Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study.

OBJECTIVE: To compare the effectiveness of two different treatment regimens of dydrogesterone in the management of endometriosis-related chronic pelvic pain. DESIGN: Observational, prospective cohort study over six months. SETTING: Twenty gynecology clinics in the Russian Federation. PATIENT(S): Three hundred fifty women from 18 to 45 years of age with endometriosis and chronic pelvic pain with or without dysmenorrhea. INTERVENTION(S): Dydrogesterone 10 mg 2 or 3 times daily, either between the 5th and 25th days of the menstrual cycle (prolonged cyclical treatment regimen) or continuously (continuous treatment regimen). For all patients, the data cutoff was at six months of treatment. MAIN OUTCOME MEASURE(S): Intensity of chronic pelvic pain on the 11-point numerical rating scale (after 6 months). RESULT(S): A marked reduction in chronic pelvic pain was observed with both the prolonged cyclical and continuous treatment regimens (mean ± standard deviation change from baseline -3.3 ± 2.2 and -3.0 ± 2.2, respectively), with no significant difference between the two groups. With both regimens, patients experienced significant improvements in the intensity of chronic pelvic pain, number of days in which analgesics were required, severity of dysmenorrhea, sexual well-being, and health-related quality-of-life parameters. A favorable safety profile of dydrogesterone was confirmed, and no serious adverse drug reactions were reported during the study. CONCLUSION(S): Prolonged cyclical and continuous treatment regimens of dydrogesterone therapy both demonstrated a pronounced and similar reduction in the severity of chronic pelvic pain and dysmenorrhea and led to marked improvements in all study parameters related to quality of life and sexual well-being. REGISTRATION NUMBER: NCT03690765.

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.

A Comparative Study on the Effects of High-Intensity Focused Electromagnetic Technology and Electrostimulation for the Treatment of Pelvic Floor Muscles and Urinary Incontinence in Parous Women: Analysis of Posttreatment Data.

OBJECTIVES: Pelvic floor muscles (PFMs) weakening and urinary incontinence (UI) represent health issues that have a negative impact on daily life. This study compares the immediate efficiency of high-intensity focused electromagnetic (HIFEM) therapy and electrostimulation for the treatment of weakened PFMs, accompanied by the UI. METHODS: Ninety-five parous women were considered for the study. Symptomatic patients received either HIFEM or electrostimulation treatment. Treated patients completed 10 therapies scheduled 2 to 3 times per week (HIFEM) or every other day (electrostimulation). Patients underwent examination by 3-dimensional transperienal ultrasound at the baseline and posttreatments. Levator-urethra gap, anteroposterior diameter, laterolateral diameter of levator hiatus, and hiatal area were measured. In addition, Pelvic Floor Disability Index 20 questionnaire and subjective evaluation of patient's intimate health were assessed. RESULTS: Enrolled patients were divided into group I (n = 50, HIFEM), group II (n = 25, electrostimulation), and group III (n = 20, control) according the indication and treatment modality. Three-dimensional ultrasounds showed positive changes in dynamics of the pelvic floor posttreatment (decreased anteroposterior diameter, laterolateral diameter, and hiatal area). However, the significant (P < 0.05) changes of pelvic floor integrity were observed only in group I. In addition, group I achieved greater level of improvement in Pelvic Floor Disability Index 20 questionnaire compared with group II (52% and 18% respectively; P < 0.001). Substantially fewer patients in group I reported urine leakage after treatments. CONCLUSIONS: Posttreatment results suggest that HIFEM technology is suitable for treatment of PFMs weakening and showed to be more effective when compared with electrostimulation in short-term. Therefore, we recommend HIFEM as treatment option for weakened PFMs and UI.

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.

The role of cholecalciferol deficiency in the pathogenesis of polycystic ovary syndrome.

