Evaluation of HLA-DQ2 and HLA-DQ8 haplotypes in patients with endometriosis, A case-control study.

OBJECTIVE: To evaluate the relationship between genetic haplotypes associated with celiac disease (Human Leucocyte Antigen [HLA] DQ2 and DQ8) with the diagnosis, clinical presentation, and location of endometriosis in Brazilian women. METHOD: A retrospective cross-sectional study, was conducted in a Tertiary hospital. PATIENTS: Women aged 18-50 years who underwent HLA-DQ2 and HLA-DQ8 haplotype analysis. INTERVENTION: The patients were divided into endometriosis and control groups and evaluated for symptoms; endometriosis location, American Society for Reproductive Medicine (ASRM) stage, and the presence of anti-tissue transglutaminase IgA (anti-TgA), HLA-DQ2, and HLA-DQ8 markers. RESULTS: A total of 434 consecutive patients with (n = 315) and without (n = 119) endometriosis were included. Pain and infertility were more frequent in the endometriosis group than in the control group. The presence of HLA-DQ2, HLA-DQ8, and anti-TgA was similar between both groups. The presence of HLA-DQ2 and HLA-DQ8 markers did not differ based on age, pain symptoms, ASRM stage, or endometriosis location. CONCLUSION: Although there are similarities in inflammatory markers and pathophysiology between celiac disease and endometriosis, this study found no significant associations in the presence of HLA-DQ2 or HLA-DQ8 haplotypes and endometriosis.

Women's perspectives on impact on the post menopause of use of the 52 mg levonorgestrel intrauterine device during the menopausal transition.

OBJECTIVES: To assess perimenopausal users of 52 mg levonorgestrel intrauterine devices (LNG-IUD) regarding the IUD impact after menopause. MATERIAL AND METHODS: a cross-sectional study with users aged 40 and 49 years old, without cognitive impairment that answered a questionnaire regarding worries and benefits after the menopause due to LNG-IUD use. RESULTS: Almost half of 221 users (52.9%) have concerns that LNG-IUD use could influence aspects after menopause, 111 (50.3%) that the post-menopause symptoms get worse and 92 (41.6%) that interfere with recognition of menopausal symptoms. CONCLUSION: Half of perimenopausal LNG-IUD users expressed concerns about how device use could affect post-menopause symptoms.

The 52 mg hormonal-IUD who were at menopausal transition reported worries that the use of the IUD can affect menopausal symptoms. It is important that health professionals can routinely guide these women.

Expression of ezrin protein and phosphorylated ezrin in pelvic endometriotic lesions.

OBJECTIVE: To evaluate the expression of Ezrin and Phosphorylated Ezrin (Phospho-Ezrin) in endometriosis lesions and its relation to the menstrual cycle phase, stage of endometriosis, histological classification, and clinical symptoms. MATERIAL AND METHODS: The authors conducted a retrospective study, with endometriotic lesions collected from women with endometriosis (n = 57) who underwent laparoscopy from 2017 to 2018. The expression of Ezrin and Phosphorylated Ezrin proteins was analyzed by immunohistochemistry. RESULTS: All the endometriotic lesions contained immunostaining for Ezrin in the glands. Phosphorylated Ezrin was expressed in the stroma of all endometriotic lesions. There was no difference in the Ezrin and Phosphorylated Ezrin's expression in the retrocervical, ovarian, superficial, and intestinal lesions in the same patient. Dysmenorrhea, dyspareunia, acyclic pain, infertility, and dysuria were similar in the three groups of Ezrin staining. There was an inversely proportional relationship between severe dyschezia and Ezrin's intensity, being 66.7% of Ezrin 1 (weak intensity), 36.7 Ezrin 2 (moderate intensity), and 10.0% of Ezrin 3 (p = 0.013). Regarding Phospho-Ezrin there wasn't a significant difference between all the analyzed variables. Histological classification and menstrual cycle phase had also no significant difference between Ezrin and Phospho-Ezrin immunostaining. CONCLUSION: Ezrin protein and Phospho-Ezrin can be considered important markers to elucidate the mechanisms related to migration and attachment of endometriotic lesions. It is still unclear if Ezrin and Phospho-Ezrin are a cause or consequence of endometriosis. Further studies comparing different types of lesions and eutopic endometrium are necessary to elucidate the role of these proteins in the pathogenesis of endometriosis.

Reasons for satisfaction with the use of the 52-mg levonorgestrel intrauterine system.

