cryptorchidism cryptorchidism cryptorchidism, also known as undescended testis, is the failure of one or both testes to descend into the scrotum. the word is from greek κρυπτός (kryptos) 'hidden' and ὄρχις (orchis) 'testicle'. 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 (the majority within three months), making the true incidence of cryptorchidism around 1% overall. cryptorchidism may develop after infancy, sometimes as late as young adulthood, but that is exceptional. different forms of cryptorchidism, depending on the position of the undescended testicle. sometimes the retractile testicle is added. cryptorchidismcryptorchidism on scrotal ultrasoundspecialtymedical genetics 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 (retroperitoneal) 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 (hypoplastic) or severely abnormal (dysgenetic) missing (also see anorchia). about two-thirds of cases without other abnormalities are unilateral; most of the other third involve both testes. in 90% of cases, an undescended testis can be felt in the inguinal canal. in a small minority of cases, missing testes may be found in the abdomen or appear to be nonexistent (truly "hidden"). 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 subsequent infarction) 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" (move back up) 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 develops 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 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 ten 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 (65%); in contrast, after orchiopexy, seminomas represent only 30% of testicular tumors. causes in most full-term infant boys with cryptorchidism but no other genital abnormalities, a cause cannot be found, making this a common, sporadic, unexplained (idiopathic) 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 descent of 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 (five or more drinks per week, 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 development of cryptorchidism. in 2008, a study was published that investigated the possible relationship between cryptorchidism and prenatal exposure to a chemical called phthalate (dehp), which is used in the manufacture of plastics. the researchers found a significant association between higher levels of dehp metabolites in pregnant mothers and several sex-related changes, including incomplete descent of the testes in their sons. according to the lead author of the study, a national survey found that 25% of u.s. women had phthalate levels similar to the levels that were found to be associated with sexual abnormalities. 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 (e.g. advil) and paracetamol (acetaminophen). 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. 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 develops 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 (or at least greatly influenced) by anti-müllerian hormone (amh). the second phase, in which the testes move through the inguinal canal into the scrotum, is dependent on androgens (most importantly testosterone). 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 ("degenerates") in microscopic appearance between two and four years after birth. some evidence indicates early orchiopexy reduces this degeneration. pathophysiology at least one contributing mechanism for reduced spermatogenesis in cryptorchid testes is temperature. the temperature of testes in the scrotum is at least a few degrees cooler than in the abdomen. animal experiments in the middle of the 20th century suggested that raising the temperature could damage fertility. some circumstantial evidence suggests tight underwear and other practices that raise the testicular temperature for prolonged periods can be associated with lower sperm counts. nevertheless, research in recent decades suggests that the issue of fertility is more complex than a simple matter of temperature. subtle or transient hormone deficiencies or other factors that lead to a lack of descent also may impair the development of spermatogenic tissue. the inhibition of spermatogenesis by ordinary intra-abdominal temperature is so potent that continual suspension of normal testes tightly against the inguinal ring at the top of the scrotum by means of special "suspensory briefs" has been researched as a method of male contraception, and was referred to as "artificial cryptorchidism" by one report. an additional factor contributing to infertility is the high rate of anomalies of the epididymis in boys with cryptorchidism (over 90% in some studies). even after orchiopexy, these may also affect sperm maturation and motility at an older age. diagnosis scrotal ultrasonography of undescended testis: (a) normal testis in the scrotum (b) atrophic and decreased echogenicity of the contralateral testis of the same patient seen in the inguinal region the most common diagnostic dilemma in otherwise normal boys is distinguishing a retractile testis from a testis that will not descend spontaneously into the scrotum. retractile testes are more common than truly undescended testes and do not need to be operated on. in normal males, as the cremaster muscle relaxes or contracts, the testis moves lower or higher ("retracts") in the scrotum. this cremasteric reflex is much more active in infant boys than older men. a retractile testis high in the scrotum can be difficult to distinguish from a position in the lower inguinal canal. though various maneuvers are used to do so, such as using a cross-legged position, soaping the examiner's fingers, or examining in a warm bath, the benefit of