Roberto de Azevedo Antunes

Intercorrências clínicas na Síndrome de Turner

A retrospective study was held on data of 60 patients with Turners Syndrome (TS), aiming to report the most prevalent diseases in this syndrome. Diagnosis was confirmed by kariotype from the prenatal period to the age of 49 years. At the time of the study the age of the patients ranged from 1 to 50 years, and they were observed during 4 months to 29 years. Thirty-one patients presented 45XO kariotype, 24 were mosaic and 5 were 46Xi, (i,Xq). All presented with low stature and some stigmas. Five (8.3%) did not present other diseases and are currently healthy. In 55 (91.6%) the following associate diseases were observed: 23 (38.3%) had endocrine, 16 (26.6%) ear, throat and nose, 15 (25%) cardiologic, 14 (23.3%) renal and 6 (10%) gastrointestinal diseases. The most common endocrine diseases were hypothyroidism (36.6%), osteoporosis (18.3%) and hyperlipidemia (11.6%). The most frequent ear, nose and throat diseases were infections (media otitis and tonsillitis). Congenital diseases of the aorta valve (bicuspid aorta valve) and double collecting systems with renal rotation were the most prevalent cardiac and renal diseases, respectively. Two patients had a diagnosis of Meckels diverticulum. Although congenital diseases were more common in 45XO patients, no statistical significant difference was found concerning the prevalence of the diseases on other karyotypes. We conclude that special support must be given to patients with TS, with periodical assistance by multiple specialists.

Body weight and 25-hidroxyvitamin D follicular levels: a prospective study of women submitted to in vitro fertilization

Objective Vitamin D deficiency has been largely related to infertility in animals. However, data demonstrating a direct association between hypovitaminosis D and infertility in humans are still conflicting. Increased body weight and an elevated body mass index (BMI) are known for their association with infertility. Therefore, this study attempted to verify whether increases in body weight and the BMI were associated with lower 25-hidroxyvitamin D [25(OH)D3] levels in the follicular fluid (FF) of patients treated for infertility with intracytoplasmic sperm injections (ICSI). This study aimed to assess the FF levels of 25(OH)D3 in women submitted to ICSI and correlate these levels with the different body weight and BMI values observed in the enrolled cohort. Methods The FF aspirates of 199 patients submitted to ICSI were collected after oocyte aspiration to check whether FF 25(OH)D3 levels were associated with weight regardless of the etiology of infertility. Chemiluminescent assays were used to assess FF 25(OH)D3 levels. The etiology of infertility was defined based on patient clinical history and follow-up. Results The patients enrolled in the study were divided into three groups according to their FF 25(OH)D3 levels, as follows: a) deficient (n=71; <20 ng/ml); b) insufficient (n=64; 21< 25(OH) D3>29 ng/ml); and c) sufficient (n=56 >30ng/ml) levels. Patients with lower FF 25(OH)D3 levels had a greater mean weight (64.1kg) when compared to patients with higher 25(OH)D3 levels (60.7kg), p<0.01. No differences were observed in terms of age or etiology of infertility. Conclusion The body weight of the individuals with FF 25(OH)D3 deficiency measured in single follicles was significantly higher regardless of the etiology of infertility. Further epidemiologic and molecular studies are required to verify whether the amount of follicular 25(OH)D3 affects the outcome of IVF procedures.

Prediction of metaphase II oocytes according to different serum Anti-Müllerian hormone (AMH) levels in antagonist ICSI cycles

