Fertility after an undescended testicle

What about fertility?

The number one question I get asked by parents is “will my son be able to father children?”. (The number two question is “will my son get cancer” – and I’ll address that in a future article)

Good news! The majority of men who had an undescended testicle can have children.

Less good news! The chances of having children are lower than the rest of the population. Let me break it down to be clearer…

Mechanics

cells dying when inside the body. When doctors have cut into previously undescended testicles, brown cells (dead cells) instead of alive ones

Testicular volume equates to …

Older statistics skewed by surgery previously being done at an older age – which as the figures below show, would reduce fertility

“In boys older than 3 years of age at biopsy, 64% had a complete lack of germ cells”
source

If your son had palpable undescended testicles

The testicles contain different types of cells. Germ cells produce sperm, while Leydig cells are responsible for producing the hormone Testosterone.

When a testicle doesn’t descend properly, its germ cells can fail to develop properly, and are at risk of dying or developing abnormally (increasing the risk of cancer).

Recent research has found that for every month the testicles remain inside the body (undescended), there’s a 2% risk that many of the sperm producing cells will die, and a 1% risk that the testosterone producing cells will die.

To make that easier to understand, let’s do some worked examples:

If your son has surgery when 12 months old, there’s a 24% risk of the testicle producing few sperm, and a 12% risk of less testosterone

If he has surgery at 18 months, there’s a 36% risk of the testicle producing little sperm, and a 18% risk of lower testosterone

I had surgery when I was nearly 3 1/2 years old (42 months). I have an 84% risk that my previously undescended testicle will not produce viable sperm, and a 42% risk that its testosterone production is impaired.

Yikes!

A 2% risk/month of severe germ cell loss and 1% risk/month of Leydig cell depletion for each month a testis remains undescended, and a 50% greater risk of germ cell depletion in nonpalpable testes has been reported, thus emphasising the need for early relocation of an undescended testis (Tasian 2009).

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010978/full

Germ cell depletion was considered severe when <33 % of the tubules contained germ cells.
— source: https://www.researchgate.net/publication/262696562_Surgical_approach_to_the_palpable_undescended_testis

 

Feyles et al. [5] compared total sperm count and sperm motility in 51 men between 18 and 26 years of age having had an orchidopexy in childhood. They used World Health Organisation (WHO) criteria of normal count [15 million/mL and sperm motility [15 % to define normalcy. Group A had their orchidopexy in the first year of life and Group B between the first and second years of life. The proportion of subjects from Group A with a normal sperm count (96 %) was significantly higher than those in Group B (75 %) [5]. The proportion of subjects with normal sperm motility was also significantly higher in Group A than in Group B (96 vs. 67 %) [5].

— source: https://www.researchgate.net/publication/262696562_Surgical_approach_to_the_palpable_undescended_testis

 

Antibodies to sperm – affected by the way the testicles were fixed in the scrotum. The modern approach makes a pouch in the scrotum and holds the testicle in place without stitches, is much better. The approach used before 1995, and used on me, used insoluble stitches to anchor the testicle in the scrotum. As well as giving a poorer visual appearance and being uncomfortable, these stitches let blood and sperm mix. When this happens ther’s a risk that your body’s white blood cells will attack the sperm and destroy it – and this will affect both testicles.

According to research done in 2002 on rats, if the testicle was stitched in place there was up to 60% more chance of tubular atrophy. The modern way of putting the testicle inside a pouch in the scrotum removes this risk, and ensures it cannot twist.

 

Orchiopexy or testicular fixation for ascending testes (acquired undescended testes). The diagnosis of ascending testes (i.e. testes in an undescended location after being noted to have been completely descended) is being made with increasing frequency in recent years (Tasian 2010). The precise aetiology remains unclear. We have chosen to exclude the ascending testes from this review due to the underlying differences in the age of diagnoses, pathogenetic mechanisms and outcomes of treatment.

