IVF News

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Moderators: Dr. Michael Baker and Prof. Deirdre Zander-Fox

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3pm ET/ 8pm UK/ 9pm CET, Tuesday 11th Feb 2025

Moderators: Irene Cuevas-Saiz, Dr Chelsey Leisinger and Giles Palmer
Panellist: Matt Pettit

Presenters:
Alejandra Boix: Traceable Progress: The Integration of Technology in IVF Labs
A talk kindly sponsored by IMT Matcher

Dr Alejandro Chavez: Integration of new technologies in the Lab
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Recent studies have provided new insights into the role of antimüllerian hormone (AMH) in female fertility. AMH, produced by granulosa cells in ovarian follicles, serves as a marker of ovarian reserve—the quantity of remaining eggs. Traditionally, while AMH has been used to assess ovarian reserve, its direct relationship with natural conception has been debated. However, emerging research indicates that lower AMH levels are associated with reduced odds of conception and longer times to achieve pregnancy.

A study published in Fertility and Sterility examined the association between AMH levels and time to pregnancy. The researchers analyzed data from 3,150 women aged 21 to 45 who were attempting to conceive. Participants provided blood samples to measure AMH levels and tracked their menstrual cycles and conception attempts using a digital application. The findings revealed that women with lower AMH levels had a decreased likelihood of conception compared to those with normal or higher AMH levels. Specifically, low AMH levels were linked to a lower chance of conception, with an adjusted odds ratio of 0.77. This association persisted across all age groups, suggesting that AMH is a significant predictor of fertility potential. 

Further analysis indicated that the probability of conception was highest around the fourth menstrual cycle of attempting to conceive, regardless of AMH levels. However, women with low AMH levels had consistently lower probabilities of conception at each cycle compared to those with normal or high AMH levels. For instance, at cycle four, the conception probabilities were 11.2% for low AMH, 14.3% for normal AMH, and 15.7% for high AMH levels. These findings underscore the importance of AMH as a biomarker in reproductive counseling, aiding in the planning of reproductive timelines. 

It’s important to note that while low AMH levels are associated with reduced fertility, they do not preclude the possibility of natural conception. Many women with low AMH levels can and do conceive naturally, especially if other factors such as regular ovulation and good overall reproductive health are present. Therefore, AMH should be considered as part of a comprehensive fertility assessment rather than a definitive predictor of infertility.

In clinical practice, AMH testing is valuable for assessing ovarian reserve and guiding fertility treatments. For women considering assisted reproductive technologies like in vitro fertilization (IVF), AMH levels can help predict ovarian response to stimulation. Higher AMH levels often correlate with a better response to ovarian stimulation, while lower levels may indicate a need for adjusted treatment protocols. However, it’s crucial to interpret AMH levels alongside other clinical findings and patient history to make informed decisions.

Age remains a critical factor in fertility, often outweighing the influence of AMH levels. As women age, both the quantity and quality of their eggs decline, leading to decreased fertility. The studies highlight that within each age category, higher AMH levels are associated with better odds of conception, but advancing age still significantly impacts fertility outcomes. Therefore, while AMH provides valuable information, it should be considered in the broader context of a woman’s age and overall reproductive health.

For women with low AMH levels, early consultation with a fertility specialist is advisable. Such consultations can provide personalized assessments and guidance on fertility preservation options, such as egg freezing, or alternative conception methods, including IVF. Lifestyle modifications, such as maintaining a healthy weight, avoiding smoking, and managing stress, can also support fertility. It’s essential for women to have open discussions with their healthcare providers to understand their individual fertility profiles and make informed decisions about family planning.

In conclusion, while low AMH levels are linked to reduced odds of conception and longer times to achieve pregnancy, they are not definitive indicators of infertility. AMH is a valuable tool in assessing ovarian reserve and guiding fertility planning, but it should be interpreted within the context of other factors, including age, overall health, and lifestyle. Women concerned about their fertility should seek comprehensive evaluations and personalized advice from healthcare professionals to make informed decisions about their reproductive health.

Sources

5 February 2025. Contemporary OB/GYN

• Low antimüllerian hormone levels linked to reduced odds of conception

2 July 2024. Fertility and Sterility

• Antimüllerian hormone levels are associated with time to pregnancy in a cohort study of 3,150 women

Recent advancements in in-vitro gametogenesis (IVG) suggest that lab-grown eggs and sperm could become viable within the next decade. This technology holds the promise of revolutionizing fertility treatments, particularly for individuals facing infertility and same-sex couples desiring biological children. However, it also raises significant ethical and medical considerations that must be carefully addressed.

