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The Myth of Unexplained Infertility

I felt like I have to write another article about the mysterious diagnosis called “unexplained infertility” after seeing a number of patients in their early 30s with this diagnosis recently. I often hear from patients that “everything is normal” or “nobody could identify any problems”. It’s also not uncommon to hear “I went to different doctors and they could not do anything for me”. I think we need to clear the misperception and shed some light on this issue!


Well, what is unexplained infertility? It is when the basic testing for infertility comes back “normal”.


Basic testing includes a semen analysis, ovulation testing and evaluation of the uterus and tubes. More recently, basic testing has been extended to include hormone testing of ovarian/egg reserve using FSH and estrogen levels. A hormone called AMH also has been popular and added to most hormone panels.


Whereas these tests are helpful in identifying major problems, when they are normal or within range, they do not explain much other than giving false reassurance that everything is “normal”. The main problem with false reassurance is the possible loss of precious time to conception. This is more impactful when the egg reserve is low and not clearly identified because the work up had been normal.


Can it be the sperm?

If there is no sperm or very low sperm, it is obvious that there is male factor, but what happens if the semen analysis is normal? Advanced sperm testing for sperm DNA fragmentation and careful history taking can identify sperm quality problems. These issues can result in abnormal or absence of fertilization of the eggs.


It is a fact that improvement of life-style and other variables can improve sperm quality. For example, if there is DNA fragmentation in the sperm, support with anti-oxidant treatment or repair of a varicocele can improve the outcome. In regards to the anti-oxidants, I would recommend trying the Fertile Vitamin for Men. Ultimately, IVF and microinjection (ICSI) of selected sperm can bypass majority of such problems.


How about ovulation dysfunction?

If someone has regular menstrual cycles or the presence of ovulation symptoms and parameters, ovulation is presumed to be confirmed, but in 5% of patients with regular menstrual cycles, there can still be ovulation dysfunction. In such cases, one might assume that the egg is being released into the pelvis, but in fact it’s not, which can clearly result in infertility. Ovulation induction can resolve this problem in most cases.


Are the fallopian tubes important?

When the hysterosalpingogram (HSG) test (commonly used to evaluate the tubes and the uterus) is reported to be normal, one assumes that there are no anatomical problems. It is not uncommon to identify tubal disease or uterine problems in the presence of a “normal HSG”. It is also possible that some patients may have endometriosis or pelvic adhesions. It is crucial that the HSG images are reviewed by an infertility doctor because even if the tubes appear to be open at the end, there can still be findings of tubal damage or even significant tubal disease. If there is tubal disease based on HSG findings, natural conception or success through intrauterine insemination (IUI) will be very low. Surgical treatment of the tubes or IVF can be valuable treatment options in such cases.


Ovarian reserve – The most important variable!

If the FSH and estrogen levels are normal, one assumes that the egg reserve is normal. Unfortunately, these tests can only detect 70% of low egg reserve cases accurately. Addition of AMH level can enhance this sensitivity, but the best method is examination of the ovaries with pelvic ultrasound to count the antral follicles (potential eggs ready to be used for that cycle). A direct examination of the ovaries often identifies any egg reserve related infertility.


The assessment of ovarian reserve is so crucial that if the ovarian reserve is low, there is absolutely no time to lose. Egg reserve declines during reproductive years physiologically, but if the reserve is already low, especially in someone over 35, waiting further will result in an even lower egg reserve resulting in refractory infertility. It’s best in such cases to start treatment as soon as possible because time may be running out. This is why the concept of “unexplained infertility” is a confusing and a tricky one.


The take home message is not to assume that everything is working when in fact it’s not and seek a consultation with an infertility specialist soon. Unexplained infertility can be a significant burden on patients psychologically which can further complicate things. Psychological stress can impact ovulation and possibly implantation of the embryo. Furthermore, stress can negatively affect the immune system which is extremely important for implantation of the embryo and continuation of the pregnancy.


Even though each case of unexplained infertility can be unique, the most common cause is typically declining ovarian reserve. It’s best to identify and “explain” the cause and target the treatment towards that cause. Such an approach not only achieves the ultimate goal of a healthy live birth, but also relieves anxiety and may possibly avoid third party reproduction. Third party reproduction refers to the use of donor sperm, donor eggs or the use of a gestational carrier (formerly known as surrogacy).


When you hear that your diagnosis is unexplained infertility, don’t stop until someone explains it. At LA IVF, we focus on diagnosis and believe that each case can be explained with proper work up and attention to detail.

TEL: 310-286-2800 | FAX: 310-691-1116