Maternal age and successful egg freezing with PGS: an interview with Dr. Santiago Munné

insights from industryDr. Santiago Munné Founder and Director of Reprogenetics

Please can you give a brief introduction to Preimplantation Genetic Screening (PGS)?

The leading cause of of pregnancy loss or infertility is chromosomal abnormality or imbalance, where extra genetic material is present or some is missing - what’s called aneuploidy. This imbalance leads to the inability to produce viable embryos or pregnancy.

As women age, the percentage of their eggs (oocytes) that carry a chromosomal abnormality increases, and with it, their risk of infertility, miscarriage or delivering babies with aneuploidies such as Down syndrome.

PGS is a process used for in vitro fertilization (IVF) in which a small number of cells (3-10) is removed from a cultured embryo while it is still in the blastocyst stage and screened for aneuploidy or other chromosomal abnormalities. This allows the chromosomally normal embryos with the highest likelihood for success to be chosen for implantation.

Preimplantation Genetic Diagnosis (PGD) is a similar process that looks for specific genetic diseases and chromosomal disorders in at-risk couples.

We use an advanced genetic testing technique called Array Comparative Genomic Hybridization (aCGH) or next generation sequencing (NGS) for PGS.

What effect does PGS have on pregnancy rates in frozen donor egg embryo transfer cycles?

PGS effectively increases the success rate in both frozen and ‘fresh’ donor egg embryo transfers because it screens out those embryos with chromosomal abnormalities that would ultimately not implant or miscarry, while it also avoids giving birth to babies with aneuploidy syndromes.

Could you please outline the data that was presented recently at the American Society for Reproductive Medicine (ASRM) annual meeting that showed a sharp decline in the number of normal eggs available for successful in vitro fertilization (IVF) as a woman’s age increases?

Because most of the research on the successful freezing of eggs (OC) has been conducted on women under the age of 35, the authors wanted to know how OC performs with women who are older.

The study that was presented at the ASRM meeting looked at – based on age- the number of oocytes a woman would need to have retrieved and frozen in order to produce one embryo with the normal number of chromosomes.

The data showed that the numbers increase dramatically for women over the age of 37. For a 42 year old, about 11 stimulation cycles would be required to produce 103 oocytes to yield that one normal embryo.

How does this data differ from previous results?

This was one of the first studies that looked at the effect of donor age on the rate of successful embryo creation from frozen eggs.

What is interesting here is that because older women don’t typically store their eggs for the future, there was very little data on the impact of age on frozen oocyte viability.

The research found that chromosomal abnormality rates in frozen donor eggs correlated closely with the age of the women from whom they were retrieved.

So the older the donor, the higher the rate of chromosomal abnormalities, and therefore, far more eggs produced fewer viable embryos than from younger donors.

What impact do you think the results of this study will have?

OC was initially explored as an option for patients who for medical reasons, such as cancer treatment, wanted to preserve their oocytes for later use. It was also an option for patients wanting to avoid the creation and storage of fertilized embryos.

Particularly for those who are delaying child bearing, this may cause women to consider oocyte cryostorage (OC) at a younger age, when their oocytes are better candidates for producing viable embryos later on, if and when they choose to become pregnant.

This data may also discourage women who are in the upper end of advanced maternal age from retrieving and storing their eggs because the projected success rate was low.

Given the pregnancy success rates with OC, ASRM and the Society for Reproductive Technologies published guidelines on OC in 2013 stating that OC is no longer considered experimental (these were later endorsed by the American College of Obstetrics and Gynecology, ACOG).

How much research has been done on the long-term impact of egg-retrieval in women?

At least four well-controlled clinical trials have compared pregnancy rates of ‘fresh’ IVF with frozen oocytes and found them to be comparable.

In the context of other, conclusive scientific research, the amount of data available is not particularly large, but it is convincing.

To-date there are no indications that the rate of birth defects or other negative outcomes are increased with OC, but over coming years we are sure to learn more as the techniques become more widely used and evidence mounts.

What are your thoughts on Facebook’s and Apple’s recent announcements to offer females financial help towards egg freezing?

I think these policies are very forward thinking and represent an important step for women of reproductive age who are not ready to conceive.

The cost of OC and IVF can be a barrier for many women so these companies are stepping forward in an unprecedented way to support their employees. I think from an employer point of view it also makes sense.

What are Reprogenetics’ plans for the future?

Today’s PGS/PGD can successfully address the chromosome aneuploidy issues associated with advancing maternal age, which is proving very helpful for many women, but not all, in achieving pregnancy.

We remain very excited about whole genome sequencing approaches to analyze an embryo’s entire genome for all abnormalities known to cause disease.

The nature of biology is that you cannot predict or control with absolute certainty how DNA and genes will choose to express themselves or remove all possibility of disease, but with full genome sequencing we can dramatically increase the percentage of successful, healthy deliveries.

Whole genome sequencing for PGS is now achievable but it has, so far, been too costly to implement on a broad scale.

Reprogenetics, our collaborators and our peers continue our research to refine and improve the techniques, and the platforms on which it is based continue to decrease in cost.  It is just a matter of time before this becomes routine.

Where can readers find more information?

Reprogenetics.com provides a great deal of information on assisted reproduction and cryopreservation for patients and physicians.

There are also very good resources available on the websites of ASRM and it patient site, reproductivefacts.org, and at SART.org.

About Santiago Munné

Dr. Munné is the Founder and Director of Reprogenetics (www.Reprogenetics.com). Originally from Barcelona, Dr. Munné gained his Ph.D. in Genetics from the University of Pittsburgh and in 1991, joined Dr. Jacques Cohen at the Cornell University Medical College located in New York City.

It was at Cornell where he developed the first Preimplantation Genetic Diagnosis (PGD) test to detect embryonic numerical chromosome abnormalities to avoid Down’s syndrome and other abnormalities.

The Society for Assisted Reproductive Technology recognized this and his following work with two consecutive prizes in 1994 and 1995.

Dr. Munné became the Director of Preimplantation Genetic Diagnosis at The Institute for Reproductive Medicine and Science of Saint Barnabas in 1995. It was at the institute, he developed the first test to detect chromosome translocations in human embryos, which significantly reduces the chance of select patients losing their pregnancy, while avoiding birth defects associated with this condition.

April Cashin-Garbutt

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April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.

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