Innovative IVF Technology: Enhancing Success Rates by Utilizing Internal Processes
Credit: Zephyr/Science Photo Library
Recent advancements in IVF technology involve creating embryos from magnetized spermatozoa, allowing them to be guided remotely to eggs. This groundbreaking method facilitates in vivo fertilization, reducing invasiveness while potentially increasing success rates in assisted reproduction.
“Our ultimate vision is to utilize the body as a natural incubator for assisted reproduction,” states Mariana Medina Sanchez, a researcher at CIC nanoGUNE in Spain.
Low sperm count or motility can complicate natural conception, making IVF a challenging process. Traditional IVF involves invasive steps such as hormone injections and egg retrieval, which can lead to side effects and unsuccessful cycles. The artificial environment often negatively impacts embryo viability due to multiple manipulations.
To combat these issues, Medina Sanchez and her team developed a method for transporting sperm through the female reproductive tract to the fallopian tubes, enabling fertilization under natural conditions. By applying a weak magnetic field, researchers transformed sperm into magnetic entities, which can be directed into the body seamlessly. “We aimed to create a sperm preparation protocol that integrates into standard IVF workflows, so we consulted IVF specialists,” Medina Sanchez elaborates.
The research team incubated cow sperm with tiny iron oxide and polystyrene magnetic beads, with about 30 beads attaching to the sperm’s head, leaving the tail free for movement. Tests confirmed that magnetized sperm showed no adverse effects on swimming speed or overall health.
After incubating magnetic sperm with eggs, the researchers noted that embryo formation rates were comparable to those of non-magnetic sperm. The beads detached from the sperm upon entering the egg, without affecting initial embryo development.
The researchers demonstrated that external magnetic fields could accurately direct magnetic sperm toward eggs during experiments in vitro.
“This represents a significant breakthrough and validates our concept,” states Kylie Dunning from the University of Adelaide, Australia. “However, several challenges remain before this can enter clinical practice,” she warns, highlighting the need to prove that magnetic sperm can reach fallopian tubes and successfully fertilize eggs outside laboratory settings, ultimately resulting in healthy pregnancies.
The visibility of magnetic beads on ultrasound provides an advantage for tracking sperm locations within the body. Encouragingly, preliminary findings have indicated that entire embryos, incorporated with small magnetic structures, can be navigated into mouse fallopian tubes using external magnets.
Once detached, the beads are expected to be naturally expelled by the body’s waste removal system. However, if necessary, they can be extracted using a magnet attached to a catheter, according to Medina Sanchez. “This holds great promise for the future of assisted reproduction,” she concludes.
Color scanning electron micrograph of human sperm cells
PDC/Science Photo Library
Male infertility is a sensitive subject, yet it’s a prevalent issue affecting about 1 in 10 couples trying to conceive. Notably, half of infertility cases are linked to sperm quality. Traditional fertility solutions often fall short, but a pioneering U.S. startup, Paterna Biosciences, aims to revolutionize the field.
Paterna proposes that stem cells can be extracted from the testicles and transformed into viable sperm cells in a laboratory setting. This breakthrough could potentially enable almost all men who face infertility challenges to achieve fatherhood.
However, some experts express skepticism, suggesting that the method’s viability may hinge on the integration of CRISPR gene editing—essentially enabling the creation of gene-edited offspring.
Let’s delve deeper. Male infertility can stem from various issues, including low sperm count, poor sperm motility, or sperm failing to penetrate the egg. In such cases, direct injection of sperm into the egg, known as intracytoplasmic sperm injection (ICSI), can often yield successful results.
Approximately 1 in 100 men may face a complete absence of sperm in their semen. This might be due to blockages preventing sperm from reaching the prostate, which can often be corrected through medical procedures to retrieve sperm directly from the testicles.
In instances where no sperm is found, it’s frequently due to the testicles producing little or none. According to Alex Pastuzak, Co-founder and President of Paterna, the process begins with a small testicular tissue sample, which can yield anywhere from a few to tens of thousands of sperm cells.
Pastuzak claims they identified signals that stimulate sperm stem cells to differentiate into sperm within about a month in the lab.
