Cryptorchidism
Cryptorchidism, also known as undescended testis, is the failure of one or both testicles to descend into the scrotum. The word is. It is the most common birth defect of the male genital tract. About 3% of full-term and 30% of premature infant boys are born with at least one undescended testis.
However, about 80% of cryptorchid testes descend by the first year of life, making the true incidence of cryptorchidism around 1% overall. Cryptorchidism may develop after infancy, sometimes as late as young adulthood, but that is exceptional.
Cryptorchidism is distinct from monorchism, the condition of having only one testicle. Though the condition may occur on one or both sides, it more commonly affects the right testis.
A testis absent from the normal scrotal position may be:
- Anywhere along the "path of descent" from high in the posterior abdomen, just below the kidney, to the inguinal ring
- In the inguinal canal
- Ectopic, having "wandered" from the path of descent, usually outside the inguinal canal and sometimes even under the skin of the thigh, the perineum, the opposite scrotum, or the femoral canal
- Undeveloped or severely abnormal
- Missing.
Undescended testes are associated with reduced fertility, increased risk of testicular germ-cell tumors, and psychological problems when fully-grown. Undescended testes are also more susceptible to testicular torsion and inguinal hernias. Without intervention, an undescended testicle will usually descend during the first year of life, but to reduce these risks, undescended testes can be brought into the scrotum in infancy by a surgical procedure called an orchiopexy.
Although cryptorchidism nearly always refers to congenital absence or maldescent, a testis observed in the scrotum in early infancy can occasionally "reascend" into the inguinal canal. A testis that can readily move or be moved between the scrotum and canal is referred to as retractile.
Cryptorchidism, hypospadias, testicular cancer, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.
Signs and symptoms
Infertility
Many men who were born with undescended testes have reduced fertility, even after orchiopexy in infancy. The reduction with unilateral cryptorchidism is subtle, with a reported infertility rate of about 10%, compared with about 6% reported by the same study for the general population of adult men.The fertility reduction after orchiopexy for bilateral cryptorchidism is more marked, about 38%, or six times that of the general population. The basis for the universal recommendation for early surgery is research showing degeneration of spermatogenic tissue and reduced spermatogonia counts after the second year of life in undescended testes. The degree to which this is prevented or improved by early orchiopexy is still uncertain.
Cancer risk
One of the strongest arguments for early orchiopexy is reducing the risk of testicular cancer. About one in 500 men born with one or both testes undescended develop testicular cancer, roughly a four- to 40-fold increased risk. The peak incidence occurs in the third and fourth decades of life. The risk is higher for intra-abdominal testes and somewhat lower for inguinal testes, but even the normally descended testis of a man whose other testis was undescended has about a 20% higher cancer risk than those of other men.The most common type of testicular cancer occurring in undescended testes is seminoma. It is usually treatable if caught early, so urologists often recommend that boys who had orchiopexy as infants be taught testicular self-examination, to recognize testicular masses and seek early medical care for them. Cancer developing in an intra-abdominal testis would be unlikely to be recognized before considerable growth and spread, and one of the advantages of orchiopexy is that a mass developing in a scrotal testis is far easier to recognize than an intra-abdominal mass.
Orchidopexy was originally thought to result in easier detection of testicular cancer, but it did not lower the risk of actually developing cancer. However, recent data have shown a paradigm shift. The New England Journal of Medicine published in 2007, that orchidopexy performed before puberty resulted in a significantly reduced risk of testicular cancer than if done after puberty.
The risk of malignancy in the undescended testis is 4 to 10 times higher than that in the general population and is about one in 80 with a unilateral undescended testis and one in 40 to one in 50 for bilateral undescended testes. The peak age for this tumor is 15–45 years old. The most common tumor developing in an undescended testis is a seminoma ; in contrast, after orchiopexy, seminomas represent only 30% of testicular tumors.
Causes
Environmental hypotheses
In most full-term infant boys with cryptorchidism but no other genital abnormalities, a cause cannot be found, making this a common, sporadic, unexplained birth defect. A combination of genetics, maternal health, and other environmental factors may disrupt the hormones and physical changes that influence the development of the testicles.- Severely premature infants can be born before the descent of the testes. Low birth weight is also a known factor.
- A contributing role of environmental chemicals called endocrine disruptors that interfere with normal fetal hormone balance has been proposed. The Mayo Clinic lists "parents' exposure to some pesticides" as a known risk factor.
