I did a quick medline search for further info on MTX prior to conception and
did find a more recent review article (though I'm not really familiar with
this journal, so I don't know if it is peer reviewed):
Lloyd ME. Carr M. McElhatton P. Hall GM. Hughes RA. The effects of
methotrexate on pregnancy, fertility and lactation. [Review] [101 refs]
[Journal Article. Review] Qjm. 92(10):551-63, 1999 Oct.
They have a paragraph on MTX prior to conception stating:
"After administration, methotrexate is widely distributed in body tissues,
the highest concentrations being in the kidneys, gallbladder, spleen, liver
and skin. Its presence in the liver has been reported up to 116 days after
exposure, although the amount of drug retained does not appear to be related
to the dose received.7,49 There is thus a theoretical risk of fetal exposure
in babies of mothers who have taken the drug up to 4 months prior to
conception. Table 5 summarizes the largest prospective study of pregnancy
outcome in women on MTX prior to conception.40 It is also the only study
where low-dose MTX was used within 1 year of pregnancy. A high rate of
spontaneous abortion is seen (as mentioned above), but there were no
abnormalities of surviving fetuses. However, the numbers (nine in total) are
small. A study looked at 368 pregnancies in 210 women who had had single-
and combined-agent chemotherapy for gestational trophoblastic tumours over a
20-year period. All patients were given MTX, followed in the majority by
folinic acid. The mean duration between cessation of treatment and pregnancy
was 2.7 years, the mean cumulative dose of MTX around 1.2 g, and the maximum
dose over 6 g. Abnormalities included two anencephalic stillbirths, and one
case each of spina bifida, tetralogy of Fallot, talipes equinovarus,
collapsed lung and umbilical hernia. One child of a mother who had received
MTX developed desquamative fibrosing alveolitis 1 month after birth. The
mother later gave birth to a healthy child, but 3 years later, a further
child suffered the same problem. In the study overall, there was a slightly
higher but statistically insignificant incidence of stillbirth and
congenital abnormality compared to the expected background rate.50 In an
earlier report of a smaller number of patients, presumably from the same
sample, the authors describe four cases of abnormality in 130 women who had
received MTX alone. The abnormalities were: umbilical hernia, doliocephaly
plus talipes, anencephaly and fibrosing alveolitis. Again, the fetal wastage
rate was not raised.51 These authors, from an oncology unit, advise delaying
conception for a year after the cessation of chemotherapy. This advice
differs from manufacturer's recommended 'washout period' before MTX
cessation and conception, which varies between 3 and 6 months.52 In order to
allow for the persistence of MTX in tissues and to avoid potential
chromosomal damage to the dividing follicle, a minimum delay of 6 months
would seem logical."
Jayne Charlamb, MD
Syracuse
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