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40 YEARS OF IVF: A LOOK BACK INTO THE FUTURE

Thirteen minutes before midnight on July 25, 1978, several hundred miles outside of London, a baby girl was born. Her name was Louise Brown, and she was the first person born through IVF. Wednesday is her 40th birthday.

Since 1978, about 8 million babies have been born around the world through IVF and other assisted reproduction methods, making IVF commonplace, safe and successful, and representing one of the fastest developing fields in all of medicine.

How did the industry get here, what advancements were most crucial, and what’s next?

Our IVI-RMA Global flagship practice in the U.S. is Reproductive Medicine Associates of New Jersey (RMANJ), which was founded in 1999 by three pioneering doctors: Dr. Richard Scott, Dr. Mike Drews and Dr. Paul Bergh, who offers some perspective on the biggest breakthrough from the past and what holds the most promise for tomorrow.

Dr. Drews, what are the biggest breakthroughs in infertility science since 1978?

Dr. Drews: The biggest breakthrough in this field has come from being far more selective in the embryos we choose to transfer. This selection leads to greater confidence that we have chosen a viable embryo for transfer, allowing us to transfer just one embryo at a time without sacrificing chances for conception.

What exactly has allowed you to be more selective?

Dr. Drews: Two things in particular: growing embryos to the blastocyst stage, and being able to conduct chromosomal testing on those blastocyst embryos. Let’s start with growing to the blastocyst stage. We always assumed that growing embryos to their 5th day instead of their 3rd day prior to transfer would allow for a sort of natural selection process to occur, where more competent embryos would survive and thrive, while less biologically-capable embryos would not. However, in the early days of IVF, we had not yet perfected methods to grow the embryos to Day 5 in the laboratory. Around the late 1990s, and into the 2000s, RMANJ began making big advances in the science of embryo culture. We got much better at adjusting the lab environment to the changing needs of embryos as they grew from Day 3 to Day 5. Once we perfected the culture process, we routinely succeeded in growing embryos to the blastocyst stage (day 5), and eventually evolved to exclusively transferring Day 5 blastocysts. That really broke a barrier for us because these Day 5 blastocysts had a higher chance of leading to pregnancy.

And what about chromosome testing? How has that advanced?

Dr. Drews: The science of preimplantation diagnosis/screening has also evolved over the years. Before embryos could be routinely grown to Day 5, embryos were biopsied on Day 3 to sample the chromosomal blueprint of embryos. The science was crude by modern standards, with potential for misleading results, with undue stress placed upon these early-stage embryos. Only one cell was analyzed – we now know some embryos have the ability to self-correct genetic errors as they grow, so making a definitive diagnostic call on one cell was a gamble. But it was the only game in town, so to speak. Once we figured out methods to culture embryos to Day 5, when they consist of roughly 200 cells, we were able more safely take several cells for biopsy and chromosomal analysis. This gave us a bigger, more predictive sample to work with, with far less stress placed upon the embryo. This was crucial. Additionally, creating and validating a more accurate, comprehensive chromosomal screening test that would analyze these cells and let us know whether they were genetically normal or abnormal, was a critical advancement. By 2013, RMANJ scientists had developed the test – SelectCCS – and began using it routinely on Day 5 embryo biopsies. This dramatically improved embryo implantation rates and reduced miscarriage rates by avoiding inadvertent transfer of genetically-abnormal embryos.

What about the future? What are the next big breakthroughs in this field?

Dr. Drews: There is excitement in the field of embryonic metabolism, which tries to measure which embryos have adequately-functioning mitochondria. The mitochondria, which come exclusively from the egg, are vital to the growth of the embryo, and researchers are honing in on how to test mitochondrial quantity and function in embryos. The goal is to perform this testing at the same time as CCS testing, from the same biopsy. This way, we would know which embryos are both genetically normal and which ones have the cellular energy needed to utilize a normal genetic blueprint to grow into a healthy baby. This will allow us to even more confidently choose which embryos have the best chances to result in pregnancy and birth.

Dr. Bergh, what are the biggest breakthroughs in infertility science since 1978?

Bergh: Other than growing embryos to the blastocyst stage and being able to do CCS, the biggest breakthrough has been ICSI, or Intracytoplasmic Sperm Injection, which was a turning point for cases involving male factor. In the past, we only had one option during IVF – to place sperm on top of the egg in a dish and hope fertilization occurred. But with low functioning sperm, fertilization rarely happened in this manner, and men had to opt for sperm donation. Then, there came an advancement that allowed doctors to inject sperm between the outside shell of the egg and the egg itself. Fertilization did occur, but often by more than one sperm, which was problematic. So, in the early 90s, doctors tried what was then the unthinkable – to inject a single sperm directly into the center of the egg. This was ICSI, and it was a game-changer for male factor cases. It worked, and studies have proven it is not harmful to the egg or sperm. Best of all, it allows men with sperm issues to use their own sperm to father children instead of relying on donor sperm. Now, ICSI is pretty common in IVF, even for couples not experiencing male factor, because it is a requirement for chromosome testing. Why? Because allowing sperm and egg to meet naturally in a dish results in a lot of sperm who did not make it, all stuck to the outside of the embryo. Taking a biopsy of this intersection results in a contaminated sample that does not produce clear results for embryologists.

What about the future? What are the next big breakthroughs in this field?

Bergh: Genetic engineering, or editing, is a place we’ll see more advancement. Commonly known as CRISPR, this developing technology allows scientists to fix pieces of the genetic code that correspond to certain diseases, and there is a lot of promise there. But it is still so new, and scientists still need to do a lot of work to ensure the safety and efficacy of this technique, so it’s not yet ready for primetime.