Delphi consensus on add-ons and social midia in Assisted Reproductive Technology.

This article reports the annals of a national consensus meeting on add-ons and social networks in Assisted Reproduction Techniques (ART). The panel of experts has developed a set of consensus points and this document is intended to be referenced as a national consensus to allow social networks and add-ons to be used in ART, following the standards of the Code of Medical Ethics and the Federal Council of Medicine, in a safe ethical and responsible way.

Association of BMP15 and GDF9 variants to premature ovarian insufficiency.

PURPOSE: To identify genetic variation associated to premature ovarian insufficiency (POI). METHODS: A total of 74 women with POI (group POI), 45 women with increased FSH levels (group high FSH), and 88 controls (non-POI) were studied. Genotyping of BMP15:c.-9C>G (rs3810682), BMP15:c.328+905A>G (rs3897937), and BMP15:c.852C>T (rs17003221); and GDF9:c.134-694G>A (rs4705974), GDF9:c.-31-951G>A (rs11748063), GDF9:c.-152G>C (rs30177), and GDF9:g.1073C>T (rs803224) was performed by the TaqMan methodology. Chi-square and Fisher's exact tests were performed to evaluate the distribution of genotypes, alleles, odds ratio, and the Hardy-Weinberg equilibrium of each variation. Haplotype analysis was performed for each gene considering the case and control groups. Bonferroni's correction was applied to chi-square and Fisher's exact test data, and p values < 0.007 for genotypes and alleles and < 0.006 for haplotypes were considered significant. RESULTS: It was observed a statistically significant difference in genotype distribution of BMP15:c.852C>T between group POI and controls (p < 0.001). TT and TC genotypes were more frequently observed in group POI. Genotype distribution in case group POI, however, was not in the Hardy-Weinberg equilibrium, due to the increased number of heterozygotes in the sample. Concerning GDF9, no association was found among the studied genetic variants and POI or high FSH groups. CONCLUSION: It is concluded from the present study that the genotypes CT and TT from BMP15:c.852C>T variation may be risk factors for the development of POI.

Next Generation Sequencing (NGS) in chromosome translocation 46, XX, t (9; X) (q22; q28) - a case report.

This paper reports the case of a patient who sought assisted reproductive technology (ART) treatment and was referred to pre-implantation genetic diagnosis (PGD) on account of a chromosomal translocation presented with secondary infertility. The patient underwent a highly complex ART treatment and had 14 metaphase II oocytes collected on the day of follicular aspiration. The embryos were taken to extended culture and five were biopsied and vitrified. The embryo genetic report showed aneuploidy in four of the blastocysts, while the other resulted in 46, XX. In conclusion, chromosome translocations involving the X chromosome might result in the deregulation of gene expression and defective ovarian formation. Therefore, the genes present in the X chromosome are believed to be essential in normal ovarian function.

How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency.

OBJECTIVE: To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls. METHODS: A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software. RESULTS: Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide. CONCLUSION: There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

Progesterone level on the day of hCG administration in relation to the pregnancy rates of patients undergoing assisted reproduction techniques.

OBJECTIVE: To evaluate the predictive capacity for pregnancy of the progesterone level on the day of administering human chorionic gonadotropin, in women submitted to assisted reproductive techniques. METHODS: An observational study with 914 women submitted to assisted reproductive techniques from August 2014 to June 2016. RESULTS: Total pregnancy rate was 34.58%; in that, the pregnancy rate in women <35 years, between 35 and 38, and >38 years was, respectively, 42.3%, 38.7% and 16.1% (p<0.001). For embryo transfer in the same cycle, and progesterone of 1.3ng/dL, sensitivity was 4.78%, specificity, 84.18%, accuracy, 56.72%, positive likelihood ratio of 0.3019, and negative likelihood ratio of 1.1312, with receiver operating characteristic curve of 0.46 (95%CI: 0.42-0.49). CONCLUSION: The progesterone level on the day of administering human chorionic gonadotropin of 1.3ng/dL differs from that empirically adopted at the study site (1.7ng/dL), and has a better predictive capacity for pregnancy in the patients studied. However, the low sensitivity of this examination raises questions about its real importance.