The question of validity arises. Paterna has yet to release conclusive evidence to back their claims, citing the need to protect their intellectual property. Pastuzak states, “I won’t disclose anything to the public until our protections are established.”
Previous efforts, such as those by French biotech firm Callistem, made similar announcements but did not deliver substantial outcomes.
Paterna asserts that the sperm produced successfully fertilized human eggs, leading to early embryonic development.
While acknowledging Paterna’s scientific team’s qualifications, independent researchers await more evidence before drawing conclusions. “If they can achieve this, it represents a significant advancement,” remarks Helt Hammer from the Amsterdam Institute of Reproductive Development.
Potential Genetic Risks
If Paterna’s claims hold true, the next critical inquiry is their safety. Sperm originate from stem cells in the testes, which undergo a complex meiotic process to develop into spermatozoa. Any disruption during meiosis may lead to genetic abnormalities—a potential risk heightened in laboratory environments.
Moreover, imprinting errors during sperm development can lead to serious developmental issues. Although Paterna believes its approach minimizes these risks, past research indicates common errors in mouse sperm derived from stem cells.
Pastuzak asserts, “Molecular studies show our in-vitro sperm is identical to natural sperm produced in the testes. In some cases, it even surpasses natural quality.”
Paterna envisions implanting embryos fertilized with laboratory-grown sperm into women as early as next year. “Our inaugural clinical trial will likely occur outside the U.S., still awaiting regulatory approvals,” Pastuzak adds.
However, it’s unclear what evidence regulators require before sanctioning the use of lab-grown sperm in fertility treatments. Historically, fertility specialists have employed techniques like IVF and micromanipulation without comprehensive safety validations.
If deemed safe, it remains to be seen how many men can benefit from this technique. A small segment may not possess functional sperm stem cells, confining this approach’s applicability.
For others, infertility could stem from genetic mutations, complicating treatment efficacy. Professor Hammer suggests that if a mutation hampers spermatogenesis, lab methods are likely to replicate the same issues. The most likely beneficiaries may be men who became infertile due to childhood cancer treatments and had testicular tissue preserved prior to that.
“We could provide hope for young boys rendered infertile by chemotherapy,” he asserts, though this demographic is limited.
Wilkinson notes that another potential group could be men with restricted spermatogenesis, who currently undergo invasive procedures like microdissecting testicular sperm extraction (mTESE). “Avoiding such invasive techniques would be a significant improvement,” he claims.
Lab-Grown Sperm and Future Generations
Lab-grown sperm could help men have children, but additional genetic techniques may be required
Maite Torres/Getty Images
Pastuzak claims that their lab successfully harvested sperm from men whose testicles do not naturally produce it. “Most of these germ cells exhibit maturation potential. The defect seems linked to the signaling from supportive cells,” he states.
Despite skepticism, the possibility that lab-grown sperm could offer solutions to infertility is encouraging. However, it raises the concern that boys born from such sperm may inherit genetic mutations associated with fertility issues—paralleling concerns raised with ICSI techniques.
“I do ponder this,” Pastuzak admits, noting that there are various stages in the process where harmful mutations can be screened out during testing.
If lab-grown sperm extraction fails for most men with infertility-causing mutations, an alternative solution may arise through CRISPR gene editing to rectify such mutations, potentially resulting in gene-edited children.
This approach, while promising, comes with challenges, mainly due to limited knowledge about potential infertility mutations and their complexities. “Evidence remains scarce,” Wilkinson warns.
Nonetheless, if precise mutations are identified, utilizing gene editing might be justified. Pre-implantation genetic screening could also mitigate unintended modifications during the process.
Paterna is open to exploring these avenues, with Pastuzak stating, “I’m not ruling anything out. Advancements in science should benefit as many people as possible.”
A female sperm whale holds her newborn calf above the water until it can swim on its own.
Project CETI
The recent birth of a sperm whale was notably supported by ten other females within its pod, marking an unprecedented instance of assisted childbirth outside of primate species.
In July 2023, researchers monitoring a sperm whale pod in the Caribbean since 2005 noticed the eleven females gathering at the surface. Remarkably, they were flying a drone at the time and captured this event on record.
