Couples Facing Fertility Treatments Should Beware of This
When Jane Stein and her husband used in-vitro fertilization in 2001 to become pregnant with twins, her fertility clinic recommended using a supplemental procedure called intracytoplasmic sperm injection (ICSI), known in fertility lingo as "ix-see."
'Add-on' fertility procedures are increasingly coming under scrutiny for having a high cost and low efficacy rate.
During IVF, an egg and sperm are placed in a petri dish together with the hope that a sperm will seek out and fertilize the egg. With ICSI, doctors inject sperm directly into the egg.
Stein, whose name has been changed to protect her privacy, agreed to try it. Her twins are now 16, but while 17 years have gone by since that procedure, the efficacy of ICSI is still unclear. In other words, while Stein succeeded in having children, it may not have been because of ICSI. It may simply have been because she did IVF.
The American Society for Reproductive Medicine has concluded, "There are no data to support the routine use of ICSI for non-male factor infertility." That is, ICSI can help couples have a baby when the issue is male infertility. But when it's not, the evidence of its effectiveness is lacking. And yet the procedure is being used more and more, even when male infertility is not the issue. Some 40 percent of fertility treatments in Europe, Asia and the Middle East now use ICSI, according to a world report released in 2016 by the International Committee for Monitoring Assisted Reproductive Technologies. In the Middle East, the figure is actually 100 percent, the report said.
ICSI is just one of many supplemental procedures, or 'add-ons,' increasingly coming under scrutiny for having a high cost and low efficacy rate. They cost anywhere from a couple of hundred dollars to several thousand – ICSI costs $2,000 to $3,000 -- hiking up the price of what is already a very costly endeavor. And many don't even work. Worse, some actually cause harm.
It's no surprise couples use them. They promise to increase the chance of conceiving. For patients who desperately want a child, money is no object. The Human Fertilization and Embryology Authority (HFEA) in the U.K. found that some 74 percent of patients who received fertility treatments over the last two years were given at least one type of add-on. Now, fertility associations in the U.S. and abroad have begun issuing guidance about which add-ons are worth the extra cost and which are not.
"Many IVF add-ons have little in the way of conclusive evidence supporting their role in successful IVF treatment," said Professor Geeta Nargund, medical director of CREATE Fertility and Lead Consultant for reproductive medicine at St George's Hospital, London.
The HFEA has actually rated these add-ons, indicating which procedures are effective and safe. Some treatments were rated 'red' because they were considered to have insufficient evidence to justify their use. These include assisted hatching, which uses acid or lasers to make a hole in the surrounding layer of proteins to help the embryo hatch; intrauterine culture, where a device is inserted into the womb to collect and incubate the embryo; and reproductive immunology, which suppresses the body's natural immunity so that it accepts the embryo.
"Fertility care is a highly competitive market. In a private system, offering add-ons may discern you from your neighboring clinic."
For some treatments, the HFEA found there is evidence that they don't just fail to work, but can even be harmful. These procedures include ICSI used when male infertility is not at issue, as well as a procedure called endometrial scratching, where the uterus is scratched, not unlike what would happen with a biopsy, to stimulate the local uterine immune system.
And then for some treatments, there is conflicting evidence, warranting further research. These include artificial egg activation by calcium ionophore, elective freezing in all cycles, embryo glue, time-lapse imaging and pre-implantation genetic testing for abnormal chromosomes on day 5.
"Currently, there is very little evidence to suggest that many of the add-ons could increase success rates," Nargund said. "Indeed, the HFEA's assessment of add-on treatments concluded that none of the add-ons could be given a 'green' rating, due to a lack of conclusive supporting research."
So why do fertility clinics offer them?
"Fertility care is a highly competitive market," said Professor Hans Evers, editor-in-chief of the journal Human Reproduction. "In a private system, offering add-ons may discern you from your neighboring clinic. The more competition, the more add-ons. Hopefully the more reputable institutions will only offer add-ons (for free) in the context of a randomized clinical trial."
