You did everything they told you to do. You tracked ovulation, cut back on alcohol, took your prenatal vitamins, showed up for every blood draw and finger prick. Your partner did a semen analysis, and one by one, the results came in: “normal”.

Everyone kept saying, “This is great news!”

The only problem? You still aren’t pregnant, but nobody can seem to give you a clear reason as to why you’ve been unsuccessful. The medical world calls it “unexplained infertility,” a term that feels like a shrug. But as Francesca Hume, RN PNC(C), a nurse specializing in fertility care at Monday Fertility, often says, the real issue isn’t that it’s unexplained, it’s that it’s “unexplored”. The testing ends long before the biology does.

So let’s crack open that silence. Here’s what “unexplained” actually means, what it doesn’t, and why normal results don’t always tell the real story of your fertility.

What this piece can actually help with.

Unexplained infertility isn’t necessarily an indication of any particular problem. It’s a gap, between what current tests can see and what is actually happening in your body.

This piece will help you:

The goal isn’t to “fix” you. It’s to help you feel more informed, less alone, and more prepared for conversations with your own doctor.

In a standard fertility workup, doctors are checking big, measurable factors:

These are what Francesca Hume, RN PNC(C), a nurse specializing in fertility care at Monday Fertility, calls “macro‑level functions” . These are the big systems that need to be monitored and verified before identifying more micro trends. As the Cleveland Clinic explains in its overview of unexplained infertility, this basic workup is designed to rule out major, obvious causes first, such as blocked tubes, ovulation disorders, severe sperm issues, before anyone uses the word “unexplained.”​

But conception doesn’t just depend on big systems working. It depends on hundreds of tiny events lining up at the cellular, molecular, and timing levels. That’s where current medicine starts to hit its limits.

Hume puts it this way: “Testing is finite, but biology is not.” In her words, the workup we rely on today “captures macro level functions and not always micro, cellular, molecular, or dynamic processes.” The tests do provide some critical insights into how your reproductive system is functioning, but only scratch the surface in terms of the big picture of fertility readiness.

Some of the most important pieces we can’t reliably test for yet include:

Until recently, most data regarding physiological stress was impossible to test for. Now, tools like OTO Fertility are starting to change that by tracking more than 50 real‑time physiological signals, such as heart‑rate variability, nervous system regulation, and stress‑recovery patterns to give insight into how your body is actually responding to stress during the fertility journey. Instead of guessing how “stressed” your system is, OTO’s clinical‑grade biosensor and platform turn those signals into a Fertility Index, offering a more concrete picture of when your stress biology may be working against implantation and when it’s better supported.

Hume offers a simple analogy: “We can check that a car has gas, oil, and a working engine, but we can’t see what’s happening in the fuel injectors or the timing belt while it’s driving on the highway.” Your fertility workup confirmed the major components are there. What no one can see is the complex choreography happening inside your body, and that’s often where the problem lives.​

That’s why Hume describes unexplained infertility as “a diagnosis of limitation, not of reassurance.” It reflects the limits of what tests can currently measure, not the absence of a problem. “The reality is something is wrong,” she says, “but we just don’t have tests to figure out what that is yet.”​

That 2023 Human Reproduction guideline from the European Society of Human Reproduction and Embryology echoes this, describing unexplained infertility as a label used “when standard investigations fail to identify a cause,” while acknowledging that many cases are likely due to subtle, multifactorial issues we simply don’t have the tools to see yet.

​If that brings up feelings of both validation and anger, you’re not alone. 

Living with unexplained infertility can be uniquely maddening. There’s no villain you can point to, no blocked tube, no clear diagnosis, nothing you can easily “fix.”

