GENECTICS AND TESTING

What has become clear over the last several years is that our ability to treat men with severe male factor infertility has far surpassed our understanding of its causes. Over 20% of male cases were considered idiopathic i.e. "we don't know why". Recent advances and interest in molecular biology, genetics and technology have enabled scientists to discover some of the genes that control sperm production. We now know that almost 20% of men with azoospermia (no sperm production) or severe oligospermia (sperm counts under 5-10 million for no apparent reason) will have an identifiable genetic cause for infertility. It is possible that certain genetic diseases can be passed on to children since intracytoplasmic sperm injection (ICSI) bypasses the natural selection process.

Congenital Absence of the Vas Deferens
Congenital absence of the vas deferens (CAVD) is a syndrome whereby a portion or all of the reproductive ducts (including the epididymis, vas, and seminal vesicle) are missing. This causes an obstruction and while the sperm are produced normally within the testicle, they are in essence "trapped". CAVD is associated with several diseases including cystic fibrosis (CF) and renal malformation. Sixty-five percent of men with CAVD will have a detectable mutation in one of the cystic fibrosis genes and 15% will have a missing or misplaced kidney. This does not mean that the man has or will develop CF but it means that he could be a carrier of the gene. If his wife is also a carrier then there is a 25% chance of a child born to them having CF. It is imperative that all men with CAVD and/or their wives have genetic screening for CF gene mutations prior to undergoing In-Vitro Fertilization. Sperm can be successfully harvested from these men by a technique known as MESA (microsurgical epididymal sperm aspiration). The sperm can then be used to fertilize an egg and establish a pregnancy.

Y Chromosome Microdeletions
The human genome consists of 23 pairs or 46 chromosomes. The are 44 autosomes and two sex chromosomes (see picture normal karyotype). The sex chromosomes are called X and Y. A woman has XX ( 2 X) and a man has XY. All of the eggs contain an X chromosome but the sperm can be either X or Y. The type of sperm that fertilizes the egg will decide the sex of the child. A karyotype is a picture of all the pairs of chomosomes arranged in order. Recent research has identified the genes that control sperm production to the Y chromosome (see picture at right). We have also found that small mutations or deletions in any of the genes can cause problems with fertility. Ten to 13% of men with absent sperm count will be found to have a mutation on one of these genes. If a man with a Y chromosome deletion has a male child through ICSI, then the child will also have this same type of problem. A blood test has been developed to detected some of these mutations and should be offered to all men with very low sperm counts who are thinking of fathering a child through ICSI.

Klinefelter's Syndrome
Klinefelter's Syndrome is a disorder characterized by infertility, abnormal male breasts (gynecomastia) and small firm testes. It is the most common genetic cause of azoospermia (no sperm production). Klinfelter's is caused by an abnormal number of sex chromosomes. Instead of the normal male XY pattern, an extra X chromosome is present resulting in XXY or 47 chromosomes. It has now been discovered that these men can have small amounts of sperm production within the testicles and can be used to have a child. It is important to test men with absent or low sperm counts for Klinefelter's Syndrome before offering IVF.

Genetic Screening and Counseling
There are many other genetic diseases that can cause infertility. Many of these conditions can be detected through a complete male fertility evaluation consisting of a history, physical examination, semen analyses, and genetic tests when indicated. These conditions can effect a man's health and the health of a future child. If a genetic defect is detected then genetic counseling is offered to the couple so they can be completely informed and can make decisions about what is best for them. We advocate that all men with fertility problems see a male fertility specialist.