IVF News

3pm EST/ 8pm UK/ 9pm CET, Tuesday 2nd July, 2024.

Moderators:
Andrew Thomson, Dr. Amber Cooper, and Radhika Kakulavarapu

Presenters:
Dr. Alejandro Chavez Badiola “AI consequences”
Kindly sponsored by IVF 2.0

John Whitney " Using data to facilitate compliance in Cryostorage”
Kindly sponsored by CooperSurgical

Dr. Christine Allen "Overcoming the Tower of Babel: Fusion of technologies for streamlined laboratories"
Kindly sponsored by Reproductive Laboratory Services

Q and A

VIEW HERE

A recent study has revealed a significant decline in sperm motility among men applying to be sperm donors at a prominent Danish sperm bank, Cryos International. The study, conducted from 2017 to 2022, observed a notable decrease in both motile sperm concentration and total motile sperm count (TMSC), shedding light on potential implications for human fertility and sperm donor recruitment.

The research analyzed semen samples from 6758 donor candidates aged 18 to 45, collected at sperm bank locations in Aarhus, Aalborg, Copenhagen, and Odense. Despite minor year-to-year variations in semen volume, sperm concentration, and total sperm count, a significant decline in motile sperm concentration and TMSC was evident from 2019 to 2022. Specifically, motile sperm concentration decreased by 16%, and TMSC declined by 22%.

This decline in semen quality among donor candidates is concerning, as motile sperm concentration is a crucial selection criterion for sperm donor acceptance due to its impact on fertility. The study controlled for variables such as age, donation site, and average monthly high temperature, ensuring the reliability of the findings. Notably, the observed decline coincided with the COVID-19 pandemic, suggesting that changes in lifestyle during this period may have influenced sperm quality.

The study also examined data from 1839 accepted donors who provided multiple semen samples during the same period. The results were consistent with the donor candidate data, showing similar trends in declining sperm motility. This decline was observed in both grade A and grade B sperm, indicating an overall reduction in the population of motile sperm rather than a decrease in sperm swimming speed.

These findings underscore the importance of continuous monitoring of semen quality in populations of sperm donors. Gathering health and lifestyle data on donor candidates could help identify causal factors for the decline in sperm quality, potentially leading to personalized interventions to optimize ejaculate quality. This research has significant implications for those involved in medically assisted reproduction and highlights the need for further investigation into the external factors affecting sperm motility.

3pm ET/ 8pm UK/ 9pm CET, Tuesday 25th June, 2024.
This webinar is kindly sponsored by Future Fertility

Moderators:
Sharon Corcoran and Dr. Catello Scarica
Panelist: Jullin Fjeldstad

Presenters:
Dr. Dan Nayot “AI anxiety”
Dr. Jason Swain “IVF staffing”
Prof. Mara Simopoulou “The role of oocyte morphology in preimplantation embryo development”

Q and A

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Recent research from Helmholtz Munich and the German Center for Diabetes Research reveals that fathers' diets and overweight status can impact their children's health even before conception. These findings highlight the importance of a healthy diet for men planning to become fathers, suggesting that a father's nutritional habits can play a crucial role in reducing the risk of their children developing conditions such as obesity and diabetes later in life.

Impact of Paternal Diet on Children's Health

Dr. Raffaele Teperino, head of the "Environmental Epigenetics" research group at Helmholtz Munich, along with his team, explored the significant effects of paternal diet on children's health. Their research focused on small RNA molecules in sperm, known as mitochondrial tRNA fragments (mt-tsRNAs), which are pivotal in the inheritance of health traits by regulating gene expression.

Using data from the LIFE Child cohort, which includes over 3,000 families, the analyses showed a significant correlation between the father's body weight and the weight of their children, as well as their susceptibility to metabolic diseases. This influence was found to be independent of other factors such as the mother's weight, genetic predispositions, or environmental conditions.

Verification through Animal Studies

To validate their findings, the research team conducted a series of experiments using mice. Mice were fed a high-fat diet, which had a greater fat content than a normal diet, to observe the effects on their reproductive organs, specifically the epididymis. The epididymis is a critical area in the male reproductive system where freshly formed sperm mature. The study found that sperm exposed to a high-fat diet in the epididymis resulted in offspring with an increased propensity towards metabolic diseases.

Further laboratory studies using in-vitro fertilization (IVF) demonstrated that mt-tsRNAs from sperm exposed to a high-fat diet significantly influenced gene expression in early embryos. This, in turn, affected the development and health of the offspring, supporting the hypothesis that acquired traits like diabetes and obesity could be transmitted through epigenetic mechanisms across generations.

