scholarly journals Assessing the epigenetic risks of assisted reproductive technologies: a way forward

2019 ◽  
Vol 63 (3-4-5) ◽  
pp. 217-222 ◽  
Author(s):  
Federica Zacchini ◽  
Silvestre Sampino ◽  
Adrian M. Stankiewicz ◽  
Thomas Haaf ◽  
Grazyna E. Ptak
Keyword(s):  
Assisted Reproductive Technologies ◽  
Safety Evaluation ◽  
Reproductive Technologies ◽  
Long Term Effects ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Health And Disease ◽  
Civilization Disease

Since the birth of the first baby conceived by in vitro fertilization (IVF), assisted reproductive technologies (ART) have been constantly evolving to accomodate needs of a growing number of infertile couples. Rapidly developing ART procedures are directly applied for human infertility treatment without prior long-term safety evaluation. Although the majority of ART babies are healthy at birth, a comprehensive assessment of the long-term risks associated with ART is still lacking. An increased risk of epigenetic errors has been associated with the use of ART, which may contribute to the onset of civilization disease later in adolescence/adulthood and/or in subsequent generations. Therefore, our investigations should not focus on (or be limited to) the occurrence of a few very rare imprinting disorders in ART children, which might be associated with parental age and/or the use of ART, but on the possibly increased disease susceptibilities later in life and their potential transmission to the subsequent generations. Retrospective studies do not offer exhaustive information on long-term consequences of ART. Animal models are useful tools to study long-term effects including transgenerational ones and the epigenetic risk of a given ART procedure, which could then be translated to the human context. The final goal is the establishment of common guidelines for assessing the epigenetic risk of ART in humans, which will contribute to two key objectives of the Horizon2020 programme, i.e. to improve our understanding of the causes and mechanisms underlying health and disease, and to improve our ability to monitor health and prevent/manage disease.

scholarly journals Prevalence of pathogenic copy number variants among children conceived by donor oocyte

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sandra Monfort ◽  
Carmen Orellana ◽  
Silvestre Oltra ◽  
Mónica Rosello ◽  
Alfonso Caro-Llopis ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Copy Number ◽  
Assisted Reproductive Technologies ◽  
Copy Number Variants ◽  
Reproductive Technologies ◽  
Significant Excess ◽  
Vitro Fertilization ◽  
Donor Oocyte ◽  
Increased Risk

AbstractDevelopment of assisted reproductive technologies to address infertility has favored the birth of many children in the last years. The majority of children born with these treatments are healthy, but some concerns remain on the safety of these medical procedures. We have retrospectively analyzed both the fertilization method and the microarray results in all those children born between 2010 and 2019 with multiple congenital anomalies, developmental delay and/or autistic spectrum disorder (n = 486) referred for array study in our center. This analysis showed a significant excess of pathogenic copy number variants among those patients conceived after in vitro fertilization with donor oocyte with respect to those patients conceived by natural fertilization (p = 0.0001). On the other hand, no significant excess of pathogenic copy number variants was observed among patients born by autologous oocyte in vitro fertilization. Further studies are necessary to confirm these results and in order to identify the factors that may contribute to an increased risk of genomic rearrangements, as well as consider the screening for genomic alterations after oocyte donation in prenatal diagnosis.

scholarly journals Reproductive technologies, female infertility, and the risk of imprinting-related disorders

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Patricia Fauque ◽  
Jacques De Mouzon ◽  
Aviva Devaux ◽  
Sylvie Epelboin ◽  
Marie-José Gervoise-Boyer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Intrauterine Insemination ◽  
Reproductive Technologies ◽  
Female Infertility ◽  
Global Risk ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Genomic Imprints

Abstract Background Epidemiological studies suggest that singletons born from assisted reproductive technologies (ART) have a high risk of adverse perinatal outcomes, specifically for imprinting disorders. Because ART processes take place at times when epigenetic reprogramming/imprinting are occurring, there is concern that ART can affect genomic imprints. However, little is currently known about the risk of imprinting defects according to the type of ART or the type of underlying female infertility. From the French national health database, a cohort of 3,501,495 singletons born over a 5-year period (2013–2017) following fresh embryo or frozen embryo transfers (fresh-ET or FET from in vitro fertilization), intrauterine insemination, or natural conception was followed up to early childhood. Based on clinical features, several syndromes/diseases involving imprinted genes were monitored. The effects of ART conception and the underlying cause of female infertility were assessed. Results Compared with infants conceived naturally, children born after fresh-ET had a higher prevalence of imprinting-related diseases, with an aOR of 1.43 [95% CI 1.13–1.81, p = 0.003]. Namely, we observed an increased risk of neonatal diabetes mellitus (1.96 aOR [95% CI 1.43–2.70], p < 0.001). There was an overall independent increase in risk of imprinting diseases for children with mothers diagnosed with endometriosis (1.38 aOR [95% CI 1.06–1.80], p = 0.02). Young and advanced maternal age, primiparity, obesity, smoking, and history of high blood pressure or diabetes were also associated with high global risk. Conclusions This prospective epidemiological study showed that the risk of clinically diagnosed imprinting-related diseases is increased in children conceived after fresh embryo transfers or from mothers with endometriosis. The increased perturbations in genomic imprinting could be caused by controlled ovarian hyperstimulation and potentially endometriosis through the impairment of endometrial receptivity and placentation, leading to epigenetic feto-placental changes. Further studies are now needed to improve understanding of the underlying molecular mechanisms (i.e. genetic or epigenetic causes).

