Infertility in patients with uterine fibroids: a debate about the hypothetical mechanisms

Fibroids are benign tumours of the myometrium and are the most common gynaecologic abnormality. Although most fibroids are asymptomatic, they can cause symptoms like heavy menstrual bleeding, pelvic pain, sexual dysfunction, pressure complaints, and infertility. The association between fibroids and infertility has been debated for decades. It is generally acknowledged that the closer the fibroid is to the uterine cavity and the endometrium lining, the more unfavourable effect it might have on fertility, reducing the odds for successful implantation and gestation. Based on the limited available literature, we propose and discuss seven hypotheses on the underlying mechanism by which fibroids may reduce fertility. (i) Fibroids can cause sexual dysfunction, as fibroids can cause dyspareunia, pelvic pain, and prolonged and heavy menstrual bleeding, which could interfere with sexual arousal and as a consequence the frequency of intercourse, resulting in a reduced probability of conception. (ii) Mechanical compression by fibroids on theinterstitial part of the fallopian tubes or deformation of uterine cavity could disturb oocyte and sperm transport. (iii) Fibroids can disturb peristalsis of the junctional zone in the myometrium, which could negatively influence oocyte and sperm transport as well as implantation. In addition, fibroids could induce a detrimental environment for implantation in other ways, by: (iv) changing the vagino-uterine microbiome; (v) disturbing the levels of inflammation and autophagy; (vi) inducing molecular changes in the endometrium; and (vii) inducing aberrant angiogenesis and altering the endometrial blood supply. After the discussion of these hypotheses, the implication of the influence of fibroids on early pregnancy loss is discussed. Surgical fibroid treatment is not tailored nor focussed on the pathophysiology of the fibroid; consequently it may be accompanied by recurrence of fibroids and risks of complications. Unravelling the pathogenic mechanisms about how fibroids influence fertility is essential to evolve classic surgical fibroid treatment. Instead of treatment of fibroid-related symptoms, the research should supports development of fibroid-targeted (pharmaceutical) treatment that is compatible with an active wish to become pregnant.