IVF News

Last spring, engineers from Barcelona shipped their sperm-injecting robot to New York City's New Hope Fertility Center, where they reassembled the instrument, including a microscope, mechanized needle, petri dish, and laptop. An engineer with no experience in fertility medicine then used a PlayStation 5 controller to position the robotic needle, which autonomously penetrated a human egg and delivered a single sperm cell. Over a dozen eggs were fertilized using the robot, resulting in healthy embryos and eventually two baby girls.

The robot, developed by startup Overture Life, represents an initial step towards automating in vitro fertilization (IVF) and potentially making the procedure more affordable and widespread. Currently, trained embryologists earning over $125,000 per year delicately handle sperm and eggs using ultra-thin hollow needles under a microscope in IVF labs. Overture envisions an automated process, with their patent application describing a "biochip" containing hidden reservoirs of growth fluids and small channels for sperm.

Santiago Munné, chief innovation officer at Overture Life, believes that if IVF could be performed in a desktop instrument, patients might not need to visit specialized clinics, where a single attempt at pregnancy can cost $20,000 in the US. Instead, a patient's eggs could be directly input into an automated fertility system at a gynecologist's office, significantly reducing costs.

With approximately 500,000 children born through IVF globally each year, automating the process could increase access to fertility medicine for those who cannot afford or access it. However, fully automating IVF is challenging, as test-tube conception involves numerous procedures, and Overture's robot currently performs only one of them and only partially.

Some doctors are skeptical that robots can or should replace embryologists soon, while others see automation playing a more limited role, such as dispensing consistent droplets of growth medium for embryos. Despite the hurdles, automating parts of the IVF process could make it less expensive and pave the way for more radical innovations like gene editing or artificial wombs.

Sources and References

MIT Technology Review

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Researchers have recently published findings of a retrospective study comparing natural cycle IVF (NC-IVF) and conventional IVF (cIVF) treatments to investigate the impact of high-dose gonadotrophin stimulation on oocyte and early-stage embryo development. The study analyzed 616 NC-IVF and 167 cIVF cycles, involving a total of 2110 oocytes.

In NC-IVF cycles, only human chorionic gonadotrophin was used to trigger ovulation. In contrast, cIVF cycles employed antagonist protocols, with daily doses of 150-300 IU of human menopausal gonadotrophins. The primary outcomes of the study were the presence of mature (metaphase II) eggs, zygotes, and embryos with good morphology two days after egg retrieval.

The study found that the mature oocyte rate, the zygote rate per oocyte retrieved, and the zygote rate per mature oocyte were all significantly higher in NC-IVF cycles than in cIVF cycles. However, no difference was observed in the percentage of zygotes that developed into cleavage-stage embryos. For transferred embryos the likelihood of having a good embryo morphology with four blastomeres and a fragmentation of <10% in cleavage-stage embryos was also higher in NC-IVF cycles.

These results suggest that high-dose gonadotrophin stimulation affects oocyte maturity, fertilization, and morphology of cleavage-stage embryos in fresh IVF cycles. Despite the retrospective nature of the study and the inclusion of several treatment cycles per participant, the research offers valuable insights into the impact of gonadotrophin stimulation on oocyte and embryo development.

It is important to note that while the study found differences in oocyte and embryo parameters, no significant differences were detected in pregnancy and live birth rates. Additional research is needed to determine whether the observed effects on oocyte and embryo development also impact pregnancy and live birth outcomes.

This study contributes to the growing body of evidence suggesting that high-dose exogenous gonadotrophins may affect oocyte and embryo quality, with potential implications for IVF treatments, particularly for poor and very poor responders. Further research is needed to evaluate the potential impact of these findings on pregnancy and live birth rates, as well as to explore alternative treatment strategies for patients with diminished ovarian reserve.