Assisted Reproductive Technology and Reproductive Options for the At-Risk Couple

2018 ◽  
Author(s):  
Amber Mathiesen ◽  
Kali Roy
Keyword(s):  
At Risk ◽  
In Vitro Fertilization ◽  
Assisted Reproductive Technology ◽  
Assisted Reproductive Technologies ◽  
Genetic Diagnosis ◽  
Reproductive Technologies ◽  
Reproductive Technology ◽  
Vitro Fertilization ◽  
Increased Risk

For those with an increased risk of having a child with a genetic condition, reproductive options include avoiding pregnancy altogether, undertaking prenatal diagnosis in a current pregnancy, and preventing the transmission of the genetic changes responsible for the condition to a child. This chapter on assisted reproductive technology and reproductive options for the at-risk couple describes the basic techniques of assisted reproductive technologies as well as reproductive testing options prior to in vitro fertilization, including preimplantation genetic screening (PGS) and preimplantation genetic diagnosis (PGD). It includes a brief overview of ovarian stimulation, intrauterine insemination (IUI), and in vitro fertilization. This chapter discusses the details of PGS including the process and its limitations. It also includes a discussion of PGD, including the process, such as linkage analysis, and limitations, such as allele dropout.

scholarly journals Long-Term Phenotypic and Proteomic Changes Following Vitrified Embryo Transfer in the Rabbit Model

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1043 ◽  
Author(s):  
Ximo Garcia-Dominguez ◽  
Francisco Marco-Jiménez ◽  
David S. Peñaranda ◽  
José Salvador Vicente
Keyword(s):  
Growth Performance ◽  
Embryo Transfer ◽  
Developmental Plasticity ◽  
Assisted Reproductive Technologies ◽  
Rabbit Model ◽  
Reproductive Technologies ◽  
Long Term Effects ◽  
Mammal Species

Nowadays, assisted reproductive technologies (ARTs) are considered valuable contributors to our past, but a future without their use is inconceivable. However, in recent years, several studies have evidenced a potential impact of ART on long-term development in mammal species. To date, the long-term follow-up data are still limited. So far, studies have mainly focused on in vitro fertilization or in vitro culture, with information from gametes/embryos cryopreservation field being practically missing. Herein, we report an approach to determine whether a vitrified embryo transfer procedure would have long-term consequences on the offspring. Using the rabbit as a model, we compared animals derived from vitrified-transferred embryos versus those naturally conceived, studying the growth performance, plus the weight throughout life, and the internal organs/tissues phenotype. The healthy status was assessed over the hematological and biochemical parameters in peripheral blood. Additionally, a comparative proteomic analysis was conducted in the liver tissue to investigate molecular cues related to vitrified embryo transfer in an adult tissue. After vitrified embryo transfer, birth weight was increased, and the growth performance was diminished in a sex-specific manner. In addition, vitrified-transferred animals showed significantly lower body, liver and heart weights in adulthood. Molecular analyses revealed that vitrified embryo transfer triggers reprogramming of the liver proteome. Functional analysis of the differentially expressed proteins showed changes in relation to oxidative phosphorylation and dysregulations in the zinc and lipid metabolism, which has been reported as possible causes of a disturbed growth pattern. Therefore, we conclude that vitrified embryo transfer is not a neutral procedure, and it incurs long-term effects in the offspring both at phenotypic and molecular levels. These results described a striking example of the developmental plasticity exhibited by the mammalian embryo.

