Unexplained infertility is a diagnosis given to couples who are unable to conceive despite having normal results from standard fertility tests. It accounts for approximately 10-30% of infertility cases. When all known causes of infertility, such as ovulatory disorders, blocked fallopian tubes, low sperm count, or poor sperm motility, have been ruled out, and yet conception does not occur, the diagnosis of unexplained infertility is often given.
This article will discuss the potential reasons behind unexplained infertility, the diagnostic challenges, and available treatment options.
What is Unexplained Infertility?
Unexplained infertility is defined by the absence of an identifiable cause after thorough fertility evaluation. Both partners typically undergo standard tests to assess reproductive function:
- For women: Ovulatory function, ovarian reserve, and the health of the uterus and fallopian tubes are evaluated.
- For men: Semen analysis is performed to assess sperm count, motility (movement), and morphology (shape).
In cases of unexplained infertility, all of these tests return normal results, yet conception does not occur after a year or more of trying (or six months if the woman is over 35). Despite no apparent abnormalities, something is still preventing pregnancy.
Potential Causes of Unexplained Infertility
While traditional fertility tests may not pinpoint an exact problem, unexplained infertility does not mean there is no underlying cause. Instead, it suggests that current medical testing may not be advanced enough to detect certain subtle or complex issues. Below are several potential reasons that may contribute to unexplained infertility:
1. Subtle Ovulatory Dysfunction
Ovulation is a complex process, and while a woman may appear to be ovulating regularly, there can be underlying issues with the quality of the eggs released or the timing of ovulation.
- Luteinised Unruptured Follicle Syndrome (LUFS): This is a condition in which a follicle matures, but the egg is not released, even though hormone levels suggest ovulation has occurred. This can prevent fertilisation despite normal menstrual cycles.
- Suboptimal Hormone Levels: Slight hormonal imbalances that are not detected by routine blood tests could affect the maturation of eggs or the uterine environment, making it more difficult to conceive.
2. Poor Egg Quality
Even if a woman is ovulating regularly and appears to have a good ovarian reserve, the quality of the eggs could be poor. This is particularly true for women in their late 30s or 40s, where aneuploidy (abnormal chromosome numbers in eggs) becomes more common.
- Poor egg quality may not be detected by standard fertility tests but can result in eggs that are less likely to be fertilised or that lead to abnormal embryos, which fail to implant or cause miscarriage.
3. Sperm Dysfunction
A normal semen analysis primarily looks at sperm count, motility, and morphology. However, these basic parameters do not always reveal deeper sperm issues that could contribute to infertility.
- Sperm DNA Fragmentation: Even if sperm appear normal in shape and function, they may carry damaged or fragmented DNA, which can impair the ability to fertilise an egg or result in embryos that cannot develop properly.
- Capacitation Defects: Capacitation is the process by which sperm become capable of fertilising an egg. Subtle defects in this process could prevent fertilisation from occurring, even when the sperm appears healthy under a microscope.
4. Fertilisation and Embryo Development Issues
Fertilisation is a complex process, and problems with either fertilisation or early embryo development can contribute to unexplained infertility. These issues are difficult to detect without advanced testing or IVF.
- Oocyte Activation Failure: After sperm penetrates an egg, the egg must activate and complete its development. If this process fails, fertilisation does not result in a viable embryo.
- Embryo Arrest: Even after successful fertilisation, embryos may stop developing early in the process, making implantation impossible.
5. Implantation Failure
Implantation is when the fertilised embryo attaches to the uterine wall to begin pregnancy. Several subtle factors could lead to implantation failure, which may not be picked up in routine tests.
- Endometrial Receptivity Issues: The lining of the uterus, known as the endometrium, needs to be properly prepared to allow an embryo to implant. Minor abnormalities in the uterine lining, such as insufficient thickness or hormonal imbalances, can prevent successful implantation.
- Immune System Dysfunction: Some women may have immune system issues that lead to their body attacking the embryo, preventing implantation. This includes natural killer (NK) cells or autoimmune disorders that may cause the body to reject a developing embryo.
Cervical mucus plays a crucial role in helping sperm travel from the vagina into the uterus. It can act as a barrier or facilitator for sperm, depending on its quality and consistency.
- In some cases, hostile cervical mucus, which is too thick, acidic, or contains antibodies that attack sperm, may prevent sperm from reaching the egg.