As the birth commenced, the calf’s flukes gradually revealed themselves over a 30-minute period during which the accompanying females coordinated in a synchronized formation to ensure the safety of both the mother and her calf.
Upon the calf’s arrival, the female whales circled and took turns watching over it, keeping it afloat to ensure it could breathe properly, as newborn sperm whales lack buoyancy and cannot stay at the surface by themselves for the initial hours.
This groundbreaking observation of assisted childbirth in non-primates was highlighted by Shane Gero, a team member at Project CETI in New York.
Such intricate behaviors were previously believed to be exclusive to humans but are now emerging in non-human species as well.
“Sperm whale societies thrive on strong female leadership,” Gero explains. “It’s fascinating to witness intergenerational support during childbirth among females, even those not related by blood.”
When a short-finned pilot whale approached approximately 18 minutes post-birth, the adult female sperm whales exhibited defensive behaviors.
The newborn sperm whale emerges from the water after giving birth, supported by an adult female.
Project CETI
“They consistently placed at least one adult whale between the newborn calf and the approaching pilot whale,” reports Giovanni Petri from Northeastern University London. “The adult females displayed aggression towards the pilot whale, changing direction and even ramming into it.”
Researchers deployed underwater audio recording devices to monitor the vocalizations of the sperm whales. Another study highlights the significance of these findings.
“The acoustics of this event were remarkable,” states Petri. “Statistically significant shifts in vocal patterns were noted during critical moments such as labor and interactions with the pilot whale.”
These behavioral changes were unlike the usual vocal shifts observed in the pod, returning to normalcy following the birth.
By merging audio analysis with observation, the researchers “established a connection between the behaviors of the sperm whales and their vocalizations,” Petri noted.
Gero also mentioned they have yet to determine the sex of the calf but expressed hope to see it thrive in the following months, and a name will be given if they encounter the calf again. They know, however, that it has survived the crucial first year, a period characterized by high calf mortality rates.
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The origins of the sperm swimming mechanism date back to ancient times.
Christoph Burgstedt/Alamy
The evolutionary roots of sperm can be traced to the unicellular forerunners of all existing animals.
Nearly all animals go through a unicellular phase in their life cycle, which involves two forms of sex cells, or gametes. Eggs are sizeable cells that hold genetic information and the nutrients necessary for early development, while sperm transport genetic material from one organism to another to fertilize eggs and create new life.
“Sperms play a crucial role in the process that allows life to be transmitted from generation to generation,” states Arthur Matt from Cambridge University. “It carries the legacy of over 700 million years of evolutionary history and is likely linked to the origins of animals themselves. Our aim was to explore this extensive evolutionary narrative to understand the origins of sperm.”
Matt and his team utilized an open science dataset containing information about sperm proteins from 32 animal species, including humans. They combined this data with the genomes of 62 organisms, including various related single-cell groups, to track the evolution of sperm across different animal lineages.
The research revealed a “sperm toolkit” comprising about 300 gene families that make up the last universal common sperm core genome.
“We have now identified numerous significant advancements in sperm mechanisms occurring long before multicellular animals emerged, even before the sperm themselves,” explains Matt.
This indicates that the sperm mechanics, represented by a “flagellum that propels a single cell,” were already evolving prior to the development of multicellular organisms.
Thus, our ancient progenitors were once all single-celled oceanic swimmers, and the sperm toolkit was present in our earliest swimming unicellular predecessors long before the advent of animals.
“Animals evolved multicellularity and cellular differentiation, but they did not create sperm from nothing. They repurposed the body structure of their swimming forebears as the foundation for sperm,” states Matt. “In essence, sperm are not a novel creation of multicellular organisms but are constructed upon the designs of a single-celled organism repurposed for reproduction.”
The study also indicated that the significant technological developments leading to the vast variety of current sperm primarily affected the cell heads, while the tails have remained largely constant since their common ancestor.
According to the research team members, fertilization can occur in various manners, with some sperm reaching the egg within the body, while others swim in open waters, notes Adria Leboeuf, also from the University of Cambridge. “Finding eggs in these different settings presents unique challenges and requires specialized machinery,” she explains. “However, the tail remains well-preserved since it must be capable of swimming in all environments.”