OBJECTIVES: To assess the reasons to use, reasons they liked, satisfaction with, and possibilities of recommendation to other women of the levonorgestrel 52-mg intrauterine system (LNG-IUS) by users. MATERIALS AND METHODS: A cross-sectional study was conducted at the University of Campinas, Campinas, Brazil from January to July 2021. We enrolled users who came to the clinic, and we applied a pre-tested structured questionnaire with open-ended questions. We performed descriptive analyses of the variables, assessing the level of satisfaction with, and the reasons regarding the possibility of continuing to use, the IUS. RESULTS: Of the 517 enrolled women, 251 (48%) were aged 35 years or older (mean age 33.9 ± 9.0 years), 276 (53%) were white, 14 (3%) were adolescents, 155 (30%) were nulligravidas, and 307 (59.4%) reported experiencing amenorrhea in the last 90 days. Common reasons why women liked to use the LNG-IUS included both the reduction of menstrual bleeding (419 women; 81%) and dysmenorrhea (290 women; 56.1%). Nine out of 10 users (517 women; 91%) were satisfied with the method, and the majority would recommend it to other women. CONCLUSION: We found a high satisfaction rate among LNG-IUS users mainly due to the reduction of both menstrual bleeding and dysmenorrhea.

Perspectives of health care providers regarding the levonorgestrel-releasing intrauterine system.

OBJECTIVES: The aims of the study were to assess the number of insertions per month of the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) and gauge the knowledge and opinions of health care providers with regard to some of its characteristics and the reasons why women liked using the method. METHODS: An online questionnaire survey was conducted between January and July 2021 at the University of Campinas, Brazil. The survey comprised physicians and nurses from centres that had requested and received donated devices. RESULTS: A total of 65 health care providers answered the questionnaire (41 physicians and 24 nurses). The main misconceptions were related to insertion after an ectopic pregnancy: 60/65 (92.3%) answered that users with previous ectopic pregnancy must have frequent follow-up. Wrong answers were also given on the occurrence of acne (37/65, 56.9%) and depression (32/65, 49.2%). Participants reported that the LNG-IUS was highly effective (100%), long-acting (93.9%) and an appropriate method for controlling uterine bleeding (90.8%) and that it had few side effects (86.2%). CONCLUSION: Our study suggests that health care providers from centres that requested and received LNG-IUS donations, even though they reported adequate knowledge about the device, still had misconceptions with regard to its clinical management.

Reasons reported by women for choosing the levonorgestrel intrauterine system as a contraceptive method.

OBJECTIVE: To assess the reasons provided by women for choosing the use of the 52 mg levonorgestrel intrauterine system (LNG-IUS) as a contraceptive method. METHODS: We conducted a cross sectional study from January 2021 to August 2021 at the University of Campinas, Campinas, SP, Brazil. Women who had never used the 52 mg LNG-IUS and were requesting it for contraception answered a questionnaire asking for their sociodemographic characteristics, the last contraceptive method in use, how they received information about the device, and their main reasons for choosing the method. RESULTS: We enrolled 516 women, 365 (70.7%) of whom were under the age of 35 and 352 (68.2%) of whom were parous. The last contraceptive method in use was a short-acting reversible method among 387 (80.8%) women, 454 (88%) reported that they wanted to use the IUS only for contraception, and the main source of information was their health care providers. The main reported reasons for choosing the method were because it is safe, has high contraceptive efficacy, and reduces menstrual bleeding. CONCLUSION: Health care providers should continue their efforts to provide guidance about the LNG-IUS, including the non-contraceptive benefits, which may contribute to a reduction in the number of unplanned pregnancies.

Expression of ezrin protein and phosphorylated ezrin in pelvic endometriotic lesions

Abstract Objective: To evaluate the expression of Ezrin and Phosphorylated Ezrin (Phospho-Ezrin) in endometriosis lesions and its relation to the menstrual cycle phase, stage of endometriosis, histological classification, and clinical symptoms. Material and methods: The authors conducted a retrospective study, with endometriotic lesions collected from women with endometriosis (n = 57) who underwent laparoscopy from 2017 to 2018. The expression of Ezrin and Phosphorylated Ezrin proteins was analyzed by immunohistochemistry. Results: All the endometriotic lesions contained immunostaining for Ezrin in the glands. Phosphorylated Ezrin was expressed in the stroma of all endometriotic lesions. There was no difference in the Ezrin and Phosphorylated Ezrin's expression in the retrocervical, ovarian, superficial, and intestinal lesions in the same patient. Dysmenor-rhea, dyspareunia, acyclic pain, infertility, and dysuria were similar in the three groups of Ezrin staining. There was an inversely proportional relationship between severe dyschezia and Ezrin's intensity, being 66.7% of Ezrin 1 (weak intensity), 36.7 Ezrin 2 (moderate intensity), and 10.0% of Ezrin 3 (p = 0.013). Regarding Phospho-Ezrin there wasn't a significant difference between all the analyzed variables. Histological classification and menstrual cycle phase had also no significant difference between Ezrin and Phospho-Ezrin immunostaining. Conclusion: Ezrin protein and Phospho-Ezrin can be considered important markers to elucidate the mechanisms related to migration and attachment of endometriotic lesions. It is still unclear if Ezrin and Phospho-Ezrin are a cause or consequence of endometriosis. Further studies comparing different types of lesions and eutopic endometrium are necessary to elucidate the role of these proteins in the pathogenesis of endometriosis. HIGHLIGHTS The implantation of endometrial cells in the pelvic cavity has been related to some factors such as a receptive environment that allows the implantation and proliferation of these cells. Several studies have shown the participation of the Ezrin protein in the process of invasion of malignant cells. The expression of Ezrin and its activated form was observed in endometriotic lesions providing great evidence that these proteins can play an important role in the migration and attachment of endometriotic lesions.

