Endometriosis and Infertility: A Review of the Pathogenesis and Treatment of Endometriosis-associated Infertility

Deep endometriosis (DE) is the most severe form of endometriosis and is commonly associated with infertility. Surgical treatment of DE appears to increase chances of spontaneous conception in appropriately selected patients wishing to conceive. Identifying, however, the exact impact of DE, and its surgical removal, on natural conception is highly challenging. The surgical approach should be favoured in symptomatic patients with pregnancy intention. Limited data from infertile patients suggest that outcomes may not differ from patients without known infertility. Complex DE surgery carries a risk of serious complications, therefore, it should be performed in centers of expertise. Such complications may, however, not have a significant negative impact on fertility outcomes, according to limited available data. Data on obstetric outcomes of spontaneous conceptions after DE surgery are too scarce. In asymptomatic, infertile patients the debate between primary surgery or Artifial Reproductive Technology is ongoing, until randomized studies report their results.

Similar to diabetes and unlike many pathogen-induced diseases, endometriosis is likely a result of maladaptation to the evolutionary heritage of humans. The objective of this article is to review the literature and improve understanding of the evolutionary factors behind endometriosis, leading to more effective prevention and treatment approaches. In primates, spontaneous decidualization of the endometrium evolved to ensure optimal implantation of a limited number of early embryos, unlike many non-primates which depend on early embryos to induce decidualization and subsequent pregnancy. Spontaneous decidualization results in menstrual bleeding when embryo implantation does not occur, and endometriosis is commonly believed to be caused by retrograde menstruation. Although direct evidence is lacking, it is likely that hunter–gatherer women experienced fewer menstrual periods due to pregnancy shortly after menarche, followed by repeated pregnancies and lactation. However, the mismatch between the evolved uterine physiology and rapid societal changes has led to modern women delaying pregnancy and experiencing numerous menstrual periods, potentially increasing the incidence of endometriosis. The symptoms of endometriosis are often managed by suppressing menstruation through systemic hormonal treatments, but these may have side effects. For patients with a family history of endometriosis or in the early stages of the disease, intrauterine devices releasing progesterone locally could prevent uterine bleeding and the development of endometriosis while preserving fertility and minimizing side effects.

Endometriosis is a benign, chronic, inflammatory condition affecting up to 10 % of women and characterised by the presence of glands and stroma tissue outside the uterus. Epidemiological and clinical studies demonstrate a consistent association between endometriosis and infertility. However, this relationship is far to be clearly understood and several mechanisms are involved. Available data show that patients with endometriosis have an increased estimated risk of infertility between two and four times compared with the general population. On the other hand, the probability of patients with infertility to have endometriosis is reported up to about 50 % of the cases. Future studies should aim to better elucidate the mechanisms behind endometriosis-associated infertility in order to offer the more appropriate and tailored management for the patients.

To evaluate uterine contractility in patients with adenomyosis compared with healthy controls using a quantitative two-dimensional transvaginal ultrasound (TVUS) speckle tracking method.

A multicenter prospective observational study took place in three European centers between 2014 and 2023.

One university teaching hospital, 1 teaching hospital and 1 specialised clinic.

A total of 46 women with a sonographic or magnetic resonance imaging diagnosis of adenomyosis were included. 106 healthy controls without uterine pathologies were included.

Four-minute TVUS recordings were performed and four uterine contractility features were extracted using a speckle tracking algorithm.

The extracted features were contraction frequency (contractions/min), amplitude, velocity (mm/s), and coordination. Women with adenomyosis were compared with healthy controls according to the phase of the menstrual cycle.

