CYP19A1 TC/CC Polymorphism, along with Deletion of GSTM1 and GSTT1 Genes, Strongly Influences Female Infertility Risk.

Oxidative stress has a fundamental role in the pathophysiology of various conditions, like infertility. This case-control study was performed to assess the potential role of CYP19A1, GSTM1, and GSTT1 in modifying individual predisposition to female infertility. Genotyping of 201 women with established infertility and 161 fertile female controls was performed, and statistical associations were analyzed. For carriers of GSTM1 null genotype along with CYP19A1 C allele, there is a significant association with female infertility risk (OR 7.023; 95% CI (3.627-13.601; p < 0.001), and, also for carriers of GSTT1 null genotype along with the CYP19A1 TC/CC genotype (OR 24.150; 95% CI (11.148-52.317; p < 0.001). A positive association with female infertility risk for carriers of the C allele in CYP19A1 and null genotypes in GTSM1 (OR 11.979; 95% CI (4.570-31.400; p < 0.001) or GSTT1 (OR 13.169; 95% CI (4.518-38.380; p < 0.001) was found. When both GSTs are deleted, the risk of developing female infertility is significant, independently of the CYP19A1 genotype; when all the presumed high-risk genotypes are present, we found a significant association with female infertility risk (OR 47,914; 95% CI (14,051-163,393; p < 0.001).

The Ala307Thr polymorphism of the follicle-stimulating hormone receptor (FSHR) gene is associated with the dose of recombinant FSH received during IVF/ICSI treatment.

OBJECTIVE: Follicle-stimulating hormone (FSH) is essential for folliculogenesis, acting through the follicle-stimulating hormone receptor (FSHR) that is present on the membrane of granulosa cells. Polymorphisms in the FSHR gene may lead to an altered pattern of receptor expression on the cell surface or to changes in affinity for FSH. The aim of this prospective study was to detect any association between the follicle-stimulating hormone receptor (FSHR) gene Ala307Thr polymorphism (rs6165) and ovarian reserve, ovarian response or clinical results in IVF/ICSI treatment. METHODS: This prospective cohort study included 450 women who underwent IVF/ICSI cycles. DNA was extracted from peripheral blood, and the Ala307Thr FSHR polymorphism (rs6165) was genotyped using the TaqMan SNP genotyping assay. Participants were divided into three groups according to their Ala307Thr FSHR genotype: Thr/Thr (n:141), Thr/Ala (n=213) and Ala/Ala (n=96). The results were tested for associations with age, anti-Mullerian hormone (AMH) levels, antral follicle count (AFC), total dose of r-FSH, follicle size, number of retrieved oocytes, and clinical outcome of IVF/ICSI cycles. The statistical analyses were performed using Fisher's exact test and the Kruskal‒Wallis test. RESULTS: An association between the genotype of the FSHR (Ala307Thr) polymorphism and the dose of r-FSH was observed. Patients with the Ala/Ala genotype received a higher r-FSH dose than patients with the Ala/Thr (p=0.0002) and Thr/Thr (p=0.02) genotypes. No other correlation was observed. CONCLUSION: The Ala/Ala genotype was associated with the use of higher doses of recombinant FSH (r-FSH), suggesting that homozygosis of this allelic variant (Ala) provides lower sensitivity to r-FSH.

Cell-Free DNA as a New Biomarker of IVF Success, Independent of Any Infertility Factor, Including Endometriosis.

Cell-free DNA fragments detected in blood and in other biological fluids are released from apoptotic/necrotic cells. In this study, we analyzed cfDNA levels in follicular fluid (FF) samples from patients with infertility. Samples were collected from 178 infertile women and cfDNA was extracted and quantified by qPCR, using ALU115 and ALU247 primers, and statistical correlations were performed. We found that cfDNA concentration was significantly higher in FF pools from women aged 35 and over than in women under 35 years of age (p = 0.017). We also found that q247 cfDNA levels were significantly higher in women with an associated female factor, such as endometriosis, PCOS and POF, compared with women with no specific cause of infertility (p = 0.033). The concentration of cfDNA did not vary significantly in each group of women with an associated female factor. The concentration of cfDNA was significantly higher in the FF of women that obtained embryos with a high fragmentation rate, compared to embryos with a low fragmentation rate (p = 0.007). Finally, we found that women who did not become pregnant during IVF treatments had higher q247 cfDNA levels (p = 0.043). The quantification of cfDNA could be an important biomarker of follicular micro-environment quality to predict embryo quality and the success of IVF, making them more specific and effective.

