Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gametes or embryos, and/or the use of fertility medication. When used to address infertility, ART may also be referred to as fertility treatment. ART mainly belongs to the field of reproductive endocrinology and infertility. Some forms of ART may be used with regard to fertile couples for genetic purpose (see preimplantation genetic diagnosis). ART may also be used in surrogacy arrangements, although not all surrogacy arrangements involve ART.The existence of sterility will not always require ART to be the first option to consider, as there are occasions when its cause is a mild disorder that can be solved with more conventional treatments or with behaviors based on promoting health and reproductive habits..
Introdução: A maioria das mulheres na fase da menopausa apresenta sintomas climatéricos em decorrência da diminuição dos hormônios femininos. A terapia de reposição hormonal representa a principal conduta para o manejo desses sintomas. No entanto, evidências na literatura apontam que a terapia de reposição hormonal é contraindicada para pacientes com câncer de mama, uma vez que está associada ao aumento das chances de recidiva da doença. Objetivo: Analisar as evidências disponíveis na literatura sobre as opções terapêuticas para o manejo dos sintomas climatéricos em pacientes com câncer de mama. Métodos: Estudo de revisão integrativa utilizando as bases de dados PubMed, Cochrane e SciELO. A pesquisa foi conduzida considerando os termos “Therapeutics”, “Menopause”, “Breast neoplasms" e “Estrogen replacement therapy”. Resultado: Um total de 152 estudos foram identificados e 18 estudos foram elegíveis e incluídos. Os principais sintomas climatéricos apontados foram ondas de calor (n=5). O tratamento com terapia hormonal foi predominante entre os estudos incluídos (n=9), estrogênio (n=3), estrogênio combinado com progesterona (n=2), progesterona isolada (n=1), progesterona micronizada e progestagênios (n=1). Terapia não hormonal foi identificada em 2 estudos. Conclusão: Os resultados sugerem a terapia de reposição hormonal como a principal conduta para o manejo dos sintomas climatéricos em pacientes com câncer de mama. Entretanto, a escassez de opções de tratamento não hormonais influência na qualidade de vida dessas mulheres, uma vez que a terapia de reposição hormonal possui consideráveis contraindicações em casos de câncer de mama devido a fisiopatologia da doença.
INTRODUCTION:Kagami-Ogata syndrome (KOS14) and Temple syndrome (TS14) are two disorders associated with reciprocal alterations within the chr14q32 imprinted domain. Here, we present a work-up strategy for preimplantation genetic testing (PGT) to avoid the transmission of a causative micro-deletion. METHODS:We analysed DNA from the KOS14 index case and parents using methylation-sensitive ligation-mediated probe amplification and methylation pyrosequencing. The extent of the deletion was mapped using SNP arrays. PGT was performed in trophectoderm samples in order to identify unaffected embryos. Samples were amplified using multiple displacement amplification, followed by genome-wide SNP genotyping to determine the at-risk haplotype and next-generation sequencing to determine aneuploidies. RESULTS:A fully methylated pattern at the normally paternally methylated IG-DMR and MEG3 DMR in the KOS14 proband, accompanied by an unmethylated profile in the TS14 mother was consistent with maternal and paternal transmission of a deletion, respectively. Further analysis revealed a 108 kb deletion in both cases. The inheritance of the deletion on different parental alleles was consistent with the opposing phenotypes. In vitro fertilisation with intracytoplasmatic sperm injection and PGT were used to screen for deletion status and to transfer an unaffected embryo in this couple. A single euploid-unaffected embryo was identified resulting in a healthy baby born. DISCUSSION:We identify a microdeletion responsible for multigeneration KOS14 and TS14 within a single family where carriers have a 50% risk of transmitting the deletion to their offspring. We show that PGT can successfully be offered to couples with IDs caused by genetic anomalies.
Oocyte maturation is a coordinated process that is tightly linked to reproductive potential. A better understanding of gene regulation during human oocyte maturation will not only answer an important question in biology, but also facilitate the development of in vitro maturation technology as a fertility treatment. We generated single-cell transcriptome and used our previously published single-cell methylome data from human oocytes at different maturation stages to investigate how genes are regulated during oocyte maturation, focusing on the potential regulatory role of non-CpG methylation. DNMT3B, a gene encoding a key non-CpG methylation enzyme, is one of the 1,077 genes upregulated in mature oocytes, which may be at least partially responsible for the increased non-CpG methylation as oocytes mature. Non-CpG differentially methylated regions (DMRs) between mature and immature oocytes have multiple binding motifs for transcription factors, some of which bind with DNMT3B and may be important regulators of oocyte maturation through non-CpG methylation. Over 98% of non-CpG DMRs locate in transposable elements, and these DMRs are correlated with expression changes of the nearby genes. Taken together, this data indicates that global non-CpG hypermethylation during oocyte maturation may play an active role in gene expression regulation, potentially through the interaction with transcription factors.
(Abstracted from Fertil Steril 2019;112:1071–1079.e7) The rate of embryonic aneuploidy increases exponentially in women over the age of 35 years, coinciding with a dramatic decrease in the success of in vitro fertilization (IVF) in women of advanced maternal age. Despite advancements in preimplantation genetic testing for aneuploidy (PGT-A) including the introduction of next generation sequencing (NGS), morphologic assessment remains the primary method of embryo selection in IVF.
Using comprehensive screening techniques, several small and single-center RCTs have shown that Preimplantation genetic testing for aneuploidy (PGT-A) increases pregnancy and live birth rates per transfer compared to morphology alone. These studies were mostly performed by very experienced IVF and PGT laboratories.Next generation sequencing (NGS) based PGT-A has the advantage over previous techniques of having a larger dynamic range and resolution allowing the detection of mosaicism in the 20-80% range and therefore allowing for better selection of embryos.A new RCT study was designed to test if NGS applied in regular fertility centers in a multicenter setting would improve ART outcomes. The RCT, called STAR, was multicentre, pragmatic RCT, involving 662 women ages 25-40 undergoing IVF with at least two blastocyst biopsied, no history of RPL or RIF. The patients were randomly assigned to a SET with either PGT-A or morphology alone. Only euploid embryos were transferred to the PGT-A arm and mosaic embryos were not replaced. The primary outcome was a clinical pregnancy at 20 weeks gestation following a single embryo transfer.Clinical pregnancy occurred in 137/274 (50%) of transfers with PGT-A and in 144/314 (46%) with morphology alone. However, post hoc analysis of pregnancy/live birth rates in women aged between 25- 34 and 35-40 years was 49 and 51% (not significant) and 51% and 37% (p=0.035), respectively.Overall clinical pregnancy and live birth rates were similar between groups, however, there was a significant increase in live birth in women ages 35-40 years when PGT-A was used for embryo selection. There results resemble those reported by SART in 2014. Some reasons for the lack of improvement in the young age group are the exclusion of RIF and RPL patients, the rule of not replacing mosaic embryos when no euploid ones were available, and probably sub-optimal biopsy or transfer techniques in some clinics in this real-world study.
