Low sperm count may be genetic defect, scientists find

Low sperm count may be genetic defect, scientists find

Scientists have found that a specific defect in the male sex (Y) 

chromosome, known to cause azoospermia, or the inability to make sperm, 

can also cause the most common form of male infertility -- low sperm 

production, or oligozoospermia. 

This study is the first to definitively show that genetic defects can 

cause low sperm counts in some males and suggests that intracytoplasmic 

sperm injection (ICSI) -- the now-popular technology of injecting a 

single sperm into an egg to circumvent low sperm counts -- may cause the 

sons of these men to inherit infertility. 

The scientists recommend that infertile couples who are contemplating 

ICSI should be offered genetic counseling and the option of a DNA test 

for the mutation before they begin assisted reproductive procedures. The 

study, published in the May 11 issue of the British journal Lancet, was 

conducted by Dr. David Page, Dr. Renee Reijo, and Raaji Alaggappan at 

the Whitehead Institute for Biomedical Research and the Howard Hughes 

Medical Institute (HHMI) using DNA samples from their collaborator, Dr. 

Pasquale Patrizio at the Fertility Center of San Antonio, TX. 

In the study, the Whitehead/HHMI researchers examined the Y chromosomes 

of 35 men who had extremely low sperm counts and found that two of these 

men were missing a tiny fragment of the long arm of the Y chromosome. 

The Y chromosomes of their fathers (who obviously had no fertility 

problems) were intact in this region, proving that the mutation was in 

fact the cause of oligozoospermia. The scientists further found this 

mutation was also present in the sperm of one oligozoospermic man they 

tested, confirming that the mutation is likely to be transmitted by 

ICSI. 

Last year, the Whitehead/HHMI scientists found similar mutations in 12 

of 89 men who produced no sperm. The fathers of these men also had 

intact Y chromosomes, as did 90 fertile men who were studied for 

comparison. Based on these findings researchers believe that a gene or 

genes located in this fragment of the Y chromosome are involved in 

proper sperm production. 

"Low sperm counts are much more common in men -- one in 30 men has a low 

sperm count -- than the complete absence of sperm, which affects one in 

1,000 men. Our finding of the Y chromosome defect in men with low sperm 

counts suggests that this defect is more common than we previously 

estimated," Dr. Page said. 

About one in six American couples is infertile, and each year as many as 

20,000 couples seek assisted reproductive technologies to help them 

conceive. In a fifth of the infertile couples, a key factor is a defect 

in sperm production, which could result from a variety of reasons, 

including infections and other illnesses. Scientists are only now 

beginning to understand the role of genetic factors in infertility. 

The Whitehead/HHMI studies provide the first clear cut indication that 

genetic defects are the underlying problems in some men with genetic 

defects in sperm production. They suggest that some "unexplained" cases 

of male infertility can be traced to genetic defects in the Y chromosome 

and that these genetic defects can be transmitted to male offspring. 

"Normally, these men would not be able to have children, and people 

thought of genetically transmitted infertility as an oxymoron," Dr. Page 

said. "However, the explosion in assisted reproductive technologies is 

now making it possible for these men and their wives to have children 

and raises the possibility that they will pass on their infertility to 

their sons. It is for these cases that we recommend genetic counseling." 

Physicians consider sperm counts of 50 million or more sperm per 

milliliter (mL) of semen as being in the normal range. In the most 

common form of male infertility, men have less than 10-15 million sperm 

per mL of semen. Some men produce even fewer sperm -- a million or less 

per mL of semen. Men with such severely low sperm production were the 

subject of the Whitehead/HHMI study. The researchers say that further 

studies will be needed to ascertain the role, if any, of Y chromosome 

mutations in less severe cases of oligozoospermia.