IVF News

18th November, 3pm EST, 8pm UK, 9pm CET
This webinar is kindly sponsored by Future Fertility

Moderators:

Dr Munevver Serdarogullari and Dr Nacho Landaburu Mari

Panelist:
Jullin Fjeldstad

Presenters:
Dr Yosu Franco Iriarte: The history of eggs
Dr Dan Nayot: Oocyte quality and stimulation protocols
Dr Daniela Braga: Can oocyte quality be an additional KPI in cases with severe male factors?

Q and A

VIEW HERE

In a recently published case report, researchers describe the first known instance of a healthy live birth following the microsurgical removal of an extra female pronucleus (PN) from a tripronuclear (3PN) human zygote derived from intracytoplasmic sperm injection (ICSI). 

Background

In conventional in-vitro fertilisation (IVF) and ICSI treatments, a normally fertilised zygote is characterised by the presence of two pronuclei (one from sperm, one from oocyte) and two polar bodies.  Zygotes with three pronuclei (3PN) are typically regarded as non-viable because they often imply triploidy or other major chromosomal abnormalities, and have historically been discarded.  However, prior studies have shown that a proportion of ICSI-derived 3PN embryos may in fact be biparental diploid (for example due to pronuclear fragmentation or chromosomal dispersion rather than true additional sets of chromosomes). 

Case summary

A 33-year-old woman with a history of five spontaneous miscarriages was treated with ovarian stimulation and ICSI. Of 20 oocytes retrieved, 10 were mature and injected; 8 were fertilised but only one reached a normal 2PN configuration, while seven zygotes showed 3PN.  Among the 3PN zygotes, six had only one polar body (1 PB), which the authors interpret as indicative of a female PN derived from a failure of the second polar body extrusion.  With appropriate patient consent and ethical approval, the laboratory team performed microsurgical enucleation to remove the female PN in those six 3PN zygotes at approximately 19 hours after ICSI (about 10 :00 a.m. on Day 1). 

All six zygotes survived the enucleation and were cultured further. Four of the six cleaved, and by Day 6 two reached blastocyst stage (grades 4AB and 4BB). Genetic screening using non-invasive chromosome screening (NICS) revealed that one of the blastocysts (4BB) was mosaic with a 51% deletion on chromosome 15, while the other (4AB) was euploid.  The euploid blastocyst was cryopreserved, thawed and transferred in a subsequent cycle. The resulting pregnancy progressed uneventfully (aside from placenta previa requiring cesarean section at 35 weeks and 2 days) and produced a live boy weighing 2,540 g who at nine months of age showed no developmental or health impairments. 

Mechanistic and technical considerations

The authors emphasise that performing microsurgical enucleation in ICSI-derived 3PN embryos is potentially safer than in conventional IVF-derived 3PN embryos, because in ICSI only a single sperm is injected, reducing the risk of introducing an extra set of centrioles.  They further describe criteria by which the female pronucleus was distinguished (smaller size, fewer nucleolar precursor bodies, closer proximity to the polar body) prior to removal.  Technical details of the micromanipulation procedure are provided, including needle parameters, fixation of the zygote, and removal of the PN.  The authors also note that the patient’s oocytes displayed spindle abnormalities and other meiotic errors (giant polar bodies, multipolar spindles, nondisjunction) suggesting the underlying cause of the 3PN formation. 

Significance and caveats

This report presents a proof of concept that a subset of 3PN zygotes can be rescued via targeted microsurgery, cultured to blastocyst, undergo genetic screening and lead to a healthy live birth. It challenges the blanket policy of discarding all 3PN embryos and suggests that under stringent conditions such rescue may be feasible. The authors stress however that this remains experimental; the method is not yet standard of care, the efficiency remains low (only two blastocysts from six enucleated zygotes) and long-term follow-up of offspring is required to exclude imprinting disorders or epigenetic effects.  They caution that patient selection (e.g., very few viable embryos, unwilling to repeat cycle) and robust ethical oversight are essential. 

Implications for practice and research

For embryology labs dealing with rare cases of 3PN zygotes in patients with limited oocyte yield or repeated embryo failure, this technique may in the future become an option, pending further research. From a research perspective this opens avenues to explore the developmental potential of abnormal-looking zygotes, improve micromanipulation survival rates, and address the epigenetic and long-term safety outcomes of such rescued embryos. It also suggests refining the criteria by which 3PN zygotes are evaluated (for example presence of two polar bodies vs one) and investigating mechanisms behind spontaneous diploidisation or pronuclear fragmentation.

