Originally published in Synapse on Dec. 2, 1993.
Every year there are some four million unintended pregnancies in the United States, approximately 1.6 million end in abortion. These figures were cited during a recent discussion with UCSF students by Mitchell Creinin, assistant professor in the Department of Ob/Gyn and Reproductive Sciences. According to Creinin, surgery remains the safest method of abortion, but it is both costly and emotionally disruptive to the patient.
The alternative, pharmacological abortion with a drug such as RU4B6, is less invasive and 95% effective; but RU4B6 has not been approved for use in the United States. Creinin has been investigating the use of the cytotoxic drug methotrexate as an abortifacient.
Methotrexate is currently used as a chemotherapy agent for the treatment of trophoblastic neoplasia (cancer of the placental tissue) because of its toxicity to the most rapidly dividing cells, i.e., the cancerous cells. It has also been shown to be safe and effective in low doses in the treatment of ectopic pregnancy, a life-threatening condition in which the fertilized ovum implants outside of the uterus — for example, in the fallopian tube.
Classical treatment of ectopic pregnancy involves removal of the fallopian tube or dissection of the tube to remove the developing embryo. Such treatment can have harmful complications, including infertility. Methotrexate treatment, on the other hand, causes no such complications and allows the patient to have subsequent pregnancies.
Creinin, along with Philip Darney, a UCSF professor in Ob/Gyn, conducted several studies to investigate the hypothesis that methotrexate would achieve the same effect on an intrauterine pregnancy as an ectopic pregnancy.
The first study, published in the October issue of Contraception, studied the effectiveness of methotrexate plus misoprostol (a prostaglandin analog) in 10 healthy women who were less than eight weeks pregnant. They agreed to surgical abortion if their pregnancy was still viable after 14 days following the beginning of the study.
On day one of the study, the patient was given an intramuscular injection of methotrexate. The patient returned to the clinic for the next six days to have serum human chorionic gonadotropin (B-hCG) levels determined. (B-hCG is a hormone produced during pregnancy which falls when the pregnancy has been successfully terminated.)
On day four the patient received misoprostol orally or vaginally to contract the uterus and expel the pregnancy tissue. Patients kept a log to monitor side effects such as nausea, bleeding and cramping. The six patients who received vaginal misoprostol aborted within three to eight hours. (One had an incomplete abortion and subsequently received a surgical abortion.)
The oral regimen, on the other hand, required weeks to produce an abortion. Two of the four who received the oral misoprostol aborted after approximately 25 days and two elected for surgical abortion after 14 days.
No methotrexate side effects were reported, but nausea and cramping were noted following misoprostol administration. A second study, which will appear in the December issue of Contraception, investigated the effectiveness of methotrexate without misoprostol. After three weeks, all 10 subjects aborted the pregnancy with essentially no side effects.
Creinin has completed a larger study involving approximately 100 women. The results have yet to be published. Although these studies are too small to make valid comparisons between methotrexate and RU4B6, they are promising.
The methotrexate-misoprostol regimen is inexpensive and readily available in the United States. The drugs needed for the treatment of one patient cost about $5, as opposed to RU4B6, which would be expensive if ever approved in the United States.
