IVF News

Tuesday 16th September 3pm ET, 8pm BST, 9pm CET
Moderator:
Prof. Nick Macklon
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Prof. Nick Macklon - How to write a good paper in 18 paragraphs. 
Dr. Gareth Dyke - Overview of AI tools for research, writing and publishing: Maintaining ethics and integrity while making your life easier
Duncan Nicholas - What authors can expect from the submission and review process. How to respond to decision letters
Fiona Warrander - The Editing after Acceptance; making good papers better
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New models provide insights into early human development and infertility

Researchers have created advanced stem cell–based embryo models that are beginning to unlock the molecular events driving implantation and early pregnancy. These models, derived from human stem cells, replicate key stages of development and provide a window into processes that are otherwise hidden in the uterus.

The models recapitulate the transition from a cluster of undifferentiated cells to a structured blastocyst, with segregation of the epiblast, hypoblast, and trophectoderm lineages. This organization is critical for implantation, when the trophectoderm interacts with the endometrium while the epiblast gives rise to the embryo proper. The Caltech-led team used their model system to map signaling pathways that coordinate these events, with a particular focus on how cell–cell communication ensures proper timing.

One key finding centers on the role of FGF and MAPK signaling in establishing epiblast identity and maintaining balance between embryonic and extraembryonic fates. Perturbations of these pathways in the model disrupted lineage allocation, producing structures that failed to mimic natural embryos. This provides direct evidence that dysregulation of growth factor signaling may contribute to implantation failure in IVF, where embryos often appear morphologically normal yet do not progress.

The models also revealed crosstalk between the trophectoderm and epiblast mediated by NODAL and BMP pathways. These signals are thought to regulate differentiation of extraembryonic tissues that support implantation. By manipulating these pathways, the researchers were able to reproduce scenarios resembling early developmental arrest. This work highlights the importance of precise paracrine signaling between compartments of the embryo, and suggests that even subtle misalignment can block the establishment of pregnancy.

Another insight came from studying the interface between the embryo model and an endometrial mimic. The researchers observed that successful adhesion depended on a specific cascade involving integrins and extracellular matrix remodeling. When the signaling was blocked, the embryo model failed to implant, underscoring how molecular dialogue between embryo and uterus is indispensable.

Together, these findings show that stem cell–based embryo models can go beyond structural resemblance and act as functional systems for dissecting signaling dynamics. For reproductive medicine, the implications are significant. These models could help identify biomarkers of implantation competence, refine embryo culture media by targeting supportive pathways, and suggest therapeutic strategies for recurrent implantation failure or early miscarriage.

By combining stem cell biology with developmental systems modeling, researchers are providing a mechanistic framework for one of the most elusive steps in reproduction. The ability to probe early human development at this level may ultimately improve IVF outcomes by aligning embryo assessment with underlying molecular health rather than morphology alone.

Sources

9 September 2025. Caltech

Stem cell–based embryo models reveal pathway to understanding fertility

5 September 2025. Developmental Cell

Stem cell–based embryo models reveal a pathway to understanding fertility

New research from the University of Hawaiʻi at Mānoa has revealed how the loss of a single gene on the Y chromosome can disrupt male fertility. The study focused on the zinc finger transcription factors Zfy1 and Zfy2 in mice. These genes are expressed during sperm development and were suspected to play essential roles, but their precise contribution had remained unclear. By using CRISPR to generate mice lacking one or both copies, researchers were able to observe the consequences of these deletions across multiple stages of spermatogenesis.

The findings show that loss of Zfy2 alone significantly reduces sperm quality, while removal of both Zfy1 and Zfy2 results in complete infertility. Germ cells in the knockout mice failed to progress normally through meiosis, and defects were most pronounced at later stages when spermatids undergo chromatin remodeling. Without the Zfy genes, sperm DNA packaging was abnormal, leading to poor structural integrity and loss of function. Increased rates of programmed cell death were also observed, further reducing the pool of viable sperm.

Transcriptomic analysis revealed the scale of disruption caused by the absence of these Y-linked factors. Hundreds of genes were misregulated in the knockout mice, particularly those associated with chromatin organization, alternative splicing, and apoptosis. This highlights Zfy as a master regulator, with its influence extending across the gene networks required for healthy sperm production.