Volatilomics as an Emerging Strategy to Determine Potential Biomarkers of Female Infertility: A Pilot Study.

Due to its high prevalence, infertility has become a prominent public health issue, posing a significant challenge to modern reproductive medicine. Some clinical conditions that lead to female infertility include polycystic ovary syndrome (PCOS), endometriosis, and premature ovarian failure (POF). Follicular fluid (FF) is the biological matrix that has the most contact with the oocyte and can, therefore, be used as a predictor of its quality. Volatilomics has emerged as a non-invasive, straightforward, affordable, and simple method for characterizing various diseases and determining the effectiveness of their current therapies. In order to find potential biomarkers of infertility, this study set out to determine the volatomic pattern of the follicular fluid from patients with PCOS, endometriosis, and POF. The chromatographic data integration was performed through solid-phase microextraction (SPME), followed by gas chromatography-mass spectrometry (GC-MS). The findings pointed to specific metabolite patterns as potential biomarkers for the studied diseases. These open the door for further research into the relevant metabolomic pathways to enhance infertility knowledge and diagnostic tools. An extended investigation may, however, produce a new mechanistic understanding of the pathophysiology of the diseases.

Follicular Fluid: A Powerful Tool for the Understanding and Diagnosis of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) represents one of the leading causes of anovulatory infertility and affects 5% to 20% of women worldwide. Until today, both the subsequent etiology and pathophysiology of PCOS remain unclear, and patients with PCOS that undergo assisted reproductive techniques (ART) might present a poor to exaggerated response, low oocyte quality, ovarian hyperstimulation syndrome, as well as changes in the follicular fluid metabolites pattern. These abnormalities originate a decrease of Metaphase II (MII) oocytes and decreased rates for fertilization, cleavage, implantation, blastocyst conversion, poor egg to follicle ratio, and increased miscarriages. Focus on obtaining high-quality embryos has been taken into more consideration over the years. Nowadays, the use of metabolomic analysis in the quantification of proteins and peptides in biological matrices might predict, with more accuracy, the success in assisted reproductive technology. In this article, we review the use of human follicular fluid as the matrix in metabolomic analysis for diagnostic and ART predictor of success for PCOS patients.

Evaluation of Protocols of Controlled Ovarian Stimulation in Obtaining Mature Oocytes (MII): Retrospective Study on Assisted Reproductive Technology Procedures.

OBJECTIVE: To understand which of the controlled ovarian stimulation (COS) protocols used in different patients are associated with greater amounts of oocytes retrieved. METHODS: The study population was divided into three groups, considering AMH and AFC to obtain the Ovarian Response Predictor Index (ORPI); they were grouped into: G1-Low Reserve (ORPI <0.5); G2-Normal Reserve (ORPI:0.5-0.9); and G3-High Reserve (ORPI≥0.9). 246 cycles were selected in which COS was used: recombinant FSH - follitropin alfa or beta (Protocol 1) or corifollitropin alfa (Protocol 2), both associated with urinary HMG and the GnRH antagonist, with the trigger performed using recombinant hCG or GnRH agonist. RESULTS: The number of oocytes obtained was higher in protocol 1 in all groups, with higher counts seen in G1 than in G2 or G3. The number of days required in COS for protocol 2 was greater than for protocol 1 in all groups. The total dose of recombinant FSH alfa or beta / urinary HMG used in protocol 1 was inversely proportional to the ovarian reserve. The lower the ORPI, the greater the average number of international units administered. In protocol 2, there was a need to supplement with higher doses of urinary HMG when compared to protocol 1. The dosage of the GnRH antagonist was dependent on the number of COS days until the trigger was used. In obtaining MII oocytes, the percentages were similar regardless of the trigger used. CONCLUSIONS: The use of follitropin leads to greater numbers of retrieved oocytes than corifollitropin alfa in all ORPIs. The dose of recombinant FSH used with urinary HMG increases inversely proportional to the ORPI value. The fixed dose of recombinant FSH deposit requires a sharp increase in the dose of urinary HMG.

