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

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).

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

Scientific Reports ◽

10.1038/s41598-021-86242-x ◽

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.

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Use of an oncology sperm bank: a Canadian experience

Canadian Urological Association Journal ◽

10.5489/cuaj.1076 ◽

2013 ◽

Vol 3 (3) ◽

pp. 219 ◽

Cited By ~ 4

Author(s):

Amanda Selk ◽

Timea Belej-Rak ◽

Heather Shapiro ◽

Ellen Greenblatt

Keyword(s):

Assisted Reproductive Technologies ◽

Intrauterine Insemination ◽

Tertiary Care ◽

Retrospective Chart Review ◽

Reproductive Technologies ◽

Success Rates ◽

Oncology Patients ◽

Vitro Fertilization ◽

Sperm Bank

Background: We performed a retrospective chart review in 2006to review oncology patients’ use of banked semen samples infertility treatments at a tertiary care centre.Methods: From 2002 to 2005, 367 oncology patients bankedsemen. During the same period, 31 patients used banked samplesin 48 treatment cycles. Samples were used for intrauterine insemination(IUI) in 28 cycles and for in vitro fertilization (IVF) withor without intracytoplasmic sperm injection (ICSI) in 20 cycles.Results: Pregnancy rates per cycle were 21% for IUI and 50%for IVF with or without ICSI. Overall, 16 of the 31 couples achieveda pregnancy with assisted reproductive technologies (52%).Conclusion: This data indicates high pregnancy success rates withthe use of banked semen samples from men with cancer.Contexte : Une revue rétrospective de dossiers a été effectuée afind’examiner le recours à des échantillons de sperme provenantde patients cancéreux pour le traitement de l’infertilité dans uncentre de soins tertiaires.Méthodes : Entre 2002 et 2005, des échantillons de spermeprovenant d’un total de 367 patients atteints de cancer ont été misen banque. Durant la même période, 31 patientes ont utilisé ceséchantillons au cours de 48 cycles de traitement. Les échantillonsont été utilisés pour insémination intra-utérine (IIU) lors de28 cycles et pour fertilisation in vitro (FIV) avec ou sans injectionintracytoplasmique de sperme (ICSI) lors de 20 cycles.Résultats : Le taux de grossesse par cycle était de 21 % avecl’IIU et de 50 % pour la FIV avec ou sans ICSI. Au total, 16 des31 patientes sont devenues enceintes (52 %).Conclusion : Ces données montrent des taux élevés de grossesseobtenus par l’utilisation d’échantillons de sperme provenantd’hommes atteints de cancer.

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Clinical significance of sperm morphology in male infertility treatment

Experimental and Сlinical Urology ◽

10.29188/2222-8543-2021-14-3-127-132 ◽

2021 ◽

Vol 14 (3) ◽

pp. 127-132

Author(s):

Yu.V. Olefir ◽

◽

D.M. Monakov ◽

◽

Keyword(s):

Male Infertility ◽

Clinical Significance ◽

Sperm Morphology ◽

Assisted Reproductive Technologies ◽

Intrauterine Insemination ◽

Reproductive Technologies ◽

Vitro Fertilization ◽

Normal Sperm ◽

Starting Point

Introduction. Sperm morphology is one of the most common tests in fertility practice. The interlaboratory variability is the main drawback of the method. The clinical significance of sperm morphology in assisted reproductive technologies is controversial. The aim of the review is to address this question. Materials and methods. The search of relevant publications was carried out in PubMed and e-Library databases using the keywords «male infertility», «sperm morphology», «teratozoospermia», «IUI», «IVF», «ICSI». Conference abstracts and dissertations were excluded from analysis and 56 publications were included in this literature review. Results. The small numbers of studies were evaluated to the effect of teratozoospermia on the likelihood of natural pregnancy. The pregnancy rate was higher in the group of couples with normozoospermia. In the couples with severe teratozoospermia pregnancies rate was also detected. The most studies did not reveal a statistically significant effect of tertozoospermia on the frequency of pregnancy during intrauterine insemination. The data about the influence of sperm morphology on in vitro fertilization are contradictory. Early studies showed a positive correlation between normal sperm morphology and frequency of conception, but these results were not confirmed in further studies. The most studies have not been revealed the correlation between normal sperm morphology male fertility status, clinical and live birth rate. Discussion. To date the spermatozoa mofophology studying remains the «starting point» ofa man's examination for infertility. However, the data available do not confirm its role in choosing the method ofassisted reproductive technologies or predicting their results. Conclusions. To date the role of sperm morphology on conceive and pregnancy frequencies in ART use is controversal. The data available does not confirm the value of this test as a proxy of higher pregnancy and birth of healthy child probability. The further studies are required to address this question.