Sources and References

Does high-dose gonadotrophin stimulation have an effect on oocyte and early-stage embryo development?
Reproductive BioMedicine Online

Egg cells have been generated from male mouse cells and, once fertilised and implanted into female mice, have developed seemingly healthy, fertile offspring.

The research was presented at the Third International Summit on Human Genome Editing at the Francis Crick Institute in London, by Professor Katsuhiko Hayashi, now at Osaka University, Japan. However, the work has yet to be published in a peer-reviewed journal. This early, proof-of-concept technique could assist with some types of infertility and, if able to overcome a number of technical and ethical barriers, could eventually lead to children with two biological fathers.

'This is the first case of making robust mammal oocytes [egg cells] from male cells,' Professor Hayashi said in his presentation.

The original aim of the research was to address infertility in women with Turner syndrome who only have one X chromosome, since egg development requires two X chromosomes. The researchers chose to use male cells which have an X and a Y chromosome, since the Y chromosome is smaller, and can be lost naturally when cells are grown in the lab.

The process first involved turning male mouse skin cells into induced pluripotent stem cells (iPSCs), which have the potential to develop into almost any type of cell. They then extracted the cells which had naturally lost the Y chromosome. The researchers then used a technique to generate cells with two X chromosomes. By providing a mixture of signals, they were able to turn the XX iPSCs into immature eggs. The eggs were then fertilised with mouse sperm and the embryos were transferred to the uterus of female mice.

The mouse pups generated from this technique were healthy, grew normally, and were fertile adults. However, the success rate was low, with only seven pups developing from 630 transferred embryos.

'The trick of this, the biggest trick, is the duplication of the X chromosome,' said Professor Hayashi. 'We really tried to establish a system to duplicate the X chromosome.'

During his speech, Professor Hayashi confirmed that much work still needs to be undertaken and that any medical applications of this work are still a long way off. The research team are currently comparing the mice generated from this technique to those bred using conventional methods.

'There are big differences between a mouse and the human,' said Professor Hayashi. He explained that these differences can complicate the transfer of research from the lab to the clinic, in particular because egg and embryo development takes much longer in humans than in mice.

'If you're going to apply this in humans, you really want to err on the side of safety, caution and efficiency,' Professor Keith Latham, a developmental biologist at Michigan State University (who was not involved in the research) told New Scientist.

Sources and References

• 9 March 2023. Nature
  The mice with two dads: scientists create eggs from male cells

• 8 March 2023. New Scientist
  Mice have been born from eggs derived from male cells

• 8 March 2023. The Guardian
  Scientists create mice with two fathers after making eggs from male cells

A new technique for selecting sperm during assisted reproduction appears to produce embryos of a desired sex with 80 percent accuracy.

The research took place in the USA where it is legal for parents having IVF to select the sex of their child. The sperm were sorted by weight, as the X chromosome is larger than the Y chromosome, meaning that X-bearing sperm are, on average, heavier than those containing a Y. While this sperm sorting technique appears safe and effective, the study has raised long-standing ethical concerns surrounding embryo sex selection.

Study leader, Professor Gianpiero Palermo, from Weil Cornell Medicine in New York described the technique as 'extremely safe as well as efficient, inexpensive, and ethically palatable.'

'The sperm [in the study group] moved well, and the sorting technique didn't impair sperm in any shape or form', he said.

The study, published in PLOS One, involved 1317 couples who were having IVF, of whom 105 wanted a child of a particular sex.

For those couples, the sperm sorting technique was used, and then in all cases, the collected eggs were fertilised using ICSI. There were no significant differences between the couples who used sorted or unsorted sperm in terms of fertilisation or pregnancy rates. All embryos in both groups underwent PGT-A, which was also used to determine the sex of the embryos.

For the couples who wanted a girl, 79 percent of their embryos were XX, and for those who wanted a boy 80 percent were XY. The 29 children born as a result have been followed up for three years so far and are healthy and developmentally normal.

