What is adenomyosis?
Adenomyosis is a benign gynaecological condition characterised by the presence of endometrial glands and stroma within the myometrium.
Approximately one-third of patients are asymptomatic. When symptoms occur, the most common include abnormal uterine bleeding, dysmenorrhoea, dyspareunia and chronic pelvic pain. In younger women, the most frequent symptom is dysmenorrhoea that does not respond to treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or hormonal contraceptives. The severity of the pain often correlates with the severity of the disease.
The prevalence of adenomyosis among infertile women has increased in recent years, partly due to improvements in diagnostic imaging and partly because more women are attempting pregnancy at an older age (1).
The impact of adenomyosis on fertility
Several studies have shown that adenomyosis negatively affects fertility by reducing pregnancy rates following in vitro fertilisation (IVF).
It is estimated that the presence of adenomyosis reduces pregnancy rates by 28% and doubles the risk of miscarriage (2).
For this reason, careful screening for adenomyosis before starting fertility treatment is essential.
Several mechanisms may explain its negative impact on reproductive outcomes:
- Chronic inflammation caused by the infiltration of endometrial glands into the myometrium.
- Alterations in cell adhesion molecules, apoptosis and increased oxidative stress, reducing endometrial receptivity.
- Increased uterine contractility, which may interfere with embryo implantation.
- Increased local oestrogen production due to overexpression of aromatase P450, together with progesterone resistance caused by reduced progesterone receptor expression.
Progesterone has important anti-inflammatory and immunomodulatory effects. Progesterone resistance, combined with increased inflammatory mediators, disrupts the balance of immune cells within the endometrium, negatively affecting embryo implantation.
Treatment options for adenomyosis
In infertile patients, the first-line treatment usually involves the use of GnRH agonists.
These medications induce a hypoestrogenic state, reduce aromatase activity, promote apoptosis and decrease inflammation.
When GnRH agonists are used before an IVF cycle, ovarian stimulation is often longer and requires higher doses of hormonal medication. Therefore, a freeze-all strategy followed by frozen embryo transfer is generally recommended after two to three months of GnRH agonist treatment.
More recently, several studies have suggested that in cases of severe adenomyosis, GnRH agonists may successfully suppress ovarian oestradiol production but may not be sufficient to suppress oestradiol production within adenomyotic lesions.
In these patients, combining GnRH agonists with an aromatase inhibitor such as letrozole may improve reproductive outcomes.
The study published by Cozzolino et al. (3) described a series of patients with severe adenomyosis and recurrent implantation failure who continued to show elevated oestradiol levels despite GnRH agonist suppression. The combination of GnRH agonists and letrozole significantly improved treatment outcomes in this group.
The Clínica Fertia approach
At Clínica Fertia, we provide fully personalised fertility treatments tailored to each patient’s specific condition.
During the initial consultation, we routinely screen for adenomyosis using both 2D and 3D ultrasound. When appropriate, we combine antioxidant therapy before IVF treatment with personalised nutritional plans designed to reduce the inflammatory environment within the uterus.
We also perform deferred embryo transfer and monitor oestradiol levels to identify patients who may benefit from combined treatment with GnRH agonists and letrozole.
We’re here to help you achieve your dream of becoming a mother.
References
- Younes G, Tulandi T. Effects of adenomyosis on in vitro fertilization treatment outcomes: a meta-analysis. Fertility and Sterility. 2017;108:483–490.
- Vercellini P, Consonni D, Dridi D, Bracco B, Frattaruolo MP, Somigliana E. Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis. Human Reproduction. 2014;29:964–977.
- Cozzolino M, Pellicer N, Galliano D, Pellicer A. Pituitary suppression with GnRH agonists before ART may be insufficient to treat women with severe adenomyosis. Reproductive BioMedicine Online. 2023;46.
