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."
Therapies for Healthy Aging with Dr. Alexandra Bause
My guest today is Dr. Alexandra Bause, a biologist who has dedicated her career to advancing health, medicine and healthier human lifespans. Dr. Bause co-founded a company called Apollo Health Ventures in 2017. Currently a venture partner at Apollo, she's immersed in the discoveries underway in Apollo’s Venture Lab while the company focuses on assembling a team of investors to support progress. Dr. Bause and Apollo Health Ventures say that biotech is at “an inflection point” and is set to become a driver of important change and economic value.
Previously, Dr. Bause worked at the Boston Consulting Group in its healthcare practice specializing in biopharma strategy, among other priorities
She did her PhD studies at Harvard Medical School focusing on molecular mechanisms that contribute to cellular aging, and she’s also a trained pharmacist
In the episode, we talk about the present and future of therapeutics that could increase people’s spans of health, the benefits of certain lifestyle practice, the best use of electronic wearables for these purposes, and much more.
Dr. Bause is at the forefront of developing interventions that target the aging process with the aim of ensuring that all of us can have healthier, more productive lifespans.
This man spent over 70 years in an iron lung. What he was able to accomplish is amazing.
It’s a sight we don’t normally see these days: A man lying prone in a big, metal tube with his head sticking out of one end. But it wasn’t so long ago that this sight was unfortunately much more common.
In the first half of the 20th century, tens of thousands of people each year were infected by polio—a highly contagious virus that attacks nerves in the spinal cord and brainstem. Many people survived polio, but a small percentage of people who did were left permanently paralyzed from the virus, requiring support to help them breathe. This support, known as an “iron lung,” manually pulled oxygen in and out of a person’s lungs by changing the pressure inside the machine.
Paul Alexander was one of several thousand who were infected and paralyzed by polio in 1952. That year, a polio epidemic swept the United States, forcing businesses to close and polio wards in hospitals all over the country to fill up with sick children. When Paul caught polio in the summer of 1952, doctors urged his parents to let him rest and recover at home, since the hospital in his home suburb of Dallas, Texas was already overrun with polio patients.
Paul rested in bed for a few days with aching limbs and a fever. But his condition quickly got worse. Within a week, Paul could no longer speak or swallow, and his parents rushed him to the local hospital where the doctors performed an emergency procedure to help him breathe. Paul woke from the surgery three days later, and found himself unable to move and lying inside an iron lung in the polio ward, surrounded by rows of other paralyzed children.
Hospitals were commonly filled with polio patients who had been paralyzed by the virus before a vaccine became widely available in 1955. Associated Press
Paul struggled inside the polio ward for the next 18 months, bored and restless and needing to hold his breath when the nurses opened the iron lung to help him bathe. The doctors on the ward frequently told his parents that Paul was going to die.But against all odds, Paul lived. And with help from a physical therapist, Paul was able to thrive—sometimes for small periods outside the iron lung.
The way Paul did this was to practice glossopharyngeal breathing (or as Paul called it, “frog breathing”), where he would trap air in his mouth and force it down his throat and into his lungs by flattening his tongue. This breathing technique, taught to him by his physical therapist, would allow Paul to leave the iron lung for increasing periods of time.
With help from his iron lung (and for small periods of time without it), Paul managed to live a full, happy, and sometimes record-breaking life. At 21, Paul became the first person in Dallas, Texas to graduate high school without attending class in person, owing his success to memorization rather than taking notes. After high school, Paul received a scholarship to Southern Methodist University and pursued his dream of becoming a trial lawyer and successfully represented clients in court.
Paul Alexander, pictured here in his early 20s, mastered a type of breathing technique that allowed him to spend short amounts of time outside his iron lung. Paul Alexander
Paul practiced law in North Texas for more than 30 years, using a modified wheelchair that held his body upright. During his career, Paul even represented members of the biker gang Hells Angels—and became so close with them he was named an honorary member.Throughout his long life, Paul was also able to fly on a plane, visit the beach, adopt a dog, fall in love, and write a memoir using a plastic stick to tap out a draft on a keyboard. In recent years, Paul joined TikTok and became a viral sensation with more than 330,000 followers. In one of his first videos, Paul advocated for vaccination and warned against another polio epidemic.
Paul was reportedly hospitalized with COVID-19 at the end of February and died on March 11th, 2024. He currently holds the Guiness World Record for longest survival inside an iron lung—71 years.
Polio thankfully no longer circulates in the United States, or in most of the world, thanks to vaccines. But Paul continues to serve as a reminder of the importance of vaccination—and the power of the human spirit.
““I’ve got some big dreams. I’m not going to accept from anybody their limitations,” he said in a 2022 interview with CNN. “My life is incredible.”