Report Cards for Embryos 

Recently I received an email from a supporter of the Center for Bioethics and Culture Network looking for more information on “embryo grading” and the ethics of this technology as it is used in assisted reproduction. Although most people don’t discuss it, or may not even be aware of it, prior to starting any fertility treatment, embryo grading, as well as sperm sorting, are technologies we are aware of and have discussed on Venus Rising with Joyce Harper, BSc, PhD and Breaz, and have written about in the last few years. However, as an educational non-profit, when people reach out to us seeking information in bioethics, we get to work. In this article I will discuss sperm sorting, egg quality, and embryo grading. 

Boy or girl? The sperm hold the answer. 

First, Assisted Reproductive Technologies (ART) includes any technology where eggs and embryos are handled. It does not include technologies where only sperm is handled, like intrauterine insemination (IUI) for example. Therefore, sperm sorting can be utilized outside of the context of ART. Sperm sorting is used for sex selection. The sperm carries either a Y chromosome or an X chromosome and determines a person’s sex once combined with the egg’s X chromosome. For those of us who know and understand that sex is binary, females have XX chromosomes and males have XY chromosomes. According to some fertility centers, the cost for sperm sorting is about one to three thousand dollars per cycle and has a success rate of 70-80% when selecting sperm with an X chromosome and 60-70% when selecting sperm with a Y chromosome. Sperm sorting is not the only way to attempt sex selection of offspring. Preimplantation genetic testing for aneuploidy (PGT-A) is a method used to select sex of an embryo prior to implantation in IVF and surrogacy. 

Of course, either by sperm sorting or embryo genetic testing, sex selection is a controversial practice. The American Society for Reproductive Medicine (ASRM) expressly states that “sex selection should not be encouraged for nonmedical indications” however, in the same document also state that “practitioners offering assisted reproductive services are under no ethical obligation to provide or refuse to provide nonmedically-indicated methods of sex selection”. There are, of course, couples who undergo IUI or ART, not for any medical necessity, but rather just so they can improve the success rate of having either a boy or girl.

According to research:

The primary arguments against the use of PGT-A in otherwise fertile couples for nonmedical sex selection… include harm to offspring, harm to women and also to men, misuse of medical resources for nonmedical purposes, and risks of discrimination and perpetuation of social injustice. It also can be argued that framing sex selection as a neutral patient option may increase the acceptability of its use in countries where there is a clear preference for a particular sex.

An entire paper could be written on the ethics of sex-selection, but that isn’t the focus of this article so I’ll continue on with sperm’s much needed companion, the egg. 

Egg Quality Determines Embryo Quality

Egg quality matters a great deal in ART or IVF and when someone is paying thousands of dollars, spending years of their lives to try and conceive utilizing ART, success can come down to egg quality- which is why third party reproduction has gained so much momentum. Let’s say it’s determined that a woman in a heterosexual relationship has poor egg quality. Well, she and her partner might be encouraged by the fertility clinic to buy an egg from another woman (known in the industry as an egg “donor”). There is no technology that exists (yet) to directly determine egg quality, so egg sorting like we see in sperm sorting isn’t a thing. Instead, blood tests, ultrasounds, reproductive history, and age are all utilized and factored when determining egg quality. Boston IVF states on their website: 

We know with certainty that age is linked with a decline in ovarian reserve or the number of eggs in your ovaries. Decline in ovarian reserve is connected with a decline in your chances of a viable pregnancy. Age is also tied with egg quality: only twelve percent of all eggs in most thirty-year-old women have the potential to become babies. Only four percent of those eggs remain by age forty. So although egg quality cannot be tested directly, a woman’s age is often an excellent predictor/indicator of the quality of her eggs.

A point worth making here is that aging and fertility have always been closely related. The reality is that there is a timeclock on a woman’s ability to conceive and an often unpopular opinion is that egg freezing and ART are not a solution to waiting to have children. Just like puberty, menopause is a normal bodily process, not a diagnosis, and there is no pressing pause.