Given your work at IVF Store supporting labs and embryology services, this case could influence how labs counsel patients in scenarios of 3PN zygote formation, how they track outcomes of “abnormal” fertilisation events, and how rescue manipulations may be evaluated. It would be prudent to keep a balanced view: while promising, the technique is still very limited in scale, and standard practice remains to discard 3PN embryos due to the high risk of chromosomal abnormalities. Larger series, randomized data and long-term follow-up are needed before broader adoption.

Sources

4 November 2025. Bioengineer.org

• Successful live birth from tripronuclear zygote enucleation

4 November 2025. Journal of Ovarian Research

• Healthy live birth after microsurgical enucleation of tripronuclear human zygote derived from ICSI: a case report

4 November 2025. Gene Online

• Healthy baby born after microsurgical removal of extra pronucleus in tripronuclear zygote

The independent UK regulator for fertility treatment and human embryo research, the Human Fertilisation and Embryology Authority (HFEA), has published its annual sector report covering the period from 1 April 2024 to 31 March 2025. The report provides an overview of inspections, incidents, clinic licensing, patient feedback and other regulatory activity in UK-licensed fertility clinics.

One of the headline findings is reassurance around safety: during the year over 100,000 fertility treatment, storage or donation cycles took place across licensed clinics, with incidents occurring in less than 1% of those cycles.  The total number of incidents reported rose by 36 %, from 581 in 2023/24 to 792 in 2024/25.  However, none of the incidents in 2024/25 were at the most serious “Grade A” level, and the majority of the increase was due to lower-grade (Grade C) incidents, many of which relate to clinic administration, laboratory process and minor clinical issues. 

In terms of regulatory oversight, the HFEA conducted 88 inspections in 2024/25 (down from 104 in the prior year), reflecting changes in licence term lengths introduced during the COVID-19 period.  During those inspections, 131 non-compliances were identified, down from 226 in the previous year (though also reflecting fewer inspections overall).  The number of licensed clinics rose to 141 in total, of which 107 were licensed to provide treatment (an increase of six clinics). 

The report also highlights evolving market dynamics. Private ownership remains dominant among treatment clinics: of the 107 treatment-licensed clinics, 71 (66 %) were privately owned and 49 of those were part of larger clinic groups.  Another noteworthy trend is that an increasing share of cycles are self-funded rather than funded via the UK National Health Service (NHS). The HFEA reports that only 27 % of cycles in recent periods were NHS-funded, compared with 35 % in 2019. 

Patient feedback remains broadly positive. Around 2,500 patients (about 5 % of patients treated or storing material in that period) submitted feedback via the HFEA’s “Choose a Fertility Clinic” web-platform. Of those, 84 % said they would be likely to recommend their clinic to friends or family, 95 % reported being treated with dignity and privacy, and 93 % said they understood what was happening during treatment. 

The HFEA signals particular concern around administrative incidents and communication failures. Many of the Grade C incidents (which increased notably by 53 %) involved administrative or laboratory process issues—examples include emails sent to the wrong recipient or treatment delay caused by scheduling or billing errors.  The regulator emphasises this as an area for improvement even in a broadly safe sector.

For labs, clinics and treatment-centres, the report offers a useful benchmarking tool. It suggests that while major safety failures remain extremely rare, there is ongoing need for attention to non-clinical aspects of service delivery—workflow, documentation, patient-communication and process consistency. Given the rise in self-funded patients and the diversification of treatment pathways (including virtual or app-based referral models), the regulatory landscape may become more complex. The HFEA notes that only licensed clinics can carry out certain treatment steps (such as embryo creation or storage) and warns patients may be confused about which services are regulated. 

In summary, the 2024/25 report from the HFEA shows a mature UK fertility treatment sector operating safely under regulatory oversight. Some operational and administrative challenge areas remain, but the data reinforce that major adverse events are rare and patient experience metrics are strong. For stakeholders in labs, clinics and research-partners, these findings provide context for quality assurance, process improvement and strategic planning.

Sources

13 November 2025. Human Fertilisation and Embryology Authority

• HFEA publishes the Fertility Sector 2024/25 report

13 November 2025. Human Fertilisation and Embryology Authority

• The fertility sector 2024/25: Annual publication on HFEA licensed clinics (1 April 2024 – 31 March 2025)

Tuesday, 4th November, 3pm EST/8pm UK
This webinar is kindly sponsored by Nexpring Health. 