Correlation of TP53 (rs1625895), TP73 (rs3765730), MMP9 (rs17576), and MTHFR (rs868014) polymorphisms with low ovarian reserve.

OBJECTIVE: To investigate the influence of the Single Nucleotide Polymorphisms (SNPs) TP53 rs1625895, TP73 rs3765730, MMP9 rs17576, and MTHFR rs868014 on ovarian reserve (OR) in infertile patients. STUDY DESIGN: A prospective cross-sectional study was carried out in 145 infertile women. The patients were divided into two groups according to ovarian reserve, characterized by association between AMH levels and AFC:After patient distribution, both groups were compared (LOR X NOR) regarding the genotypes of the SNPs TP53 T/C rs1625895, TP73 G/A rs3765730, MMP9 Gln/Arg rs17576, and MTHFR A/G rs868014. RESULT(S): The frequency of the TP53-T/T genotype was greater in the LOR and the TP53-C/C genotype was more frequent in patients with NOR. This association was confirmed by the frequency of alleles, where the presence of the T allele was significantly higher in patients who exhibited LOR (P = 0.0003). The frequency of the TP73-G/G genotype and of the G allele was higher in the LOR group (P = 0.01). Considering the MMP9 gene, the frequency of the Gln/Gln genotype was higher in the LOR group. However, the Gln/Arg genotype and the Arg allele prevailed in the NOR group (P = 0.006). The frequency of the MTHFR-A/A genotype was higher in the LOR group, whereas that of the MTHFR-GG genotype was higher in the NOR group. The presence of allele A was significantly higher in the LOR group (P = 0.002). The regression analysis shows that patients who present the TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A genotypes are 3.6X, 3.1X, 3.2X, and 3.7X more likely of having LOR, respectively. In addition, the association of the TP53/TT + TP73/GG genotypes increased the chance of women being included in the LOR group in 5.7-fold. CONCLUSION(S): The genotypes TP53-T/T, TP73-G/G, MMP9-Gln/Gln, and MTHFR-A/A increase the chance of women to exhibit LOR. These polymorphisms could be useful as genetic markers of low ovarian reserve in infertile patients.

Impact of Intracytoplasmic Morphologically Selected Sperm Injection (IMSI) on Birth Defects: A Systematic Review and Meta-Analysis.

OBJECTIVE: It is generally accepted that the incidence of birth defects in spontaneously conceived children ranges between 2.0-4.0%. However, several studies have shown that babies born after assisted reproductive technology (ART) procedures tend to present more congenital malformations than naturally conceived children, with 6.5% of the children born after intracytoplasmic sperm injection (ICSI) presenting birth defects. The use of high magnification sperm selection before ICSI was introduced in the early 2000s to allow the identification of spermatozoa with low risk of sperm DNA damage. Intracytoplasmic morphologically selected sperm injection (IMSI) is expected to change the incidence of congenital malformations, although data on the incidence of birth defects in children conceived after IMSI are still scarce. METHODS: A systematic review based on searches performed in electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials) including articles published by February 2021 was conducted to identify trials comparing the neonatal outcomes of ICSI and IMSI. The outcome measured was the rate of birth defects in children born after ICSI or IMSI. Three trials were included as targets for data extraction and meta-analysis. RESULTS: Our meta-analysis included 3907 children conceived after IMSI (1280) or ICSI (2627). The incidence of birth defects was statistically different, with 2.5% (32/1280) in IMSI and 4.5% (119/2627) in ICSI (RR=0.59; 95% CI=0.40-0.87; p=0.007). The results demonstrated that IMSI decreased the incidence of structural defects compared to ICSI - 2.2% (18/830) vs. 3.8% (78/2049) - in a statistically significant manner (RR=0.58; 95%CI=0.35-0.96; p=0.04). No significant difference was observed in chromosomal abnormalities (Trisomy 13; 18; 21 and Triple X) between children conceived after IMSI (8/830) or ICSI (19/2049) (RR=1.07; 95%CI=0.47-2.43; p=0.87). CONCLUSIONS: IMSI seems to be an effective tool at reducing the incidence of structural defects compared to ICSI. However, IMSI does not change the incidence of chromosomal abnormalities.

