Many Embryos are Chromosomally Abnormal

Studies from many different IVF clinics have shown that even embryos with good physical appearance or “morphology” can have chromosome problems. Even in women younger than 35, at least one third of the embryos have abnormal numbers of chromosomes. The number of embryos that have abnormal chromosomes increases each year as a women ages.

A technique called Preimplantation Genetic Diagnostics or PGD can select most of those embryos that are chromosomally normal.  Embryos with the correct number of chromosomes can be transferred to uterus (womb) or can be frozen for future use. PGD can improve the chance of getting pregnant and carrying to term, and it can reduce the chance of having a baby with a condition like Down syndrome. It also may decrease the chance of losing a pregnancy early.

What are Chromosomes?

Chromosomes are string-like structures found in the center of every cell (the nucleus). Chromosomes contain genes that are made of DNA. Therefore, out inherited information is housed on the chromosomes. Normal human cells (embryo, fetus, baby or adult) contain 46 Chromosomes or 23 pairs. We receive 23 chromosomes from each parent. The first 22 pairs of are the same for men and women and labeled largest to smallest: 1 through 22. The 23 rd pair determines our sex. To test for a chromosome abnormality such as Down syndrome, the chromosomes are studied.

Chromosomal Aneuploidy

Spermatozoa or eggs that have extra or missing chromosomes will pass this problem on to the embryo after fertilization. This situation is known as aneuploidy. There can be extra (trisomy) or missing (monosomy) chromosomes. Both conditions are a problem. If the aneuploidy involves the larger chromosomes, the embryo may not attach to the wall of the uterus or may stop developing soon after and miscarry. In some cases, however, the aneuploidy may cause the fetus to be abnormal but carry to birth. Down syndrome is an example of this, but there are several other types. The features of the chromosome condition depend upon which chromosome is extra or missing, but can include physical abnormalities and mental retardation.

Risk of Aneuploidy and Maternal Age

As a woman advances in age, the chance of aneuploidy in her pregnancies increases. This association is due to the fact that a woman’s eggs are as old as she is. Females have all of their eggs from the fetal stage on, therefore they are born with all the eggs they will have in their lifetime. As such, the theory regarding aneuploidy risk and advancing maternal age is that, over time, the chromosomes in the egg are less likely to divide properly leading to the egg having an extra or missing chromosome. The risk of conceiving an abnormal baby increases with maternal age, but the frequency of aneuploidy in embryos is much higher than at delivery. This difference in percentages of affected embryos versus live born is due to the fact that a pregnancy with aneuploidy is less likely to attach to the uterus or go to term. Most will not implant or will be miscarried. The percentage of affected pregnancies is reduced over the course of the pregnancy. The lack of implantation and loss rate of aneuploidy embryos are believed to be the main reasons why pregnancy rates decrease with advancing maternal age.

Avoiding Transfer of Chromosomally Abnormal Embryos

Aneuploid embryos are mostly indistinguishable morphologically and developmentally from chromosomally normal ones, thus, without genetically testing them, the embryologists doing your IVF procedure cannot recognize them.

The PGD Procedure

A technique called Preimplantation Genetic Diagnostics (PGD) has been developed to test embryos prior to the embryo transfer. This technique involves removing (biopsy)  one or more cells from each embryo, followed by a very fast genetic analysis using a technique called array CGH (aCGH).  Subsequently, embryos with a normal number of chromosomes can be transferred back to the uterus. Normal embryos have a higher chance of implanting, resulting in pregnancy and not miscarrying, than abnormal embryos.

Day 3 embryo

Blastomere Biopsy on Day 3 of Culture:

A blastomere is a cell from an embryo. To obtain the blastomere, an opening is made in the shell of the embryo (zona pellucida) during its third day of development when the embryo has 6 to 10 cells. A blastomere is removed by gentle suction. The embryo is placed in an incubator while the cell is sent to a genetics lab for analysis.  

Blastocyst Biopsy on Day 5 of Culture:  Main Line Fertility is one of the few centers in the USA that has the specialized equipment and trained embryologists to perform biopsy of blastocysts.  Blastocysts are embryos that have hundreds of cells that have differentiated into an inner cell mass (that will become the fetus) and the trophectoderm (that will become the placenta).  During blastocyst biopsy, a hole is made in the shell of the embryo and several cells are removed from the trophectoderm.  The advantages of blastocyst biopsy are that more cells are sampled for a more accurate diagnosis.  It is thought to be less stressful to the embryo compared to day 3 embryo biopsy, in which 1/6 to 1/8 of the embryo is removed.  In addition, it is now possible to test blastocysts on day 5 and transfer the chromosomally normal ones back to the womb the following day.  Extra normal blastocysts can be frozen for future attempts at pregnancy.

Advantages of the PGD Procedure

Most chromosomally abnormal embryos either do not implant or spontaneously abort shortly after implantation. Thus, if only normal embryos are replaced, which have higher chances of implanting and reaching term, the probability of conceiving a healthy child may increase if PGD is applied.

PGD of aneuploidy has been proven to double implantation rates in several studies, reduce the rate of pregnancy loss by half and increase take-home baby rates. Unpublished data from Reprogenetics also indicate a four-fold reduction in the frequency of chromosomally abnormal conceptions after PGD. 

Risks of the PGD Procedure

While PGD is a relatively new procedure in IVF, the micromanipulation or biopsy techniques required to perform the procedure have been in use for many years. The risk of accidental damage to an embryo during the removal of the cell(s) is less than 1% in experienced fertility centers. Additionally, no part of the future fetus will be compromised or missing because of the removal of a cell.

The test may occasionally classify an abnormal embryo as normal. Very few of such pregnancies have occurred. The reverse may happen, too – a normal embryo that is tested may be classified as abnormal by mistake, though the chance of this is also small. Again, due to the small chance of misdiagnosis as well as the presence of conditions not tested for via PGD, prenatal testing is still recommended.

Not all genes or chromosomes can be studied by PGD and one cannot test for both genes and chromosomes from the singles cell concurrently. Neither test is 100% accurate because we can only biopsy a single cell from the embryo, thus follow-up prenatal testing via chorionic villous sampling (CVS) or amniocentesis is highly recommended.

Which Patients Benefit the Most

• Women 37 and older: Any IVF patient 37 years of age or older may benefit from PGD, provided that they produce 5 or more embryos.
• Women with a prior history of multiple miscarriage or aneuploid pregnancies:
  Regardless of age, these patients could benefit from PGD. In all these patients, higher implantation rates, reduced pregnancy loss and reduced risk of chromosomally abnormal conceptions are expected after PGD. It is not clear yet if patients with repeated IVF failure benefit from PGD.
• Patients with a chromosome condition:
  Individuals with certain chromosome conditions can reduce their chance of passing the condition to their child via PGD.
• Severe male infertility: A high rate of chromosome abnormalities has been seen in embryos from men with non-obstructive azoospermia. PGD may also be indicated for other cases of very severe male infertility.
• Couple who are interested in family balancing

How Can You Have PGD?

 One of the embryologists at the Main Line Fertility Center will perform the biopsy, process the cell/s, and then send the biopsy to a very specialized genetics center – Reprogenetics, Gene Security Network, or LabCorp.  If you would like general information about PGD, you can contact Sharon Anderson, PhD at andersons@mainlinefertility.com.  If you are an IVF patient interested in PGD information or scheduling, please contact our PGD coordinator Tyl Taylor, MS at taylort@mainlinefertility.com or call him at 484-337-8969.

What About Cost?

This procedure may add $6,000 to the cost of IVF. Few insurance policies cover the expense.