Unexplained Infertility

Unexplained infertility is not exactly a “real” diagnosis. It is more of a place holder, letting you know that our testing was unable to help you find out exactly what’s going on. By the time this label is applied, after 6-12 months of trying, surely something’s not working quite right, we’re just not sure what it is. Testing and treatment for unexplained infertility are, as you can imagine, a little different than those of other diagnoses. We explore this in more detail below.


How it’s tested

Let’s take a step back: remember that when a couple first starts trying to get pregnant, they have very good opportunities for success. Depending on age, the odds for getting pregnant the very first time the couple tries is somewhere between 30% and 55%. But it drops off every month after that. And the reason for the cycle drop off is not the passage of time, per say, but the statistical reality.

Let me explain: most people are aware that something like one in eight couples will suffer from subfertility, but the first month trying, we do not know if we are that couple, or if we are in the fertile majority.  The very fertile people are pregnant the first month, and they leave the group. By definition, then, whoever is left after the first month of trying is slightly less fertile. If you have been trying for six months, the odds per month are now about 5%. If you have been trying for twelve months, the odds are approximately 2%. This is without doing any tests. Of course, what we hope is that the testing will help to pinpoint the reason and from there find solutions that increase your chances back up again.

As you probably know, clinics provide screening tests for eggs, sperm, tubes, uterus and overall health. But the definition of a screening test is not that it necessarily picks up every instance of the disease, but just that it picks up most of them with good frequency, the majority of the time, without accidentally declaring a condition where there isn’t one. There’s a tradeoff between the sensitivity and specificity of a test – no test is 100% in both categories.

Tests get things a little (or a lot) wrong all the time. Of course, we intuitively all know this, which is why tests are often repeated, or the same parameter can be tested in more than one way. (For example, for the ovarian reserve testing, we can do day-three FSH levels, serum AMH, or ultrasound antral follicle counts). Therefore, when you present yourself to the fertility clinic, it has to be an appropriate balance between all the tests that have ever existed and finding tests that might help with your particular situation.

Consider testing for overall health. There are many useful tests, of course, but we are not going to do a full body CT scan for everybody who walks into the clinic. Generally, we focus on hormone levels such as thyroid, prolactin, testosterone and estrogen. Perhaps we will do a genetic screen as well, but even here, the appropriate tests get murky: do we do a simple karyotype to confirm you have the correct number of chromosomes? Or do we offer one of the newer panels such as the ones offered by Counsyl, which try to screen for the most known autosomal recessive diseases? Or do we go further, looking for experimental associations between DNA and conditions that have not been historically linked to specific markers, such as autism?

The point is, you and your doctor will choose a level of testing-intensity you’re comfortable with. And, just to be clear, the same is true for tubes and uterus. The gold standard of testing is laparoscopy, the rarest patient will need to consider surgery at her first visit to confirm if her tubes are open as they should be. But that brings up a challenge: Imaging tests for fallopian tubes (sonohystogram and hystosalpingogram) are deeply flawed, with poor sensitivity and specificity. That is, they get the diagnosis wrong (blocked tubes, or a single blocked tube, or open tubes), with rather high frequency. It is not the fault of the test so much as the reality that very subtle changes to tubal function will be missed by any imaging technique and can even be missed by laparoscopy.

Sperm tests are quite accurate, however, especially when we include DNA fragmentation, but there are no direct tests for eggs except through in vitro fertilization – and even then, they test fertilized eggs through pre-implantation genetic screening (check out Chromosome Screening for more on this).

In short, if you have been trying for more than 6 – 12 months, have regular cycles and good health, have had a clinic confirm you are ovulating when you think you are, and have had all your the tests come back as “normal”, it does not mean that all is well. It just means that the clinic is unable to identify what’s not working properly.

How it’s treated

In theory, your clinic likely could help you, but it would probably take surgery and/or IVF to get more information. Most people don’t jump into this very quickly during the investigative process. Many find themselves exploring treatments that they hope will be successful and sometimes they are. These treatment types include supplements to maximize egg and sperm quality, lifestyle modification to help patients live as healthy as we believe is necessary to maximize the chance for pregnancy, and perhaps to introduce low-dose medications to increase the number of eggs available, and/or intrauterine inseminations to increase the available sperm presented to eggs.

Are these measures going to work? Well, it ultimately depends on the underlying diagnosis. If the issue is egg quality – if you are waiting for the right egg to come along – then, yes, the low-dose fertility medications will help to boost pregnancy rates. If, on the other hand, the issue is with tubes, then none of the above will be effective. And so, with unexplained infertility my suggestions are always as follows:

1. Consider – but don’t necessarily follow through – with deeper levels of testing. After all, the further the testing goes, the more invasive it becomes (such as laparoscopy), and sometimes the more controversial the tests are. That is, they do not always reveal what the test was intended to reveal.

2. Next, it is totally reasonable to consider options ranging from naturopathic approaches to lifestyle management to low-dose medications and intrauterine insemination. But my strong advice would be to try any and all of these for a set period of time. Perhaps dedicate two to three months to any one solution, probably no more than six months. After all, the notion that there is “no harm in trying” is not strictly true: There is a lot of emotional harm in unsuccessful cycle after unsuccessful cycle, and when an approach is not working, it takes a real toll from the couple.

For this reason, with unexplained infertility, after three, six, or at most nine months of trying other means, we would strongly recommend IVF. It is going to be therapeutic for fallopian tubes (which, in the end, proves to be the cause of the majority of unexplained infertility), and help enable a diagnosis for any embryo-quality problems. It can even let you know if implantation is the final challenge. Nobody would ever wish to rush to IVF, but it is a reasonable solution, even to “unexplained infertility”. After all, it’s the procedure with the highest pregnancy rates and, beyond the goal of achieving pregnancy, it may also finally help you understand just what might be happening.

3. Lastly, it is not unreasonable to have a second opinion for your unexplained infertility. Sometimes, you do not even need to do any more tests: A clearer explanation of the tests on hand can provide the understanding you need to make the choices that are the best for you.