“This illustrates how evolution can modify existing structures instead of creating mechanisms from scratch,” says Jenny Graves, from La Trobe University in Melbourne, Australia.
Selfish behavior is alarmingly prevalent in biological contexts. A recent study underscores this, illustrating how genetic mutations accumulate in the sperm of older men. Research indicates that as men age, new stem cells increase the likelihood of carrying disease-related mutations, potentially affecting up to 5% of their sperm by the time they reach 70.
This discovery highlights not only the advantages of having children at a younger age but also the indifferent nature of mutated stem cells, which do not consider the consequences for future offspring as long as their genetic material is passed on. This serves as a potent reminder that the notion of “selfish genes” remains a foundational concept in evolutionary biology. Genes prioritize their own survival over any altruistic intentions, continually bringing discussions back to genetic selection, contrary to the idea of “survival of the fittest.”
The ongoing debate is weary and centers around whether evolution through natural selection favors cooperation or promotes competitive and ruthless organisms that prioritize reproduction above all else. Over the past century, numerous biologists have debated this issue, labeling differing perspectives on group versus individual selection. These distinctions fundamentally shape our understanding of the natural world and our role within it.
The divide between these views has consistently straddled ideological lines. Earlier animal behaviorists believed that organisms act for the benefit of their species. The idea was that individual survival is advantageous for the entire group, creating a potential contributor to the continuation of humanity. Homo sapiens can achieve this common goal through mutual assistance.
However, as highlighted by key biologists from Ronald Fisher to contemporary thinkers like Richard Dawkins, organisms that accept help from others without reciprocating consistently outperform those that give help. Those that disrupt group dynamics tend to position themselves for greater success—as long as their impact isn’t so destructive that it eliminates all competition.
From an evolutionary standpoint, the optimal strategy for individuals is to encourage cooperation while withholding it from others—ideally, without detection. Instead of fostering good and altruistic qualities, cooperation can create an environment where competitive and exploitative behaviors thrive unnoticed.
The issue of destruction undermines populations, whether they are gametes, bacteria, animals, or humans. Stem cells, which reproduce at the expense of a host’s descendants, are indifferent to whether their proliferation harms future generations. The welfare of both the host and its species is irrelevant.
This logic extends to human societies, both ancient and modern. Individuals in power—often older men—tend to monopolize resources and frequently choose younger women as partners. Given the adverse effects of older men on fertility, it’s challenging to take the group selection model seriously in light of new findings regarding sperm.
Crucially, these unsettling realities about our biological roots do not dictate our behavior today. We should strive for mutual aid and not take it for granted. Recognizing our inherent selfish tendencies at every biological level is the initial step toward overcoming them.
A South Carolina man admitted guilt on Thursday for bringing in and selling sperm whale teeth and bones from four countries in the United States, according to federal prosecutors.
Lauren H. Deloha, 69, of St. Helena, South Carolina, pleaded guilty to violating the Lacy Act and the Marine Mammal Protection Act by importing and selling sperm whale parts. The US Attorney’s Office in South Carolina reported this.
Deloach is said to have imported sperm teeth and bones into South Carolina from July 2022 to September 2024, including at least 30 shipments from Australia, Latvia, Norway, and Ukraine, as revealed in court documents and statements made in court.
He allegedly sold around $18,000 worth of at least 85 pieces on eBay, falsely labeling them as “plastic” to evade detection by customs officials, according to prosecutors.
Authorities mentioned that they confiscated about $20,000 worth of sperm whale parts while searching his residence.
It remains unclear how Deloach acquired these items and who purchased them from him. Teeth and bones are sought after for use in artworks like sculptures, prosecutors stated.
Sperm whales, the largest toothed whales, inhabit deep waters worldwide, from the equator to the edges of ice in the Arctic and Antarctic, according to the National Oceanic and Atmospheric Administration. Females can grow up to 40 feet long, while males can reach up to 52 feet long, as per the agency.