Psychologist Alice Domar, PhD, a reproductive health psychologist who developed one of the first mind–body programs for infertility at Harvard‑affiliated centers, has written extensively about how often people in your position slide into catastrophizing and self‑blame. Thoughts like “my body is broken,” “this means I’ll never be a parent,” or “if I were calmer/healthier/better, this wouldn’t be happening.” In her book Conquering Infertility and in multiple clinical trials, Domar has shown that structured mind–body programs can significantly reduce anxiety and depression in fertility patients, and in some studies have been associated with higher treatment continuation and improved outcomes.

Self-compassion researcher Kristin Neff, PhD, has also demonstrated that treating yourself with kindness, especially when you feel like you’re failing, is linked to lower anxiety, less rumination, and better coping in a range of health challenges.

 Articles applying her work to fertility, including a piece in Psychology Today on shame and guilt in secondary infertility and blogs from clinics like Bourn Hall, suggest that self‑compassion can help reduce shame and guilt during infertility.

A 2021 review on infertility and psychological distress in Human Reproduction Update found that rates of anxiety and depression among fertility patients are similar to those seen in people facing serious medical illnesses, which helps explain why unexplained infertility can feel so destabilizing even when your labs are “fine.”

So when your brain jumps to “it must be me,” it’s not you being dramatic. It’s a very human response to a scary, ambiguous situation. You can’t flip a switch to stop those thoughts, but you can learn to answer them with something softer, like:

That kind of internal voice doesn’t change your AMH or magically fix implantation. But it does change how you experience this chapter, and how much space you have to breathe, decide, and keep going if you want to.

Fertility clinics see versions of your story every day. The Cleveland Clinic openly describes unexplained infertility as one of the most emotionally loaded diagnoses they give, precisely because there’s no clear “why” to work with.

A case shared by Reproductive Medicine & Infertility Associates (RMIA) in 2023 follows a couple in their early 30s who tried for more than two years. All baseline tests were normal. They were labeled “unexplained” and offered IVF.

During IVF, a different picture emerged:

The lab patterns suggested subtle egg quality issues that hadn’t shown up on standard lab work. With that information, their team adjusted the stimulation protocol in a second cycle and worked with them on sleep, nutrition, and stress‑management strategies. In that second cycle, they produced more blastocysts and eventually had a successful transfer and pregnancy.​

The point isn’t “IVF fixes everything” or “you just need to relax.” It’s that “unexplained” often becomes “better understood” once you move further into treatment, and that information can shape what happens next.

When you’ve been trying to conceive for a while, it’s very easy for your brain to jump straight to the worst case scenario. It can help to gently check whether your expectations for how long this “should” take match what the data and guidelines actually say for your age and situation.

Francesca Hume, RN PNC(C), a nurse specializing in fertility care at Monday Fertility, emphasizes that needing several cycles to conceive is often still within a normal range and “not automatically a sign of dysfunction.” Medical bodies like the American Society for Reproductive Medicine (ASRM) and clinics such as Mayo Clinic and Cleveland Clinic generally advise that if you’re under 35 and haven’t conceived after 12 months of regular, unprotected sex, or after 6 months if you’re 35 or older, it’s reasonable to seek a fertility evaluation, with earlier evaluation at any age if you have irregular or absent cycles, very painful periods, or known conditions like PCOS or endometriosis. It makes complete sense if you feel impatient long before those numbers; the goal is not to invalidate that, but to give you a clearer sense of when professionals start to consider medical interventions like IVF,  and what you can safely start doing in the meantime.​

Hume talks about stress biology as “one piece of the puzzle”, not the only reason someone isn’t getting pregnant, but one that can meaningfully shape the environment an embryo is trying to land in. Until recently, stress was something clinicians mostly had to infer from how you said you were feeling rather than what your body was actually doing.​

Tools like OTO Fertility are trying to close that gap by giving real, physiological feedback instead of guesswork. OTO uses a clinical‑grade wearable and an AI‑powered platform to track 50+ body signals, such as heart‑rate variability and patterns in nervous system regulation, and turns them into a Fertility Index that reflects how well your body is recovering from stress over time. It doesn’t replace medical care or guarantee an outcome, but it can:​

For many people, starting with something like OTO feels more doable than jumping straight to procedures: you’re not forcing your body to do anything; you’re learning how it’s already responding and where there’s room to support it more intentionally.