 

In another work from the 1970s, Ludwig et al. showed that boys who were operated on in the first two years of life had a 90% rate of fertility. This was in contrast to those boys operated on in years 3-4 (50% rate) and in those who had operations in years 9-12 (30%). While this study did not include the original position of the testicle at time of orchidopexy, a factor possibly not recognized as important at the time, these results certainly speak to a recommendation for earlier orchidopexy.
— source https://www.ncbi.nlm.nih.gov/pubmed/235412 – old, but shows what was currently thought

 

If your son had impalpable undescended testicles

In another analysis of germ cells, boys who underwent surgery before 6 months of age were compared to those having surgery between 6 and 24 months (32). Authors were able to demonstrate a negative correlation between age at orchidopexy and germ cell counts. All of the 14 boys who had surgery before 6 months of age had a normal number of GC/T compared to the lower numbers seen in those having surgery between 6 and 24 months of age. However, the data from 20 years post-operatively called into question the use of these fertility predictors as there was no association between germ cell counts on biopsy and the total sperm count on semen analysis. Interestingly, among the boys who had surgery at less than 6 months, 31% had a sperm count less than 40 million and sperm counts between groups were not statistically different (<6 months: 136×106 sperm/ejaculate; >6 months: 96×106 sperm/ejaculate, P=0.28) despite the more frequent abnormal histology in the boys undergoing orchidopexy at greater than 6 months of life. The authors then examined results based not on patient age at orchidopexy, but on presence of AdS on biopsy. Almost all males who had developed this more mature cell line had a normal sperm count. This was in stark contrast to the group who had not undergone the transformation, wherein a majority of the men had azoospermia or oligospermia. These results are muddied by the inclusion of both unilateral and bilateral UDT in the cohort, but more clearly show that this maturational step is likely paramount to future fertility and that care decisions should be made to optimize the ability of the testicle to undergo this maturational change. In another study of testicular biopsies performed at the time of orchidopexy, a lower age at surgery was correlated with presence of spermatogonia (r=0.37, P<0.0001) and decreasing tubular atrophy (r=0.59, P<0.001) (33).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708134/

 

The volume of the testicles at orchidopexy is often reduced the later the surgery is performed on the cryptorchid testis (25,26). However, testicular volume may not be an appropriate proxy for future fertility based on studies following paternity rates of men with cryptorchid testes. A study by Lee et al. found no relationship to testicular size at orchidopexy for unilateral UDT on future fertility as measured by actual paternity rates (27). Possible explanations for this include hypertrophy of the normally descended testicle, which could compensate for impaired fertility of the abnormal testis.
source

In English, the above quote means…

Around 9% of men who had a single undescended testicle have fertility problems

Both my son’s testicles are undescended (bilateral cryptorchidism)

Unfortunately, over 50% of men who were born with both testicles undescended will have fertility problems. This number is likely to decline and be less for your son, as now surgery is regulary done before the age of 2, whereas the 25-year studies in medical journals often had children operated on aged 3-8, with a corresponding increase in damage to the testicle.

Despite surgical treatment by orchiopexy, the long-term outcome still remains problematic and controversial. Impaired fertility (33% in unilateral cases and 66% in bilateral undescended testes) and a cancer risk 5-10 times greater than normal is observed over time (2). Hadziselimovic et al (56) reported infertility in 35% of the patients with undescended testes with normal germ cell number before surgery despite early orchiopexy performed under age 6 months. They suggested that this might be explained by defective transformation of germ cells due to lack of a mini-pubertal period (56). During mini-puberty, progenitor spermatozoa are transformed into Ad (dark) spermatogonial cells owing to the peak effect of LH and testosterone, an effect which occurs particularly in the postnatal 2-3 months (24,56). The infertility rate may increase up to 90% in patients who have not undergone a mini-pubertal period (56).
https://www.researchgate.net/publication/237084024_Epidemiology_Classification_and_Management_of_Undescended_Testes_Does_Medication_Have_Value_in_its_Treatment

 

Men with a history of undescended testis have a reduced probability of fertility with a low sperm count and generally poorer semen quality than men with normal testicular descent (e24, 20). This subfertility is not compensated by a normally descended contralateral testis. The probability of a fertility impairment is addi- tionally increased in bilateral cryptorchidism and delayed treatment of the non-descended testicle. Almost all adult men with bilateral undescended testis have azoospermia, whereas more than 20% of boys achieve a normal sperm count after orchidopexy. Only few studies have evaluated semen quality in relation to the time of life at which treatment was performed, the original position of the testicle, and the surgical technique.

