Contraception can be a busy subject for many reasons. It's very personal, of course. It is often political. And the stakes, if your method of choice fails, are obviously very high.
Which may explain why there has not been a lot of innovation in space – unless you count the prospect of a male pill that does not have a lot of space. is not yet on the market.
None of these challenges prevented the European start-up Natural Cycles from pushing to establish what it considers a "digital contraceptive" on the market as another method to consider for couples – assuming they are comfortable having unprotected sex. no protection against the risk of STDs).
Last July, the team announced a $ 6 million Series A round. Today, the EQT Ventures Fund invests $ 30 million in Series B, with the participation of existing investors Sunstone, E-Ventures and Bonnier.
In August, the product also obtained certification in the EU as a means of contraception, which gave a regional boost to its ambition to disrupt the market for contraceptive choices.
Their subscription product, which now has more than 500,000 users in about 160 countries, is a fertility tracking application powered by algorithms that work from individual data, including daily temperature measurements. a basal thermometer. subscription price if users register for one year).
The purpose of the product is to predict which days a woman is fertile and what it is not. A user sees a calendar view in the app with some days of the month in red – to signify that she should not have unprotected sex that day unless she wants to try to get pregnant
Days on which the algorithm judges that there is no risk of pregnancy are colored green – to signify that the system is sure that the woman can have unprotected sex and do not risk getting pregnant.
For Natural Cycles to work, women must measure their body temperature with a basal thermometer to two decimal places each morning (ideally), and do it before getting up – by recording the data in the application. He then uses these readings as an indirect measure of hormone levels, and uses it to calculate each woman's fertility (taking into account other relevant factors such as sperm survival rates) .
The algorithms that fuel product function by understanding the probabilities and uncertainties around each individual, says co-founder Dr Elina Berglund, who previously worked as a particle physicist at CERN.
"What the algorithm really tries to evaluate, is to understand how well do we know this woman? Because every woman is unique and her cycle is unique, and you have to apply a statistical review to understand when can you really say that if you have unprotected sex today, it will not result in pregnancy, "she explains to TechCrunch.
"And it's all about probabilities, so you have to combine the probability of sperm survival, how well do you know the ovulation profile of these women, how far do you see the profile of This woman's temperature.Do you really know that she has ovulated and how far do you rate she has ovulated and is able to predict that.
It is important to understand the uncertainties surrounding the data and the unique cycle of this woman.
"So it's about understanding the uncertainties surrounding the data and the unique cycle of this woman."
A woman's body temperatures can of course fluctuate for all kinds of reasons – like illness or even alcohol consumption. Although the menstrual cycle can also vary in length, month to month, or be irregular for all kinds of reasons related to lifestyle or health.
Berglund says that Natural Cycles algorithms are designed to interpret and accommodate these kinds of individual differences and fluctuations without reducing the overall efficiency of the product exactly because it is designed to take into account these uncertainties when predicting fertile / non-fertile days. . (Although the website FAQ warns that the product may not be suitable for women with very irregular cycles.)
The algorithm also adapts if users do not enter their temperature every day, as they are supposed to do in the "perfect use" scenario.
"The accuracy rate of course takes all of that into account," she says. "There are no women who take their temperature every day, on average 73% of the days, but of course you have a wide circulation – some women take only 40% of the days and others do it at 95% and this failure rate of the method is based on all the actual data in real time.Thus, it's not based on women who take their temperature on 100 percent of days. "
There is also an initial learning period for the application, with each woman starting to receive more red days while the algorithms wait to be fed into more data. Gradually, the user will have more green days – but there will always be red days a month.
"At the very first cycle, there are usually a lot of red days, so we get an average of only 40% green days in the first cycle, and then it goes up fast," says Berglund. "Usually, after nine cycles, you reach a point where you do not get more green days on average." But that's just the average, so it looks very, very different from 39, one woman on the other. "
In a published study on the effectiveness of the product, which was conducted by Natural Cycles using existing users of the product as subjects of study (and followed up with those who discontinued it. use to try to determine if they have become pregnant), they say it has demonstrated a 93 percent effectiveness with "typical use" – although this research is not the "standard". excellence "of the research of a randomized controlled trial.
Natural Cycles also did not conduct a randomized controlled trial comparing the product to other contraceptive methods. Thus, users who want to know how Natural Cycles compares to the pill, for example, or who use condoms do not have a way to find out yet.
And because the product has not been tested to the basic standard used for scientific research, there have been some criticisms of the claims of effectiveness that Natural Cycles make.
"I am concerned about the current effectiveness of 93% typical use," says Victoria Jennings, director of the Institute for Reproductive Health at Georgetown University, who has participated in several Efficacy studies for fertility awareness. contraceptive methods based. "As stated in the published document, there is a significant amount of missing data, and abandonment rates are quite high.The study was not designed according to the standards of An efficiency test, it therefore seems inappropriate and misleading to offer this claim.
"The authors themselves state that the results can not be compared to the effectiveness of other contraceptive methods, but the goal of a trial is to be able to do just that. to be comparable, what we have here is much more in line with post-marketing research, which is useful for understanding the real-world experience of a large number of people, but not the basis of allegations of effectiveness. "
"Any application [fertility awareness] that makes claims of effectiveness should have been considered in a standard efficacy study," she adds.
Asked to find out if he will use the B-series funding to perform a randomized controlled trial, Berglund says that Natural Cycles would like to do so to substantiate its claims of effectiveness. She says that a year or more ago she was asking for a randomized controlled trial of the contraceptive pill. But its application was rejected by the local medical products agency, in Sweden, for "several reasons" – of which "they did not see the purpose of such a study".
