Introduction

According to studies, in each of 30-35% of cases of unfulfilled desire to have a child, a cause can be found either only in the woman or only in the man, in 20% of cases a cause can be found in both partners, and in 10-20% of cases no cause can be found.

Here we would like to give an overview of the most common causes of an unfulfilled desire to have children. Importantly, this is a patient-centered review. Before starting fertility treatment, a medical clarification of the causes of infertility should always be made, so that the treatment can be adapted as individually as possible and thus successfully to the specific situation of the patient.

Common causes in women

1. hormonal causes

Hormones play a central role in a woman’s body, especially for the menstrual cycle and ovulation. Therefore, hormonal imbalances are also among the most common causes of infertility.

1a: Polycystic ovary syndrome (PCOS)

Description: PCOS is considered one of the most common hormonal disorders in women of childbearing age. Behind the name is a hormonal disorder that causes various symptoms and in which a large number of follicular cysts form in the ovaries. The ovaries themselves may be enlarged or normal in size.

PCOS leads to disruption or absence of ovulation.

Effects on fertility: Due to the disruption or absence of ovulation, PCOS has a negative effect on a woman’s fertility – if ovulation fails to occur, the egg cannot be fertilized either.

Frequency: PCOS affects an estimated 5-10% of women.

Most common symptoms:

• Moderate overweight
• Irregular or absent menstrual periods
• Increased hair growth (hirsutism)
• Acne

1b. Early menopause

Description: Early menopause is defined as the end of menstruation before the age of 40. This means that regular ovulation no longer occurs in the ovaries and fewer and fewer hormones are produced.

Effects on fertility: If ovulation fails to occur, the egg cannot be fertilized.

Frequency: Premature menopause affects about 1% of women (0.3% before the age of 35).

Most common symptoms:

• Some women have no symptoms except that they can no longer get pregnant
• Other women develop symptoms that correspond to the typical symptoms of menopause, e.g. hot flashes, night sweats, mood swings, lighter or absent menstruation, vaginal dryness

1c. Other hormone disorders

There are a number of other hormonal imbalances that can be causative for female infertility, which will be briefly listed here:

• Thyroid dysfunction: Both hypothyroidism and hyperthyroidism can contribute to an unfulfilled desire to have a child; the thyroid hormone is also involved in the child’s brain development. Thyroid disorders are one of the most common causes of infertility in younger women.
• Increases in prolactin levels (hyperprolactinemia): Prolactin is the hormone that stimulates milk production during breastfeeding of a baby. When prolactin levels are elevated, the cycle becomes irregular at the same time and ovulation occurs infrequently or irregularly.
• Progesterone deficiency (luteal hormone deficiency): Progesterone is responsible for the implantation of the fertilized egg in the uterus and the build-up of the uterine lining. A lack of progesterone can lead to the fertilized egg not implanting in the uterus or not being sufficiently supplied with nutrients and dying.

2. endometriosis

Description: Endometriosis is one of the most common causes of infertility in women. Endometriosis is when tissue of the uterus grows outside the uterus, such as in the abdomen or ovaries.

Effects on fertility: Women with endometriosis can in principle become pregnant, but their fertility is reduced by about 50%. In addition, there is an increased risk of complications during pregnancy, for example, the risk of miscarriage is increased by about 75%.

Frequency: An estimated 6-10% of women are affected by endometriosis

Most common symptoms:

• Frequently experience severe pain during periods with corresponding pain medication and sick days
• In addition, there are a number of other symptoms that indicate endometriosis (pain during sexual intercourse, bloating during menstruation, abdominal pain independent of menstruation, back pain, menstrual cycle disorders, fatigue and exhaustion, increased susceptibility to infections, blood in the urine, blood in the intestines).

3. organic disorders

3a. Fallopian tube disorders

Description: The fallopian tubes connect the ovaries to the uterus and are responsible for transporting the egg to the uterus. In addition, fertilization of the eggs takes place in the fallopian tubes. Disorders of the fallopian tubes, such as a blockage or occlusion, can prevent pregnancy because the egg cannot enter the uterus to implant.

Clogging of the fallopian tubes can occur for very different reasons, for example, endometriosis can contribute to it or a chlamydia infection can cause it.

Effects on fertility: If the fallopian tubes are blocked, pregnancy cannot occur.

Frequency: In about 30% of cases where the cause of infertility is in the woman, there is a disorder of the fallopian tubes. This may be associated with other causes of involuntary childlessness, such as endometriosis.

Most common symptoms: The first symptom of tubal dysfunction is often unwanted childlessness.

In addition, there are no typical symptoms that indicate tubal blockage, as it can have different causes. Thus, tubal adhesions can be due to (unnoticed) abdominal inflammation or appendicitis, but also to endometriosis or surgical scars.

