What Is Unexplained Infertility?

Being told you have unexplained infertility can be upsetting and frustrating, yet it is one of the most common diagnoses in fertility care. Despite the uncertainties unexplained infertility may bring, it does not mean you have to give up your dreams of parenthood. Conception is a complex process, and just because you haven’t become pregnant yet, it doesn’t necessarily mean that you won’t. The path may not be easy, but the availability of modern fertility treatments has helped many people become parents.

Infertility is when a couple fails to achieve pregnancy after one year (or more) of having regular unprotected intercourse. However, for women over the age of 35 years, healthcare professionals often advise starting infertility assessments after six months of unsuccessful attempts to achieve a pregnancy. Infertility is said to be unexplained when all standard fertility tests return normal results, showing no cause to explain the infertility in either partner. Between 15% and 30% of couples experiencing infertility will be diagnosed with unexplained infertility after their diagnostic assessment.¹

This article explores unexplained infertility, a condition affecting a notable proportion of couples dealing with fertility issues. It outlines the diagnostic tests employed, potential causes, and the available treatment options, including IUI and IVF. Additionally, it touches upon the emotional aspects of unexplained infertility and the benefit of seeking support during this process.

How is unexplained infertility diagnosed?

The American Society for Reproductive Medicine (ASRM) has shared guidelines for a typical infertility assessment that should include the following tests: 

• Semen analysis
• Ovulation assessment
• Evaluation for ovarian reserve testing (an estimate of the number of eggs left in a woman’s pair of ovaries that affect her ability to conceive)
• X-ray test to check your uterus and fallopian tubes (Hysterosalpingogram)    
• Laparoscopy -a surgical procedure that involves inserting a thin lighted tube with a camera through small incisions in the abdomen to check the organs in the abdomen. 

When these tests show normal results, healthcare professionals diagnose unexplained infertility.

Commonly used tests to diagnose unexplained infertility

Semen analysis

Approximately 30% of couples encounter infertility related to men's problems, while in another 20–30%, the male factor contributes to the couple’s fertility issues.

A semen analysis, done using a microscope, checks the volume and quality of a man’s sperm. It evaluates key factors such as the number, motility (movement) and morphology (shape) of the sperm cells, all of which are important in achieving a successful pregnancy.

Some men may receive a diagnosis of a low sperm count, indicating that they have fewer than 15 million sperm per ml or less than 39 million sperm total per release.

The lower the sperm count, the lower the chances of achieving a pregnancy. However, some men with low sperm counts successfully become parents without any treatment.

In some instances, there may be an absence of sperm in the ejaculate, a condition known as azoospermia.

It is important to consult with a fertility specialist to explore options and discuss treatment if needed.

Ovulation assessment

About 40% of women who face difficulties getting pregnant and 15% of couples facing infertility have problems with ovulation (the release of an egg from one of the ovaries). This often shows up as irregular periods.

If you have irregular cycles, your doctor will check for conditions like polycystic ovarian syndrome, high levels of prolactin (a hormone involved in making breast milk), problems with your thyroid or hormonal issues resulting from changes in body weight.

If your periods are regular, it is a good sign that you ovulate consistently. But if you are unsure, there are several methods available to confirm whether or not ovulation is happening. These include tracking your basal body temperature (your body’s temperature at rest), using ovulation predictor kits that measure luteinizing hormone (LH) in your urine and measuring the levels of a hormone called progesterone on cycle day 21.

For women with irregular cycles, it is recommended to use an ovulation kit and measure the levels of progesterone levels 7 or 8 days after a surge in LH is detected.¹

Ovarian reserve assessment

Your doctor may recommend a blood test to assess your ovarian reserve. This test measures two key hormones:

• Follicle-stimulating hormone (FSH) is responsible for controlling the growth of eggs in your ovaries. This is usually measured on the third day of your menstrual cycle 
• Anti-Mullerian Hormone (AMH) which is produced by the follicles in your ovaries and can be measured on any day of your cycle.

Ovarian antral follicle counting is a supplementary test also used by healthcare professionals to assess women’s ovarian reserve. This test uses transvaginal ultrasound to count the antral follicles (the small sacs filled with fluid where your eggs are stored) in your ovaries, giving you an estimate of the number of eggs in your ovaries.

Hysterosalpingography (HSG)

Hysterosalpingography (HSG) is a specialist type of X-ray examination used to look at the inside of your uterus and fallopian tubes. It is a typical way to view whether your uterus is normal and determine if your fallopian tubes are damaged, fully or partly blocked, or if there is any tissue sticking to them (adhesions). 

