI is more accurate, but children are less likely to cooperate with the examination, and not all nonpalpable testes can be probed. Angiography is generally not used. Laparoscopic techniques are of great interest in exploring the nonpalpable testis. If the testicular vessels are blind-ended, the testis is absent and no further exploration is necessary. If the vessels enter the inguinal canal, further open or transperitoneal descending fixation of the testis or orchiectomy may be performed. If the testis is located in the abdominal cavity, the decision to choose one-stage testicular descent fixation or two-stage surgery is required. 2.Treatment Because of the great chance of infertility in patients with bilateral cryptorchidism, at least one side of the testis should be saved, preferably both sides should be successfully descended into the scrotum at the same time. Timing of treatment: In order to prevent infertility, surgical treatment should be performed before the disappearance of germ cells, which rarely occurs before 15 months of age. The American Academy of Pediatrics recommends treatment at about one year of age. Most scholars believe that the testes should be lowered to the scrotum within 12-18 months. Every effort should be made to bring the testicle down to at least a palpable position, otherwise the testicle on that side should be removed. Post-pubertal patients should also consider orchiectomy if they find that the testicle has a tendency to degenerate or malignant. 1.Hormone therapy Hormone therapy is the only option for conservative treatment. There are two kinds of hormone preparations available: hCG and GnRH (gonadotropin-releasing hormone). hCG stimulates Leydig cells to increase serum testosterone levels, prompting testicular descent. In some patients, hypothalamic GnRH secretion is abnormal, as evidenced by low LH levels, so replacement therapy is effective. hCG usage varies, with total doses ranging from 3,000 IU to 40,000 IU applied daily or weekly for a few days to several months. Testicular descent to the scrotum is achieved in 15-50% of patients. Job et al. believe that for maximum stimulation of Leydig cells, the total amount of hCG should be at least 10,000 IU, and that side effects begin to occur above 15,000 IU. But 15000IU or less will not affect the bone age and other side effects. GnRH usage is 1.2mg nasal spray daily for 4 weeks, the effective rate of 18-70%. Surgical treatment: If drug treatment is not effective, surgical treatment is necessary. The purpose of surgical treatment is to free the undescended testis and bring it into the scrotum, at least in a palpable position. It is currently believed that surgery should be performed before the age of 2 years. The key to surgery is to free the spermatic cord sufficiently to facilitate the descent of the testicle and to allow the testicle to lie tension-free within the scrotum, otherwise the testicle will retract after surgery. The testicle is immobilized between the scrotal skin and the meatus so that it cannot retract. A hernia repair should be performed at the same time. If the length of the isolated spermatic cord is still insufficient, according to the Fowler-Stephens experience, clamping of the internal spermatic artery can be tried, and if the blood supply is good, this artery can be cut off to lengthen the length of the spermatic cord and reduce tension. Those with high cryptorchidism or short spermatic cords can also be operated without the inguinal canal, and the spermatic cord can be brought from the posterior peritoneum through Hirschsprung’s triangle and the external ring directly into the scrotum, which can improve the success rate of the operation. Laparoscopic surgery can achieve both diagnostic and therapeutic goals. Firstly, the inner ring is found under microscopic observation. If the spermatic cord and vas deferens are seen, it can be judged that the testis has descended to the inner ring or below, and then open surgery is feasible to fix the testis. If there are no blood vessels and vas deferens at the inner ring, the testis should be found in the pelvis. If the testis is well-developed, open surgery is feasible; if it has become markedly atrophied, it should be removed laparoscopically. Regardless of the procedure, orchidectomy should be performed when the testis cannot be fixed in a palpable site, or when the testis has become markedly atrophied or has a tendency to become malignant. Even after successful fixation, the patient should be instructed to undergo regular follow-up.