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
Sexual maturity is the capability of an organism to reproduce. In humans, it is related to both puberty and adulthood. ''Puberty'' is the biological process of sexual maturation, while ''adulthood'', the condition of being socially recognized ...
, so
children
A child () is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The term may also refer to an unborn human being. In English-speaking ...
who have not undergone
puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...
, which is the body's start of
reproductive capacity, are excluded. It is also a normal state in women after
menopause
Menopause, also known as the climacteric, is the time when Menstruation, menstrual periods permanently stop, marking the end of the Human reproduction, reproductive stage for the female human. It typically occurs between the ages of 45 and 5 ...
.
In humans, ''infertility'' is defined as the inability to become
pregnant
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
after at least one year of unprotected and regular
sexual intercourse
Sexual intercourse (also coitus or copulation) is a sexual activity typically involving the insertion of the Erection, erect male Human penis, penis inside the female vagina and followed by Pelvic thrust, thrusting motions for sexual pleasure ...
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. Many more couples, however, experience involuntary childlessness for at least one year, with estimates ranging from 12% to 28%.
Male infertility
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. Male infertility can wholly or partially account for 40% of infertility among couples who are trying to have children. "A problem with the male is the s ...
is responsible for 20–30% of infertility cases, while 20–35% are due to
female infertility
Female infertility refers to infertility in women, which is the inability to Fertilisation, conceive after sexual intercourse. It affects an estimated 48 million women, globally.
Female infertility varies widely by region. The highest rates of ...
, 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
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
, imbalanced GnRH secretion, 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 (eggs) decline, leading to a reduced ovarian reserve. Some women undergo primary ovarian insufficiency (also known as 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
Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origi ...
). Tubal infertility, in which there is a structural problem 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
Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...
, the presence of endometrial tissue (which normally lines the uterus) outside of the uterus, accounts for 25-40% of female infertility.
Women who are fertile experience a period of fertility before and during ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
, and are infertile for the rest of the menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
. Fertility awareness methods are used to discern when these changes occur by tracking changes in cervical mucus or basal body temperature.
Male infertility is most commonly due to deficiencies in the semen
Semen, also known as seminal fluid, is a bodily fluid that contains spermatozoon, spermatozoa which is secreted by the male gonads (sexual glands) and other sexual organs of male or hermaphrodite, hermaphroditic animals. In humans and placen ...
, and semen quality is used as a surrogate measure of male fecundity
Fecundity is defined in two ways; in human demography, it is the potential for reproduction of a recorded population as opposed to a sole organism, while in population biology, it is considered similar to fertility, the capability to produc ...
. Male infertility may also be due to retrograde ejaculation
Retrograde ejaculation occurs when semen which would be ejaculated via the urethra is redirected to the urinary bladder. Normally, the sphincter of the bladder contracts before ejaculation, inhibiting urination and preventing a reflux of semen ...
, 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
The vas deferens (: vasa deferentia), ductus deferens (: ductūs deferentes), or sperm duct is part of the male reproductive system of many vertebrates. In mammals, spermatozoa are produced in the seminiferous tubules and flow into the epididyma ...
) is obstructed.
Definition
"Demographers tend to define infertility as childlessness in a population of women of reproductive age," whereas 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 and diminishes after 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, but 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
The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
defines infertility as follows:
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 intercourse.
* a woman over 35 has not conceived after six months of contraceptive-free sexual intercourse
Sexual intercourse (also coitus or copulation) is a sexual activity typically involving the insertion of the Erection, erect male Human penis, penis inside the female vagina and followed by Pelvic thrust, thrusting motions for sexual pleasure ...
.
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.
Primary vs. secondary infertility
Primary infertility is defined as the absence of a live birth for women who desire a child and have been in a union for at least 12 months, during which they have not used any contraceptives. The World Health Organisation 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'.
Secondary infertility is defined as the difficulty in conceiving a live birth in couples who previously had a child.
