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Does methotrexate therapy for tubal pregnancy affect subsequent ovarian reserve?

Methotrexate is a cancer drug (chemotherapy) that is used to treat tubal pregnancy. A single dose of the medication will treat a tubal pregnancy in up to 90% of properly selected patients. Thus a single injection is useful for treating a condition that previously required surgery. Sometimes, a second weekly injection is required (and rarely a third). Chemotherapeutic agents are known to have adverse effect on ovarian follicles (eggs) and fertility. This is definitely the case when they are given in high and repeated doses. It is therefore reasonable to ask, “Does methotrexate therapy for tubal pregnancy affect subsequent ovarian reserve and number of eggs retrieved during in vitro fertilization (IVF)?

This very issue was discussed in a recent publication (Fertility and Sterility 2013; In Press) by a group of researchers from a large fertility clinic with offices in Maryland and Washington DC. Hill et al. analyzed data from 153 patients that were treated with methotrexate and 36 patients treated with surgery for tubal pregnancy (or pregnancy of unknown location, PUL) from 2004 to 2010. Pregnancy of unknown location (PUL) included patients with multiple plateaued quantitative values of human chorionic gonadotropin (hCG) (values not increasing over 50% in 48 hours) or with hCG values >2,000 and no ultrasonographic evidence of intrauterine pregnancy. They analyzed basal antral follicle count (AFC), basal serum follicle-stimulating hormone (FSH) levels and number of eggs retrieved from IVF. This is what they found:

They compared result from patients treated with methotrexate (n = 153) and those treated with surgery (n = 36)

  • Neither group demonstrated differences in ovarian reserve or oocyte yield in a comparison of the before and after treatment values.
  • The change in ovarian reserve and oocyte yield after treatment were similar between the two groups.
  • The number of doses of methotrexate was not correlated with changes in ovarian reserve, indicating no dose-dependent effect.
  • Time between treatment and repeat ART was not correlated with outcomes.
  • Live birth in subsequent cycles was similar in the two groups.

The authors therefore conclude that there was no difference between the use of methotrexate or surgery to treat tubal pregnancy or PUL in IVF patients. This was a large study (23,000 fresh IVF cycles were performed during the study period) that confirmed that there is no negative effect of methotrexate on ovarian reserve in IVF patients.

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Dr. Vishvanath Karande

Dr. Vishvanath Karande

Dr. Karande is Board Certified in the specialty of Obstetrics and Gynecology as well as the subspecialty of Reproductive Endocrinology and Infertility. He is a Fellow of the American College of Obstetricians and Gynecologists and Member of the American Society for Reproductive Medicine.


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