History Session - 2011 Meeting, Copenhagen, Denmark - Infertility and Cryptorchidism – A Historical Perspective

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Infertility and Cryptorchidism – A Historical Perspective

Faruk Hadziselimovich

In 1786, John Hunter attributed the cause of congenital malformation of one of both testes to   infertility development. During last three centuries, different hypotheses were put forth as possible causes of infertility in cryptorchid males. They included: 1) congenital malformation, 2) secondary damage to initially normal testis due to persistent malposition, or 3) endocrinopathy leading to defective spermatogenesis.Research into infertility caused by cryptorchidism was greatly influenced by studies of testicular histology. The first histological description of pre-pubertal undescended testes was published by Felizet and Branca in 1898. In 1940, Charny reported the feasibility of performed sequential biopsies of cryptorchid testis in boys who had  successful orchidopexy. He realized that in those boys with severe pathological changes in their undescended testes at the time of the surgery, no improvement of testicular tissue was seen for several years/months after the successful orchidopexy. Therefore, he postulated that cryptorchid testis must be a congenital malformation.  Performing the surgery early in life, from age 2 years up to shortly before puberty was recommended in the early 70es, but this had already been propagated by Eisendrath in 1916 and was later supported by histological examination Southam and Cooper in 1927. However in 1965, Hedinger was able to show, using an improved histological technique, that testis of cryptorchid boys younger than 2 years of age had normal numbers of germ cells. Therefore, it was postulated that orchidopexy of cryptorchid boys had to be performed before the second birthday. During the last 70 years, substantial evidence has appeared in the literature to support a strong correlation between unilateral or bilateral testicular malposition and the incidence of azoospermia. This mean incidence for bilateral malposition is 23% and, for unilateral, 10% , regardless of the age at the time of surgery. Thus early and successful surgery could not prevent the development of azoospermia. In 1977, the Nobel Prize was awarded to  eminent peptide chemists for their pioneering work on neuropeptides including GnRH.  Soon after GnRH synthesis was realized, Job et al found LH deficiciency in unilateral cryptorchid boys and were later the first to describe a blunted T increase during physiological T surge in infancy. The importance of T surge become clear, only recently when the results of histological analyses of the biopsies taken at the surgery were compared with the fertility results. It became clear that mini-puberty is not an insignificant physiological gonadotropin rebound phenomenon, but rather the critical point for determination of future male fertility. Recently, advances in molecular genetics of cryptorchidism have provided necessary evidence to disprove Hunters more than 220 year old thesis that cryptorchid testis is a congenital abnormality that is ab initio imperfect and incapable of development into normal testicular structure and function.