Women with combined adenomyosis and endometriosis on MRI have worse IVF/ICSI outcomes compared to adenomyosis and endometriosis alone: A matched retrospective cohort study

The reproductive impact of adenomyosis and endometriosis is widely researched but the extent of these impacts remains elusive. It has been demonstrated that endometriosis, in particular, is known to result in subfertility but endometriosis and adenomyosis are increasingly linked to late pregnancy complications such as those caused by placental insufficiency. At the molecular level, the presence of ectopic endometrium perturbs the endometrial hormonal, cellular, and immunological milieu, negatively influencing decidualization, placentation, and developmental programming of the embryo. It is unclear if and how such early aberrant reproductive development relates to pregnancy outcomes in endometriosis and adenomyosis. The aims of this systematic review and meta-analysis were to (i) investigate the association of adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes of women through both assisted reproduction and natural conception and (ii) determine whether endometriosis disease subtypes have specific impacts on different stages of the reproductive process. A systematic literature review of NHS evidence electronic databases and the Cochrane database identified all comparative and observational studies between 1980 and December 2018 in any language on adenomyosis and endometriosis with fertility, obstetric, and neonatal outcomes (23 search terms used). A total of 104 papers were selected for data extraction and meta-analysis, with use of Downs and Black standardized checklist to evaluate quality and bias. We found that endometriosis consistently leads to reduced oocyte yield and a reduced fertilization rate (FR), in line with current evidence. Milder forms of endometriosis were most likely to affect the fertilization (FR OR 0.77, CI 0.63–0.93) and earlier implantation processes (implantation rate OR 0.76, CI 0.62–0.93). The more severe disease by American Society for Reproductive Medicine staging (ASRM III and IV) influenced all stages of reproduction. Ovarian endometriosis negatively affects the oocyte yield (MD −1.22, CI −1.96, −0.49) and number of mature oocytes (MD −2.24, CI −3.4, −1.09). We found an increased risk of miscarriage in both adenomyosis and endometriosis (OR 3.40, CI 1.41–8.65 and OR 1.30, CI 1.25–1.35, respectively), and endometriosis can be associated with a range of obstetric and fetal complications including preterm delivery (OR 1.38, CI 1.01–1.89), caesarean section delivery (OR 1.98 CI 1.64–2.38), and neonatal unit admission following delivery (OR 1.29, CI 1.07–1.55). Adenomyosis and the subtypes of endometriosis may have specific complication profiles though further evidence is needed to be able to draw conclusions. Several known pregnancy complications are likely to be associated with these conditions. The complications are possibly caused by dysfunctional uterine changes leading to implantation and placentation issues and therefore could potentially have far-reaching consequences as suggested by Barker’s hypothesis. Our findings would suggest that women with these conditions should ideally receive pre-natal counselling and should be considered higher risk in pregnancy and at delivery, until evidence to the contrary is available. In order to expand our knowledge of these conditions and better advise on future management of these patients in reproductive and maternal medicine, a more unified approach to studying fertility and reproductive outcomes with longer term follow-up of the offspring and attention to the subtype of disease is necessary.

The aim of the present review, conducted according to PRISMA statement recommendations, was to evaluate the contribution of transvaginal sonography (TVS) and magnetic resonance imaging (MRI) to diagnose adenomyosis. Although there is a lack of consensus on adenomyosis classification, three subtypes are described, internal, external adenomyosis, and adenomyomas. Using TVS, whatever the subtype, pooled sensitivities, pooled specificities, and pooled positive likelihood ratios are 0.72-0.82, 0.85-0.81, and 4.67-3.7, respectively, but with a high heterogeneity between the studies. MRI has a pooled sensitivity of 0.77, specificity of 0.89, positive likelihood ratio of 6.5, and negative likelihood ratio of 0.2 for all subtypes. Our results suggest that MRI is more useful than TVS in the diagnosis of adenomyosis. Further studies are required to determine the performance of direct signs (cystic component) and indirect signs (characteristics of junctional zone) to avoid misdiagnosis of adenomyosis.

Until recently, adenomyosis has been associated with multiparity, not impaired fertility. Currently, adenomyosis is diagnosed with increasing frequency in infertile patients since women delay their first pregnancy until their late 30s or early 40s. Although an association between adenomyosis and infertility has not been fully established, based on the available information, recent studies suggested that adenomyosis has a negative impact on female fertility. Several uncontrolled studies with limited data also suggested that treatment of adenomyosis may improve fertility. This article discusses (i) the hypothesis and epidemiology of adenomyosis, (ii) diagnostic techniques, (iii) clinical evidence of correlation between adenomyosis and infertility, (iv) proposed mechanism of infertility in women with adenomyosis, (v) different treatment strategies and reproductive outcomes, and (vi) assisted reproductive technology outcome in women with adenomyosis. Target Audience Obstetricians and gynecologists, family physicians. Learning Objectives After completing this activity, the learner should be better able to: Recall the hypothesis and epidemiology of adenomyosis; Evaluate the important findings on improved imaging techniques to diagnose adenomyosis; Understand that the presence of adenomyosis may impair the reproductive outcomes in women with adenomyosis; Explain the proposed mechanism of infertility in women with adenomyosis; Give the most appropriate treatment for better reproductive outcomes in women with adenomyosis; and Advise patients that surgery could be effective in women with adenomyosis with a history of IVF failure although latter finding could be partly attributed to the higher rate of early miscarriage.