Learn More About Preimplantation Genetic Diagnosis (PGD)/Preimplantation Genetic Screening (PGS)
Article written by Dr. Edward Ditkoff
The association between advancing age and decline in fertility has been known for years. This natural decline is related to the creation of genetically abnormal (aneuploid) embryos. Although Assisted Reproduction Techniques (ART) are very effective and assists reproduction by being more efficient then nature, it’s effectiveness is still limited by age and the creation of these abnormal embryos. These aneuploid embryos have too much or not enough genetic material, and the vast majority are nonviable. If nonviable, most will not implant, causing a delay in conception as women age. If implantation does occur, early pregnancy loss is most common, which is traumatic and causes further delay in childbearing. Rarely aneuploid embryos are viable and survive with syndromes like Down’s, Turner’s, or Klinefelter’s . Other aneuploid embryos could be associated with death soon after delivery, as in Edward’s or cri-du-chat syndrome.
Since we are aware of this direct correlation between aneuploidy, advanced age decreasing fertility, pregnancy loss, and lower IVF success, a technique called preimplantation genetic (diagnosis or screening) (PGD or PGS) has been evolving over the last 20 years. Today, both PGD/PGS and ART enable us to improve reproductive success rates in advanced aged women. PGD/PGS also assists in excluding embryos affected by single gene mutation that could be lethal or significantly have a negative impact on an individual’s life (Spinal Muscular Atrophy (SMA) or Cystic Fibrosis (CF)). Finally, and less common, PGD/PGS may be offered if couples are interested in family balancing (gender selection).
Another challenge for women (36 years of age and older) at risk for having aneuploid embryos (greater then 50%) is the individual/couple’s inability to produce a number of oocytes/embryos to favor having a normal genetic embryo. As the number of normal appearing embryos increases, so does one’s prognosis for having a healthy pregnancy. Without PGD/PGS, we attempt to choose embryos with the best overall appearance (morphology), but data has shown a limited correlation with the genetic integrity of these embryos. Recent data has demonstrated that the adverse maternal age effect on fertility is disappearing with a full chromosomal analysis by PGD/PGS of one’s embryos.
Recently, PGD performed on a mature blastocyst (day 5-7, trophectoderm biopsy) is becoming the standard and offers a better outcome then PGD done at an earlier embryonic stage (6-8 cell/ day #3). The advantages of a trophectoderm biopsy are as follows, biopsies are multicellular (have more DNA, results more likely), are more reliable with a lower error rate, the embryo biopsy has a reduced impact on the remaining embryo, there are less embryos to process (less expensive and more logical), may facilitate single embryo transfer, and could be used during a frozen embryo cycle with an ideal prepared uterine lining for implantation. The major disadvantages of a trophectoderm PGD biopsy are patients may not have embryos to biopsy and may prefer to have a fresh embryo transfer. A disadvantage for the lab is embryos may require biopsy on different days (5-7).
In summary, PGD/PGS performed on the biopsy from the trophectoderm is becoming the new standard in a field that is ever changing. PGD/PGS offers the best IVF outcome available by excluding aneuploid embryos most reliably. It is also helpful for excluding lethal single genes or those that have an adverse effect on quality of life. Gender selection for family balancing/medical reasons may also be desired. PGD/PGS improves success rates in advanced aged women (between 36- 42 years of age) to those of younger women by excluding their aneuploid embryos from being transferred. Unfortunately, as women age, the probability of aneuploid embryos increases, but the ability to produce oocytes decreases if they have decreased ovarian reserve. Less embryos may become biopsied per IVF cycle supporting a need to consider pooling multiple embryos by undergoing several IVF cycles with one PGD event and hopefully have a normal embryo that may lead to a healthy pregnancy.