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

10.1093/med/9780190681098.003.0008 ◽

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.

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Reproductive Technologies

Anthropology ◽

10.1093/obo/9780199766567-0200 ◽

2019 ◽

Author(s):

Amy Speier ◽

Caridad Zamarripa

Keyword(s):

Assisted Reproductive Technologies ◽

Intrauterine Insemination ◽

Petri Dish ◽

Reproductive Technologies ◽

Human Reproduction ◽

Vitro Fertilization ◽

Gay Fathers ◽

The People ◽

Future Child

Reproductive technologies are those technologies that aid in animal and human reproduction. Assisted reproductive technologies (ARTs) are more narrowly defined as those technologies that help people suffering from social or bodily infertility create a family. Socially infertile includes single women and men as well as homosexual couples who rely on donated gametes for the creation of a future child. Intrauterine Insemination (IUI) is usually the first step taken by couples having trouble conceiving. The most general type of reproduction technology is in vitro fertilization (IVF), which means that the egg is retrieved from a woman’s uterus and sperm is introduced to these eggs in a petri dish. In the case of male infertility, intracytoplasmic sperm injections (ICSI) may be employed, which means that sperm are injected directly into the egg. IVF may include the use of donated sperm, oocytes, and embryos. In addition to gamete donation, surrogacy may be employed in cases where an intended mother or intended gay fathers cannot carry a pregnancy to term. In addition to being used to create families, contraception is also considered a reproductive technology. Anthropologists have been conducting ethnographic analyses of reproductive technologies by studying the people intimately engaged with these varying technologies. Scholarship revolves around major questions about markets and gift exchange, kinship, and how our understandings of family have shifted with the advent of reproductive technologies, as well as globalization and the ways in which bodies, people, and technologies traverse the globe.

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

The International Journal of Developmental Biology ◽

10.1387/ijdb.180402gp ◽

2019 ◽

Vol 63 (3-4-5) ◽

pp. 217-222 ◽

Cited By ~ 6

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.

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

GYNECOLOGY ◽

10.26442/2079-5696_20.1.113-116 ◽

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.

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

10.21516/2413-1458-2019-18-2-162-168 ◽

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.

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

Journal of Clinical Medicine ◽

10.3390/jcm10122687 ◽

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.

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GAMETE DONATION. ETHICAL AND LEGAL ASPECTS

Reproductive Medicine ◽

10.37800/rm2020-1-21 ◽

2020 ◽

pp. 13-19

Author(s):

L. Chalova ◽

V. Lokshin ◽

A. Guseva ◽

A. Kinzhibayev

Keyword(s):

In Vitro Fertilization ◽

Literature Review ◽

World Literature ◽

Assisted Reproductive Technologies ◽

Reproductive Technologies ◽

Legal Aspects ◽

Gamete Donation ◽

Vitro Fertilization ◽

National Legislation

This world literature review tries to determine the significance of the gamete donation in the field of assisted reproductive technologies as well as the availability of treatment methods using donation in in vitro fertilization programs. Gamete donation is regulated by every country's national legislation system, and quite often the laws vary between the states. There are practically no universal standards and/or rules in this area, which, in turn, leads to an ambivalent reaction towards reproductive practices.

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