How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency / Como os marcadores polimórficos contribuem para as doenças genéticas em diferentes populações? O estudo da inibina A para insuficiência ovariana prematura

ABSTRACT Objective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls. Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software. Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide. Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.

RESUMO Objetivo Verificar a incidência da mutação G679A no éxon 2 do gene da inibina alfa (INHA) em mulheres com amenorreia secundária e diagnóstico de insuficiência ovariana prematura e em controles. Métodos Uma amostra de 5mL de sangue periférico foi coletada de todos os participantes do estudo em tubo de EDTA e utilizada para a extração de DNA. Para o grupo de pacientes, foram coletados também 5mL de sangue em tubo contendo heparina para realização de cariótipo, e 5mL um tubo seco para dosagem de hormônio folículo-estimulante. As amostras de pacientes e controles foram inicialmente submetidas à análise da variante G679A no éxon 2 do gene INHA pela técnica de PCR-RFLP. As amostras de pacientes com insuficiência ovariana prematura após PCR-RFLP foram submetidas ao sequenciamento de Sanger dos éxons codantes 2 e 3. O sequenciamento foi realizado em equipamento ABI 3500 GeneticAnalyzer, e os resultados foram avaliados pelos programas SeqA and Variant Reporter. Resultados Foram avaliadas amostras de 70 mulheres com insuficiência ovariana prematura e de 97 controles férteis. A variante G769A foi encontrada em apenas uma paciente do Grupo Insuficiência Ovariana Prematura e em nenhum controle, e parece ser rara nas pacientes brasileiras com insuficiência ovariana prematura. Este polimorfismo foi previamente associado à insuficiência ovariana prematura em diversas populações no mundo. Conclusão O estudo evidenciou que há heterogeneidade genética quanto ao INHA em diferentes populações e entre as causas de insuficiência ovariana prematura.

Progesterone level on the day of hCG administration in relation to the pregnancy rates of patients undergoing assisted reproduction techniques / Valor da progesterona no dia do hCG em relação à taxa de gravidez de pacientes submetidas às técnicas de reprodução assistida

ABSTRACT Objective To evaluate the predictive capacity for pregnancy of the progesterone level on the day of administering human chorionic gonadotropin, in women submitted to assisted reproductive techniques. Methods An observational study with 914 women submitted to assisted reproductive techniques from August 2014 to June 2016. Results Total pregnancy rate was 34.58%; in that, the pregnancy rate in women <35 years, between 35 and 38, and >38 years was, respectively, 42.3%, 38.7% and 16.1% (p<0.001). For embryo transfer in the same cycle, and progesterone of 1.3ng/dL, sensitivity was 4.78%, specificity, 84.18%, accuracy, 56.72%, positive likelihood ratio of 0.3019, and negative likelihood ratio of 1.1312, with receiver operating characteristic curve of 0.46 (95%CI: 0.42-0.49). Conclusion The progesterone level on the day of administering human chorionic gonadotropin of 1.3ng/dL differs from that empirically adopted at the study site (1.7ng/dL), and has a better predictive capacity for pregnancy in the patients studied. However, the low sensitivity of this examination raises questions about its real importance.

RESUMO Objetivo Avaliar a capacidade preditiva para gravidez do valor de progesterona no dia da administração da gonadotrofina coriônica humana em mulheres submetidas às técnicas de reprodução assistida. Métodos Estudo observacional com 914 mulheres submetidas a reprodução assistida de agosto de 2014 até junho de 2016. Resultados Engravidaram 34,58% das mulheres, sendo a taxa de gravidez naquelas >35 anos, entre 35 e 38 anos e >38 anos, respectivamente, de 42,3%, 38,7% e 16,1% (p<0,001). Para o valor de progesterona até 1,3ng/dL visando à transferência embrionária no mesmo ciclo, encontraram-se sensibilidade de 4,78%, especificidade de 84,18%, acurácia de 56,72%, razão de verossimilhança positiva de 0,3019 e razão de verossimilhança negativa de 1,1312, com área sob a curva característica de operação do receptor de 0,46 (IC95%: 0,42-0,49). Conclusão O valor de progesterona no dia da administração de gonadotrofina coriônica humana até 1,3ng/dL difere daquele empiricamente adotado no local do estudo (1,7ng/dL) e apresenta melhor capacidade preditiva para gravidez nas pacientes estudadas. No entanto, a baixa sensibilidade deste exame abre questionamentos sobre sua real importância.

