What is infertility?

Infertility is defined as the inability to conceive after one year of unprotected heterosexual intercourse for females less than 35 years of age and after six months for females 35 years and older.^viii Individuals over 35 years meet the diagnostic criteria in a shorter period due to the negative effect of increasing female age on fertility. They can then seek medical intervention sooner. Infertility can be further subdivided into two main categories:

• ‍Primary infertility: The inability to achieve a first pregnancy despite one year of unprotected intercourse.
• ‍Secondary infertility: The inability to conceive despite one year of unprotected intercourse and despite having previously achieved a pregnancy and live birth.

Among couples trying to conceive, causes of infertility can be related to female factors, male factors, or both. It is estimated that the inability to conceive is due solely to female infertility in 40 percent of cases. In 20 percent of cases, the inability to conceive is due solely to male infertility. The remaining 40 percent of the time, both male and female factors lead to infertility.^ix

People sometimes confuse the terms subfertility, infertility, and sterility. Subfertility and infertility are essentially the same thing and describe couples who experience a significant delay in conceiving or who require assisted reproductive technology (ART) to achieve a pregnancy. It is important to note that an infertility (or subfertility) diagnosis is different than sterility, which is the inability to produce a live child. Many couples experiencing infertility or subfertility are eventually able to achieve a successful pregnancy, with or without assisted reproductive techniques. The International Glossary on Infertility and Fertility Care argued in 2017 that the term “subfertility” is redundant, and “infertility” should be used exclusively instead.^x

By definition, any prolonged, unwanted period of not being able to conceive, despite having appropriately timed intercourse, is one of the key signs of infertility in a couple. If an individual or couple faces difficulty conceiving, it is best to consult with a fertility specialist to determine next steps.

What is the role of age in fertility for women and men?

Age is one of the most significant factors to affect fertility, largely because the quality and quantity of eggs decline as females age.   

A decline in egg quality (due to an increase in chromosomal errors in the egg) typically begins around age 34 to 35 years and continues over time.^xi,xii It is the primary reason that achieving a successful pregnancy becomes more difficult with age. For example, females in their 20s have a 25 percent chance of getting pregnant per cycle if they are trying to conceive. The chance of conceiving gradually decreases to approximately 15 percent by age 35.^xiii By the time someone is 40 years old, the chance of conception per cycle is 5 percent.^xiv

These figures are only estimated averages and may not apply to everyone. Many individuals in their late 30s and even early 40s conceive within the first few months of trying, while some people may have premature age-related fertility issues in their early 30s. Additionally, these numbers do not consider people who have impaired fertility or challenges in carrying a baby to term.^xv

At birth, females have approximately 1 million eggs in their ovaries. No new eggs are generated after birth, and the number declines over time down to about 1,000 eggs at menopause.^xvi When the number or quality of oocytes is reduced such that it results in a reduction in fertility, the result is diminished ovarian reserve.^xvii Reductions in ovarian reserve do not usually cause infertility until the reserve is low enough that the time between each ovulation is prolonged, which results in irregular or no menstrual cycles.

Males, on the other hand, generate new sperm throughout their entire life. For this reason, age does not significantly affect sperm production and male fertility. While there is a general decline in sperm quantity and quality over time, the total number of sperm produced typically remains quite high.^xviii,xix Therefore, increasing male age has a lesser effect on natural fertility compared to the effect of female age.

While age is the most crucial factor affecting fertility — especially among females — there are some lifestyle factors shown to affect fertility in both males and females. Here are some examples:

• ‍Obesity: Individuals who are obese are more likely to be diagnosed with infertility. Obesity impacts hormone production, which can have detrimental effects on a person’s ability to conceive.^xx,xxi
• ^‍Diet: Eating a healthy, balanced diet that includes whole grains, vegetables, and fish is associated with improved female fertility and improved semen quality in males in some studies.^xxii Conversely, diets high in saturated fats and sugar are associated with poorer fertility outcomes in both sexes.^xxiii
• ^‍Sexually transmitted infections (STIs): Prior exposure to STIs such as gonorrhea and chlamydia may lead to infertility in both male and female patients.^xxiv,xxv
• ^‍Alcohol: While the effects of alcohol on fertility continue to be explored, some studies suggest that heavy drinking may have negative effects on fertility,^xxvi,xxvii while other studies suggest that lower alcohol consumption does not appear to have an effect.^xxviii,xxix

What causes infertility for women?

There are multiple causes of female infertility. Collectively, these causes are known as female factor infertility. It is estimated that about 40 percent of cases of infertility among couples are due to female factors alone.^xxx

Often female factor infertility is categorized based on the reproductive system, such as conditions of the fallopian tubes, the uterus and/or cervix, and/or ovaries. Other causes of infertility may be hormone-related, which can affect any of these reproductive structures.

