Adenomyosis and infertility

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ACHAIKI IATRIKI | 2024; 43(3):107–110

Editorial

Christiana Zafeirati1, Angelos Daniilidis2

1Division of Rheumatology, University of Patras Medical School, Patras University Hospital, 26504 Patras, Greece
2Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, 26504 Patras, Greece

Received: 25 Nov 2023; Accepted: 24 Jan 2024

Corresponding author: Angelos Daniilidis, 1st University Department in Obstetrics and Gynecology, Papageorgiou General Hospital, School of Medicine, Aristotle University of Thessaloniki, Greece, e-mail: angedan@hotmail.com

Key words: Adenomyosis, infertility, IVF outcomes

 

INTRODUCTION

Adenomyosis is a complex medical condition that affects a significant number of women around the world. It is characterized by an abnormal growth of endometrial tissue within the muscle wall of the uterus, causing symptoms in some of the women affected. In this editorial we explore the relationship of adenomyosis with infertility, shedding light on the most recent scientific data and the challenges ahead.

As time has gone by, adenomyosis has remained a histopathological diagnosis made after hysterectomy. During the last years, adenomyosis has been identified as a condition found in young fertile-age women due to the recent advancements in imaging studies. However, a common definition and classification system are still lacking. Despite the advances in technology that improved the performance of the diagnostic imaging, the awareness of the condition is still inadequate. The introduction of new medication and surgical techniques has allowed healthcare professionals to conservatively manage the disease.

Pathogenesis

The pathogenesis of adenomyosis is still unclear and cannot be understood by only a unique theory, since the phenotypes are heterogeneous and not clearly defined. Two main theories have prevailed over the years. The first being the tissue injury and repair theory (TIAR) which highlights the important role that tissue damage plays to the endometrial– myometrial interface and supports the common understanding that adenomyosis is associated with the risk factors of prior uterine surgery, previous caesarean section and multiparity [1]. The second theory suggests that the disease arises de novo from metaplasia of embryonic or adult stem cells in the myometrium. However, this theory has not been sufficiently examined to draw any robust conclusions [1,2,].

Clinical picture

Despite its growing prevalence, adenomyosis is frequently underdiagnosed, contributing to delayed or missed opportunities for intervention. This disease often coexists with other gynaecological problems such as endometriosis and uterine fibroids, making diagnosis very challenging. The epidemiological profile of the condition has changed, and even though the most common risk factors include age of more than 40 years, multiparity, and prior uterine surgery, adenomyosis has been increasingly diagnosed in young women, in patients struggling with infertility, or in those with pain or abnormal uterine bleeding (AUB) or both [3,4].

Diagnosis and classification

The diagnostic investigation of adenomyosis should start with the suspicion of condition supported by the clinical presentation of relevant symptoms and signs. The confirmation of the presence of adenomyosis should be performed by the imaging techniques, which may also help to define the presence of comorbidities [5].

Pelvic ultrasound constitutes a straightforward, minimally invasive, and inexpensive examination. Ultrasonography aids to observe the size and shape of the uterus, the location of heterogeneous myometrium and the focal abnormal echotexture. It also evaluates the junctional zone (JZ) between the endometrium and the myometrium, which can appear uneven, poorly defined, and interrupted or absent. Lastly, it assesses the myometrial lesions; an affliction is considered localized if it is less than 50% of the volume of the uterus or it is considered diffuse if it is greater than 50% of the uterine volume [5]. The diagnosis of adenomyosis is often performed based on ultrasound (US) features, even though no agreement on US features for adenomyosis exists. The Morphological Uterus Sonographic Assessment (MUSA) consensus published in 2015 aimed to identify a standardized terminology for describing ultrasound images of normal and pathological myometrium [5,6].

MRI allows evaluation of the inner myometrium and observation of its thickness and nature of changes, which is considered the hallmark of adenomyosis [6]. Although pelvic MRI is more expensive and less available, it is a more reproducible examination, as the sensitivity, specificity, and positive and negative prediction values are high. Several classification systems based on MRI have been proposed in the literature. A classification system that has been proposed by Bazot et al., describes three types of adenomyosis by MRI. These include (i) Internal adenomyosis (focal, superficial and diffuse), (ii) adenomyoma and (iii) posterior or anterior external adenomyosis [5]. Another classification system that has been proposed by Chapron et al., defines two main adenomyosis subtypes: diffuse internal adenomyosis and focal adenomyosis of the external myometrium. In this classification, diffuse adenomyosis is defined by the association of two criteria. The first being a JZ of at least 12 mm and the second being a JZ/Myometrium ratio over > 40%. Focal adenomyosis is characterized by the presence of a poorly defined subserosal mass affecting the posterior or anterior wall of the myometrium, separated from the JZ by an area of healthy myometrium [5].

