Reducing time to pregnancy and facilitating the birth of healthy children through functional analysis of embryo physiology†

2019 ◽  
Vol 101 (6) ◽  
pp. 1124-1139 ◽  
Author(s):  
Laura Ferrick ◽  
Yee Shan Lisa Lee ◽  
David K Gardner

Abstract An ever-increasing number of couples rely on assisted reproductive technologies (ART) in order to conceive a child. Although advances in embryo culture have led to increases in the success rates of clinical ART, it often takes more than one treatment cycle to conceive a child. Ensuring patients conceive as soon as possible with a healthy embryo is a priority for reproductive medicine. Currently, selection of embryos for transfer relies predominantly on the morphological assessment of the preimplantation embryo; however, morphology is not an absolute link to embryo physiology, nor the health of the resulting child. Non-invasive quantitation of individual embryo physiology, a key regulator of both embryo viability and health, could provide valuable information to assist in the selection of the most viable embryo for transfer, hence reducing the time to pregnancy. Further, according to the Barker Hypothesis, the environment to which a fetus is exposed to during gestation affects subsequent offspring health. If the environment of the preimplantation period is capable of affecting metabolism, which in turn will affect gene expression through the metaboloepigenetic link, then assessment of embryo metabolism should represent an indirect measure of future offspring health. Previously, the term viable embryo has been used in association with the potential of an embryo to establish a pregnancy. Here, we propose the term healthy embryo to reflect the capacity of that embryo to lead to a healthy child and adult.

Infertility rates in India becoming increased in last decade principally due to the urbanization conditions and the lifestyle habits. It is giving alarm by continuously reporting the progress in incident cases of infertility amongst the young Indian adults of both male and female population. Among the various Assisted Reproductive Technologies (ART) available today in the treatment of infertility, In Vitro Fertilization (IVF) is found to be the most applicable treatment method of choice. This involves the administration of different hormones and drugs to treat infertility. In the present scenario technically IVF treatment process is tedious, laborious, high cost and most importantly success rates reported to be very low (20-30%). The prediction of IVF success rates is becoming an important scientific knowledge and practice, which helps both the doctor and the candidate couple to know about the conditions hence to take the right decision. The accurate prediction of the IVF success rate is really a challenging task in obstetrics and gynecology medicine. The success rates of the IVF depends on the various factors such as Intrinsic factors i.e, Genetic predisposition, Age, Body mass Index, Hormonal balance, Embryo viability, Sperm quality, Endometriosis and overall patient’s response level of the candidate couple and the Extrinsic factors such as Medical equipment technology, Treatment methods, Personal experiences of clinicians and embryologists, Process time, Stress due to the lifestyle etc.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Iman Halvaei ◽  
Julia Litzky ◽  
Navid Esfandiari

AbstractMany factors, including postponement of marriage, increased life expectancy, and improved success with assisted reproductive technologies have been contributing to increased paternal age in developed nations. This increased average paternal age has led to concerns about adverse effects of advanced paternal age on sperm quality, assisted reproductive outcomes, and the health of the offspring conceived by older fathers. This review discusses the association between advanced paternal age and sperm parameters, assisted reproduction success rates, and offspring health.


2021 ◽  
Vol 99 (Supplement_1) ◽  
pp. 113-113
Author(s):  
Phillip H Purdy

Abstract Assisted reproductive technologies (ART) can be used across most agricultural species and will result in some degree of fertility when employed correctly. Still, conversations with agricultural producers and scientists (corporate, academic, governmental) repeatedly reveal that they do not know what success rates they should anticipate when using some ARTs, specifically semen cryopreservation and artificial insemination, with agricultural species (beef and dairy cattle, goats, pigs, poultry, sheep). These perceptions hinder ART application within the agricultural and scientific communities. Understanding these expected results is a critical component that is used to guide the USDA National Animal Germplasm Program laboratory operations for collecting, freezing and using germ plasm (semen, eggs, embryos, DNA, tissues, organs, cells), has consequently resulted in growth of the national collection, and provided tools, technologies, and educational opportunities for agricultural producers with documented success. Therefore, the intent of this presentation is to provide an overview of what results should be expected when using semen cryopreservation and artificial insemination across livestock species, explain the factors that influence successful use of these ARTs, which should encourage a more broad acceptance of their use with all agricultural species, and discuss opportunities for research and optimization that will improve fertility when using these technologies.


