Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI).

Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.

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.

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.

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.

High Progesterone levels in the beginning of ICSI antagonist cycles and clinical pregnancy: still a concern?

OBJECTIVE: In controlled ovarian hyperstimulation (COH) using antagonist cycles, an incomplete luteolysis could happen after an inefficient previous luteolysis. Since antagonist cycles are frequent today, this study aims to access the impact of serum progesterone in the beginning and at the end of stimulation, and pregnancy outcomes. METHODS: single-center cohort study, 461 fresh embryo transfers in ICSI antagonist cycles. Serum progesterone levels was measured in the beginning of COH (P4i) and on hCG day (P4f) using threshold values of 1.5ng/mL. Four groups were created: Group 1, P4i and P4f ≤ 1.5; Group 2, P4i ≤ 1.5 and P4f > 1.5; Group 3, P4i > 1.5 and P4f ≤ 1.5 and Group 4, P4i and P4f > 1.5. The clinical pregnancy rate (CPR) and live birth rates (LBR) were the primary outcomes. RESULTS: The number of cycles per group was: 393, 51, 6 and 11, respectively. Group 1 was considered the expected normal, while group 4 represented the persistence of higher levels. There was no difference in age, basal FSH and Estradiol, days of stimulation endometrium thickness and total amount of gonadotropins between group 1 versus group 4. However, significant differences occurred in embryological and clinical outcomes between these 2 groups. CONCLUSION: The impact of serum progesterone in the beginning of stimulation and pregnancy outcomes is a matter of concern. Basal elevated levels could help identify patients that will repeat it on hCG day, being probably a marker to define a freeze-all strategy to these cycles.

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.

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 husband's 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.

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.

Intercorrências clínicas na síndrome de Turner / Clinical intercurrence in Turner's syndrome

Neste trabalho descrevemos as malformaçöes e co-morbidades observadas em pacientes com síndrome de Turner (ST). Foi realizado um estudo retrospectivo, avaliando os prontuários de 60 pacientes cujo diagnóstico de ST foi confirmado através do cariótipo, desde a fase pré-natal até a idade de 49 anos. As pacientes encontram-se com idades entre 1 e 50 anos e foram evoluídas num período de 4 meses a 29 anos. Trinta e uma apresentavam o cariótipo 45X0, 24 eram mosaico e 5 apresentavam o padräo 46Xi, (i,Xq). Todas tinham baixa estatura e algum tipo de estigma. Cinco (8,3 por cento) näo apresentavam outras malformaçöes congênitas e eram saudàveis; 55 (91,6 por cento) apresentavam doenças associadas, sendo que em 23 (38,3 por cento) foram detectadas doenças endócrinas, em 16 (26,6 por cento) otorrinolaringológicas, 15 (25 por cento) cardiológicas, 14 (23,3 por cento) nefrológicas e 6 (10 por cento) gastrointestinais. Entre as doenças endócrinas mais comuns, observamos hipotireoidismo (36,6 por cento), seguido de osteo-porose (18,3 por cento) e hiperlipemia (11,6 por cento). As doenças otorrinolaringológicas mais comuns foram as infecçöes (otite média e amigdalite); das doenças cardiológicas, as valvulopatias (principalmente aorta bicúspide), das nefrológicas as duplicaçöes do sistema coletor e rotaçöes renais e das gastrointestinais foram observados dois casos de divertículo de Meckel. Encontramos maior prevalência de malformaçöes cardíacas nas pacientes com cariótipo 45X0, embora sem significância estatística quando considerados os demais cariótipos. Concluímos que, devido à alta ocorrência de doenças nesta síndrome, estas devem ser acompanhadas periodicamente em diferentes especialidades.