Although this work was performed in mice, the human genome contains a single ZFY gene that may serve a comparable role. Human male infertility is often idiopathic, with no clear explanation in many cases. Insights from this study suggest that mutations or dysregulation of ZFY could be a hidden factor contributing to some of these cases. By clarifying how Y-linked transcription factors shape sperm development, the research opens new avenues for diagnostic testing and potentially therapeutic strategies.

The study underscores how removal of a single Y-chromosome gene can cascade into widespread disruption of reproductive biology. For scientists seeking to understand the molecular origins of male infertility, these findings position ZFY at the center of the regulatory landscape governing spermatogenesis.

Sources

9 September 2025. University of Hawaii News

• Missing Y gene linked to male infertility

27 August 2025. Cell Death & Differentiation

• Large-scale transcriptomic analyses reveal downstream target genes of ZFY1 and ZFY2 transcription factors in male germ cells

For decades, scientists have believed that human eggs accumulate harmful genetic mutations as women age, contributing to infertility and pregnancy complications. A new study is reshaping that understanding, showing that eggs are far more resilient to DNA damage than previously thought.

Researchers analyzed thousands of eggs and compared them with other types of cells, focusing on how mutations arise and persist over time. They found that, unlike sperm and somatic cells, eggs accumulate very few mutations as women get older. This discovery challenges a long-standing assumption in reproductive biology: that maternal age effects are primarily driven by mutation load in the egg.

The study highlights that oocytes, which remain dormant in the ovaries for decades, have built-in protective mechanisms that safeguard them from genetic damage. One striking finding is that eggs appear to avoid common age-related mutations, such as those caused by oxidative stress. This contrasts sharply with sperm, which continue dividing throughout a man’s life and accumulate mutations with every cell division.

While this protective mechanism does not eliminate the well-documented age-related decline in egg quality, it suggests that other biological processes may be more responsible. Chromosomal errors, such as nondisjunction leading to aneuploidy, still increase with maternal age and remain the primary factor behind reduced fertility and miscarriage risk in older women. However, the new evidence indicates that point mutations in DNA play a smaller role than once feared.

These insights have implications for fertility treatment and genetic counseling. By refining our understanding of how eggs age, researchers may be able to develop new strategies to preserve fertility or improve outcomes in assisted reproduction. It also deepens our knowledge of how the female germline is uniquely adapted to protect genetic integrity across decades, ensuring healthy transmission of DNA to the next generation.

This research shifts the narrative from one of inevitable mutation buildup to one of remarkable biological resilience, opening new avenues in the study of reproductive longevity and human development.

Sources

6 August 2025. New Scientist

• Human eggs don't accumulate as many mutations with age as we thought

6 August 2025. Science Advances

• Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations

13 August 2025. Live Science

• Human eggs have special protection against certain types of aging, study hints

7 August 2025. Medical Xpress

• Human eggs are protected from age-related genetic mutations, mtDNA study finds

First 3D images reveal the forces driving this crucial stage of development

For the first time, scientists have recorded a human embryo implanting into the uterine lining in real time. Using advanced 3D imaging and bioengineered models, researchers have shown that the process is not passive but relies on strong traction forces exerted by the embryo itself.

The work, published in Science Advances, compared human and mouse embryos and revealed distinct species-specific implantation patterns. Human embryos generated powerful pulling forces that allowed them to penetrate the endometrial tissue, while mouse embryos relied on different mechanical strategies. This highlights how mechanosensitivity and force generation drive implantation in a uniquely human manner.

Researchers at the Institute for Bioengineering of Catalonia developed a synthetic hydrogel that mimics uterine tissue. With this system, they were able to capture live, 3D recordings of human embryos embedding themselves for the first time. The footage shows embryos actively gripping, deforming, and burrowing into the tissue-like substrate.

These findings reshape our understanding of implantation, a critical stage that often determines the success or failure of pregnancy and IVF treatments. Implantation failure is one of the main barriers in assisted reproduction, and better insight into the mechanics involved may help refine embryo selection and improve culture conditions.

