Male fertility startup state of the union
Market map, deep dive, and where things are going next
Before we start…
IVF embryos now have the same legal rights as children in the state of Alabama. As stated in the dissenting opinion, this ruling by Alabama’s Supreme Court will almost certainly end the creation of frozen embryos in the state. It will also restrict access to and drive up costs to the already limited fertility care available in Alabama.
The spectre of personhood statues, or equating the rights of embryos with those we give humans, has loomed over the fertility industry since the fall of Roe v Wade. And now, patients considering fertility care there or in other states with similarly restrictive anti-abortion laws may need to think about their options, as the implications are wide-reaching and slippery. Here are two questions to ask yourself to see how the aftershocks of this ruling could ripple: Do cell biopsies done during PGT-A and other screenings cause harm to an embryo? Or what happens to frozen embryos if a patient does not plan to use them?
Male fertility startup market overview
Beyond the existential dread I feel related to the above (especially with a presidential election on the horizon), I’m doubling down on my prediction that 2024 is the year male fertility startups go mainstream. Why? Men are responsible for around half of all infertility (1/3 = issues in women’s bodies, 1/3 in men’s, 1/3 a combination or unexplained), yet a quarter of men are still not tested or treated during an infertility examination. Also, studies suggest around 1 in 5 couples who go through IVF later conceive naturally, which means that the lack of male treatment likely leads to overtreatment for women.
So I’ll say it again, loudly: women are serving as treatment surrogates for men, and until that changes, male fertility is a women’s health issue.
How big is this market?
According to one report, the global male infertility market hit $4 billion in 2022 and will climb to nearly $6 billion by 2030. The growth is driven by increased awareness (and acceptance) of male infertility, growth in the infertility category overall, and media headlines on declining sperm counts. Many companies in that analysis were focused on diagnostic tests like DNA fragmentation, which indicates the amount of damaged DNA in a sperm cell. Worth noting: this outlook only includes testing and treatment of infertility, not preventive or routine care. So do the few others out there.
Fertility status indicates a man’s overall health. Men already die an average of five years younger than women (and lifespans continue to decline), and have more chronic conditions. There is potential for a semen analysis to supplement or, in some cases, replace the yearly physical that men currently (mostly) avoid, making the market much bigger than analysts project. However, even with at-home testing, there is no full replacement for in-person care, as some fertility conditions (and later prostate screenings) require a physical exam.
Startup market map
For a snapshot, allow me to present the first market map of startups working on male fertility. Included are venture-funded companies operating in the US, UK, and EU from pre-seed through growth and a few very early-stage research spin-outs. The other criteria: there must be an exclusive focus on male fertility or a clearly defined product or pathway just for men. For a full market map of the fertility industry, see the analysis I co-wrote with Chrissy Farr on her excellent Substack, Second Opinion.
Digital clinics
There are two players exclusively focused on men’s health: Bastion, a digital clinic that provides a male reproductive and prostate health assessment, and Posterity Health, which handles the full spectrum of care from at-home semen analysis to surgeries, including sperm extractions and vasectomy reversals. Posterity Health employs the largest team of reproductive urologists (specialists trained to treat male fertility issues) in the US, too. This is meaningful since there are fewer than 200 of them, and it can be impossible to get an appointment even if you can track one down. Posterity is digital-first, and 75% of patients are seen within two weeks. I’ve been bullish on Posterity’s potential for a while and continue to track its growth and impact. So, too, are fertility benefit managers who are turning to Posterity to manage the male side of the house as it becomes a non-negotiable in the eyes of employers.
Kranus provides virtual urology care (EU/UK only), from telemedicine appointments to multi-week therapy programs that can treat erectile dysfunction (ED) without drugs. One little-known cause of ED is porn addiction, a condition that is more common than you might think and requires more than pills to manage. Maven’s recently launched male fertility program, in combination with its digital clinic and a wide network of providers, is there to support the needs of men on a range of fertility journeys from the very start into parenting. Hera Fertility is a virtual-first fertility clinic with a membership that grants access to consults with fertility doctors, lab testing, and group support sessions. MIA here is Ro, because after acquiring at-home semen testing company Dadi several years ago, it appears they only support those previous customers and are not selling new kits.
Hormone testing
Everlywell and Let’s Get Checked offer male hormone testing. Everlywell has two options: one that tests cortisol, DHEA, estradiol, and free testosterone and another that tests only total testosterone. Let’s Get Checked has a larger range of tests that start with testosterone only to a complete version that includes testosterone, free androgen index, prolactin, sex hormone binding globulin, estradiol, and cortisol.
Hormone imbalances are a rarer cause of infertility for men. A reality of all at-home and consumer testing is that if you transition to in-person care, your provider will re-run that test on their equipment. The healthcare system still doesn’t really know what to do with direct-to-consumer testing results (and they don’t always trust them), so it’s best suited to the fertility-curious or those who aren’t yet ready to see a fertility doctor. Hormone-related problems are a less common cause of male factor infertility, which is, in part, why this segment is small. That said, both companies promise to help with the next steps through virtual consultations, and Posterity Health offers a comprehensive hormone management program that can start virtually and transition to in person if needed.