The Human Fertilisation and Embryology Authority (HFEA), the UK’s fertility regulator, has reported that the development of lab-grown gametes, known as in-vitro gametogenesis (IVG), may become a practical option within the next decade. This technology involves creating eggs and sperm from reprogrammed skin or stem cells, potentially transforming fertility treatments by removing age-related barriers and enabling same-sex couples to have biological children. 

IVG represents a significant advancement in reproductive science. By generating gametes in the laboratory, scientists can overcome challenges associated with traditional fertility treatments. This approach could provide new avenues for individuals with infertility issues and offer same-sex couples the opportunity to have children genetically related to both partners. 

Despite its potential, IVG raises complex ethical and medical concerns. One such issue is “solo parenting,” where both eggs and sperm are derived from a single individual. This practice carries a high risk of genetic disorders due to the lack of genetic diversity and is considered highly unsafe, leading experts to suggest it should be prohibited. 

Another concept under consideration is “multiplex parenting,” which involves genetic contributions from multiple individuals. While this approach poses fewer biological risks compared to solo parenting, it still necessitates thorough ethical evaluation. The possibility of creating embryos with multiple genetic parents challenges traditional notions of parenthood and could have far-reaching social implications. 

The HFEA emphasizes that any clinical application of IVG must be stringently regulated to ensure safety and ethical integrity. The authority is considering these unprecedented challenges in its proposed overhaul of fertility laws, aiming to establish a framework that accommodates scientific advancements while safeguarding ethical standards. 

The rapid progress in IVG research is evident in recent studies. For instance, scientists have successfully created mice with two biological fathers by generating eggs from male cells, demonstrating the potential of IVG to redefine reproductive possibilities. However, translating such techniques to humans involves additional layers of complexity and ethical considerations. 

As IVG technology advances, it is crucial to engage in public discourse to navigate the ethical landscape. Discussions should encompass the potential benefits of IVG, such as expanded reproductive options, as well as the risks, including genetic abnormalities and societal impacts. Policymakers, scientists, and the public must collaborate to develop guidelines that ensure responsible development and application of IVG.

In conclusion, lab-grown gametes through IVG hold transformative potential for fertility treatments, offering hope to individuals and couples seeking biological children. However, this promise is accompanied by significant ethical and medical challenges that require careful consideration. As the technology approaches viability, it is imperative to establish robust regulatory frameworks that balance innovation with ethical responsibility, ensuring that the benefits of IVG are realized in a safe and socially acceptable manner.

In a remarkable advancement in genetic research, a team of Chinese scientists has successfully created mice with two biological fathers, bypassing the need for maternal DNA. This pioneering work utilized CRISPR gene-editing technology to modify specific imprinted genes, enabling the development of embryos solely from male genetic material. The study represents a significant step forward in understanding mammalian reproduction and the potential for same-sex genetic parenthood.

The researchers began by injecting sperm from one male mouse into an enucleated egg—an egg cell from which the nucleus had been removed—creating a structure with only paternal DNA. This initial step resulted in a blastocyst, a cluster of cells that forms early in embryonic development but lacks the full genetic complement necessary for viability. To overcome this limitation, the team employed CRISPR to edit 20 imprinted genes that are typically required from the mother. Imprinted genes are those that are expressed in a parent-of-origin-specific manner, meaning that certain genes are active only when inherited from a particular parent. By modifying these genes, the scientists aimed to mimic the maternal genetic contribution.

Following the gene editing, the modified genetic material was injected into another enucleated egg along with sperm from a second male mouse. This process resulted in embryos containing genetic material exclusively from two male parents. These embryos were then implanted into surrogate female mice for gestation. The experiment led to the birth of male mice that survived to adulthood, marking the first instance of viable bi-paternal offspring in mammals.

Despite this success, the study revealed significant challenges. Many of the bi-paternal mice died prematurely or failed to mature properly, and those that reached adulthood were infertile. These outcomes suggest that while the gene-editing approach can facilitate the development of embryos from two male parents, it also introduces unforeseen alterations that can impact health and viability. The researchers believe that these issues likely stem from the CRISPR editing process, which, despite its precision, can result in unintended genetic modifications.

This research builds upon previous studies exploring same-sex reproduction in mammals. In 2023, Japanese scientists created mice with two fathers using a different technique, involving the conversion of male skin cells into stem cells that were then used to produce eggs. However, the success rate was low, and the resulting mice faced significant health challenges. The Chinese team’s approach differs by directly modifying imprinted genes to replicate the maternal genetic contribution, resulting in a higher success rate, though challenges remain.

The implications of this study are profound, offering insights into the complexities of genomic imprinting and the potential for same-sex genetic parenthood. However, the findings also underscore the significant technical and ethical hurdles that must be addressed before such techniques could be considered for application in humans. The infertility and health issues observed in the bi-paternal mice highlight the need for a deeper understanding of the genetic and epigenetic factors involved in mammalian development.

