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Unexplained Infertility: Causes, Diagnosis & Treatment Options

When fertility testing hasn't uncovered a clear cause for an individual or couple's inability to conceive, they are diagnosed with unexplained infertility. Here's what you should know.

April 17th, 2023 | 10 min. read

By Spencer Richlin, MD

We all want answers, and being told you have "unexplained infertility" can feel defeating. The good news? According to a study from the National Institutes of Health, 92% of couples with unexplained infertility who had fertility treatment ultimately had a child. So while this diagnosis may be frustrating, the odds are still in your favor that you'll become a parent!

In this article:

What is unexplained infertility?

There are five general causes of infertility: ovulatory dysfunction, pelvic factor, male factor, genetic issues and unexplained infertility. Unexplained infertility is the general term used when fertility testing has not been able to reveal a specific cause of an individual or couple's inability to conceive. 

As a reproductive endocrinologist, whenever I meet a new patient, my first task is figuring out why they have not yet been successful in their quest to get pregnant.

The way we do this is by performing a complete review of a patient's medical history, and by having them undergo a series of diagnostic fertility tests, which usually include the following:

How is unexplained infertility diagnosed? 

The results of the diagnostic tests mentioned above usually reveal specific issues and help us to create an individualized plan of action to help patients grow their families.

However, in some cases, no specific issues are uncovered, and all test results are deemed "normal" (i.e. normal semen analysis, open fallopian tubes, clean uterine cavity, regular cycles). When this happens, and you are also under age 35, this leads to a diagnosis of unexplained infertility.

How common is unexplained infertility?

Approximately 10% of the time, individuals or couples will receive a diagnosis of unexplained infertility. Other causes of infertility are actually more common, such as:

  • Ovulatory dysfunction or irregular menstrual cycles (15% of cases)
  • Male factor infertility (35% of cases)
  • Tubal/pelvic factor infertility (35% of cases)

Lastly, 5% of couples will have a unique cause for their infertility that isn't mentioned above.

Possible Causes of Unexplained Infertility

Frustratingly for patients (and their doctors), when it comes to unexplained infertility, it is sometimes impossible to pinpoint a cause. However, there are a few known issues that can contribute to unexplained infertility.


A common culprit for declining pregnancy rates, especially in patients over 35, the "biological clock" is unfortunately a real challenge for many trying to conceive after their mid-30s.

Irregular Cycles

Most individuals or couples are able to become pregnant after trying for one year (if the female partner has regular menstrual cycles). If cycles are irregular, it is more difficult to decipher when the optimal window for conception might be and get egg and sperm to meet at the right time.

General Sub-Fertility

Some individuals or couples are simply what we call sub-fertile, and it may take them a little longer to successfully conceive. This is where we come in with fertility treatment methods to help our patients become pregnant faster!

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Anatomical Issues 

When we think about the uterus, fallopian tubes and ovaries, we know that the hysterosalpingogram (HSG) will tell us if the fallopian tubes are open (what we call "patent") and able to pick up the egg from the ovary when ovulation occurs.  

For this to happen, there must be a perfect relationship between the end of the fallopian tube (called the fimbriae) and ovary in order for the fimbriae to sweep across the ovary and bring the egg into the fallopian tube.

The HSG test only signifies that the fallopian tubes are open. It unfortunately cannot reveal if there is a good "relationship" between the end of the fallopian tube and the ovary.

Patients may also not know that they have endometriosis or pelvic adhesions which distort pelvic anatomy, decreasing the chance of the tube is close enough to the ovary for egg pickup. The good news? We have great treatment options to help overcome unexplained infertility!

Treatment Options for Unexplained Infertility

The best fertility treatment methods for those with unexplained infertility often depend on a patients' age. Whether you are under or over age 35 will likely inform your reproductive endocrinologist's suggested course of treatment. 

For those under age 35, superovulation with intrauterine insemination (IUI) is often the best first course of treatment. Let's explore how this treatment method works.

Superovulation with Intrauterine Insemination (IUI)

Superovulation with IUI is most effective in patients who are 35 or younger, due to the fact that they typically have good egg quality and more time on the "biological clock" to try to conceive.

How does it work? An oral medication (such as Letrozole) is taken for five days, causing the ovary to release (ovulate) more than the usual one egg per menstrual cycle. With Letrozole, the main goal is to have you instead release two eggs.

By releasing two eggs instead of one, you have a better chance that one of those eggs will be healthy and able to end up in the fallopian tube, leading to a higher chance of pregnancy.

We often recommend that our patients try this treatment method for 3-4 months. Why? Because most pregnancies will usually occur within the first 3-4 months (or 3-4 IUI cycles). 

What if it doesn't work? If you are not successful after 3-4 cycles, we move to in vitro fertilization (IVF) treatment, which produces even higher pregnancy rates.

In Vitro Fertilization (IVF)

In vitro fertilization (IVF) is a powerful and effective fertility treatment option, because we are able to overcome any obstacles in your way and simply place an embryo directly into the uterus, bypassing many potential roadblocks to conception.

