Prenatal Findings in Postnatal Cases of Disorders of Sex Development: Experience from a Tertiary-Specialized Center in Brazil.

INTRODUCTION AND OBJECTIVE: Prenatal suspicion of disorders/differences of sex development (DSDs) is a relatively new phenomenon. The aim of this study was to review the prenatal findings of DSD cases postnatally diagnosed in our tertiary referral center. METHODS: We evaluated 57 DSD cases with sex ambiguity who had undergone prenatal ultrasound with phenotypic sex assessment and/or cell-free fetal DNA (cffDNA) for genotypic sex assessment. RESULTS: Prenatal cffDNA had been performed in 32 cases, being positive (suggestive of male genotypic sex) in 26 and negative (suggestive of female genotypic sex) in 6. Five with cffDNA negative had a prenatal ultrasound indicating female external genitalia, in turn, in those with cffDNA positive, only two had a prenatal ultrasound indicating male external genitalia. Our postnatal data showed that when external genitalia were female or poorly virilized, prenatal ultrasound indicated female sex, but in cases of higher degree of virilization, ultrasound showed similar rates of male, female, or undetermined sex. Regarding the karyotype, our data showed those with XY karyotype had positive cffDNA, those with XX karyotype had negative cffDNA, and all five with sex chromosome anomalies had positive cffDNA because they were 45,X/46,XY. We suggested an algorithm to investigate these cases during gestation, including evaluation of uterus, fetal growth, and malformations. CONCLUSION: We suggest that the parents should be counseled prenatally by a dedicated multidisciplinary team with experience in DSD management and evaluated as soon as possible after birth.

Subclinical cardiovascular disease parameters after one year in new users of depot medroxyprogesterone acetate compared to copper-IUD.

PURPOSE: To evaluate markers of cardiovascular disease in women with normal insulin sensitivity who had recently initiated use of depot medroxyprogesterone acetate (DMPA) as a contraceptive. MATERIALS AND METHODS: A prospective, non-randomised, comparative study. Data of 30 women of 18-40 years of age, with normal hyperinsulinaemic-euglycaemic clamp at baseline and body mass index (BMI) < 30, who opted to use DMPA or a copper intrauterine device (IUD) as a contraceptive, were analysed. Serum samples were collected for evaluation of the lipid and hepatic profile, C-reactive protein, TNF-α, interleukin-6, leptin/adiponectin ratio and free fatty acids; body composition was evaluated using DXA, blood pressure and carotid intima-media thickness were measured. Evaluations were performed at baseline and 12 months later. The groups were compared using repeated measures analysis of variance (ANOVA). Significance level was 5%. RESULTS: The mean age of the women in the DMPA and IUD group was 28.7 ± 6.5 and 28.3 ± 5.8 years, respectively; the BMI was 23.0 ± 3.4 and 24.3 ± 2.7 kg/m2, respectively, in the same groups. At 12 months, triglyceride levels were higher in the DMPA group compared to the IUD group and there was an increase in apolipoprotein B-100 in relation to baseline in DMPA group; there were no other difference between the groups. CONCLUSIONS: No clinical cardiovascular effect was found but deterioration in CV markers was observed in the first year of use of DMPA.

Insulin resistance parameters in users of the injectable contraceptive depot medroxyprogesterone acetate during one year of use.

OBJECTIVES: The aim of the study was to assess insulin resistance parameters using successive homeostasis model assessment (HOMA) and clinical evaluations in healthy new users of depot medroxyprogesterone acetate (DMPA). METHODS: A prospective 12-month study was carried out to compare 31 DMPA users with 25 copper intrauterine device (Cu-IUD; TCu380A) users, matched for age (± 1 year) and body mass index (BMI; ± 1 kg/m(2)). Participants met the following criteria: age 18 to 40 years, BMI < 30 kg/m(2), fasting glucose < 5.5 mmol/l, 2-h glucose after a 75 g oral glucose load < 140 mg/dl. BMI, waist circumference, fasting glucose, fasting insulin and HOMA of insulin resistance (HOMA-IR) were evaluated at baseline and after 6 and 12 months of contraceptive use. Insulin resistance was defined as a HOMA-IR value > 2.7. RESULTS: The DMPA group showed significant increases in BMI, waist circumference, fasting insulin and HOMA-IR throughout the observation period in relation to baseline. Significant increases in BMI and waist circumference were observed in the DMPA group at 12 months compared with the Cu-IUD group. Five DMPA users had abnormal HOMA-IR values, three of whom had gained > 5 kg in weight at 12 months. CONCLUSIONS: HOMA-IR represents a useful tool to indicate changes in carbohydrate metabolism in non-obese DMPA users, especially when accompanied by measurement of clinical parameters such as BMI and waist circumference.

Use of interstitial brachytherapy in pelvic recurrence of cervical carcinoma: Clinical response, survival, and toxicity.

PURPOSE: The purpose of this study was to evaluate clinical response, postrecurrence survival, disease-free survival (DFS), and toxicity related to reirradiation in pelvic recurrence of cervical carcinoma. METHODS AND MATERIALS: A retrospective cohort study of 45 women undergoing high-dose-rate interstitial brachytherapy (HDR-IB) was conducted from 1998 to 2014. Clinical information, as well as data on the malignancy, primary treatment, HDR-IB technique, and toxicity, was collected. Statistical analysis used chi-square or Fisher's exact test, Kaplan-Meier survival curves and log-rank test, and Cox regression, with p < 0.05 for significance. RESULTS: There were 30 cases (67%) of complete clinical response, with a followup period of 9-129 months (20 alive, 10 died). The 5-year postrecurrence survival rate was 52%. Among 15 women without complete clinical response, the survival rate was low (<8 months). In the 30 women with complete clinical response, the 5-year DFS was 42%. All analyzed variables were not associated with survival. Ultrasonography-based needle placement was not associated with disease control or toxicity. Toxicity was reported in 23 women (51%) with 14 fistulas, unrelated to clinical response. However, there was a higher occurrence of fistula when chemotherapy was used. CONCLUSIONS: Reirradiation using HDR-IB for pelvic recurrence of cervical carcinoma yielded a good complete clinical response rate. Postrecurrence survival and DFS rates were higher than expected, equivalent to salvage surgery, but with significant toxicity. Despite toxicity, this technique can be an alternative for selected cases.

