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."
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
Listen on Apple | Listen on Spotify | Listen on Stitcher | Listen on Amazon | Listen on Google
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.
This podcast originally aired on March 3, 2023.
Breakthrough drones deliver breast milk in rural Uruguay
Until three months ago, nurse Leopoldina Castelli used to send bottles of breast milk to nourish babies in the remote areas of Tacuarembó, in northern Uruguay, by way of ambulances or military trucks. That is, if the vehicles were available and the roads were passable, which wasn’t always the case. Now, five days per week, she stands by a runway at the hospital, located in Tacuarembó’s capital, watching a drone take off and disappear from view, carrying the milk to clinics that serve the babies’ families.
The drones can fly as far as 62 miles. Long distances and rough roads are no obstacles. The babies, whose mothers struggle to produce sufficient milk and cannot afford formula, now receive ample supplies for healthy growth. “Today we provided nourishment to a significantly larger number of children, and this is something that deeply moves me,” Castelli says.
About two decades ago, the Tacuarembó hospital established its own milk bank, supported by donations from mothers across Tacuarembó. Over the years, the bank has provided milk to infants immediately after birth. It's helped drive a “significant and sustained” decrease in infant mortality, says the hospital director, Ciro Ferreira.
But these children need breast milk throughout their first six months, if not longer, to prevent malnutrition and other illnesses that are prevalent in rural Tacuarembó. Ground transport isn't quick or reliable enough to meet this goal. It can take several hours, during which the milk may spoil due to a lack of refrigeration.
The battery-powered drones have been the difference-maker. The project to develop them, financed by the UNICEF Innovation Fund, is the first of its kind in Latin America. To Castelli, it's nothing short of a revolution. Tacuarembó Hospital, along with three rural clinics in the most impoverished part of Uruguay, are its leaders.
"This marks the first occasion when the public health system has been directly impacted [by our technology]," says Sebastián Macías, the CEO and co-founder of Cielum, an engineer at the University Republic, which collaborated on the technology with a Uruguayan company called Cielum and a Swiss company, Rigitech.
The drone can achieve a top speed of up to 68 miles per hour, is capable of flying in light rain, and can withstand winds of up to 30 miles per hour at a maximum altitude of 120 meters.
"We have succeeded in embracing the mothers from rural areas who were previously slipping through the cracks of the system," says Ferreira, the hospital director. He envisions an expansion of the service so it can improve health for children in other rural areas.
Nurses load the drone for breast milk delivery.
Sebastián Macías - Cielum
The star aircraft
The drone, which costs approximately $70,000, was specifically designed for the transportation of biological materials. Constructed from carbon fiber, it's three meters wide, two meters long and weighs 42 pounds when fully loaded. Additionally, it is equipped with a ballistic parachute to ensure a safe descent in case the technology fails in midair. Furthermore, it can achieve a top speed of 68 miles per hour, fly in light rain, and withstand winds of 30 miles per hour at a height of 120 meters.
Inside, the drones feature three refrigerated compartments that maintain a stable temperature and adhere to the United Nations’ standards for transporting perishable products. These compartments accommodate four gallons or 6.5 pounds of cargo. According to Macías, that's more than sufficient to carry a week’s worth of milk for one infant on just two flights, or 3.3 pounds of blood samples collected in a rural clinic.
“From an energy perspective, it serves as an efficient mode of transportation and helps reduce the carbon emissions associated with using an ambulance,” said Macías. Plus, the ambulance can remain available in the town.
Macías, who has led software development for the drone, and three other technicians have been trained to operate it. They ensure that the drone stays on course, monitor weather conditions and implement emergency changes when needed. The software displays the in-flight positions of the drones in relation to other aircraft. All agricultural planes in the region receive notification about the drone's flight path, departure and arrival times, and current location.
The future: doubling the drone's reach
Forty-five days after its inaugural flight, the drone is now making five flights per week. It serves two routes: 34 miles to Curtina and 31 miles to Tambores. The drone reaches Curtina in 50 minutes while ambulances take double that time, partly due to the subpar road conditions. Pueblo Ansina, located 40 miles from the state capital, will soon be introduced as the third destination.
Overall, the drone’s schedule is expected to become much busier, with plans to accomplish 20 weekly flights by the end of October and over 30 in 2024. Given the drone’s speed, Macías is contemplating using it to transport cancer medications as well.
“When it comes to using drones to save lives, for us, the sky is not the limit," says Ciro Ferreira, Tacuarembó hospital director.
In future trips to clinics in San Gregorio de Polanco and Caraguatá, the drone will be pushed to the limit. At these locations, a battery change will be necessary, but it's worth it. The route will cover up to 10 rural Tacuarembó clinics plus one hospital outside Tacuarembó, in Rivera, close to the border with Brazil. Currently, because of a shortage of ambulances, the delivery of pasteurized breast milk to Rivera only occurs every 15 days.
“The expansion to Rivera will include 100,000 more inhabitants, doubling the healthcare reach,” said Ferreira, the director of the Tacuarembó Hospital. In itself, Ferreira's hospital serves the medical needs of 500,000 people as one of the largest in Uruguay's interior.
Alejandro Del Estal, an aeronautical engineer at Rigitech, traveled from Europe to Tacuarembó to oversee the construction of the vertiports – the defined areas that can support drones’ take-off and landing – and the first flights. He pointed out that once the flight network between hospitals and rural polyclinics is complete in Uruguay, it will rank among the five most extensive drone routes in the world for any activity, including healthcare and commercial uses.
Cielum is already working on the long-term sustainability of the project. The aim is to have more drones operating in other rural regions in the western and northern parts of the country. The company has received inquiries from Argentina and Colombia, but, as Macías pointed out, they are exercising caution when making commitments. Expansion will depend on the development of each country’s regulations for airspace use.
For Ferreira, the advantages in Uruguay are evident: "This approach enables us to bridge the geographical gap, enhance healthcare accessibility, and reduce the time required for diagnosing and treating rural inhabitants, all without the necessity of them traveling to the hospital,” he says. "When it comes to using drones to save lives, for us, the sky is not the limit."