Objective This paper aims to assess a qualitative aspect of ovarian response in terms of metaphase II oocytes according to different serum Anti-Müllerian hormone levels in antagonist ICSI cycles. A prediction index might contribute to the individualization of care. Methods This observational study looked into 287 antagonist ICSI cycles carried out with patients treated in a single center between January of 2012 and January of 2016. Serum AMH and subgroup analyses were performed based on five AMH ranges (≤ 0.3 ng/mL;> 0.3 and ≤ 0.7 ng/mL; > 0.7 and ≤ 1.0 ng/mL; > 1.0 and < 3.0 ng/mL; ≥ 3.0 ng/mL). The variables analyzed included patient age; serum FSH and antral follicle count at the start of the cycle; number of stimulation days and number follicles ≥ 15 mm on hCG day; number of oocytes retrieved and number of metaphase II oocytes. Results AMH is a better predictor of ovarian response to controlled ovarian stimulation than AFC or serum FSH, while age is an independent marker. AMH levels ≤0.70 (patients with poor prognosis) were observed in 140 patients (48.7%). Patients within this AMH level range accounted for 92% of the 24 failed cycles (cancelled cycles, no oocytes or immature oocytes retrieved). Conclusion AMH predicts the quality of ovarian response to stimulation, regardless of patient age. Women with AMH levels ≥1.0 and ≤3.0 ng/mL are probably normal responders with good prognosis. Clinical application relies on the examination of the data from each individual center and on the establishment of correlations between AMH levels and ovarian response in the form of metaphase II oocytes.

Zika virus and Assisted Reproductive Technology: to test or not to test, that is the question. Is it an unnecessary cost? The first two months of mandatory testing in an outbreak area in Rio de Janeiro, Brazil.

Objective Infection by the Zika virus is a Public Health Emergency of International Concern as defined by the World Health Organization. Resolution no. 72, issued by the Collegiate Board of the Brazilian Health Surveillance Agency (ANVISA) on March 30, 2016, made ZKV testing mandatory prior to procedures involving germ cells and tissues. This paper aims to discuss the aforementioned Resolution from the standpoint of evidence and cost-effectiveness of the measures taken within the first two months of mandatory testing. Methods The medical staff at the clinic looked into the steps needed to comply with the new rules and checked laboratories in the city to perform the tests with their lead times and costs, health insurance refunds, data maintenance capabilities, how to contact patients, decision-making processes in ongoing cases, deadlines for implementation, in addition to exchanging ideas with other clinics and gathering information from the guidelines being produced. A SWOT analysis was performed. Results A total of 152 tests were performed within the first two months of mandatory testing, in five different clinical situations: one previously symptomatic woman with a negative PCR test before starting the cycle; two asymptomatic women had positive IgM (1.3%) and negative PCR tests on days 25 and 60; one husband enrolled as a suspect with a negative RT-PCR on day 13 and another untested suspected case; a couple decided to have their oocytes cryopreserved because the husbands test result was not available on pickup day. The mean cost of USD 200 per couple is equivalent to 1.2 day of the stimulation protocol. The staff worked more efficiently and was able to respond promptly to the increased demand for ZKV testing; however, the tests failed to reassure patients of the safety of the procedure and increased costs. Conclusion The testing requirement for asymptomatic patients prior to ART should be reviewed.

Lower follicular fluid vitamin D concentration is related to a higher number of large ovarian follicles

Vitamin D receptor-knockout mice fail to produce mature oocytes, indicating vitamin D is crucial for folliculogenesis in mice. However, the actions of vitamin D during folliculogenesis remain unknown. This prospective study aimed to assess whether follicular fluid (FF) vitamin D (25OHD3) concentrations are related to specific responses to ovarian stimulation. Women undergoing ovarian stimulation for IVF participated in the study. FF 25OHD3 concentrations were assessed in the first follicle aspirate on oocyte retrieval day. Oestradiol and progesterone concentrations were assessed on the trigger day. K-means grouping analysis showed that 25OHD3 FF concentrations clustered into a higher and lower group (mean ± SEM 17.4 ± 6.61 ng/ml and 35.5 ± 7.17 ng/ml, respectively, P < 0.001). The clusters were analysed according to the oestradiol and progesterone concentrations, follicle number and size and resulting oocyte number and maturity. The FF 25OHD3 concentrations were no different among the infertility diagnoses. The lower 25OHD3 group had more follicles (≥16.0 mm, P = 0.009) and higher serum oestradiol concentrations (P < 0.03) on the day of HCG administration. In this study, lower follicular 25OHD3 concentrations predicted a better response to ovarian stimulation shown by a greater production of larger follicles and higher serum oestradiol concentrations.

