Current Knowledge on Endometriosis Etiology: A Systematic Review of Literature.

OBJECTIVE: To review the mechanisms of endometriosis development, including those related to epigenetic mutations, cellular dysregulation, inflammatory processes, and oxidative stress. METHODS: A systematic literature review regarding current aspects of endometriosis etiology, genesis and development was performed using the PubMed, Google Scholar, and eLibrary databases. Keywords included endometriosis, etiology, development, genesis, associations and mechanisms. A multilingual search was performed. RESULTS: Several mechanisms underline the pathophysiological pathways for endometriosis development. Epigenetic mutations, external and internal influences, and chronic conditions have a significant impact on endometriosis development, survival and regulation. Several historically valid theories on endometriosis development were discussed, as well as updated findings. CONCLUSION: Despite recent advances, fundamental problems in understanding endometriosis remain unresolved. The identification of unknown circulating epithelial progenitors or stem cells that are responsible for epithelial growth in both the endometrium and endometriotic foci seems to be the next step in solving these questions.

Pathogenesis of pelvic pain syndrome associated with endometriosis in patients resistant to surgical treatment.

AIM: Endometriosis is one of the most common gynecological diseases diagnosed in almost 70% of patients with chronic pelvic pain (CPP). However, a quarter of women with pelvic pain is diagnosed with external genital endometriosis (EGE) during laparoscopy. A special group is represented by patients with PP that did not stop after the removal of endometrial foci. The mechanisms of the pathogenesis of the formation of pain syndrome are not completely explored yet. According to several authors, a significant role in the pathogenesis of pelvic pain recurrence after surgical treatment of EGE is played by active neuroangiogenesis, both in ectopic and eutopic endometrium. The aim of the study was to expand the understanding of the pathogenesis of pelvic pain that did not stop (recurrence) after surgical treatment of external genital endometriosis. MATERIAL AND METHODS: The study involved 2 stages. At the first stage (algological), data from B&B, NRS and VRS algological questionnaires, which were completed by patients with recurrent PP after surgical treatment of EGE, were analyzed (n = 130, aged 18-45 years old, average age 32.5 ± 7.6 years). All women were operated on for EGE no later than 3-6 months after assessing the patients by the algological questionnaires; they did not receive drug therapy after surgical treatment and sought medical attention for recurrent pelvic pain. Materials for the study of the endometrium were obtained by the pipelle biopsymethod. The control group was formed from a number of women with EGE without PP, who applied for surgical treatment of infertility (n = 30). RESULTS: The results of the study have shown that the basis of pathogenesis of pelvic pain recurrence in patients who did not receive medical therapy after surgical treatment of EGE is the activation of neuro-angiogenesis processes and reduction of apoptosis. The results show a statistically significant 1.6 times increasing expression of NGF in eutopic endometrium (57.9 ± 2.5 vs 35.3 ± 2.1% of patients with the silent form of the gene and its receptor NTRK1 1.8 times (2.78 ± 0.25 versus 1.56 ± 0.21.e. respectively). Conclusion: The pathogenesis of pelvic pain in patients who did not receive medical therapy after surgical treatment of endometriosis compared to no pain form of the disease is the activation of the processes of neurogenesis in the eutopic endometrium.

Oxytocinergic regulation in pathogenesis of pelvic pain caused by adenomyosis.

OBJECTIVE: The aim of the study was to expand the understanding of pathogenesis of adenomyosis-associated pelvic pain. MATERIAL AND METHODS: We studied 30 (n = 30) biopsy samples obtained after hysterectomy in women with diffuse adenomyosis of grade II-III, accompanied by severe pain syndrome, who did not receive hormonal therapy. The morphologic comparison group comprised 30 (n = 30) biopsy samples obtained from women with adenomyosis, without pain syndrome, operated on for abnormal uterine bleeding, who also did not receive hormone therapy. RESULTS: The total density of immunological OTR labeling in the adenomyotic lesion foci was 73.7 ± 1.8%, and in the morphological control group it was 35.2 ± 1.4% (p <0.05), which indicates a significant effect of oxytocin as a ureterotonic peptide. Processes of local neurogenesis and growth of nerve fibers was established due to an increase in the expression of the nervous system growth factor NGF in the myometrium stroma, in comparison with biopsy samples of morphological control.Conclusion: Pelvic pain pathogenesis in women with diffuse adenomyosis compared with the painless form of the disease is an increase in the activity of ureterotonic factors of OTR oxytocin. Compared to the painless form of adenomyosis, the myometrial innervation apparatus of patients with pelvic pain is characterized by a significantly higher expression of nerve growth factor.

Implantation failures in women with infertility associated endometriosis.