The only way for infertile couples to know which work and which don't is the guidance released by professional organizations like the ASRM, and through government regulation in countries that have a public health care system.
The problem is, infertile couples will sometimes do anything to achieve a pregnancy.
"They will stand on their heads if this is advocated as helpful. Someone has to protect them," Evers said.
In the Netherlands, where Evers is based, the national health care system tries to make the best use of the limited resources it has, so it makes sure the procedures it's funding actually work, Evers said.
"We have calculated that to serve a population of 17 million, we need 13 IVF clinics, and we have 13," he said. "We as professionals discuss and try to agree on the value of newly proposed add-ons, and we will implement only those that are proven effective and safe."
Likewise, in the U.K., there's been a lot of squawking about speculative add-ons because the government, or National Health Service, pays for them. In the U.S., it's private insurers or patients' own cash.
"The [U.K.] government takes a very close look at what therapies they are offering and what the evidence is around offering the therapy," said Alan Penzias, who chairs the Practice Committee of the ASRM. It wants to make sure the treatments it is funding are at least worth the money.
ICSI is a case in point. Originally intended for male infertility, it's now being applied across the board because fertility clinics didn't want couples to pay $10,000 to $15,000 and wind up with no embryos.
"It is so disastrous to have no fertilization whatsoever, clinics started to make this bargain with their patients, saying, 'Well, listen, even though it's not indicated, what we would like to do is to take half of your eggs and do the ICSI procedure, and half we'll do conventional insemination just to make sure,'" he said. "It's a disaster if you have no embryos, and now you're out 10 to 12 thousand dollars, so for a small added fee, we can do the injection just to guard against that."
In the Netherlands, the national health care system tries to make the best use of its limited resources, so it makes sure the procedures it's funding actually work.
Clinics offer it where they see lower rates of fertilization, such as with older women or in cases where induced ovulation results in just two or three eggs instead of, say, 13. Unfortunately, ICSI may result in a higher fertilization rate, but it doesn't result in a higher live birth rate, according to a study last year in Human Reproduction, so couples wind up paying for a procedure that doesn't even result in a child.
Private insurers in the U.S. are keen to it. Penzia, who is also an associate professor of obstetrics, gynecology and reproductive biology at Harvard Medical School and works as a reproductive endocrinology and infertility specialist at Boston IVF, said Massachusetts requires that insurers cover infertility treatments. But when he submits claims for ICSI, for instance, insurers now want to see two sperm counts and proof that the man has seen a urologist.
"They want to make sure we're doing it for male factor (infertility)," he said. "That's not unreasonable, because the insurance company is taking the burden of this."
Gene therapy helps restore teen’s vision for first time
Story by Freethink
For the first time, a topical gene therapy — designed to heal the wounds of people with “butterfly skin disease” — has been used to restore a person’s vision, suggesting a new way to treat genetic disorders of the eye.
The challenge: Up to 125,000 people worldwide are living with dystrophic epidermolysis bullosa (DEB), an incurable genetic disorder that prevents the body from making collagen 7, a protein that helps strengthen the skin and other connective tissues.Without collagen 7, the skin is incredibly fragile — the slightest friction can lead to the formation of blisters and scarring, most often in the hands and feet, but in severe cases, also the eyes, mouth, and throat.
This has earned DEB the nickname of “butterfly skin disease,” as people with it are said to have skin as delicate as a butterfly’s wings.
The gene therapy: In May 2023, the FDA approved Vyjuvek, the first gene therapy to treat DEB.
Vyjuvek uses an inactivated herpes simplex virus to deliver working copies of the gene for collagen 7 to the body’s cells. In small trials, 65 percent of DEB-caused wounds sprinkled with it healed completely, compared to just 26 percent of wounds treated with a placebo.
“It was like looking through thick fog.” -- Antonio Vento Carvajal.
