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Unexplained infertility: what it is, how it

Unexplained infertility: what it is, how it's diagnosed, and how it's treated

7 min read

Thanks to the wonders of modern medicine, doctors have many ways to identify and treat the different diagnosable causes of infertility (like polycystic ovary syndrome or thyroid disorders, for example). Sometimes, though, people can have trouble conceiving without any known reasons revealed by a basic infertility workup. This is what doctors call "unexplained infertility." The condition doesn't mean you can't get pregnant — it just means your doctor's unable to explain what may be going on.

"While unexplained infertility can be a really frustrating diagnosis, it is a real diagnosis," explains Dr. Temeka Zore, MD, FACOG, a reproductive endocrinologist at Spring Fertility and Modern Fertility medical advisor. "It is not made up, it is not in your head, and no, you did not cause it!" You're also not alone if you experience it: about 5% to 10% of couples face this issue, and up to 30% of couples who are in treatment for infertility end up being diagnosed with it.

Although unexplained infertility is by definition without explanation, the more knowledge you have around the diagnosis, the more prepared you'll be as you think through your next steps. That's why, in this article, we’re diving into what we know about unexplained infertility, whether or not there actually are any possible explanations for the "unexplainable," and what your options for treatment may be if you end up dealing with the condition down the line.

What are the most common causes of infertility?

Before we get into unexplained infertility in particular, let's talk about infertility in general. In the US, about 1 in 8 people with ovaries and 10% of people with sperm experience infertility.

Infertility is diagnosed after you've been trying to conceive without getting pregnant for one year. An infertility evaluation is recommended if you have been trying without conceiving after 12 months if the partner with ovaries is under age 35 and after six months if they're over age 35. During your evaluation, you'll be seen by a fertility doctor (a reproductive endocrinologist who specializes in infertility) to understand why you may be experiencing issues with conceiving.

For people with ovaries, the infertility evaluation may include a review of their medical history, fertility hormone testing, vaginal ultrasounds, and/or X-rays. People with sperm may undergo a review of their medical history and fertility hormone testing, as well as semen analysis.

These are some of the most common diagnosable causes of infertility:

  • Ovarian issues: Infertility can be caused by conditions that involve and impact the ovaries, like polycystic ovary syndrome (PCOS).
  • Endometriosis or tubal diseases: Whether it’s caused by endometriosis (a condition where tissue similar to the uterine lining grows outside of the uterus), PID, or untreated STIs (the most common STIs are chlamydia and gonorrhea), tubal factor infertility results in 25%-35% of infertility cases in people with ovaries.
  • Fibroids or adenomyosis: Benign growths of the uterine muscle (fibroids) or uterine lining that grows into the uterus' muscular wall (andenomyosis) can potentially result in fallopian tube blockages, miscarriage, or uterine abnormalities that affect the fertilized egg planting itself on the uterine wall.
  • Thyroid conditions or insulin resistance: While these conditions can affect your fertility, you can work on a treatment plan with your doctor to mitigate the risk of fertility and other health issues down the line. (Your Fertility Hormone Test results can give you important insight for these conversations.)
  • Male factor infertility: About 40% of opposite-sex couples visiting infertility specialists will be diagnosed with male infertility problems.

If you find out that you're experiencing one of the above causes for infertility, fertility treatment (like ovulation-inducing medications and/or assisted reproductive technology) can help.

What does it mean to have unexplained infertility?

Unexplained infertility is a broad term that generally means infertility with no known cause. It's diagnosed when a fertility specialist rules out common factors for infertility after evaluating opposite-sex partners who are trying to conceive. Getting these "normal" evaluation results might lead to a diagnosis of unexplained infertility:

  • At least one fallopian tube that's free from any obstruction
  • Demonstrated ovulatory menstrual cycles
  • A high enough amount of motile (aka capable of movement) sperm

"Just because we can't find an actual answer for why you can't conceive doesn't mean one doesn't exist," says Dr. Zore. "The process of fertilization, embryo development, and implantation is a series of highly complex biological processes — and we don't have good testing to establish where an issue could occur during 'natural' fertilization."

As we'll explain a little later, undergoing in vitro fertilization (IVF), a form of assisted reproductive technology (ART), may actually help your doctor get a better understanding of any issues that may be coming up during this complicated process.

Are there any possible explanations for unexplained infertility?