Continuous endometrial volumetric analysis for endometrial receptivity assessment on assisted reproductive technology cycles.

BACKGROUND: Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. In order to assess endometrial receptivity in Assisted Reproductive Technology (ART) cycles serial evaluation of endometrial volumetric analysis may have a predictive value on a positive outcome. METHODS: Serial 3D transvaginal ultrasound performed in women on ART cycle to evaluate embryo implantation predictors. Prospective case control study of 169 subjects were assessed. Endometrial pattern, thickness, volume and adjusted endometrial volume (ratio between endometrial volume and uterine volume) was performed to all subjects on a continuous process from baseline, during controlled ovarian stimulation, trigger day with human chorionic gonadotropin hormone (hCG) and at embryo transfer day. RESULTS: Demographics and ART procedures and scores, was similar between the two groups. Endometrial morphology also showed no difference between the two groups. Endometrial volume and adjusted endometrial volume was significantly higher in the positive group as soon as day 6 of ovarian controlled stimulation. CONCLUSIONS: Serial 3D endometrial volume and adjusted endometrial volumes provides a predicting clinical tool enhancing elective embryo transfers in fresh ART cycle. Thus providing a non-invasive continuous technique for endometrial receptivity assessment that reflects endometrial changes during ART procedures.

Women with polycystic ovary syndrome and other causes of infertility have a higher prevalence of GSTT1 deletion.

RESEARCH QUESTION: Is GSTM1 and GSTT1 deletion associated with the development of polycystic ovary syndrome (PCOS)? DESIGN: A case-control study was designed to investigate the association between GSTM1 and GSTT1 gene polymorphisms with PCOS. Blood samples from 201 women diagnosed with infertility were taken, of which 69 women were diagnosed with PCOS. Genomic DNA was extracted, and genotyping analyses were conducted by polymerase chain reaction-based methods. Odds ratios and 95% confidence intervals were calculated by unconditional logistic regression. RESULTS: An increased risk of PCOS was found to be associated with GSTT1 null genotype (OR 4.890, 95% CI 2.261 to 9.122; P < 0.001). A strong association between GSTT1 null genotype was found with female infertility, regardless of the associated cause (OR 5.300, 95% CI 3.238 to 8.675; P < 0.001) as well as with the GSTM1 null genotype (OR 1.620, 95% CI 1.067 to 2.459; P = 0.026). A statistically significant association with the development of infertility was also found when carriers of the combined genotype GSTT1+/GSTM1+ was compared with carriers of the combined genotype GSTT1-/ GSTM1+ (OR 3.600 95% CI 1.864 to 6.956; P < 0.001). The two-way combination of GSTT1 and GSTM1 null genotypes resulted in an increased susceptibility to infertility development (OR 11.136; 95% CI 5.035 to 24.629; P < 0.001). CONCLUSIONS: Carriers of GSTT1 null genotype seem to have higher susceptibility to developing PCOS and infertility from other causes. Also, GSTT1 null genotype, alone or in association, are related with increased susceptibility to infertility development, independently of its cause. GSTM1 null genotype is only associated with all cause of infertility when the GSTT1 is null.

Relationship between age and blastocyst chromosomal ploidy analyzed by noninvasive preimplantation genetic testing for aneuploidies (niPGT-A).