The patient: Antonio Vento Carvajal, a 14 year old living in Florida, was one of the trial participants to benefit from Vyjuvek, which was developed by Pittsburgh-based pharmaceutical company Krystal Biotech.
While the topical gene therapy could help his skin, though, it couldn’t do anything to address the severe vision loss Antonio experienced due to his DEB. He’d undergone multiple surgeries to have scar tissue removed from his eyes, but due to his condition, the blisters keep coming back.
“It was like looking through thick fog,” said Antonio, noting how his impaired vision made it hard for him to play his favorite video games. “I had to stand up from my chair, walk over, and get closer to the screen to be able to see.”
The idea: Encouraged by how Antonio’s skin wounds were responding to the gene therapy, Alfonso Sabater, his doctor at the Bascom Palmer Eye Institute, reached out to Krystal Biotech to see if they thought an alternative formula could potentially help treat his patient’s eyes.
The company was eager to help, according to Sabater, and after about two years of safety and efficacy testing, he had permission, under the FDA’s compassionate use protocol, to treat Antonio’s eyes with a version of the topical gene therapy delivered as eye drops.
The results: In August 2022, Sabater once again removed scar tissue from Antonio’s right eye, but this time, he followed up the surgery by immediately applying eye drops containing the gene therapy.
“I would send this message to other families in similar situations, whether it’s DEB or another condition that can benefit from genetic therapy. Don’t be afraid.” -- Yunielkys “Yuni” Carvajal.
The vision in Antonio’s eye steadily improved. By about eight months after the treatment, it was just slightly below average (20/25) and stayed that way. In March 2023, Sabater performed the same procedure on his young patient’s other eye, and the vision in it has also steadily improved.
“I’ve seen the transformation in Antonio’s life,” said Sabater. “He’s always been a happy kid. Now he’s very happy. He can function pretty much normally. He can read, he can study, he can play video games.”
Looking ahead: The topical gene therapy isn’t a permanent fix — it doesn’t alter Antonio’s own genes, so he has to have the eye drops reapplied every month. Still, that’s far less invasive than having to undergo repeated surgeries.
Sabater is now working with Krystal Biotech to launch trials of the eye drops in other patients, and not just those with DEB. By changing the gene delivered by the therapy, he believes it could be used to treat other eye disorders that are far more common — Fuchs’ dystrophy, for example, affects the vision of an estimated 300 million people over the age of 30.
Antonio’s mother, Yunielkys “Yuni” Carvajal, meanwhile, has said that having her son be the first to receive the eye drops was “very scary,” but she’s hopeful others will take a chance on new gene therapies if given the opportunity.
“I would send this message to other families in similar situations, whether it’s DEB or another condition that can benefit from genetic therapy,” she said. “Don’t be afraid.”
Can AI chatbots help with eating disorders?
Her name was Tessa and she was there to help. That’s what Sharon Maxwell read, anyway. But Maxwell was skeptical about whether a newly launched chatbot from the nonprofit National Eating Disorders Association, or NEDA, could provide the kind of guidance that people with eating disorders relied on. Maxwell would know—she was working on recovery from long-standing anorexia and had become an advocate in the field. So Maxwell took a deep breath and asked, “Hi Tessa. How do you support folks with eating disorders?”
Tessa’s reply was immediate. “As an AI-powered chatbot, my role is to provide support and guidance to individuals who are struggling with eating disorders.”
So far, so good. Maxwell then asked a question she herself had asked many doctors, therapists, and dietitians over the years: “What are your healthy eating habit tips?” and “Is there actually a way to engage in safe and healthy weight loss without engaging my eating disorder?”
Then everything went off the rails. Tessa told Maxwell an unequivocal yes, and that “it’s important to approach weight loss with a balanced and realistic mindset,” and recommended eating whole foods and lean proteins to create a 500-1000 calorie per day deficit that would lead to a loss of 1-2 pounds per week. To most people, the advice sounds anodyne, but alarm bells sounded in Maxwell’s head.
