Antisperm Antibodies or immunity to sperm, whether in the male or female, is not an absolute cause of infertility.
Sperm antibodies reduce fertility, but do not invariably prevent conception. Rather, the effects are graduated; i.e., the larger the immunologic response, the less likely it is that a pregnancy will occur. Like any other kind of antibody manufactured by the body, sperm antibodies are formed in response to antigens. These antigens are proteins, which appear on the outer sperm membranes as the young sperm cells, develop within the male testes. Antigens can only stimulate antibody production when they come in contact with components of the blood. Under normal conditions, blood and sperm do not mix. Direct contact between the two is prevented by a cellular structure in the testes called the blood/testis barrier. This barrier is formed by Sertoli cells, which abut very closely against each other, forming tight junctions that separate the developing sperm cells from the blood and prevent immunologic stimulation. However, the blood/testis barrier can be broken by physical or chemical injury or by infection. When this barrier is breached, sperm antigens escape from their immunologically protected environment and come in direct contact with blood elements that launch an immunologic attack.
In the female’s body, deposited sperm are regarded as foreign invader cells and as such would normally be targeted for attack and destruction by circulating antibodies. Yet sperm, which are immunologic aliens to the woman, do not usually cause an antibody response. Although usually exposed to billions of sperm during her lifetime, few women develop sperm antibodies. Why this is so is not well understood. It is known that the cellular construction of the vagina provides a physical barricade somewhat similar to the blood: testis barrier in the male. Here, too, physical damage or infection will increase the likelihood of sperm and blood mixing and subsequent antibody production.
Once sperm and blood come in contact, whether in the male or female, specific antibodies are produced against them by specialized blood cells called T- and B-lymphocytes. The three main types of sperm antibodies produced are Immunoglobulin G (IgG), Immunoglobulin A (IgA) and Immunoglobulin M (IgM). These antibodies bind to the proteins (antigens) on the sperm head, midpiece or tail. The antibodies formed may be of the circulatory type (in the blood serum) or secretory type (in the tissue). This is important because high levels of antibodies in the blood do not always antibodies will find their way to the semen where they can affect the sperm. For example, the concentration of IgG is much lower in secretions of the reproductive tract that it is in the blood. Conversely, the local level of IgA is higher in the reproductive secretions than in the blood. This is an important point, which we will return to later.
Once sperm antibodies have formed, they can affect sperm in several different ways. Some antibodies will cause sperm to stick together (agglutinating antibodies). Agglutinated sperm clump together in huge masses and are unable to migrate through the cervix and uterus. Other antibodies mark the sperm for attack by Natural killer (NK) cells of the body’s immune system (opsonizing antibodies). Some antibodies cause reactions between the sperm membrane and the cervical mucus preventing the sperm from swimming through the cervix (immobilizing antibodies). Antibodies can also block the sperm’s ability to bind to the zona pellucida of the egg, a prerequisite for fertilization. Finally, there is evidence that the fertilized egg shares some of the same antigens that are found on the sperm. It is possible that sperm antibodies present in the mother can react with the early embryo, resulting in its destruction by phagocytic cells.
There are a number of diagnostic tests available to detect the presence of sperm antibodies. These are flow cytometry and the ELISA (enzyme-linked immunoabsorbent assay), the Franklin-Dukes sperm agglutination assay or the Immunobead Binding Test (IBT), to name a few. At New York Fertility Services (NYFS), the Indirect Immunobead Binding Test (IBT) is used to detect antibodies present in the blood serum, in cervical mucus or on the sperm surface. All patients at NYFS are screened for sperm antibodies in the blood serum. If that test is positive (antibodies are present), a second direct test is sometimes recommended to determine if antibodies are present on the surface of male’s sperm or in the secretions of the female’s cervix. As mentioned earlier, certain antibodies are more likely to be found in some parts of the body than in others. The presence of high levels of antibodies in the serum does not mean that they will find their way to the semen or cervix. Antibodies present in the serum will have little effect on fertility if they are not also present where sperm are manufactured (testes) or deposited (cervix).
IgA is the most common antibody in secretions of the cervix, uterus and fallopian tubes. IgG may also be present, but IgM is found only rarely. In the male, IgA and IgG are found in the semen although there is controversy as to whether they originate locally (secreted by testicular cells) or cross over from the circulation. Antibodies of the IgM class are not found in semen.
Like the source of some antibodies, the question of the critical levels of sperm antibodies is also hotly debated among clinicians. There seems to be general agreement that blood serum levels above 40% by the IBT are associated with significant fertility problems.
Once an antibody problem has been identified, there are generally 3 options.
In some patients, the administration of corticosteroids (prednisone) to temporarily suppress antibody production. Pregnancy rates are poor and steroid treatment carries with it the risk of significant side effects. Spontaneous fractures have been reported in 2 – 4% of cases. As such, we do not routinely recommend this treatment.
Intracytoplasmic sperm injection
The best option is a form of in vitro fertilization (IVF) known as intracytoplasmic sperm injection (ICSI) where each egg is injected with a single sperm), high pregnancy and birth rates have been reported.
Other treatments for sperm antibodies such as prolonged use of condoms or antibiotic therapy have also proven to be of no value in increasing the chances of pregnancy in antibody-positive couples.
Sperm antibodies occur in about 7% of infertile women and are even more common in men, especially those who have previously undergone reproductive surgery such as vasectomy or vasectomy reversal. In fact, when a vasectomy was performed more than ten years prior, more than 70% of such men will have high concentrations of sperm antibodies, representing a severe form of male infertility. Fortunately ICSI has optimized IVF pregnancy in cases of male immunologic infertility, to the point that success rates are virtually unaffected by the presence or concentration of antisperm antibodies.