Ascertaining an embryo's sex by PGT-A is close to 100 percent accurate and US couples can already use this to choose the sex of the embryo transferred. However, the new technique can give them more embryos of their desired sex from a single round of egg collection.

Attitudes to sex selection vary around the globe, and in the UK its use is strictly limited to preventing transmission of gender-specific inherited diseases.

'At present, in the UK, it is not permitted to choose the sex of a child for non-medical reasons', said Sarah Norcross, director of PET. She added, 'there was a loophole in the 1990 legislation that originally governed this area, but this loophole was closed in 2008.'

However, while embryo sex selection remains controversial, there may be some indications that attitudes are changing according to research conducted last year by Ipsos, and commissioned by PET.

'Overall, permitting sex selection was opposed by 57 percent of the UK public, and was supported by only 28 percent', said Norcross. However, among 16- to 24-year-olds, half supported sex selection.

Sources and References

• 22 March 2023. PLOS ONE
  A non-randomized clinical trial to determine the safety and efficacy of a novel sperm sex selection technique

• 22 March 2023. Medical Xpress
  New technique 80 percent effective in selecting a baby's gender

• 22 March 2023. Daily Mail
  Scientists develop IVF technique that allows parents to choose the sex of their babies - and it works 80 percent of the time

• 22 March 2023. The Telegraph
  British scientists call for urgent IVF regulation as USA unveils technique to pick sex of child 

• 22 March 2023. Sky News
  New technique 'about 80 percent effective' at producing babies of desired sex, study suggests

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Egg cells have been generated from male mouse cells and, once fertilised and implanted into female mice, have developed seemingly healthy, fertile offspring.

The research was presented at the Third International Summit on Human Genome Editing at the Francis Crick Institute in London, by Professor Katsuhiko Hayashi, now at Osaka University, Japan. However, the work has yet to be published in a peer-reviewed journal. This early, proof-of-concept technique could assist with some types of infertility and, if able to overcome a number of technical and ethical barriers, could eventually lead to children with two biological fathers.

'This is the first case of making robust mammal oocytes [egg cells] from male cells,' Professor Hayashi said in his presentation.

The original aim of the research was to address infertility in women with Turner syndrome who only have one X chromosome, since egg development requires two X chromosomes. The researchers chose to use male cells which have an X and a Y chromosome, since the Y chromosome is smaller, and can be lost naturally when cells are grown in the lab.

The process first involved turning male mouse skin cells into induced pluripotent stem cells (iPSCs), which have the potential to develop into almost any type of cell. They then extracted the cells which had naturally lost the Y chromosome. The researchers then used a technique to generate cells with two X chromosomes. By providing a mixture of signals, they were able to turn the XX iPSCs into immature eggs. The eggs were then fertilised with mouse sperm and the embryos were transferred to the uterus of female mice.

The mouse pups generated from this technique were healthy, grew normally, and were fertile adults. However, the success rate was low, with only seven pups developing from 630 transferred embryos.

'The trick of this, the biggest trick, is the duplication of the X chromosome,' said Professor Hayashi. 'We really tried to establish a system to duplicate the X chromosome.'

During his speech, Professor Hayashi confirmed that much work still needs to be undertaken and that any medical applications of this work are still a long way off. The research team are currently comparing the mice generated from this technique to those bred using conventional methods.

'There are big differences between a mouse and the human,' said Professor Hayashi. He explained that these differences can complicate the transfer of research from the lab to the clinic, in particular because egg and embryo development takes much longer in humans than in mice.

'If you're going to apply this in humans, you really want to err on the side of safety, caution and efficiency,' Professor Keith Latham, a developmental biologist at Michigan State University (who was not involved in the research) told New Scientist.

Sources and References

• 9 March 2023. Nature
  The mice with two dads: scientists create eggs from male cells

• 8 March 2023. New Scientist
  Mice have been born from eggs derived from male cells

• 8 March 2023. The Guardian
  Scientists create mice with two fathers after making eggs from male cells

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