Hormone Used in Place of Chemotherapy for Ectopic Pregnancy

Megan Brooks

November 25, 2019

PHILADELPHIA — Ectopic pregnancy can be ended just as effectively with letrozole, an aromatase inhibitor, as with methotrexate, a chemotherapeutic agent, according to a small study that generated excitement here at the American Society for Reproductive Medicine 2019 Scientific Congress.

"This has never been shown before" and, if confirmed, "could be huge," said investigator Mohamed Mitwally, MD, from the Odessa Reproductive Medicine Center in Helotes, Texas, who presented the findings at the congress.

In contrast to methotrexate, letrozole works hormonally, "so this is potentially a huge breakthrough, in that you wouldn't need a chemotherapy regimen to treat an ectopic pregnancy," said Eve Feinberg, MD, from the Northwestern University Feinberg School of Medicine in Chicago, who is vice president of the Society for Reproductive Endocrinology and Infertility.

"It's really novel and exciting. This is one of my favorite abstracts," she told Medscape Medical News.

"In the absence of estrogen priming, progesterone may not exert its physiological functions due to a negative effect on progesterone receptors. We hypothesized that by inhibiting the estrogen synthetase (the aromatase enzyme), the progesterone would not exert its physiological function in maintaining pregnancy, including ectopic pregnancy," Mitwally and his colleagues explain in their abstract.

For their study, the team assessed 42 women with undisturbed ectopic pregnancy. Fourteen were treated with methotrexate, 14 were treated with letrozole, and 14 underwent surgery.

Drug treatment led to a complete resolution of the ectopic pregnancy — confirmed with laboratory-detected serum levels of the pregnancy hormone hCG — in 86% of the women.

This treatment can be fast-tracked.

However, in the methotrexate group, two women required surgery after they became hemostatically unstable. And in the letrozole group, one woman required surgery when she became hemostatically unstable and another underwent surgery when her hCG level failed to decrease 4 days after treatment.

The metabolic and hormonal effects of the two medications are different. Women in the methotrexate group experienced a significant elevation in liver enzymes and a significant decrease in platelet levels. Hormone profiles were more favorable in the letrozole group, and hCG levels declined more rapidly in the letrozole group than in the methotrexate group.

And 3 months after treatment, anti-Mullerian hormone levels were lower in the methotrexate group than in the letrozole or surgery groups.

The "promising" high resolution rate and better safety profile with letrozole warrants more definitive study with randomized clinical trials that are adequately powered, the researchers report.

"Theoretically, this treatment can be fast-tracked," said Mitwally, who holds a patent on the use of aromatase inhibitors for the treatment of ectopic pregnancy.

"Number one, it's been used for years, so we know it's safe; number two, it's off patent; and number three, and very importantly, we know it works," he told Medscape Medical News.

"This small study, while preliminary, shows the great promise letrozole holds for the treatment of ectopic pregnancy," Bradley Hurst, MD, president of the Society for Reproductive Endocrinology and Infertility, said in a news release.

"Methotrexate has been a medical alternative to surgery for some time. But as an antimetabolite and immune suppressant chemotherapeutic drug, methotrexate comes with toxic effects that may threaten a patient's health and future fertility. Further research is needed, but based on this study, letrozole appears a safe and effective alternative," he added.

American Society for Reproductive Medicine (ASRM) 2019 Scientific Congress: Abstract O-194. Presented October 16, 2019.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.