Latest Developments in ART
Dr. Dana Ambler from Denver Fertility/Albrecht Women’s Care was gracious enough to share her knowledge on the latest developments in ART. Dr. Ambler is board certified in Obstetrics, Gynecology, Reproductive Endocrinology and Infertility. Her accomplishments are extensive however her compassion for this industry is undeniable. Thank you, Dr. Ambler for sharing your knowledge.
The use of Assisted Reproductive Technology (ART) has revolutionized the treatment for male and female fertility. Forty years ago on 25th July 1978, Louise Brown, the first baby in the world was born as a result of In Vitro Fertilization (IVF). Now millions of babies later, IVF is a routine medical treatment offering hope to potential parents around the globe.
While the basics of IVF have stayed the same, eggs are fertilized with sperm in a laboratory and the embryos placed back into the womb, we have seen IVF evolve tremendously in the last four decades. Costs have decreased and the process itself has streamlined. Gonadotropins are now readily available and safe for use. Transvaginal Ultrasound has replaced laparoscopic retrievals and fallopian tube transfers. Intracytoplasmic sperm injection (ICSI) has helped thousands of infertile males become fathers. Preimplantation genetic screening (PGS) has helped thousands of couples have children unaffected by disease. IVF studies are now larger and able to look at pregnancy outcomes instead of intermediate outcomes. In addition to new techniques, studies now focus on refining protocols and identifying which patients may better benefit from our techniques and protocols. Advances in both science and technology mean that we can help more people achieve their dreams of having a family.
One of the largest breakthroughs in the field was the technology associated with pre-implantation genetic testing. Pre-implantation genetic testing allows for a biopsy of the embryo and testing for either a single gene disorder, such as cystic fibrosis or sickle cell anemia, or Aneuploidy screening. It is this arena of ART that is rapidly expanding and uses cutting edge technology.
Preimplantation genetic screening, or PGS, is a genetic test performed on embryos produced through in vitro fertilization (IVF). This test gives information on the embryo’s chromosome content, identifying potential chromosomal abnormalities and helping to select the best embryo for transfer. The increased use of preimplantation genetic screening (PGS) in recent years has resulted in improved outcomes for couples with infertility who are going through IVF. It is now routine to transfer a single embryo and maintain excellent pregnancy rates and minimize the risk of miscarriage across age groups. All couples are at risk of producing embryos with the incorrect number of chromosomes. These embryos are called “aneuploid”, and do not lead to successful pregnancies. PGS tests a small cell sample from embryos to determine whether they have the correct number of chromosomes (“euploid”), the wrong number (“aneuploid”), or a mix of normal and abnormal cells (“mosaic”).
Mosaicism, or mosaic embryos, have brought about new controversies surrounding PGS. High-profile articles have emerged in the New York Times and the New England Journal of Medicine, as well as a story on CBS news, focusing on the challenge of what to do with mosaic embryos created during the IVF process.
Mosaicism is when an embryo is composed of two or more genetically different cell types. As an embryo rapidly divides after fertilization, mistakes in cell division sometimes produce abnormal cell lines. If those cells die off and the embryo manages to self-correct, or if the abnormal cells wind up segregated in the placenta, the embryo may develop into a normal baby. But if abnormal cells proliferate in the embryo, it will probably fail to implant, result in a miscarriage or, more rarely, the birth of a child with serious defects. As currently performed, PGS involves using a laser to biopsy several cells from the outer layer of a blastocyst, known as the trophectoderm. The amount of DNA obtained in a trophectoderm biopsy for PGS is minute (typically 5-10 cells). That creates a problem because the cells cannot be cultured or visually inspected. The DNA also cannot be directly analyzed from individual cells. Rather, the aggregate of the DNA from the biopsy is extracted from the cells and copied millions of times over to be able to obtain a quantity sufficient for analysis. This amplification step and secondary analysis has the potential to introduce errors. The prevalence of mosaic embryos is controversial with some labs finding approximately 5% of embryos are mosaic and others up to 30%.
So, has this new categorization created more problems for PGS? I think that Dr Richard Scott said it best: “Every research program is fearful of throwing away a healthy embryo, but on the other hand, mosaicism is not always a benign thing. Now we are paying attention to these mosaics, but we don’t know exactly what to do with them.”
There have now been multiple publications showing that the transfer of mosaic embryos can result in the births of healthy euploid babies with no apparent evidence of mosaicism. These mosaic range embryos appear to have roughly half the chance of implanting as the normal-range embryos. But how do we know these embryos were truly mosaic, rather than euploid embryos that happened to fall in the mosaic range? Due to this conundrum, some experts have expressed caution about making a diagnosis of mosaicism. Furthermore, there is a huge controversy among fertility experts about what to do if mosaics are the only viable embryos a couple has left after IVF. Should would-be parents discard them because they contain potential abnormalities? Or transfer them in the hopes of achieving a normal pregnancy?
The introduction of this classification of embryos has the potential to further enhance selection for elective single embryo transfer and reduce the risk of miscarriage, which is the ideal and safest way to perform IVF. The next several years will be an exciting time as laboratory and clinical studies help to further elucidate this challenge of diagnosing mosaicism and what to do with the embryos deemed to be mosaic or at risk of mosaicism. Only time will tell….
Again, Thank You Dr. Ambler for this amazing information. If you are needing a consult or to talk with someone about your infertility Dr. Ambler can be reached through https://www.albrechtwomenscare.com. We are here for you! If you need a gestational carrier, click here to set up your free consultation.