2020 ◽  
pp. ijgc-2020-001783
Author(s):  
Katherine Stewart ◽  
Sukhkamal Campbell ◽  
Michael Frumovitz ◽  
Pedro T Ramirez ◽  
Laurie J McKenzie

Fertility-sparing management of early-stage gynecologic cancers is becoming more prevalent as increasing evidence demonstrates acceptable oncologic and reproductive outcomes in appropriately selected patients. However, in the absence of randomized controlled trials, most of the commonly used treatment algorithms are based only on observational studies. As women are increasingly postponing childbearing, the need for evidence-based guidance on the optimal selection of appropriate candidates for fertility-sparing therapies is paramount. It is imperative to seriously consider the fertility potential of a given individual prior to making major oncologic treatment decisions that may deviate from the accepted standard of care. It is a disservice to patients to undergo a fertility-sparing procedure in hopes of ultimately achieving a live birth, only to determine later they have poor baseline fertility potential or other substantial barriers to conception including excess financial toxicity. Many women with oncologic diagnoses are of advanced maternal age and their obstetric and neonatal risks must be considered. In the era of advanced assisted reproductive technologies, patients should be provided realistic expectations regarding success rates while understanding the potential oncologic perils. A multidisciplinary approach to the conservative treatment of early-stage gynecologic cancers with early referral to reproductive specialists as well as maternal-fetal medicine specialists is warranted. In this review, we discuss the recommended fertility evaluation for patients with newly diagnosed, early-stage gynecologic cancers who are considering fertility-sparing management.


2018 ◽  
Vol 36 (03/04) ◽  
pp. 211-220 ◽  
Author(s):  
Sneha Mani ◽  
Monica Mainigi

AbstractAssisted reproductive technologies (ARTs) lead to an increased risk for pregnancy complications, congenital abnormalities, and specific imprinting disorders. Epigenetic dysfunction is thought to be one common mechanism which may be affecting these outcomes. The timing of multiple ART interventions overlaps with developmental time periods that are particularly vulnerable to epigenetic change. In vitro embryo culture is known to impact blastocyst development, in vitro fertilization (IVF) success rates, as well as neonatal outcomes. Embryo culture, in contrast to other procedures involved in ART, is obligatory, and has the highest potential for causing alterations in epigenetic reprograming. In this review, we summarize progress that has been made in exploring the effects of embryo culture, culture media, and oxygen tension on epigenetic regulation in the developing embryo. In humans, it is difficult to isolate the role of embryo culture on epigenetic perturbations. Therefore, additional well-controlled animal studies isolating individual exposures are necessary to minimize the epigenetic effects of modifiable factors utilized during ART. Findings from these studies will likely not only improve IVF success rates but also reduce the risk of adverse perinatal outcomes.


2018 ◽  
Author(s):  
Noga Fuchs Weizman ◽  
Brandon A. Wyse ◽  
Ran Antes ◽  
Zenon Ibarrientos ◽  
Mugundhine Sangaralingam ◽  
...  

ABSTRACTImproved embryo selection is crucial in optimizing the results from assisted reproduction. Preimplantation genetic screening reduces time to pregnancy and miscarriages. Correlating the transcriptome of an embryo, with fertility treatments and outcomes, holds promise in improving the overall results. We developed a novel method for embryo selection in fertility treatments that integrates embryonic genomic and transcriptomic data and evaluated it in this pilot study.A total of 21 embryos donated for research were included. Three were used for the initial development and optimization of sample processing and sequencing. Thereafter, 18 embryos were used to demonstrate the clinical safety and reproducibility of our method. Two trophectoderm biopsies were taken from each embryo: one was processed as a clinical sample for genomic profiling (control, n=18), while the other biopsy (n=18) was split and utilized for independent, simultaneous genomic and transcriptomic analysis, here termed Preimplantation Genetic and Transcriptomic Testing (PGT2).High quality genomic and transcriptomic data were obtained from all analyzed samples. The concordance between genomic data obtained with PGT2 and control samples was 100% with clinical grade quality metrics. Euploid embryos showed downregulation of genes involved in anaerobic metabolism, oxidative phosphorylation, and fatty-acid oxidation. This is the first study to provide full genomic and transcriptomic profiles from a single TE biopsy from human embryos in a clinical setting unleashing the potential of improving embryo selection and outcomes in infertility treatments. Clinical trials are needed to correlate transcriptomic data with outcomes.SUMMARYDespite advances in assisted reproductive technologies, the success rate has remained relatively constant. Under the age of 35, there is a 40% chance of delivering a child per embryo transfer, which decreases with increasing maternal age. Prioritizing embryos for transfer is based on morphological assessment and, in some cases, incorporates genetic testing as well. Selection of euploid embryos for transfer shortens the time to pregnancy and reduces the risk for miscarriages. Adding the mRNA analysis to the genomic assessment of an embryo has the potential of improving the outcomes of fertility treatments.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Bing Qu ◽  
Yunhe Xiong ◽  
Xiaofan Yu ◽  
Jinli Ding ◽  
Jing Weng ◽  
...  

