In biology, infertility is the inability of a male and female organism to reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity. As a medical term, infertility does not apply before and after the normal period of natural, age-dependent reproductive function: in children before puberty, or in women after menopause.
In humans, infertility is defined as the inability to become pregnant after at least one year of unprotected and regular sexual intercourse involving a male and female partner. There are many causes of infertility, including some that medical intervention can treat. Estimates from 1997, suggest that worldwide about five percent of all heterosexual couples have an unresolved problem with infertility. That figure has been on the rise, with the World Health Organization (WHO) reporting in 2023 that about 17.5% of people experience infertility during their lifetime, while prevalence at a given time point is 12.6%. Many more couples, however, experience involuntary childlessness for at least one year, with estimates ranging from 12% to 28%.
Male infertility is responsible for 20–30% of infertility cases, while 20–35% are due to female infertility, and 25–40% are due to combined problems in both partners. In 10–20% of cases, no cause is found.
The most common causes of female infertility are hormonal in nature, including low estrogen, imbalanced gonadotropin-releasing hormone (GnRH) secretion, polyendocrine metabolic ovarian syndrome (PCOS), and aging, which generally manifests in sparse or absent menstrual periods leading up to menopause. Page last reviewed 15 July 2014 As women age, the number of ovarian follicles and oocytes (immature eggs) decline, leading to a reduced ovarian reserve. Some women undergo primary ovarian insufficiency (premature menopause) or the loss of ovarian function before age 40, leading to infertility. 85% of infertile couples have an identifiable cause, and 15% is designated unexplained infertility. Of the 85% of identified infertility, 25% is due to disordered ovulation (of which 70% of the cases are due to polycystic ovarian syndrome). Tubal infertility (structural issues with the fallopian tubes) is responsible for 11–67% of infertility in women of childbearing age, with the large range in prevalence due to different populations studied. Endometriosis, the presence of endometrial tissue (which normally lines the uterus) outside of the uterus, accounts for 25–40% of female infertility.
During the menstrual cycle, there is a limited physiological fertile window of up to seven days before and during ovulation, when conception may be possible. Both the length of the menstrual cycle and the length of the fertile window are highly variable. Fertility awareness methods are used to discern when these changes occur by tracking changes in cervical mucus, basal body temperature, or hormone measurements.
Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity. Male infertility may also be due to retrograde ejaculation, low testosterone, functional azoospermia (in which sperm is not produced or not produced in enough numbers) and obstructive azoospermia in which the pathway for the sperm (such as the vas deferens) is obstructed.
Definition "Demographers tend to define infertility as childlessness in a population of women of reproductive age." The epidemiological definition refers to "trying for" or "time to" a pregnancy, generally in a population of women exposed to a probability of conception. Currently, female fertility normally peaks in young adulthood. It diminishes after age 35, with pregnancy occurring rarely after age 50. A female is most fertile within 24 hours of ovulation. Male fertility peaks usually in young adulthood and declines after age 40.
The time needed to pass (during which the couple tries to conceive) for that couple to be diagnosed with infertility differs between different organizations. Existing definitions of infertility lack uniformity, rendering comparisons in prevalence between countries or over time problematic. Therefore, data estimating the prevalence of infertility cited by various sources differ significantly. A couple that tries unsuccessfully to have a child after a certain period (often a short period, but definitions vary) is sometimes said to be subfertile, meaning less fertile than a typical couple. Both infertility and subfertility are defined similarly and often used interchangeably. Subfertility is the delay in conceiving within six to twelve months, whereas infertility is the inability to conceive naturally within a full year.
World Health Organization The World Health Organization defines infertility as follows:
The World Health Organization also adds that "women whose pregnancy spontaneously miscarries, or whose pregnancy results in a stillborn child, without ever having had a live birth, would present with primarily infertility".
United States One definition of infertility that is frequently used in the United States by reproductive endocrinologists, doctors who specialize in infertility, to consider a couple eligible for treatment is: A woman under 35 has not conceived after 12 months of contraceptive-free sexual intercourse. A woman over 35 has not conceived after 6 months of contraceptive-free sexual intercourse.
United Kingdom In the UK, previous NICE guidelines defined infertility as failure to conceive after regular unprotected sexual intercourse for two years in the absence of known reproductive pathology. Updated NICE guidelines do not include a specific definition, but recommend that "A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner, with earlier referral to a specialist if the woman is over 36 years of age."