She now hopes to lead a comparative study against a condom in the future, which she hopes "easier to recruit women willing to use condoms or use condoms with Natural Cycles"
.
"We want to do it again," she adds. "We will now try a second round but instead of doing it against the contraceptive pill, because it seems to be too controversial, we would do it against a condom."
That said, there is no specific timetable for the study – beyond Berglund who says, "It will take several years to complete this test." Thus, users wanting to see the product claims wait.
"We are pleased that until now we have achieved the largest study ever published on natural birth control, so we think that as a start-up, as a" family ", we have the largest study ever. business, we do a lot of research, "she adds. "But we want to achieve even more – and we also realize that this comparison process is the only thing missing."
Another criticism that some women reproductive health specialists have addressed to the product is that there is a risk of being misleading – given its relative complexity of use and the need for it. alternative contraception on red days (or that users do not have sex).
Berglund rejects this view by arguing that it provides users with clear advice and information via the application, including on the relative risks of pregnancy related to the use of different alternative methods contraception.
"We try to be very clear in our communication that if you use the withdrawal [as a contraceptive method] on the red days then your probability of pregnancy is much higher – and we inform them about it in the following way. because we ask them what they use, and they tell us, "she says.
"We really try to be very transparent … Who is the best for who is not the best.We have a limit of 18, so no one under 18 can use Therefore, I think we are very good at providing an effective alternative to women, but also be very transparent about the advantages and disadvantages of our method for women. "
"The app is just a tool for women to use as they see fit," she adds. "It puts the information in their hands, understanding their body when they are fertile, when they are not fertile.But, in the end, it's up to them to use this tool like that to them. and their lives. "
Who are the users?
At this point, the average age of a user of Natural Cycles is 29 years old. While the renewal rate after the first year of subscription is currently 60%.
"Most women are between 25 and 35 years old, they are in a stable relationship, they often think that they want to have children in a few years and that they do not want to take any more. hormones, "says Berglund. "Most of our users come from hormonal contraception – and they think I will use this method at the same time to understand how my body works."
The product can also be used by women to help them try to get pregnant, even though she says that it is currently a minority of users (about 25%).
"We often see that after about two years [users] we switch to the application to get pregnant, then they get pregnant very quickly because they already know their body and the application knows them also, "she adds.
Another feature encourages women to continue using Natural Cycles for the first three months following their pregnancy – because the application provides a miscarriage alert related to the risks of falling hormone levels during pregnancy .
The algorithm can also entice a user to do a pregnancy test – based on his calculations of their hormone levels (so maybe understand that they are pregnant before that. they do not)
Series B funding is intended to fund clinical research and product development – including the growth of the team with additional recruits in medicine and science. (Berglund says Natural Cycles currently has 40 people, including seven PhDs in physics, with the goal of increasing the number of employees between 100 and 120 in one year.)
The research portion of the funding will not only be used to carry out the aforementioned random control study. The team also wants to study various aspects of women's reproductive health and fertility to fuel the development of their products.
"We have published three clinical studies to date and we have a fourth one that measures what affects pregnancy time and infertility among our users who are trying to conceive but we want to do even more than that, " she says. "So we have a fairly ambitious research plan, looking at acceptability – how much of a contraceptive method is suitable for what type of person and when it is alive."
International expansion is another goal of funding. The US market is the third largest Natural Cycles market at this stage, after its domestic market in Sweden and then the United Kingdom, where Berglund claims the product is growing fastest.
"We really want to establish ourselves as a world leader in digital contraception – so expansion to other markets is essential," she adds.
Its European activities have undoubtedly enjoyed a big boost when the product was certified as contraception in the European Union. Although this certification is region-specific, and although Berglund confirms that the company has applied for equivalent accreditation in the United States, via the FDA, one must now wait to see if it works. And she concedes that waiting for an FDA visa for a contraceptive application could take some time.
"As it is an innovative and new product, it can take a lot of time, I think it's been 15 years since the FDA last approved a medical device for contraception. We think that may take some time, but we have started the process, "she notes, adding," We have submitted all our documentation and clinical data, etc. So we have already done this work on our side have to wait and see what they come back. "
There may be inevitably some degree of skepticism when strong marketing claims are attached to a new product that – at least in part – takes advantage of an existing approach that is generally not considered reliable (and tested) in the alternative market. Especially when the company in question has not yet made the standard science necessary to solidly support its claims.
Although, at the point of follow-up based on knowledge of fertility at least, Natural Cycles asserts that its algorithms do more than the standard calendar method of tracking fertile days. And so, he says, are more accurate than a person could be sure they were trying to track their own fertility by themselves.
"It is very important not to do this analysis by hand because many studies have shown that even if you are good at applying simple rules in your own monitoring of temperature, 25% of women end up pregnant in a year." Berglund claims.
Although she also says that the company's original idea came after she and her husband searched for a natural contraceptive method – and she developed the idea that she was not pregnant. original algorithm to use on itself, so manually followed its own fertile days (albeit with a doctorate in physics to support its methodology).
"We care about our users," she adds. "We would not have released [the product] – and we would not have been certified for contraception if we had not done that [comparison with the standard calendar method algorithm] either.
"Part of the certification is made up of many documents and studies that are not published but are reviewed by the oversight body that gave us the certification for contraception and approved our marketing allegations that the Failure rate of our algorithm is 0.5% per year. "
In the end, contraception is a personal choice and existing options already vary greatly in accessibility, complexity and more. The challenge of Natural Cycles is that a sizeable proportion of couples will be open to an app-packed addition to join the mix.