Moderators:
Xiao Zhang and Dr Antonio Alcaide Raya

Presenting:
Dr Meurig Gallagher: Sperm assessment accuracy and its importance for the type of fertilization method
Dr Catello Scarica: IVF Master
Dr Gemma Arroyo Cardona: ICSI Master

Q and A
REGISTER HERE

A new study led by researchers at the University of Cambridge has raised questions about the reliability of one of the most commonly used techniques for assessing embryos in IVF. Published in Nature Biotechnology, the findings indicate that preimplantation genetic testing for aneuploidy (PGT-A), which aims to identify embryos with abnormal numbers of chromosomes, may not always provide an accurate picture of an embryo’s genetic health.

PGT-A has long been used to select embryos most likely to result in successful pregnancies and healthy births. The method typically involves removing a few cells from the outer layer of the blastocyst and analysing them for chromosomal abnormalities. However, the Cambridge team’s work suggests that this sampling approach can miss abnormalities in the inner cell mass, which forms the fetus, or can overstate risks when the outer layer carries errors that would otherwise be corrected during development.

Using advanced real-time imaging and single-cell sequencing, the researchers tracked chromosomal changes in early embryos. They found that embryos frequently exhibit a degree of mosaicism, meaning that some cells carry abnormal chromosome numbers while others are normal. This dynamic process often resolves itself naturally, with healthy cells outcompeting abnormal ones as development progresses. As a result, embryos labelled as “abnormal” under current testing standards may, in fact, be viable and capable of producing healthy pregnancies.

The study also points to inconsistencies in how laboratories interpret test results. Variability in cell sampling and thresholds for determining abnormality may lead to embryos being discarded unnecessarily. These findings call for a reevaluation of how genetic screening is integrated into IVF decision-making and highlight the potential need for improved, less invasive diagnostic tools that consider the embryo as a whole rather than a static snapshot.

Clinics and embryologists may need to weigh these results carefully when counselling patients. While PGT-A can still play a valuable role in identifying major chromosomal imbalances, its limitations underscore the importance of combining genetic testing with other forms of embryo assessment, such as morphology and time-lapse imaging. Ongoing advances in multi-omic and live imaging technologies could pave the way toward more accurate, holistic embryo evaluation in the near future.

Sources

23 October 2025, University of Cambridge

Widely-used technique for assessing IVF embryos may be flawed, study suggests

23 October 2025, Nature Biotechnology

Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors

23 October 2025, BBC News

IVF test could misjudge embryo health, study finds

23 October 2025, Genetic Engineering and Biotechnology News

Real-time embryo imaging raises questions about IVF screening accuracy

23 October 2025, New Scientist

Common IVF test misses some genetic abnormalities in embryos

Researchers at Baylor College of Medicine have successfully restored fertility in a mouse model of non-obstructive azoospermia (NOA), a form of male infertility in which sperm production fails despite unobstructed reproductive ducts. The work, published in Proceedings of the National Academy of Sciences (PNAS), presents a promising step toward the development of therapeutic approaches that could help men with this currently untreatable condition.

Non-obstructive azoospermia affects roughly one percent of men and is one of the most severe forms of infertility. In these cases, the testes are unable to produce mature sperm, often due to genetic mutations that disrupt spermatogenesis. Conventional treatments such as hormone therapy or surgery offer little benefit, leaving assisted reproductive technologies as the only potential route to conception—often relying on donor sperm rather than the patient’s own.

The Baylor research team focused on a key gene, Tex14, which is essential for forming intercellular bridges between developing germ cells. These bridges are critical for coordinating sperm development. In mice lacking Tex14, the germ cells fail to progress beyond early stages, resulting in azoospermia. Using a novel lipid nanoparticle-based mRNA therapy, researchers delivered a functional Tex14 transcript directly into the testes. Remarkably, the treated mice began producing functional sperm capable of fertilizing eggs and producing healthy offspring.

This study highlights how mRNA therapy, best known for its role in vaccines, can be repurposed to temporarily restore missing or defective proteins within the testes. Because the approach does not alter the genome, it may offer a reversible and safer alternative to permanent gene editing. It also opens a path for treating a range of genetic causes of male infertility, particularly those where a single gene defect disrupts sperm development.