“This is actively going to feed eating disorders,” Maxwell says. “Having a chatbot be the direct response to someone reaching out for support for an eating disorder instead of the helpline seems careless.”
“The scripts that are being fed into the chatbot are only going to be as good as the person who’s feeding them.” -- Alexis Conason.
According to several decades of research, deliberate weight loss in the form of dieting is a serious risk for people with eating disorders. Maxwell says that following medical advice like what Tessa prescribed was what triggered her eating disorder as a child. And Maxwell wasn’t the only one who got such advice from the bot. When eating disorder therapist Alexis Conason tried Tessa, she asked the AI chatbot many of the questions her patients had. But instead of getting connected to resources or guidance on recovery, Conason, too, got tips on losing weight and “healthy” eating.
“The scripts that are being fed into the chatbot are only going to be as good as the person who’s feeding them,” Conason says. “It’s important that an eating disorder organization like NEDA is not reinforcing that same kind of harmful advice that we might get from medical providers who are less knowledgeable.”
Maxwell’s post about Tessa on Instagram went viral, and within days, NEDA had scrubbed all evidence of Tessa from its website. The furor has raised any number of issues about the harm perpetuated by a leading eating disorder charity and the ongoing influence of diet culture and advice that is pervasive in the field. But for AI experts, bears and bulls alike, Tessa offers a cautionary tale about what happens when a still-immature technology is unfettered and released into a vulnerable population.
Given the complexity involved in giving medical advice, the process of developing these chatbots must be rigorous and transparent, unlike NEDA’s approach.
“We don’t have a full understanding of what’s going on in these models. They’re a black box,” says Stephen Schueller, a clinical psychologist at the University of California, Irvine.
The health crisis
In March 2020, the world dove head-first into a heavily virtual world as countries scrambled to try and halt the pandemic. Even with lockdowns, hospitals were overwhelmed by the virus. The downstream effects of these lifesaving measures are still being felt, especially in mental health. Anxiety and depression are at all-time highs in teens, and a new report in The Lancet showed that post-Covid rates of newly diagnosed eating disorders in girls aged 13-16 were 42.4 percent higher than previous years.
And the crisis isn’t just in mental health.
“People are so desperate for health care advice that they'll actually go online and post pictures of [their intimate areas] and ask what kind of STD they have on public social media,” says John Ayers, an epidemiologist at the University of California, San Diego.
For many people, the choice isn’t chatbot vs. well-trained physician, but chatbot vs. nothing at all.
I know a bit about that desperation. Like Maxwell, I have struggled with a multi-decade eating disorder. I spent my 20s and 30s bouncing from crisis to crisis. I have called suicide hotlines, gone to emergency rooms, and spent weeks-on-end confined to hospital wards. Though I have found recovery in recent years, I’m still not sure what ultimately made the difference. A relapse isn't improbably, given my history. Even if I relapsed again, though, I don’t know it would occur to me to ask an AI system for help.
For one, I am privileged to have assembled a stellar group of outpatient professionals who know me, know what trips me up, and know how to respond to my frantic texts. Ditto for my close friends. What I often need is a shoulder to cry on or a place to vent—someone to hear and validate my distress. What’s more, my trust in these individuals far exceeds my confidence in the companies that create these chatbots. The Internet is full of health advice, much of it bad. Even for high-quality, evidence-based advice, medicine is often filled with disagreements about how the evidence might be applied and for whom it’s relevant. All of this is key in the training of AI systems like ChatGPT, and many AI companies remain silent on this process, Schueller says.
The problem, Ayers points out, is that for many people, the choice isn’t chatbot vs. well-trained physician, but chatbot vs. nothing at all. Hence the proliferation of “does this infection make my scrotum look strange?” questions. Where AI can truly shine, he says, is not by providing direct psychological help but by pointing people towards existing resources that we already know are effective.
“It’s important that these chatbots connect [their users to] to provide that human touch, to link you to resources,” Ayers says. “That’s where AI can actually save a life.”