While fallopian tubes may appear normal in imaging tests, subtle dysfunctions in the cilia (small hair-like structures that help transport the egg) could prevent the egg from reaching the uterus or sperm from reaching the egg.
8. Lifestyle and Environmental FactorsUnexplained infertility could also be the result of several external factors that are not detectable in typical fertility evaluations.
- Stress: Chronic stress can disrupt the hormonal balance necessary for ovulation and conception.
- Environmental Toxins: Exposure to environmental chemicals such as pesticides, endocrine-disrupting chemicals, or heavy metals can negatively affect reproductive health in both men and women, even at low levels.
Diagnosis of Unexplained Infertility
A diagnosis of unexplained infertility is typically made after a couple undergoes standard fertility testing, which includes:
- Ovulation Tests: To confirm regular ovulation (e.g., blood tests for hormone levels like luteinizing hormone [LH] and progesterone).
- Semen Analysis: To check for sperm quantity, motility, and morphology.
- Hysterosalpingography (HSG): An X-ray procedure to evaluate the health of the fallopian tubes and uterus.
- Ultrasound: To look for ovarian cysts, uterine fibroids, or other structural issues.
- Ovarian Reserve Testing: Blood tests for Anti-Müllerian Hormone (AMH) levels and follicle-stimulating hormone (FSH) to assess ovarian reserve.
- Laparoscopy: In some cases, a laparoscopy may be performed to look for conditions like endometriosis, which may not show up on other tests.
If all of these tests return normal results, a diagnosis of unexplained infertility is typically made.
Treatment Options for Unexplained Infertility
Although unexplained infertility can be frustrating, various treatment options are available. The choice of treatment often depends on factors such as the woman's age, the duration of infertility, and personal preferences.
1. Lifestyle ChangesFor some couples, addressing lifestyle factors may help improve fertility outcomes:
- Diet and Exercise: Maintaining a healthy weight, eating a balanced diet rich in antioxidants, and regular exercise may improve fertility.
- Stress Reduction: Managing stress through practices such as yoga, meditation, or counselling can have a positive effect on fertility.
For couples with unexplained infertility, medications that stimulate ovulation, such as clomiphene citrate (Clomid) or letrozole, can help increase the chances of conception. These medications are often combined with timed intercourse to increase the likelihood of fertilisation.
3. Intrauterine Insemination (IUI)IUI involves placing sperm directly into the uterus around the time of ovulation, bypassing the cervix to increase the chances of fertilisation. It is often combined with ovulation induction to improve success rates.
- This method helps if there are issues with cervical mucus, sperm transport, or subtle male infertility factors.
IVF is a more advanced fertility treatment and is often recommended when simpler treatments are unsuccessful. It involves stimulating the ovaries to produce multiple eggs, retrieving those eggs, fertilising them with sperm in a laboratory, and then transferring one or more embryos into the uterus.
- IVF is particularly useful for detecting problems with fertilisation or embryo development, which may not be apparent in standard testing.
- Preimplantation Genetic Testing (PGT) can be done to screen for chromosomal abnormalities in embryos before they are implanted, improving the chances of a successful pregnancy.
If unexplained infertility persists despite treatment, laparoscopy may be performed to look for subtle issues such as endometriosis, pelvic adhesions, or tubal abnormalities that may not have been detected with less invasive tests.
6. Advanced Sperm Function TestsIn some cases, further testing of sperm quality may be needed. Sperm DNA fragmentation tests or other advanced sperm function tests may reveal previously undetected male fertility issues.
Prognosis for Couples with Unexplained Infertility
Despite the frustration of not knowing the specific cause of infertility, the outlook for couples with unexplained infertility is generally positive. Many couples go on to conceive, either naturally or with the help of fertility treatments.
- Studies show that 30-50% of couples with unexplained infertility will conceive naturally within three years without treatment, although the chances decrease as the woman’s age increases.
- Treatments such as IUI and IVF have good success rates, particularly in younger women or those with shorter durations of infertility.
Conclusion
Unexplained infertility can be a frustrating diagnosis, as it offers no clear answers as to why conception is not occurring. However, it does not mean that treatment is hopeless. There are likely underlying reasons for unexplained infertility, including subtle ovulatory or sperm dysfunctions, issues with egg or embryo quality, implantation failures, or lifestyle factors.
Understanding that unexplained infertility is a common challenge for many couples can help those facing this diagnosis remain hopeful on their journey to parenthood.