A randomized controlled pilot study of ulipristal acetate for abnormal bleeding among women using the 52-mg levonorgestrel intrauterine system.

OBJECTIVE: To assess the efficacy of ulipristal acetate (UPA) for reducing abnormal bleeding among women using the 52-mg levonorgestrel intrauterine system (LNG-IUS). METHODS: A randomized, double-blind, placebo-controlled pilot study conducted from September 1, 2016 to September 30, 2018, at the University of Campinas, Brazil. LNG-IUS users reporting prolonged or frequent uterine bleeding for at least 1 year were randomized to receive 5 mg UPA per day for 5 days or placebo at an identical regimen. Bleeding was recorded for 90 days after treatment began and was compared between the groups. RESULTS: Of 94 eligible women, 64 with abnormal bleeding associated with LNG-IUS use declined treatment or device removal after counselling regarding anticipated bleeding patterns. For the 25 study participants, differences were nonsignificant between the UPA and placebo groups for number of days before bleeding stopped and days free of bleeding; however, UPA users displayed a trend for shorter duration before bleeding stopped and longer time free of bleeding. A similar trend for mean number of bleeding days at 30-, 60-, and 90-day follow-up was observed. CONCLUSION: A nonsignificant trend in reduction of abnormal bleeding was observed among LNG-IUS users taking 5 mg UPA per day for 5 days compared with placebo; however, further research is needed. CLINICALTRIALS.GOV: NCT03186586.

Zika virus exposure in pregnancy and its association with newborn visual anomalies and hearing loss.

Exposure to Zika virus (ZIKV) in pregnancy leads to a spectrum of congenital effects in the newborn. Recent studies have begun to evaluate the impact of ZIKV during pregnancy. Among 39 relevant studies, nine were related specifically to clinical studies of ophthalmologic disorders and one was related to hearing loss impairment; most of these studies were case reports and case series reports. Importantly, congenital toxoplasmosis was ruled out in all studies. The data show that, in addition to microcephaly, ZIKV exposure in pregnancy may result in subtle ocular impairments in the newborn. The most common anomalies are macular pigment mottling and/or chorioretinal atrophy, and optic nerve disorders. Sensorineural hearing loss has also been noted in 5.8% of infants with microcephaly. The effects of ZIKV infection during pregnancy are potentially devastating to the fetus and newborn. Although microcephaly is an important signal, the current information emphasizes the importance of ocular and auditory screenings, otherwise sight and hearing anomalies may be underestimated. Healthcare providers should fully understand the spectrum of anomalies related to ZIKV exposure in pregnancy in order to counsel pregnant women living in high-risk areas, in addition to those wanting to become pregnant.

Expectant care versus surgical treatment for miscarriage.

BACKGROUND: Miscarriage is a common complication of early pregnancy that can have both medical and psychological consequences such as depression and anxiety. The need for routine surgical evacuation with miscarriage has been questioned because of potential complications such as cervical trauma, uterine perforation, hemorrhage, or infection. OBJECTIVES: To compare the safety and effectiveness of expectant management versus surgical treatment for early pregnancy failure. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (9 February 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2011, Issue 4 of 4), PubMed (2005 to 11 January 2012), POPLINE (inception to 11 January 2012), LILACS (2005 to 11 January 2012) and reference lists of retrieved studies. SELECTION CRITERIA: Randomized trials comparing expectant care and surgical treatment (vacuum aspiration or dilation and curettage) for miscarriage were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial quality and extracted data. We contacted study authors for additional information. For dichotomous data, we calculated the Mantel-Haenszel risk ratio (RR) with 95% confidence interval (CI). For continuous data, we computed the mean difference (MD) and 95% CI. We entered additional data such as medians into 'Other data' tables. MAIN RESULTS: We included seven trials with 1521 participants in this review. The expectant-care group was more likely to have an incomplete miscarriage by two weeks (RR 3.98; 95% CI 2.94 to 5.38) or by six to eight weeks (RR 2.56; 95% CI 1.15 to 5.69). The need for unplanned surgical treatment was greater for the expectant-care group (RR 7.35; 95% CI 5.04 to 10.72). The mean percentage needing surgical management in the expectant-care group was 28%, while 4% of the surgical-treatment group needed additional surgery. The expectant-care group had more days of bleeding (MD 1.59; 95% CI 0.74 to 2.45). Further, more of the expectant-care group needed transfusion (RR 6.45; 95% CI 1.21 to 34.42). The mean percentage needing blood transfusion was 1.4% for expectant care compared with none for surgical management. Results were mixed for pain. Diagnosis of infection was similar for the two groups (RR 0.63; 95% CI 0.36 to 1.12), as were results for various psychological outcomes. Pregnancy data were limited. Costs were lower for the expectant-care group (MD -499.10; 95% CI -613.04 to -385.16; in UK pounds sterling). AUTHORS' CONCLUSIONS: Expectant management led to a higher risk of incomplete miscarriage, need for unplanned (or additional) surgical emptying of the uterus, bleeding and need for transfusion. Risk of infection and psychological outcomes were similar for both groups. Costs were lower for expectant management. Given the lack of clear superiority of either approach, the woman's preference should be important in decision making. Pharmacological ('medical') management has added choices for women and their clinicians and has been examined in other reviews.