Coaching
Many, many companies and influencers offer female fertility coaching and protocols. But for men or couples to do together? Not so much. Doveras and Frame have very different approaches but broadly provide a mix of education, assessment, and coaching for male and female clients. With Frame, the pathway is based on an intake followed by testing and includes 1:1 coaching and access to a care team. Doveras offers a bespoke twelve-week program based on data from over 100,000 studies. The programs are designed for those trying to conceive naturally or planning to start fertility treatments. Both companies feature men on the homepage, which may seem obvious or unimportant, but is an important signal for consumers, especially women, to include male partners from the very beginning of a fertility journey. In a move I especially love, Doveras makes you click to opt your partner out during sign-up.
At-home semen analysis
Customers wondering about the state of their swimmers range from the fertility-curious to men checking on their vasectomy’s effectiveness. Exseed (UK/EU only) and Yo use a combination of devices and smartphone cameras to record and interpret a semen sample to give a result within minutes. Proov is bundling Yo’s test, and Yo is doing the same with Proov’s ovulation confirmation tests. SpermCheck is the most simplistic and works like a pregnancy test with one line for low sperm count and two lines if it’s normal. Mojo and Jack Fertility (both UK-only) ask you to mail in a sample to a lab, with results shared during a practitioner appointment in a week or so. Even Labcorp has joined the action via the 2021 acquisition of Sandstone Diagnostics, maker of Trak, the OG of at-home sperm testing. These tests are a good gut check for those concerned about their fertility and will be increasingly useful as male birth control enters the market (more on those shortly). But again, their usefulness is limited for those facing fertility treatment as providers will (and should) run diagnostic tests on their own equipment in clinic.
At-home semen analysis + preservation
Will I gift sperm freezing to sons at their high school graduation a decade+ from now? Yes. With the mysteriously decreasing semen parameters for reasons unknown and an increasing number of chemicals found in our bodies (are they related? Probably!), I consider it a worthy insurance policy. Sperm can be frozen for decades and holds up far better during unfreezing than eggs, and there are no injections or medications required. At that point, it will also be an affordable one, as the recurring monthly costs to store a sample will continue to decline as facilities reach scale. Age is another reason men freeze, as is military deployment, having a vasectomy, and undergoing cancer treatments or a gender transition.
Cryochoice, Fellow, Legacy, and Sparre.me provide a mail-in semen analysis like the players in the previous category, and add the option to freeze sperm. It’s cheaper than going to a fertility clinic or sperm bank for preservation, and you can do it from home instead of the specimen room (yes, that’s what it’s called). There are a few distinctions between companies, primarily where the samples are banked and if they are split. While there are fewer risks to freezing sperm versus eggs because a) there are many sperm cells in a sample and b) sperm is less fragile than eggs, it’s still important to consider where your sample is being stored and if there are redundancies in place. Legacy, for example, stores sperm samples at multiple locations, ensuring there is a failsafe should one facility go down. Different use cases will continue to present themselves, but long-term success in this category requires a strong, thoughtful brand that men know and trust.
Biotech
There is a LOT we do not understand about sperm. Here’s a great example: sperm may have a fertile window. Arex Life Sciences spun out of livestock research, as so many fertility treatments do (fun fact: IUI was first used to speed up genetic improvements in farm animals), and sells an assay that determines and optimizes sperm performance related to this previously unacknowledged fertile window. The notion that sperm have a fertile window is novel, but if they’re correct (and early studies indicate they may be) it would be a huge breakthrough and could lead to the creation of more high-quality embryos during IVF.
Another company I am enthusiastically tracking is Fecundis. Based in Barcelona, Fecundis develops sperm-enhancing technologies that increase the success of infertility treatments. More specifically, their first product, HyperSperm, reproduces the biochemical changes that the sperm undergo naturally in the female reproductive tract before fertilization. These changes allow the sperm to acquire a movement pattern called hyperactivation, critical to the success of fertilization, which is not reproduced well with today’s capacitation-esque techniques.
In the whoa, science! category, Paterna Biosciences transforms pluripotent stem cells into sperm, a process called in vitro gametogenesis (IVG). This approach hard launched when Japanese researchers turned stem cells from a mouse’s tail into eggs and produced a healthy litter of baby mice. The promise of IVG for sperm is a reduction of heritable diseases and so that azoospermic men (no sperm in the ejaculate) can have genetically related children. Around 10 percent of all infertile men and 1 percent of all men are azoospermic. The issue can be obstructive, meaning there is a varicocele or other physical blockage in the testicles, or nonobstructive which is caused by genetic conditions, medical treatments, drugs, environmental toxins, and reasons we do not yet understand. The existence of intracytoplasmic sperm injection (ICSI), which only requires a single viable sperm to fertilize an egg, means that even if a man has very little sperm or an untreatable obstructive condition, a physician can retrieve a sample from the testicles, and an embryologist can usually find one from that sample that works. Based on the science and ethics and all of the questions around the long-term health of future children or possible epigenetic changes, IVG is many years away from clinical use. But considering the scarcity and fragility of eggs, expect IVG to be more applicable there.
