Gateway to IVF Success: The ABCs of PGS

October 1, 2014 – Experts Down The Hall – Ronald Feinberg

Source: The Wall Street Journal – March 11th 2014

In a poignant New York Times interview in 2010 with the highly revered Dr. Howard Jones, he asserted, “Fertility investigators today should figure out which one embryo is likely to make a baby rather than transfer several. That will reduce costs, the number of multiple births and significantly increase success rates of in vitro fertilization.”

Approaches to PGS have become much more sophisticated and reliable over the past 10 years by utilizing streamlined DNA analysis, ensuring evaluation of all 46 chromosomes within a few cells carefully removed from each embryo.

Dr. Jones established the first U.S. IVF clinic over 30 years ago in Norfolk, VA with his wife, Dr. Georgeanna Jones, and their team achieved the first IVF pregnancy in the U.S. Since that time IVF treatments have become more complex, and thousands of women and men face a myriad of “alphabet soup” IVF jargon to learn. How intimidating does it sound when an IVF blogger writes, “I went to the XYZ Center for IVF, ICSI, TE biopsy, and PGS so I could have a euploid blastocyst SET with my FET”? Can some of this IVF “alphabet jargon” be more clearly explained?

From Our Expert, Dr. Ronald Feinberg

“The key value of PGS and CCS is our ability to predict which embryo or embryos have a normal complement of 46 chromosomes prior to uterine transfer. When a normal mature egg containing 23 chromosomes is fertilized with a normal sperm (containing another set of 23 chromosomes), an embryo with 46 chromosomes can develop.”

IVF has actually become more efficient over recent years, with the development of newer and better lab culture conditions. Exciting research developments exploring genes and DNA have yielded a perfect collaboration between IVF centers and genetics experts. With these advances, Dr. Jones’ long-standing goal of “one embryo, one healthy baby” is now a reality. This advice can be embraced because we are able to learn more about the chromosome health of embryos through pre-implantation genetic screening, or PGS. 

Approaches to PGS have become much more sophisticated and reliable over the past 10 years by utilizing streamlined DNA analysis, ensuring evaluation of all 46 chromosomes within a few cells carefully removed from each embryo. Some centers also refer to PGS as comprehensive chromosome screening, or CCS. 

The key value of PGS and CCS is our ability to predict which embryo or embryos have a normal complement of 46 chromosomes prior to uterine transfer. When a normal mature egg containing 23 chromosomes is fertilized with a normal sperm (containing another set of 23 chromosomes), an embryo with 46 chromosomes can develop. However, many embryos start out with an incorrect number of chromosomes stemming from an abnormal egg, sperm, or improper chromosome movement within the fertilized egg. 

As certain embryos develop in the lab to become blastocysts, usually four to five days after fertilization, it is not possible to accurately distinguish normal (euploid) versus abnormal (aneuploid) embryos under the microscope, making accurate embryo selection a major challenge. This dilemma has led to several exciting discoveries demonstrating the importance of incorporating PGS into current IVF treatments:

 

The chance of successful pregnancy after single embryo transfer (SET) and PGS is 55% to 65%.

When Dr. Jones and others performed IVF treatments in the 1980s, the success rates were only about 10% to 20%, even when multiple embryos were transferred. For many years, IVF doctors didn’t think success rates would ever surpass 20%, the average monthly chance of natural conception for a fertile couple in their 20s. Transferring multiple embryos at one time became the norm to enhance IVF success rates, but with that strategy came the unintended consequences of multiple gestation, profound prematurity, cost, and significant emotional turmoil.

 

Age matters, but not as much with PGS.

If a 40-year-old woman has a euploid blastocyst transferred to her uterus, her chance of normal pregnancy is about the same as a 25-year-old IVF patient. While this is an astounding finding, it is very clear that older women are much less likely to create multiple embryos that are normal when compared to younger women. It is also more likely that older women might not produce any normal embryos in a given IVF cycle. A very high percentage of abnormal PGS results are caused by an abnormal number of chromosomes within the mature egg—a significant age-dependent event.

 

A single normal embryo can be transferred in a fresh or frozen embryo transfer (FET) cycle following PGS, yielding similar success rates.

This provides great flexibility in how and when treatments are carried out and empowers women and men to design their own specific family building pathways. Our colleagues in the maternal-fetal medicine and neonatal fields have published compelling data to suggest that FET actually yields fewer maternal and fetal pregnancy complications. They have also strongly urged that SETs be carried out to minimize risks. Most IVF clinics offering PGS utilize FET cycles.

 

Miscarriage rates are much lower after PGS.

Since the majority of early miscarriages—including “chemical” pregnancies—are caused by chromosome errors in the embryo, it makes sense that many miscarriages can be prevented with PGS testing. Transfer of a single euploid (46 chromosome) embryo results in miscarriage in less than 10% of pregnancies. Miscarriage creates a significant emotional burden for our patients in addition to other costs and delays in care.

 

PGS as performed in 2014 is just the beginning.

As DNA testing becomes more sophisticated and less costly, PGS will be fine-tuned to further enhance IVF success. IVF researchers are already discussing the use of DNA sequencing and other molecular modalities to better predict the health status of an embryo. The tiny trophectoderm  (TE) cells biopsied from the blastocyst for PGS contain a powerhouse of molecular information about the embryo, which can be analyzed for many different diagnostic markers.

In the future, it is possible that maternal age alone will not be the “done deal” many have come to accept. Univfy researchers and collaborators have clearly found that many factors other than age alone can greatly impact and predict IVF success. Individualized patient and clinic-customized prediction testing holds great promise when our patients seek guidance for their IVF decision-making.

One major goal of IVF physicians is to identify proven health interventions that will optimize the vitality of eggs, sperm, and embryos, leading to enhanced fertility and family building options for our patients. PGS has given us a significant glimpse into the mysteries and wonders of human reproduction. With PGS, the vision of Dr. Howard Jones and the future of IVF are looking much brighter.

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