Beyond Tex14, the researchers believe this platform could be adapted for other testicular genes and eventually refined for human use. Translating this therapy from mice to men will require addressing delivery challenges, dosage control, and immune responses, but the proof of concept demonstrates a powerful new tool in reproductive medicine.

The findings suggest that male infertility—often regarded as irreversible when due to genetic defects—may one day be treatable through targeted molecular replacement rather than invasive procedures or donor gametes.

Sources

13 October 2025, Proceedings of the National Academies of Science

Sperm and offspring production in a nonobstructive azoospermia mouse model via testicular mRNA delivery using lipid nanoparticles

14 October 2025, Baylor College of Medicine

Researchers restore fertility in mouse model of non-obstructive azoospermia

17 October 2025, Drug Target Review

New mRNA therapy could inform future male infertility treatments

Sperm cells must undergo a remarkable transformation to reach and fertilize an egg. In a new study published in Proceedings of the National Academy of Sciences (PNAS), researchers at Michigan State University have identified a key molecular mechanism that enables sperm to achieve “overdrive” motion, a rapid and forceful swimming pattern known as hyperactivation. This discovery sheds light on the finely tuned processes that determine male fertility and could provide new avenues for treating infertility or developing non-hormonal contraceptives.

The study focuses on CatSper, a calcium ion channel located in the sperm tail that controls how calcium ions enter the cell. These ions trigger the whip-like movements required for sperm to navigate the female reproductive tract and penetrate the egg’s protective layers. The MSU team used advanced molecular and imaging techniques to show how CatSper transitions from a basal to a hyperactivated state, allowing sperm to dramatically increase their motility at the crucial moment before fertilization.

This “overdrive” mode is essential for sperm to overcome physical barriers such as cervical mucus and the zona pellucida surrounding the oocyte. The researchers found that specific chemical signals within the female reproductive tract stimulate the CatSper channel, changing its structure and activity. These modifications effectively act as a molecular switch that shifts sperm from steady swimming to the powerful thrusts needed for fertilization.

Understanding this process at the molecular level provides new insight into why certain genetic mutations in CatSper lead to male infertility. It also opens possibilities for designing drugs that can either enhance or inhibit this signaling pathway. Enhancing CatSper activity could help couples struggling with fertilization failure, while targeted inhibitors could serve as a reversible, non-hormonal form of contraception that prevents sperm from reaching hyperactivation.

This work not only deepens our understanding of reproductive biology but also demonstrates how precise molecular mechanisms underlie the seemingly simple behavior of sperm motility. By revealing how sperm achieve overdrive, scientists are one step closer to harnessing or regulating this process for clinical benefit.

Sources

28 October 2025. Michigan State University News

Fuel for the finish line: How sperm achieve 'overdrive'

28 October 2025. Proceedings of the National Academy of Sciences (PNAS)

Sperm meet the elevated energy demands to attain fertilisation competence by increasing flux through aldolase

A recent study by researchers at the Wellcome Sanger Institute and their collaborators has uncovered how sperm evolve within the human body as men age, leading to an accumulation of harmful genetic mutations that may raise disease risk in their children. Published in Nature (October 2025), the research provides a new understanding of how so-called “selfish” sperm cells gain an advantage, multiplying over time while carrying mutations that can disrupt normal development.

Human sperm are produced continuously throughout life, giving rise to billions of cells from a pool of stem cells within the testes. Each division of these cells introduces small errors in DNA, and over decades of sperm production, mutations accumulate. The study reveals that certain mutations give sperm-producing stem cells a competitive edge, allowing them to expand at the expense of normal cells. This evolutionary process means that as men age, their sperm population becomes dominated by these “selfish” lineages, increasing the likelihood of passing on disease-related mutations to offspring.

Using single-cell genetic sequencing, the team analyzed testicular tissue to map how these mutated cells evolve and spread. The findings show clear patterns of clonal expansion—small pockets of sperm-producing stem cells carrying identical mutations—indicating that natural selection is occurring at the cellular level. Many of these mutations affect genes involved in cell signaling and development, including those linked to conditions such as achondroplasia, Apert syndrome, and potentially autism spectrum disorders.

This research highlights an underappreciated aspect of reproductive biology: that natural selection operates not only at the organismal level but also within individual tissues. As men age, this internal competition reshapes the genetic landscape of their sperm, increasing both diversity and the potential for transmitting harmful variants.