3b. Changes in the uterus

Description: Changes in the uterus, such as small muscle lumps of the uterus (fibroids) or scarring can get in the way of pregnancy.

Effects on fertility: Changes in the uterus, depending on its size and position, can have a negative effect on the implantation of a fertilized egg in the uterus or even lead to miscarriages.

Frequency: 40-80%of all women have fibroids, but only 25-30% of women have fibroids that cause discomfort, which does not necessarily result in infertility.

Most common symptoms: symptoms of fibroids depend on their size and location, in 50% of those affected there are no symptoms.

Typical symptoms of fibroids are heavier bleeding during menstruation and menstrual pain, in addition there are a number of other symptoms (e.g. lower abdominal pain, pain during urination, infrequent bowel movements/constipation, pain during sexual intercourse).

3c. Changes of the cervix

Description: Sperm must pass through the cervix to reach the egg, which is normally closed by a mucus plug that loosens at the time of ovulation to allow the sperm to pass.

Infections or hormonal imbalances can interfere with this process, resulting in abnormal cervical mucus that prevents sperm from successfully passing through the cervix.

Effects on fertility: If sperm cannot pass through the cervix, fertilization of the egg and thus pregnancy cannot occur.

Frequency: problems with the cervix are rarely the cause of fertility problems in women, except in women who suffer from chronic inflammation of the cervix (cervicitis) or have a narrowed cervix (cervical stenosis).

Most common symptoms: Cervicitis does not always cause symptoms.

The most common symptoms are a noticeable (sometimes yellow-green and purulent) vaginal discharge and vaginal bleeding between two menstrual cycles or after sexual intercourse. In addition, there are a number of other symptoms of cervicitis (pain during sexual intercourse and/or urination, redness and inflammation of the vagina and the area around the vaginal opening).

4. genetic causes

Certain changes in a woman’s DNA can reduce the likelihood of pregnancy or make it impossible altogether, these include in particular:

• Triple X syndrome: In this syndrome, women have three X chromosomes instead of the usual two. This chromosomal disorder affects approximately one in 1000 women and is often undiagnosed because there are few symptoms associated with it. Triple X syndrome is associated with decreased fertility, often due to premature aging of the ovaries or early menopause.
• Turner syndrome: In this syndrome, only one X chromosome or only an incomplete second X chromosome is present in a female. Girls with this syndrome are typically short in stature, have excess skin on the neck, and do not go through puberty. Most women with Turner syndrome have ovarian malformation and are infertile, only 2% of women with Turner syndrome have natural pregnancies with a high risk of miscarriage and malformation of the child. Turner syndrome affects approximately one in 2000 women and in most cases is detected no later than the onset of puberty.
• Other changes: There are a variety of other genetic changes that contribute to female infertility. Some contribute to the physical causes of female infertility listed above, while others cause errors in embryonic development that result in the embryo resulting from the fertilized egg not being viable.

5. lifestyle and environmental influences

Other factors can have a negative impact on women’s fertility, such as.

• Psychological and physical stress (e.g. at work, during competitive sports)
• Smoking, alcohol and drug use
• Overweight, underweight and malnutrition
• Environmental toxins

6. age

With age, fertility declines in all women even in early adulthood, but the decline in fertility is particularly more pronounced after age 35. Generally, the older a woman is, the higher the risk that she will have to deal with impaired maturation of her eggs or that her egg reserve will be limited.

Here is an overview of the woman’s chances of pregnancy by year of life:

Under 25 years	90%
26-35 years	70%
35-40 years	20%

Age as a cause of female infertility is an increasing factor as more and more women postpone starting a family for a variety of reasons.

Common causes in men

As mentioned at the beginning, in 30-40% of cases of an unfulfilled desire to have children, the cause lies only with the man. The following is an overview of the most common causes of infertility in men.

Basics: sperm quantity and sperm quality

There are three primary quality characteristics regarding a man’s sperm that affect fertility:

• Sperm concentration / total sperm count: According to WHO, sperm concentration should be above 15 million sperm per milliliter or total sperm count in ejaculate should be above 39 million sperm. If the values are below these guideline values, doctors speak of oligozoospermia; if there are no sperm at all in the ejaculate, the term azoospermia is used. The lower the number of sperm in the ejaculate, the lower the probability that a sperm will successfully reach the target egg.
• Mobility or motility of the sperm: What matters most here is that sperm can move forward to reach the egg, or in technical jargon, that they are progressively mobile. In addition to progressively motile sperm, there are also non-progressively motile sperm and immotile sperm in every man’s sperm, neither of which can reach an egg on its own. If the percentage of motile sperm is too low (below 32%), physicians speak of asthenozoospermia.
• Shape or morphology of the sperm: A healthy sperm must have an oval-shaped head, a midpiece (the neck), and a tail. When the percentage of normally shaped sperm is less than 4%, physicians speak of teratozoospermia. Most abnormally shaped sperm cannot penetrate the egg because of their shape and therefore cannot fertilize it.

