Reproductive Immunology involves events related to pregnancy and those that prevent conception or sustenance. Mor proposed a model in which the fetus and maternal immune system work synchronously to avoid distressing outcomes (1). There are many events that can lead to blunders of the immune system, such as anti-phospholipid antibodies, anti-sperm antibodies and luekocytospermia.
Anti-phospholipids antibodies are created erroneously and bind to cell walls of self- cells rendering them sticky and resistant to flow. This often results in blood clots that can be detrimental to the fetus. These are commonly found in patients with unexplained infertility along with several other diseases. Increased levels are associated with repeat miscarriages, stillbirths, implantation failure, placental insufficiency and increased rates of IVF failure. The anti-phospholipids impair placental formation and therefore limit fetal nutrition. This inappropriate clotting can also lead to an unsuccessful implantation and subsequent miscarriage (2). Another detrimental effect of these antibodies is that it initiates the complement system of the innate immune system. The local increase in complement activation fragments, leading to the recruitment of inflammatory cells harmful to the fetus, which leads to complications. Currently in conjunction with fertility clinics researchers are working on biomarkers that may predict poor pregnancy outcomes. Heparin is given to prevent blood clotting and acts as an inhibitor to the blood-clotting cascade (2). A 2007 study at Cornell University found that administration of Heparin could inhibit the activation of the complement cascade (3). In mice models they were able to prove the positive correlation between complement activation and placental injury and fetal growth restriction and loss(3).
Anti-sperm antibodies (ASA) found in 10% of infertile men also significantly decreases reproductive ability. The blood-test barrier prevents immune cells from recognizing sperm as foreign. If there is insult to this barrier, autoantibodies will result. The ASA bind to the sperm causing decreased motility, penetration through cervical mucus and capacitation (2). In a 2007 study from infertile and vasectomized patients was analyzed to see qualify alloantigen. The study resulted in a repertoire of antigens strongly recognized in infertile patients and not in fertile patients. The goal is to create an alloantigen index that will eventually lead to the targeted treatment of ASA infertility(4).
In addition, luekocytospermia is another cause of immunological infertility. Luekocytospermia is characterized by a dramatic increase in seminal white blood cell count. Semen normally contains white blood cells, but its numbers rise dramatically as in the case of infection. The excessive count causes a surplus release of reactive oxygen species. This leads to the oxidation of sperm cells, resulting in dimorphic and immotile sperm. In order to treat this setback in fertility, antibiotics are given to eradicate infection and the man is urged to ejaculate often in order to move superfluous cells from the tract (2).
It is clear that the immune system plays an important role in all conception. This is highlighted by the results of anti-phospholipid antibodies, anti-sperm antibodies and luekocytospermia. Thanks to technological advancements, any defect can be targeted and ameliorated.
QUESTIONS TO INSURE COMPREHENSION
Multiple Choice questions
1. A 25-year-old man visits the local fertility clinic after being unable to successfully impregnate his wife. A physician ascertains a medical background and unearths a remarkable finding. The man was diagnosed with gonorrhea seven months before his visit to the clinic and other than medication to relieve his symptoms; he has not had another VDRL test done. The physician orders a sperm analysis and finds several revealing clues to the man’s unsuccessful reproductive status. Keeping the man’s gonorrhea diagnosis in mind, what could be an adequate reason for his infertility? Also, what measures should be taken to help his current reproductive futility?
A) The blood-testes barrier prevents immune cells from recognizing sperm as foreign, if there is insult to this barrier, autoantibodies will result. The patient is given corticosteroids to lessen the number of antibodies.
B) The effect of antibodies is that they initiate the complement system of the innate immune system. Heparin is administered to reduce the activation of the complement cascade and reduce blood clotting.
C) A dramatic increase in seminal white blood cell count causes a surplus release of reactive oxygen species (ROS), which lead to the oxidation of sperm cells. Dimorphic and immotile sperm results from the reactive oxygen species. Antibiotics are given to eradicate infection and the man is urged to ejaculate often in order to move superfluous cells from the tract.
D) Anti-phospholipid antibodies are created erroneously and bind to cell walls of self- cells rendering the sticky and resistant to flow. This resistance often results in blood clots that can be detrimental to the fetus. Anticoagulation agents like heparin are administered to prevent clot formation.
Answer: C
2.A 27-year-old male is unable to successfully impregnate his 24-year-old wife and visits his physician. Tests reveal the formation of anti-sperm antibodies by the wife. Anti-sperm antibodies form when:
A) Blood-testes barrier is broken
B) Congenital complication
C) Male has low sperm count
D) Female vaginal pH is too high
E) The male is immuno-comprimised
Answer: A
3.A 22-year-old woman was unable to successfully maintain a pregnancy. She went to see a specialist after 3 consecutive miscarriages within the first two weeks of finding out she was pregnant. It was found that she had a very high titer of anti-phospholipid antibodies. These antibodies
a) bind cell walls rendering them sticky and resistant to flow
b) cause an excess of nutrients for the fetus
c) cause hyperoxemia in the fetus
d)inhibit the complement cascade
e)produce a combination of events that leads to the complete inactivation of fetal circulation
Answer: A
Discussion questions
1. A 30-year-old man comes in to your office because he and his wife are having trouble conceiving a child. The wife has been to a fertility specialist and everything seems to be in order. 10 years ago the patient was poked in the scrotum with a pencil during a basketball game, as a result the blood testes barrier was broken. It is your suspicion that the patient has formed anti-sperm antibodies. Is this likely? And By what mechanism do anti-sperm antibodies cause infertility?
2. A 37-year-old women comes in to your office complaining that she and her husband are unable to conceive a child. After months of trying and thousands of dollars wasted in fertility clinics they have given up hope. You order a blood analysis and notice that she may suffer form a rare disorder. Her test results show an increase in Anti-phospholipids antibodies. Recent studies show that glycosomynoglycans administered to a patient may interrupt the complement cascade. State the cascade of events that are triggered by the anti-phospholipids antibodies and how is the administration of Heparin to this patient helpful?
3. Jill and John have been married for 2 years now, even though John has admittedly cheated on Jill many times they have decided to have a child. John contracted Gonorrhea from on of his extramarital partners. Jill and John have found it increasingly hard to conceive What is the clinical importance of a recent sexually transmitted infection in a man who is trying to conceive with his partner? and What steps need to be taken to alleviate their situation?
WORKS CITED
(1) Sarmast S. Miraculous Birth: How We Defy Biology and Survive Pregnancy.
Yale Scientific Magazine. Published Spring 2005.
http://research.yale.edu/ysm/article.jsp?articleID=353. Accessed April 4, 2008.
(2) Shared Journey: Your Path to Fertility. http://www.sharedjourney.com/index.html
Updated 2008. Accessed April 4, 2008.
(3) Salmon JE, Girardi G. Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation. J Reprod Immunol. 2008; 77:51-56.
(4) Shetty J, Bronson RA, Herr JC. Human sperm protein encyclopedia and alloantigen index: mining novel allo-antigens using sera from ASA-positive infertile patients and vasectomized men. J Reprod Immunol. 2008; 77:23-31.