Surgical treatments in boys between the ages of ten months and four years with bilateral cryptorchidism lead to a normal sperm count in 76% of cases compared to 26% in the boys who were operated between the age of 4 and 14 years (21). This time effect is not so pro- nounced with unilateral cryptorchidism (21). This may well be due to the impaired spermatogenesis which is already characterized histologically in the first months of life by an increasing reduction in the testosterone- producing Leydig cells, delayed onset of spermatogonia, and a quantitatively and qualitatively reduced matura- tion process of the germ cells (e25). It is found that fertility may still be impaired after treatment and that early management confers distinct benefits (e24, 22).

https://www.researchgate.net/publication/26797740_The_Undescended_Testis_Diagnosis_Treatment_and_Long-Term_Consequences

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708134/ too – some quotes above are from it

although boys with one undescended testis have a lower fertility rate, they have the same paternity rate as boys with bilateral descended testes. Boys with bilateral undescended testes have a lower fertility and a paternity rate (9).
http://journal.frontiersin.org/article/10.3389/fendo.2014.00063/full

READ THIS PAPER to get a readable description of the biology http://journal.frontiersin.org/article/10.3389/fendo.2014.00063/full. Also covers cancer risk.

Several data suggest that AD spermatogonia form between 3 and 9 months of age. This developmental cycle needs normal testicular hormones and the optimal scrotal temperature of 33°C …

The failure of transformation of gonocytes into AD spermatogonia may produce infertility in boys. …Moreover, in undescended testes, germ cells loss starts at 6 months of age. Testicular biopsies at time of orchidopexy confirmed the importance of AD spermatogonia for fertility in cryptorchid patients. Tasian and coworkers (22) observed greater germ cell depletion in abdominal testes compared with palpable testes and a progressive germ cell loss for each month the testes remain undescended. …

However, early orchidopexy does not guarantee normal fertility in adulthood. Hadziselimovic showed that despite orchidopexy before 6 months of age, up to 35% of boys will grow up to be infertile regardless of the normal total germ cell count on testicular biopsies performed at the time of orchidopexy (44).

Conclusion

The greatest concern for papers predicting outcome of undescended testes is that they are just that, predictions. It takes an extremely long study to actually document fertility and paternity and the threshold of Leydig cell depletion which affects adult hormone function is not clear.

Testicular size/volume

Van Brakel et al. [22] from Erasmus MC Rotterdam, The Netherlands, assessed the fertility potential of 62 men aged between 20 and 38 years who had undergone orchi- dopexy between 1 and 12 years of age for both palpable and impalpable undescended testes and compared them to a group of 55 controls. Adult testicular volumes of both the previously undescended and descended sides were signifi- cantly lower in subjects than controls.

When an undescended testis has been brought into a scrotal position, catch-up growth generally occurs, but the previ- ous UDT still lags behind its descended counterpart and the final volume reached appears not to be influenced by the boys’ age at time of orchidopexy.

 

— source: https://www.researchgate.net/publication/262696562_Surgical_approach_to_the_palpable_undescended_testis

 

A smaller
testicle is common in adults who were
formerly surgically treated for unilateral UDT.
Formerly cryptorchid testes usually reach a
volume in the adult of only about a half of
that of the contralateral side. Possible causal
factors might include a primary abnormality
resulting in impaired growth of the retained
testis and compensatory hypertrophy of its
counterpart.

Q&A

You need two testicles to father a child

Wrong! Each testicle produces sperm. A man with one testicle can get a woman pregnant. Having two is nature’s way of ensuring that if one is damaged, he still has a second one.