As infertility became a significant public health problem, assisted reproductive technologies (ARTs) were introduced. However, the fertilization rate of in vitro fertilization (IVF) per cycle varied, and patients needed to repeat IVF or change to intracytoplasmic sperm injection (ICSI). Here, 75 couples suffering from female fallopian tubal blockage (tubal group) and 42 spouses beset by male abnormal sperm status (dysspermia group) were recruited. We comprehensively explored the relationship among couples’ clinical factors, follicular metabolites, and IVF/ICSI stepwise outcomes. IVF/ICSI outcomes were affected by follicular metabolites and physical status in both women and men, regardless of which side infertility came from. Particularly, in the tubal group, the energy supporting pathways—glycolysis and pyruvate metabolism—were most essential in follicles, and IVF/ICSI outcomes were also related to sperm parameters. However, in the dysspermia group, in addition to sperm conditions, oocyte quality acted as a compensation for poor sperm quality, for which aminoacyl-tRNA biosynthesis and the related supporting metabolism were critical in the follicular environment, and ultimately played a decisive role in IVF/ICSI outcomes. The respective logistic regression models in combination with selective male sperm parameters, estradiol (E2), follicular alanine, glutamine, glycoprotein, lipid, and acetic acid, were constructed to predict IVF or ICSI outcomes. No matter which sex infertility comes from, factors from both men and women should be considered. The current study provides a feasible option for pre-IVF evaluation, as well as guidance for follow-up clinical intervention to improve IVF/ICSI success rates.


2018 ◽  
Author(s):  
Ning Ma ◽  
Nabora Reyes de Mochel ◽  
Paula Duyen Anh Pham ◽  
Tae Yeon Yoo ◽  
Ken WY. Cho ◽  
...  

AbstractDevelopment of quantitative, safe and rapid techniques for assessing embryo quality provides significant advances in Assisted Reproductive Technologies (ART). We apply the phasor-FLIM method to capture endogenous fluorescent biomarkers of pre-implantation embryos as a non-morphological caliber for embryo quality. Here, we identify the developmental, or “D-trajectory”, that consists of fluorescence lifetime from different stages of mouse pre-implantation embryos. The D-trajectory correlates with intrinsic fluorescent species from a distinctive energy metabolism and oxidized lipids, as seen with Third Harmonic Generation (THG) that changes over time. In addition, we have defined an Embryo Viability Index (EVI) to distinguish pre-implantation embryo quality using the Distance Analysis, a machine learning algorithm to process the fluorescence lifetime distribution patterns. We show that the phasor-FLIM approach provides a much-needed non-invasive quantitative technology for identifying healthy embryos at the early compaction stage with 86% accuracy. This may increase embryo implantation success for in vitro fertilization clinics.HighlightsA label-free method of tracking metabolic trajectories during pre-implantation mouse embryo development.A non-invasive approach for assessing embryo quality and viability by a phasor-FLIM analysis.


2020 ◽  
Author(s):  
Leah May Roberts ◽  
Rashmi Kudesia ◽  
Huaqing Zhao ◽  
Shaliz Dolan ◽  
Marisa Rose

Abstract PURPOSE: To evaluate fertility knowledge among current Obstetrics and Gynecology (OB-GYN) residents using a recently published validated instrument, the Fertility and Infertility Treatment Knowledge Score (FIT-KS).METHODS: OB-GYN residents in the United States were recruited through an email to all residency coordinators nationwide. They were asked to voluntarily respond to a short questionnaire including demographic information and the FIT-KS instrument, through an online survey platform.RESULTS: The sample was 91% female, with 69% between the ages of 26 and 30. Participants evenly represented all four years of training. Mean FIT-KS score was 21.2 (73% correct). No statistically significant differences were noted across the level of training. Several knowledge gaps were noted. Residents could define the common assisted reproductive technologies; however overestimated their success rates per cycle. CONCLUSIONS: Substantial gaps exist in fertility knowledge among OB-GYN residents, with understanding of male fertility and success rates of Assisted Reproductive Technologies (ART) being particularly limited. Knowledge of fertility does not change throughout residency training, demonstrating consistent gaps in fertility knowledge. Knowledge during post graduate year (PGY)-1 year is consistent with mean scores found in prior research in Internal Medicine residents (65%), as well as a cohort of female medical students and obstetrics and gynecology residents and fellows (64.9%)(1, 2).


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