Recurrent Early Pregnancy Loss - 10 - Empiric Treatment
If a woman has regular menstrual cycles and has never had trouble conceiving (and no abnormalities found during the diagnostic evaluation which is more often than not the case), I usually offer the following advice and empiric treatment regimen: discontinue smoking and alcohol and limit caffeine intake; begin a prenatal vitamin daily; start supplemental folic acid 4 mg daily; take a baby aspirin (81 mg) once daily (this antagonizes the ‘platelet side’ of the coagulation system); offer ‘progesterone support’ either in the luteal phase, or as soon as a pregnancy is confirmed and continue this until 10-12 weeks. I will also offer a course of a broad spectrum antibiotic (azithromycin or doxycycline) to BOTH partners early during the first cycle she attempts to conceive. These antibiotics treat organisms such as mycoplasma and ureaplasma (rather than culture for these organisms) among many others.
After conceiving, I ask that she return by about 6 weeks (two weeks after the missed menstrual cycle), perform an ultrasound to confirm an intrauterine pregnancy, repeat the lupus anticoagulant and anticardiolipin antibody screens (even if these were negative between pregnancies), and also screen for circulating complement levels. The complement system (the 'classical pathway') is activated by certain antibodies once they have attached to something ‘foreign’ (forming ‘immune complexes’) and help to destroy that to which the antibodies have attached. If complement levels are low or low normal during pregnancy (normally during pregnancy they increase), this might reflect ‘complement consumption’, the presumption being that the invading trophoblasts may be the targets against which the complement-fixing antibodies are directed. (Another possibility is that the 'alternative complement pathway', that does not require antibodies, is somehow being activated, but I do not want to get into that here and it doesn't change what I do at this point anyway!) I have used this approach (the low complement levels) over the years (although I have never seen a published study to justify it) to guide more aggressive therapy in women with known autoimmune disorders, lupus anticoagulants, or anticardiolipin antibodies, and even those with no other abnormal findings (the rationale being that there are things we still do not know, other factors which have not yet been found or implicated in pregnancy loss and, therefore, are not tested for at this time).
If the studies noted above are all ‘normal’, and the patient has a history of 3 or fewer losses, I recommend that no other therapy be started during this pregnancy. If the patient has had more than 3 losses, has previously failed this initial empiric approach to therapy, has any abnormal immunologic or coagulation studies, or just plain insists because "I want to do everything possible now," I offer to add either heparin (inexpensive) or low-molecular weight heparin (very expensive) therapy (which antagonize the other side of the clotting system), both of which must be given by subcutaneous injection. This regimen has replaced the immunosuppressive steroid (e.g., prednisone) therapy (except in the patient with an overt and active autoimmune disorder) that we used, also emprically, years ago when I first became interested in recurrent early pregnancy loss and it appears to be just as effective (with far fewer side-effects such as gestational diabetes, swelling, and increased risk for infection).
This approach to therapy is the foundation upon which I build for any woman with recurrent early pregnancy loss. In the absence of other specific abnormalities, 'success rates' are extraordinarily high using this approach. Others would argue that success rates in this group of patients are high regardless of what is done. I don't necessarily disagree with that, but I have had patients over the years who had far more than 3 losses who only successfully carried after starting this regimen, and quite frankly, I don't think any of us are smart enough at this time to know who actually needs it and who doesn't! In our next post let’s address what we do if specific abnormalities are found during the diagnostic workup, always keeping in mind that multiple factors may be in play and the 'empiric regimen' (or parts of it) might still be warranted, even after these other factors are addressed…