Unexplained infertility: when all the tests are normal, what can be done?

This is a common diagnosis, and many of the patients I support have heard it at some point in their journey. It is experienced as a lack of an answer, and sometimes as a suspicion: ‘if nothing explains it, perhaps it’s all in my head’. This is not the case. In 2023, the European Society of Human Reproduction and Embryology (ESHRE) published a comprehensive set of guidelines on the subject. These help to clarify what we do, and above all, what we can avoid.

What ‘unexplained’ means

According to the ESHRE, infertility is considered ‘unexplained’ in a couple who have not achieved pregnancy after at least twelve months of regular unprotected intercourse, whilst basic tests show normal results: ovulation, patent fallopian tubes, uterus, cervix, pelvis and semen analysis. The definition adopted by the expert group applies to women aged 40 or under.

This last point is important. After the age of 40, the decline in egg quality becomes a valid explanation in its own right, even if the tests appear normal, and the approach is no longer the same. See pregnancy after the age of 40.

Useful tests, and those that can be avoided

The assessment must be comprehensive before any conclusions are drawn, but it does not need to be endless. The recommendation clarifies several issues:

• The fallopian tubes are assessed by hysterosalpingography or contrast-enhanced ultrasound (hysterosonography to assess tubal patency): both are considered reliable.
• Routine diagnostic laparoscopy is not recommended for making this diagnosis.
• AMH does not explain infertility in a woman with regular cycles: it predicts the response to stimulation, not the chances of a natural pregnancy. See what the AMH level really tells us.
• Routine hysteroscopy, to look for an abnormality not detected by ultrasound, is not recommended in this specific context. It remains appropriate in cases of suspicious imaging or implantation failure, which is a separate issue.

The list of basic tests, organised by day of the cycle, can be found in the fertility assessment.

Wait, or start treatment straight away?

The ESHRE does not set a single rule: the decision to start treatment depends on the prognosis for the couple, that is to say, primarily on the woman’s age, the duration of infertility and any previous pregnancies. A young couple who have been trying for a year still have a real chance of a spontaneous pregnancy in the coming months. A couple who have been trying for four years, with the woman aged 38, would be better off not waiting any longer.

The order of treatments

This is the most surprising point. For unexplained infertility, the European recommendation prioritises intrauterine insemination with ovarian stimulation over IVF as a first step. Stimulation is carried out at a low dose, with ultrasound monitoring, to avoid multiple pregnancies and hyperstimulation. The medicines used are described in the article on simple stimulation.

According to the ESHRE, IVF is probably not to be preferred over stimulated insemination from the outset: this is a conditional recommendation, based on low-quality evidence. The expert group specifies that the decision must be tailored to the individual, taking into account age, duration of infertility, previous treatments and pregnancies. In practice, for older women or those who have been infertile for several years, IVF is often discussed at an earlier stage. And in IVF, ICSI is not recommended as an alternative to conventional IVF when the sperm is normal; see ICSI or conventional IVF.

In the UK, the NICE guidance, revised in 2026, takes a similar line. After two years of trying to conceive, it recommends either considering up to four cycles of insemination with gonadotrophin stimulation prior to IVF, or proceeding directly to IVF, depending on the couple’s circumstances and preferences. However, it advises against stimulation alone, without insemination.

What is not recommended

Several options, often suggested to discouraged couples, are ruled out by the guidance: endometrial ‘scratching’, antioxidants for the woman, acupuncture and inositol. None of these has demonstrated sufficient benefit in this context. A more general distinction between useful and useless options is set out in the article on add-ons. Psychological support, a balanced diet and physical activity are, however, encouraged.

What about IVF abroad, in this case?

I’m quite frank with my patients about this: coming to Greece for inseminations rarely makes sense. It often takes several cycles, and each one requires a trip timed to coincide with ovulation. Inseminations are much simpler to have carried out closer to home. Going abroad becomes an option when it comes to IVF, if waiting times, age limits or costs are preventing you from proceeding at home: see which country to choose.

A diagnosis of unexplained infertility also has a distinctive feature: IVF itself provides information that tests do not, such as the number of eggs retrieved, the fertilisation rate and the development of the embryos up to the blastocyst stage. It is sometimes at this stage that an explanation finally emerges.

If you find yourself in this situation and don’t know where to start again, write to me: we can go through your medical records together and see what’s missing, or what’s unnecessary.

Frequently asked questions

Source: https://fertilitegrece.com/en/blog/unexplained-infertility-what-next/ — Triada Baloukoudis, IVF patient coordination in Greece. General information, not medical or legal advice. Printed on

Triada Baloukoudis
Independent IVF patient coordinator in Thessaloniki, with 24 years of experience supporting patients travelling from abroad. More · Contact · Facebook