Making Sense of Unexplained Infertility: 8 Potential Causes

by Jan 26, 2021

An unexplained infertility diagnosis can be devastating, leaving you feeling helpless and out-of-control. Unlike other types of infertility, it may not be as clear why you are struggling to get pregnant or what you can do about it. 

A woman is upset

If you are facing unexplained infertility, you are not alone: approximately 30% of couples worldwide struggle with unexplained infertility. In other words, doctors haven’t been able to identify a clear reason why the couple cannot conceive.

Doctors used to use a “wait-and-see” approach for unexplained infertility, but this is now changing. Today, many researchers say that unexplained infertility just means the explanation hasn’t been found yet — not that an explanation is impossible (if you’re suffering from secondary infertility check out our guide here).

A variety of potential causes have since been identified for unexplained infertility. In this article, we’ll go over eight of the most significant ones, and what they mean for your unexplained infertility diagnosis.

What is unexplained infertility?

Infertility, defined as the inability to conceive after trying naturally for one year (or six months if you are over age 35), affects 12% of women worldwide. Sometimes, infertility is caused by a medical problem, such as polycystic ovarian syndrome (PCOS) or endometriosis. However, many times, doctors are not able to identify a clear reason why couples cannot conceive on their own. This may lead them to give a diagnosis of unexplained infertility.

Ideally, doctors say that an unexplained infertility diagnosis is a diagnosis of exclusion, meaning it should only be given after a full workup is done on both the woman and her male partner that fails to determine another cause of infertility. A full infertility evaluation includes semen analysis, ovulation tracking, assessment of ovarian reserve, imaging, and, in some cases, laparoscopic surgery to visualize the reproductive organs.

What are the chances of getting pregnant with unexplained infertility?

Receiving an unexplained infertility diagnosis can be heartbreaking, but it does not necessarily mean that you will be unable to conceive. Some studies even show that women with unexplained infertility go on to conceive naturally in many cases. 

One six-month study found that 32% of women who received no treatment were able to conceive naturally, and one-third of women were able to conceive with intrauterine insemination (IUI), a type of assisted reproductive technology (ART). Another study found that expected management, or the “wait-and-see” approach, was slightly more effective than the use of Clomid, a fertility medication, in women with unexplained infertility.

So, whether or not you choose to use fertility treatments or to go at it without any fertility support, couples with unexplained infertility do have the possibility of conceiving. Your doctor will help you decide which option is best for you while taking into consideration your age and overall health.

Idiopathic Infertility or Unexplained Infertility?

When sperm quality is normal, a woman is ovulating regularly, and a laparoscopy does not show damage to the pelvic organs, the cause of infertility is said to be unexplained. In other words, unexplained infertility is diagnosed when there is no medical reason, on paper at least, why the couple should be unable to conceive.

Other times, a couple’s fertility workup may discover changes in sperm quality or ovulation that are abnormal but cannot be explained by another medical condition. This is known as idiopathic infertility. When the workup finds unexplained problems with the man’s sperm, doctors call it idiopathic male infertility; when the woman is not ovulating as she should for unknown reasons, it is called idiopathic female infertility.

Potential Causes of Unexplained Infertility

The idea that there could be a “cause” of unexplained infertility, which is supposed to have no clear cause, seems counterintuitive. However, more and more experts believe that unexplained infertility is not truly unexplainable, but rather, caused by a variable that hasn’t been identified yet. They have even started to theorize about what some of those potential causes may be. 

Below, we’ll list eight of the potential causes doctors have identified for unexplained infertility and talk about how they impact your reproductive health.

1. Diet

Folate, iron, and vitamins D, C, and B12 are the building blocks of fertility. They maintain egg health, especially as you age, and ensure your ovaries are timing the release of your eggs so they’re more likely to be fertilized.

Studies show that women who are anemic (deficient in iron, vitamin B12, or both) are at risk for having anovulatory cycles, and almost 50% of women whose vitamin D levels measure below 20ng/mL are unable to get pregnant.

The good news is that a Harvard study showed that women who changed five lifestyle factors, one of which was shifting to a fertility diet, saw an 80% reduction in infertility due to ovulatory disorders.

2. Genes

Chromosomal polymorphism is when a portion of one chromosome has been transferred to another (translocation) or a piece of a chromosome has been flipped upside down (inversion). If you have either of these conditions but your partner does not, the genetic material carried in your egg and his sperm won’t be able to combine.

Chromosomal polymorphism affects roughly 4% of the population, but a study published in July of 2017 found that chromosomal polymorphism was disproportionately present in couples diagnosed with unexplained infertility. The good news is that if you both have the same chromosomal polymorphism, researchers believe it won’t affect your fertility at all.