Throughout the different phases of the menstrual cycle, trends of increased amplitude, decreased frequency and velocity, and reduced contraction coordination were seen in patients with adenomyosis compared with healthy controls. These were statistically significant in the late follicular phase, with a higher amplitude (0.087 ± 0.042 vs. 0.050 ± 0.018), lower frequency and velocity (1.49 ± 0.22 vs. 1.68 ± 0.25 contractions/min, and 0.65 ± 0.18 vs. 0.88 ± 0.29 mm/s, respectively), and reduced contraction coordination (0.34 ± 0.08 vs. 0.26 ± 0.17), in the late luteal phase, with higher amplitude (0.050 ± 0.022 vs. 0.035 ± 0.013), lower velocity (0.51 ± 0.11 vs. 0.65 ± 0.13 mm/s), and reduced contraction coordination (0.027 ± 0.06 vs. 0.18 ± 0.07), and in the midfollicular phase, with decreased frequency (1.48 ± 0.21 vs. 1.69 ± 0.16 contractions/min) in patients with adenomyosis compared with healthy controls. During menses, a higher pain score was significantly associated with lower frequency and velocity and higher contraction amplitude. Results remained significant after correcting for age, parity, and body mass index.

Uterine contractility differs in patients with adenomyosis compared with healthy controls throughout the phases of the menstrual cycle. This suggests an etiologic mechanism for the infertility and dysmenorrhea seen in patients with adenomyosis. Moreover, it presents new potential therapeutic targets and diagnostic markers.

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  Los factores de riesgo que más fuertemente se asocian a endometriosis son una historia previa de infertilidad y la presencia de dismenorrea o dolor pélvico.

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  Se debe sospechar la presencia de endometriosis en pacientes que consulten por dolor pélvico no cíclico, dismenorrea o dispareunia que persisten a lo largo del tiempo o se intensifican.

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  En pacientes con episodios de disquecia, disuria y rectorragia coincidentes con la menstruación, hay que sospechar una endometriosis infiltrativa profunda.

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  El uso de biomarcadores para el diagnóstico de endometriosis no han demostrado ser útiles. Podrían utilizarse con fines pronósticos para el seguimiento de pacientes con endometriosis.

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  Ante la sospecha clínica de endometriosis, la prueba de elección para su diagnóstico por imagen es la ecografía transvaginal.

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  No está justificada la realización de una laparoscopia diagnóstica para la confirmación de endometriosis.

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  Incluso aquellas pacientes con endometriosis que presenten pocos síntomas pueden beneficiarse de tratamientos médicos que eviten la progresión de la enfermedad.

We report a case of an accessory cavitated uterine mass (ACUM) in a patient with infertility and chronic pelvic pain. In addition, we summarize the literature to better characterize ACUM diagnosis and management.

A comprehensive literature search using the PubMed database was performed through April 2023. Historical ACUM diagnostic criteria were applied as inclusion criteria. Descriptive statistics and statistical evaluation were reported.

A 31-year-old nulligravid woman presented with chronic pelvic pain, dysmenorrhea, primary infertility, and history of endometriosis. Three-dimensional ultrasonography identified an ACUM and laparoscopic excision provided complete resolution of symptoms. Subsequently, she conceived without assistance twice with uncomplicated vaginal deliveries. A total of 154 articles were identified, 34 papers met inclusion criteria and were individually reviewed, consisting of 70 reported cases. The most common presenting complaints were dysmenorrhea (81.4%), chronic pelvic/abdominal pain (54.1%), and refractory pain (34.3%). Diagnostic imaging included magnetic resonance imaging (62.9%) and transvaginal ultrasound (55.7%). Management included resection via laparoscopy (75.7%) or laparotomy (18.6%), or hysterectomy (5.7%). Of cases with reported outcomes, 90.7% had complete relief of symptoms after surgery.

ACUM often presents with dysmenorrhea, chronic pelvic pain, or abdominal pain and is identifiable on magnetic resonance imaging as a hyperenhancing mass. Three-dimensional transvaginal ultrasound can also accurately identify ACUM. A total of 90.7% of patients had complete relief of symptoms after intervention. It is important to identify ACUM early to relieve pain and reduce unnecessary interventions. Like our patient, other reports have demonstrated concomitant infertility and endometriosis. However, further investigation is needed to explore the association between infertility and ACUM.