Epigenetic Mechanisms and Generational Health

This study reinforces the idea that epigenetic mechanisms serve as a molecular bridge between the environment and the genome, affecting health traits across generations. Traditionally, epigenetic transmission was thought to occur primarily through the maternal line. However, this research highlights that paternal health and environmental factors, such as diet, also play a crucial role in this process.

Preventive Health Care for Prospective Fathers

The implications of these findings are profound, particularly for preventive health care. The research suggests that more attention should be given to the health and diet of men who plan to become fathers. Developing targeted health programs focusing on diet and lifestyle for these men could significantly reduce the risk of obesity and diabetes in their children.

Background: The Indirect Influence of Fathers

Mitochondria, often described as the powerhouses of the cell, have their own distinct DNA (mt-DNA) separate from the DNA in the cell nucleus. This mt-DNA is usually inherited from the mother. However, recent studies, including this one, show that sperm also carry fragments of mitochondrial RNA (mt-tsRNAs) into the egg during fertilization. These mt-tsRNAs play a crucial role in epigenetics by regulating gene expression in the early embryo. This regulation can indirectly influence the development and health of the offspring by modifying the activity of certain genes in the mitochondria. Therefore, fathers have an important, albeit indirect, influence on the genetic imprinting of mitochondria and the energy metabolism of their children.

This groundbreaking research underscores the need for a broader perspective on reproductive health, highlighting the significant role that paternal factors play in the health of future generations. By acknowledging and addressing these factors, we can take important steps towards improving preventive health measures for both men and their children.

UNINVITED

3pm ET/ 8pm UK/ 9pm CET, Tuesday 4th June, 2024.

Moderators
Edel Roche, Yaren Yilancilar and Giles Palmer

Presenters:
Dr. Kimball Pomeroy "IVF microbial contamination”

Matt Pettit "Lions and tigers and bears, oh my!"
A talk kindly sponsored by IMT Matcher

Dr. Lotte Stroebech "The role of embryo assays in ensuring media manufacturing quality"
A talk kindly sponsored by ARTSMedia Denmark

Q and A

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Designed for professionals studying alongside their work, the University of Dundee introduced part-time online distance-learning courses in Clinical Embryology and IVF last year, expanding on their considerable experience in delivering full-time on-campus teaching in this subject area. 

To give you the maximum flexibility, you can choose to start off with a Postgraduate Certificate (60 credits over 12 months), or a Postgraduate Diploma (120 credits over 24 months) or go for the full Master's (180 credits over 36 months). You can also start off with the Certificate course, and if that works out well for you, you can continue on to complete the Diploma or full MSc. The courses are taught asynchronously, meaning you can learn when and where it suits you.

The courses will provide you with the wide-ranging education required to become a leader in the field of Assisted Reproductive Technology (ART), including training in basic science, embryology, andrology, clinical and controversial issues and business management. You will also explore research in reproductive medicine, designing and undertaking your own project, joining a world-leading research team in reproductive medicine.

There will be a joint clinical and laboratory focus, due to our dynamic collaboration with a busy clinical ART centre at Ninewells Hospital (one of Europe’s largest University Hospitals). You will have the opportunity to observe various activities within our ART centre, including embryology procedures and following patient journey from initial scans through the entire ART process.

Courses start in August each year. Find out more: https://www.dundee.ac.uk/postgraduate/clinical-embryology-ivf-dl?utm_campaign=pgt-medicine&utm_medium=profile&utm_source=ivf.net

Infertility is a pervasive issue, affecting about one in six people globally. According to the World Health Organization (WHO), millions of couples struggle with this condition, posing significant challenges to reproductive health. The American Society for Reproductive Medicine (ASRM) defines infertility as a disease marked by the inability to achieve a successful pregnancy due to a mix of medical, sexual, and reproductive factors. Often, medical intervention, such as using mature donor gametes, is necessary to achieve pregnancy.

While assisted reproductive technologies (ARTs) like in vitro fertilization (IVF) have transformed the treatment landscape for certain types of infertility, they are not universally effective. Various forms of infertility remain untreatable with current ART methods, motivating researchers to explore new avenues in reproductive medicine.