Endometriose profunda: como abordar? / Deep endometriosis: how to approach?

A endometriose é uma doença crônica de mulheres em idade reprodutiva com sintomas que levam à diminuição na qualidade de vida e à infertilidade. As formas infiltrativas da doença penetram mais que 5 mm abaixo da superfície peritoneal, representando lesões ativas e fortemente relacionadas com dor pélvica e dispareunia profunda. A abordagem da mulher com endometriose profunda representa nos dias de hoje grande desafio para muitos ginecologistas. O diagnóstico pode ser realizado por várias técnicas, porém a ultrassonografia transvaginal e a ressonância magnética são métodos que aumentam as chances de se detectar múltiplos nódulos, as camadas envolvidas e a distância da borda anal. Não existem dados consistentes na literatura que afirmem qual a melhor opção de tratamento, clínico ou cirúrgico. A terapêutica clínica envolve medicamentos direcionados à melhora da dor, enquanto a cirúrgica baseia-se nas possíveis técnicas operatórias com menor índice de morbidade e de complicações. Assim, a mulher com endometriose deve ser abordada individualmente e de preferência com uma equipe multidisciplinar, para que se obtenham os melhores resultados, visando exclusivamente à melhora dos sintomas

Endometriosis is a chronic disease of reproductive-aged women with symptoms that lead to decreased quality of life and infertility. The infiltrative forms of the disease penetrate more than 5 mm the peritoneal surface, representing active lesions and strongly related to pelvic pain and deep dyspareunia. Nowadays, the treatment of deep endometriosis is a great challenge for many gynecologists. The diagnosis can be performed by many techniques, but the vaginal ultrasound and the magnetic resonance imaging are methods that increase the chances in detecting multiple nodules, layers involved and the distance from the anal verge. There are no consistent data in the literature that state which is the best treatment, medical or surgical. The medical therapy involves drugs related to pain relief, while the surgery is based on surgical techniques with less morbidity and complications. Therefore, women with endometriosis should be treated individually and preferably with a multidisciplinary team, to achieve the best results, in order exclusively to improve the symptoms

Endometrial chemokines, uterine natural killer cells and mast cells in long-term users of the levonorgestrel-releasing intrauterine system.

OBJECTIVE: The objective was to assess endometrial chemokines in users of the levonorgestrel-releasing intrauterine system (LNG-IUS) and correlate them with leucocyte populations, uterine natural killer cells (uNK) and mast cells (MCs). MATERIALS AND METHODS: Endometrium was obtained from two groups of women who had been using LNG-IUS for 3 years or more: 11 amenorrhoeic women formed the non-bleeding group and 15 women who maintained some form of cyclic bleeding comprised the bleeding group. Specific antibodies were used for the assessment of neutrophils, uNK cells and MCs. Immunohistochemistry was performed to locate the chemokines 6Ckine and interleukin-8 (IL-8). RESULTS: Neutrophils were few and without differences between the two groups. uNK cells were significantly higher in the bleeding group (P < 0.0001). There was no difference between the total number of MCs and activated MCs, but there was a greater extracellular area stained for MC tryptase (P < 0.05). Chemokines 6CKine and IL-8 were abundant in the stroma and in the epithelium, and there was no difference between the groups. CONCLUSIONS: We observed more uNK cells in users with bleeding and a greater extracellular area stained for MC tryptase, although there were no differences between the number of MCs and activated MCs or the chemokines 6CKine and IL-8. uNK cells and MC products may play a role in provoking breakthrough bleeding in long-term users of the LNG-IUS.