Why do myomas occur?

They derive from a monoclonal tumour, i.e. from a cell of the myometrium (muscular layer of the uterus), which acquires a mutation so that this cell is capable of recruiting the surrounding cells, the cells grow in a disordered way and with a lot of extracellular matrix, giving rise to the myoma. Some 168 genes have been described in myomas that are expressed differently compared to the normal myometrium. There are many factors that favour these mutations such as: endocrine disruptors that damage the cell, reprogram it (epigenetic change), diet, vitamin D deficiency… And hormonal and inflammatory factors that favour vascularisation at the level of the myoma and its growth. Some of these disruptors can induce epigenetic changes, changes in the programming of cells from the foetal stage and later hormonal factors and growth factors will favour their proliferation.

What are the risk factors for the development of fibroids and how do they affect fertility?

Risk factors for the development of fibroids include age over 35-40 years, African race, genetic factors, being more frequent if there is a history in first-degree relatives, early menarche, hypertension, vitamin D deficiency and a diet poor in vegetables and fruit. However, there are protective factors such as contraceptive use, multiparity and late menarche.

Their impact on fertility depends primarily on the number, location and volume of fibroids. Fibroids can affect fertility by various mechanisms, such as:

• Distortion of the uterine cavity: if fibroids grow inside it or deform it.
  Modification of uterine contractility: this affects the transport of spermatozoa to the tubes, the transport of the embryo to the uterine cavity or may interfere with implantation.
• Alteration of endometrial-myometrial vascularisation.
• Alteration of tubal peristalsis and anatomy.
• Production of inflammatory mediators: these are capable of modifying the expression of genes related to implantation, decreasing endometrial vascularisation and altering hormonal and immunological receptors.

All these factors interfere with embryo implantation, even if the myoma is not directly affecting the uterine cavity.

Treatment options for women who want to become pregnant

Surgery

Surgery is recommended for fibroids growing inside the cavity type 0, 1 and 2 according to the FIGO (International Society of Gynaecology and Obstetrics) classification. It is performed by hysteroscopy, in most cases on an outpatient basis. This increases the gestation rate and decreases the incidence of miscarriage. As for fibroids that grow in the uterine wall and do not deform the cavity, each case is evaluated individually, as we know that if there are more than two and the size is greater than 2cm, this will affect the probability of gestation. The SEF (Spanish Fertility Society) recommends that in a woman over 35 years of age with more than 6 months of attempted gestation and after having performed two unsuccessful embryo transfers of good quality, surgery is recommended for fibroids that grow in the uterine wall or outside it, even if they do not deform the cavity. For so-called subserosal fibroids that grow outside the uterine wall, surgery is recommended only if they are large (12-15cm).

Uterine Artery Embolisation

Not recommended in infertile patients due to the risk of diminishing ovarian reserve.

Radiofrequency

Consists of applying an electric current that heats and coagulates the tissue, it is performed on an outpatient basis. It achieves the greatest reduction in the size of the myoma during the first 6 months, after which it continues to decrease, but more slowly. After the procedure, it is recommended to wait at least 6 months before carrying out assisted reproduction therapy. It is indicated for fibroids with an intramural component (2 to 5 classifications FIGO).

In terms of medical treatment

Vitamin D, the vitamin D receptor is diminished in the myoma cells, it is recommended to supplement with vitamin D, due to its immunomodulatory effect on cell proliferation and differentiation. Thus, black women with a high incidence of vitamin D deficiency have larger fibroids compared to Caucasian patients.

GnRh antagonists, in our country we currently only have the following available
Relugolix, associated with hormone replacement therapy (Ryeqo), reduces bleeding, however the reduction in myoma volume is small, ideal for patients with no desire for pregnancy, but not so effective in infertile patients. In time, other antagonists will become available that have already demonstrated their efficacy in reducing myoma size.

In the future, a better understanding of the impact of genetic factors, epigenome, transcriptome, microbiome, will allow us to develop new therapeutic options.

At Clinica Fertia we thoroughly evaluate each case by means of 2D and 3D ultrasound studies and hysteroscopic evaluation in order to establish the best treatment regimen for each specific patient with fibroids.

Bibliography

1. Yang Q, Ciebiera M, Bariani MV, Ali M, Elkafas H, Boyer TG, Al-Hendy A.
Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment. Endocr Rev. 2022 Jul 13;43(4):678-719. doi: 10.1210/endrev/bnab039.
2. Lee S, Stewart EA. New treatment options for nonsurgical management of uterine fibroids. Curr Opin Obstet Gynecol. 2023 Aug 1;35(4):288-293. doi: 10.1097/GCO.0000000000000880. Epub 2023 May 3. PMID: 37144584; PMCID: PMC10330353.
3. Alkhrait S, Malasevskaia I, Madueke-Laveaux OS. Fibroids and Fertility. Obstet Gynecol Clin North Am. 2023 Dec;50(4):663-675. doi: 10.1016/j.ogc.2023.08.006. Epub 2023 Oct 3. PMID: 37914486.