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News: Groundbreaking Study Advances Human In Vitro Gametogenesis for Infertility Treatment

IVF.net Newsdesk 01 June 2024

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


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News: Unveiling the Secrets of Early Human Development: Totipotency and Cell Fate Bias in Embryos

IVF.net News 01 June 2024

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

13 May 2024. The Scientist


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Announcement: ART & Embryology training program

Chennai Fertility Centre and Research Institute 01 June 2024
ART & Embryology training program

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 


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News: ART & Embryology training program

Chennai Fertility Centre and Research Institute 02 May 2024
ART & Embryology training program

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 


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Webinar: ARE ONLINE WEBINARS HELPING EMBRYOLOGISTS TO PASS THE CERTIFICATION EXAMS ?

Marc Van den Bergh 26 April 2024

Based on a published curriculum, 39 webinars were and are still accessible as records to view on demand between begin 2022 and september 2023.

For 35 webinars a self-assessment multiple questionnaire was available, together with handouts and a printout of the questions. A total of 640 questions were at the disposal of the participants. As there was no obligation to participate in all webinars the number of attendees varied between 15 and 42.
The completed questionnaires were analysed and the attendees received a report indicating the false answers. Attendees who had less than 60% correct answers were invited to review the topic. 
In January 2024 a global evaluation of all answers was made. The mean percentage of correct answers was calculated for 35 questionnaires, The minimum and maximum number of correct answers was analysed and the percentage of participants who had 65% or more correct answers was calculated. 
The mean % of attendees who had 65% or more correct answers was 80% +/- 12 % SD. The webinar with the lowest mean % of attendees who had 65% or more good answers was: " Cell structure and Cell Organelles".
The lowest median score of correct answers was obtained for the " Risk Management" webinar, with only 47% of attendees who had 65% or more correct answers.The webinars with lowest interest- number of attendees-was " Treaths of microorganisms in ART". The webinar with the largest number of attendees was "Controled Ovarian Stimulation": 42 . 

From the embryologists who obtained their certification or senior certification in 2022 and 2023, 12 participated to the webinars and completed the self-assesment questionnaires.


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News: ART & Embryology training program

Chennai Fertility Center and Research Institute 23 April 2024
ART & Embryology training program

Training Batch Schedule 2024  

  •    May    =      06th to 20th 2024
  •   June    =    03rd to 17th 2024
  •   July      =    01st to 15th 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 


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News: MERLN Pioneers New Approach for Studying Monozygotic Twin Formation

IVF.net Newsdesk 21 April 2024
MERLN Pioneers New Approach for Studying Monozygotic Twin Formation

Researchers at Maastricht UMC+ and the MERLN Institute have developed the first embryo structure capable of mimicking the formation of human identical twins, utilizing only stem cells without the need for gametes. This breakthrough allows unprecedented insight into the formation of identical twins, where the rapid expansion of the blastocyst—a sac comprised of placental cells that houses the stem cells from which life originates—causes the embryo to split into two. Published in the prestigious journal Advanced Materials, this research leverages a sophisticated technological platform that has been revealing intricate biological processes over the years, facilitating the controlled growth of cells, tissues, organs, and embryos. The focus of this current study is on understanding the crucial early stages of healthy embryo implantation and development, offering a new avenue to explore foundational micro-processes that have traditionally been obscured within the womb. This research aims to enhance biomedical care, making it more accessible and affordable globally.

Applications in Medicine

The creation of synthetic embryos from stem cells has reached a fidelity that provides essential insights into natural embryonic development. This research has practical implications, particularly in enhancing our understanding of miscarriages and infertility. It offers potential solutions to fertility issues and improvements in contraception methods. Historically, three-quarters of identical twins have shared a single placenta, a phenomenon that until now was poorly understood. This new discovery could illuminate the underlying mechanisms of this occurrence. Moreover, twin pregnancies often involve complications that manifest during the early stages of implantation, which can now be studied more effectively, potentially leading to preventive measures or treatments.

Innovative Research Platforms: High Throughput and Implantation-on-Chip

In the lab, these early-stage synthetic embryos are cultivated for up to 14 days and subjected to thousands of parallel high-throughput experiments. Each experiment uses unique combinations of growth factors and signaling molecules to determine the optimal conditions for embryonic growth during the first week, including precise timing. For the second week of growth, researchers have developed an "implantation-on-chip" platform, which enables the cultivation and examination of small samples of uterine tissue on a microfluidic chip to optimize conditions for embryo implantation in the uterus. Lead researcher Erik Vrij noted that this platform could predict the success of treatments following procedures like IVF and PGT.

Enhancing Medical Care Through Advanced Technologies

The integration of robotics and machine learning is refining the simulation of biological processes, with the high-throughput approach increasing the likelihood of successfully creating a twin embryo model. According to MERLN's founder, Professor Clemens van Blitterswijk, the identified formulas from this research could lead to the development of tissue-specific stem cells, tissues, and organ parts for patient treatment. The goal is to enable these advancements on a scale that could significantly help a large number of people while keeping costs manageable.

