National Women’s Health Week
Menstruation May Precondition the Uterus for Successful Pregnancy: A Review
By: Kathy Fatovic
Editor’s Note: As part of National Women’s Health Week, we are featuring an article about the potential role of menstruation to precondition the uterus for future pregnancy. Kathy Fatovic, a former participant in the FACTS elective, summarized the article published by Brosens et al in the American Journal of Obstetrics and Gynecology. The authors explore the role of menstruation in achieving a successful pregnancy by investigating parallels between inflammation present in both menstruation and pregnancy. A healthy pregnancy requires a healthy cycle, and charting with a fertility awareness-based method (FABM) is a valuable tool for patients and their clinicians to gain insight into a woman’s menstrual cycle as well as her overall health.
A common misconception exists that menstruation serves no purpose beyond restarting the endometrial cycle in the absence of pregnancy. However, an association has been found between cyclic endometrial decidualization following menstrual shedding and protection against placentation-related disorders such as preeclampsia. Both menstruation and pregnancy are inflammatory conditions that cause a degree of tissue injury. In the 2009 article summarized below, Brosens et al postulate an evolutionary advantage to menstruation as protection against hyperinflammation and oxidative stress, a process called preconditioning. According to the authors, cyclic menstruation may prepare the uterus for placentation in a future pregnancy.
“An association has been found between cyclic endometrial decidualization following menstrual shedding and protection against placentation-related disorders such as preeclampsia.”
In this article, Brosens et al describe a link between menstruation and placentation. Menstruation is a process that has evolved in a way that limits the likelihood of pregnancy while maximizing its frequency. It has therefore been suggested that cyclic menstruation serves as preparation and protection for future placentation in the event of pregnancy. The authors bring up the idea that it may appear to be an unfortunate evolutionary phenomenon that humans have low monthly fecundity. However, repeated menstrual preconditioning may be vital for successful pregnancy development. In the case of preeclampsia, which is largely characterized by ineffective placentation and spiral artery remodeling, the condition is most severe and prevalent in young and nulliparous women, especially those under 20 years. 
The article explores whether events in the menstrual cycle impact pregnancy outcome. The vascular changes that occur during placentation are exponential: from <1% of blood supply to a nonpregnant uterus to 25% by the end of gestation. If menstruation can prepare a uterus for the instrumental vascular changes that occur during pregnancy, it can be highly beneficial for both fetal and maternal health. Preeclampsia is associated with ineffective placental growth and invasion of spiral arteries in the decidua. The reason for the impaired deep invasion is unknown but may be from an extreme maternal inflammatory response to pregnancy. There may be a connection between the development and severity of preeclampsia and a woman’s history of cyclic menstruation.
Menstruation and pregnancy are both inflammatory events associated with a variable degree of free radical production, oxidative stress, ischemia-reperfusion injury, vascular remodeling, and angiogenesis. For preconditioning to be adequate, its effects must be prolonged and sustained through time to have a lasting result. Evidence for cyclic endometrial preconditioning comes from the observation that stromal cells purified from endometrial biopsy specimens from patients with and without endometriosis show different responses to decidualizing stimuli.
“Menstruation and pregnancy are both inflammatory events associated with a variable degree of free radical production, oxidative stress, ischemia-reperfusion injury, vascular remodeling, and angiogenesis.”
Prior to pregnancy, preparation involves decidualizing endometrial stromal cells during the secretory phase of a woman’s cycle. These cells regulate hemostasis and provide support to the developing early embryo. Decidual cells are adapted to resist stressors that occur through defense and repair mechanisms. Free radical scavengers such as superoxide dismutase 2, peroxiredoxin 2, thioredoxin, glutaredoxin, and glutathione peroxidase 3 are induced on decidualization. Uterine tissue undergoes decidualization to protect the embryo and ensure hemostasis and tissue integrity during deep trophoblast invasion and placentation.
“Uterine tissue undergoes decidualization to protect the embryo and ensure hemostasis and tissue integrity during deep trophoblast invasion and placentation.”
In all, there is a connection between regular menstrual cycles and pregnancy development in terms of adequate placentation. This is an important development in women’s health to educate women on their menstrual cycles and to know what is normal, especially if a future pregnancy is desired. Many women do not have cyclic menstruation for various reasons, whether it be stress, diet, or medical conditions. Therefore, more education is needed to help women better understand their reproductive health. This article also brought to light the utility of tracking cycles to know their baseline bleeding, dry, and mucus patterns.
A strength of this article includes the evidence provided on endometrial preconditioning in patients with endometriosis as well as examples of how preeclampsia is worse in younger women who have less preconditioning than older women. More research is needed to investigate preconditioning and adverse pregnancy outcomes in at-risk patients. This article makes one consider the evolutionary goals of menstruation, and one of them may be to protect and prepare the uterus and associated vasculature for a healthy pregnancy later. This emphasizes the importance of having regular menstrual cycles and the value of tracking a woman’s cycle with an established fertility awareness-based method (FABM).
 Brosens JJ, Parker MG, McIndoe A, Pijnenborg R, Brosens IA. A role for menstruation in preconditioning the uterus for successful pregnancy. Am J Obstet Gynecol. 2009 Jun;200(6):615.e1-6. doi: 10.1016/j.ajog.2008.11.037. Epub 2009 Jan 10. PMID: 19136085.
 Brosens JJ, Pijnenborg R, Brosens IA. The myometrial junctional zone spiral arteries in normal and abnormal pregnancies: a review of the literature. Am J Obstet Gynecol 2002;187: 1416-23.
 Brosens IA, Robertson WB, Dixon HG. The role of the spiral arteries in the pathogenesis of preeclampsia. ObstetGynecol Annu 1972; 1:177-91.
 Brosens IA, De Sutter P, Hamerlynck T, et al. Endometriosis is associated with a decreased risk of pre-eclampsia. Hum Reprod 2007; 22:1725-9.
ABOUT THE AUTHOR
Kathy Fatovic is a fourth-year medical student at University of New England College of Osteopathic Medicine in Biddeford, Maine. She completed her undergraduate education at Northeastern University in Boston, MA. She is pursuing residency in family medicine at the University of Maryland and is interested in health equity and education. She enrolled in the FACTS elective to gain a better understanding of natural family planning methods and ways to share these methods with future patients so they can feel more empowered over their health and reproductive decisions.