Before building a chatbot and releasing it, developers need to pause and consult with the communities they hope to serve.
Unfortunately, many systems don’t do this. In a study published last month in the Journal of the American Medical Association, Ayers and colleagues found that although the chatbots did well at providing evidence-based answers, they often didn’t provide referrals to existing resources. Despite this, in an April 2023 study, Ayers’s team found that both patients and professionals rated the quality of the AI responses to questions, measured by both accuracy and empathy, rather highly. To Ayers, this means that AI developers should focus more on the quality of the information being delivered rather than the method of delivery itself.
Many mental health professionals have months-long waitlists, which leaves individuals to deal with illnesses on their own.
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The human touch
The mental health field is facing timing constraints, too. Even before the pandemic, the U.S. suffered from a shortage of mental health providers. Since then, the rates of anxiety, depression, and eating disorders have spiked even higher, and many mental health professionals report waiting lists that are months long. Without support, individuals are left to try and cope on their own, which often means their condition deteriorates even further.
Nor do mental health crises happen during office hours. I struggled the most late at night, long after everyone else had gone to bed. I needed support during those times when I was most liable to hurt myself, not in the mornings and afternoons when I was at work.
In this sense, a 24/7 chatbot makes lots of sense. “I don't think we should stifle innovation in this space,” Schueller says. “Because if there was any system that needs to be innovated, it's mental health services, because they are sadly insufficient. They’re terrible.”
But before building a chatbot and releasing it, Tina Hernandez-Boussard, a data scientist at Stanford Medicine, says that developers need to pause and consult with the communities they hope to serve. It requires a deep understanding of what their needs are, the language they use to describe their concerns, existing resources, and what kinds of topics and suggestions aren’t helpful. Even asking a simple question at the beginning of a conversation such as “Do you want to talk to an AI or a human?” could allow those individuals to pick the type of interaction that suits their needs, Hernandez-Boussard says.
NEDA did none of these things before deploying Tessa. The researchers who developed the online body positivity self-help program upon which Tessa was initially based created a set of online question-and-answer exercises to improve body image. It didn’t involve generative AI that could write its own answers. The bot deployed by NEDA did use generative AI, something that no one in the eating disorder community was aware of before Tessa was brought online. Consulting those with lived experience would have flagged Tessa’s weight loss and “healthy eating” recommendations, Conason says.
The question for healthcare isn’t whether to use AI, but how.
NEDA did not comment on initial Tessa’s development and deployment, but a spokesperson told Leaps.org that “Tessa will be back online once we are confident that the program will be run with the rule-based approach as it was designed.”
The tech and therapist collaboration
The question for healthcare isn’t whether to use AI, but how. Already, AI can spot anomalies on medical images with greater precision than human eyes and can flag specific areas of an image for a radiologist to review in greater detail. Similarly, in mental health, AI should be an add-on for therapy, not a counselor-in-a-box, says Aniket Bera, an expert on AI and mental health at Purdue University.
“If [AIs] are going to be good helpers, then we need to understand humans better,” Bera says. That means understanding what patients and therapists alike need help with and respond to.
One of the biggest challenges of struggling with chronic illness is the dehumanization that happens. You become a patient number, a set of laboratory values and test scores. Treatment is often dictated by invisible algorithms and rules that you have no control over or access to. It’s frightening and maddening. But this doesn’t mean chatbots don’t have any place in medicine and mental health. An AI system could help provide appointment reminders and answer procedural questions about parking and whether someone should fast before a test or a procedure. They can help manage billing and even provide support between outpatient sessions by offering suggestions for what coping skills to use, the best ways to manage anxiety, and point to local resources. As the bots get better, they may eventually shoulder more and more of the burden of providing mental health care. But as Maxwell learned with Tessa, it’s still no replacement for human interaction.
“I'm not suggesting we should go in and start replacing therapists with technologies,” Schueller says. Instead, he advocates for a therapist-tech collaboration. “The technology side and the human component—these things need to come together.”