Effects
Psychological
The consequences of infertility are manifold and can include societal repercussions and personal suffering. Advances in assisted reproductive technologies, such as IVF, can offer hope to many couples where treatment is available, although barriers exist in terms of medical coverage and affordability. The medicalization of infertility has unwittingly led to a disregard for the emotional responses that couples experience, which include distress, loss of control, stigmatization, and a disruption in the developmental trajectory of adulthood. One of the main challenges in assessing the distress levels in women with infertility is the accuracy of self-report measures. It is possible that women "fake good" to appear mentally healthier than they are. It is also possible that women feel a sense of hopefulness/increased optimism before initiating infertility treatment, which is when most assessments of distress are collected. Some early studies concluded that infertile women did not report any significant differences in symptoms of anxiety and depression than fertile women. The further into treatment a patient goes, the more often they display symptoms of depression and anxiety. Patients with one treatment failure had significantly higher levels of anxiety, and patients with two failures experienced more depression when compared with those without a history of treatment. However, it has also been shown that the more depressed the infertile woman, the less likely she is to start infertility treatment and the more likely she is to drop out after only one cycle. Researchers have also shown that despite a good prognosis and having the finances available to pay for treatment, discontinuation is most often due to psychological reasons. Fertility does not seem to increase when the women takes antioxidants to reduce the oxidative stress brought by the situation.
Infertility may have psychological effects. Parenthood is one of the major transitions in adult life for both men and women. The stress of the non-fulfilment of a wish for a child has been associated with emotional consequences such as anger, depression, anxiety, marital problems, and feelings of worthlessness.[Deka, P. K., & Sarma, S. (2010). Psychological aspects of infertility. British Journal of Medical Practitioners, 3(3), 336.]
Partners may become more anxious to conceive, increasing sexual dysfunction
Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction ...
.[Donor insemination Edited by C.L.R. Barratt and I.D. Cooke. Cambridge (England): Cambridge University Press, 1993. 231 pages., page 13, citing Berger (1980)] Marital discord often develops, especially when they are under pressure to make medical decisions. Women trying to conceive often have depression rates similar to women who have heart disease or cancer. Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.[Donor insemination Edited by C.L.R. Barratt and I.D. Cooke. Cambridge (England): Cambridge University Press, 1993. 231 pages., page 13, in turn citing Connolly, Edelmann & Cooke 1987]
Male
Male (Planet symbols, symbol: ♂) is the sex of an organism that produces the gamete (sex cell) known as sperm, which fuses with the larger female gamete, or Egg cell, ovum, in the process of fertilisation. A male organism cannot sexual repro ...
and female partners respond differently to infertility problems. In general, women show higher depression levels than their male partners when dealing with infertility. A possible explanation may be that women feel more responsible and guilty than men during the process of trying to conceive. On the other hand, infertile men experience psychosomatic distress.
Social
Having a child is considered to be important in most societies. Infertile couples may experience social and family pressure, leading to a feeling of social isolation. Factors of gender, age, religion, and socioeconomic status are important influences. Societal pressures may affect a couple's decision to approach, avoid, or experience an infertility treatment.
Moreover, the socioeconomic status influences the psychology of infertile couples: low socioeconomic status is associated with increased chances of developing depression.
In many cultures, the inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether.
In the United States, some treatments for infertility, including diagnostic tests, surgery, and therapy for depression, can qualify one for Family and Medical Leave Act leave. It has been suggested that infertility be classified as a form of disability.
Sexual
Couples that suffer from infertility have a higher risk than other couples of developing sexual dysfunctions. The most common sexual issue facing the couples is a decline in sexual desire and erectile dysfunction.
Causes
Male infertility
Male infertility refers to a sexually mature male's inability to impregnate a fertile female. Male infertility can wholly or partially account for 40% of infertility among couples who are trying to have children. "A problem with the male is the s ...
is responsible for 20–30% of infertility cases, while 20–35% are due to female infertility
Female infertility refers to infertility in women, which is the inability to Fertilisation, conceive after sexual intercourse. It affects an estimated 48 million women, globally.
Female infertility varies widely by region. The highest rates of ...
