Unexplained Infertility, Explained: Possible Causes and Treatment Options

If you’ve been trying to conceive for months (or even years) without success, receiving a diagnosis of “unexplained infertility” can feel both frustrating and confusing. After all, hearing that there’s “no obvious reason” for your fertility struggles doesn’t bring much clarity — or comfort.

The good news is, there are steps you can take to get to the bottom of why you’re not conceiving, as well as effective treatment for unexplained infertility. In this article, we’ll break down what exactly unexplained infertility is, how common it is, some of the most common unexplained infertility causes, and, of course, potential treatments so you can finally see that beautiful positive pregnancy test.

What is unexplained infertility?

Unexplained infertility is often considered a “non-diagnosis,” used when standard fertility evaluations cannot pinpoint a concrete reason why you’re having trouble conceiving. According to the American Society for Reproductive Medicine, a full fertility workup typically includes:

• Assessing ovulation
• Semen analysis
• Evaluating ovarian reserve
• Checking the uterus via hysteroscopy
• Investigating the fallopian tubes through a hysterosalpingogram (HSG)
• Occasionally performing a diagnostic laparoscopy to look for hidden issues (like endometriosis)

When all of these tests come back normal, your doctor may label your situation as unexplained infertility. Though it can feel discouraging in the moment, remember that this diagnosis doesn’t mean there isn’t a cause — only that it hasn’t been identified yet by standard testing.

How common is unexplained infertility?

While it might feel like you’re alone in this diagnosis, you’re certainly not. In fact, studies show that unexplained infertility could account for up to 25% (1 in 4) of all infertility cases. This makes unexplained infertility one of the most common diagnoses fertility specialists see.

Although that statistic may be surprising, it also means there’s a robust community of patients, doctors, and researchers actively seeking answers — and that many individuals eventually go on to have successful pregnancies despite this initial lack of clarity.

Reasons for unexplained infertility

It’s important to remember that “unexplained” does not necessarily mean “unsolvable.” Some lesser-known or harder-to-diagnose issues might be at play. Potential unexplained infertility causes include:

Undiagnosed underlying conditions

Autoimmune disorders, thyroid imbalances, untreated Celiac disease, and diabetes may interfere with fertility — even if they aren’t explicitly linked to fertility. If you have symptoms that could point to one of these conditions, talk to your doctor about ordering further tests.

Silent endometriosis

Unlike the more common forms of endometriosis — which can cause painful periods — silent endometriosis might go unnoticed due to mild or nonexistent symptoms; sometimes not diagnosed until surgeries for other conditions. Women with undiagnosed, mild endometriosis, might still ovulate and have clear fallopian tubes. Experts are still unsure how the silent form of this condition affects fertility, but it could be a good place to start when trying to determine the cause of unexplained infertility — even mild endometriosis can impact egg quality, fertilization, or implantation.

“Hostile” cervical mucus

Healthy, “fertile” cervical mucus helps sperm travel smoothly from the vagina to the uterus. In rare cases, cervical mucus may contain antibodies that attack sperm, creating a barrier to conception.

Egg or sperm quality issues

While standard testing can show whether ovulation and sperm counts are normal, it can’t always measure egg or sperm quality. Age, environmental factors, or subtle DNA issues (in either partner) can contribute to unexplained infertility. Oftentimes, these issues are diagnosed during the IVF process, and once identified can be treated and overcome with the assistance of IVF.

Sheer luck

Sometimes there is no ‘reason’ — medically speaking, your fertility and health could be as optimal as they ‘should’ be, but each cycle has a 25-30% chance of conceiving. Your chances improve with each cycle, but they’re never 100% certain. For many people, TTC can be a ‘luck of the draw’ scenario each cycle, if other fertility challenges have been exhausted.

