How IVF With Preconception Genetic Testing Can Empower Your Family-Building Journey
Attention to fertility has increased in recent years, fueled by the trend of women delaying childbirth until late 30s and early 40s. This is being driven by women meeting partners later in life as well as focusing on their careers. Understanding the profound impact of reproductive aging is vital for women who delay starting or expanding their family. While the quality of a woman’s eggs is highest in her mid-20s through early 30s, as women approach their mid-30s and beyond, both the quality and quantity of eggs begin to decline. This can result in longer times to conception and increased miscarriage rates with advancing age, as older eggs are more prone to abnormal fertilization.
In vitro fertilization (IVF) has evolved dramatically over the last few decades. However, advancements in IVF and genomics have shifted the goal from simply assisting individuals to achieve pregnancy to achieving a single healthy baby. For years, it was common practice to transfer multiple embryos back into a woman’s uterus after a retrieval and fertilization in hopes achieving one or more implantations. Unfortunately, one of the consequences of this action was multiple gestations, which increases risk of premature delivery and its associated complications.
Current technology has now provided an improved methodology. Following fertilization, embryos are cultured to the blastocyst stage (day 5-7 embryo), biopsied, and frozen or “vitrified.” If the biopsy reveals that the embryo is chromosomally normal (euploid), a single embryo is thawed and transferred to the uterus a few weeks later in a frozen embryo transfer cycle (FET). Embryo biopsy with Preimplantation Genetic Testing (PGT) can be utilized to screen for aneuploidy, now referred to as Preimplantation Genetic Testing-Aneuploidy (PGT-A). PGT-A does not require any specialized prep work and is recommended for all couples undergoing an IVF cycle as it greatly reduces the chances of failed implantation or miscarriage.
Aneuploid screening allows for assessment of chromosomal abnormalities in the embryo, such as extra or missing chromosomes (the structures that hold all our genes) in the embryos (i.e. Down Syndrome, Turner Syndrome, trisomies, monsomies, etc.). This type of genetic issue is usually not inherited and can happen randomly in the eggs or sperm of both women and men at any age, although chromosome abnormalities do occur more frequently in the eggs of women over 35 years of age. Aneuploidy (a chromosomally abnormal embryo) is a significant contributing factor in implantation failure and spontaneous miscarriages and is likely responsible for the majority of IVF failures utilizing unscreened embryos. Aneuploidy rates increase with increasing maternal age which is why older women have lower pregnancy rates and higher miscarriage rates in an IVF cycle using unscreened embryos. Aneuploid screening, therefore, allows us to identify the single healthiest and chromosomally normal (euploid) embryo. Excess euploid embryos can be saved for future attempts at pregnancy, since these embryos can remain frozen indefinitely. Accurate diagnosis and enhanced safety with biopsy at the blastocyst stage have resulted in increased implantation and delivery rates and have led to further development and use of PGT-A. This embryo screening technique has resulted in:
- Increased frequency of single embryo transfers
- Decreased incidence of multiple gestations
- Decreased incidence of miscarriage
- Reduced time to pregnancy since time lost to both failed cycles and miscarriages are minimized
Couples who are joint carriers for a specific genetic disorder (i.e. Cystic Fibrosis, Tay Sachs), one of the two parents is affected with a dominant disorder (i.e. Neurofibromatosis, Polycystic Kidney Disease), the female partner is a carrier for an X-linked disorder (i.e. Fragile X syndrome, Duchenne Muscular Dystrophy,) or have a genetic predisposition to cancer (i.e. BRCA), and therefore are at risk for having a child with the specific disorder or predisposition to cancer, may undergo PGT-M (preimplantation genetic testing for monogenic/single gene defects), previously known as PGD (preimplantation genetic diagnosis), to prevent having a child with the disorder or cancer predisposition. PGT-M identifies embryos affected by the specific genetic mutation and those that are not.
PGT-M allows couples to prevent a pregnancy with a specific genetic condition and is the only way to determine whether an embryo will be affected with a genetic condition prior to achieving pregnancy. This process requires a DNA sample from the patient and partner for an outside specialized genetics laboratory to create a “DNA probe” for the specific genetic mutation. DNA samples from the couple’s parents and other relatives are sometimes required to create an accurate test. An IVF cycle involving PGT-M includes the process of fertilizing the egg, culture of the embryo to the blastocyst stage, embryo biopsy, embryo freezing by vitrification, and DNA analysis to determine if the embryo carries the specific genetic mutation. In almost all PGT-M cycles, embryos also undergo PGT-A. This process allows us to identify the single healthiest embryo that is unaffected with the specific genetic mutation and is chromosomally normal. These embryos are later thawed and transferred during a frozen embryo transfer cycle (FET). Excess euploid and unaffected embryos can be saved for future attempts at pregnancy since these embryos can remain frozen indefinitely.
Advancements in IVF and genomics over the last few years have dramatically shifted recent focus to no longer simply assisting individuals in achieving pregnancy, but with the goal of achieving a single healthy baby. As a result, IVF with PGT-A and transfer of a single screened embryo in an FET cycle has become the preferred method of IVF at RMA of New York. While we work with our patients to offer the most effective treatment on an individualized basis, this approach enhances the ability to prevent a nonviable pregnancy, helping patients avoid the devastating and emotional suffering from a miscarriage, as well as the emotional and ethical challenges presented by prenatal diagnosis or of having a child born with a heritable disease. The use of this technology is just one way that RMA of New York is using scientific breakthroughs to help patients achieve their family-building goals in the most supportive and effective way possible.