By Laurel F. Pietrzak
Editor’s Note: During the FACTS elective, Laurel Pietrzak summarized an analysis of the available evidence regarding the impact of fibroids on fertility. The article reviewed was published by Somigliana et al in Human Reproduction Update in 2007. [1] Since then, the evidence continues to highlight the importance of discussing patients’ fertility goals when deciding whether to pursue surgical treatment of uterine fibroids. [2] To learn more about the management of fibroids and the role of FABMs, check out Part L of our CME course.
Introduction
Uterine leiomyomas, also known as fibroids, are benign tumors of the uterine muscle wall. They are commonly diagnosed in women of reproductive age, and their prevalence increases as women reach perimenopause. [1] Fibroids pose a large disease burden, with an incidence of approximately 70% by age 50; it’s even higher, at 80%, among African American women. [1] Fibroids present with variable symptoms and severity based on the location and size of the lesions. They are classified as submucosal, intramural, or subserosal based on anatomical location within the uterine wall. While symptomatic individuals commonly present with hypermenorrhea, menorrhagia, pelvic fullness, pelvic pain, or urinary symptoms, most patients with fibroids are asymptomatic. [1]
“Uterine leiomyomas, also known as fibroids, are benign tumors … (that) present with variable symptoms and severity based on the location and size of the lesions.”
It is estimated that 10-15% of couples experience infertility, with fibroids playing a role in 2-3% of those cases. [1] It is still under debate whether fibroids are more clinically relevant than currently predicted when it comes to female reproduction. From 1970 to 2020, the average age at which women had their first child increased from 21 to 27 years. [3] As more women today start trying to conceive later in their reproductive years — when the incidence of fibroids increases and fertility declines — it is imperative to understand the potential threat fibroids may pose to fertility.
Current proposed mechanisms for how fibroids negatively impact fertility include alterations of the uterine cavity shape, a poor endometrial environment from local inflammation, and decreased blood supply to the endometrium that inhibits embryo implantation, sperm migration, and ovum transport. [1] While some studies have tried to investigate these hypotheses, study design limitations have made it difficult to reach conclusions.
“Current proposed mechanisms for how fibroids negatively impact fertility include alterations of the uterine cavity shape, a poor endometrial environment from local inflammation, and decreased blood supply to the endometrium that inhibits embryo implantation, sperm migration, and ovum transport.”
Methods
A comprehensive review evaluating the relationship between fibroids and infertility was completed by the department of obstetrics and gynecology at the University of Milan. Medical journal articles published between 1990 and 2006 were found via PubMed by using 18 different terms associated with fibroids, fertility, IVF, ART, and pregnancy. [1]
Results
With a variety of options available to manage fibroids, surgery is a common choice for treatment. Techniques used include hysteroscopic resection of submucosal lesions or myomectomy, via laparotomy or laparoscopy, for intramural and subserosal lesions. In this review, two studies provide clinical evidence supporting the notion that fibroids negatively impact fertility.
The first study consisted of two groups of 106 women diagnosed with fibroids and either a previous miscarriage or infertility. A comparative study examined delivery rates in the two groups after they underwent a laparoscopic myomectomy or received no treatment. Most of the women were diagnosed with three or more lesions, with at least one lesion larger than 6 cm in diameter. The delivery rate of women in the surgical group was 42% compared to 11% in the ‘no treatment’ group, suggesting removal of fibroids can positively impact pregnancy outcomes in patients with infertility. [1] Of note, this study was not randomized, so definitive conclusions cannot be made. While numerous other studies have also reported increased pregnancy rates after myomectomy, there is a lack of large randomized controlled trials (RCTs) to provide additional evidence.
The second study involved a meta-analysis of 15 studies that investigated pregnancy rates after completed IVF cycles in women with and without fibroids at an average diameter of 3 cm. [1] The study concluded that submucosal and intramural lesions had a significant negative impact on pregnancy rate, whereas subserosal lesions did not. [1] It is important to recognize that while the location of lesions was the focus of this analysis, the size of fibroids may play a key role on implantation failures in IVF cycles. It is suggested that lesions larger than 4 cm may have a negative impact on implantation. [1] Thus, results from this study may underestimate the true impact fibroids have on pregnancy rate. Additionally, this study only evaluated embryo implantation through IVF, so results cannot be used to determine the effects of fibroids on ovum transport through the fallopian tubes.
Discussion
While questions remain unanswered regarding the degree of impact fibroids have on infertility, clinicians need to consider multiple factors to determine a management plan. It is suggested that before committing to surgery to improve fertility outcomes, clinicians should consider age, location and size of lesions, number of lesions, presence of other infertility factors, and the presence of symptoms related to lesions. [1]
In a 2017 review, the American Society of Reproductive Medicine recommended that to improve pregnancy rates, myomectomy may be considered in patients with fibroids that distort the normal uterine cavity, while surgery is not advised in asymptomatic patients who have no lesions that interfere with the typical cavity structure. [4] The scarcity of guidelines available for practicing clinicians highlights the importance and necessity of continued research. As treatment options to manage fibroids continue to evolve, including the addition of uterine artery embolization and laparoscopic myolysis, it will be vital to evaluate pregnancy outcomes following these procedures in patients with infertility.
“Exploring the impact fibroids have on fertility remains crucial, especially since the average age of a woman at her first pregnancy has trended toward the later reproductive years when the incidence of fibroids is higher.”
Multiple studies have attempted to discern the relationship between fibroids and infertility, but few have been able to provide enough evidence to reach firm conclusions. The lack of larger RCTs limits the available evidence to develop clinical guidelines for the management of fibroids in patients with infertility and to help determine which lesions to operate on to improve fertility outcomes. Exploring the impact fibroids have on fertility remains crucial, especially since the average age of a woman at her first pregnancy has trended toward the later reproductive years when the incidence of fibroids is higher. Until additional evidence is elicited, it is important for clinicians to counsel patients diagnosed with fibroids that these lesions may negatively impact future fertility even if asymptomatic. The authors propose a personalized approach when establishing whether it is appropriate for a patient with infertility to undergo surgery for fibroids. While the debate continues, shared decision making with patients is always key.
References
[1] Somigliana, E., Vercellini, P., Daguati, R., Pasin, R., De Giorgi, O., & Crosignani, P. G. Fibroids and female reproduction: A critical analysis of the evidence. Human Reproduction Update , 2007;13(5), 465–476.
[2] Frisch EH, Mitchell J, Yao M, et al. The Impact of Fertility Goals on Long-term Quality of Life in Reproductive-aged Women Who Underwent Myomectomy versus Hysterectomy for Uterine Fibroids. J Minim Invasive Gynecol. 2023;30(8):642-651. doi:10.1016/j.jmig.2023.04.003
[3] Pregnancy at Age 35 Years or Older: ACOG Obstetric Care Consensus No. 11. Obstetrics and Gynecology, 2022 Aug 1;140(2):348-366.
[4] Practice Committee of the American Society for Reproductive Medicine. Removal of myomas in asymptomatic patients to improve fertility and/or reduce miscarriage rate: a guideline. Fertility and Sterility. 2017 Sep;108(3):416-425.
ABOUT THE AUTHOR
Laurel F. Pietrzak is a fourth-year medical student at Des Moines University College of Osteopathic Medicine in Des Moines, IA. She completed her undergraduate education at the Carthage College in Kenosha, WI. She plans to pursue residency in obstetrics and gynecology and is interested in breastfeeding medicine and educating women about menopause. She enrolled in the FACTS elective to gain a better understanding of natural family planning methods so she can share them with her future patients.
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