Embryo Grading: An Ethical Landmine 

 According to San Diego Fertility Center, embryos for IVF are cultured for five or six days, corresponding to the stage when the embryo is a blastocyst, and receives a grade each day. This grading helps determine which embryos are selected for transfer and which are discarded. Most embryos are subject to this 5 or 6 day grading prior to transfer, but other clinics offer an option to stop grading at day three when the embryo has reached cleavage stage (the embryo has started to divide). Selected embryos are then transferred to the uterus. For those interested in details and data, a 2019 study, analyzing over 900 blastocysts, offered the following to show that the better the grade, the higher the live birth rate:

Those embryos not selected for transfer are usually discarded. For those readers that believe human life starts at conception, this is problematic, or should be. If you believe that life begins at conception, then the destruction of embryos is the destruction of human life. For this reason, I often don’t understand how those who do believe life starts at conception can support the IVF industry. Of course, we know of many people that don’t believe life starts at conception, but still oppose IVF on the basis of the harm it does to women and children. 

That stated, let’s focus on how grading systems were developed and who or what really determines an early embryo’s grade in the first few days of development. According to an article from 2010, there are and have been numerous systems created and used to grade and rank embryos at day 3 and days 5 or 6. Simple grading systems assign one grade to account for the overall appearance where more complex grading scales use a formula to predict pregnancy likelihood based on the appearance and development of the embryo in question. Grading of embryos at day five or six (blastocyst stage embryos) depends on the quality of three key elements: blastocyst expansion, the inner cell mass (which will develop the fetus), and trophectoderm epithelium (which will become the placenta). There really hasn’t been, nor is there still, an international agreed-upon standard for embryo grading. However, the Society for Assisted Reproductive Technology (SART) created (in 2006) and implemented (in 2010) a simple grading system with a goal of unifying a standard method of grading the human embryo. This scoring system still has its limitations. First, according to one review “very few studies have evaluated the efficacy of the SART embryo grading method.” Secondly, in recent years there has been a shift to only transfer one embryo (the best embryo) in order to minimize the occurrence of twins or multiples thereby reducing risk to the mother or fetus(es). The grading system implemented by SART “lacks criteria for describing the cohort specific best embryo and thus is of limited use in single embryo transfer.” That is, it’s impossible to pick the very best embryo for a single embryo transfer.  Grading is subjective depending on who the “teacher” (embryologist) is. 

Beyond the daily grading of early embryos, hopeful parents can choose to put their embryos through stricter testing via costly IVF add-ons to further grade and select the most desirable embryo. Basically, if you pay enough money you can generate a report card so detailed that it will outline the likelihood of common diseases or traits. From that detailed report, men and women can select the most desirable embryo to implant. Dr. Harper and I spoke about these technologies known as preimplantation genetic diagnosis (PGD) and polygenic embryo selection/screening (PES) on Venus Rising and I cover them in detail on our website so I won’t re-write it here. Instead, I’ll briefly outline some ethical issues to consider here. First, there is limited data and research on the efficacy of these technologies and because of this, a warning has been given stating that “patients, and even in vitro fertilization clinicians, may think that the service is more effective and less risky than it is.” Dr. Harper gave the same vibes in her interview. Secondly, we must consider, should we be experimenting on embryos in the first place? Finally, these technologies have the “potential to alter population demographics, exacerbate socioeconomic inequalities and devalue certain traits.”  There are ethical landmines all over the place, but rather than stop to consider them before implementation, #BigFertilty saw dollar signs and plowed ahead. 

Over and over again on fertility clinic websites, readers will get the impression that embryo grading is key to IVF success and that preimplantation genetic screening is a recommended and useful technology. However, interestingly though, these same clinics are also “happy to share poor-quality embryo success stories from patients who have achieved their dream of becoming a parent despite a lower-grade embryo.” It seems the fertility industry will use whatever wording they need to in order to convince women and men to board the high-tech fertility rollercoaster to create a child or children of their dreams.