If you haven’t already seen a reproductive endocrinologist (fertility specialist), this is a good time. The American Society for Reproductive Medicine (ASRM) and other expert bodies advise seeking evaluation after 12 months of trying if you’re under 35, or after 6 months if you’re 35 or older.​

A specialist can:

A widely cited review in JAMA notes that IVF can function as both a treatment and a diagnostic tool in unexplained infertility by revealing patterns of fertilization failure or embryo arrest that suggest underlying egg or sperm issues.

Hume, RN PNC(C), sees this clinically as well and often reminds patients that “In itself, IVF is diagnostic.”​

A 2024 Human Reproduction paper on prognosis‑based management of unexplained infertility also suggests that once the basic evaluation is complete, decisions about expectant management versus IUI or IVF are best guided by personalized estimates of your chances over the next year or two, rather than rigid rules.

​

Domar’s mind–body program has been studied over several decades. A classic randomized trial in Fertility and Sterility tested a new behavioral treatment approach for women with infertility and found significant reductions in distress and an associated increase in pregnancy rates compared with routine care.

A 2024 study in Human Reproduction on the clinical effectiveness of the Mind/Body Program for Infertility compared Domar’s structured program with a support group and found that participants in the program had larger reductions in anxiety and depressive symptoms.

The evidence isn’t perfect, and no reputable expert will claim these programs “cure” infertility. But they can make the experience more bearable and may help you stay engaged with treatment decisions that are right for you.

Instead of trying to “positive think” your way out of this, Neff’s work suggests the more powerful move is self‑compassion: acknowledging your pain, recognizing you’re not alone, and speaking to yourself like you would to a close friend.

In practice, that could look like:

Here’s the part no one tells you: self-compassion isn’t about floating through your fertility journey on a cloud of lavender oil and good vibes. It’s about creating a tiny bit of breathing room inside your own head. Think of it as switching from your inner drill sergeant to your inner best friend, the one who shows up with snacks, refuses to let you spiral alone, and reminds you that being human is not a moral failure. It’s not soft or indulgent; it’s a strategy for surviving something objectively hard with your sanity intact.

Because unexplained infertility is often multifactorial, small shifts in several areas together may matter more than one big change. A practical framework article on infertility in the Cleveland Clinic Journal of Medicine, highlight the basics:

Here, Hume’s framing is also helpful in understanding how this can make a difference in your greater TTC journey: “There’s things we can optimize without assuming there’s something pathologically wrong.” 

Unexplained infertility can feel invalidating, like your suffering doesn’t “count” because nothing is technically wrong. It absolutely counts. Remember that 2021 review in Human Reproduction Update found that rates of anxiety and depression in fertility patients are comparable to those in people with serious medical diagnoses.

It may help to:

The goal isn’t to be endlessly “strong.” It’s to not have to hold this by yourself.

“Unexplained infertility” is a misleading label, one that describes the limits of current testing rather than the reality of what’s happening in your body.

Hume, RN PNC(C), offers a more honest reframe: “Unexplained infertility is a diagnosis of limitation, not of reassurance. Your tests have ruled out some big, obvious obstacles. There are still smaller, more complex factors that current tools can’t fully see.​”

There are things you can try medically, emotionally, and practically that may support your chances of successful conception and definitely better support you holistically. Your labs are information, not a verdict. Your thoughts and feelings are part of this story, but they are not the whole story.

You’re not “unexplained.” You are a whole human navigating something complex.

And you deserve care, answers, and help, even when medicine has to say, with honesty, that it doesn’t know everything yet.

Please note that this isn’t personal medical advice; it’s meant to help you feel more prepared for conversations with your own doctor.

On unexplained infertility & medical workup