OBJECTIVE: To assess the relationship between human blastocyst chromosomal ploidy established by niPGT-A and increasing age. METHODS: This is a prospective multicenter study carried out by ten assisted reproduction centers after their embryologists acquired training and validated their results with the previous use of niPGT-A. A total of 94 couples with indication for niPGT-A due to increase maternal age, male factor, repeated implantation failures, recurrent abortion or because they requested niPGT-A were included in this study. The couples had no karyotype abnormalities. After ICSI, the embryos were cultured until blastocyst stage using one or two step culture systems, single or sequential media respectively, at 37°C in an atmosphere of 6-7% CO2 and 5-20% O2 incubators. On day 3, we re-evaluated cleavage embryos to complete cumulus cells removal. The embryos were then cultured in individual well, with 20µl of medium under oil until they reached blastocyst stage. The blastocysts were vitrified and stored in liquid nitrogen. After that, the spent blastocyst culture medium (20µl) was transferred to a PCR tube and sent for analysis in the genetic laboratory, where it was stored at -80°C until sequencing. A total of 243 samples of spent blastocyst culture medium were collected on the 5th/6th day. Cell-free DNA secreted on culture medium was amplified using NICS Sample Preparation Kit (Yikon Genomics), based on the MALBAC technology. After whole genome amplification, the DNA was measured using a Qubit 2.0 fluorometer and subjected to next generation sequencing (NGS) using Illumina MiSeq® platform. The data were analyzed using the ChromGo® software (Yikon Genomics). RESULTS: The mean age of the patients was 38±4.08 years with an interval of 20-44 years. The euploid was diagnosed in 36.4% (80/220) of cases, aneuploidy in 31.3% (69/220), and mosaicism in 32.3% (71/220; with ≥60% aneuploidy) of blastocysts. Mosaic values ranged from 29.8% to 33.8% in different age groups. Individually, the most frequent chromosomal abnormality was XXY (Klinefelter Syndrome) occurring in 18 cases, followed by chromosome 21 (trisomy/monosomy) in 8 cases. The niPGT-A data showed a ≥60% incidence of aneuploid cells in all cases of chromosomal mosaicism (n=71). CONCLUSION: A high degree of mosaicism with aneuploidy cells was detected, and some hypotheses were suggested for this data (niPGT-A sensitivity in detecting the self-correction of chromosomal abnormalities phenomenon). However, it did not vary remarkably with age. On the other hand, euploidy levels had a negative correlation with age and aneuploidy levels had a positive relationship. This is the first report in the literature to relate chromosomal ploidy in blastocysts using niPGT-A and increasing patient age.

The involvement of annexin A1 in human placental response to maternal Zika virus infection.

The association of Zika virus infection (ZIKV) with congenital malformation and neurological sequelae brought a significant global concern. Recent studies have shown that maternal viral infection leads to inflammation in the placental tissue. In this context, the antiinflammatory protein annexin 1 (ANXA1) has a major determination of the resolution of inflammation and it has been positively associated with antiparasitic activity in infected placental explants. Although these effects have been explored to some degree, ANXA1 expression and potential properties have not yet been fully elucidated in placentas infected with ZIKV. This study was conducted to evaluate the histopathology, inflammatory process and elucidate if ANXA1 were differently expressed in placentas of ZIKV-infected mothers. Three classification groups were used in this study: Neg/Neg (mother and placenta negative for the virus), Pos/Neg (infected mother, but no virus detected in placenta) and Pos/Pos (mother and placenta infected with ZIKV). ANXA1 was expressed in syncytiotrophoblast cells of all studied groups, and its expression was decreased in Pos/Neg group, which displayed also an increase of the inflammatory response, as evinced from the recruitment of inflammatory cells, increased levels of placenta cytokines, and evidence of impaired tissue repair. The presence of ZIKV in placentas of Pos/Pos group shows structural alterations, including detachment and disorganization of the trophoblastic epithelium. In summary, our results suggest that maternal infection with ZIKV, even without direct tissue infection, leads to a placental inflammatory response probably related to the modulation of ANXA1. After placental infection, structural changes - including inflammatory cells influx - are observed leading to placental dysfunction and reduced fetal weight. Our study sheds additional light on the outcomes of ZIKV infection in trophoblast and reveals a potential involvement of ANXA1 in the placental biology.

FUT3 and FUT2 genotyping and glycoconjugate profile Lewisb as a protective factor to Toxoplasma gondii infection.