SOCIAL AND ETHICAL ASPECTS OF IN VITRO FERTILIZATION

1999 ◽  
Vol 15 (1) ◽  
pp. 22-35 ◽  
Author(s):  
Elizabeth Heitman
Keyword(s):  
In Vitro Fertilization ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Oocyte Donation ◽  
Social Needs ◽  
Vitro Fertilization ◽  
The Social ◽  
Definition Of

In vitro fertilization (IVF) stands out as one of the contemporary period's most extraordinary technologies, and its social and ethical consequences among the most far reaching. Despite its uncertain effectiveness and medical consequences, IVF has contributed significantly to the medicalization of infertility and the increasingly imperative character of reproductive technology. New developments in IVF, particularly oocyte donation, have created new definitions of treatable infertility and new social needs for IVF; when the technology does not result in pregnancy or healthy babies, these developments have created profound new disappointments. IVF and the commodification of the extracorporeal embryo have also confused the social meaning and legal definition of parenthood. Ultimately the relationship between prospective parents, infertility specialists, and the embryos that they create is a highly ambiguous one. This ambiguity is likely to be a long-term characteristic of efforts to develop, use, and assess assisted reproductive technologies.

Thickness of endometrium: predictor of the effectiveness of IVF/ICSI programs (literature review)

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (1) ◽  
pp. 113-116
Author(s):  
L A Bagdasaryan ◽  
I E Korneyeva
Keyword(s):  
Assisted Reproductive Technologies ◽  
Endometrial Thickness ◽  
Molecular Genetic ◽  
Uterine Cavity ◽  
Reproductive Technologies ◽  
Genetic Characteristics ◽  
Vitro Fertilization ◽  
Need To Evaluate ◽  
The Relationship

The aim of the study is to systematically analyze the data available in the modern literature on the relationship between endometrial thickness and the frequency of pregnancy in the program of assisted reproductive technologies (ART). Materials and methods. The review includes data from foreign and domestic articles found in PubMed on this topic. Results. The article presents data on the relationship between the thickness of the endometrium and the frequency of pregnancy in ART programs. The greatest number of studies is devoted to the evaluation of the relationship between the thickness of the endometrium and the frequency of pregnancy on the day of the ovulation trigger. Data are presented on the existence of a correlation between the thickness of the endometrium measured on the day of the ovulation trigger and the frequency of clinical pregnancy, as well as data on the need to evaluate the structure of the endometrium and the state of subendometric blood flow. The importance of multilayered (three-layered) endometrium as a prognostic marker of success in in vitro fertilization/intracytoplasmic sperm injection programs in the ovum is emphasized. The conclusion. The thickness of the endometrium can not be used as an argument for canceling the cycle or abolishing embryo transfer to the uterine cavity. Further studies in this direction are needed with a study of the morphological and molecular genetic characteristics of the endometrium, which in the future will allow us to evaluate the relationship between the thickness of the endometrium and the probability of pregnancy.

Legal restrictions on pre-implantation genetic diagnostics in the framework of in vitro fertilization procedure: foreign experience and Russian perspective

2019 ◽  
Author(s):  
N.A. Altinnik , S.S. Zenin , V.V. Komarova et all
Keyword(s):  
In Vitro Fertilization ◽  
Assisted Reproductive Technologies ◽  
Genetic Diseases ◽  
Genetic Diagnosis ◽  
Reproductive Technologies ◽  
Legal Regulation ◽  
Genetic Diagnostics ◽  
Vitro Fertilization ◽  
Medical Indications

The article discusses the factors that determine the content of the legal limitations of pre-implantation genetic diagnosis in the framework of the in vitro fertilization procedure, taking into account international experience and modern domestic regulatory legal regulation of the field of assisted reproductive technologies. The authors substantiates the conclusion that it is necessary to legislate a list of medical indications for preimplantation genetic diagnosis, as well as the categories of hereditary or other genetic diseases diagnosed in the framework of this procedure.

scholarly journals Sperm Selection Procedures for Optimizing the Outcome of ICSI in Patients with NOA

2021 ◽  
Vol 10 (12) ◽  
pp. 2687
Author(s):  
Kaan Aydos ◽  
Oya Sena Aydos
Keyword(s):  
In Vitro Selection ◽  
Assisted Reproductive Technologies ◽  
Reproductive Technologies ◽  
Testicular Sperm Extraction ◽  
Obstructive Azoospermia ◽  
Sperm Retrieval ◽  
Vitro Fertilization ◽  
Great Hope ◽  
Future Fertility

Retrieving spermatozoa from the testicles has been a great hope for patients with non-obstructive azoospermia (NOA), but relevant methods have not yet been developed to the level necessary to provide resolutions for all cases of NOA. Although performing testicular sperm extraction under microscopic magnification has increased sperm retrieval rates, in vitro selection and processing of quality sperm plays an essential role in the success of in vitro fertilization. Moreover, sperm cryopreservation is widely used in assisted reproductive technologies, whether for therapeutic purposes or for future fertility preservation. In recent years, there have been new developments using advanced technologies to freeze and preserve even very small numbers of sperm for which conventional techniques are inadequate. The present review provides an up-to-date summary of current strategies for maximizing sperm recovery from surgically obtained testicular samples and, as an extension, optimization of in vitro sperm processing techniques in the management of NOA.