The American College of Obstetricians and Gynecologists states that uterine or fallopian tube scarring and abnormalities can cause infertility and pregnancy problems.

Laparoscopy

Laparoscopy is considered the most reliable method for evaluating problems related to the fallopian tubes and uterus. Nevertheless, HSG is often the first choice for many patients and doctors due to its lower cost, less invasive nature, and the fact that it doesn't require anaesthesia or a hospital stay. ²

What are the possible reasons for unexplained infertility? 

The exact cause of unexplained infertility is not known. Potential reasons for unexplained infertility may include:

• An undiagnosed pre-existing condition. An undiagnosed condition, for example, an autoimmune disease, can reduce your chances of getting pregnant or even cause infertility.
• Endometriosis. Specialists in fertility suggest that there is a link between endometriosis and infertility, and even mild cases of this condition can make it more difficult to get pregnant.³
• Egg quality. Many are aware that egg quality and quantity decline with age. While the egg quantity can be measured, the quality can only be guessed from a woman’s age and the reproductive outcome, whether successful or not.⁴
• Sperm quality. Even if the results from the semen analysis come back normal, there may be other problems with sperm contributing to unexplained infertility.
• Cervical mucus. During ovulation, your cervical mucus becomes thinner so sperm can swim upstream and reach the egg. If there are any problems with your cervical mucus, this could potentially affect your fertility.
• Not having intercourse in the fertile window. Having intercourse during the fertile window is crucial. Conception can only occur from roughly five days before up to several hours after ovulation.

Management and treatment of unexplained infertility

Is there anything I can do to improve my chances of getting pregnant?

There are a few things you can do to increase your odds of conceiving:

• Avoid smoking, alcohol, and recreational drugs
• Maintain a healthy body weight
• Exercise regularly (at least 30 minutes per day)
• Eat a healthy, balanced diet
• Minimise stress
• Reduce caffeine intake (Cleveland Clinic).

What are the treatments available for unexplained infertility?

Since there is no specific cause for infertility, your treatment will be mostly empiric, meaning that your doctor will use their experience with couples who share similarities with you. Assisted reproductive technologies (ART), Intrauterine insemination (IUI) and in-vitro fertilization (IVF) are widely used treatments for unexplained infertility.

IUI

IUI is a type of fertility treatment, often the first used for unexplained infertility, in which washed sperm (specially prepared to separate the healthy, motile sperm cells from the others) is injected into the uterus around the time of egg release. It can be done alongside natural ovulation or ovulation induction using medications such as clomiphene citrate or injectable gonadotropins.¹

IVF/ICSI

IVF is another type of ART in which the embryos are formed outside the body.  This process involves using both your eggs and your partner's sperm. In some instances, a donor’s sperm or eggs can be used. Mature eggs are collected from the ovaries and fertilised by sperm in a lab. A few days after fertilisation, the fertilised eggs (embryos) are moved to your uterus to grow. IVF is often complemented with intracytoplasmatic sperm injection (ICSI), a technique where a single sperm is directly injected into the centre of the egg. ICSI is particularly beneficial when infertility is linked to sperm quality issues.

While the majority of couples facing unexplained infertility eventually achieve parenthood, the process can be emotionally and physically demanding, especially for women undergoing fertility treatments like IVF. This path may sometimes lead to feelings of loneliness and isolation. In such situations, finding support is essential. Speaking to a mental health professional, such as a counsellor, or participating in online support forums can offer valuable guidance and emotional help.

5) Add a header called “Summary” at the end of the article, discussing the key points and anything else you think needs to be added. 

Summary

Unexplained infertility occurs when standard fertility tests yield normal results, affecting 15% to 30% of couples among those experiencing infertility. It is often diagnosed after a year of unsuccessful attempts to conceive (or six months for women over 35).

Potential causes include undiagnosed conditions, endometriosis, age-related egg quality decline, and subtle sperm issues. Treatment typically involves empirical approaches, where the doctor draws from experience with similar cases. Intrauterine Insemination (IUI) is a treatment option that injects prepared sperm into the uterus during natural or medicated ovulation. By comparison, Vitro Fertilization (IVF), sometimes with Intracytoplasmic Sperm Injection (ICSI), is considered when sperm quality is a concern.

While many couples with unexplained infertility eventually achieve parenthood through these treatments, the emotional and physical toll can be challenging. Seeking support from mental health professionals or online forums can be invaluable during this journey.