Are FSHR polymorphisms risk factors to premature ovarian insufficiency?

Premature ovarian insufficiency (POI) is an ovarian dysfunction characterized by increased FSH levels and amenorrhea before 40 years old. In recent years, the search for genetic causes of POI intensified and studies have been published relating the presence of mutations and polymorphisms in genes associated with development, recruitment and oocyte atresia. The aim of this study was to evaluate the presence of FSHR polymorphisms in our population and contribute with the elucidation of POI etiology. To achieve it, we have studied 100 patients with POI (G1), 60 patients with border line levels of FSH (G2) and 123 controls with regular menopause onset. Cytogenetic analysis of patients' samples and genotyping of Asn680Ser and Ala307Thr polymorphisms were performed in cases and controls. Cytogenetic analysis showed that 92% of G1 patients had normal karyotype, 4% presented polymorphic variants, 3% presented mosaic karyotype involving X chromosome. In G2, 91.6% had normal karyotype results, 3.2% displayed polymorphic variants, and 3.3% presented a mosaic karyotype involving X chromosome. Statistical comparison showed that the polymorphic allele of Ala307Thr polymorphism is more frequent in patients than in controls (G1: p < 0.001 and G2: p = 0.0259). This association has not been previously reported. We concluded that Ala307Thr polymorphism in FSHR can be potentially associated to POI development and can be considered as a screening marker in patients with ovarian failure signals.

AMH and AMHR2 polymorphisms and AMH serum level can predict assisted reproduction outcomes: a cross-sectional study.

BACKGROUND: In human assisted reproduction, the ovarian response to exogenous recombinant Follicle-stimulating Hormone (FSH) therapy is variable and difficult to predict. The standard protocol of ovarian hyperstimulation can result in satisfactory response; however, an unsatisfactory response necessitates FSH dose adjustment or results in ovarian hyperstimulation syndrome (OHSS). Polymorphisms in AMH and AMHR2 genes appear to affect hormone biological activities, thus affecting follicle recruitment and development, leading to infertility. We aimed to evaluate AMH and AMHR2 polymorphisms in infertile women, and correlate those findings with AMH, FSH and estradiol serum level response to controlled ovarian hyperstimulation (COH), as well as assisted reproduction outcomes. METHODS: A cross-sectional study comprising 186 infertile women that underwent one cycle of high complexity assisted reproductive treatment. Blood samples were collected and a TaqMan assay was used for AMH G146T/rs10407022 and AMHR2 A-482G/rs2002555, A10G/rs11170555, C1749G/rs2071558 and G4952A/rs3741664 genotyping, and FSH, estradiol and AMH levels were measured. The findings were correlated to human reproduction outcomes. RESULTS: AMH rs10407022 and AMHR2 rs2002555 polymorphisms were not associated with hormonal measurements, whereas AMHR2 rs11170555 and rs3741664 were positively associated with AMH, estradiol and FSH levels. The genotype distribution of AMH and AMHR2 genes according to Controlled Ovarian Hyperstimulation did not show a positive association. However, an association with AFC, degree of oocyte maturation (allele G of AMHR2 rs2071558) the number of embryos produced (alleles T and G of AMH rs10407022 and AMHR2 rs2002555, respectively) and frozen embryo (allele G of AMHR2 rs11170555) were found to be statistically associated. Considering COH, serum AMH and AFC were a positive predictor to OHSS. Regarding serum AMH and assisted reproduction outcomes, a positive correlation with all variables studied was found. Comparing AFC and AMH as predictors of human reproduction outcomes, the AFC was less effective than serum AMH. Considering pregnancy rates, no marker was positively associated. CONCLUSION: AMHR2 polymorphisms were associated with estradiol, AMH and FSH measurements, as well as number and quality of embryos, while AMH polymorphisms was associated with number of embryos produced. Serum AMH was correlated with nearly all variables analyzed in assisted reproductive treatment, demonstrating that it represents a better biomarker of OHSS and human reproduction outcomes compared to AMH and AMHR2 polymorphisms.

