Publications by authors named "Paula Amato"

Years of growing research demonstrate that transgender and gender diverse (TGD) people desire fertility counseling and family building, however social and medical factors can impact future fertility options. Fortunately, TGD individuals have many viable options for family building using their own gametes and/or reproductive organs. However, the nuanced ways in which different gender affirming treatments affect reproduction, the interplay with non-treatment related infertility factors, and mitigation of likely dysphoria triggers are all critical to actual utilization.

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Canonical mitotic and meiotic cell divisions commence with replicated chromosomes consisting of two sister chromatids. Here, we developed and explored a model of premature cell division, where nonreplicated, G/G-stage somatic cell nuclei are transplanted to the metaphase cytoplasm of mouse oocytes. Subsequent cell division generates daughter cells with reduced ploidy.

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Objective: To study the impact of unhealthy air quality from the 2020 Oregon wildfires on outcomes for patients undergoing in vitro fertilization (IVF) treatment.

Design: A retrospective cohort study.

Setting: A university-based fertility clinic.

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Introduction: Improved reproductive endocrinology and infertility (REI) curricula are needed to address educational deficiencies both at our institution and on a national level. To improve REI education for OB/GYN residents and medical students, we developed and piloted a curriculum with in-person and virtual flexibility.

Methods: We developed three clinical vignettes for a facilitator-led case-based discussion among OB/GYN residents: two office cases and one emergency scenario.

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Objective: To investigate associations between reproductive endocrinology and infertility (REI) providers' prior training and current knowledge, skills, attitudes, and behaviors regarding fertility preservation and family building for transgender and gender-diverse (T/GD) patients.

Design: The survey was distributed to members of the Society for Reproductive Endocrinology and Infertility, the REI-physician-focused professional body within the American Society for Reproductive Medicine, with additional participants recruited through snowball sampling.

Results: Participants (n = 206) reported on training in T/GD care; 51% endorsed prior training.

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Objective: To assess predictors of desire for genetically related children among a national cohort of reproductive-age transgender and gender-diverse patients aged 18 to 44 years initiating gender-affirming hormone therapy for the first time.

Design: Cross-sectional study.

Setting: National telehealth clinic.

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Objective: Evidence strongly supports the use of mifepristone-misoprostol combination treatment for early pregnancy loss (EPL) among pregnancies conceived without assisted reproductive technologies. No literature exists, however, regarding the efficacy of this treatment in the medical management of EPL among pregnancies after in vitro fertilization and embryo transfer (IVF-ET). These patients differ as some use exogenous hormonal supplementation to provide pregnancy support.

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Range of DNA repair in response to double-strand breaks induced in human preimplantation embryos remains uncertain due to the complexity of analyzing single- or few-cell samples. Sequencing of such minute DNA input requires a whole genome amplification that can introduce artifacts, including coverage nonuniformity, amplification biases, and allelic dropouts at the target site. We show here that, on average, 26.

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Objective: To evaluate aneuploidy rates and in vitro fertilization (IVF)/pregnancy outcomes for patients undergoing IVF and preimplantation genetic testing for aneuploidy (PGT-A) with a recurrent pregnancy loss (RPL) diagnosis compared to infertility diagnoses without RPL.

Design: Retrospective cohort study.

Setting: Academic fertility center.

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Cells transmit their genomes vertically to daughter cells during cell divisions. Here, we demonstrate the occurrence and extent of horizontal mitochondrial (mt)DNA acquisition between cells that are not in a parent-offspring relationship. Extensive single-cell sequencing from various tissues and organs of adult chimeric mice composed of cells carrying distinct mtDNA haplotypes showed that a substantial fraction of individual cardiomyocytes, neurons, glia, intestinal, and spleen cells captured donor mtDNA at high levels.

