Dr. Carolyn Coulam is one of the world’s most renown experts in the area of Reproductive Immunology including Recurrent Pregnancy Loss. Dr. Coulam is board certified in the specialty of obstetrics and gynecology and in the subspecialty of reproductive endocrinology. Prior to joining Team RMI, Dr. Coulam graduated from the University of Utah College of Medicine in 1967 with a degree in medicine and a masters degree in biochemistry. She completed a rotating internship at Mary Hitchcock Memorial Hospital at Dartmouth College, and her residency at the Mayo Clinic, where she remained for 17 years. While on the staff of the Mayo Clinic, Dr. Coulam was chair of the Division of Reproductive Endocrinology and established the first in vitro fertilization (IVF) program at this institution, in 1983.
On the topic of this case, and others like it, Dr. Coulam had this to say…
While anatomic abnormalities have been associated with late pregnancy losses and hormonal abnormalities have been associated with implantation failures, their roles in post-implantation early pregnancy losses have been controversial. The mechanism of the losses in post-implantation pregnancy failures seems to involve clotting off the small placental vessels so that the pregnancy “withers on the vine”. Clotting of these vessels can be caused by cytokines that are produced by immunologic cells (most notably natural killer or NK cells) within the endometrium, antiphospholipid antibodies or a genetic predisposition contributed by thrombophilia genes. Tests available to diagnose which of the above risk factors are contributing to the recurrent pregnancy losses include evaluation of NK cells with the Reproductive Immunophenotype and NK activity assay, measurement of serum concentrations of antiphospholipid antibodies as well as lupus-like anticoagulant and determination of polymorphisms or mutations in thrombophilia genes. Other test that can detect clotting as a result of an inflammatory process included the measurement of antinuclear and antithyroid antibodies as well as the embryotoxicity assay. A description of each of these tests follows:
· Antinuclear Antibodies– The presence of ANA indicates there may be an underlying autoimmune process that affects the clotting off of the placenta and can lead to early pregnancy loss.
· Antiphospholipid Antibodies– Antiphospholipid antibodies have a direct action on the blood vessel to cause clotting. About 17% of women experiencing recurrent pregnancy losses display positive antiphospholipid antibodies. Since some women do not test positive until they are pregnant or have suffered a pregnancy loss, repeat testing during early pregnancy is highly recommended when there is a history of recurrent post0implantation pregnancy loss.
· Antithyroid Antibodies– Women with thyroid antibodies face double the risk of miscarriage as women without them. Increased levels of thyroglobulin and thyroid microsomal (thyroid peroxidase) autoantibodies show a relationship in an increased miscarriage rate, and as many as 31 percent of women experiencing RSA are positive for one or both antibodies. Chances of a loss in the first trimester of pregnancy increase to 20 percent, and there is also an increased risk of post-partum thyroid dysfunction.
· Embryotoxicity Assay– The embryotoxicity assay (ETA) is looking measures substances in blood that kill embryos. Embryotoxic factors have been identified in as many as 60 percent of women with recurrent, unexplained miscarriage, and also reported among women endometriosis-associated infertility.
Effective treatment depends on the cause of the pregnancy loss. If the cause of the pregnancy loss is a problem within the embryo itself, elimination of the problem involves treatments including donor egg, donor sperm or IVF with preimplantation genetic diagnosis (PGD). If, however, the cause is related to activated immune cells and their cytokines, treatments include: Intravenous Immunoglobulin (IVIg) or Intralipid. If either acquired or inherited thrombophilia is causing clotting of the placental vessel and subsequent pregnancy loss, then heparin and aspirin is the treatment of choice. If the blood clotting is the result of an immune process, then steroids may be added to the treatment regimen. If the cause of the recurrent pregnancy loss resides within the uterine environment and if that cause cannot be corrected as was the case in the recent newspaper article, then a host uterus may be a final solution for treatment. In this particular situation, the grandmother was physically and emotionally fit and did an unquestionably loving and generous deed for her daughter.