When all three factors are present at once, physicians refer to it as OAT syndrome (oligo astheno teratozoospermia).

The number of spermatozoa, motility and morphology each represent a continuum, in extreme cases i.e. no spermatozoa in the ejaculate (azoospermia) or at 0% spermatozoa with progressive motility (complete asthenozoospermia) or at 0% spermatozoa with normal morphology, the successful fertilization of an egg is as good as impossible, already above the above guideline values there can be problems with fertility in men.

Up to 2% of men have suboptimal parameters in terms of sperm concentration, motility or shape. In 1% of men, no sperm can be detected in the ejaculate.

Often there are no symptoms in the male with impaired sperm quality or sperm quantity, however depending on the underlying cause there may be symptoms, more on this in the following sections.

1. infections

Description: Some diseases can have a long-term negative effect on sperm quantity and quality. For example, an undetected and untreated chlamydia infection can worsen a man’s sperm counts. This can lead to a chronic urinary tract infection with pain in the testicle and epididymis and may also affect the prostate.

Similarly, contracting mumps after puberty can lead to painful testicular or epididymitis with permanent damage to the testicles.

Effects on fertility: Chronic chlamydial infection can lead to a deterioration in sperm quantity and quality with corresponding negative consequences for fertility. In addition, chlamydial infection can lead to adhesion of the vas deferens.

Mumps infection can have similar consequences.

Frequency: In Switzerland, 3-10% of the sexually active population is affected by chlamydia, but it is unclear how often chlamydial infection specifically contributes to male infertility. In a 2018 study of 1080 male patients with impaired fertility, 14.3% were found to have chlamydial infection.

Mumps is much rarer, with fewer than 1000 cases per year in Switzerland in recent years.

Most common symptoms: Half of men infected with chlamydia are asymptomatic. For the others, there are the following common symptoms: pain during urination, discharge from the penis, testicular pain.

Mumps is manifested by flu-like symptoms such as faintness, loss of appetite, headache, aching limbs, and fever. In addition, the parotid glands and salivary glands in the lower jaw may swell. However, at least one third of infections progress without symptoms or with only minor symptoms.

2. physical changes

2a. Injuries or malformations of the testicles

Description: Only intact testes can produce fertile sperm. Numerous factors, some of which are already present at birth, can damage the testicles, e.g. undescended testicles (congenital), tumor diseases of the testicles, injuries (e.g. testicular torsion), operations (e.g. on the prostate).

Effects on fertility: the effects on fertility depend on the specific injury or malformation.

Frequency: There are no reliable figures on the frequency of testicular injuries. Malformations of the testicles in the form of undescended testicles occur in about 1% of all one-year-old boys – this is often corrected, but can still have long-term negative effects on male fertility.

Most common symptoms: Injuries or malformations of the testicles – especially if they occurred many years ago – are often not (or no longer) known to the affected persons and sometimes without long-term symptoms. Testicular undescendancy in children is detected by palpation of the testicles, but is often corrected during childhood. Acute testicular injuries usually result in severe pain and are often accompanied by nausea/vomiting and sometimes fainting – however, men may not remember the injury specifically either.

2b. Damaged vas deferens

Description: A blocked or severed vas deferens can prevent sperm cells from reaching the semen, resulting in sperm without sperm cells (called obstructive azoospermia). Damage to the vas deferens can be caused by a variety of things, including infection and inflammation (e.g., chlamydia), surgery (e.g., a hernia), cystic fibrosis, or be congenital.

A vasectomy works on the same principle: this is the deliberate cutting and sealing of the vas deferens to sterilize a man.

Effects on fertility: In the case of complete blockage of the vas deferens, the man is naturally unable to conceive due to the lack of sperm cells in his ejaculate.

Frequency: Exact statements about the frequency of damaged vas deferens as a cause of infertility are difficult to make, since the damage can be due to different causes.

Most common symptoms: The most obvious symptom of damaged vas deferens is low or absent sperm in the man’s semen (oligozoospermia / azoospermia).

In addition, damage to the vas deferens is not symptomatic in itself; any symptoms are due to the original cause of the damage (e.g., chlamydial infection).

2c. Varicocele

Description: Varicose veins in the scrotum are also called varicocele, sometimes they are also called “varicocele hernia”, although it is not a hernia.

Effects on fertility: it is thought that a varicocele may reduce male fertility as it is more common among infertile men (25-37%) than fertile men, however many men are fertile despite having a varicocele.

The cause of reduced fertility due to a varicocele is still unclear, but it is suspected that the blood congestion in the area of the varicocele heats up the testicle and thus negatively affects sperm production in the long term.