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Haploidy is naturally observed in gametes; however, attempts of experimentally inducing haploidy in somatic cells have not been successful. Here, we demonstrate that the replacement of meiotic spindles in mature metaphases II (MII) arrested oocytes with nuclei of somatic cells in the G0/G1 stage of cell cycle results in the formation of de novo spindles consisting of somatic homologous chromosomes comprising of single chromatids. Fertilization of such oocytes with sperm triggers the extrusion of one set of homologous chromosomes into the pseudo-polar body (PPB), resulting in a zygote with haploid somatic and sperm pronuclei (PN).

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Objective: To identify changes in current practice patterns, salaries, and satisfaction by gender and by years in practice among board-certified reproductive endocrinology and infertility (REI) subspecialists in the United States.

Design: Cross-sectional web-based survey including 37 questions conducted by the Society for Reproductive Endocrinology and Infertility.

Setting: Not applicable.

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Study Question: What are the long-term developmental, reproductive and genetic consequences of mitochondrial replacement therapy (MRT) in primates?

Summary Answer: Longitudinal investigation of MRT rhesus macaques (Macaca mulatta) generated with donor mtDNA that is exceedingly distant from the original maternal counterpart suggest that their growth, general health and fertility is unremarkable and similar to controls.

What Is Known Already: Mitochondrial gene mutations contribute to a diverse range of incurable human disorders. MRT via spindle transfer in oocytes was developed and proposed to prevent transmission of pathogenic mtDNA mutations from mothers to children.

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Introduction: The majority of early pregnancy losses are due to chromosomal abnormalities, which can be evaluated by testing the products of conception (POCs). Traditionally, a dilation and curettage (D&C) is recommended to patients to obtain suitable tissue for analysis. This case series sought to determine whether patients with first-trimester pregnancy losses can successfully obtain analysis of POCs if they pass tissue with expectant management or misoprostol, rather than D&C.

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Heritable mitochondrial DNA (mtDNA) mutations are common, yet only a few recurring pathogenic mtDNA variants account for the majority of known familial cases in humans. Purifying selection in the female germline is thought to be responsible for the elimination of most harmful mtDNA mutations during oogenesis. Here we show that deleterious mtDNA mutations are abundant in ovulated mature mouse oocytes and preimplantation embryos recovered from PolG mutator females but not in their live offspring.

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Eisenmenger syndrome (ES) is regarded as a contraindication to pregnancy, with therapeutic abortion recommended in the event of unintended pregnancy. However, women with ES continue to desire and attempt pregnancy despite grave risks to their own health. This study compares the costs and outcomes of pregnancy in women with ES to the use of gestational surrogates in their pregnancies.

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Change history In this Letter, there are several errors regarding the assignments of mtDNA haplotypes for a subset of egg donors from our study. These errors have not been corrected online.

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Genome editing has potential for the targeted correction of germline mutations. Here we describe the correction of the heterozygous MYBPC3 mutation in human preimplantation embryos with precise CRISPR-Cas9-based targeting accuracy and high homology-directed repair efficiency by activating an endogenous, germline-specific DNA repair response. Induced double-strand breaks (DSBs) at the mutant paternal allele were predominantly repaired using the homologous wild-type maternal gene instead of a synthetic DNA template.

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Maternally inherited mitochondrial (mt)DNA mutations can cause fatal or severely debilitating syndromes in children, with disease severity dependent on the specific gene mutation and the ratio of mutant to wild-type mtDNA (heteroplasmy) in each cell and tissue. Pathogenic mtDNA mutations are relatively common, with an estimated 778 affected children born each year in the United States. Mitochondrial replacement therapies or techniques (MRT) circumventing mother-to-child mtDNA disease transmission involve replacement of oocyte maternal mtDNA.

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Oocyte defects lie at the heart of some forms of infertility and could potentially be addressed therapeutically by alternative routes for oocyte formation. Here, we describe the generation of functional human oocytes following nuclear transfer of first polar body (PB1) genomes from metaphase II (MII) oocytes into enucleated donor MII cytoplasm (PBNT). The reconstructed oocytes supported the formation of de novo meiotic spindles and, after fertilization with sperm, meiosis completion and formation of normal diploid zygotes.

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