In the 8th edition of Yen & Jaffe's Reproductive Endocrinology, the authors — Drs. Jerome F. Strauss III, Robert L. Barbieri, and Antonio R. Gargiulo — hypothesize that unexplained infertility is most likely caused by the presence of multiple factors that don't on their own lead to infertility (like age and "normal" but low semen parameters), but decrease the chances of conception when in combination. According to the authors, some of the physiological differences that have been reported in people with unexplained infertility include subtle changes in:

  • Follicle development
  • Ovulation
  • Oocyte function
  • The luteal phase of the menstrual cycle (the second half, after ovulation)
  • Sperm function
  • Sperm concentration or motility at the lower end of "normal"

In some cases, the infertility workups that can lead to a diagnosis of unexplained infertility (which, because they aren't standardized, may vary across providers) could actually miss another possible cause. "There are just so many things we can't test for," adds Dr. Zore. "For example, we are unable to determine whether sperm is able to penetrate an egg or how embryo development actually progresses inside the body because we don't have any specific tests for that during 'naturally' conceived pregnancies." The same goes for whether or not there are any issues with implantation.

More research into the different causes of unexplained infertility could help doctors align on standards for diagnosing the condition and minimize the chances of other issues being inadvertently overlooked. The National Institutes of Health is currently conducting a comprehensive research program in an effort to build a large, multifactorial health database in part to better understand unexplained infertility.

Can you still get pregnant with unexplained infertility?

Yes! Having unexplained infertility doesn't mean there's a 0% chance of getting pregnant, but it does mean that your chances of conceiving without medical assistance are lower per cycle. A couple diagnosed with infertility (unexplained or otherwise) has about a 2%-4% chance of conceiving on their own per month — and your doctor will likely recommend infertility treatment options to improve those monthly chances.

If you get diagnosed with unexplained infertility, the American Society for Reproductive Medicine (ASRM) recommends the following treatment protocol:

  • Intrauterine insemination (IUI): Start with 3-4 cycles of ovarian stimulation and intrauterine insemination (IUI) with ovulation-inducing medication (aka clomiphene citrate or letrozole). "Clomid or letrozole alone, timed intercourse alone, or IUI alone do not significantly increase the per monthly chance of conceiving with unexplained infertility," adds Dr. Zore. "It's the combination of ovulation-inducing medication plus IUI that can start to increase fecundability rate." While other options, like injectable medications plus IUI, may also be recommended and can improve monthly pregnancy rates, Dr. Zore says the twin and higher-order multiples rate is also significantly higher. It's for this reason that treatment isn't recommended as a starting regimen.
  • In vitro fertilization (IVF): If IUI doesn't lead to pregnancy and a live birth or if the age of the partner with ovaries may be a factor, the next step is in vitro fertilization (IVF).

Like we mentioned earlier, IVF may also help your doctor better understand exactly what's causing infertility by examining factors that aren't possible to assess through diagnostic testing alone. "Sometimes once a couple starts the treatment process, some of these causes can be revealed based on how eggs fertilize or how embryos develop in the lab," explains Dr. Zore.

Is unexplained infertility the same as idiopathic infertility?

No. People with idiopathic infertility may have some "abnormal" test results while people with unexplained infertility will show "normal" test results — even though, in both cases, there's no clear medical explanation for why they're not conceiving.

For example, one review found that people with sperm who have unexplained infertility have typical sperm analysis test results, but people who have idiopathic infertility have reduced sperm production (despite having no history of fertility problems and no abnormal findings on physical examination and blood work).

The bottom line

The most important thing to remember is that unexplained infertility doesn't necessarily mean you can't have biological children — there are evidence-based treatments available to help you meet your reproductive goals. If you're frustrated by the lack of a clear diagnosis, you can always consider running additional tests or getting a second opinion. Talk to your healthcare provider if you have any questions about your specific situation.

If you're interested in having kids and you'd like to know more about possible factors that could make getting pregnant more challenging, the Modern Fertility Hormone Test can help you with a deep dive into your reproductive hormones. Your results can give you insight into your ovarian reserve (aka egg count), the possible timing of menopause, the likelihood of having conditions that can impact fertility (like polycystic ovary syndrome, or PCOS, and thyroid disorders), and potential outcomes for egg freezing and IVF. You can use this info to start a conversation with your doctor about your plans for kids. (Psst: We also have an Ovulation Test if you're looking to get in sync with your cycle and your unique time of ovulation!)

Whatever your goals and plans are, and whatever you're dealing with fertility-wise, Modern Fertility is here for you to help you understand your options and build the future you want.

This article was medically reviewed by Dr. Temeka Zore, MD, FACOG, a fellowship-trained reproductive endocrinologist and infertility specialist and board-certified OB-GYN at Spring Fertility in San Francisco.

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Jocelyn Solis-Moreira

Jocelyn Solis-Moreira is a health and science journalist focusing on research about medicine, public health, and women's health.

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