‘Unexplained infertility’ is a common phrase in the reproductive world. It is the term used when there is no cause found for infertility. A diagnosis of unexplained infertility is given to about 15-25% of heterosexual couples with infertility. It does not necessarily mean that there is no cause – rather, it may mean that the cause has just not been found.
Infertility may be said to be unexplained if the woman is ovulating regularly, has patent fallopian tubes with no adhesions or endometriosis, if the man has normal sperm parameters and the couple have been having frequent intercourse at the time of ovulation for at least one year. The final diagnosis is made only after all the necessary tests have been performed and all results are found to be normal.
That the infertility is unexplained is not the couple or individual’s problem, it is due to the limitations of science and medicine. The most difficult aspect is not knowing whether unexplained infertility is due to a cause that cannot be identified or just bad luck. These criteria also apply to single people and same-sex couples who have had failed attempts at conception using donor sperm or eggs.
Diagnosis of Unexplained Infertility
Although a diagnosis of infertility can’t formally be made unless there are at least 12 months of unprotected intercourse without conception in the absence of an obvious cause, in couples where the woman is more than 35 years old most doctors will recommend commencing investigations after 6 months
Investigations should include a semen analysis, assessment of ovulation and ovarian reserve, a pelvic ultrasound (female) and tubal patency check by hysterosalpingogram (HSG) or laparoscopy.
The most accurate way currently to assess ovarian reserve is a serum Anti Mullerian Hormone (AMH) assay. This blood test can be performed at any time of the menstrual cycle and should be very helpful in determining ovarian reserve and likely ovarian response if treatment with ovarian stimulation is recommended.
A heterosexual couple with unexplained infertility still have a fairly good chance of getting pregnant naturally without needing treatment at all, although this will be dependent on the age of the woman and the length of timing trying to conceive to date.
The principal treatments for unexplained infertility include expectant management with timed intercourse and lifestyle change, clomiphene citrate or letrozole with or without intra uterine insemination (IUI), lipiodol tubal flushing, and IVF.
Expectant Management and Lifestyle changes
A preconception health programme can help by ensuring that the factors that people have some control over, i.e nutritional, lifestyle, and environmental factors, are optimised to enhance their overall reproductive health. Cigarette smoking, abnormal BMI, and excessive caffeine and alcohol consumption can reduce fertility in both women and men. Both women and men should aim to achieve a normal BMI and reduce caffeine intake to less than 250mg (2 cups) daily. This will have the added benefit of helping to ensure a healthier pregnancy as well.
For more information on lifestyle, environmental, weight and nutrition which can optimise your fertility, click here.
Your fertility specialist can discuss these options with you and recommend them if appropriate.
Lipiodol or Laparoscopy
Use of Lipiodol tubal compared to using waterbased contrast medium has been shown to increase the chance of natural conception in women having an HSG as part of fertility investigations. The reason is unknown, but the iodine in Lipiodol may inhibit silent uterine inflammation.
The use of Clomiphene with timed intercourse in patients with unexplained infertility has been shown to only have a small benefit.
Intrauterine insemination involves placing washed prepared sperm in the uterine cavity at ovulation either on a natural cycle or with stimulation. A recent Cochrane review confirmed that IUI with stimulation increased the live birth rate when compared to IUI alone.
This is the most effective treatment for unexplained infertility where simpler options have been unsuccessful. IVF will also give an explanation for the infertility in some couples. Many IVF clinics recommend ICSI (sperm microinjection) as part of the IVF cycle for long term unexplained infertility, or a 50/50 IVF/ICSI split for inseminating eggs in case there is a subtle sperm defect that might reduce the fertilisation rate with conventional IVF.
A thorough and timely investigation is required before making a diagnosis of unexplained infertility. Various treatment modalities are available with maternal age and length of infertility with current ovarian reserve (as determined by AMH) being the best predictors of success.
As for all types of infertility, it is important for people to try and achieve optimal health. Dealing with any health issues (either managing or resolving) can help people understand if those particular health problems were having an impact on their fertility. Both men and women experiencing unexplained infertility are equally responsible for addressing factors within their control.
The most important information when trying-to-conceive is being able to successfully identify ovulation. The best indicator is when the cervical mucus becomes the consistency of egg white prior to ovulation. This is the mucus that sperm needs to swim through, so is the best time to have sex. Waiting until ovulation is detected (e.g. through a urinary LH kit) to have sex may be too late in the cycle, as the egg quality declines within 12 hours after the egg is released. Do not ‘save’ sperm – trying to have sex every 2-3 days around the time of ovulation is usually sufficient for most people.
For more information on the timing of sex click here.
It is very important to see a fertility specialist for guidance regarding investigative tests in order to try to find a cause of infertility – unexplained
infertility is different from under-investigated infertility!
For more information on the emotional impact of infertility, click here.
If you have been trying to conceive for at least twelve months, your GP will be able to refer you for a consultation with a fertility specialist (First Specialist Appointment) in the same way that if your GP had identified a medical condition. However, those with unexplained infertility must have been trying-to-conceive for five years to qualify for publicly funded fertility treatment. Once you qualify, you can be enrolled for public treatment as for people with other causes of infertility.
For more information on public funding, click here.