Sperm whales have been safeguarded since 1970 under the Endangered Species Act and the International Treaty on Endangered Species of Wild Fauna and Flora. The Lacey Act criminalizes the illegal sale of wildlife that was imported illegally, prosecutors mentioned.
“Illegal wildlife trafficking is a multi-billion dollar global enterprise, with animals and fuels protecting organized crime,” stated Brooke B. Andrews, acting US attorney for South Carolina. “We will uphold the Lacey Act and the Marine Mammal Protection Act. Vulnerable species like sperm whales have been slaughtered for profit.”
Deloach’s attorney, Nathan S. Williams, mentioned in a statement on Sunday that Deloach “regretted his actions and took responsibility for them.”
Deloha faces a maximum of five years in prison, a $250,000 fine for felony Lacey Act violations, and up to one year in prison for misdemeanor violations of the Marine Mammal Protection Act.
This incident was the latest involving protected wildlife.
In February, a California couple reached a plea agreement in Butte County, California. They were caught by wildlife officers smuggling mountain lion trophies and turtle skulls in their carry-on bags, breaching fish and game laws. The California Department of Fish and Wildlife stated.
With the abundance of news stories, one might believe that humanity is on a path to self-destruction due to pollution, microplastics, and harmful chemicals. Reports of decreasing sperm counts have led to discussions about a possible “Spermageddon,” with politicians even considering incentivizing women to have children (source).
However, after speaking with experts like Professor Alan Pacey, a male infertility researcher, and Professor Sarah Harper, director of the Oxford Institute of Population Ageing, it seems that while there is reason to be concerned, we are not currently in a crisis.
Why are some people concerned about “Spermageddon”?
The concern dates back to a study from 1974 that showed a decrease in sperm counts among American men compared to the data from the 1950s (source). While various factors like climate change, genetic defects, and microplastics have been suggested as causes for declining sperm counts, not all experts are convinced about the severity of the issue.
Recent studies, including those conducted in Denmark, have not shown significant declines in sperm quality, leading to doubts about the extent of the problem. While concerns about microplastics and chemicals are valid, they may not be directly linked to infertility as some believe.
Recent research published in the journal Nature also suggests that semen quality worldwide may not be declining significantly.
Is global infertility on the rise?
While birth rates are indeed falling, experts argue that there is no concrete evidence of a widespread increase in infertility. Factors like delayed childbearing, improved access to fertility treatments, and reduced stigma around infertility may be contributing to more people seeking assistance at fertility clinics.
Why are populations declining in many areas?
The declining birth rates in countries like South Korea, China, and the United States are influenced by various factors, including economic growth and changing societal norms. While it may seem like an “infertility epidemic,” some experts see it as a demographic outcome of broader trends.
Should we be concerned?
Experts have differing perspectives on the issue. While some, like Professor Harper, believe that falling birth rates are not a cause for alarm, others, like Professor Pacey, are concerned about the barriers to fertility treatment and the impact on individuals facing infertility. Both emphasize the need for a nuanced approach to addressing the complex factors affecting fertility rates.
About our experts
Professor Alan Pacey MBE is a renowned researcher in male fertility and sperm biology at the University of Manchester, with over 30 years of experience in the field.
Professor Sarah Harper CBE is a gerontology expert at the University of Oxford, focusing on population aging and fertility trends.
Sperm whale (physeter macrocephalus) They are highly social mammals that use clicks to communicate. New research shows that, just like in human language, they can combine and coordinate different clicks and rhythms to create complex calls.
Sperm whale (physeter macrocephalus). Image credit: Gabriel Barathieu / CC BY-SA 2.0 Certificate.
Communication is important for social animals to make group decisions and coordinate collaborative tasks such as foraging and raising children.
Sperm whales are social mammals that communicate with each other by clicking repeatedly.
Little else is known about sperm whales' communication systems, although some of their clicks have previously been shown to communicate their identity.
“Cetaceans are an important group for studying evolution and the development of sophisticated communication systems,” said Pratyusha Sharma, a researcher at the Massachusetts Institute of Technology (MIT), and colleagues.
“Among cetaceans, long-term observational studies of sperm whales describe both a culturally defined, multilayered matrilineal society and a socially transmitted communication system.”