This research forms part of the PhD thesis of Dorian Luijkx under the supervision of Erik Vrij, Stefan Giselbrecht, Clemens van Blitterswijk, with collaboration from Asli Ak and Ge Guo of the University of Exeter.

Source: 

MERLN Develops the First Model for Monozygotic Twinning

https://merlninstitute.com/news-and-events/news/um-merln-institute-develops-the-first-model-for-monozygotic-twinning


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Announcement: Cryopreservation in Assisted Reproduction - A Practitioner's Guide to Methods, Management, and Organization

IVF.net Newsdesk 21 April 2024
Cryopreservation in Assisted Reproduction - A Practitioner's Guide to Methods, Management, and Organization

We are excited to announce the upcoming release of "Cryopreservation in Assisted Reproduction: A Practitioner's Guide to Methods, Management, and Organization" by Springer Nature. This comprehensive guide delves deep into the critical aspects of cryopreservation, a cornerstone of assisted reproductive technologies, and goes beyond traditional protocol books by covering organizational strategies, auditing, and inventory management.

Highlights Include:

  • Integration of AI and Automation: Learn how advanced technologies are transforming reproductive tissue banking.
  • Adapting to New Legal Frameworks: Explore the emerging regulations that are shaping the future of reproductive medicine.

Innovative Breakthroughs in Reproductive Technology:

  • CryoSentinel: Thermographic Imaging for Safety - This innovative approach utilizes advanced monitoring to ensure the safety of cryopreserved specimens through the use of thermographic technology.
  • Advanced Robotic Cryostorage Solutions – Explore how robotic systems from TMRW are transforming sample storage, enhancing safety, and improving accessibility.
  • Automating Vitrification – Learn about Fertilesafe's innovations designed to streamline vitrification processes for better efficiency and outcome predictability.

Featuring contributions from over 50 key opinion leaders in the field of in vitro fertilization (IVF), this book is a treasure trove of knowledge and expertise. It serves as an essential resource for clinicians, embryologists, lab technologists, IVF lab directors, and researchers. The guide presents well-established procedures in cryopreservation while also highlighting novel techniques and the latest innovations in the field.

Your Comprehensive Guide to Cryobiology: This publication promises to revolutionize the approach to cryopreservation in assisted reproduction, focusing on both the scientific and practical aspects of managing and organizing advanced reproductive technologies.

Prepare to dive into a world of groundbreaking innovations and advanced platforms that are setting new standards in the field of reproductive medicine. "Cryopreservation in Assisted Reproduction" is set to be an indispensable resource, guiding professionals through the complexities of modern reproductive technologies with the latest scientific advancements.

https://link.springer.com/book/9783031582134


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Conference: IVIRMA Assisted Reproduction Symposium

IVIRMA Global 02 April 2024
IVIRMA Assisted Reproduction Symposium

We are thrilled to extend a warm invitation to you for the upcoming 2nd IVIRMA Assisted Reproduction Symposium scheduled from May 8th to 11th, 2024.

This four-day symposium is specially designed for physicians, embryologists, nurses, and geneticists. It will be conducted online and is free of charge.

The event will feature distinguished international speakers who will cover cutting-edge topics such as PGT-A findings, experimental therapies for ovarian aging, non-invasive embryo assessment, immunological treatments, and the significance of the endometrium in reproductive success.

Chairman

  • Emre Seli

Scientific Secretary

  • María Delgado

Scientific Committee Members

  • Jason Franasiak
  • Juan Antonio García-Velasco
  • Sonia Herraiz
  • Jessica Medvedich
  • Marcos Meseguer
  • Thomas Molinaro
  • Laura Rienzi
  • Denny Sakkas
  • Emre Seli
  • Dagan Wells
  • Marie Werner

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Webinar: UP CLOSE AND CLINICAL

International IVF Initiative 02 April 2024
UP CLOSE AND CLINICAL

3pm ET/ 8pm UK/ 9pm CET, Tuesday 23rd April 2024.

This webinar is kindly sponsored by Future Fertility

Moderators:
Dr. Rita Vassena and Dr. Kathy Miller

Panelist: Dr. Sergio Papier

Presentations:

Moonshots and last miles: what it may take to treat
infertility for all- Dr. Rita Vassena

Opening the black box: why do euploid blastocysts fail to
implant? A systematic review and meta-analysis- Dr. Danilo Cimadomo

An artificial intelligence tool predicts blastocyst
development from static images of fresh mature oocytes- Jullin Fjeldstad

Storage trends, usage and disposition outcomes following egg
freezing- Molly Johnson

Q and A

REGISTER HERE


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