PREGNANCY AFTER METHOTREXATE: ANALYZING THE EFFECTS OF POST-TREATMENT CONCEPTION TIMING ON PREGNANCY OUTCOME

Anisa Alizaidy; Salomeh M. Salari; Karen M. Summers; Rachel B. Mejia

doi:10.1016/j.fertnstert.2025.07.259

OBJECTIVE There is no data-driven consensus on the time interval that patients should wait prior to conception after methotrexate (MTX) treatment. Therefore, we explored maternal-fetal complications in relation to time interval between MTX administration and pregnancy conception (time to pregnancy, TTP). MATERIALS AND METHODS A retrospective cohort study at a single academic center was conducted on patients who conceived after receiving MTX regardless of diagnosis code. A total of 355 pregnancies delivered between 2012 and 2024 were included (N=355). The time between last MTX dose and subsequent conception was assigned as TTP for each pregnancy. For patients who conceived multiple times after MTX treatment, each pregnancy was included independently. Conception date was calculated from last menstrual period, estimated date of delivery, or date of intrauterine insemination or embryo transfer. Pregnancies were subdivided into two arms based on TTP of < 3 months (n=27) versus TTP of 3 months or greater (n=328). Maternal demographics, obstetric outcomes, and fetal/neonatal characteristics were collected and descriptive statistics were calculated. RESULTS Indications for MTX treatment were ectopic pregnancy, pregnancy of unknown location (PUL), chronic autoimmune conditions, and gestational trophoblastic disease. On average, TTP was 66±26 days in the < 3 months arm and 767±672 days in the 3 months or greater arm. Live birth rate was 77.8% in the < 3 months arm and 74.8% in the 3 months or greater arm. First trimester miscarriage rate was 14.8% in the < 3 months arm and 17.5% in the 3 months or greater arm. While there were no second trimester miscarriages in the < 3 months arm, second trimester miscarriage rate was 0.6% in the 3 months or greater arm. Ectopic pregnancy/PUL rate was 3.7% in the < 3 months arm and 5.5% in the 3 months or greater arm. The incidence of common birth defects such as cardiac, cleft palate, congenital diaphragmatic hernia, limb anomalies and urogenital anomalies was 0% in the < 3 months arm. The incidence of other anomalies in this same arm, such as benign dermatologic lesions, urinary tract anomalies, and many others, was 21.1%. In the 3 months or greater arm, the incidence of cardiac defects was 4.5%, cleft palate was 0.9%, congenital diaphragmatic hernia was 0.9%, limb anomalies was 0.4%, urogenital anomalies was 7.6%, and other anomalies was 24.4%. CONCLUSIONS This study illustrates the likelihood that pregnancies conceived fewer than 3 months after MTX administration progress without significant complication related to teratogenicity. Although larger, multi-center prospective trials are critical, our data preliminarily suggests that pregnancies conceived fewer than 3 months after MTX treatment are not inherently at higher risk than those conceived 3 or more months after MTX treatment. IMPACT STATEMENT Research on pregnancies conceived fewer than 3 months after MTX administration is limited and guidelines from both the American College of Obstetricians and Gynecologists (ACOG) and the Food & Drug Administration (FDA) are inconsistent. Such studies are integral in guiding family planning in patients being treated with MTX for all indications

PREGNANCY AFTER METHOTREXATE: ANALYZING THE EFFECTS OF POST-TREATMENT CONCEPTION TIMING ON PREGNANCY OUTCOME

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