The 3D images and live recordings also provide a new platform to study how embryos interact with the maternal environment. This opens possibilities for exploring why implantation sometimes fails and how endometrial receptivity and embryo quality together contribute to outcomes.

The research demonstrates that implantation is a dynamic, force-driven process and not simply a matter of embryo adhesion. As this knowledge is refined, it may guide new approaches to both clinical IVF practice and reproductive biology research.

Sources

15 August 2025

Science Advances

• Traction force and mechanosensitivity mediate species-specific implantation patterns in human and mouse embryos

15 August 2025

Institut for Bioengineering of Catalonia

• Human embryo implantation recorded in real time for the first time

15 August 2025

Nature News

• Watch a human embryo implant itself – with brute force

15 August 2025

The Scientist

• Scientists watched human embryos implant for the first time

16 August 2025

ScienceAlert

• World first: scientists film the exact moment a human embryo implants

19 August 2025

Smithsonian Magazine

• See the first 3D images of a human embryo implanting, shedding light on the crucial but little-known process

Wednesday, 24 September 2025, 5.30pm - 7.30pm (BST) Online Event

A free-to-attend online event marking the 100th birthday of the late IVF pioneer Professor Sir Robert Edwards, known widely (and affectionately) as 'Bob'.

This event will explore Bob's life and legacy, including the recent dramatisation of his work with Patrick Steptoe and Jean Purdy in the film Joy. The discussion will be chaired by Sarah Norcross, with speakers including:

• Dr Jenny Joy (Bob's daughter)
• Professor Barry Bavister (who worked with Bob to achieve the first human IVF in the laboratory in 1968)
• Grace MacDonald (who gave birth to the world's second IVF baby, Alastair MacDonald, in 1979)
• Professor Geraldine Hartshorne (who completed her PhD under Bob's supervision in 1988)
• Jane Blower, Professor Alfonso Martínez Arias and Professor Nick Hopwood (who will discuss the impact of Bob's work on various aspects of science, medicine and history)

This event is produced by the Progress Educational Trust (PET), in partnership with the Association of Reproductive and Clinical Scientists.

All are welcome. To attend/participate via the web, please [ Register Now ].

Speakers

Dr Jenny Joy

Daughter of the late IVF pioneer Professor Sir Robert Edwards, and was responsible for cataloguing the bulk of what is now the extensive Robert Edwards Archive at the Churchill Archives Centre

Previously worked at Bourn Hall Clinic, the IVF clinic that Edwards established

Professor Barry Bavister

Worked with Robert Edwards and Patrick Steptoe – and drew upon his own earlier research with animal embryos – to achieve human IVF in the laboratory in 1968, and then coauthored the 1969 paper (with Edwards and Steptoe) describing this achievement. Was previously Professor of Conservation and Reproductive Biology at the University of New Orleans, and at the Audubon Centre for Research of Endangered Species (part of the Audubon Nature Institute).

Grace MacDonald

Gave birth to the world's first IVF boy – Alastair MacDonald – in Glasgow in January 1979, becoming the second woman (after Lesley Brown) ever to have a child following IVF

Was one of at least 282 volunteer patients to be treated with (then experimental) IVF at Oldham between 1969 and 1978 – only two of these patients (Lesley and Grace) went on to have a live birth

Professor Geraldine Hartshorne

Completed her PhD under the supervision of Robert Edwards in 1988, and is now Scientific Director of the Coventry Centre for Reproductive Medicine and a Professorial Fellow at Warwick Medical School

Contributor to books including Visualisation in Medicine and Life Sciences(buy from Amazon UK), the Textbook of Clinical Embryology (buy from Amazon UK), The First 12 Weeks of Gestation (buy from Amazon UK), Essential IVF (buy from Amazon UK) and the Textbook of IVF and Assisted Reproduction (buy from Amazon UK)

Jane Blower

President of the Association of Reproductive and Clinical Scientists, and the first person in the UK to achieve a master's degree in Assisted Reproduction Technology (at the University of Nottingham in 1992)

Previously worked for more than 30 years at University Hospitals of Leicester NHS Trust (in roles including Consultant Embryologist and HFEA Person Responsible), and also worked at NHS England as Deputy Chief Scientific Officer for England