Control of endometriosis-associated pain with etonogestrel-releasing contraceptive implant and 52-mg levonorgestrel-releasing intrauterine system: randomized clinical trial.

OBJECTIVE: To assess the efficacy of an etonogestrel (ENG)-releasing contraceptive implant or the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) in the control of endometriosis-associated pelvic pain. DESIGN: Noninferiority randomized clinical trial in which women with endometriosis were assigned to use an ENG implant (experimental treatment) or an LNG-IUS (active comparator). Monthly follow-up visits were conducted up to 6 months. SETTING: University teaching hospital. PATIENT(S): One hundred three women, with endometriosis-associated chronic pelvic pain, dysmenorrhea, or both for more than 6 months. In cases of deep endometriosis, vaginal ultrasonography and magnetic resonance imaging were used as additional diagnostic tools. INTERVENTION(S): The ENG implant or the LNG-IUS were inserted within the first 5 days of the menstrual cycle. MAIN OUTCOME MEASURE(S): Daily scores of noncyclic pelvic pain and dysmenorrhea were evaluated using a daily visual analogue scale. Health-related quality of life was evaluated using the Endometriosis Health Profile-30 questionnaire at baseline and up to 6 months. Bleeding patterns were assessed daily from a menstrual calendar. RESULT(S): Both contraceptives improved significantly the mean visual analogue scale endometriosis-associated pelvic pain and dysmenorrhea, without significant differences between treatment group profiles. Health-related quality of life improved significantly in all domains of the core and modular segments of the Endometriosis Health Profile-30 questionnaire, with no difference between both treatment groups. The most common bleeding patterns at 180 days of follow-up were amenorrhea and infrequent bleeding and infrequent bleeding and spotting among ENG implant and LNG-IUS users, respectively. CONCLUSION(S): In this noninferiority study both contraceptives improved significantly pelvic pain, dysmenorrhea, and health-related quality of life in endometriosis. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov under number NCT02480647.

Dienogest and deep infiltrating endometriosis: The remission of symptoms is not related to endometriosis nodule remission.

OBJECTIVE: To evaluate the effectiveness of dienogest in controlling pain caused by deep infiltrating endometriosis (DIE), its influence on the quality of live (QoL) of women affected by the disease, and the effect of the drug on the volume of endometriotic lesions. STUDY DESIGN: A prospective cohort study including 30 women with a sonographic diagnosis of DIE (intestinal and posterior fornix) treated with dienogest 2mg per day for 12 months. We evaluated the pain symptoms and the volume of the intestinal and posterior fornix lesions before and after 12 months of use of dienogest. To perform the statistical analysis, we used the Wilcoxon signed-rank test, and the relationship between the data was tested using the Spearman correlation coefficient. RESULTS: Women were on average 36.13±6.24years old. Pain symptoms most commonly reported were dyspareunia (83.3%), dysmenorrhea (73.3%), and pelvic pain (66.7%). After 12 months of treatment with dienogest, there was significant improvement of various symptoms (dyspareunia p=0.0093, dysmenorrhea p<0.0001; pelvic pain p=0.0007; and bowel pain p<0.0001), without a reduction in the volume of endometriotic nodules. There were significant improvements in the parameters that comprise the QoL (physical p<0.0001; p=0.0007 psychological) and the self-assessment of QoL (p=0.0069) and health (p=0.0001). CONCLUSION: Dienogest is an effective medication to control symptoms of pain related to DIE, even without reducing the volume of DIE nodules.

Successful developmental outcome in intrauterine myelomeningocele repair.

INTRODUCTION: Myelomeningocele (MM) is one of the forms of dysraphism. Hydrocephalus secondary to Arnold-Chiari (AC) malformation is responsible for the morbidity and mortality of the disease. The intrauterine repair of MM may reverse AC and limit hydrocephalus progression. OBJECTIVE: The aim of this work is to report the successful outcome of a case of intrauterine correction of MM, with favorable evolution and birth at 36 weeks of pregnancy. CASE REPORT: KCMC, 19 years old, was submitted to intrauterine repair of MM at 24 weeks of gestational age after approval by the family and the Research Ethics Committee of the School of Medical Sciences-UNICAMP. CONCLUSION: Although it is not the standard option for surgical correction, selected MM cases with early fetal diagnosis may be eligible for intrauterine repair, when there is consensus with the Research Ethics Committees and family members.

Abruptio placentae during fetal myelomeningocele repair.

Myelomeningocele (MM) is a congenital neural tube defect with serious consequences, including hydrocephaly. An important hope for intrauterine repair is that hydrocephaly may be prevented by reversing the Arnold-Chiari malformation. Three medical centers in the United States are doing trials with this objective. We describe an intrauterine correction of MM in a Brazilian research center of fetal medicine, which resulted in abruptio placentae and fetal death, to illustrate factors that influence fetal-maternal risks during this surgical procedure.