What are PGD and PGS?

PGD is preimplantation genetic diagnosis of embryos after IVF.  PGD identifies which embryos carry (or are affected) a specific genetic disease. Some examples of single gene diseases are cystic fibrosis and Tay Sachs disease.  Both partners first undergo carrier screening, which is when a blood sample from each partner is sent to a genetics lab to determine if he or she is a carrier for a specific genetic disease.  Being a carrier of a genetic disease generally does not affect your individual health.  However, being a carrier does mean that that there is an increased chance for your children to have the disease.  If both the partners are carriers of the same disease, and you want to minimize the chance of having an affected child, PGD is an option.  Embryos are tested during PGD, and only the ones without the genetic disorder are transferred back to the uterus.

PGS is pre-implantation genetic screening (PGS) of embryos after IVF.  PGS can identify which embryo is chromosomally normal.  Embryos with the correct number of chromosomes can be transferred to uterus (womb) or can be frozen for future use. PGS 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 can also decrease the chance of miscarriage due to aneuploidy.

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, our 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 are the same for men and women and labeled largest to smallest: 1 to 22. The 23-rd pair determines our gender. To test for a chromosome abnormality such as Down syndrome, the chromosomes are studied.

Gender Selection or Sex Selection

The PGS report will indicate which embryos are males and which ones are females. If an embryo has one X chromosome and one Y chromosome, the gender is male.  If there are two X chromosomes, then the gender is female.

Many Embryos have an abnormal number of chromosomes

Studies 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 women ages.

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 can be an issue. 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 and condition of chromosome depend upon which chromosome is extra or missing, but can include physical abnormalities and mental retardation.

Risk of Aneuploidy and Maternal Age

As the age of a woman increases, the chance of aneuploidy increases in pregnancies. 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 is that, over time, as the age increases the chromosomes in the egg are less likely to divide properly which leads extra or missing chromosome. With the increase of woman’s age, the risk of conceiving an abnormal baby increases, 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 main reasons why pregnancy rates decrease with advancing maternal age is the lack of implantation and loss rate of aneuploid embryos.

Avoiding Transfer of Chromosomally Abnormal Embryos

Aneuploid eggs most of the times are impossible to differentiate morphologically and developmentally from chromosomally ordinary ones. The PGS report will show which embryos have the right number of chromosomes for transmission.

The PGS Procedure

PGS 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) or Next Generation Sequencing (NGS).  Subsequently, embryos with a normal number of chromosomes can be transferred back to the uterus. Euploid embryos (those having the correct number of chromosomes) have a higher chance of implanting and resulting in a healthy pregnancy.

Blastocyst Biopsy on Day 5 or 6 of Culture:

Acme IVF  is one of the few centers in the India 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.    Chromosomally normal blastocysts can be frozen for future attempts at pregnancy.

In addition, it is possible to thaw cryopreserved embryos, perform PGS or PGD, and then transfer the healthy embryo/s in a frozen embryo transfer (FET) cycle.

Advantages of the PGS

Most chromosomally abnormal embryos either don’t embed or suddenly prematurely end soon after implantation. In this manner, if typical normal embryos are replaced, which have higher shots of implanting and coming to term, the chances of giving birth to a healthy baby increases if PGS is applied.

PGS of aneuploidy has been demonstrated to twofold implantation rates in a few studies, lessen the rate of pregnancy misfortune by half, and expand take-home child rates.

Advantages of Freezing Embryos after PGS or PGD

Embryos can be frozen after biopsy and then later transferred in a frozen embryo transfer (FET) cycle.  An advantage of this is the best embryo can be selected from day 5 and day 6 blastocysts.  In addition, the uterus may be more receptive.

Banking or Batching

Patients have the opportunity to freeze and bank multiple biopsied embryos from several IVF cycles.  When patients have the desired number of biopsied blastocysts, they can analyze the frozen biopsied cells at the genetics lab, and pay for testing only once.  One or two tested embryo/s can be transferred back to the uterus in a frozen embryo transfer (FET) cycle.

Risks of the PGS Procedure

While PSS 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 cells.

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 PGS and one cannot test for both genes and chromosomes from the single cells 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 PGS, 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 PGS. In all these patients, higher implantation rates, reduced pregnancy loss and reduced risk of chromosomally abnormal conceptions are expected after PGS. It is not clear yet if patients with repeated IVF failure benefit from PGS.
• Patients with a different chromosome condition: Individuals with certain chromosome conditions can reduce their chance of passing the condition to their child via PGS.
• Severe male infertility: A high rate of chromosome abnormalities has been seen in embryos from men with non-obstructive azoospermia. PGS may also be indicated for other cases of very severe male infertility.
• Couples who are interested in family balancing

What about Cost?

This procedure may add $5,000 to $6,000 to the cost of IVF. In some of the cases, the insurance policies cover the expense.