Oocyte Quality in Patients with Increased FSH Levels.

OBJECTIVE: The present study consists of quality comparison among oocytes retrieved from women under 37 years old showing increased levels of FSH (prone to premature ovarian insufficiency) and women at the same age with normal hormone levels. METHODS: Oocyte quality was accessed according to Lucinda L. Veeck parameters (1986) and the statistical analyses were carried out using Chisquared, SPSS for Windows 13.0 (SPSS, Inc., Chicago, IL). All pvalues were twotailed, and 95% confidence intervals (CIs) were calculated. A P value <0.05 was considered statistically significant. RESULTS: Eight morphologic changes variables were considered in the study and two of them showed statistically significant differences between cases and controls: granular cytoplasm (P=0.002) and presence of vacuoles (P=0.025), both more frequent among the study group patients. CONCLUSION: As a conclusion, patients with increased FSH levels presented oocytes with worst quality variables than controls. This can be an indicative of ovarian aging and can impact negatively on oocyte development into viable embryos.

ESR1 and ESR2 gene polymorphisms are associated with human reproduction outcomes in Brazilian women.

BACKGROUND: Important candidate genes involved in the ovarian response to exogenous FSH are the estrogen receptor genes (ESRs), since the effects of estrogens on follicle growth, maturation and oocyte release. It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, thus preventing excessive wear of the patient. Inspired on this information we aimed to analyze four different polymorphisms in the estrogen receptor genes ESR1: rs2234693/T-397C (PvuII) and rs9340799/A-351G (Xbal) and ESR2: rs4986938/G1082A (RsaI) and rs1256049/A + 1730G (AluI), and their association with assisted reproduction outcomes in Brazilian women that underwent in vitro fertilization (IVF). METHODS: A cross-sectional study was performed involving 136 infertile women less than 39 years of age with normal ovarian reserve. Patients were divided according to the same COH protocol for statistical analysis. The Taqman assay was used for PvuII and XbaI of ESR1, and RsaI and AluI of ESR2 genotyping. Serum estradiol and FSH were measured by Elisa assay. RESULTS: The PvuII (ESR1) TT and RsaI (ESR2) GG genotypes were associated with a longer induction period and higher doses of medication (p < 0.03). The XbaI (ESR1) AA genotype was associated with better COH results, including a larger number of follicles, mature oocytes, embryos, and good quality embryos (p < 0.05). The AluI GG genotype showed an association with the Ovarian Hyperstimulation Syndrome (OHSS) (p = 0.03). According to the haplotype analysis of ER1 (PvuII/XbaI), we demonstrated that the CA combination increases by 0.68 the number of good quality embryos while the TG decreases it by 0.71 (p = 0.04). CONCLUSION: ER polymorphisms have an association with the assisted reproduction outcomes in Brazilian women.

Ala307Thr and Asn680Ser polymorphisms of FSHR gene in human reproduction outcomes.

BACKGROUND/AIMS: It is known that some markers of ovarian stimulation can help to personalize the treatment, adjusting the dose of exogenous rFSH, thus preventing excessive wear of the patient. We aimed to evaluate Ala307Thr and Asn680Ser genotypes of the FSHR gene in infertile women and correlate the findings with the results of ovarian response and assisted reproduction outcomes. METHODS: Cross-sectional study covering 149 infertile women submitted to assisted reproduction treatment. Genotyping of FSHR variants were performed using TaqMan methodology by real time PCR. FSH and estradiol were measured by ELFA. The data was analyzed statistically. RESULTS: The frequencies of the FSHR Ala307Thr and Asn680Ser genotypes considering the ovarian hyper stimulation response also did not differ statistically. Considering assisted reproduction outcomes, we observed that the polymorphism Ala307Thr have a statistical difference for the number of MII oocytes and embryos (p=0,051 and p=0.037, respectively), which the genotype Ala/Ala showed more embryos. The polymorphisms did not determine the FSH and estradiol serum levels and the ovarian response in the assisted reproduction treatment. CONCLUSIONS: The polymorphisms Ala307Thr and Asn680Ser did not determine the FSH and estradiol serum levels and the ovarian response in the assisted reproduction treatment. However, we observed that the Ala307Thr may influence the number of embryos produced.

