Ethical dilemmas in genetic embryo testing: A discussion with Sigal Klipstein, MD

As a child, Sigal Klipstein, MD, would visit the Museum of Science and Industry in Chicago with her parents and be intrigued by the developing human exhibit, where she saw the progression of embryos to fetuses.

“I remember being fascinated by how a tiny tadpole-looking speck develops into a cute little baby,” Klipstein, a physician at InVia Fertility Specialists and assistant professor at the University of Chicago, told Healio. “I always enjoyed the fact that lessons learned from studying science and technology could be practically applied to helping people maintain and improve health. My desire to use my hands to fix problems surgically was one of the reasons I went into medicine.”

Outside of women’s health, Klipstein is a parent, avid reader and a lover of travel. Her travels also include visits to ancient archaeological sites, where she ponders the commonalities that tie past cultures to current civilization. Her children often kid her about her love of “really old rocks.”

Klipstein is the recipient of the Arnold P. Gold Foundation Humanism in Medicine Award for Practicing Physicians from the American Society for Reproductive Medicine and was presented with the award at the ASRM Scientific Congress & Expo in 2023 for her work in reproductive medicine. Klipstein is a member of the Donor Conceived People Task Force and has previously contributed to the Embryo Research Task Force for ASRM. She currently chairs the ASRM Ethics Committee.

Healio spoke with Klipstein about medical ethics in women’s health and what the future of reproductive endocrinology and infertility might hold.

Healio: What area of research in women’s health most interests you right now and why?

Klipstein: From the beginning of my career, I've been involved in medical ethics. I’m interested in questions surrounding emerging technologies. How should new technologies be utilized? What is the difference between what can be done and what should be done?

By way of example, we have the ability to genetically test embryos for a variety of diseases and disease predispositions. This ability grows with each new disease that is discovered. And so, there's a question about what you should test for. Should you test only for life-limiting diseases that lead to death in childhood? Should you test for diseases that can decrease life expectancy? Should you test for diseases that don't develop until later in life? And what about predispositions for diseases like breast cancer?

There is a debate going on about embryos for the risk for developing diabetes, high blood pressure, elevated cholesterol, schizophrenia and other late onset diseases. So, is that something that we should even be screening embryos for? And in order to screen embryos, people must undergo in vitro fertilization. Is it justified to pursue in vitro fertilization for the sole purpose of testing these embryos? What does that do to equity and distribution of resources in society? The fact is that not everybody will be able to afford to utilize this technology, so how do we determine how to ration this relatively scarce resource among the members of society who most stand to benefit from it? I am captivated by the ethical implications of these decisions.

The other interesting thing to me is looking at understanding what happens in the embryo after it's placed back in the uterus. We used to be able to grow embryos for 1 day or 2 days, and now we routinely allow them to develop for 5 days or 6 days before returning them to the uterus. There's an international debate going on right now about how long we should grow embryos. A group of experts gathered together half a century ago and developed the historic “14-day rule.” It was decided that embryos should not be allowed to grow beyond 14 days due to ethical considerations. At the time this was suggested, embryos could not be grown for anywhere near that length of time. Today, we are approaching this limit.

So, I’m interested in the question of how long we should grow embryos outside of the body, what we can learn from them and how we can better understand what happens after we put back the embryo. Certainly not every embryo we put back becomes a baby, and sometimes we know why not, but oftentimes, we don't know. That area of research – what happens within the black box of the uterus after an embryo implants and before we can see anything by ultrasound – is full of opportunity. However, we need to consider the ethics of growing embryos for longer in the lab. I feel strongly that these ethical questions should be considered prior to the technology being developed or utilized. Ethics should help determine how to best conduct science. Often, it is science that happens first, and ethics is an afterthought. I would like to see this order be reversed.

Healio: Have you ever been fortunate enough to witness or to have been part of health care history in the making?

