Fertility Treatment May Boost Migraine Frequency

Fertility treatment in women with migraine is linked to an increase in headache frequency, new research suggests.

Preliminary results from a prospective cohort study showed participants with a history of migraine had an increased number of headaches vs their counterparts without migraine while undergoing fertility treatment.

The findings underscore the importance of identifying and monitoring these patients, said co-investigator Joseph Safdieh, MD, professor and vice chair of education, Department of Neurology, Weill Cornell Medicine, New York City.

“Physicians should counsel women with migraine who are undergoing infertility treatment and monitor their migraine attack frequency during the treatment,

and if things are changing, they should be proactive about ensuring patients have appropriate therapies available so women are not suffering unnecessarily,” Safdieh told Medscape Medical News.

The findings were presented at the American Headache Society (AHS) Annual Meeting 2022.

More Difficult to Manage

Hormones play an important role in the pathophysiology of migraine in women, and fluctuating estradiol levels during the menstrual cycle can affect the frequency of attacks.

Other factors that influence the frequency of attacks include diet, stress, and exercise, said Safdieh.

In addition, an increasing number of women face infertility problems, due in part to delayed childbearing, which is leading to more seeking fertility assistance. The obesity epidemic in the US may also play a role in infertility, Safdieh noted.

Co-investigator Jasmin M. Harpe, a headache fellow at Mass General Brigham in Boston at the time, and colleagues had noticed anecdotally that women reported their headaches got worse and were more difficult to manage while undergoing in vitro fertilization (IVF).

Safdieh noted there has been little systematic prospectively collected data to try to understand the relationship between migraines and fertility treatment.

For the current study, the investigators screened for migraine among women scheduled to undergo fertility treatment. Participants completed the ID Migraine screening tool, which asks about nausea, light sensitivity, and activities of daily living; and the Depression, Anxiety and Stress scale (DASS 21).

The study included 28 women with migraine and 42 without migraine (mean age, 37 years), all of whom were undergoing IVF or egg/embryo freezing. Safdieh noted this is “about halfway to our goal” of study enrollment.

About 75% of the migraine group and 65% of the control group had received fertility treatment in the past. In addition, 81% and 37%, respectively, experienced headache with prior fertility treatment.

About 77% of the migraine group reported having menstrual migraine vs 11% of the control group.

Greater Headache Burden

The primary outcome was change in migraine attack frequency measured by the Headache-Attributed Lost Time 30 (HALT 30) scale, a modified version of HALT 90 scale. Measurements were recorded at three timepoints: pretreatment (baseline), during treatment, and posttreatment.

Safdieh noted that during the fertility treatment period, women received daily estrogen injections that boost egg production in the ovary. Once estrogen levels are high enough and the follicle growth is sufficient, they get an “ovulation trigger,” an injection of beta-human chorionic gonadotropin (β-hCG) that facilitates egg retrieval.

Results showed women with migraine had significantly greater headache burden than those without. In the migraine group, the mean HALT 30 scores were 4.52 pretreatment, 5.7 during treatment, and 6.95 posttreatment. The rates also increased in the control group but not by much, with scores of less than 1.

“Women who screen for migraine clearly have a lot more headaches during their treatment than women who don’t,” said Safdieh. “While you might say that seems apparent, that is not something that has ever been formally assessed or reported before.”

There was a trend toward increasing headache frequency through the course of treatment among those with migraine. However, this wasn’t statistically significant because the study was underpowered to detect a difference, said Safdieh. Still, he believes the power will increase as more patients are enrolled.

The “mega-dose” of estrogen women receive creates a “massive peak” and then rapid drop of the hormone may be responsible for worsening headaches during fertility treatment, Safdieh said.

About 22% of the control group had a history of migraine in their chart but the quick ID Migraine screen, which asks about migraine only in the past 3 months, did not capture this information. Researchers plan to reanalyze the data to determine if this made a difference to results, Safdieh reported.

The investigators are also completing secondary analyses looking at changes in stress, lifestyle, and other measures. Already, the results show the group with migraine has significantly more anxiety and stress symptoms than the control group.

A First Step?

Commenting for Medscape Medical News, Lauren Doyle Strauss, DO, associate professor of neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, said the new study is most welcome.

As it stands, there is so little work being done related to fertility, pregnancy, or lactation that it’s difficult to draw conclusions from it, said Strauss, who was not involved with the research.

This new study “is a first step and it’s very exciting,” she said.

Strauss noted headaches can become worse in the setting of infertility treatments because of having to deal with the stress and emotions of being infertile, the treatments and associated physician appointments involved, and concerns about the future. “It’s a very challenging period not only for the patients but for the families,” she said.

Some women with migraine may experience changes in their headaches. For example, they may get “a weird, difficult, and long headache” while undergoing fertility treatment, said Strauss. This may trigger further investigation, which just adds to the stress and uncertainty of the situation.

“To pursue infertility treatment is a very serious decision, but we don’t want someone not to pursue it because they have a history of headache or migraine,” Strauss concluded.

Safdieh reported having received an American Academy of Neurology Editorial Stipend and royalties from Elsevier.

American Headache Society (AHS) Annual Meeting 2022. OR-11, Scientific Session 2A. Presented June 11, 2022.

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