By Zaira Salvador BSc, MSc (embryologist).
Last Update: 10/15/2018

When one attempts to classify the origin of infertility, the usual distribution is 30% female, 30% male, and 20% having a mixed cause, that is, both partners presenting infertility issues.

The remaining 20%, conversely, has unexplained infertility. A couple is diagnosed this type of infertility when they are unable to conceive in spite of getting normal results in male and female fertility tests.

Diagnosis

Unexplained infertility is also known as unknown infertility and sometimes infertility of unknown origin or idiopathic infertility.

It should be noted that, the fact that one is unable to discover the underpinning causes of childlessness does not mean there exists no cause. All infertility cases have a cause; the problem is, sometimes detecting it is highly complicated.

For all these reasons, unexplained infertility is diagnosed whenever the following premises are met:

  • Regular menstrual cycles
  • A hormonal panel performed on days 3-5 of the menstrual cycle shows normal results.
  • Anti-müllerian hormone (AMH) is within the normal range.
  • A hysterosalpingography (HSG) confirms the existence of tubal patency.
  • Multiple ultrasound scans reveal a normal uterus, without anatomical anomalies, fibroids, or polyps.
  • The antral follicle count (AFC) via ultrasound is above 5, with a regular, homogeneous lining of the uterus
  • A semen analysis report reveals all sperm parameters are normal
  • The couple engages into sexual intercourse on a regular basis, particularly near the fertility window of the female partner
  • The couple has been trying to conceive (TTC) for, at least, one year without luck

Aside from all the diagnostic tests mentioned so far, the are others available for use that could help us identify the cause of infertility. However, sometimes, moving on to a particular infertility treatment is preferable.

In other cases, the cause is finally found out after several failed attempts with reproductive technologies in spite of having obtained a diagnosis of unexplained infertility at the beginning.

Causes

As the name itself suggests, the causes of this type of infertility unknown. For this reason, explaining the real causes that lead a couple to be unable to conceive is highly complicated.

Nevertheless, throughout the history of fertility treatments, experts have been able to identify certain common patterns amongst these couples, including:

Genetic abnormalities in sperm
Sperms with errors in their DNA sequences can lead to fertilization failure or result in poor-quality embryos. In both cases, they would lead to a non-viable pregnancy. For these anomalies to be detectable, sperm must be genetically screened with a DNA fragmentation test, among other types of tests.
Chromosomal abnormalities in oocytes
The number of aneuploidies or genetic mutations present in a woman’s egg count increases as she ages. Even if a woman has normal ovulation cycles, egg quality may be affected, which results in non-viable embryos.
Abnormal embryonic development
When the eggs are fertilized in the lab with sperms, embryo morphology can be observed. Embryos with non-symmetric cells, with fragmentation, multiple nuclei, or slow growing are qualified as poor-quality embryos. The chances for developmental arrest, leading to implantation failure or chemical pregnancy.
Implantation failure
For embryos to be able to attach to the uterine lining and start developing, having a receptive endometrium is essential. Also, there must exist a perfect embryonic-endometrial synchrony. If the implantation window occurs earlier or later, the chances for pregnancy decrease dramatically, or even disappear.

The alterations listed above are common causes of both primary and secondary unexplained infertility. In other words, they can cause infertility in all types of couples, whether they were able to conceive in the past or have never had children before.

One should note that the age of the woman is a key factor when it comes to uncovering the actual cause of infertility. From the moment a woman turns 35, the chances for getting pregnant naturally diminish dramatically due to ovarian aging.

Treatment

The most adequate treatment option in cases of unexplained infertility is dependent on the woman’s age.

Broadly speaking, in young couples whose diagnostic tests don’t indicate any relevant or serious issues, specialists usually apply a stepwise approach, that is, from the simplest to the most technically challenging techniques.

Conversely, in women of an advanced maternal age, it is likely that they are directly referred to In Vitro Fertilization (IVF).

The following are the most recommendable options for couples with unexplained infertility:

Natural remedies

Sometimes, just little changes in one’s lifestyle turn out being the solution to a specific fertility issue. Some important tips to achieve pregnancy for these couples include:

  • Follow a healthy, balanced diet. It should include fruit and vegetables that add vitamins, minerals, and antioxidants, all of them essential to boost reproductive health.
  • Avoid toxic substances, like tobacco, alcoholic drinks, and products containing caffeine.
  • Do moderate sports, since they contribute to reducing the levels of stress and anxiety often caused when a couple is TTC.
  • Consider losing weight in case you have overweight or obesity issues.
  • Monitor your fertile days, and engage into sexual intercourse during those days. Sexual abstinence helps increase sperm quality.

Moreover, your doctor may indicate several cycles of scheduled intercourse. The follicular phase of the menstrual cycle is monitored, and the couple is indicated to have intercourse just on the expected day of ovulation.

Read more: What Is Scheduled Intercourse?

Intrauterine Insemination (IUI)

In case scheduled intercourse failed, IUI would be the next option for the couple to try.