Klipstein: What I find interesting is that the field that I have spent my entire career pursuing didn't even exist in the year that I was born. The first IVF baby was born in 1978 in the U.K., and then the first IVF baby in the U.S. – Elizabeth Carr – was born in 1981. I was fortunate enough to meet her at ASRM this year and take a picture with her. It's humbling to see living history through the embodiment of this person that technology helped bring to fruition.

In that sense, I've been witnessing history in the making throughout my career. There's so much we can do that we weren't able to do when I started specializing in this field. We rarely performing genetic testing of embryos and now, in some centers, 80% or 90% of the embryos are being screened for their chromosomal makeup or for genetic anomalies.

There's a lot of history in the making, which then opens ethical questions like what should we be testing for? And how does that change your perception of parenthood? Will we get to a point where we expect to have the perfect child and is there really such a thing?

Healio: What do you think will have the greatest influence on your field in the next 10 years?

Klipstein: There's a growing awareness that not everybody can afford fertility care, but everybody should have access to it. The distribution of resources and access to care is going to be a big topic of conversation depending on where you live and what job you have. You may or may not have access to insurance coverage for fertility treatment and that seems not right. Reproduction is a basic human right. I hope that, as a society, we will continue to find ways to provide fertility services to all those who seek them out.

The other thing that's going to impact the field is genetic testing of embryos. And beyond this, genetically altering embryos. Gene therapy already exists for children and adults, and this technology can be used in embryos to fix or cure a disease before it even becomes a disease, before babies are even born. I do think that is going to be a significant game changer in our field. And this is another area where we should – as a society – spend significant efforts on determining whether we should pursue this area of research. And, just as importantly, have a plan on how to move forward in an ethically and just manner. This is one of the reasons I find my work on the ASRM Ethnics Committee so important, as we consider these difficult issues and provide guidance on how to tackle them.

Healio: If you weren’t a physician or researcher, what would you be doing?

Klipstein: In an alternate reality, I'm an archaeologist. I love studying ancient cultures and ancient people, and I love going to visit ancient sites and wondering why people built what they built, how societies were formed, how societies were destroyed and how civilizations ended. My fantasy is to go on an archeological dig and use my OB/GYN training to understand what effects there might have been on pregnancy outcomes when different cultures interacted. Perhaps people who had never previously mated were incompatible in the sense that babies were larger and maternal and infant mortality was higher because the pelvis could not accommodate the birth of bigger babies. Or perhaps not.

I love ancient history. I've been to Rome, Greece, Southeast Asia and Peru, and it’s interesting that there are a lot of similarities in cultures, including the fact that many of their basic needs are universal. Most cultures have fertility figures, and why is that? Reproduction is central to the success of any society. I enjoy digging into different societies and understanding their fertility figures and what they might have represented to those who worshipped them.

Healio: Whom do you admire and what would you ask that person if you had 5 minutes with them?

Klipstein: I would love to talk to either the author of a medical papyrus in ancient Egypt or a physician in ancient Rome ask: How do you know what you know? What frustrates you? What diseases can you cure? What's your understanding of health and disease? And what do you wish you knew?

I went to Pompeii where archaeologists unearthed speculums for vaginal exams that look amazingly similar to the speculums of today. Even then, doctors understood the importance of pelvic exams and the need to differentiate if bleeding was coming from the uterus or the cervix and what that meant in terms of diagnosis.

So, I'd love to talk to someone who practiced 2,000 or even 5,000 years ago and ask if they think they’re at the top of their career. And ask: Do you think that this is the most medicine we'll ever know? We think medicine is moving so quickly that in 5 years, 10 years, 50 years, things will be different. Did my ancient counterparts ever feel like they've reached the pinnacle of their career? And once they become an expert in their particular field, did they know that there is so much yet to discover? What did they hope medicine could achieve in the future? Could they have even begun to envision the treatment modalities that we enjoy today? I'd love to glean wisdom from ancient physicians and look to the past to better understand the future.

For more information:

Sigal Klipstein, MD, can be reached at sklipstein@inviafertility.com and found on https://www.inviafertility.com/.