Experts caution that while the study represents a significant advancement in genetic engineering and reproductive biology, its applicability to humans remains a distant prospect. The complex interplay of imprinted genes and the potential for unintended consequences make it imperative to approach such applications with caution. Further research is necessary to refine these techniques and to thoroughly assess the long-term implications of genetic modifications in reproduction.

In conclusion, the successful creation of mice with two biological fathers marks a milestone in genetic research, demonstrating the potential to overcome traditional reproductive barriers through advanced gene editing. While the path to human application is fraught with challenges, this study provides a foundation for future explorations into same-sex reproduction and the role of imprinted genes in development. As research progresses, it will be essential to balance scientific innovation with ethical considerations, ensuring that advancements in reproductive technology are pursued responsibly.

Sources

28 January 2025. Cell Stem Cell

• Adult bi-paternal offspring generated through direct modification of imprinted genes in mammals

28 January 2025. New Scientist

• Mice born with two fathers - but don't expect the same for people

28 January 2025. MIT Technology Review

• Mice with two dads have been created using CRISPR

30 January 2025. Science Alert

• Mouse created with two fathers and no mother survives to adulthood

30 January 2025. BBC Science Focus

• Mouse with two dads created in major biological breakthrough

28 January 2025.The Times

• 'Motherless' mice created from embryos with only male genes

Air pollution has long been linked to various health issues, but its impact on pregnancy, particularly for women who conceive through in vitro fertilization (IVF), is an emerging area of concern. A recent study in Guangzhou, China, analyzed the effects of air pollution exposure on fetal growth restriction (FGR) in IVF pregnancies. Researchers found that exposure to fine particulate matter (PM2.5, PM10) and nitrogen dioxide (NO2) during early and mid-pregnancy significantly increased the risk of FGR. The findings highlight the potential risks that air pollution poses to fetal development and underscore the need for increased awareness and protective measures for expectant mothers, especially those over 35 years old.

Fetal growth restriction is a serious pregnancy complication that can lead to perinatal health issues, increased infant morbidity, and long-term developmental concerns, including cardiovascular and neurological disorders. While maternal health, genetics, and lifestyle factors have been well-documented contributors to FGR, the role of environmental exposure remains less understood. This study aimed to address that gap by examining how air pollution impacts pregnancies conceived via IVF, a group that may be particularly vulnerable to external environmental stressors.

The study collected data from 1,433 pregnant women in Guangzhou who conceived through IVF and delivered singleton babies between 2018 and 2023. Researchers matched this data with air pollution records from Guangzhou’s environmental monitoring system to track exposure to PM2.5, PM10, NO2, and ozone (O3) throughout pregnancy. Using statistical models, they assessed the impact of these pollutants on FGR risk while controlling for variables such as age, occupation, and pregnancy-related health conditions.

Results showed a strong association between air pollution exposure and FGR, particularly during the first two trimesters. Women exposed to high concentrations of PM10 and NO2 during the first trimester were significantly more likely to experience FGR, with odds ratios of 6.4 times higher for PM10 and 10.7 times higher for NO2. During the second trimester, the risk increased further with exposure to PM2.5, PM10, and NO2, with PM10 exposure in the highest quartile associated with a 21-fold increase in FGR risk. Interestingly, the study did not find significant associations between air pollution exposure and FGR in the third trimester, suggesting that early and mid-pregnancy are the most critical windows for fetal vulnerability to environmental toxins.

One of the most striking findings was that older mothers, particularly those aged 35 and above, faced an even greater risk. NO2 exposure in this group significantly heightened the likelihood of FGR, suggesting that maternal age may compound the harmful effects of air pollution. Given that pregnancies achieved through IVF are more common among older women, this finding raises additional concerns for this demographic.

Despite these significant findings, previous research on the subject has been inconsistent. Some studies have linked air pollution to lower birth weights and increased FGR risk, while others have found no correlation. The differences in results may stem from variations in geographical location, pollution levels, study populations, and methodologies. Additionally, this study did not account for personal lifestyle factors such as diet, smoking, and prenatal care, which could influence the overall risk of FGR. Another limitation was the assumption that all participants experienced similar levels of pollution exposure, without factoring in personal mobility, indoor pollution, or other environmental variables.

Given the growing evidence of air pollution’s impact on pregnancy outcomes, expectant mothers, particularly those undergoing IVF, should take precautions to minimize exposure. Using air purifiers indoors, avoiding outdoor activities on high-pollution days, and advocating for cleaner air policies are all steps that can help reduce risks. Healthcare providers should also incorporate environmental exposure assessments into prenatal care discussions, particularly for older mothers and those in high-pollution urban areas.