Frequency: Varicoceles are common, it is estimated that a total of 5-15% of all men have a varicocele. However, varicoceles are not necessarily associated with fertility limitations.

Most common symptoms: In most cases, a varicocele does not cause any symptoms, but it can sometimes be noticeable through swelling, tightness or dull, pulling pain in the testicle.

2d. Retrograde ejajulation

Description: In retrograde ejaculation, ejaculation does not occur out of the penis but backward into the urinary bladder; partial ejaculation still occurs in some cases. Retrograde ejaculations can result from prostate surgery for a benign enlarged prostate; other common causes include diabetes, spinal cord injury, certain medications, and certain abdominal/pelvic surgeries.

Effects on fertility: If no semen is ejaculated at all, retrograde ejaculation may be the cause of male infertility.

Frequency: Retrograde ejaculations are relatively common, but estimated to account for only 0.3-2% of cases of infertility.

Most common symptoms: a man experiences a “dry” orgasm without ejaculate or an orgasm with only a small amount of ejaculate. Shortly after orgasm, sperm may be detected in the urine, which may also be indicated by cloudy urine.

3. hormonal causes: Testosterone deficiency

Description: Testosterone is the central male sex hormone and is, among other things, jointly responsible for sperm production. Testosterone levels can be measured; if blood testosterone levels are below 12 nmol/L (below 350 ng/dL), a condition called hypogonadism or androgen deficiency may be present.

Effects on fertility: Decreased testosterone does not always cause fertility problems because testosterone levels are higher in the testes, where sperm production occurs, than in the rest of the body. However, it may contribute to male infertility.

Incidence: testosterone levels in men normally decrease with age, it is estimated that testosterone deficiency is present in approximately 2-4% of those over 40 years of age.

Most common symptoms: Usually there are two main symptoms of testosterone deficiency: decrease in desire for sex (libido) and erectile dysfunction. In addition, there are a variety of other symptoms (e.g., decrease in muscle mass and strength, decreased physical performance, weight gain with especially more fat accumulation in the abdomen).

4. genetic causes

In about 15% of males with azoospermia, deviations from the norm are present in the sex chromosomes; the two most frequent ones are mentioned here:

• Klinefelter syndrome: Klinefelter syndrome is when a man has an extra X chromosome in his DNA (i.e. the sex chromosomes are XXY). Physical features can vary widely, but often sufferers are tall and have long arms and legs, and sometimes wider hips. It usually happens that the testicles remain small during puberty and the affected males are often, but not always, infertile.
• 46,XX males (or de la Chapelle syndrome): These are males according to the phenotype (appearance) but born with 2 X chromosomes instead of one X and one Y chromosome. In 80% of cases, this is due to a so-called translocation (transfer) of a Y chromosome fragment to the X chromosome of the father. 46,XX Males are outwardly normal in build, but with small testes and a cluster of hypospadias (malformation of the male urethra with an opening of the urethra on the underside of the penis, an atypical foreskin, and a curved penile shaft) and male breast enlargement (gynecomastia). 46.XX Men are unable to procreate.

Furthermore, there are genetic factors that directly prevent spermatogenesis (production of sperm), e.g.:

• AZF deletions on the Y chromosome: Azoospermia factor (AZF) refers to a specific region on the male Y chromosome. If this is affected by deletions or microdeletions, the man usually cannot produce sperm or can only produce very few sperm. In infertile males, AZF deletions occur in less than 2% of cases.

5. lifestyle and environmental influences

Generally speaking, a healthy lifestyle also has a positive effect on male fertility. On the other hand, the “usual suspects” can have a negative effect on sperm production and thus on sperm quantity and quality in men:

• Psychological and physical stress (e.g. at work, during competitive sports)
• Smoking, alcohol and drug use
• Overweight, underweight and malnutrition
• Environmental toxins

An additional influence in men is heat in the testicular area, not for nothing the testicles are located outside the man’s body – so high temperatures e.g. from hot baths, showers or saunas can contribute to low quality of male sperm.

As a rule of thumb, it takes about 3 months for a sperm cell to mature – so this is also the time a man needs to give his body to improve sperm quality with adjusted habits.

6. age

As with women, age also plays a role in fertility for men. From about 40 years of age, a man’s sperm production and motility decreases. According to a British study, it can take men over 40 up to 3 times as long as younger men to successfully conceive their partner (from 7 months to up to 21 months).

In addition, the frequency of genetic changes in sperm cells is greater in older men, increasing the risk of miscarriage and genetic diseases of the child.

Conclusion

Overall, there are a variety of possible causes for a couple’s unfulfilled desire to have children. It is important that if the cause is unclear, both partners undergo a detailed examination, as it is purposeful for treatment options to address the underlying cause as best as possible.

Last update: 02 November 2022

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