Unexplained Infertility

Unexplained infertility is the situation in which no cause preventing pregnancy can be found on the standard investigations done on you. For couples who say "everything is normal, but pregnancy is not happening", this diagnosis can be confusing. The information below draws a general framework and does not replace a diagnosis or treatment recommendation specific to you.

What does unexplained infertility mean?

This diagnosis is a diagnosis of exclusion: a cause is looked for, but it cannot be found with standard tests. The term "unexplained" does not show that there is no problem at all, or that it is psychological; there may be a factor that cannot be detected with the tests available.

According to current guidelines, this diagnosis is made for you only when all of the following conditions are present together: a certain period of unprotected intercourse, normal history and examination in both partners, confirmed ovulation and open tubes in the woman, and normal semen values in the man. The period needed varies from person to person; your doctor determines it.

Which tests are done for the diagnosis of unexplained infertility?

According to current guidelines, four areas come to the fore in the diagnosis. A semen analysis is done on your partner according to standard criteria. The patency of your tubes is shown with hysterosalpingography (HSG) or contrast ultrasound (HyCoSy); both are valid tests and their diagnostic power is similar. For the structure of your uterus, ultrasound may be sufficient; if the cavity looks normal, no additional assessment is needed. Confirmation of your ovulation is done if your menstrual cycle is not regular or if it is thought necessary; it is not recommended routinely in a regular cycle.

Which tests are not recommended routinely?

In the assessment of unexplained infertility, current guidelines do not recommend the routine use of many tests: ovarian reserve testing, taking a sample from the lining of the uterus, the post-coital test, certain blood values and vitamin levels, thrombophilia and immune-related tests, genetic investigations, and routine hysteroscopy and diagnostic laparoscopy when the ultrasound is normal are on this list. If your partner's semen analysis is normal, hormone tests, DNA fragmentation and similar additional sperm tests are also not recommended routinely. Doing more tests does not always mean a more thorough investigation; unnecessary tests can cause time, cost and unnecessary anxiety.

Should you try waiting first, or insemination?

Guidelines on this subject recommend different treatment orders in unexplained infertility; most of these recommendations are not definitive, and the data they rest on are limited. The first step recommended by some guidelines is to wait for natural pregnancy for a time, instead of moving straight to insemination or ovarian stimulation. The waiting period has varied in studies; you decide how long you can wait by talking with your doctor. If waiting gives no result, some guidelines prefer insemination stimulated with oral medicines over insemination stimulated with injections; the best number of cycles is not known. Other guidelines count stimulated insemination as the first treatment option from the start. If stimulation with injections is needed, it should be done at a low dose and with close monitoring in order to avoid multiple pregnancy and ovarian hyperstimulation syndrome.

If insemination gives no result, should IVF be considered?

According to some guidelines, if no result is obtained from stimulated insemination, IVF is preferred over waiting. Other guidelines recommend that IVF should not be preferred over stimulated insemination, and individualise the move to IVF according to your age, the duration of infertility, your previous treatments and your previous pregnancies. In both approaches, microinjection has not been shown to be superior to conventional IVF; both prefer the conventional method to microinjection.

Why do the sources recommend different treatment orders?

The difference appears particularly in the first step: some guidelines follow the order of waiting, stimulated insemination, IVF, while others count stimulated insemination as a treatment option from the start. The common points are that attention is paid to the risk of multiple pregnancy and ovarian hyperstimulation, and that no superiority is given to microinjection. For this reason you need to make the decision together with your doctor, according to your situation; the order of one of the guidelines is not held to be superior to the other.

What affects the decision to start treatment?

Current guidelines recommend that the decision to start active treatment be made according to your situation. Your age, the duration of your attempts to conceive, and your previous pregnancy and treatment history are the main factors that determine this. If your situation is good, monitoring may be appropriate; if your time is more limited, a move to treatment can be made earlier. In choosing between treatments, the expected benefit and the possible harms, such as multiple pregnancy and ovarian overstimulation, are weighed together.

Are there practices whose benefit has not been proven?

Yes, there is not enough evidence for some common practices. Current guidelines do not recommend the following practices in unexplained infertility: scratching the lining of the uterus, oral antioxidant supplements for you or your partner, acupuncture in the woman, and inositol. There are not enough data that they bring benefit. Instead of starting supplements or products on your own, it is appropriate to tell your doctor what you are using.

What are lifestyle adjustments and emotional support good for?

Current guidelines point to low-cost lifestyle adjustments aimed at diet, alcohol, smoking, physical activity and body weight as a non-definitive recommendation. Healthy eating and regular exercise are recommended, together with behavioural support if needed. The quality of life of women with unexplained infertility is similar to that of couples whose cause is known; that is, having "no cause" does not lighten your emotional burden. Getting psychological support when needed is recommended.