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

Abstract

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.

Hormonal profile features in patients with infertility against the background of uterine leiomyoma and chronic endometritis

“…Згідно з даними ВООЗ, опублікованими на початку 2023 року, близько 17,5 % дорослого населення, а це майже кожна шоста людина у світі, хоч раз у житті стикається із безпліддям на певному етапі життя [1]. [5].…”

Administration of Oxytocin Receptor Antagonist during Frozen Embryo Transfer: Potential Improvement in Live Birth Rates for Women with Recurrent Implantation Failure, Adenomyosis, and Myoma

“…Abnormal uterine peristalsis has been suggested as one of the pathogenic factors contributing to myoma-related infertility [20][21][22]. In a prospective study, infertile patients with uterine myomas were evaluated by MRI at the time of implantation, and no pregnancies were achieved in the group with high-frequency (≥ 2 times/3 min) uterine peristalsis [15].…”

Reproductive outcomes in patients with uterine fibroid and infertility after laparoscopic myomectomy

“…Therefore, it is important to determine whether myomectomy can lead to improved reproductive outcomes and, if so, to identify the optimal surgical approach.Although there are many studies evaluating the relationship between uterine fibroids and infertility, the mechanisms by which fibroids negatively impact reproductive function remain largely unknown. Many hypotheses have been proposed to explain how fibroids can cause infertility, such as increased uterine contractility, abnormal cytokine profile, abnormal vascularization, and chronic inflammation [19]. The tumor can disrupt the anatomy of the uterine cavity, causing obstruction of the proximal openings of the fallopian tubes and the anatomy of the pelvic organs, pushing the fallopian tube away from the ovary [20].…”

“…The tumor can disrupt the anatomy of the uterine cavity, causing obstruction of the proximal openings of the fallopian tubes and the anatomy of the pelvic organs, pushing the fallopian tube away from the ovary [20]. It is likely that the displacement of the cervix towards the symphysis by large myomatous nodes makes it difficult for sperm to enter it, and an enlargement or deformation of the uterine cavity may interfere with the normal transport of sperm [19]. Myomatous nodes, especially with a submucosal location, disrupt blood flow in the endometrium and cause an excessive inflammatory reaction, which negatively affects implantation [17].…”

“…Some studies have reported no differences between laparoscopic and laparotomic approaches in terms of pregnancy rates and early pregnancy loss rates [9,19,26].…”