The interaction between the ABO, FUT2 and FUT3 genes results in the synthesis of different glycoconjugates profiles expressed in gastrointestinal tract. Moreover, the protozoan Toxoplasma gondii, which causes toxoplasmosis, utilizes this organ as an infection route. We analyzed the frequencies of the different glycoconjugate profiles which were determined by phenotyping ABO and genotyping the status secretor (FUT2; substitution G428A) and Lewis (FUT3; substitution T202C and C314T) histo-blood systems, assessed by PCR-RFLP and PCR-SSP, respectively. A total of 244 pregnant women (G1: Seropositive; G2: Seronegative) for IgG T. gondii antibodies were enrolled. IgG anti-T. gondii antibodies were determined by ELISA. G1 was composed of 158 (64.8%) sample and G2 by 86 (36.2%). The glycoconjugate profile was accessed in 151 seropositive and 85 seronegative samples by the combination of ABO and Lewis phenotyping as well as FUT2 and FUT3 genotyping. In G1, 36 (22.8%) presented the glycoconjugate profile ALeb, 5 (3.3%) A, 13 (8.6) BLeb, 1 (0.6%) B, 41 (27.1%) Leb, 13(8.6%) H, 38(25.2%) Lea and 4 (2.6%) Lec. G2 was composed of 13 (15.3%) of ALeb, 15 (17.6%) BLeb, 1 (1.2%) B, 42 (49,4%) Leb and 14 (16.5) Lea. H and Lec glycoconjugate profiles were not found in G2. The frequencies of the glycoconjugates profiles Leb (p = 0.001) and H (p = 0.005) were significantly different compared between G1 and G2. The glycoconjugate profile H inferred from the ABO phenotyping and FUT3 and FUT2 genotyping is associated with infection by T. gondii in pregnant women and the Leb profile appears to protect the infection by this parasite.

Zika-virus-infected human full-term placental explants display pro-inflammatory responses and undergo apoptosis.

Zika virus (ZIKV) is a flavivirus that has been highly correlated with the development of neurological disorders and other malformations in newborns and stillborn fetuses after congenital infection. This association is supported by the presence of ZIKV in the fetal brain and amniotic fluid, and findings suggest that infection of the placental barrier is a critical step for fetal ZIKV infection in utero. Therefore, relevant models to investigate the interaction between ZIKV and placental tissues are essential for understanding the pathogenesis of Zika syndrome. In this report, we demonstrate that explant tissue from full-term human placentas sustains a productive ZIKV infection, though the results depend on the strain. Viral infection was found to be associated with pro-inflammatory cytokine expression and apoptosis of the infected tissue, and these findings confirm that placental explants are targets of ZIKV replication. We propose that human placental explants are useful as a model for studying ZIKV infection ex vivo.

Novel multidisciplinary approach to monitor and treat fetuses with gastroschisis using the Svetliza Reducibility Index and the EXIT-like procedure / Nova abordagem multidisciplinar para monitorizar e tratar fetos com gastrosquise utilizando o Svetliza Reducibility Index e o procedimento EXIT-like

ABSTRACT Objective: To describe our initial experience with a novel approach to follow-up and treat gastroschisis in "zero minute" using the EXITlike procedure. Methods: Eleven fetuses with prenatal diagnosis of gastroschisis were evaluated. The Svetliza Reductibility Index was used to prospectively evaluate five cases, and six cases were used as historical controls. The Svetliza Reductibility Index consisted in dividing the real abdominal wall defect diameter by the larger intestinal loop to be fitted in such space. The EXIT-like procedure consists in planned cesarean section, fetal analgesia and return of the herniated viscera to the abdominal cavity before the baby can fill the intestines with air. No general anesthesia or uterine relaxation is needed. Exteriorized viscera reduction is performed while umbilical cord circulation is maintained. Results: Four of the five cases were performed with the EXIT-like procedure. Successful complete closure was achieved in three infants. The other cases were planned deliveries at term and treated by construction of a Silo. The average time to return the viscera in EXIT-like Group was 5.0 minutes, and, in all cases, oximetry was maintained within normal ranges. In the perinatal period, there were significant statistical differences in ventilation days required (p = 0.0169), duration of parenteral nutrition (p=0.0104) and duration of enteral feed (p=0.0294). Conclusion: The Svetliza Reductibility Index and EXIT-like procedure could be new options to follow and treat gastroschisis, with significantly improved neonatal outcome in our unit. Further randomized studies are needed to evaluate this novel approach.