• ‍Infertility related to the fallopian tubes
  • Blocked fallopian tubes: Endometriosis (described below), pelvic inflammatory disease (PID, described below), and previous ectopic pregnancy managed by fallopian tube removal can all result in blocked tubes.
• ‍Infertility related to the uterus or cervix
  • Fibroids: These benign (non-cancerous) growths on the uterus are common. In many cases, fibroids are not large or numerous enough to cause any symptoms or infertility. However, sometimes they cause infertility by preventing the embryo from successfully implanting in the uterus.^xxxi
  • ^‍Polyps: Uterine polyps, also known as endometrial polyps, are atypical growths in the lining of the uterus. They often have no negative effects, but in some cases can impact menstruation and fertility.
  • ‍Cervical stenosis: This condition, in which the opening to the cervix is abnormally narrow, may interfere with sperm transport through the cervix into the uterus. Cervical stenosis can be either congenital (something you are born with) or acquired due to an infection or trauma.
  • ‍Uterine or cervical cancer
  • Endometriosis and pelvic inflammatory disease (PID): Described below
• ‍Infertility related to the ovaries
  • Primary ovarian insufficiency (POI): Formerly called premature ovarian failure, this condition occurs when the ovaries stop working effectively before age 40.
  • ‍Polycystic ovary syndrome (PCOS): Described below
  • Turner syndrome: Described below
• ‍Hormone-related infertility
  • Hypothyroidism: Described below
  • ‍Hyperprolactinemia: This condition is marked by elevated levels of the hormone prolactin.

Between 10 to 30 percent of couples who are unable to conceive have unexplained infertility, which means no underlying causes have been identified.^xxxii,xxxiii

Below are some of the medical conditions (not selected based on prevalence) that may be diagnosed in females with infertility.

Endometriosis

Endometriosis is a condition in which endometrial tissue (the tissue that comprises the lining of the uterus) implants outside of the uterine cavity. This abnormally located endometrial tissue typically grows inside the pelvis, most often along the ovaries, fallopian tubes, ligaments that support the uterus, and even the rectum, bladder, and intestines.^xxxiv

Endometriosis affects about 10 percent of females between the ages of 25 to 35, although there is some controversy over the true prevalence since the condition is difficult to diagnose without performing abdominal surgery to directly visualize the tissue.^xxxv For example, some patients with endometriosis do not have any symptoms, and the condition might only be discovered incidentally, such as when surgery is performed for other reasons. Patients who do have symptoms of endometriosis often present with cyclic pelvic pain that occurs during menses and pain with intercourse.

It is estimated that 30 to 50 percent of people with endometriosis experience infertility.^xxxvi Ectopic endometrial tissue can distort or obstruct the fallopian tubes, disrupt the uterus and ovaries, and create a hostile or inflamed environment that can inhibit conception.^xxxvii

Pelvic inflammatory disease

Pelvic inflammatory disease (PID) is a severe infection of the uterus, cervix, fallopian tubes, and pelvic cavity that can be caused by sexually transmitted infections (STIs). The most common STIs associated with PID are Chlamydia trachomatis, Neisseria gonorrhea and Mycoplasma genitalium, as well as bacterial vaginosis-associated microorganisms. Fortunately, while many females contract an STI in their lifetime, the incidence of PID with an STI is low.

PID can cause severe scarring of the uterine lining, fallopian tubes, and ovaries, which can lead to infertility or ectopic pregnancy, as well as chronic pelvic pain. PID can also lead to an abscess (collection of pus) on the ovary or fallopian tube, which can cause a life-threatening emergency if the ovary or tube ruptures as a result.^xxxviii

PCOS

Polycystic ovary syndrome (PCOS) is a condition related to dysfunction of the ovaries. PCOS can present with many symptoms that can vary from person to person.  

In PCOS, the hormonal milieu produced by the ovaries is altered, often reflected by an increase in androgen production. The side effects may include irregular menstrual cycles, obesity, and signs of masculinization such as male-pattern hair growth.

PCOS can also lead to the development of many small antral follicles that give the ovaries a classic “string of pearls” appearance on an ultrasound. The name “polycystic” ovary syndrome comes from the appearance of the ovaries; however, it is important to note that the “pearls” are oocyte-containing follicles, not actual cysts.

Females diagnosed with PCOS are also at increased risk of developing high cholesterol, high blood pressure, diabetes, mood disorders, and obstructive sleep apnea.^xxxix

Statistics show that 70 percent of females diagnosed with PCOS experience infertility — roughly 15 times more than females without PCOS.^xl In these cases, infertility is most often due to prolonged periods of time between each ovulation, which is reflected by irregular or sometimes a total lack of menstrual cycles.

