Migraine in women undergoing fertility treatment: A prospective study

OBJECTIVE: To determine if there is increased headache burden and disability among women with and without migraine during an in vitro fertilization (IVF) cycle. BACKGROUND: Migraine and infertility commonly impact women of childbearing age. Estradiol fluctuations influence migraine, yet the impact of exogenous estrogen on migraine during fertility treatments such as IVF is not well characterized. We assessed migraine burden and disability among women with and without a history of migraine during an IVF cycle. Secondary outcomes included psychological symptoms and estradiol levels. We hypothesized that although all women may be at risk of migraine symptoms during an IVF cycle, women with migraine would be more likely to experience greater headache-related disability and associated psychological symptoms during an IVF cycle. Furthermore, we hypothesized that women with migraine would experience an increase in headache-related disability between time point 2 (when estrogen peaks after ovulation trigger) and time point 3 (when estradiol levels reach a nadir). Women without a history of migraine were included to assess the development of de novo migraine during IVF due to shifts in estradiol. METHODS: A prospective cohort study of adult women undergoing an IVF cycle at the Weill Cornell Medicine Center for Reproductive Medicine (New York, NY) from 2020 to 2023 completed an initial health questionnaire and follow-up throughout an IVF cycle at three time points. Data collected included a measure of headache disability (Headache-Attributed Lost Time over the past 30 days HALT-30); psychological scales (Depression Anxiety and Stress Scale-21 item); and serum estradiol, follicle-stimulating hormone, luteinizing hormone, and progesterone levels. RESULTS: Seventy-six participants completed all study time points, including 52 with migraine (18 with aura) and 24 controls. At each time point, the migraine group had higher total HALT-30 scores compared to controls. HALT-30 scores were 5.6 (confidence interval: 2.1 to 9.1) higher, on average, in the migraine group compared to the control group after controlling for time and the interaction between the two (p = 0.002). There were no statistically significant differences in HALT-30 scores over time when analyzing the migraine with aura and migraine without aura groups separately. However, in the combined model, with each week that passed, the HALT score increased, on average, by 0.09 in the migraine without aura group (p = 0.011). Despite the migraine group having greater headache-related disability scores at each time point, the level of disability as measured by the HALT-30 did not change over time throughout the IVF cycle. Serum estradiol levels peaked at the second time point in both groups without significant differences between groups. Participants with migraine consistently reported greater psychological distress (stress, anxiety, and depression) than controls across multiple time points. Depression Anxiety and Stress Scale-21 item stress scores decreased, on average, by 4 interquartile range: -5, 0 points in the control group compared to 0 interquartile range: -4, 4 points in the migraine group (p = 0.019) between the second and final time points. CONCLUSION: This prospective cohort study demonstrated that women without migraine history maintained a low level of headache-related disability during IVF. It did demonstrate that women with history of migraine experienced elevated migraine disability during an IVF cycle; however, headache-related disability did not change over time, specifically between time point 2 and time point 3 when there is the largest change (peak-to-nadir) in estradiol levels post-ovulation trigger. This study highlights that the shifts in estradiol during an IVF cycle may not exacerbate headache-related disability beyond baseline in women with migraine. However, participants with migraine reported higher levels of psychological distress at different time points in three domains throughout the study-stress, anxiety, and depression-highlighting the importance of mental health support for women with migraine during an IVF cycle. Overall, this study found that participants maintained a low level of headache-related disability throughout the IVF cycle; however, this study cannot rule out the possibility of transient exacerbations in disability that were not captured by the HALT-30.