What is infertility?

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Infertility is defined as the inability to conceive after one year of unprotected intercourse for women less than 35 years of age and after six months for women 35 years and older.^viii  Women over 35 years meet the diagnostic criteria in a shorter time period, which allows for medical intervention to be sought sooner (due to the negative effect of increasing female age on fertility, as described below).  

Infertility can be further subdivided into two main categories: primary infertility and secondary infertility. Primary infertility is defined as the inability to achieve a first pregnancy despite one year of unprotected intercourse. Secondary infertility is defined as 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, infertility can be a result of female factors, male factors, or both. It is estimated that 40 percent of the time, the inability to conceive is due solely to female infertility, while 20 percent of the time the inability to conceive is due solely to male infertility. Furthermore, 40 percent of the time both male and female factors lead to infertility.^ixSome individuals may be unclear on the difference between subfertility, infertility, and sterility. The terms subfertility and infertility essentially mean the same thing, and can be used to describe couples who have a significant delay in conceiving or who require medical assistance to achieve a pregnancy. It is important to note that a diagnosis of infertility (or subfertility) is different than sterility, as many of these couples are eventually able to achieve a successful pregnancy with the former, with or without assisted reproductive techniques. It has been suggested that the term “subfertility” should no longer be used since it is redundant with the term “infertility”.^xBy 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 a woman or couple is dealing with this situation, it is best to consult with a fertility specialist to determine next steps.

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

Age is one of the biggest factors contributing to fertility challenges, largely because the quality and quantity of eggs decline as females age. 

In women, a decline in egg quality (due to an increase in chromosomal error in the egg) typically begins around age 34-35 years and continues to decline over time.^xi,xii This effect of increasing female age on chromosomal errors is the primary reason that achieving a successful pregnancy becomes more difficult as women age. For example, women 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 35yr.^xiii By the time a woman is 40 years old, the chance of conception per cycle is 5 percent, again typically driven by age-related decline.^xiv

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

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Table 1. Age-related decline in female fecundity. The data is based on a sample of 2 962 heterosexual couples trying to conceive naturally.

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

Men, on the other hand, generate new sperm throughout their entire life. For this reason, age does not have as significant of an effect on 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 smaller effect on natural fertility compared to the effect of female age.  

While age is the most important factor affecting fertility—especially among women—there are some lifestyle factors shown to affect both male and female fertility. These include:

• Obesity: Women and men 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 was associated with improved fertility in women and improved semen quality in men in some studies.^xxii Conversely, diets high in saturated fats and sugar are associated with poorer fertility outcomes in both men and women.^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
• While the effects of alcohol on fertility continue to be studied, 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 affect male or female fertility.^xxviii,xxix

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What causes infertility for women?

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

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Often female factor infertility is categorized based on female reproductive anatomy, 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.  

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Infertility related to the fallopian tubes

• Blocked fallopian tubes. Examples causing blocked tubes include: endometriosis (described below), pelvic inflammatory disease (PID, described below), previous ectopic pregnancy managed by fallopian tube removal.

Infertility related to the uterus or cervix

• Fibroids: these are common benign (non-cancerous) growths on the uterus. In many cases, fibroids are not large or numerous enough to cause any symptoms or infertility. However, sometimes they may cause infertility by preventing the embryo from successfully implanting in the uterus.^xxxi‍
• Polyps
• Cervical stenosis: this is a condition in which the opening to the cervix is abnormally narrow. This 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
• PID and endometriosis (described below)

Infertility related to the ovaries

• Premature ovarian insufficiency
• Polycystic ovarian syndrome (PCOS described below)

Hormone-related infertility

• Hypothyroidism (described below)
• Hyperprolactinemia  

In 10-30 percent of couples who are unable to conceive, no underlying causes are identified. This is called unexplained infertility.^xxxii,xxxiii

The following are some of the medical conditions that may be diagnosed in those with infertility (not selected based on prevalence):  

Endometriosis

Endometriosis is a condition in which endometrial tissue, which is 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 women between the ages of 25-35, 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 30-50 percent of women with endometriosis experience infertility.^xxxvi This is because 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 women 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 woman to woman.  

