Is a Mosaic Embryo Better Than No Embryo?

For nearly five decades, in vitro fertilization (IVF) has been a solution for people who struggle to build a family. In the past three decades, genetic testing for embryos has become more common. Preimplantation genetic testing for aneuploidy (PGT-A) is commonly used today to select the healthiest embryos for transfers. Embryology laboratories frequently encounter embryonic mosaicism, which is the presence of two or more distinct cell lines in the same embryo (Greco et al, 2020). There are various levels of mosaicism, and different chromosomes may be affected in each embryo. Individuals who face fertility challenges are in sensitive situations; they may be emotionally and financially drained and/or physically and mentally hurt.

For some, transferring a mosaic embryo is more feasible, because the alternative means undergoing additional painful and expensive IVF cycles in hopes of a euploid embryo. After a long infertility journey, this alternative is not any easier than transferring a mosaic embryo and performing additional prenatal tests once a pregnancy is achieved. Therefore, it is imperative to treat each mosaic embryo individually when considering an embryo transfer. Some mosaic embryos might have high chances of implanting and developing into healthy babies.

According to the Centers for Disease Control and Prevention (2020), ∼2% of babies born in the United States every year are a result of assisted reproductive technology (ART) treatments. As women age, they have fewer eggs and lower egg quality, thus their embryos are more prone to chromosomal abnormalities. Many factors contribute to infertility, such as genetic conditions, diminished ovarian reserve, and male factor infertility. Therefore, fertility treatments that combine IVF and PGT-A can help improve reproductive care success rates.

IVF is the process of stimulating a woman's ovaries to produce follicles and excavating the eggs to fertilize them in vitro. Although some are grown to day 3, most embryos are grown to day 5 or 6, to a blastocyst stage. At this point, if the patients consented to PGT-A, a biopsy of about six to eight cells is taken from the trophectoderm portion of the embryo that forms the placenta (Abhari and Kawwass, 2021). Results include normal (euploid), mosaic, and abnormal (aneuploid).

The cutoff ranges of mosaicism, analysis methods, and interpretation of PGT reports may vary substantially between fertility clinics and embryology laboratories (Cram et al, 2019). Mosaic embryos can either have a single chromosome loss or gain, a complex (three or more affected chromosomes), or a structural aneuploidy, with varying ratios of normal to abnormal cells (Greco et al, 2020; Zhou et al, 2021). Occasionally, rebiopsying mosaic embryos can help better the diagnosis, since in some cases the rebiopsy of complex mosaicism resulted in euploidy (Zhou et al, 2021).

PGT is costly. It varies by the clinic and the number of embryos, but generally, it costs on average $1500 per embryo. Most insurance plans do not cover IVF and rarely cover PGT. Therefore, many patients choose not to move forward with the testing and take the increased risk of their embryos miscarrying or not implanting. Some of those who do proceed to PGT-A may only yield a small number of embryos, if any. Unfortunately, sometimes only mosaic and abnormal embryos are obtained.

In such cases, it is more likely that the specialists will support the transfer of the mosaic embryos. These cases would likely require more prenatal monitoring and might also be classified as high-risk pregnancies. Yet, especially in such cases, the chance of this embryo developing into a normal fetus and a healthy baby is sometimes worth taking.

Despite the advances in ART today, the data on mosaic embryo transfers (METs) are still limited. Understandably, euploid embryos have a higher chance of implanting and surviving to term than mosaic embryos. The level of mosaicism and the specific genetic anomaly should be taken into consideration when predicting the success of an MET. One prospective study by Zhang et al (2020) compared mosaic, euploid, and non-PGT tested embryo transfer outcomes across three different clinics and found that mosaic embryos resulted in a lower implantation rate and a higher miscarriage rate—as expected.

In a retrospective study by Munné et al (2017), 41% of METs implanted successfully. A possible explanation that supports some METs is the idea of self-correction. When the normal cells outnumber the abnormal cells (in low mosaic—up to 40% abnormal cells), they often replicate faster and more efficiently than the abnormal cells that become apoptotic (Chavkin, 2021; Esfandiari et al, 2016). This is where things get complicated for patients to make choices; therefore, integrating genetic counseling into the process is critical to ensure they are understanding all their options clearly.

Carefully and correctly interpreting PGT results, counseling patients about their options, and reminding them that after all it is their choice are essential in such sensitive situations. Regrettably, the ability to choose an MET was not offered to this author (O.G.W.). The two fertility clinics I worked with as a patient did not staff a genetic counselor and did not take my mosaic embryo into consideration, despite my repeated requests to investigate this option.

The increased incidence of infertility and consequently the demand for ART affect millions of people in the United States and around the world. The benefits of PGT-A in reproductive care are vast, and having the privilege to screen and select embryos based on the quality of their genetic material is incredible. Although mosaic embryos are generally less favored, some might need to pursue METs as their best option. Many mosaic embryos can grow into healthy babies. Therefore, it is essential to have the support of their medical team to investigate each case individually, carefully examine the possible outcomes of the specific chromosomal anomaly, and educate the patients about these uncertain outcomes and the additional steps that might need to be taken throughout these pregnancies.