In those cases where the couple have been TTC for a very long time, they may be referred to IUI directly.

IUI involves undergoing mild ovarian stimulation to promote the growth of one to two ovarian follicles. Then, ovulation is induced, and the capacitated sample of sperm from the partner is place in the uterine fundus.

Due to its simplicity, a maximum of 4 IUI attempts are recommendable. The chances of getting pregnant increase with each insemination cycle, but they level off after the fourth attempt.

Get more info by clicking the following link: What Is Artificial Insemination (AI)? – Process, Cost & Types.

In Vitro Fertilization (IVF)

When previous IUI cycles have failed, or if the intended mother is 36 or older, the first choice is IVF.

The success rates of IVF are much higher than those of IUI. Additionally, it offers more information as regards the potential causes of infertility in the couple.

IVF allows the specialist to evaluate under the microscope the oocytes, and the resulting embryos in order to classify them according to their quality.

The embryo with the best quality will be chosen for being transferred back to the womb of the intended mother, so that it hopefully implants and marks the beginning of a new pregnancy.

Whether you need to undergo IUI or IVF to become a mother, we recommend that you use "The Calculator". In 3 simple steps, it will show you a list of clinics that fit your preferences and meet our strict quality criteria. Moreover, you will receive a report via email with useful tips to visit a fertility clinic for the first time.

Also, the report will inform you about the promotions or special prices that the clinics selected offer so you can benefit from them as well.

Additional testing

When none of the methods listed above work, your doctor may refer you to a series of additional tests, often the most technically challenging ones. The following are the most common:

Karyotyping
It is a genetic test used to see the structure and the number of chromosomes, as well as to see potential abnormalities, including duplications, inversions, etc.
PGD/PGS
A genetic test of embryos that is performed in IVF procedures. It allows the specialist to see healthy embryos and select them for the transfer, whilst dismissing unhealthy embryos (with genetic abnormalities).
ERA test
To evaluate endometrial receptivity, and determine the most adequate moment for the embryo transfer.
Tests for thrombophilia
Blood clotting disorders can lead to repeated implantation failure (RIF), or recurrent miscarriages, only detectable with these tests.
Donor eggs and/or sperm
If the cause of infertility is impossible to detect, or when none of the treatments already explained works, moving on to donor gametes (eggs and/or sperm) can be used as the last resort.

Unfortunately, unexplained infertility is one of the most disappointing diagnoses for couples who have been trying for a baby for years.

Not being able to discover the reason why pregnancy doesn’t occur, and therefore being unable to find a viable solution creates a great level of distress in these patients, hence the need for psychological support in most of the cases.

FAQs from users

Is natural pregnancy possible with unexplained infertility?

By Zaira Salvador BSc, MSc (embryologist).

Yes. Surprisingly, some couples who have been trying to conceive for a long time manage to achieve pregnancy naturally all of a sudden.

Obviously, this can only happen in those cases where the cause of infertility is a mild-to-moderate one. Oftentimes, the cause has a psychological origin when this occurs.

How can I overcome unexplained infertility?

By Zaira Salvador BSc, MSc (embryologist).

The most important thing one can do to overcome infertility after having been trying to get pregnant for a long time is to visit a specialist who is well-versed in the field of infertility.

What we recommend is that you look for trustworthy fertility clinics, and then follow all instructions given by the doctor taking care of you. It’s likely to be a long journey, with many tests required, but it’s important that you keep calm all the way.

We can help you take the first step with “The Calculator”, a useful tool that will provide you with a list of recommended clinics, tips, and cost estimates to help you get started.

Suggested for you

The first time a woman visits a fertility clinic, they will be required to undergo a series of diagnostic tests in order for the right treatment option to be recommended. Check them out: Female Fertility Tests – How Do You Know if You Can’t Get Pregnant?

As regards men, a series of tests are required as well. Recommended reading: Male Fertility Testing – How Do You Know if You Are Infertile?

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References

Aboulghar, MA, Mansour RT, Serour GI, Amin Y, Ramzy, AM, Sattar MA and Kamal, A (1999). Management of long-standing unexplained infertility: a prospective study. Am K. Obstet. Gynecol.

Gleicher N, Barad D. Unexplained infertility: Does it really exist? Hum Reprod 2006; 21: 1951-55.

Pandian Z, Gibreel A, Bhattacharya S. In vitro fertilisation for unexplained subfertility. Cochrane Database of Systematic Review 2015, Issue 11. Art. No.: CD003357.

Pashayan N, Lyratzopoulos G, Mathur R (2006). Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility. BMC Health Serv Res; 6: 80.

Authors and contributors

 Zaira Salvador
BSc, MSc
Embryologist
Bachelor's Degree in Biotechnology from the Polytechnic University of Valencia (UPV). Embryologist specializing in Assisted Procreation, with a Master's Degree in Biotechnology of Human Assisted Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI). More information
License: 3185-CV
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