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Alcohol and Substance

Effect of methotrexate treatment of ectopic pregnancy on subsequent pregnancy

Rinat Hackmon, MD, Sachi Sakaguchi, MD and Gideon Koren, MD, FRCPC, FACMT

January 2011



My last pregnancy was diagnosed as ectopic, and I was treated successfully with intramuscular methotrexate (MTX) 8 weeks ago. I am currently planning for another pregnancy; however, I have read that MTX causes birth defects and that it stays in my body for a very long time, ranging from 1 to 12 months after treatment. When is it safe to conceive?


We suggest that the outcomes of pregnancies conceived shortly after MTX therapy for extrauterine pregnancy are most likely to be favourable and similar to those pregnancies conceived 6 months after MTX treatment. However, as data are not sufficient to draw a definitive conclusion or to confirm the exact safetiming after MTX treatment, at least a 3-month waiting period is recommended for women who are planning pregnancy. Nevertheless, conception within 3 months of MTX treatment of extrauterinepregnancy should not be considered a definite indication of termination, and further targeted fetal anatomy assessment is recommended. Further retrospective and prospective studies areneeded to define the safety period before 3 months and to solidify this recommendation.


J’ai eu un diagnostic de grossesse ectopique et on m’a traitée avec succès, il y a 8 semaines, par injection intramusculaire au méthotrexate (MTX). Je planifie actuellement une autre grossesse, mais j’ai lu que le MTX cause des malformations congénitales et que la substance persiste dans le corps pendant une très longue période après le traitement, pouvant aller de 1 à 12 mois.


Nous sommes d’avis que l’issue d’une grossesse conçue peu après une thérapie au MTX pour une grossesse ectopique sera probablement favorable et semblable à celle d’une grossesse conçue 6 mois après le traitement au MTX. Par ailleurs, puisque les données ne sont pas suffisantes pour tirer des conclusions définitives ou pour confirmer un délai d’attente exact après un traitement au MTX, nous recommandons aux femmes qui prévoient une grossesse d’attendre au moins 3 mois. Néanmoins, la conception dans les 3 mois suivant un traitement au MTX pour une grossesse extra-utérine ne devrait pas être considérée comme une indication définitive pour y mettre un terme et il est recommandé de procéder à une évaluation plus approfondie de l’anatomie fœtale. Il faut un plus grand nombre d’études rétrospectives et prospectives pour déterminer les risques d’une conception dans les 3 mois suivant la thérapie, et renforcer cette recommandation.

Recent studies suggest that at least 10% of all pregnant women meet the criteria for major depression, 1 and up to 18% exhibit elevated depressive symptoms. 2 Untreated depression in pregnancy has been associated with poor maternal health and adverse pregnancy outcomes. The Edinburgh Postnatal Depression Scale (EPDS)* is a 10-item self-rating scale. It was developed by Cox et al in 1987 for detection of postpartum depression 3 and was later validated for use during pregnancy. 4 Scores range from 0 to 30, with a cutoff score of 11 or higher being recommended for need of monitoring of major and minor depressive disorder. Although not diagnostic per se, a cutoff score of 14 or higher is recommended for detection of major depressive disorder, with sensitivities of up to 100%. Owing to our growing awareness of the fact that many women with depression go undiagnosed, in 2007 Motherisk added the EPDS to our routine assessment in the clinic. Women complete the questionnaire while in our clinic waiting for their appointments. Following the appointment, we report the EPDS results to the patient and follow the appropriate recommendations (Box 1).

Upon analyzing the outcomes from the first 2.5 years of using this assessment, we were very surprised by the findings and clinical implications. From October 2007 to April 2010, 404 women completed the questionnaire, 176 (43.6%) of whom were pregnant at the time. Overall, a quarter of the women (25.7%, 104 of 404) received a score of 13 or higher on the EPDS scale, which is highly suggestive of major depressive disorder.

Box 1.

Recommended follow-up to results of the Edinburgh Postnatal Depression Scale (EPDS)*:

The EPDS is a 10-item self-rating scale. The total score is calculated by adding together the scores of the 10 items; maximum score is 30.

 Forty-three percent of the pregnant subpopulation (75 of 176) scored 11 or higher on the EPDS scale, and nearly a third (31.2%, 55 of 176) scored 14 or higher. Most of these women came to our clinic for counseling on conditions unrelated to depression. For the final statement on the EPDS (ie, The thought of harming myself has occurred to me "yes, quite often," "sometimes," hardly ever," or "never"), 32.0% (24 of 75) of women chose responses other than "never." One hundred fifty-seven women came to the clinic for counseling specifically regarding antidepressant medications. Of these diagnosed and treated women, 32.5% scored 13 or higher.

It is alarming that a large number of women in our population, not previously diagnosed with depression, appear to be exhibiting depressive symptoms and occasional suicidal thoughts. In addition we noted that a substantial number of women currently treated pharmacologically for depression also scored high on the EPDS scale, suggesting undertreatment. These results strongly support implementing this depression-screening tool as part of a routine medical investigation during early pregnancy, in an effort to identify, monitor, and treat these women.



Motherisk questions are prepared by the Motherisk Team at The Hospital for Sick Children in Toronto, On. Mr. Sermer was a summer student at Motherisk. Drs. Walfisch and Matok are members of the Motherisk Program. Dr. Koren is Director of the Motherisk Program. Ms. Einarson is a consultant for the Motherisk Program. Dr. Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation. He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at the University of Western Ontario in London.

Do you have questions about the effects of drugs, chemicals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at 416 813-7562; they will be addressed in future Motherisk Updates.

Published Motherisk Updates are available on the Canadian Family Physician website (www.cfp.ca) and also on the Motherisk website.

View abstract »»

Competing interests: none declared

The Edinburgh Postnatal Depression Scale is available at www.cfp.ca.

Canadian Family Physician
July 2011 vol. 57 no. 7 777-778
Copyright © the College of Family Physicians of Canada


  1. Einarson A. Introduction: reproductive mental health--Motherisk update 2008. Can J Clin Pharmacol 2009;16(1): e1-5. Epub 2009 Jan 22. Medline
  2. Muzik M, Marcus SM, Heringhausen JE, Flynn H. When depression complicates childbearing: guidelines for screening and treatment during antenatal and postpartum obstetric care. Obstet Gynecol Clin North Am 2009;36(4): 771-88, ix-x. Medline
  3. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry 1987;150:782-6. Abstract|Full Free Text
  4. Chatillon O, Even C. Ante Partum depression: Prevalence, diagnosis and treatment. Encephale 2010;36(6):443-51. Epub 2010 Apr 7. Medline
  5. Chaudron LH, Szilagyi PG, Tang W, Anson E, Talbot NL, Wadkins HI, et al. Accuracy of depression screening tools for identifying postpartum depression among urban mothers. Pediatrics 2010;125(3): e609-17. Epub 2010 Feb 15. Abstract|Full Free Text
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