- Risk factors may include exposure to regular alcohol consumption during pregnancy, associated with a three-fold increase in cryptorchidism when compared to nondrinking mothers. Cigarette smoking is also a known risk factor.
- Family history of undescended testicles or other problems of genital development
- Cryptorchidism occurs at a much higher rate in a large number of congenital malformation syndromes. Among the more common are Down syndrome, Prader–Willi syndrome, and Noonan syndrome.
- In vitro fertilization, use of cosmetics by the mother, and pre-eclampsia have also been recognized as risk factors for the development of cryptorchidism.
- Androgen insensitivity syndrome generally manifests itself in Cryptorchidism. In CAIS, the testis are generally located completely undescended, where the ovaries usually are. In PAIS, the testis is generally partially undescended. This also occurs with 5α-Reductase 2 deficiency however, the testis generally descend during puberty.
A 2010 study examined the prevalence of congenital cryptorchidism among offspring whose mothers had taken mild analgesics, primarily over-the-counter pain medications including ibuprofen and paracetamol. Combining the results from a survey of pregnant women prior to their due date in correlation with the health of their children and an ex vivo rat model, the study found that pregnant women who had been exposed to mild analgesics had a higher prevalence of baby boys born with congenital cryptorchidism.
New insight into the testicular descent mechanism has been hypothesized by the concept of a male programming window derived from animal studies. According to this concept, testicular descent status is "set" during the period from 8 to 14 weeks of gestation in humans. Undescended testis is a result of disruption in androgen levels only during this programming window.
Sexually antagonistic epigenetic marker hypothesis
When one identical twin is born with cryptorchidism, his identical twin also has the trait only 25% of the time, despite sharing their genes and prenatal hormonal environment. Animal studies have found that androgen antagonists during early fetal development cause elevated rates of hypospadias and cryptorchidism, however, in humans these traits rarely occur together. In addition, levels of circulating testosterone overlap for both male and female fetuses throughout fetal development. Rice et al. have proposed that sexually dimorphic development occurs through epigenetic markers which are laid down during stem cell development, which blunt androgen signalling in XX fetuses, and boost sensitivity in XY fetuses. If these marks are sexually antagonistic, and if a subset of these epigenetic marks carry over generations, they are expected to produce mosaicism of sexual development in opposite-sex offspring, sometimes producing hypospadias or cryptorchidism when passed from a mother to son. Rice's model requires further testing with currently available technology to support or falsify it.Mechanism
Normal development
The testes begin as an immigration of primordial germ cells into testicular cords along the gonadal ridge in the abdomen of the early embryo. The interaction of several male genes organizes this developing gonad into a testis rather than an ovary by the second month of gestation. During the third to fifth months, the cells in the testes differentiate into testosterone-producing Leydig cells, and anti-Müllerian hormone-producing Sertoli cells. The germ cells in this environment become fetal spermatogonia. Male external genitalia develop during the third and fourth months of gestation, and the fetus continues to grow, develop, and differentiate.The testes remain high in the abdomen until the seventh month of gestation, when they move from the abdomen through the inguinal canals into the two sides of the scrotum. Movement has been proposed to occur in two phases, under the control of somewhat different factors. The first phase, movement across the abdomen to the entrance of the inguinal canal, appears controlled by anti-Müllerian hormone. The second phase, in which the testes move through the inguinal canal into the scrotum, is dependent on androgens. In rodents, androgens induce the genitofemoral nerve to release calcitonin gene-related peptide, which produces rhythmic contractions of the gubernaculum, a ligament which connects the testis to the scrotum, but a similar mechanism has not been demonstrated in humans. Maldevelopment of the gubernaculum or deficiency or insensitivity to either AMH or androgen can, therefore, prevent the testes from descending into the scrotum. Some evidence suggests an additional paracrine hormone, referred to as descendin, may be secreted by the testes.
In many infants with inguinal testes, further descent of the testes into the scrotum occurs in the first six months of life. This is attributed to the postnatal surge of gonadotropins and testosterone that normally occurs between the first and fourth months of life.
Spermatogenesis continues after birth. In the third to fifth months of life, some of the fetal spermatogonia residing along the basement membrane become type A spermatogonia. More gradually, other fetal spermatogonia become type B spermatogonia and primary spermatocytes by the fifth year after birth. Spermatogenesis arrests at this stage until puberty.
Most normal-appearing undescended testes are also normal by microscopic examination, but reduced spermatogonia can be found. The tissue in undescended testes becomes more markedly abnormal in microscopic appearance between two and four years after birth. Some evidence indicates early orchiopexy reduces this degeneration.