Vitamin D Receptor TaqI Polymorphism Is Associated With Reduced Follicle Number in Women Utilizing Assisted Reproductive Technologies

Purpose Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female vdr-knockout mice; however, whether VDR polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that VDR polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the TaqI, BsmI, and FokI VDR polymorphisms and ovarian responses in women undergoing COS. Methods In this study, we recruited a control group (n = 121) comprising volunteers with a history of natural conception and a second group of women undergoing COS (n = 70). TaqI, BsmI, and FokI genotyping was performed via restriction fragment length polymorphism analysis or TaqMan qPCR and Sanger sequencing. Intrafollicular 25(OH)D contents were measured in follicular fluid collected from COS patients during oocyte retrieval. Ovarian response parameters were obtained from patient medical records. Results There were no significant differences in the genotype frequencies of VDR polymorphisms (TaqI, BsmI and FokI) between the control and COS groups. However, the allele frequency of TaqI (C allele) was significantly lower in the COS group than in the control group (p = 0.02). Follicle number but not oocyte number was lower in patients with TaqI polymorphic (TC/CC) genotypes (p = 0.03). Importantly, the ratio between the number of follicles retrieved and intrafollicular estradiol concentrations was higher in patients with the TC/CC TaqI genotypes (p < 0.02). Conclusion We identified an association between the VDR TaqI polymorphism and reduced follicle number in women undergoing COS, suggesting that VDR signaling affects the ovarian response to stimulation via unknown mechanisms.

Vaginismus in Assisted Reproductive Technology Centers: an invisible population in need of care

Objective Genital and sexual pain is still neglected. Consequences may be dramatic, since infertility and sexual dysfunction may be reciprocally linked. This is the first study to focus on the identification of cases of vaginismus in the ART scenario and on the introduction of intra-cycle interventions as part of a comprehensive, integrated and patient-centered perspective. Methods This observational prospective study looked into 425 IVF/ICSI cycles and 226 frozen embryo transfers carried out from January 1, 2015 to December 31, 2016, and found seven cases of vaginismus. Within a six-month period, a questionnaire placed on SurveyMonkey was sent twice to 228 ART centers in Latin America. The purpose was to learn how often cases of vaginismus were found in ART centers and the perceptions around the presence of this condition. Results The few centers that took the time to answer the questionnaire (24/10.5%) stated that the number of cases in which they had trouble performing control ultrasound examination or needed to perform transfers with patients under sedation was not significant. Although 81% agreed that the incidence of these conditions is low, no references were made to cases of vaginismus, dyspareunia or sexual dysfunction. Our multidisciplinary team found seven cases of vaginismus, involving women with higher education degrees with a mean age of 37.8 years and married for a mean of four years. Although two reported they were able to tolerate intercourse, all reported undergoing treatments such as using vaginal dilators (3), psychotherapy (4) and psychiatric care (1). The care provided by the staff was designed to mitigate patient suffering. Conclusion Gentle care and sensitive listening should be integral components in the work of multidisciplinary teams to identify women with vaginismus and offer couples better quality treatment.

Building new approaches to care in Assisted Reproduction: how can we go farther?