Peculiarities of pregnancy and delivery course in women after the application of assisted reproductive technologies against obesity (Based on the retrospective analysis)

2018 ◽  
pp. 122-126
Author(s):  
I.A. Zhabchenko ◽  
◽  
O.R. Sudmak ◽  
Keyword(s):  
In Vitro Fertilization ◽  
Pregnant Women ◽  
Retrospective Analysis ◽  
Perinatal Outcomes ◽  
Reproductive Technologies ◽  
Ischemic Lesion ◽  
Vitro Fertilization ◽  
Pregnancy And Delivery

The objective: to study the structure and frequency of complications of pregnancy, deliveries and perinatal outcomes in three groups of women: women with infertility and obesity, treated by application of in vitro fertilization (hereinafter IVF), pregnant women after IVF application with normal body weight, and pregnant women on the background of obesity which did not have an infertility in past history. Materials and methods. A retrospective analysis of 221 case histories of pregnancies and labors in women who were treated and gave birth in the Pregnancy and delivery pathology Department of SI «Institute of Pediatrics, Obstetrics and Gynecology named after Acad. O. M. Lukyanova of NAMS of Ukraine» for 2012 – 2016 years was carried out. Results. The overwhelming majority of pregnant women after IVF on the background of obesity are primaparas, who have a complicated obstetric history, hormonal changes in the form of progesterone deficiency predominantly and chronic inflammatory processes. Pregnancy with a combination of infertility, treated by the means of IVF application, and obesity, in most cases is accompanied by a long-term threat of termination of pregnancy (48.8%), threatening preterm deliveries (56%), placental dysfunction (41.5%), premature rupture of the amniotic membranes (41.5%), other problems during pregnancy, at the same time, every second woman (58.5%) had a combination of several complications, and required a long-term and repeated inpatient treatment (53.7%). The specific gravity of surgical delivery was 90%, and 16.2% of such deliveries were complicated by pathological blood loss. The number of preterm deliveries was 17.1%, with perinatal losses up to 11.3‰. Among full-term newborns 21.3% of newborns had malnutrition of the I degree and 17% of them had hypoxic-ischemic lesion of CNS. Conclusion. The course of pregnancy, delivery and the postpartum period in the studied contingent of women has a significant frequency of complications, mainly the coinciding ones, which affects on the consequences of perinatal outcomes and requires further study of this problem and the development of differentiated algorithms for antenatal observation. Key words: pregnancy, obesity, in vitro fertilization, complications, delivery, newborn.

Infertility Treatments and Long-Term Neurologic Morbidity of the Offspring

2018 ◽  
Vol 36 (09) ◽  
pp. 949-954 ◽  
Author(s):  
Shai Levin ◽  
Eyal Sheiner ◽  
Tamar Wainstock ◽  
Asnat Walfisch ◽  
Idit Segal ◽  
...  
Keyword(s):  
Medical Center ◽  
Cohort Analysis ◽  
Multivariable Analysis ◽  
Maternal Diabetes ◽  
Population Based ◽  
Vitro Fertilization ◽  
Increased Risk ◽  
Attention Deficit Hyperactivity Disorders

Objective To determine the risk of long-term neurologic morbidity among children (up to 18 years) born following in vitro fertilization (IVF) or ovulation induction (OI) treatments as compared with spontaneously conceived. Study Design A population-based cohort analysis was performed, including data from the perinatal computerized database on all singleton infants born at the Soroka University Medical Center (SUMC) between the years 1991 and 2014. This perinatal database was linked and cross-matched with the SUMC computerized dataset of all pediatric hospitalizations. Results Neurologic morbidity was significantly more common in IVF (3.7%) and OI (4.1%) offspring as compared with those following spontaneous pregnancies (3.1%; p = 0.017). In particular, attention deficit/hyperactivity disorders and headaches were more common in the OI group and sleep disorders in the IVF group, whereas autism and cerebral palsy were comparable between the groups. In the Weibull multivariable analysis, while controlling for maternal age, preterm delivery, birthweight centile, maternal diabetes, and hypertensive disorders, IVF (adjusted hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.14–1.71; p = 0.001), but not OI (adjusted HR: 1.17' 95% CI: 0.92–1.48; p = 0.196), was noted as an independent risk factor for long-term pediatric neurologic morbidity. Conclusion IVF offspring appear to be at an increased risk of long-term neurologic morbidity up to 18 years of age.

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