One promising new technology is human in vitro gametogenesis (IVG). This innovative approach uses pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs) from patients, to generate human germ cells. These germ cells have the potential to mature into gametes in culture, offering hope for treating all forms of infertility, regardless of gender. Despite its potential, human IVG research is still in its early stages. Researchers are currently focused on reconstituting the entire process of human gametogenesis in vitro.

A significant challenge in IVG research is replicating the process of epigenetic reprogramming in human primordial germ cells (hPGCs). This process involves resetting or erasing the inherited parental "memory" of cells on their DNA, a crucial step for proper germ cell differentiation. Successfully achieving this in vitro has proven difficult, hindering progress in the field.

A recent study published in Nature has made significant strides in overcoming these challenges. Led by Dr. Mitinori Saitou at Kyoto University's Institute for the Advanced Study of Human Biology (WPI-ASHBi), the research team identified robust culture conditions necessary for driving epigenetic reprogramming and germ cell differentiation into precursors of mature gametes, known as mitotic pro-spermatogonia and pro-oogonia. This achievement marks a new milestone in human IVG research.

Earlier research by Saitou's team and others successfully generated human primordial germ cell-like cells (hPGCLCs) from PSCs in vitro. These cells exhibited several fundamental features of hPGCs, including propagation capacity. However, they failed to undergo epigenetic reprogramming and differentiation. Aggregating hPGCLCs with mouse embryonic gonadal cells to mimic the microenvironment of the testis or ovary partially addressed this issue. This method, however, was inefficient and impractical for clinical applications, highlighting the need for a more effective solution.

In their new study, Saitou and his colleagues conducted a cell culture-based screen to identify signaling molecules essential for driving epigenetic reprogramming and differentiation of hPGCLCs into mitotic pro-spermatogonia and oogonia. They discovered that bone morphogenetic protein (BMP), a well-known developmental signaling molecule, played a crucial role in this process.

The discovery that BMP signaling is critical for hPGCLC reprogramming and differentiation was surprising, given its established role in germ cell specification. The hPGCLC-derived mitotic pro-spermatogonia and oogonia not only displayed similar gene expression and epigenetic profiles to actual hPGC differentiation in the body but also underwent extensive amplification. This breakthrough allows near-indefinite amplification of these cells in culture, providing the ability to store and re-expand them as needed.

The study also explored potential mechanisms by which BMP signaling facilitates epigenetic reprogramming and hPGCLC differentiation. It appears that BMP signaling attenuates the MAPK/ERK signaling pathway and the activities of DNA methyltransferase (DNMT), both de novo and maintenance. Further investigation is necessary to determine the precise mechanisms and their direct or indirect effects.

This study represents a fundamental advance in understanding human biology and the principles behind epigenetic reprogramming in humans. It also marks a significant milestone in human IVG research. Despite the remaining challenges and the long path ahead, particularly regarding the ethical, legal, and social implications of clinical applications, this research brings us closer to potentially translating IVG into reproductive medicine.

The findings of this groundbreaking study, published in Nature on May 20, 2024, provide a hopeful outlook for the future of infertility treatment. By advancing our understanding of epigenetic reprogramming and germ cell differentiation, researchers are paving the way for new, more effective treatments for infertility, bringing hope to millions of people worldwide.

Sources

News Medical. 21st May 2024. Groundbreaking study advances human in vitro gametogenesis for infertility treatment

https://www.news-medical.net/news/20240521/Groundbreaking-study-advances-human-in-vitro-gametogenesis-for-infertility-treatment.aspx

In the early stages of human embryonic development, a zygote divides into two seemingly identical totipotent cells, which eventually grow into eight cells. Totipotent cells have the potential to develop into any cell type, forming both the embryo and the extraembryonic tissues such as the placenta. Initially, it was believed that all these cells were identical and equally capable of developing into any cell type. However, recent research published in Cell has challenged this view, revealing a more nuanced understanding of early cell fate decisions.

Magdalena Zernicka-Goetz, a developmental and stem cell biologist at the California Institute of Technology and the University of Cambridge, and her team discovered that only one of the two initial cells is truly totipotent, capable of developing into both the body and the placenta. The other cell mainly contributes to the placenta. This groundbreaking finding sheds light on the critical early stages of development and the initial cell fate decisions that determine the embryo's future.