Finally, there’s male birth control. Plan A (made by Next Life Sciences) and Contraline both have a long-lasting, reversible gel-based product in clinical trials positioned as an IUD for men. It works by injecting a gel into the vas deferens to block sperm’s escape path during ejaculation. Both will require testing to ensure their effectiveness, both upfront and over time, and at the moment, it’s not clear how long they will last. The approach feels more viable if these products can hit the female IUD timeline of 3-5 years or more. NES/T gel, which is rubbed on a man’s shoulders, is also in clinical trials.
Next gen testing
This is another fascinating area that shows just how little we actually understand about sperm. Path created SpermQT, a test that goes beyond visual parameters and DNA fragmentation to look inside sperm to determine its quality and function. Illumicell is designing an AI-driven sperm testing and screening tool for clinics and healthcare providers. PS Fertility offers testing focused on the presence of a molecular marker, phosphatidylserine or PS, on the surface of sperm that binds with the same substance on the egg to facilitate fertilization. QART Medical helps clinicians increase the number of high-quality sperm cells with more data on cell structure and composition on an individual basis. HisTurn is a spin-out from McGill that uses decades of epigenetic research on animals to identify signatures found in sperm related to fertility status and lifestyle factors.
Artificial insemination
Expect to see this category rise as more people take fertility into their own hands and look for less expensive alternatives to traditional treatments. Long known as the “turkey baster method”, intracervical (ICI) and intravaginal (IVI) insemination are alternatives to intrauterine insemination (IUI). Research suggests when indicated, ICI/IVI may match the effectiveness of IUI at a fraction of the cost since it’s done at home. What’s the difference? IVI uses a syringe to place semen next to the cervix, and ICI places it directly into the cervix and holds it in place with a cervical cap. IUI happens in a clinic with washed sperm that is inserted directly into the uterus, sometimes alongside medications. Prospective parents using donor sperm are the first use case people think of, but another increasingly common group is couples who are not yet ready for clinical care or are struggling to find timed sex palatable.
Béa Fertility offers ICI and, so far, is only available in the UK. Their first data, which comes from an internal study of 56 users, shows a 39.28% pregnancy rate over three cycles. Around a third of the users were men with abnormal semen parameters, though the pregnancy rates for that specific group are not included. For IVI, the options are Two Plus (currently unavailable in the US), Frida Fertility, and Mosie Baby. Pricing varies, but an important distinction for prospective purchasers is that Mosie is the only FDA-cleared kit on the market.
IVF tech
The majority of companies focused on AI and machine learning applications for IVF are working on embryo selection and stimulation protocols. The companies here all have a stated goal to optimize sperm in some way. Baibys is an AI and robotics-powered platform for sperm selection. Conceivable Life Sciences is building a next-generation embryology lab powered by robotics, advanced microscopy, and AI that allows better sperm selection and ICSI (intracytoplasmic sperm injection, aka taking a single sperm and inserting it directly into a sperm). One of Overture’s products automates Piezo-assisted ICSI to improve fertilization rates, which can be especially effective for patients over 38.
What’s the tl;dr?
We have a long way to go in men’s health, and fertility may be the beachhead to get men on the path to preventive care and interacting with the healthcare system more generally. An equal focus on male and female fertility is long overdue, but as the map shows, this market is still nascent and has far fewer solutions than women have at their disposal. Also, while these companies offer new ways to access experts, if you’re facing infertility, there is no substitute for an in-person assessment—please go with your partner. I expect all fertility benefits providers to put more equal weight on male fertility and hope that every fertility financing company mandates a semen analysis before they will approve IVF or IUI. Right now, it’s not a guarantee that happens even though everyone agrees it should. Beyond what companies can achieve, there are still open research questions to answer, particularly around IVF add-ons like ICSI (read this pre-press which neatly sums up my less is more why are we fighting biology POV).
Male fertility media highlights
Lab-grown testicles created in male fertility breakthrough (StudyFinds)
Sperm counts are down worldwide—and researchers are discovering why (New Scientist)
Tech firms court growing demand for male fertility services (Axios)
Study: Semen microbiota are dramatically altered in men with abnormal sperm parameters (Nature)
Posterity Health raises $7.5M seed round (MedCity News)
Plan-A raises $2.5M seed round for long-acting male birth control (Business Insider)
Bonus fertility fun for data wonks
The first-ever fertility dashboard from The Human Fertilization & Embryology Authority features 30 years of data from UK-based fertility clinics on everything from cycle success rates to funding.
The economics of fertility is a banger long read that breaks down everything from income and labor force participation to family policies. One interesting (but predictable) takeaway: in the highest fertility countries, fathers make the greatest contribution to total childcare.
TIL
How does parthenogenesis (reproduction without sex!) work?
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