COMT polymorphism influences decrease of ovarian follicles and emerges as a predictive factor for premature ovarian insufficiency.

BACKGROUND: Estrogens are important factors in the female reproductive functions and are processed by a number of enzymes along their metabolic pathway. The COMT gene constitutes a crucial element in estrogen metabolism and is assumed to be involved in the development of Premature Ovarian Insufficiency (POI). This study aimed to determine whether the presence of the COMT Val/Met polymorphism (rs4680) is associated to the risk of developing POI. FINDINGS: In this case-control study, we evaluated 96 infertile women with POI and 120 fertile women as controls, after obtaining a detailed history of the disease and follicle-stimulating hormone measurements, besides karyotype determination and fragile-X premutation syndrome investigation. COMT (Val/Met) genotypes were identified by real time PCR (genotyping TaqMan assay), and the results were statistically analyzed. A statistically significant difference was found in the distribution of COMT genotypes (p = 0.003) and alleles (p = 0.015) between the POI patients and the control group. CONCLUSION: We were able to demonstrate a strong association between the COMT Val/Met polymorphism and the risk of premature ovarian insufficiency in the Brazilian women evaluated. However, further studies in larger populations are necessary to confirm these findings.

Low dose of rFSH [100 IU] in controlled ovarian hyperstimulation response: a pilot study.

BACKGROUND: The initial dose of recombinant Follicle Stimulating Hormone [rFSH] to be used in assisted reproduction treatment depends on several factors, mainly the cause of the infertility and the patient's age. For young patients [≤35 years] usually an initial dose of around 150 IU of rFSH is recommended, but there are no studies proving that this should actually be the standard initial dose. We aimed to report the experience of a low-cost Human Reproduction Center where a dose of 100 IU of rFSH was used for controlled ovarian hyperstimulation [COH]. FINDINGS: An observational prospective study was performed on 212 women aged ≤38 years old that underwent high-complexity assisted reproduction treatments. The patients' infertility was mainly caused by tuboperitoneal, idiopathic or male factors. Controlled ovarian stimulation was performed using 100 IU of rFSH. Regarding the COH, 53.8% of the patients presented a satisfactory response, 25.9% low response, 14.2% hyper-response, and 6.1% developed ovarian hyperstimulation syndrome. Of the 55 patients with poor response, 20 started a new cycle with an initial dose of 200 IU of rFSH; 65% showed a satisfactory response, 10% a poor response, 20% a hyper-response, and 5% developed OHSS. CONCLUSION: The initial dose of 100 IU of rFSH was considered adequate for controlled ovarian hyperstimulation, meeting the aim to reduce the costs of the assisted reproduction treatment.

Risk of premature ovarian failure is associated to the PvuII polymorphism at estrogen receptor gene ESR1.

PURPOSE: Estrogen plays an important role in the human reproductive system and it action is mediated mainly by two specific receptors: α (ERα) and ß (ERß). There were described polymorphic variants in ESR1 and ESR2 genes and studies showed controversial results regarding their association with premature ovarian failure. We aimed to determine the prevalence of ESR1 and ESR2 polymorphisms in Brazilian patients and controls. After associate the polymorphisms with premature ovarian failure (POF). METHODS: Genetic association study was performed with 70 women with POF and 73 normally menopaused controls. Detection of ESR1 (PvuII/and XbaI) and ESR2 (AluI and RsaI) gene polymorphisms were performed using TaqMan PCR. The single-nucleotide polymorphism (SNPs) and haplotype effects were analyzed by multivariate logistic regression and haplotype analysis and a p-value < 0.05 was considered significant. RESULTS: Individual SNP analysis revealed that PvuII polymorphism was statistically associated with POF (p = 0.034) under a recessive model. Regarding XbaI, AluI and RsaI SNPs, no statistical difference was observed between POF group and controls (p = 0.575, p = 0.258 and p = 0.483, respectively). Combined genotypes of ESR1 and ESR2 polymorphisms did not identify a risk haplotype associated with POF. CONCLUSION: In Brazilian population evaluated results have demonstrated that the genetic variation in ESR1 gene (PvuII polymorphism) is associated to POF risk.