OBJECTIVES: to evaluate and compare clinical presentations, medical history, and laboratory data of patients with polycystic ovary syndrome, including vitamin 25(OH)D3 level. METHODS: In total, 81 patients were examined. The patient group included 51 patients with signs of polycystic ovary syndrome. The control group included 30 healthy women without signs of polycystic ovary syndrome, comparable according to gender and age to the patient group. Polycystic ovary syndrome was verified based on the diagnostic Rotterdam and international polycystic ovary syndrome guidelines' criteria. The levels of cholecalciferol were determined by mass spectrometry (ng/mL). At the second stage of the study, the patient group with polycystic ovary syndrome was divided into two subgroups depending on the waist circumference and compared with each other by the level of insulin, low-density lipoproteins, triglycerides, anti-Mullerian hormone, follicle-stimulating hormone, and luteinizing hormone. Statistical analysis was carried out using the parametric t-test for two-independent samples with equal or different variance. For nominal data-Pearson's chi-test, when the means are not calculated and a test is carried out for the presence of a relationship between the nominal variables. RESULTS: Patients with polycystic ovary syndrome and without polycystic ovary syndrome did not have a statistically significant difference in 25(OH)D3 level. Statistically significant differences in the level of 25(OH)D3 were found in women with polycystic ovary syndrome with the waist circumference ⩾80 cm. In these subgroups, differences in insulin, low-density lipoprotein, and triglycerides levels were also revealed. CONCLUSION: The correlation of the 25(OH)D3 level does not differ in the groups of patients with polycystic ovary syndrome and without polycystic ovary syndrome, but significantly correlates with the metabolic profile of patients.

Electromyographic Evaluation of the Pelvic Muscles Activity After High-Intensity Focused Electromagnetic Procedure and Electrical Stimulation in Women With Pelvic Floor Dysfunction.

INTRODUCTION: Impaired coordination, relaxation, and atrophy of pelvic floor muscles (PFMs) may cause various health issues referred to as pelvic floor dysfunction (PFD). In recent years, electromagnetic noninvasive stimulation of the pelvic floor was successfully used to treat PFD symptoms. AIM: This study aims to compare the effectiveness of electrical and magnetic noninvasive stimulation for the treatment of PFD in postpartum women. METHODS: 2 intervention groups treated with high-intensity focused electromagnetic ([HIFEM]; G1) procedure and electrical stimulation (G2) were established along with the control group (G3). Patients received 10 therapies delivered at the hospital (G1; 2-3 times per week) or self-administered at home (G2; every other day) after initial training. The protocol was identical for both modalities. Functionality of the PFM was examined by surface electromyography measurements (maximal voluntary contraction [MVC]; mean MVC; muscle activity at rest; endurance of contraction) while patient's subjective perception of pelvic floor functionality was assessed by Pelvic Floor Impact Questionnaire-Short Form 7 (PFIQ-7) standardized questionnaire. Changes in electromyography values and PFIQ-7 scores were statistically evaluated from baseline to after all treatments. MAIN OUTCOME MEASURE: The main outcome measure was enhancement of PFM activity. RESULTS: In total, 95 patients (G1 = 50; G2 = 25; G3 = 20) participated in the study. The MVC, mean MVC, and endurance were lowered in symptomatic patients. After the treatments, these parameters significantly increased (P < .001) and moved toward the values of healthy population. Electrogenesis at relaxation revealed divergent tendencies in the G1 and G2 groups. PFIQ-7 scores significantly improved in treated patients (P < .001). In general, superior results were documented in the HIFEM group as it reached improvement of electromyography parameters from 48% to 59% (electrical stimulation from 7% to 36%) and similarly the improvement of PFIQ-7 score by 57% (electrical stimulation by 32%). CONCLUSION: This study documented that the HIFEM procedure was significantly more effective than electrical stimulation in treatment of PFD in postpartum women. Both the objective and subjective evaluation indicates more profound effects of magnetic stimulation. Elena S, Dragana Z, Ramina S, et al. Electromyographic Evaluation of the Pelvic Muscles Activity After High-Intensity Focused Electromagnetic Procedure and Electrical Stimulation in Women With Pelvic Floor Dysfunction. Sex Med 2020;8:282-289.

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.