Fruit of the Womb
Fruit of the Womb

Concerns Regarding Methotrexate Therapy

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In a recent post we discussed "A Complication of Methotrexate Use for Ectopic Pregnancy..." and in response to that post we had several excellent questions from our readers. The queries below should be of general interest to many women who undergo methotrexate therapy either for ectopic pregnancy or for other medical conditions, such as autoimmune or neoplastic diseases, that are not uncommon in women of childbearing age…

Hi Dr. T. I've been given conflicting answers by different gynecologists and rheumatologists in regards to methotrexate "wash out period" and pregnancy and frankly, I'm worried. Some say it's safe to get pregnant 3 months post methotrexate others say 4-6 months. Here's my scenario: I've been on methotrexate 25mg sc weekly dose, last dose being June 28, 2007. My LMP (last menstrual period) was Sept 8, 2007, and I just found out I was pregnant yesterday. Although it's been almost 4 months since my last dose of methotrexate, I'm very concerned about my child’s risk of teratogenicity. What are the chances of this happening? What would the best course of action be? Also, would folinic acid help, in my case, to decrease the chances of birth defects? Thanks

Chances are you will be just fine. When methotrexate is given by injection, peak serum concentrations are reached within 30-60 minutes. The drug is metabolized by the liver and excreted, mostly, by the kidneys. The half life ranges between 3 to 15 hours depending on the dose, chronicity of therapy and, obviously, liver and kidney function. Methotrexate does have some metabolites that may hang around “for an extended period of time” but the general consensus is that it is “safe” to get pregnant after at least one complete ovulatory cycle following the last dose. In your case, you are well beyond this recommended period and are, therefore, probably at no greater risk for fetal malformations than either the general population or other predisposing risk factors you and your partner bring into the pregnancy. There is no need for folinic acid, but since methotrexate is an antagonist of dihydrofolate reductase, I hope you started supplemental folic acid before conception and, if not, get some today! If you have regular cycles and your LMP was September 8, your baby’s neural tube should be closing even as we speak, and there probably is still time to decrease the risk for certain congenital heart defects! Best of luck to you and thanks for reading…
Dr T


Hello Dr. My question is regarding what is considered normal for betaHCG levels following MTX treatment for my ectopic pregnancy. On October 2, I was admitted to the hospital with abdominal pain and slight bleeding for the two weeks prior (last period was Aug 24). Tested positive for pregnancy with beta-hCG level at 960. Ultrasound showed nothing in the uterus. Beta-hCG tested again on October 5 was 1544 with ultrasound showing a small (1.1cm mass) in the right cornua (still nothing in the uterus). Beta-hCG tested on October 6 was 1797. Referred to OBGYN at ER for MTX treatment for ectopic pregnancy, for which an injection of 50mg was given same day (my weight 49.8kg). Beta-hCG tested on 10/10 was 2040 and I have not had the pain and abdominal cramping my Dr had prepared me for. My question is whether it is normal for the beta-hCG level to continue rising 4 days after MTX injection? Shouldn't it be falling? Scheduled for another blood test on October 13 but I was wondering when I should be worried that the MTX treatment is not working? I am 25 years old and would like to conceive in the next few years; thus, I would like to preserve both my tubes if possible and avoid surgery. Thank you kindly for your time and consideration.

This is an excellent question. You would certainly be a good prognosis candidate for methotrexate therapy with your relatively low hCG levels and no evidence of rupture or of an embryo with cardiac activity. Various studies have followed the course of hCG and progesterone over time after methotrexate administration for ectopic pregnancy. One study out of Brazil (Elito Junior, et al., Rev Assoc Med Bras. 1998;44:11-5) demonstrated an increase in beta-hCG titers between days 1 and 4 in 50% of women following methotrexate therapy. However, more than 85% of women had a decline of at least 15% by day 7. These findings were confirmed in a more recent study by Gabbur and colleagues (Am J Perinatal 2006;23:193-6). So what you described in your case is not at all unusual. Most studies demonstrate that it takes a mean of about 4 weeks before hCG levels become undetectable. Serum progesterone levels drop more quickly than hCG levels and some investigators have suggested using this as another parameter to predict the success of methotrexate therapy for ectopic pregnancy (Saraj, et al., Obstet Gynecol. 1998;92:989-94). Thank you for your question and I hope things turn out well for you!
Dr T
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About the Author

Dr. Trofatter is an expert on maternal-fetal medicine.

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