Unexplained infertility: what next when all the tests are normal?
In brief
Infertility is called unexplained when a full work-up finds no problem in either the woman or the man. A natural pregnancy is still possible, especially under 35 and when the couple has not been trying for long. Depending on age and how long you have been trying, the options are monitored waiting (expectant management), intrauterine insemination with ovarian stimulation (the first-line treatment according to ESHRE) or IVF.
What is unexplained infertility?
Unexplained infertility is a diagnosis of exclusion: it is made when the couple's fertility work-up is normal. In practice, this means:
- ovulation is taking place;
- the ovarian reserve is in line with age;
- the fallopian tubes are open and the uterine cavity is normal;
- the semen analysis is normal.
"Unexplained" does not mean "no cause": there may be factors that routine tests cannot measure, such as egg or sperm quality, how well the tube picks up the egg, or implantation. Superficial endometriosis can also be missed on ultrasound.
In 2023, ESHRE (the European Society of Human Reproduction and Embryology) published a dedicated guideline. It points out that most of the extra tests and treatments offered in this situation have not been robustly evaluated.
Can I still get pregnant naturally with unexplained infertility?
Yes. Normal test results are actually reassuring: some of the couples concerned conceive naturally in the following months or years. Your chances depend mainly on three factors:
- the woman's age, the most important factor;
- how long you have been trying: the longer the infertility, the lower the natural chances;
- a previous pregnancy together, which is a favourable sign.
Having sex regularly, every two to three days, covers the fertile window without any need to time intercourse.
It is worth checking with your doctor that the work-up is complete and recent: a semen analysis done several years ago, tubes that have not been checked or an ovarian reserve that has not been assessed do not allow a diagnosis of unexplained infertility. On the other hand, repeating tests that were already normal, without a good reason, rarely adds anything.
How long should we wait before fertility treatment?
There is no single timeframe. The decision takes into account age and how long you have already been trying:
| Situation | Usual approach |
|---|---|
| Woman under 35, trying for a short time | A period of monitored waiting, with medical follow-up, is reasonable |
| Woman aged 35 to 37 | The waiting period is shorter; assisted reproduction is discussed earlier |
| Woman aged 38 or over, or long-standing infertility | Prompt referral to a fertility centre, often straight to IVF |
Waiting longer, up to two years of trying in total, can be considered for a young couple, but it is not appropriate after 35. The French College of Gynaecologists and Obstetricians (CNGOF) recommends starting fertility tests after six months of trying from that age.
What is the recommended treatment for unexplained infertility?
| Option | How it works | What the guidelines say |
|---|---|---|
| Monitored waiting | Regular sex, medical follow-up, healthy lifestyle | A reasonable option for young couples with a good outlook |
| Ovulation induction alone, with timed intercourse | Tablets or injections to trigger ovulation, without insemination | Not recommended by the CNGOF (2022) for women who ovulate normally |
| Intrauterine insemination (IUI) with stimulation | Mild stimulation, then prepared sperm placed in the uterus at the time of ovulation | First-line treatment according to ESHRE (2023) |
| In vitro fertilisation (IVF) | Fertilisation in the laboratory, then embryo transfer | After unsuccessful inseminations, or straight away depending on age and how long you have been trying |
| Diagnostic laparoscopy | Keyhole examination of the pelvis under general anaesthetic | The CNGOF considers it probably useful under 30 to improve the chances of natural conception |
For stimulation before insemination, the CNGOF recommends gonadotrophins with monitoring of ovulation, to limit the risk of multiple pregnancy. The IVF process is described in our article on the steps of IVF.
What happens during intrauterine insemination (IUI)?
Intrauterine insemination (IUI) is the simplest assisted reproduction technique. It takes place in several stages:
- mild ovarian stimulation, with low-dose hormone injections, to obtain one or two mature follicles;
- monitoring with ultrasound scans and blood tests, essential to limit the risk of multiple pregnancy. If too many follicles develop, the cycle may be cancelled;
- triggering ovulation with an injection, at a precise time;
- the insemination, about 36 hours later: the sperm, collected the same day and prepared in the laboratory to select the motile sperm, is placed in the uterus through a thin catheter. It is quick and causes little discomfort;
- a pregnancy test about two weeks later.
Insemination requires at least one open fallopian tube and, after preparation, enough motile sperm. This is why the work-up must be complete beforehand. After repeated unsuccessful attempts, the team will suggest moving on to IVF.
Inseminations are carried out at an assisted reproduction centre, to which the practice refers you.
Do I need more tests if my fertility tests are normal?
It is tempting to order more and more tests to "find something". Guidelines urge caution: extra tests are only useful if they can change your treatment. Depending on the situation, the following may be discussed:
- a 3D ultrasound or an MRI scan if you have painful periods or pain during sex, to look for endometriosis or adenomyosis;
- a laparoscopy in a young woman, as mentioned above;
- a repeat semen analysis if the first one was borderline.
Endometrial receptivity tests, sperm DNA fragmentation tests or immunological tests are sometimes offered: their value in unexplained infertility has not been shown, and they are not recommended routinely.
How can we cope with the wait?
Having no explanation can be harder to live with than a clear diagnosis. A few pointers may help:
- agree a clear timetable with your doctor (how long to wait, what comes next), so you are not left in limbo;
- act on what both partners can change: stopping smoking and cannabis, limiting alcohol, staying active, eating a balanced diet;
- keep a sex life that is not solely focused on conceiving;
- ask for psychological support if the wait becomes a burden.
Frequently asked questions
Is unexplained infertility common?
Yes, it is a common situation among couples seeking help for infertility. It remains a diagnosis of exclusion, however, which requires a complete work-up of both partners.
Can stress cause unexplained infertility?
Stress is mainly a consequence of infertility. There is no evidence that it is a major cause, and couples should not blame themselves.
How many IUI cycles before moving on to IVF?
The number of attempts is discussed with the team according to age and circumstances; in France, the Assurance maladie (national health insurance) covers a set number of inseminations. After 38, couples often move on to IVF sooner.
Is IVF less successful in unexplained infertility?
No, results depend mainly on the woman's age and the number of eggs collected. IVF also makes it possible to observe fertilisation, which can provide extra information.
Can endometriosis be behind unexplained infertility?
Yes, superficial endometriosis may not be visible on ultrasound. Very painful periods or pain during sex should prompt a search for it, sometimes by MRI or laparoscopy.
References
- ESHRE Guideline Group on Unexplained Infertility, Romualdi D, et al. Evidence-based guideline: unexplained infertility. Human Reproduction, 2023. doi:10.1093/humrep/dead150 — PMID 37599566
- Sonigo C, et al. Prise en charge du couple infertile en première intention. Recommandations pour la pratique clinique du CNGOF 2022. [First-line management of the infertile couple: CNGOF guidelines 2022] Gynécologie Obstétrique Fertilité & Sénologie, 2024. doi:10.1016/j.gofs.2024.01.014 — PMID 38311310
- ESHRE Add-ons working group, Lundin K, et al. Good practice recommendations on add-ons in reproductive medicine. Human Reproduction, 2023. doi:10.1093/humrep/dead184 — PMID 37747409
Dr Olivier KadochObstetrician-gynaecologist and gynaecological surgeon in Paris (16th and 5th arrondissements). Former chef de clinique-assistant (senior registrar) at the Paris public hospitals (AP-HP); individually accredited by the French National Authority for Health (HAS). RPPS 10003957809. Background and practice locations
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