Endometriosis is currently considered as one of the most common diseases associated with infertility. A controversial issue is whether endometriosis per se exerts a detrimental effect on IVF outcomes. Failure of implantation due to endometriosis-associated infertility is a contradictory and widely discussed burden nowadays. The purpose of the study is to assess the quality of embryos and implantation rate in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 26 and 40 years who underwent IVF and ICSI procedures. The patients were divided into two groups: group I (n = 70) involved 70 patients with recurrent unilateral endometriomas, II control group (n = 50) with tubal factor infertility. The quality of the retrieved embryos was assessed according to the generally accepted classification of Gardner, indicating the rate of implantation in each group. Embryo transfer was performed in case of high quality embryos. Assessing the ovarian reserve indicators, in the group I patients with recurrent unilateral endometriomas the serum level of AMH was significantly lower (2.1 ± 1.75 vs. 3.2 ± 1.4, p < .005), as well as the number of retrieved oocytes (8.1 ± 3.9 and 10.1 ± 6.8, p < .005). The analysis of the results demonstrated that the duration of stimulation in the group patients with recurrent unilateral endometriomas was significantly higher in comparison with the group II (12.2 ± 1.8 and 10.2 ± 1.6 days, p < .001). Nevertheless, the number of good quality embryos retrieved was comparable in both groups (2.2 ± 1.5 and 2.8 ± 1.8). In the group I patients with recurrent unilateral endometriomas, there was a statistically significant decrease of implantation rate (17.1% vs. 24% p < .005). The results of the study revealed no statistical difference in embryo quality in the study cohort. However, it is important to note that a statistically significant difference in implantation rate in the group of endometriosis-associated infertility compared was obtained 1.5 times lower than in the control group (15.8% vs. 24.0% p < .005). The achieved results demonstrated an adverse IVF outcome in infertile women with recurrent endometrioma compared to the control group.

Oocyte quality in women with infertility associated endometriosis.

The mechanisms of endometriosis-related infertility remain still unknown. Endometriosis and clinical markers of oocyte quality are a very important problem of reproduction. The purpose of the study is to assess the quality of oocytes in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 29 and 40 years who underwent IVF and ICSI procedures. The patients were divided into three groups: group I involved 50 (n = 50) patients with recurrent unilateral endometriomas, group II included 50 patients (n = 50) unilateral endometriomas after surgical treatment and control group with 30 (n = 30) patients with tubal factor infertility. Clinical and morphological assessment of oocyte quality was performed in all IVF/ICSI cycles. The results of the study demonstrate a statistically significant increase in the number of immature oocytes of metaphase MI and immature oocytes at the GV germinal vesicle stage in patients with infertility associated with endometriosis, compared with the control group (p<.005). There is deterioration in the quality of the obtained oocytes in patients with the presence of endometrioma more than 3 cm in diameter. The results of this study allow to conclude that endometriomas negatively affect quality of oocyte and ovarian reserve, whereas endometriomas after cystectomy, have a deleterious and sustained effect on ovarian reserve.

Surgery for endometriomas within the context of infertility treatment.

BACKGROUND: The presence of an endometrioma can often be accompanied by a clinical dilemma during the course of fertility treatment. The aim of this study was to evaluate anti-Müllerian hormone (AMH) levels and spontaneous pregnancy rate in infertility patients with endometriomas depending of initial AMH levels and cyst type. METHODS: This prospective cohort study included infertility patients with unilateral endometrioma (3-5 s m in diameter) aged 25-35. A total of them underwent laparoscopic cystectomy. All patients were divided into two groups due to AMH levels and cyst type during surgery. We investigated AMH levels and spontaneous pregnancy rate in 1,3 and 12 months after surgery. RESULTS: The majority of patients with normal AMH level had type II endometriomas (70%) compared with low AMH level group (30%). There were no significant differences between AMH levels in all the patients with type II endometriomas after surgery. AMH level decreased significantly at 1 month in patients with normal AMH level and type I endometriomas (P = 0.018). But at 3 months the AMH level was compared with initial parameters. Women with low AMH levels before surgery and type I cysts had a significant decrease of AMH level at 1 and at 3 months after surgery. All patients with a time interval of 6 months after surgery had the best outcomes with significantly higher pregnancy rate (PR) in patients with normal AMH level and type II cysts (P = 0.036) and with AMH less than 2 ng/ml and type I cysts (P = 0.021). The group with normal AMH level and type II endometriomas had a significantly higher ongoing cumulative PR than others (59.4%). CONCLUSIONS: Our data suggest that laparoscopic surgery could affect ovarian reserve in case of initial low AMH levels and type I of endometriomas. We believe that the good surgical technique helps to increase pregnancy rate in infertility patients with endometriomas. Good prognosis group are the infertility patients with normal AMH level and type II endometriomas.