Effect of acupuncture on symptoms of anxiety in women undergoing in vitro fertilisation: a prospective randomised controlled study.

PURPOSE: To determine if acupuncture improves symptoms of anxiety in infertile women undergoing in vitro fertilisation (IVF) treatment. METHODS: A randomised clinical trial was performed in 43 patients undergoing IVF. The patients were randomised into two groups: test group (n=22) and control group (n=21). The anxiety level of each patient was analysed before and after treatment using the Hamilton Anxiety Rating Scale (HAS). Treatment sessions consisted of four weekly sessions. In the test group, needles were inserted at points HT7, PC6, CV17, GV20 and Yintang. In the control group, needles were inserted in areas near but not corresponding to acupuncture points. RESULTS: The mean HAS score after the 4-week experimental period was significantly lower in the test group than in the control group (19.4 ± 3.2 vs 24.4 ± 4.2; p=0.0008). CONCLUSIONS: The results indicate that acupuncture can reduce anxiety symptoms observed by the reduction of psychological parameters of women undergoing IVF. Further evidence should be sought as to whether acupuncture might be a complementary option for patients undergoing IVF.

Genetic aspects of premature ovarian failure: a literature review.

BACKGROUND: The diagnosis of premature ovarian failure (POF) is based on the finding of amenorrhea before the age of 40 years associated with follicle-stimulating hormone levels in the menopausal range. It is a heterogeneous disorder affecting approximately 1% of women <40 years, 1:10,000 women by age 20 years and 1:1,000 women by age 30 years. POF is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). METHODS: Review of significant articles regarding genetic causes that are associated with POF. RESULTS: Heterogeneity of POF is reflected by a variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Changes at a single autosomal locus and many X-linked loci have been implicated in women with POF. X chromosome abnormalities (e.g., Turner syndrome) represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Many genes have been involved in POF development, among them BMP15, FMR1, FMR2, LHR, FSHR, INHA, FOXL2, FOXO3, ERα, SF1, ERß and CYP19A1 genes. CONCLUSION: Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of cases.

Cessão temporária de útero: aspectos éticos e ordenamento jurídico vigente / Surrogate motherhood: ethical aspects and established juridical order

Maternidade de substituição é a técnica de reprodução assistida que consiste na inseminação artificial ou fertilização in vitro, em que uma mulher (doadora) gera um bebê com intenção de entregá-lo para outra mulher (receptora), solicitante do procedimento. Apesar de ser uma prática antiga, com relatos de casos na Bíblia, não há, atualmente, legislação que regulamente a prática no Brasil. Há opiniões controversas por todo o mundo - entre os países que permitem a prática e os que a proíbem e ainda entre os que se mostram ambíguos frente ao assunto. Na tentativa de estabelecer critérios para a prática, o Conselho Federal de Medicina instituiu normas éticas no que diz respeito à gratuidade da doação e à necessidade de parentesco entre as partes, além de limitar os procedimentos às situações nas quais há um problema médico que impossibilite a solicitante de gerar um filho. Trata-se de uma situação complexa, envolvendo muitos indivíduos, além de ser uma questão não somente legal, mas sobretudo ética. Esta revisão visou estimular e dar subsídios à reflexão por parte dos médicos ginecologistas que se deparam com essa questão em seu dia a dia

Surrogate motherhood is an assisted reproduction technique that consists of artificial insemination or in vitro fertilization, in which a woman (donor) generates a child with the intention of giving his/her to another woman (receiver), who is the solicitant of the procedure. Although it is an ancient practice, with cases related in the Bible, it does not have, nowadays, a legislation that regulates its practice in Brazil. There are controversial opinions in the entire world: among countries that allow the practice and those that forbid it, besides the countries that are ambiguous about the subject. In the attempt to establish criteria for this practice, the Brazilian Federal Medical Council instituted ethical rules that concern the gratuitousness of the donation and the need for kinship between the parts, and limited the procedures to the situations in which there is a medical problem that disables the solicitant to generate a child. This is a complex situation, which involves many individuals, and it is not only a legal issue, but also an ethical one. This review intended to stimulate and give subsidies for reflexion of gynecologists, which have to face this issue