Impact on fertility

Adenomyosis has been considered for many years a uterine condition of multiparous women, although an increasing amount of evidence indicates an association with infertility and reproductive failure [7]. Currently, infertility is considered one of the possible clinical presentations of adenomyosis and several theories have been suggested to explain the underlying mechanisms. Calero et al in 2022, concluded that infertility may be due to several factors that impair adequate sperm mobility through the uterus and an impaired implantation of a product [8]. Furthermore, the inner myometrium and the JZ present with dysfunctional hyperperistalsis and increased intrauterine pressure. As a result, these structural myometrial abnormalities may cause a disturbance in normal myocyte contractility with subsequent loss of normal rhythmic contraction. Data suggests that in infertile women with adenomyosis, eutopic endometrium presents a wide variety of molecular alterations, thus causing a disruption in its receptivity capacity [9].

Treatment options

Management often involves a combination of medical and surgical approaches. Hormonal therapies such as progestins and gonadotropin releasing hormone agonists (GnRH), act by treating local hyperestrogenism and alleviating the most severe symptoms of adenomyosis such as heavy menstrual bleeding, dysmenorrhea, and pelvic pain [10]. Surgery options range from excising adenomyotic lesions to more extensive ones such as hysterectomy. The choice of treatment is usually individualized, taking into consideration the wish for fertility preservation, the severity of the symptoms and overall, the clinical condition of each patient [12].

Adenomyosis and IVF outcomes

There are conflicting results regarding the effectiveness of in vitro fertilization (IVF) in women with adenomyosis. Some studies show no difference in pregnancy rates, while others show a difference, but miscarriage rates appear to be higher. The reason for the conflicting results is because of the varying ovarian stimulation protocols used and a lack of proper description of the type and severity of adenomyosis [14,17].

Several researchers have examined the impact of adenomyosis on fertility by studying women who underwent IVF since this model provides more precise data on the effect of adenomyosis on embryo implantation. However, for the purposes of infertility research, it is essential to consider that adenomyosis often coexists with other gynecological disorders, including uterine fibroids and, notably, endometriosis, which are often associated with pelvic pain and dysmenorrhea. Consequently, the proportion of women with both diseases and the diagnostic criteria remain controversial. Since endometriosis has been linked to subfertility and reduced chances of conceiving through assisted reproductive technology (ART), it is critical to conduct studies that explore IVF outcomes in women with endometriosis only, adenomyosis only, and those with both pathologies [15,18,19].

Liang et al. conducted a retrospective cohort study in 2022 which revealed that adenomyosis has a negative effect on IVF-Embryo Transfer outcomes, increasing the risk of miscarriage, reducing live birth rates, and increasing obstetric complications [20].

Researchers conducted studies aiming to evaluate the effect of adenomyosis on the outcome of pregnancy in ICSI/FET cycles and the potential benefits of pre-treatment with GnRH agonist, conservative surgery, or a combination of both on pregnancy outcomes. It was shown that women with adenomyosis who underwent ICSI/FET cycles had lower clinical pregnancy rates, higher miscarriage rates, and lower rates of live birth and ongoing pregnancy compared to those without adenomyosis. However, there was a significant improvement in clinical pregnancy rates in patients who received pre-treatment with GnRH agonist, conservative surgery, or a combination of both. The GnRH agonist long protocol and conservative surgery with GnRH agonist pre-treatment were found to be beneficial [19]. However, further large-scale prospective comparative studies are needed to confirm these findings.

According to a few studies, patients with diffuse adenomyosis who underwent adenomyomectomy showed better fertility outcomes with increased clinical pregnancy rates and reduced miscarriage rates [19,20].

CONCLUSION

Over the past two decades, there have been significant advancements in the understanding of adenomyosis, and more clinicians are aware of this condition. Non-invasive diagnostic tools have allowed for accurate diagnosis without surgery. However, there is still much debate over diagnostic criteria, as imaging features have not been correlated with clinical presentation, and many patients are asymptomatic or have other gynecological issues that make diagnosis challenging. Various classifications have been proposed, but there is no shared language or uniformity. Current evidence is limited by poor quality studies, lack of strict imaging diagnosis, and absence of a classification according to disease extent. As our understanding grows, so too the potential for finding an optimal management strategy to alleviate symptoms and improve reproductive outcomes for women affected by this disease.

Conflict of interest disclosure

None to declare.

Declaration of funding sources

None to declare.

Author Contributions

Both authors equally contributed to the literature review, the interpretation of the relevant data and the review of this editorial article, aiming to provide an insightful comprehension on adenomyosis and its impact on fertility.

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