Professor Alfonso Martínez Arias

Research Professor at the Catalan Institution for Research and Advanced Studies and at Pompeu Fabra University

Author of the book The Master Builder: How the New Science of the Cell is Rewriting the Story of Life (buy from Amazon UK), coauthor of the book Principles of Development (buy from Amazon UK), and advocate for raising standards in research involving stem-cell-based embryo models

Professor Nick Hopwood

Professor of History of Science and Medicine at the University of Cambridge, and Co-Chair of Cambridge Reproduction

Author of the forthcoming book The Many Births of the Test-Tube Baby, author of other books including Embryos in Wax (buy from Amazon UK) and Haeckel's Embryos (buy from Amazon UK), and coeditor of the book Reproduction: Antiquity to the Present Day (buy from Amazon UK)

Sarah Norcross

Director of PET and Commissioning Editor of BioNews

Host of the Progress Educational Trust podcast

A new study from Yale School of Medicine suggests that an unusually thin endometrial lining may not always reduce IVF success. The study emphasized that when the uterine cavity is structurally normal—without adhesions or other abnormalities—IVF outcomes can still be positive, even with persistently thin lining. This finding challenges previous assumptions about limiting embryo transfers solely on the basis of thin endometrium.

A complementary large-scale retrospective international study investigated over 30,000 frozen embryo transfers using single euploid blastocysts across varied cycle types. It found that live birth rates declined when endometrial thickness was under 7 mm in programmed and modified natural cycles—but not in natural cycles. The effect also varied by location and protocol. Notably, endometrial thickness alone was a poor overall predictor of live birth.

Together these findings offer important nuance. A thin lining does not automatically preclude success in IVF, especially in natural cycle protocols or when uterine conditions are good. However, when using programmed or modified natural cycles, a lining under approximately 7 mm may modestly reduce live birth chances. Rather than cancelling transfer outright, clinical decisions should consider the full context—including cycle type, uterine health, and other indicators of receptivity.

Sources

• Yale School of Medicine. August 11, 2025

Thin Endometrium May Not Hinder IVF Success

• Human Reproduction. August 11, 2025

Does endometrial thickness impact live birth rate following a frozen embryo transfer: outcomes of 30 676 euploid single embryo transfers

A baby boy named Thaddeus Daniel Pierce was born on July 26, 2025, in Ohio from an embryo first created and frozen in 1994—resulting in the longest‐known interval between embryo cryopreservation and a successful live birth.

Experimental AI conversation.

The embryo was originally one of four produced during an IVF cycle by Linda Archerd in May 1994. After Archerd used one embryo to conceive her daughter (now about 30 years old), she retained custody of the remaining three following a divorce. Becoming unable to carry any more children herself, she placed the embryos up for “embryo adoption” through Nightlight Christian Adoptions’ Open Hearts program in 2022. 

Lindsey and Tim Pierce, who had been trying to conceive for seven years, were matched with one of the donated embryos. Of the three embryos transferred, one failed post-thaw, two were transferred to Lindsey’s uterus, and one implanted and developed into Thaddeus. Despite a difficult birth, both mother and baby are reported to be doing well. 

According to Dr. John David Gordon, the nearly 31‑year duration (more than 11,000 days in storage) between embryo freezing and live birth sets a new world record. The previous record was approximately 30 years. 

Scientific data supports the viability of long-term embryo cryopreservation. A review of over 11,000 cryopreserved embryos found no significant impact of storage duration on survival, implantation, or live birth rates. Successful births from embryos stored up to 27 years had previously been recorded .

This achievement highlights remarkable advancements in IVF and cryopreservation techniques, including vitrification methods that prevent damaging ice crystal formation. It also raises ethical and legal considerations, such as management of long-term stored embryos (estimated at around 1.5 million in the U.S.), decisions around their fate, and implications of policies granting frozen embryos legal status. 

Sources

29 July 2025. MIT Technology Review

• A record-breaking baby has been born from an embryo that’s over 30 years old

31 July 2025. The Guardian

• World’s ‘oldest baby’ born from embryo frozen in 1994