The aim of this review is to clarify the relative association between adenomyosis and infertility and the possible treatment for an infertile patient. Although adenomyosis is detected more often in women of late reproductive age, its influence on pregnancy rates is important, especially considering the tendency to delay pregnancy among women in developed countries. In this article, we present a critical analysis of the literature data concerning the impact of adenomyosis on fertility. The possible effects of treatment on the pregnancy rate will also be discussed. We conducted a literature search; publications from Pubmed, Embase and Cochrane databases published from 1982 to 2019 were retrieved using terms ’adenomyosis and infertility’ and ’adenomyosis and pregnancy outcomes’, extensively studied in the aspects of diagnosis, pathogenesis of infertility and possible treatment methods. Molecular studies have given deep insight into the pathogenesis of adenomyosis in the recent few years, but there is a huge discrepancy between in vitro studies and praxis. Oral contraceptive pills, anti-prostaglandins, oral or parenteral progestins, danazol and gonadotrophin-releasing hormone (GnRH) analogues have all been used to control menstrual pain and menorrhagia in women with adenomyosis, but they temporarily suppress the menstrual cycle. Additionally, endometrial ablation and hysterectomy used to alleviate pain caused by adenomyosis exclude pregnancy planning. The development of imaging techniques—ultrasound and MRI—enables the diagnosis of adenomyosis with very high accuracy nowadays, but the methods of treatment mentioned above have not given satisfactory results in women planning pregnancy. For these patients, the high-intensity-focused ultrasound method (HIFU) and combined treatment before assisted reproductive techniques can prove beneficial in adenomyosis patients.

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Angiogenesis and inflammation are pivotal processes in developing endometriosis in the peritoneal cavity. The aim of the present study was to evaluate these two processes in women with endometriosis who had been treated with danazol to determine the sensitivity of a non-invasive test in diagnosing endometriosis. The clinical follow-up study was conducted in a group of 103 women diagnosed laparoscopically with endometriosis. Thirty-five patients qualified for danazol treatment. Pain was assessed using a visual analogue scale, whereas endometriosis was assessed using the revised American Society of Reproductive Medicine (rASRM) scale. Cancer antigen (CA)-125 and C-reactive protein (CRP) concentrations in plasma and peritoneal fluid were determined by immunoenzymatic methods, whereas vascular endothelial growth factor (VEGF) and interleukin (IL)-1β concentrations in plasma and peritoneal fluid were determined by ELISA. Endometrial expression of IL-8 and platelet-derived growth factor alpha polypeptide (PDGF-A) was determined using real-time polymerase chain reaction (PCR). Women with endometriosis (68.9% of patients) had higher plasma concentrations of CA-125, as well as higher concentrations of both CA-125 and VEGF in the peritoneal fluid. Endometrial expression of IL-8 mRNA was significantly higher, whereas that of PDGF-A was significantly lower, in contrast. After danazol treatment the patients reported lower pain scores; in addition, CA-125 concentrations in the plasma were decreased (P<0.001), whereas VEGF concentration in the plasma increased (P=0.009). For the diagnosis of endometriosis, none of the combinations of given markers had a sensitivity >60%. Danazol treatment is highly effective in relieving pain and decreasing CA-125 concentrations in the plasma. Higher plasma concentrations of VEGF after treatment could imply stimulation of angiogenesis.

Endometriosis with its estimated incidence rate of ∼7-10% of women of reproductive age is a disease with the wide spectrum of symptoms depending on form and localization of endometrial foci. One clinical form of endometriosis is deep infiltrating endometriosis (DIE), most difficult to manage and generating a lot of direct and indirect treatment costs. We search the literature from PubMed database to establish the role of conservative treatment of DIE. Randomised controlled trials are lacking but in experts opinion hormonal treatment should be the first-line treatment in DIE. After evaluation of pain or other symptoms, second-line therapy with GnRH analogs or danazol should be offered or minimally invasive surgery. Consensus is not made whether surgery is the best therapeutic treatment for affected patients. Strong depending on surgeon's experience conservative surgery should be offered if the total excision of DIE foci is possible, which is essential for a successful outcome. If available treatment options do not release pain associated with DIE, experimental treatment in clinical trials should be discussed with patients.

STUDY QUESTION Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? SUMMARY ANSWER This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. WHAT IS KNOWN ALREADY Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. STUDY DESIGN, SIZE, DURATION A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTINGS, METHODS During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. MAIN RESULTS AND THE ROLE OF CHANCE We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P &lt; 0.016 and adj. P &lt; 0.026, respectively; logFC &gt; 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P &lt; 0.029), MAGEB4 (adj. P &lt; 0.029), and TNIP2 (adj. P &lt; 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. LIMITATIONS, REASONS FOR CAUTION Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. WIDER IMPLICATIONS OF THE FINDINGS Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER N/A.