The findings may influence future fertility counseling and genetic screening strategies, helping clinicians better understand age-related reproductive risks. Researchers are now exploring whether interventions could one day slow or counteract this selfish evolution, protecting sperm integrity as men age.

Sources

28 October 2025. Wellcome Sanger Institute

Hidden evolution in sperm raises disease risk for children as men age

28 October 2025. Nature

Sperm sequencing reveals extensive positive selection in the male germline

28 October 2025. New Scientist

Selfish sperm see older fathers pass on more disease-causing mutations

The longstanding narrative that ovarian aging is driven mainly by declining egg number and quality is being reframed by new work that maps the entire cellular ecosystem of the ovary across age in mice and humans. Using whole-organ 3D imaging combined with single-cell and spatial transcriptomics, researchers show that how eggs mature, persist, and respond to stimulation depends on the surrounding microenvironment, including stromal cells, extracellular matrix, vasculature, immune components, and previously underappreciated neural elements. The analysis, published in Science on October 9, 2025, provides a reference atlas for reproductive aging and connects ovarian biology to systemic health after menopause. 

Whole-organ optical clearing and light-sheet imaging revealed striking spatial organization. In human ovaries, oocytes are not evenly distributed but cluster in discrete pockets separated by egg-sparse zones. With age, these pockets thin and the density of both resting and growing follicles falls. Equivalent age windows in mice show parallel declines in follicle reserves and IVF success, aligning model and human observations. These spatial findings, which are not apparent in conventional section-based histology, set a new baseline for interpreting follicle counts and stimulation responses in clinical and preclinical contexts. 

The atlas resolves 11 major ovarian cell classes and charts their age-related transcriptional shifts. Among non-germline compartments, fibroblasts, smooth muscle, and epithelial cells exhibit prominent remodeling signatures with age, suggesting that matrix turnover, contractility, and barrier functions collectively condition follicle fate. These insights point to testable interventions that target stroma and extracellular matrix dynamics, for example anti-fibrotic strategies to preserve tissue pliability and follicle access to nutrients and paracrine signals. 

A notable advance is the delineation of the ovarian nervous system. The atlas documents dense sympathetic nerve networks intertwined with follicles, supported by local glia. Functional perturbation in mice lacking sympathetic innervation produced fewer growing follicles and accumulation of immature follicles, implicating neural signaling in coordinating maturation cycles. This neural dimension integrates with clinical observations in disorders like PCOS and raises the prospect that neuromodulatory or neuroimmune pathways could be leveraged to optimize folliculogenesis. 

For IVF practice, several translational implications follow. First, spatial heterogeneity means that biopsy location and sectioning strategy can bias follicle metrics, arguing for standardized sampling or volumetric imaging when feasible. Second, stimulation protocols may benefit from considering stromal state and innervation rather than focusing solely on gonadotropin dosing. Third, age-linked matrix and vascular changes may alter drug penetration and oxygenation within the cortex, influencing oocyte competence even when follicle counts appear reassuring. Together, these points motivate pairing ovarian reserve measures with markers of stromal integrity and neural tone to refine prognosis and personalize stimulation. 

The work also strengthens the translational bridge between mouse and human ovaries. By aligning shared and species-specific hallmarks across age, the atlas clarifies where mouse interventions are most likely to predict human benefit. It offers a scaffold for evaluating therapies that aim to slow ovarian aging, including matrix-targeted compounds, anti-inflammatory regimens, and approaches that preserve or recalibrate sympathetic inputs. As media coverage has emphasized, the ovary functions as a coordinated ecosystem. Intervening at that systems level may extend reproductive span while improving general health trajectories tied to the menopausal transition. 

Looking ahead, incorporating these ecosystem metrics into clinical studies could refine embryo selection and cumulative live birth predictions by connecting follicle geography and stromal state to oocyte quality and response. The field now has a shared reference to test whether modifying tissue mechanics, fibrosis, or neural signaling can measurably shift outcomes in controlled ovarian stimulation, oocyte cryopreservation, and fertility preservation after gonadotoxic exposures. 

Sources

9 October 2025. Science

Comparative analysis of human and mouse ovaries across age

9 October 2025. UCSF News

Why Does Female Fertility Decline So Fast? The Key Is the Ovary

9 October 2025. The Scientist

A Cellular Atlas of the Aging Ovary Reveals How Fertility Fades

9 October 2025. New Scientist

Hidden ecosystem of the ovaries plays a surprising role in fertility