Assisted Reproduction specialists are quite aware of the issues derived from infertility. However, it is our point of view and understanding that failure to provide good patient care significantly affects our ability to develop sound relationships with them. Most Latin American countries follow the principles concerning reproductive health dictated by the WHO (UN Women, 1995), which provide for a comprehensive understanding of the matter and reinforce the right women have to a state of complete physical, mental, and social wellbeing as a vital condition for them to play an active role in every area of their public and private lives. Inequality is a frequent issue affecting men and women in Latin America. Nonetheless, women occupy an even weaker position inside our family settings. Women in Latin America are often precluded from having access to health and wellbeing, for myriad reasons linked to geographic, social, political, economic, and biologic factors (Souza & López, 2015). Although there has been some progress in this area, our patients are still a long way from representing themselves and making decisions on their own, even in the context of assisted reproduction. The implementation of a new agenda requires support from all levels. In daily practice, patients are insufficiently involved in choosing between treatment options (van Empel et al., 2010), as treatment decisions are predominantly made by professionals based on their own diagnosis of a patient’s physical condition. It has been proposed that not only the patient’s physical condition, but also the patient’s treatment preferences should be taken into account when choosing from different treatment options (Mulley et al., 2012). The notion of empowering the patient came from the ideas of Brazilian educator Freire (Gadotti et al., 1995): “To me, critical reading basically implies that the reader is an intelligent individual, capable of decrypting the text. In this sense, the critical reader is he who ‘rewrites’ what he reads, who ‘re-creates’ himself on his own terms. A non-critical reader functions as a kind of instrument of the author, a patient and docile repeater of what he reads.” And the practical implications of this notion prescribe that one should not pre-define or restrict the roster of diseaseor treatment-related outcomes, but rather discuss and negotiate with every patient or couple based on their particular situations and priorities in life. Best practice may have different meanings when analyzed from the standpoint of experts or patients. According to Dancet et al. (2013), safety and effectiveness are the main goals of treatments to physicians, embryologists and nurses, while patients care more about being in the center of care, which means they desire attention during the course of treatment. But how should we look at this? There certainly is some tension in the air, as we do not have the right answer to every patient nor a definitive protocol suitable for everyone. JBRA Assisted Reproduction 2017;21(2):59-60 doi: 10.5935/1518-0557.20170015

Live Births after Fertility-saving Surgery in Ovarian Borderline Tumor and Oocyte Donation: Case Report

A left borderline serous ovarian tumor stage I (FIGO) was discovered and treated in a 26-year-old black nulliparous woman, by conservative approach (laparotomy, salpingo- oophorectomy). In a six months interval she had a 7.5 x 7.1 x 5.7cm multilocular contralateral tumor with septa and vegetative areas and in a year interval a CT showed a 8.4 x 7.4 x 7.0 lesion that precluded a follicular aspiration. The authors discuss the multidisciplinary strategy and the approach with the couple: the best option considered would be the resection of the tumor remaining attached to a new study pelvic. If possible uterine conservation should be held for further procedure of oocyte donation. Two years from the first surgery she had the second laparotomy and six months later she had an ICSI with oocyte donation. She became pregnant and delivered two 34 week-pregnancy boys through C-section due to hypertension plus preeclampsia. There happened a post- operative intestinal obstruction that required a new surgical approach to adhesions lysis. There was no report of tumor lesions then. Seven months later, mother and children are doing well. Comments are made about borderline ovarian tumors and fertility-sparing approaches.

Nurses acting in reproductive medicine: improving patient performance on self- medication

Objective: Patients are increasingly anxious about the amount of information received regarding the drugs and between physician orders and patients, we designed a strategy to enroll them assisting patients with their daily fertility treatment injections. Methods: An exploratory survey was held by the clinicians and the nurse that resulted in a list of complaints pointing to anxiety concerning self-medication. Both groups were detecting patients characterized as insecure with medications and felt that something was needed to be done. In the second moment a nursing consultation was systematized in order to assist infertile patients with their daily fertility treatment injections. This consultation began being offered as a pilot in the clinical routine for couples who would start ART cycles. A questionnaire was introduced later to obtain feedback from nurse consultations. Results: There have been 41 accepted and scheduled appointments with 35 consultations that represented 85% of adherence. 24 patients received the questionnaire and 11 (46%) returned. 5 patients related having had problems handling medications previously. Two patients still had problems diluting drugs. Three patients caused extra distress. Concerning the way of administration patients indicated that they preferred the preloaded pens instead of manually injections with syringes. All questionnaires point that nurse consultation was clear and important and 5 out of 11 (45%) yielded an extra comment marking it as outstanding for their treatment. Conclusions: Our paper demonstrates that nurses can be involved more in ART treatments. key-words: nurses, IVF, medication