3. Sperm

Researchers at the Queen’s University Belfast tested sperm from men in couples diagnosed with unexplained infertility and they found that 80% of them had DNA-damaged sperm. Most of the male population has at least some sperm with DNA damage. And as long as those damaged sperm make up less than 15% of the total sperm supply, there’s no effect on fertility.

The problem comes when damaged sperm counts reach 25% or more of the total sperm supply. The researchers found when at least 25% of a man’s sperm showed DNA damage, the couple’s chance of having a baby dropped even with fertility treatment.

4. Mild Endometriosis

When infertility is due to endometriosis, it is not, technically, considered “unexplained.” However, mild forms of endometriosis may be more difficult for doctors to identify, even with diagnostic laparoscopy. As a result, you may receive an unexplained infertility diagnosis, when the problem is really stage I or stage II endometriosis.

During a laparoscopy to diagnose endometriosis, most doctors look for the characteristic “gun-powder” lesions that are black, dark brown, or blue. But endometriosis may also be red or even clear, making it harder to see with the naked eye. If the surgeon who performs your diagnostic laparoscopy is not well-trained in diagnosing and treating endometriosis, it is easy to miss these more atypical endometriosis lesions during surgery.

5. Tubal Damage

Another cause of infertility that is easily missed is tubal factor infertility or TFI. TFI is caused when the fallopian tubes are blocked by scar tissue, called adhesions. These adhesions can be caused by endometriosis, pelvic inflammatory disease, or another medical condition. 

Many doctors use a form of imaging called a hysterosalpingogram (HSG) to identify TFI. In HSG, dye is injected into the uterus to illuminate the fallopian tubes before taking an X-ray. This makes it easier to identify potential blockages of the fallopian tubes on imaging. 

Even if HSG finds that your tubes are not blocked, however, there may still be adhesions that cannot be seen on this test. Thus, if your doctor does not perform a diagnostic laparoscopy to visualize potential adhesions, TFI can be missed, and you might be stuck with an unexplained infertility diagnosis.

6. Premature Ovarian Failure

Premature ovarian failure, or primary ovarian insufficiency (POI), occurs when a woman’s ovaries stop functioning normally before age 40. In approximately 90% of POI cases, the exact cause is unknown. On paper, it may appear that nothing is wrong, meaning that you could receive a diagnosis of unexplained infertility. 

It’s still possible to get pregnant naturally with POI. Certain genetic disorders, diseases, and cancer treatments make a woman more likely to develop POI. However, when the cause of POI is unknown, it could potentially be related to lifestyle factors. If this is the case, then improving your lifestyle, including your diet, may help you get pregnant, even with POI.

7. Immunological Infertility

Immunological infertility describes an autoimmune response to sperm that may be present in one or both partners. In a person with immunological infertility, the body produces more anti-sperm antibodies (ASA) than the average person. The ASA can attack sperm, either in the male body prior to ejaculation or in the female body before the sperm is able to fertilize an egg, resulting in infertility. 

More research is needed to fully assess how immunological infertility works and how it can be treated. Immunological infertility is a lesser-known cause of infertility that may be overlooked by some fertility doctors, leading you to be diagnosed with unexplained infertility instead. 

8. Egg Quality

In women, it isn’t enough to simply ovulate each month. The egg that is released must be of high enough quality to be able to be fertilized and implanted in the womb. Low-quality eggs are unable to be fertilized due to genetic mutations, and the number of genetically abnormal eggs increases in frequency as women age. 

Egg quality declines naturally over age 35 for this reason, but it can also be affected by controllable lifestyle factors, such as diet, environmental toxins, and psychological stress. Thus, if your unexplained infertility is due to egg quality issues, you may be able to improve your egg quality by addressing these factors.

Getting Help vs. Making Lifestyle Changes

Nobody wants to deal with fertility issues, and going to the doctor can make those fertility problems seem more real. When it comes to unexplained infertility, many doctors still use the “wait-and-see” approach anyway. So, is there anything you can do about unexplained infertility on your own before going to see your doctor?

If you have been trying to get pregnant for over one year (or six months if you are over age 35) and have not yet seen a fertility specialist, you should make a doctor’s appointment for an official diagnosis of unexplained infertility before trying any lifestyle adjustments. 

However, if you have been diagnosed with unexplained infertility and told to “wait-and-see” before trying fertility treatments, you may want to take a look at your diet, potential environmental exposures, and psychological stress to see if improving these can help you get pregnant naturally.

Written by Fertility Nutrition Hub

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