“Sperm whales are known for their complex social and foraging behaviors, as well as their collective decision-making.”
“They communicate using codas, stereotypical sequences of three to 40 broadband clicks. Codas are exchanged when whales interact with each other and during long, deep dives foraging. .”
They analyzed the records of about 60 different whales from the eastern Caribbean sperm whale clan and used them to define a “sperm whale phonetic alphabet” of click combinations from this clan's records.
They discovered that whales' communication systems are more complex and have greater information-transfer capabilities than previously thought.
We found that the combination and structure of the generated click sequences depended on the context of the individual's conversation.
Scientists also identified a “combinatorial structure” in whale language. Whales can combine and coordinate different clicks and rhythms to create complex vocalizations, similar to human language.
“Although the function and meaning of the click combinations are still unknown, the sperm whale language could potentially express a large number of meanings,” the researchers said.
Their paper It was published in the magazine nature communications.
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P. Sharma other. 2024. Contextual and combinatorial structure in sperm whale calls. Nat Commune 15, 3617; doi: 10.1038/s41467-024-47221-8
Sperm that don't move fast enough have a hard time reaching the egg and can cause fertility problems.
Alexei Kotelnikov / Alamy
Laboratory research has revealed that applying ultrasound to immobile sperm causes it to move. If sperm does not move properly, it becomes difficult for them to reach the egg, which is a major cause of infertility. With further research, this technology could help improve the success rate of in vitro fertilization (IVF).
Previous research suggests that: High frequency ultrasound increases sperm motility. However, the study did not involve isolating the sperm to assess which individual cells would be beneficial, allowing doctors to find the best cells to use in fertility treatments.
In the latest research, Ali Vafaie The researchers, from Monash University in Melbourne, Australia, classified 50 semen samples into three groups (fast, slow, and stationary) according to sperm motility, based on guidelines for assessing swimming speed.
After separating individual sperm cells from semen samples, the researchers measured the motility of the cells before and after exposure to ultrasound waves with a power of 800 megawatts and a frequency of 40 megahertz.
After 20 seconds of ultrasound, 59 percent of the immobile sperm slowed down, and some started swimming rapidly. Changes in sperm motility peaked at an increase of 266%.
Overall, immotile sperm made up 36% of the samples at the start of the study, but this decreased to just 10% after treatment. It is unclear how long the increase in migration lasted.
Researchers believe that exposure to ultrasound improves dysfunction in sperm's mitochondria, the cells' powerhouses, contributing to increased motility.
This approach could increase the success rate of in vitro fertilization, which requires motile sperm for conception, and could avoid the need for multiple costly surgeries.
But first, Vafai says, the research group will need to test the effectiveness of the approach on sperm, particularly in people experiencing infertility due to reduced sperm mobility. Scientists also need to assess whether it is safe to create embryos from sperm exposed to ultrasound, he says.
The year was 1974. While newspaper columnists were busy talking about the development of in vitro fertilization and the possibility of “test tube babies,” the surprising discovery about male fertility completely escaped their notice.
Two doctors, Iowa State CM Kinloch Nelson and Raymond Bunge, compared semen samples from that time with historical data. Dramatic changes in a man’s sperm count Over the past 20 years. In 1951, one milliliter of semen contained 107 million sperm. By the 1970s, that number had fallen by more than 50% to just 48 million people. The average volume of semen per ejaculation also decreased.
By the 1990s, the problem began to receive considerable scientific attention, although some researchers remained skeptical. They blamed differences in technology or the fact that most of the research involved men already undergoing treatment for infertility. Those doubts are now diminishing. “There is a tremendous amount of scientific evidence showing this decline,” he says. Albert Salas-Huetos at the University of Rovira y Virgili, Spain.
For researchers like Salas-Huetos, the big question is no longer whether this so-called “Spermageddon” is really happening, but why and what to do about it. Research is beginning to uncover environmental toxins that may be the culprit, as well as other lifestyle factors that contribute to the problem. With a better idea of the prime suspects, we may finally be able to put the brakes on this trend, or even reverse it.
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