Home Health/Medical Dr. Cookingham Discusses Unexplained Infertility

Dr. Cookingham Discusses Unexplained Infertility


Lisa Marii Cookingham, M.D.

Reproductive Endocrinologist 

Columbia PREG Facility

What is unexplained infertility?

Of all couples experiencing infertility, about 30% will be diagnosed with ‘unexplained infertility’ after a complete evaluation has demonstrated no significant abnormalities. What that means is that they have no obvious problems after reviewing their medical history, performing their physical exam, and undergoing laboratory testing and imaging, for both patient and partner, and essentially everything we have in front of us appears normal. This comprehensive testing typically includes checking to make sure that one or both of the Fallopian tubes are open, that ovulation is occurring, and that there are a good number of moving sperm. During the evaluation, we are also making sure that there is nothing abnormal in or on the uterus that could potentially make getting or staying pregnant a problem. Only after all of these things are clear, will a couple be diagnosed with unexplained infertility. 

Where do they go from there once it is an unexplained infertility diagnosis?

Treatment of unexplained infertility is largely dependent upon the age of the female partner. Ifshe is less than 38 years old, we often start with oral medication for ovarian stimulation (alsocalled superovulation), and then we add intrauterine insemination (IUI) at the appropriate time. The rationale is that, if we don’t have an obvious male factor or an obvious female factor, then we try to improve the chance that a mature egg (or eggs) will meet the best sperm at the right place and the right time. For many couples with unexplained infertility, this minimally invasive strategy can be successful, but it may take a few cycles to work. If that same couple isn’t pregnant after 3-4 cycles, then we usually recommend proceeding to IVF. 

There is really good evidence to support this strategy will result in a shorter time to pregnancy and ultimately, a lower cost per pregnancy (versus continuing the same treatment or trying a strategy with more aggressive hormone therapy plus IUI). If the female partner is over 38 years old, there is good data to support moving directly to IVF, and bypassing more conservative treatments (ovarian stimulation and IUI) altogether. The rationale for this strategy of ‘immediate IVF’ is based upon studies that show a higher pregnancy rate and a shorter time to pregnancy as compared to the typical starting treatment for younger patients. It also allows for the opportunity to do genetic testing of the embryos (which are typically more abnormal as we get older) and may also increase the possibility that the couple could have additional embryos cryopreserved for future family building.

What if a couple only wants minimal intervention for treatment?

It would be great if there was something simpler than ovarian stimulation with IUI (or IVF) that would benefit patients with unexplained infertility. Unfortunately, there is consistent evidence that anything less than this is likely not more effective than expectant management alone – in other words, just continuing to try on your own without any intervention at all. Many studies have looked at different medications for ovarian stimulation alone with timed intercourse, but these don’t appear to be any better than expectant management. Similarly, undergoing IUI without any ovarian stimulation is also not shown to be more effective than expectant management alone. So if a couple has unexplained infertility and they want to pursue fertility treatment, the least invasive and most conservative route to try (with the assistance of a fertility specialist), is ovarian stimulation paired with IUI.

What if a couple wants to go directly to IVF for treatment?

If the female partner in a couple with unexplained infertility is less than 38 years old, IVF is

currently not recommended as first-line therapy over a limited course of treatment with ovarian stimulation and IUI (or even sometimes a 6 month period of expectant management). If the female partner is older, then we do often advise consideration of immediate IVF for all of the benefits previously discussed.

Why is the age of the female partner so critical in making treatment recommendations?

Female age is the number one factor that determines success for patients when it comes to fertility treatments. Obviously, there are a lot of other components that are important in achieving a successful pregnancy, but female age is consistently the number one factor for success with fertility treatments. Many published studies looking at fertility treatment success in female patients in their late 30s and early 40s show a clear benefit of moving directly to IVF. 

There can be a huge benefit to this strategy versus trying conservative treatments first since

many of these patients will ultimately end up needing IVF to achieve their family-building goals. If they try non-IVF treatments first and are not successful, then they have potentially lost invaluable time and money, without being any closer to pregnancy than if they were to have gone straight to IVF. Because lost time is so critical when dealing with advancing maternal age, sometimes delaying more aggressive treatment even for a few months, can mean the difference between a successful outcome or not. It really comes down to making sure that we are optimizing their time and efforts, and making sure we don’t lose an opportunity to help individuals or couples to achieve their family goals.

What is the social, emotional, and psychological impact for these patients?

Infertility is often a devastating diagnosis for many couples, regardless of the reason for

infertility. I think unexplained infertility is sometimes regarded as even more difficult for those

people experiencing it because they want an answer to why they haven’t been successful on

their own, and sometimes we don’t have an answer. Unfortunately, our available tests don’t tell us everything that could be going wrong. And that can be extremely frustrating and extremely difficult to accept – if there is an obvious reason that something wasn’t working, then we could just fix it. But if there is no obvious reason, we do our best to try to increase the odds of getting the right egg and the right sperm to meet at the right place at the right time. Sometimes that strategy works, and when it does, then the couple can focus on their success more than on the lack of an explanation.

But if it doesn’t work, then moving onto more aggressive treatment often comes with more

questions. When I talk to patients about moving onto IVF after other unsuccessful treatments, they are often discouraged because they still don’t have an explanation and now treatment hasn’t worked. One of the biggest benefits of IVF is that for these couples with unexplained infertility especially, IVF can be diagnostic in addition to therapeutic. When you take the process of fertilization and embryo development outside of the body, sometimes we can ‘explain’ the reason for unexplained infertility – maybe there is an issue of abnormal appearing eggs, or abnormal fertilization, or abnormal development of the embryos. But even if we don’t find an explanation, IVF is often still very successful for patients with unexplained infertility. And if we help identify why they’ve had problems getting pregnant on their own, it can offer hope and often makes it easier to accept help for their infertility diagnosis.

So you offer hope for patients with unexplained infertility?

Yes, absolutely! The downside for this diagnosis in particular is that I may not have an answer for you right away. The upside is that we may discover it along the way – but even if we don’t, we still have available treatment options that are successful for many people.

What’s the one word or parting thought you want to leave with these couples?

If you have been diagnosed with unexplained infertility, I think it’s really important that you work with a physician who will help you to achieve your family building goals as efficiently and cost-effectively as possible, taking into account your own personal preferences and, ultimately, what is right for you (and your partner and family).

PREG has IVF centers and ORs in Greenville, Columbia, and Lowcountry (Summerville) with offices in Spartanburg and Asheville.  We offer highly personalized fertility care and management. Dr. Cookingham sees patients in our Columbia center.  For more information on your reproductive options contact us today at 866.725.7734, or online at www.pregonline.com/contact-us.php

Time Image: by Nathan Dumlao 

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