In PCOS, the hormonal milieu produced by the ovaries is altered, often reflected by an increase in androgen production. This may lead to irregular menstrual cycles and obesity, as well as signs of masculinization such as male-pattern hair growth. This can also lead to the development of many small antral follicles that give the ovaries a classic “string of pearls” appearance on ultrasound. The name “polycystic” ovarian syndrome comes from the appearance of the ovaries; however, it is important to note that these are not actually cysts, they are indeed all oocyte-containing follicles. In addition, women diagnosed with PCOS are at increased risk of developing high cholesterol, high blood pressure, diabetes, mood disorders, and obstructive sleep apnea.^xxxix

Statistics show that 70 percent of women diagnosed with PCOS experience infertility—roughly 15 times more than women 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.

Hypothyroidism

Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone. This sometimes happens when a person’s immune system mistakenly attacks the thyroid, this being a type of autoimmune disease called Hashimoto’s thyroiditis (the most common cause of hypothyroidism). Other causes of hypothyroidism in adults include the use of certain medications, surgery or radiation used to treat thyroid cancer or hyperthyroidism (overactive thyroid gland).

Hypothyroidism can cause infertility when it creates hormonal fluctuations that alter the menstrual cycle as well as imbalances that prevent the release of an egg from the ovary.^xli Women with untreated hypothyroidism are also more likely to have a miscarriage. For example, women diagnosed with Hashimoto’s thyroiditis have double the risk of recurrent miscarriages.^xlii

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 disease include short stature, heart and kidney malformations, high blood pressure, diabetes, hearing loss, neck webbing, and skeletal abnormalities.  

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

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What causes infertility for men?

In approximately 20 percent of cases, a couple’s infertility is the sole result of male factors and a contributing factor in another 40 percent of cases.^xlivIn men, infertility can be caused by a variety of reasons, including sperm and/or semen issues, 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 Below are additional details on some of these factors associated with male infertility.

Sperm and semen quality

Sperm and semen issues generally revolve around primary problems with the sperm itself.^xlvi This can be caused by a variety of factors, including endocrine, genetic, and anatomical disorders, but often the cause is unknown. Doctors assess sperm and semen quality with a semen analysis, which may reveal problems such as:  

Azoospermia: no sperm is found in the semen

Oligospermia: lower than normal quantity of sperm seen in ejaculate

• Mild: 10-20 million sperm/mL of semen
• Moderate: 5-10 million sperm/mL
• Severe: <5 million sperm/mL

Hypospermia: low semen volume, defined as <1.5 mL per ejaculation

Cryptoozospermia: very low sperm concentration in the ejaculate (less than 100,000 per mL), which can only be found after centrifuging the sample^xlviiPyospermia or leukospermia: a high number of white blood cells are found in the semen^xlviii

Erectile dysfunction

Erectile dysfunction (ED) is a common condition which can be caused by psychological, neurological, cardiovascular, or hormonal factors. While men with erectile dysfunction often have no issues with sperm or semen, treatment for erectile dysfunction is often required to help with 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 the majority of men with a varicocele do not have infertility, it can be a factor even though the exact cause of infertility in males with varicoceles is not entirely known. 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 palpable.^li

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

Klinefelter syndrome

Klinefelter syndrome is the most common sex chromosomal disorder in men, affecting about 1 in 660 males. Men with Klinefelter syndrome are born with an extra X chromosome. These individuals may exhibit signs and symptoms such as small testicular size, learning disabilities, breast enlargement, increased height, obesity, diabetes, and undescended testicles.^liii,livInfertility affects about 91-99 percent of men with Klinefelter syndrome, and more than 95 percent of men with Klinefelter syndrome have azoospermia.^lv

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When should I see a fertility doctor?

Women younger than 35 years should see a fertility doctor if they have been trying to conceive for one year. Women 35 years and older should be evaluated if they have not had a successful pregnancy after six months of trying to conceive. More immediate evaluation by an infertility doctor may be warranted in women over 40 years or in women with a medical, sexual, or reproductive history that is associated with impaired fertility.^{lvi,lvii,lviii,lix}

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Conclusion

With a doctor’s help, one can learn what factor or factors are making it difficult to conceive, and then work with the doctor to map out a plan that includes the right combination of fertility treatments.^lx,lxi

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