With IVF, the fallopian tube does not need to "pick up" the egg, and in addition, we are able to join egg and sperm in the embryology lab to create embryos for future transfer. (Often more than one embryo at a time.)

Knowing how successful IVF treatment is for most patients, some with unexplained infertility opt to move directly to IVF. This decision is yours, and will depend mainly on your age and family-building goals. Your reproductive endocrinologist can help guide you through the decision-making process.

Note: The concept of embryo banking has also become more popular in recent years, with many patients doing IVF with preimplantation genetic testing (PGT) and freezing multiple chromosomally "normal" embryos now for future family building.

Unexplained Infertility FAQs

Here are some of the most commonly asked questions about unexplained infertility:

What's the difference between unexplained infertility and secondary infertility?

Primary unexplained infertility is noted in a couple who has never become pregnant, while a diagnosis of secondary infertility is reserved for patients who have become pregnant but are now not able to become pregnant (after trying for one year).

Both primary and secondary infertility treatments include superovulation with IUI and IVF, and are each great options!

What are the IUI success rates for someone with unexplained infertility?

IUI success rates depend on your age. In general, pregnancy rates with IUI and superovulation can reach approximately 20% per cycle. This is why many patients will try this treatment method 3-4 times.

Remember, when it comes to IUI with superovulation, many things have to go perfectly for it to be successful. The egg must be picked up by the fallopian tube, the sperm needs to swim up to the tube and fertilize the egg. After fertilization, the embryo must then travel through the tube and implant into the uterine cavity wall.

If superovulation with IUI is not working for you, our next move is IVF treatment, as it bypasses all of the above obstacles by placing the embryo directly into the uterine cavity.

What are the IVF success rates for someone with unexplained infertility?

At Illume Fertility, our IVF success rate for patients with unexplained infertility is exceptionally high, at around 76%*. Keep in mind that success rates depend heavily upon your age (though the quality of your chosen fertility clinic also plays a significant role).

Your clinic can give you an idea of your possible pregnancy rates.

Typically, your doctor will take into account your complete reproductive history, the results of your diagnostic tests, and then give you an idea of your per embryo transfer pregnancy rate.

*Our live birth rate for new patients 35 or under using their own eggs in 2019, with an impressive 60.9% live birth rate for new patients 35-37 years old, according to

Can special tests like ERA, EMMA, or ALICE help find a cause of infertility?

Many patients diagnosed with unexplained infertility ask if there are any additional tests they should undergo that might reveal information about the cause of their fertility challenges.

Tests like ERA (Endometrial Receptivity Array), EMMA (Endometrial Microbiome Metagenomic Analysis), and ALICE (Analysis of Infectious Chronic Endometritis) are occasionally used when patients have not been able to find success with in vitro fertilization (IVF). 

While these tests can sometimes provide additional information for select patients, they will not significantly increase your chances of success in most cases. Always talk to your doctor if you're curious about these or other fertility-related testing. 

What should I do if I have unexplained infertility?

Even if you're struggling with unexplained infertility, there are still positive steps you can take to optimize your health and wellbeing and give yourself the best chances of success! 

Here are a few reminders:

Here at Illume Fertility, we have a dedicated fertility acupuncture team, counselors, nutritionists, a Patient Advocate, plus free yoga classes and support groups, all of which can decrease your stress and increase your chances of success while trying to conceive.  

Now is the best time to optimize your health.

Get our free 90-Day TTC Checklist and learn what steps you can take to improve your health and chances of success. 

Download Now

A Doctor's Take on Unexplained Infertility

My colleagues and I know how frustrating it is to not be able to pinpoint any specific reason for your fertility struggles, and your emotions around this diagnosis are completely valid.

However, the silver lining to a diagnosis of unexplained infertility is that we have confirmed that there are no major issues with your reproductive health. As a fertility specialist, I always prefer not to find a problematic reason for your infertility.

Why? Because we have amazing treatment options for unexplained infertility - and there is even a chance that you may be still be able to become pregnant on your own, without our intervention.

Whether you suspect a specific issue or feel confused about why you are struggling to conceive, the most important step you can take is reaching out to a fertility expert early to create a plan of action for your success!

When reproductive physicians meet our patients, we figure out why they are not successful becoming pregnant.  This allows us to set up a plan of action to help them family build.  There are 5 general causes of infertility.  They include: ovulatory dysfunction, pelvic factor, male factor and unexplained infertility.  Approximately 10% of couples are diagnosed with unexplained infertility.

Spencer Richlin, MD

Dr. Spencer Richlin is Surgical Director and Partner in reproductive endocrinology at Illume Fertility. In addition, he is Division Chief of Reproductive Endocrinology at Norwalk Hospital. Dr. Richlin is board certified in both Reproductive Endocrinology and Obstetrics & Gynecology. He joined the team at Illume Fertility in 2004.

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