This study adds to the growing body of research that underscores the need to address air pollution as a reproductive health concern. With air quality declining in many cities, proactive measures to protect pregnant women and their babies are more critical than ever. Further research is necessary to explore the long-term effects of air pollution exposure on fetal development and to identify interventions that can mitigate its impact. Until then, greater awareness and protective strategies can help safeguard the health of future generations.

Source

28 January 2025. Nature

• The effect of air pollution exposure on foetal growth restriction in pregnant women who conceived by in vitro fertilisation a cross-sectional study

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Recent work on embryonic development in frogs provides important insights into how electrical signals orchestrate the earliest stages of life. Observations from these amphibian models indicate that voltage gradients across cells can guide the formation of tissues and organs. Researchers are learning that bioelectric signals do more than simply reflect cellular activity; they serve as coordinated instructions that can shape the body plan of an embryo. Understanding these signals may provide new pathways for influencing tissue repair and regeneration.

At the heart of this process are specialized ion channels and pumps that generate distinct voltage patterns across cell membranes. These patterns effectively direct cells to move, divide, or differentiate in specific ways, ensuring that vital structures emerge in the right place and time. In early embryonic development, subtle shifts in electrical potential can influence large-scale outcomes, from the establishment of body axes to the overall architecture of the developing organism. By focusing on frog embryos, scientists have found an accessible platform to study these phenomena due to the rapid and transparent growth of the embryo.

One of the main challenges is linking the visible changes in voltage to the molecular and structural transformations that shape the embryo. Technological advancements have enabled researchers to visualize electrical signals in real time and correlate them with key developmental milestones. In doing so, they have begun to piece together the blueprint through which cells communicate and self-organize. This information not only aids in understanding the normal course of development but could also highlight what goes wrong in certain birth defects.

The implications of uncovering these bioelectric mechanisms reach beyond basic developmental biology. If it becomes possible to manipulate these signals, scientists may be able to redirect or even restart embryonic-like growth pathways in damaged tissues. This approach could spark innovative therapies for organ repair, limb regeneration, and wound healing. Since many of the foundational processes revealed in frog models may also be present in other vertebrates, these discoveries hold promise for broader medical applications.

Overall, the study of bioelectricity in embryonic development is unveiling a sophisticated layer of biological control. By examining voltage gradients within frog embryos, researchers gain a clearer perspective on how crucial structures form and organize themselves. Ongoing research aims to decode and harness these electrical signals, paving the way for regenerative strategies that could potentially reshape modern medicine.

Sources

17 January 2025. Nature Materials

• Stretch-induced endogenous electric fields drive directed collective cell migration in vivo

21 January 2025. SciTech Daily

• New research decodes the electric blueprint of embryo development

A recent medical breakthrough at UZ Brussel has demonstrated the potential for restoring fertility in men who lost their reproductive function due to childhood chemotherapy. The pioneering procedure involved the transplantation of testicular tissue that had been cryopreserved before the individual reached puberty. Specialists believe this approach opens new doors for cancer survivors who face permanent infertility after treatments that were necessary to save their lives.

In this groundbreaking case, a man in his thirties underwent a procedure to re-implant the testicular tissue that was harvested and frozen when he was around ten years old. Before starting chemotherapy more than two decades ago, doctors removed a small sample of tissue from his testicles. This tissue remained in cryostorage until a specialized team determined that re-implantation was feasible. By using tissue from the patient’s own body, the chances of immune rejection were minimized, and the biological processes involved in sperm production could potentially resume.

Cryopreserving testicular tissue in prepubescent boys at high risk of infertility is considered a crucial step in protecting their future reproductive potential. Unlike mature males who can preserve sperm, young boys do not yet produce sperm, making standard sperm banking impossible. The innovative approach now demonstrated at UZ Brussel circumvents this challenge by storing the tissue itself, which contains stem cells capable of eventually producing sperm once the patient reaches adulthood.

While the procedure offers significant hope, it is still considered a specialized treatment requiring further evaluation. The safety, timing, and effectiveness of re-implantation must be explored in larger studies to confirm the success rate and determine the best practices for patient selection. There are also considerations regarding the long-term viability of the frozen tissue and the complexities of monitoring fertility outcomes in men who undergo this procedure.

This successful transplant marks a decisive step forward in safeguarding fertility for young patients who require cancer treatment. Specialists anticipate that refined techniques and deeper clinical insights will soon expand access to this therapy. For families facing difficult decisions about chemotherapy, the possibility of preserving and eventually re-implanting testicular tissue represents a promising avenue for future parenthood.

Sources

11 January 2025. VUB

• World first - First ever transplant of frozen testicular tissue after chemotherapy during childhood provides hope for fertility restoration

9 January 2025. Belga News Agency

• UZ Brussel aims to restore fertility through transplantation of frozen testicular tissue