Turner syndrome

Turner syndrome is a congenital condition that affects females and is caused by the full or partial deletion of one of the X chromosomes. Patients with Turner syndrome have a single X chromosome instead of the normal two X chromosomes, and a total of 45 chromosomes instead of 46. The severity of symptoms associated with Turner syndrome varies, depending on whether there is a full or partial deletion of an X chromosome. Typical manifestations of the medical condition include short stature, heart and kidney malformations, high blood pressure, diabetes, hearing loss, neck webbing, and skeletal abnormalities.

Females with Turner syndrome are typically unable to conceive biological children as they have primary ovarian failure: their ovaries do not mature at the time of puberty and are incapable of ovulation.^xli

Hypothyroidism

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone. The most common cause of hypothyroidism is an autoimmune condition called Hashimoto's thyroiditis, where a person’s immune system mistakenly attacks the thyroid.  Other causes of hypothyroidism in adults include the use of surgery, radiation, or certain medications to treat thyroid cancer or hyperthyroidism (overactive thyroid gland).

Hypothyroidism can cause infertility when it creates hormonal fluctuations that alter the menstrual cycle and imbalances that prevent the release of an egg from the ovary.^xlii Females with untreated hypothyroidism are also more likely to have a miscarriage. For example, in females diagnosed with Hashimoto’s thyroiditis, the risk of recurrent miscarriages doubles.^xliii

What causes infertility for men?

In approximately 20 percent of cases, male factor infertility is the sole result of a couple’s infertility. It is a contributing factor in another 40 percent of cases.^xliv

There are a variety of reasons for male factor infertility, including sperm and/or semen issues, problems with sexual function (e.g., erectile dysfunction, premature ejaculation), anatomic abnormalities (e.g., varicocele), hormonal abnormalities, infections, genetic conditions (e.g., Klinefelter syndrome, Y chromosome genetic abnormalities), prior surgeries, cancer treatments, and other medical conditions.^xlv Additional details on some of these factors associated with male infertility are listed below.

Sperm and semen quality

Sperm and semen issues generally revolve around primary problems with the sperm cells.^xlvi An endocrine, genetic, or anatomical disorder may be to blame, but often the cause is unknown. Doctors assess sperm and semen quality with a semen analysis, which may reveal the following concerns:

• ‍Azoospermia: No sperm is found in the semen.
• ‍Oligozoospermia: A lower-than-normal quantity of sperm is seen in the ejaculate.
  • Mild: 10 to 20 million sperm/mL of semen
  • Moderate: 5 to 10 million sperm/mL
  • Severe: Less than 5 million sperm/mL
• ‍Hypospermia: There is low semen volume, defined as less than 1.5 mL per ejaculation.
• ‍Cryptoozospermia: A very low sperm concentration is found in the ejaculate (less than 100,000 per mL), which can only be discovered after centrifuging the sample.^xlvii
• ^‍Pyospermia or leukospermia: There is a high number of white blood cells in the semen.^xlviii

Erectile dysfunction

Erectile dysfunction (ED) is a common condition that can be caused by psychological, neurological, cardiovascular, or hormonal factors. While erectile dysfunction usually does not affect sperm production, treatment for erectile dysfunction is often required to allow intercourse to occur and, ideally, result in natural conception.

Varicocele

A varicocele is a cluster of abnormally enlarged or dilated veins in the scrotum. An estimated 15 percent of otherwise healthy males have a varicocele, including up to 40 percent of males presenting for evaluation of infertility.^xlix

While most males with a varicocele do not experience infertility, a varicocele can still be a factor in infertility even though the reason is not entirely understood. Some experts believe varicoceles can cause infertility by leading to increased temperature in the testicles or impaired testicular blood flow.^l Surgical correction of the varicocele should be considered in a male with infertility and abnormal semen parameters if it is possible.^li

If a varicocele occurs in childhood, it may lead to a reduction in testicular size and function. Surgery may be recommended to protect future fertility if a child has a significant size discrepancy.^lii

Klinefelter syndrome

Klinefelter syndrome is the most common sex chromosomal disorder in males, affecting about 1 in 660. These individuals are born with an extra X chromosome and may exhibit signs and symptoms such as small testicular size, learning disabilities, breast enlargement, increased height, obesity, diabetes, and undescended testicles.^liii,liv

Infertility affects about 91 to 99 percent of males with Klinefelter syndrome, and more than 95 percent of males with Klinefelter syndrome have azoospermia (no sperm in the semen).^lv

When should I see a fertility doctor?

The primary indicator is length of time trying to conceive without success. If the female partner is younger than 35 years, one year of trying is recommended. When the female partner is 35 years or older, couples should be evaluated if they have not had a successful pregnancy after six months of trying to conceive. More immediate evaluation by a fertility doctor may be warranted in females over 40 years or in individuals with a medical, sexual, or reproductive history that is associated with impaired fertility.^{lvi,lvii,lviii,lix}

Conclusion

Infertility is not a life sentence. A doctor can help to uncover any factors that are making it difficult to conceive, and then map out a plan that includes the right combination of fertility treatments.^lx,lxi