, 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
Semen, also known as seminal fluid, is a bodily fluid that contains spermatozoon, spermatozoa which is secreted by the male gonads (sexual glands) and other sexual organs of male or hermaphrodite, hermaphroditic animals. In humans and placen ...
, and semen quality is used as a surrogate measure of male fecundity
Fecundity is defined in two ways; in human demography, it is the potential for reproduction of a recorded population as opposed to a sole organism, while in population biology, it is considered similar to fertility, the capability to produc ...
.[
]
Iodine Deficiency
Iodine deficiency may lead to infertility.
Natural infertility
Before puberty
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...
, humans are naturally infertile; their gonad
A gonad, sex gland, or reproductive gland is a Heterocrine gland, mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gon ...
s have not yet developed the gametes
A gamete ( ) is a haploid cell that fuses with another haploid cell during fertilization in organisms that reproduce sexually. Gametes are an organism's reproductive cells, also referred to as sex cells. The name gamete was introduced by the Ge ...
required to reproduce: boys' testicle
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is Homology (biology), homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of Androgen, androgens, p ...
s have not developed the sperm cells required to impregnate a female; girls have not begun the process of ovulation
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
which activates the fertility of their egg cells (ovulation is confirmed by the first menstrual cycle
The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...
, known as menarche
Menarche ( ; ) is the first menstrual cycle, or first menstruation, menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fe ...
, which signals the biological possibility of pregnancy). Infertility in child
A child () is a human being between the stages of childbirth, birth and puberty, or between the Development of the human body, developmental period of infancy and puberty. The term may also refer to an unborn human being. In English-speaking ...
ren is commonly referred to as '' prepubescence'' (or being ''prepubescent'', an adjective used to also refer to humans without secondary sex characteristic
A secondary sex characteristic is a physical characteristic of an organism that is related to or derived from its sex, but not directly part of its reproductive system. In humans, these characteristics typically start to appear during pubert ...
s).
The absence of fertility in children is considered a natural part of human growth and child development
Child development involves the Human development (biology), biological, psychological and emotional changes that occur in human beings between birth and the conclusion of adolescence. It is—particularly from birth to five years— a foundation ...
, as the hypothalamus
The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
in their brain is still underdeveloped and cannot release the hormone
A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
s 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
A brain tumor (sometimes referred to as brain cancer) occurs when a group of cells within the Human brain, brain turn cancerous and grow out of control, creating a mass. There are two main types of tumors: malignant (cancerous) tumors and benign ...
or other related injury.
Delayed puberty
Delayed puberty
Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormone, hormonal signs that puberty has begun. In the United States ...
, 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
Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is a deficiency, excess, or imbalance of energy, protein and other nutrients which adversely affects the body's tissues a ...
, various systemic diseases, or defects of the reproductive system
The reproductive system of an organism, also known as the genital system, is the biological system made up of all the anatomical organs involved in sexual reproduction. Many non-living substances such as fluids, hormones, and pheromones are al ...
(hypogonadism
Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...
) or the body's responsiveness to sex hormones.
Immune infertility
Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples. In both men and women, ASA production are 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
Fertilisation or fertilization (see American and British English spelling differences#-ise, -ize (-isation, -ization), spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give ...
, influence on the implantation process, and impaired growth and development of the embryo
An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...
. The antibodies are classified into different groups: There are IgA, IgG, and IgM antibodies. 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
A varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum; in a woman, it is an abnormal painful swelling to the List of related male and female reproductive organs, embryologically identical pampiniform venous plexu ...
, infections, prostatitis, testicular cancer
Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility.
Risk factors include an c ...
, failure of immunosuppression and unprotected receptive anal or oral sex with men.
Sexually transmitted infections
Infections with the following sexually transmitted pathogens hurt fertility: ''Chlamydia trachomatis
''Chlamydia trachomatis'' () is a Gram-negative, Anaerobic organism, anaerobic bacterium responsible for Chlamydia infection, chlamydia and trachoma. ''C. trachomatis'' exists in two forms, an extracellular infectious elementary body (EB) and an ...
