Unexplained Infertility, Explained: Possible Causes and Treatment Options

Picture this: you have been trying to conceive for a while without success. You finally make an appointment with a fertility clinic in search...
Brighid Flynn •Mar 28, 2022

Picture this: you have been trying to conceive for a while without success. You finally make an appointment with a fertility clinic in search of answers. You have all of the standard infertility testing done, and no obvious cause is found as to why you haven’t been able to get pregnant. You are diagnosed with unexplained infertility.  

On one hand, you might feel relieved that there are no obvious red flags to worry about. On the other hand, being told that your infertility is unexplained can feel a lot like your doctors are saying, “We have no idea what’s wrong with you.” 

Unexplained infertility is more like a non-diagnosis because it means there is no real explanation for why you are having trouble getting pregnant. However, there are still reasons to have hope despite your current lack of answers, and there are some possible causes and treatment options to look into if you are given this frustrating diagnosis. Now let’s dive into what unexplained infertility is and what it really means for your future fertility!  

What is Unexplained Infertility?

The term unexplained infertility is used by physicians when standard fertility testing does not determine a cause for a woman or couple’s inability to get pregnant. And for those in desperate search of answers as to why their family-building journey is taking way longer than expected, it can be an incredibly tough pill to swallow. 

Approximately one in four couples grappling with infertility will be diagnosed with unexplained infertility. But what constitutes this vague and maddening diagnosis? Generally speaking, unexplained infertility is a diagnosis of elimination. In other words, your fertility doctors and specialists have ruled out certain, specific causes for your difficulty conceiving and are now unsure what could be behind it. 

Doctors can only diagnose a patient with unexplained fertility after conducting a full fertility evaluation. According to the American Society for Reproductive Medicine, a complete fertility evaluation should cover an ovulation assessment, a semen analysis, an examination of the ovarian reserve, a hysteroscopy to eliminate any serious uterine issues, a hysterosalpingogram (HSG) to look at the health of the fallopian tubes, and, occasionally, a diagnostic laparoscopy, which allows physicians to internally inspect organs with a tiny camera. 

What Are Some Possible Causes of Unexplained Infertility? 

Despite its name, unexplained infertility can be explainable. The cause just may not be easily evaluated or measured, may not be linked to the reproductive organs, or, perhaps, the only way to know for certain would require an extremely invasive and/or expensive procedure. Let’s take a look at some of the possible reasons behind unexplained infertility. 

One potential cause of unexplained infertility may actually be that you are suffering from an undiagnosed (non-reproductive) underlying condition. For example, untreated Celiac disease, diabetes, thyroid disorder, and some autoimmune illnesses, can all contribute to fertility issues. If you are experiencing symptoms of any of these conditions or simply haven’t had your hormone levels checked in a while, be sure to consult with your doctor about running additional tests. 

Silent endometriosis may also be a cause of unexplained infertility. Endometriosis is an often painful condition in which endometrial tissue grows outside of the uterus, but silent endometriosis is harder to recognize and can even be asymptomatic. Often, this type of endometriosis is not diagnosed until it’s found during 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.  

Another not-so-obvious scenario behind unexplained infertility could be related to the vaginal environment. What exactly does that mean? For sperm to make its way from the vagina to the cervix, the pathway needs to be lubricated with fertile cervical mucus. In some cases, the cervical mucus may contain antibodies that target the sperm as unwanted in the body and attack it. This is called cervical mucus hostility, and it can result in fertility issues. 

After conducting a full fertility evaluation and coming up empty, doctors may turn their attention to the egg and sperm quality. While there is no test to determine egg quality, some factors like age (in women), underlying medical conditions, or other unknown causes could be affecting their viability. Another issue that may arise in sperm is poor quality DNA, which can happen as men age. Oftentimes, these issues are diagnosed during the IVF process, and once identified can be treated and overcome with the assistance of IVF. 

Unexplained Infertility: Should I Do Timed Intercourse, IUI, or IVF?

Without a definitive cause for a patient’s unexplained infertility, doctors and specialists might recommend starting treatment for the most common or likely causes, starting with timed intercourse or IUI, and then eventually moving on to IVF. 

For couples with unexplained infertility, treatment with Clomid (or a similar ovulation drug) plus Intrauterine Insemination (IUI) can help improve fertility rates. Studies have shown that for women under 35, monthly success rates are about 10% per cycle. However, after 3 tries the success rate lowers significantly. In fact, a large randomized trial on couples with unexplained infertility called FASTT showed definitively that couples who are unsuccessful after 3 cycles of Clomid and intrauterine insemination (IUI) should proceed to IVF as their next treatment.   

While more invasive and expensive, IVF definitively has the highest success rates for patients with unexplained infertility. It can also help identify the root cause of infertility, which might not seem very helpful now, but it could give you the answers you need to finally bring home your baby.

If you have been diagnosed with unexplained infertility and are feeling discouraged in your search for answers, you are not alone. We hope this article gives you the tools and resources you need to advocate for yourself at the doctor’s office and brings you one step closer to the family of your dreams. 


Brighid Flynn is a freelance writer based in Philadelphia where she lives with her husband and puppy. She is just beginning her journey toward motherhood.