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Headaches in Women Undergoing in Vitro Fertilization and Embryo-Transfer Treatment


  • Ben-Yehuda Amir BMSc,

  • Bentov Yaacov MD,

  • Bar Guy MD,

  • Potashnik Gad MD,

  • Wirguin Itzhak MD,

  • Ifergane Gal MD

  • From the Headache Clinic, Neurology Department (Mr. Ben-Yehuda Amir, Dr. Wirguin Itzhak, Dr. Ifergane Gal) and Fertility and In Vitro Fertilization Unit, Department of Obstetrics and Gynecology (Dr. Bentov Yaacov, Dr. Bar Guy, Dr. Potashnik Gad), Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Address all correspondence to Dr. Gal Ifergane, Department of Neurology, Soroka Medical Center, P.O. Box 151, Beer-Sheva, Israel.


Background.—In vitro fertilization and embryo transfer has become a common therapeutic modality in modern fertility medicines. Treatment protocols are associated with exaggerated hormonal fluctuations in order to promote multiple follicular development and support of embryo survival. Estrogen is considered to be closely linked to migraine, and its extreme serum level fluctuations have been considered to trigger migrainous headaches.

Objective.—To assess the prevalence, nature, and timing of headache attacks during the course of in vitro fertilization and embryo-transfer treatments.

Methods.—We retrospectively evaluated the prevalence and the characteristics of headache among 98 women undergoing in vitro fertilization and embryo transfer therapy using a structured telephone interview.

Results.—Out of the 98 evaluated patients 25 were migraine sufferers. Headache attacks during the in vitro fertilization and embryo transfer protocol were reported by 28.6% (n = 28) of the women and were significantly more prevalent among the migraineurs. The attacks were of debilitating severity in 82% (n = 23) of patients who reported headaches during treatment. Headache occurred most frequently following gonadotropin-releasing hormone (GnRH) analog induced hypothalamic-pituitary-ovarian axis downregulation, typically associated with very low 17-β-estradiol (17-β-E2) serum level.

Conclusions.—In vitro fertilization and embryo-transfer treatment might be associated with various degrees of headache. This is mostly observed in patients with migraine headache background and specifically during the downregulation stage of treatment, when very low levels of 17-β-E2 are observed.

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