In previous research on mouse embryos, Zernicka-Goetz demonstrated that there is already a bias at the two-cell stage, with one cell more likely to contribute to fetal tissues and the other to the placenta. This new study aimed to explore if similar biases occur in human embryos. To investigate this, Zernicka-Goetz and her team used a sophisticated technique to track cell lineage from the two-cell stage. They injected mRNA for green fluorescent protein (GFP) fused to a membrane trafficking sequence into one of the two cells of the zygote. This allowed them to visualize and determine the contribution of each cell to the development of the trophectoderm (TE) and the inner cell mass (ICM). The TE develops into the placenta, while the ICM eventually produces the epiblast, which forms fetal tissues, and the hypoblast, which forms the yolk sac.

When they tracked GFP expression, the researchers found that one population of cells predominantly contributed to either the ICM or the TE. The imbalance was most pronounced in the ICM, where progeny from one clone at the two-cell stage dominated the population of the epiblast. In contrast, the hypoblast's composition was more evenly split between the cells of the two originating clones. This observation suggests that at the two-cell stage, there is already a bias in cell fate, although it is not a deterministic process.

To further investigate the cell contribution to the ICM, the researchers labeled DNA and actin and tracked cellular positions after division using live cell imaging starting at the eight-cell stage. They observed that asymmetric cell divisions (ACDs) were crucial for forming the ICM. In ACDs, cells that intrude into the growing cell mass become part of the ICM, while those that remain on the surface contribute to the TE. Although ACDs were less common, their composition closely resembled that of the ICM.

In mice, the two-cell stage clone that contributed more to the ICM divided faster than the other cell. The team studied whether this pattern applied to human embryonic development by analyzing movies of actively dividing embryos. They found that in most embryos, one cell at the two-cell stage divided faster, and its progeny also inherited this characteristic. Additionally, the first cell to undergo ACD was usually one of these fast-dividing cells.

"This is the first study to perform detailed cell tracking in a human embryo at such early stages," noted Nicolas Plachta, a developmental biologist at the University of Pennsylvania who was not involved with the study. However, he mentioned that inherent variability in human embryos compared to established mouse models complicates drawing definitive conclusions. This complexity is further exacerbated by the limited availability of zygotes for research, as clinics typically preserve embryos at later developmental stages.

Next, Zernicka-Goetz aims to investigate the features and origins of the differences between clones at the two-cell stage. The study suggests that early cell fate decisions in human embryos are influenced by the dynamics of cell division and the position within the growing embryo, rather than being entirely deterministic.

The research has broader implications for understanding human development and potential applications in reproductive medicine and stem cell therapy. By elucidating the mechanisms of early cell fate decisions, scientists can better understand congenital abnormalities and improve techniques for in vitro fertilization (IVF).

Moreover, this study opens new avenues for exploring how early embryonic cells establish their developmental trajectories. Understanding the interplay between cell division dynamics and fate specification could lead to breakthroughs in regenerative medicine, where controlling cell fate is crucial for developing therapies for various diseases.

In summary, this research highlights the complexity of early human development and provides new insights into how initial cell divisions can influence the entire developmental trajectory of an embryo. The findings challenge the traditional view of totipotency and underscore the importance of studying early cell fate decisions to unlock the mysteries of human development.

Sources

13 May 2024. Cell

• The first two blastomeres contribute unequally to the human embryo

13 May 2024. The Scientist

• The first two cells in a human embryo contribute disproportionately to fetal development

Training Batch Schedule July 2024  

•   June = 03rd to 17th 2024
•  July  =    01st to 15th 2024
• August = 05th to 19th 2024

The International School of Embryology a unit of Chennai Fertility Centre and Research Institute was established to offer training in Advanced Reproductive Techniques and Embryology for clinicians and embryologists. It will help them to know in-depth knowledge and have good hands-on training. The members of our teaching faculty aim to bring Clinician and Embryologists to the highest level of knowledge about Assisted Reproductive Technology and practical capability.

Our courses cover basics in Andrology, Embryology, ICSI & Cryosciences (Hands-on).

Limited Seats. For admission Contact  9003111598 / 8428278218 

Training Batch Schedule 2024  

•   June    =    03rd to 17th 2024

The International School of Embryology a unit of Chennai Fertility Centre and Research Institute was established to offer training in Advanced Reproductive Techniques and Embryology for clinicians and embryologists. It will help them to know in-depth knowledge and have good hands-on training. The members of our teaching faculty aim to bring Clinician and Embryologists to the highest level of knowledge about Assisted Reproductive Technology and practical capability.

Our courses cover basics in Andrology, embryology, ICSI, and cryosciences (Hands-on).

Limited Seats. For admission Contact  9003111598 / 8428278218