'' and '' Neisseria gonorrhoeae''. There is a consistent association of ''Mycoplasma genitalium
''Mycoplasma genitalium'' (also known as ''MG','' Mgen, or since 2018, ''Mycoplasmoides genitalium'') is a sexually transmitted, small and pathogenic bacterium that lives on the mucous epithelial cells of the urinary and genital tracts in ...
'' infection and female reproductive tract syndromes. ''M. genitalium'' infection is associated with an increased risk of infertility.
Genetic
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.
Other causes
Factors that can cause male as well as female infertility are:
* DNA damage
** DNA damage reduces fertility in female ovocytes, as caused by smoking, other xenobiotic DNA damaging agents (such as radiation or chemotherapy) or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine
** DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA-damaging agents, including reactive oxygen species, fever, or high testicular temperature. The damaged DNA related to infertility manifests itself by the increased susceptibility to denaturation inducible by heat or acid or by the presence of double-strand breaks that can be detected by the TUNEL assay. In this assay, the sperm's DNA will be denaturated and renatured. If DNA fragmentation occurs (double and single-strand breaks), a halo will not appear surrounding the spermatozoa, but if the spermatozoa do not have DNA damage, a halo surrounding the spermatozoa could be visualized under the microscope.
* General factors
** Diabetes mellitus
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...
, thyroid disorders, undiagnosed and untreated coeliac disease
Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spelt ...
, adrenal disease
* Hypothalamic-pituitary factors
** Hyperprolactinemia
** Hypopituitarism
** The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility with an odds ratio
An odds ratio (OR) is a statistic that quantifies the strength of the association between two events, A and B. The odds ratio is defined as the ratio of the odds of event A taking place in the presence of B, and the odds of A in the absence of B ...
of 1.5 and 95% confidence interval of 1.1–2.0.
* Environmental factors
** Toxin
A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...
s such as glues, volatile organic solvents
A solvent (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for p ...
or silicone
In Organosilicon chemistry, organosilicon and polymer chemistry, a silicone or polysiloxane is a polymer composed of repeating units of siloxane (, where R = Organyl group, organic group). They are typically colorless oils or elastomer, rubber ...
s, physical agents, flame retardants, chemical dusts, polychlorinated biphenyls, and pesticides
Pesticides are substances that are used to pest control, control pest (organism), pests. They include herbicides, insecticides, nematicides, fungicides, and many others (see table). The most common of these are herbicides, which account for a ...
. Tobacco smokers are 60% more likely to be infertile than non-smokers.
Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring ( fallopian tube obstruction).
*Body mass, the BMI (body mass index) (either being too high or too low) may be a contributor to infertility.
** Obesity
Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...
: Obesity can have a significant impact on male and female fertility. In females, a BMI above 27 increases the risk of infertility 3-fold. Obese women have a higher rate of recurrent, early miscarriage compared to non-obese women. In males, an increase in BMI above 30 may be associated with reduced sperm quality and impaired spermatogenesis leading to infertility. In males, a high BMI is also associated with low testosterone levels (secondary hypogonadism) and erectile dysfunction
Erectile dysfunction (ED), also referred to as impotence, is a form of sexual dysfunction in males characterized by the persistent or recurring inability to achieve or maintain a Human penis, penile erection with sufficient rigidity and durat ...
, which contributes to infertility.
** Low weight: females with a very low BMI may have infertility. Common causes of low BMI leading to infertility include anorexia nervosa
Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin.
Individuals wit ...
and other eating disorders, excessive exercise or relative energy deficiency in sport. Infertility in females with a low BMI is usually due to functional hypothalamic amenorrhea due to stress-induced inhibition of the hypothalamic pituitary ovarian axis.
Females
The following causes of infertility may only be found in females.
For a woman to conceive, certain things have to happen: vaginal intercourse must take place around the time when an egg is released from her ovary; the system that produces eggs has to be working at optimum levels; and her hormones must be balanced.