RESUMO Objetivo: Descrever a experiência inicial com a nova técnica cirúrgica EXIT-like para acompanhamento e correção de gastrosquise no "minuto zero". Métodos: Foram avaliados onze fetos com diagnóstico pré-natal de gastrosquise. O Svetliza Reducibility Index foi usado prospectivamente para avaliar cinco casos, e seis foram utilizados como controles. O índice foi calculado dividindo-se o diâmetro do defeito da parede abdominal pela maior alça intestinal que coubesse neste espaço. O procedimento EXIT-like compreendeu cesárea programada, analgesia fetal e redução da víscera herniada para a cavidade abdominal, antes da deglutição de ar pelo recém- nascido. Não são necessários anestesia geral e nem relaxamento uterino. A redução da víscera exteriorizada é realizada enquanto se mantém a circulação do cordão umbilical. Resultados: Quatro casos, dos cinco, foram submetidos ao EXIT-like. A correção foi completa em três casos. Os demais casos foram partos a termo planejados, e a correção do defeito foi feita com Silo. O tempo médio de redução da víscera foi de 5,0 minutos no grupo submetido ao procedimento EXITlike, e a oximetria foi mantida dentro dos valores de variação normal em todos os casos. No período perinatal, foram observadas diferenças estatisticamente significativas no tempo de ventilação mecânica (p=0,0169), duração da nutrição parenteral (p = 0,0104) e da nutrição enteral (p=0,0294). Conclusão: O Svetliza Reducibility Index e o procedimento EXIT-like podem ser novas opções para acompanhar e tratar gastroquise, com desfecho neonatal significativamente melhor em nossa unidade. Novos estudos randomizados são necessários para avaliar esta nova abordagem.

Long-Term Viruria in Zika Virus-Infected Pregnant Women, Brazil, 2016.

During the 2016 Zika virus outbreak in Brazil, we detected Zika virus RNA in urine samples collected from Zika virus-positive pregnant women during different stages of pregnancy. Women had positive and negative intervals of viruria; 3 newborns had adverse outcomes. Further research is needed to clarify the relationship between viruria and outcomes for newborns.

Novel multidisciplinary approach to monitor and treat fetuses with gastroschisis using the Svetliza Reducibility Index and the EXIT-like procedure.

OBJECTIVE: To describe our initial experience with a novel approach to follow-up and treat gastroschisis in "zero minute" using the EXITlike procedure. METHODS: Eleven fetuses with prenatal diagnosis of gastroschisis were evaluated. The Svetliza Reductibility Index was used to prospectively evaluate five cases, and six cases were used as historical controls. The Svetliza Reductibility Index consisted in dividing the real abdominal wall defect diameter by the larger intestinal loop to be fitted in such space. The EXIT-like procedure consists in planned cesarean section, fetal analgesia and return of the herniated viscera to the abdominal cavity before the baby can fill the intestines with air. No general anesthesia or uterine relaxation is needed. Exteriorized viscera reduction is performed while umbilical cord circulation is maintained. RESULTS: Four of the five cases were performed with the EXIT-like procedure. Successful complete closure was achieved in three infants. The other cases were planned deliveries at term and treated by construction of a Silo. The average time to return the viscera in EXIT-like Group was 5.0 minutes, and, in all cases, oximetry was maintained within normal ranges. In the perinatal period, there were significant statistical differences in ventilation days required (p = 0.0169), duration of parenteral nutrition (p=0.0104) and duration of enteral feed (p=0.0294). CONCLUSION: The Svetliza Reductibility Index and EXIT-like procedure could be new options to follow and treat gastroschisis, with significantly improved neonatal outcome in our unit. Further randomized studies are needed to evaluate this novel approach.

Value of the Ultrasound in the Study of Ovarian Reserve for Prediction of Oocyte Recovery.

Purpose To identify which methods used in the assessment of the ovarian reserve are exclusive or complementary to identify the best response to follicle development. Methods Retrospective cohort study, involving patients undergoing assisted reproduction treatment at the Instituto de Medicina Reprodutiva e Fetal, from April 2009 to July 2014. Age, biochemical tests, and ultrasound were assessed. The data were analyzed to predict the follicular development and the relation between them, using, for statistical analysis, Statistical Package for Social Sciences software. Results Out of the 293 couples included, 50.2% presented infertility by ovarian factor. Considering the age as the main variable, a significant negative correlation with the volume of both ovaries was observed (right ovary, r = 0.21; left ovary, r = -0.22; both p < 0.0001), and with the antral follicle count (right ovary, r = -0.38; left ovary, r = -0.47; both p < 0.0001). Considering the antral follicle count as the main variable, a significant positive correlation with the total recruited oocytes was observed. When we correlated the antral follicle count with the recruited follicles larger than 18 mm, we observed that, with a cutoff of 12 antral follicles, there is a positive predictive value of 99%, and an area under the ROC curve of 0.76. Conclusion We concluded from our study that age and antral follicle count are effective predictors of ovarian response in cycles of assisted reproduction. The ovarian volume, as well as the anti-Müllerian hormone dosage, seem to be adequate markers of the ovarian reserve.

