Autoimmunity may cause infertility.

Autoimmunity may cause infertility

The miracle of biological conceptionhas long baffled geneticists, developmental biologists and just about everyone else who has taken a moment to think about it. But pity the immunologists who are stuck with the task of explaining how it is that a fertilized egg--which includes, after all, a fair share of father-furnished foreign material--manages to keep from being immunologically rejected by the mother.

That ultimate immunological questionhas yet to be answered (SN: 10/11/86, p.234), but scientists are making progress in understanding the many links between the fields of immunology and reproductive biology. Laboratory studies have already shown, for example, that antisperm antibodies in women can interfere with sperm function and fertilization-- although little is known about where these antibodies come from or why some women appear to be more immunologically reactive than others.

Now researchers at Mount Sinai MedicalCenter in Chicago are using immunoreproductive studies to better understand the causes of infertility, and to provide clues about the body's business of self-recognition. Norbert Gleicher and his colleagues found that in vitro- ("test- tube-') fertilized women with abnormally high levels of autoantibodies (antibodies that erroneously attack normal tissue) got pregnant at only one-fifth the rate of women with normal autoantibody levels. Their research is to be published in the August OBSTETRICS AND GYNECOLOGY.

The study is the first to compare autoantibodylevels in the blood with those in the follicular fluid--the fluid that bathes the fertilized egg near the ovaries--and hints at the possibility that the ovaries may be responsible for local production of autoantibodies.

"We found that women with abnormalautoantibodies in blood also have abnormal antoantibodies in follicular fluid,' Gleicher told SCIENCE NEWS. "But what is even more important is that one group of autoantibodies, the phospholipids, appears to be concentrated in the follicular fluid in autoantibody-positive patients.'

Gleicher kept track of in vitro fertilizationsuccesses in patients with and without these abnormal autoantibodies, and found that although the antibodies had no effect on an egg's capacity for fertilization, they were associated with a decreased chance of pregnancy. "The study therefore suggests that abnormal phospholipid autoantibodies may be associated with implantation failure,' he says. Moreover, taking into account previous studies that have implicated the same class of antibodies with autoimmune diseases such as rheumatoid arthritis and lupus erythematosis, the new research suggests that unrecognized autoimmune diseases may be to blame for many cases of infertility.

"Infertility is a huge and ever-increasingproblem,' Gleicher says. "The data suggest today that approximately 15 percent of all couples in the United States who are trying to conceive do have an infertility problem.' (Infertility is defined as one year of unprotected regular intercourse without conception.) "I think that autoantibodies will become a major issue in reproduction, from the earliest part of the reproductive process throughout pregnancy and up to delivery,' he says, noting that certain antibodies have already been associated with fetal distress and fetal death in patients with autoimmune disease.

As for the bigger questions, such ashow the dody actually distinguishes between "self' and "nonself' and why certain people develop autoimmunity, Gleicher says, "If I knew that I'd win the Nobel Prize in medicine.' However, he notes, autoantibody levels are normally regulated by specialized suppressor cells, and "suppressor activity in the female is set at a higher thermostat level than in the male,' leaving even healthy women with relatively high levels of autoantibodies. It's possible, he speculates, that women have had to evolve a certain tolerance to high levels of autoantibodies in order to accommodate the partially foreign fetus. "Normally, of course, these levels are not a problem, but sometimes there's a glitch in the system,' he says. Some cases of immunemediated infertility or autoimmune disease "may be the price that women have to pay for being generally capable of tolerating higher autoantibody levels in pregnancy.'