Uterine Leiomyomas as a Risk Factor for Infertility

Are uterine leiomyomas a risk factor for infertility?

Patients with more than one untreated leiomyoma may have decreased fertility as measured by pregnancy and live birth rates. (Strength of Recommendation: B, meta-analysis of randomized controlled trials and cohort studies.) Patients with a single leiomyoma smaller than 5 cm may have a lower pregnancy rate than those without leiomyomas. The specific location of leiomyomas (ie, subserosal, submucosal, intramural, simultaneous submucosal and intramural) may be associated with lower birth rates.

A 2024 systematic review and meta-analysis of 13 mostly prospective and retrospective studies (N = 4,788) examined pregnancy and birth rates in patients with leiomyomas vs those without leiomyomas. Mean patient age was 33 years. Patients were included if they had intramural leiomyomas (most were smaller than 8 cm) and were undergoing assisted reproductive technology or attempting conception. Patients with leiomyomas smaller than 2 to 3 cm and patients with leiomyomas larger than 2 to 3 cm were compared with those who did not have leiomyomas in terms of the clinical pregnancy rate. Primary outcomes were the rates of clinical pregnancy and live birth.¹

For patients with more than one leiomyoma of any size, the pregnancy rate was significantly lower vs that in patients without any leiomyoma (four studies; n = 1,178; odds ratio [OR] = 0.62; 95% CI, 0.44–0.86; I² = 24%). Stratified by size, compared with those without leiomyoma, patients with a leiomyoma smaller than 3 cm had a significantly lower pregnancy rate (three studies; n = 697; OR = 0.53; 95% CI, 0.38–0.76; I² = 0%), as did those with a leiomyoma smaller than 5 cm (three studies; n = 1,598; OR = 0.75; 95% CI, 0.58–0.96; I² = 0%).

The pregnancy rate was significantly lower in patients with leiomyomas between 3 and 6 cm than in those without leiomyomas (three studies; n = 743; OR = 0.43; 95% CI, 0.29–0.63; I² = 0%). For patients with leiomyomas larger than 5 cm, the reduction was not significant (three studies; n = 615; OR = 0.71; 95% CI, 0.32–1.58; I² = 57%). Patients with more than one leiomyoma of any size had a lower live birth rate vs those without (three studies; n = 868; OR = 0.53; 95% CI, 0.36–0.88; I² = 41%). Limitations included lack of age or control for body mass index in some studies. Also, most data were retrospective.

A 2021 cohort study (N = 931) examined the relationship between location and size of leiomyomas and fertility. The study compared patients with submucosal, intramural, and simultaneous submucosal and intramural fibroids with those who had subserosal fibroids on pathologic examination after hysterectomy within a single institution during a 5-year period.²

Mean patient age was 47 years, and mean body mass index was 26.9 kg/m². Patients with other possible causes of infertility were excluded. Primary outcomes were rates of birth, preterm birth, and early pregnancy loss. Compared with subserosal fibroids, submucosal fibroids (relative risk [RR] = 2.58; 95% CI, 1.03–6.47), intramural fibroids (RR = 1.18; 95% CI, 1.02–1.35), and simultaneous submucosal and intramural fibroids (RR = 1.36; 95% CI, 1.05–1.77) were associated with lower birth rates.