Value of the Ultrasound in the Study of Ovarian Reserve for Prediction of Oocyte Recovery / Valor da ecografia no estudo da reserva ovariana para predição da recuperação oocitária

Abstract Purpose To identify which methods used in the assessment of the ovarian reserve are exclusive or complementary to identify the best response to follicle development. Methods Retrospective cohort study, involving patients undergoing assisted reproduction treatment at the Instituto de Medicina Reprodutiva e Fetal, from April 2009 to July 2014. Age, biochemical tests, and ultrasound were assessed. The data were analyzed to predict the follicular development and the relation between them, using, for statistical analysis, Statistical Package for Social Sciences software. Results Out of the 293 couples included, 50.2% presented infertility by ovarian factor. Considering the age as the main variable, a significant negative correlation with the volume of both ovaries was observed (right ovary, r = 0.21; left ovary, r =0.22; both p< 0.0001), and with the antral follicle count (right ovary, r =0.38; left ovary, r =0.47; both p< 0.0001). Considering the antral follicle count as the main variable, a significant positive correlation with the total recruited oocytes was observed. When we correlated the antral follicle count with the recruited follicles larger than 18 mm, we observed that, with a cutoff of 12 antral follicles, there is a positive predictive value of 99%, and an area under the ROC curve of 0.76. Conclusion We concluded from our study that age and antral follicle count are effective predictors of ovarian response in cycles of assisted reproduction. The ovarian volume, as well as the anti-Müllerian hormone dosage, seem to be adequate markers of the ovarian reserve.

Resumo Objetivo Identificar quais métodos utilizados na avaliação da reserva ovariana são excludentes ou complementares na identificação da melhor resposta ao desenvolvimento folicular. Métodos Estudo retrospectivo de coorte, que envolveu pacientes em tratamento de reprodução assistida no Instituto de Medicina Reprodutiva de abril de 2009 a julho de 2014. Foram avaliadas idade, exames bioquímicos e ecografia. Os dados foram analisados na predição do desenvolvimento folicular e nas suas relações entre si, utilizando para análise estatística o programa Statistical Package for Social Sciences. Resultados Dos 293 casais incluídos, 50,2% apresentavam infertilidade por fator ovariano. Considerando a idade como principal variável, foi observada uma correlação significativa e negativa com volume de ambos ovários (ovário direito, r = 0,21; ovário esquerdo, r =0,22; ambos p< 0,0001), e com contagem de folículos antrais (ovário direito, r =0,38; ovário esquerdo, r =0,47; ambos p< 0,0001). Considerando a contagem de folículos antrais como a variável principal, foi observada uma correlação significativa e positiva com o total de oócitos recrutados. Quando correlacionamos a contagem de folículos antrais com os folículos recrutados maiores do que 18 mm, observamos que, com um ponto de corte de 12 folículos antrais, tem-se um valor preditivo positivo de 99%, e uma área da curva ROC de 0,76. Conclusões Concluímos com nosso trabalho que a idade e a contagem de folículos antrais são eficientes preditores da resposta ovariana em ciclos de reprodução assistida. O volume ovariano, assim como a dosagem do hormônio anti-mulleriano, parecem ser marcadores adequados de reserva ovariana.

Fetal Infection by Zika Virus in the Third Trimester: Report of 2 Cases.

Zika virus (ZIKV) infection acquired during pregnancy is associated with congenital microcephaly. We describe 2 cases of ZIKV infection in women in their 36th week of pregnancy whose fetuses had preserved head circumference at birth and findings of subependymal cysts and lenticulostriate vasculopathy in postnatal imaging. These represent the first signs of congenital brain injury acquired due to ZIKV in the third trimester.