Concerns about methotrexate embryopathy should preclude its use when the possibility of an intrauterine pregnancy exists. In his letter to the editor, Dr Sholapurkar suggests a β-hCG follow-up of 3 repeat measurements, 48 hours apart, to prevent inadvertent methotrexate administration in viable intrauterine pregnancies.

As previously reported, there are no guidelines regarding the timing of methotrexate therapy so that prompt administration before β-hCG follow-up may have serious consequences. Medical therapy with methotrexate is dangerous in cases of an intrauterine viable pregnancy but it is also redundant in cases of a spontaneously resolving ectopic pregnancy or pregnancy of unknown location. A recent publication points out the risks and suggests caution and tips with methotrexate administration. These issues were our major concerns and the basis behind the design of our protocol. Methotrexate therapy was avoided in cases where an intrauterine pregnancy was suspected based on rising β-hCG levels and an inconclusive ultrasound report. An important contraindication for methotrexate therapy was the presence on an intrauterine pregnancy, but more importantly, all of the patients with rising β-hCG levels had ultrasound scans performed and measurement of the ectopic mass documented. Using the combination of β-hCG follow-up and ultrasound scans documenting extrauterine pregnancies we were able to prevent inadvertent use of methotrexate. It follows that in our series of patients we treated patients with ectopic pregnancies rather than patients with pregnancies of unknown location.

In asymptomatic patients longer periods of follow-up before medical therapy is administered are becoming a true option, thereby obviating the use of toxic agents such as methotrexate in misdiagnosed cases of evolving intrauterine pregnancies.

In our large series of patients, we did not report a single case of inadvertent administration of methotrexate where an intrauterine viable pregnancy was later diagnosed.