You are currently browsing the Dr Licciardi blog archives for June, 2007.

Miscarriage and the Immune System (antibodies)

As many of you have noticed, I have been avoiding this one. It’s just too controversial. Actually, there are many known facts but very little data.
Let’s start with what we know. We know that there are people out there who have high levels of antibodies who have miscarriages. Who are these people? They have the “anti-phospholipid syndrome”. Which is? A condition whereby the body makes antibodies against its own cells. We all have antibodies that help us fight disease and none of us would be here if it were not for antibodies. Some, probably many of us, have extra antibodies that don’t fight disease, but rather fight ourselves. These are auto-antibodies. Probably the most common are the thyroid antibodies; antibodies that the body makes that attack the thyroid gland. Up to 10% of women have thyroid disease, and the vast majority is due to antibodies against the thyroid that slowly destroy the gland making it under-active (Hashimoto’s Thyroiditis). Grave’s Disease is thyroid antibody condition that makes the thyroid overactive. There are many other autoimmune diseases, such as Rheumatoid Arthritis, that occurs when the body makes antibodies against the cells of our joints.
Phospholipids are large molecules that are on the surface of most of our cells, so as you could imagine, antibodies that help destroy phospholpids can’t be a good thing. In patients with the Antiphospholipid Syndrome (APS), these antibodies somehow affect the blood clotting system (we don’t exactly know how). These people are very prone to large blood clots in their arteries and veins. And it’s not just the vessels of the legs and pelvis, but the arms, neck and brain can also get dangerous clots. Now the placenta also has large blood vessels and vascular spaces. In patients with true APS, clots can form between the uterus and the placenta, reducing or stopping blood flow, and this causes miscarriage. This is what we know, and this is about all we know. As you will see next time, we know very little about clotting and miscarriage in women who do not have APS.
So where does Lupus come in? Well now we are getting into some overlap and probably a little confusion. Patients with lupus can have antiphospholipids, but not necessarily the full APS. Patients with Lupus usually have other autoantibodies that attack DNA, again not a good thing. Here almost all types of the body’s cells (brain cells, joint cells, kidney cells, joint cells, to name a few) can be affected. One of the blood tests for APS is called the Lupus Anticoagulant test. So some women have both, some have one or the other, and some can have a mix. And in case you were wondering, cardiolpins are a type of phospholipid, so anticardiolipins are another type of antiphospholipid antibodies.
Next time we will tighten this up and talk about what this all means to some one with miscarriages and abnormal clotting tests.

References:

  • Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev 2005; (2):CD002859.
  • Practice bulletin no. 132: antiphospholipid syndrome. Obstet Gynecol. 2012 Dec; 120(6):1514-21.
  • Ernest JM, Marshburn PB, Kutteh WH. Obstetric antiphospholipid syndrome: an update on pathophysiology and management. Semin Reprod Med. 2011 Nov; 29(6):522-39.
  • Bradley LA, Palomaki GE, Bienstock J, Varga E, Scott JA. Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review. Genet Med. 2012 Jan; 14(1):39-50.

More Questions about Ectopic Pregnancies

Thanks for all of the comments and questions. As the weeks and months go by I will get to as much as I can. I would like to finish up a few more about ectopics. I realize this topic only applies to a few of you, but everyone having fertility treatment should know more about ectopics.

What are the Treatments for Ectopic Pregnancy? It’s surgery (almost always laparoscopy) , Methotrexate or observation. Observation is ok if the levels are falling and you feel well and you are highly supervised. Before we started using Methotrexate (about 20 years ago), everyone had surgery.
If I have surgery, does my tube need to be removed? Not always. Sometimes, if there is no rupture, the tube can be opened and the pregnancy removed. If however, the tube is removed, it’s usually for a few good reasons. Studies have shown that the natural fertility is the same after a tube is either fixed or removed for ectopic. The reasons for this may be that the tube was damaged anyway (leading to the ectopic), therefore its usefulness was low. It’s also possible that the ectopic occurred in a normal tube, but the ectopic damaged the tube. Also, having an ectopic increase the chances of another, so removing the tube will prevent that. Also, many patients who have ectopics are undergoing IVF, so if IVF is happening, removing the tube is less of a concern. Problems associated with leaving the tube in are an increased risk of re-operation bleeding from that tube. Another is that the hCG levels sometimes do not completely fall after leaving the tube in. If this is the case, methotrexate or additional surgery may be necessary.

What is Methotrexate? Methotrexate (MTX) is a medication that can treat most ectopics. It interferes with folic acid metabolism. DNA, RNA and proteins cannot be made or maintained without folic acid, therefore MTX causes cell death. The reason the other cells of the body are not harmed is because the pregnancy cells are dividing much more rapidly and need more folic acid. If the dose was higher, and the treatment longer, the other cells would have trouble surviving. MTX was developed and is still used as chemotherapy for certain cancers (other rapidly dividing cells). The dose of MTX for ectopic pregnancies is lower than for cancer chemotherapy, so the side effects are minimal. The package insert says MTX can cause hair loss, nausea and vomiting, low blood counts and other complications. The reality is that because the dose is relatively low, these side effects are very rare. I have never seen them, maybe some of you have. The dose is calculated based on a person’s height and weight.
One dose of MTX successfully treats an ectopic pregnancy 80-90% of the time. Sometimes a second injection is necessary if the first is not effective. We measure the effectiveness buy the level of the hCG. If the hCG numbers don’t fall after 1 week, a second injection may be necessary. And rarely, even after methotrexate, tubal bleeding can occur making surgery necessary.
That will do for now. Haven’t decided on the next topic yet. Please read disclaimer 5/17/06. Dr. Licciardi

References:

  • Hajenius PJ et al. Interventions for tubal pregnancy. Cochrane Database System Review, Jan 2007.
  • ACOG Practice Bulletin Number 3, December 1998.  Medical Management of Tubal Pregnancy.
  • Ankum WM, Mol BW, Van der Veen F, Bossuyt PM. Risk factors for ectopic pregnancy: a meta-analysis. Fertil Steril 1996; 65:1093–9.
  • Lipscomb GH, McCord ML, Stovall TG, Huff G, Portera SG, Ling FW. Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies. N Engl J Med 1999; 341(26):1974-8.
  • Barnhart KT, Gosman G, Ashby R, Sammel M. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol 2003; 101(4):778-84.
  • Rosman ER, Keegan DA, Krey L, Liu M, Licciardi F, Grifo JA. Ectopic pregnancy rates after in vitro fertilization: a look at the donor egg population. Fertil Steril. 2009 Nov; 92(5):1791-3.
  • Stovall, TG et al.  Single dose methotrexate: an expanded clinical trial.  Am J Obstet Gynecol 1993; 168:1759-1765