Other definitions Researchers commonly base demographic studies on infertility prevalence over five years.
Causes Male infertility is responsible for 20–30% of infertility cases, while 20–35% are due to female infertility, and 25–40% are due to combined problems in both partners.Chowdhury SH, Cozma AI, Chowdhury JH. Infertility. Essentials for the Canadian Medical Licensing Exam: Review and Prep for MCCQE Part I. 2nd edition. Wolters Kluwer. Hong Kong. 2017. In 10–20% of cases, no cause is found. The most common cause of female infertility is abnormal ovulation, usually manifested by scanty or absent menstrual periods. Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.
Before puberty Before puberty, humans are naturally incapable of reproduction; their gonads have not yet developed the gametes required to reproduce: boys' testicles have not developed the sperm cells required to impregnate a female; girls have not begun the process of ovulation which activates the fertility of their egg cells (ovulation is confirmed by the first menstrual cycle, known as menarche, which signals the biological possibility of pregnancy). The lack of fertility in children is commonly referred to as prepubescence (or being prepubescent, an adjective used to also refer to humans without secondary sex characteristics).
The absence of fertility in children is considered a natural part of human growth and child development, as the hypothalamus in their brain is still underdeveloped and cannot release the hormones required to activate the gonads' gametes. Fertility in children before the ages of eight or nine is considered a disease known as precocious puberty. This disease is usually triggered by a brain tumor or other related injury.
Delayed puberty
Delayed puberty, puberty absent past or occurring later than the average onset (between the ages of ten and fourteen), may be a cause of infertility. In the United States, girls are considered to have delayed puberty if they have not started menstruating by age 16 (alongside lacking breast development by age 13). Boys are considered to have delayed puberty if they lack enlargement of the testicles by age 14. Delayed puberty affects about 2% of adolescents.
Most commonly, puberty may be delayed for several years and still occur normally, in which case it is considered a constitutional delay of growth and puberty, a common variation of healthy physical development. Delay of puberty may also occur due to various causes such as malnutrition, various systemic diseases, or defects of the reproductive system (hypogonadism) or the body's responsiveness to sex hormones.
Iodine deficiency Iodine deficiency may lead to infertility.
Immune infertility Antisperm antibodies (ASA) have been considered as an infertility cause in around 10–30% of infertile couples. In both men and women, ASA production is directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. The antibodies are classified into different groups: IgA, IgG, and IgM. They also differ in the location of the spermatozoon they bind to (head, midpiece, tail). Factors contributing to the formation of antisperm antibodies in women are disturbance of normal immunoregulatory mechanisms, infection, violation of the integrity of the mucous membranes, rape, and unprotected oral or anal sex. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men.
Sexually transmitted infections Diseases such as chlamydia and gonorrhea can also cause infertility due to internal scarring (fallopian tube obstruction). Infections with the following sexually transmitted pathogens hurt fertility: Chlamydia trachomatis and Neisseria gonorrhoeae. There is a consistent association of Mycoplasma genitalium infection and female reproductive tract syndromes. M. genitalium infection is associated with an increased risk of infertility.
Genetics
Mutations to the NR5A1 gene encoding steroidogenic factor 1 (SF-1) have been found in a small subset of men with non-obstructive male factor infertility, where the cause is unknown. Results of one study investigating a cohort of 315 men revealed changes within the hinge region of SF-1 and no rare allelic variants in fertile control men. Affected individuals displayed more severe forms of infertility such as azoospermia and severe oligozoospermia.
Small supernumerary marker chromosomes are abnormal extra chromosomes; they are three times more likely to occur in infertile individuals and account for 0.125% of all infertility cases. See Infertility associated with small supernumerary marker chromosomes and Genetics of infertility#Small supernumerary marker chromosomes and infertility.
Pollution
Environmental pollution in both indoor and outdoor air has been linked to negative effects on reproduction. Total fertility rates (TFRs) have fallen worldwide in all recorded countries since the early 1960s. Research has consistently shown that pollution interferes with all aspects of sexual reproduction from male and female fertility to fetal development, birth outcomes, and long-term health of offspring. The risk of adverse birth outcomes such as miscarriage, stillbirth, preterm birth, low birth weight and birth defects increase when pregnant women are exposed to air pollution.