How to get pregnant with unexplained infertility

If you’ve been given this frustrating diagnosis, remember there are ways to improve your odds of conceiving naturally and via fertility treatments. Some key steps include:

• Lifestyle modifications: Optimizing nutrition, maintaining a healthy weight, reducing stress, and avoiding smoking or excessive alcohol intake can all support fertility.
• Confirming ovulation timing: Using ovulation predictor kits (OPKs), fertility tracking apps, or other methods (e.g., basal body temperature, cervical mucus monitoring) can help ensure you’re timing intercourse or insemination correctly.
• Checking for secondary causes: If you have symptoms that point to an underlying condition (thyroid disorders, autoimmune diseases, or endometriosis), request further evaluation or see a specialist.

If lifestyle changes and careful ovulation tracking don’t result in pregnancy after several months, it may be time to explore more targeted medical interventions.

Unexplained infertility treatment

When it comes to treatment for unexplained infertility, doctors typically recommend a stepwise approach, starting with less invasive options and moving to advanced treatments if needed. Fertility medications and procedures like Intrauterine Insemination (IUI) and In Vitro Fertilization (IVF) can offer promising paths toward a successful pregnancy.

Letrozole for unexplained infertility

Letrozole (an aromatase inhibitor) is often used off-label to stimulate ovulation. Several studies suggest Letrozole may lead to more favorable pregnancy outcomes compared to older fertility drugs in certain cases of unexplained infertility. It works by reducing estrogen levels, which prompts the pituitary gland to produce more follicle-stimulating hormone (FSH) — ultimately encouraging ovulation. Letrozole is sometimes paired with IUI to further boost conception chances.

Clomid for unexplained infertility

Another popular option is Clomid (clomiphene citrate). Like Letrozole, Clomid stimulates the ovaries to release eggs, but it does so by blocking estrogen receptors in the brain, prompting the release of FSH and luteinizing hormone (LH).

Research, including the FASTT trial, suggests that Clomid combined with IUI can yield about a 10% success rate per cycle in women under 35; however, success rates dip after three cycles. Experts typically advise moving on to more advanced treatments like IVF if Clomid and IUI hasn’t worked within three to four cycles.

Unexplained infertility IVF success rates

IVF (In Vitro Fertilization) remains the most effective treatment for unexplained infertility, with many couples finding success even after multiple failed IUIs or timed-intercourse cycles. IVF can also provide important insights into issues like egg and sperm quality — sometimes pinpointing the hidden reason behind unexplained infertility. While success rates depend on factors like age and overall health, many clinics report that couples with unexplained infertility can expect up to 30-50% success per IVF cycle, depending on individual circumstances.

Unexplained infertility and IUI

Intrauterine Insemination (IUI) is often the first-line procedure for unexplained infertility, especially when paired with fertility medications like Clomid or Letrozole. IUI involves placing washed sperm directly into the uterus around the time of ovulation, effectively reducing the distance sperm must travel to fertilize the egg. While IUI can work for many couples, its success rates hover around 10-20% per cycle under optimal conditions. After three to four failed cycles, most specialists recommend considering IVF to maximize pregnancy chances.

Try doing ‘nothing’

Depending on how long you’ve been trying to conceive, some fertility professionals will recommend stopping any additional supplements, nutrition, and TTC ‘hacks’ to treat unexplained infertility. It seems backward not to treat your unexplained infertility, but sticking with healthy eating, regular exercise, stress management, and regular baby-making sex can sometimes be just what the doctor ordered.

Beyond the unknown

Whether you opt for a few cycles of IUI, go straight to IVF, or simply adopt a “wait and see” approach, there is hope after an unexplained infertility diagnosis. Equipped with the right knowledge — and the right medical team — you can take actionable steps to identify potential hidden causes, explore targeted treatments, and hopefully build the family of your dreams.

If you find yourself still searching for answers, don’t hesitate to seek a second opinion or ask your doctor about additional testing and treatments. Having a supportive care team and a clear plan can make all the difference in your fertility journey.

Tassia O'Callaghan is an experienced content writer and strategist, having written about a vast range of topics from chemical regulations to parenting, for brands like Peanut App Ltd, Scary Mommy, Tally Workspace, and Office Christmas. She's an advocate for realistic sustainable living, supporting small businesses (author of A-Z of Marketing for Small Businesses), and equity across all walks of life. Follow her on LinkedIn or TikTok, or see more of her work on Authory or her website.