For women, problems with fertilization arise mainly from either structural problems in the fallopian tube
The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the Ovary, ovaries to the uterus. The fallopian tubes are part of the female reproduct ...
or uterus or problems releasing eggs. Infertility may be caused by blockage of the fallopian tube due to malformations, infections such as chlamydia, or scar tissue. For example, endometriosis
Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...
can cause infertility with the growth of endometrial tissue in the fallopian tubes or around the ovaries. Endometriosis is usually more common in women in their mid-twenties and older, especially when postponed childbirth has taken place.
Another major cause of infertility in women may be the inability to ovulate
Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
. This is usually related to low levels of the sex hormone estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
, as well as imbalanced GnRH secretion. Ovulatory disorders make up 25% of the known causes of female infertility.
Oligo-ovulation or anovulation results in infertility because no oocyte will be released monthly. In the absence of an oocyte, there is no opportunity for fertilization and pregnancy. The World Health Organization subdivided ovulatory disorders into four classes:
* Hypogonadotropic hypogonadal anovulation: i.e., hypothalamic amenorrhea
* Normogonadotropic normoestrogenic anovulation: i.e., polycystic ovarian syndrome (PCOS)
* Hypergonadotropic hypoestrogenic anovulation: i.e., premature ovarian failure
* Hyperprolactinemic anovulation: i.e., pituitary adenoma
Malformation of the eggs themselves may complicate conception. For example, polycystic ovarian syndrome
Polycystic ovary syndrome, or polycystic ovarian syndrome, (PCOS) is the most common endocrine disorder in women of reproductive age. The name is a misnomer, as not all women with this condition develop cysts on their ovaries. The name origi ...
(PCOS) is when the eggs only partially develop within the ovary, and there is an excess of male hormones. Some women are infertile because their ovaries do not mature and release eggs. In this case, synthetic FSH by injection or Clomid (Clomiphene citrate) via a pill can be given to stimulate follicles to mature in the ovaries.
Other factors that can affect a woman's chances of conceiving include being overweight or underweight, or her age as female fertility declines after the age of 30.
Sometimes it can be a combination of factors, and sometimes a clear cause is never established.
Common causes of infertility in females include:
* hormone-related ovulation problems (e.g., PCOS, the leading reason why women present to fertility clinics due to anovulatory infertility)
* tubal blockage
* pelvic inflammatory disease caused by infections like tuberculosis
Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
* age-related factors
* uterine problems
* previous tubal ligation
Tubal ligation (commonly known as having one's "tubes tied") is a surgical procedure for female sterilization in which the fallopian tubes are permanently blocked, clipped or removed. This prevents the fertilization of eggs by sperm and thus the ...
* endometriosis
Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...
* advanced maternal age
* immune infertility
Males
Male infertility is defined as the inability of a male to make a fertile female pregnant, for a minimum of at least one year of unprotected intercourse. Male infertility is estimated to contribute to 35% of infertility in couples. There are multiple causes for male infertility including endocrine disorders (usually due to hypogonadism) at an estimated 2% to 5%, sperm transport disorders at 5%, primary testicular defects (which includes abnormal sperm parameters without any identifiable cause) at 65% to 80% and idiopathic
An idiopathic disease is any disease with an unknown cause or mechanism of apparent spontaneous origin.
For some medical conditions, one or more causes are somewhat understood, but in a certain percentage of people with the condition, the cause ...
(where an infertile male has normal sperm and semen parameters) at 10% to 20%.
The main cause of male infertility is low semen quality. In men who have the necessary reproductive organs to procreate, infertility can be caused by low sperm count due to endocrine problems, drugs, radiation, or infection. There may be testicular malformations, hormone imbalance, or blockage of the man's duct system. Although many of these can be treated through surgery or hormonal substitutions, some may be indefinite.
Infertility associated with viable, but immotile sperm may be caused by primary ciliary dyskinesia. The sperm must provide the zygote with DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
, centrioles
In cell biology a centriole is a cylindrical organelle composed mainly of a protein called tubulin. Centrioles are found in most eukaryotic cells, but are not present in conifers ( Pinophyta), flowering plants ( angiosperms) and most fungi, an ...
, and activation factor for the embryo to develop. A defect in any of these sperm structures may result in infertility that will not be detected by semen analysis. Antisperm antibodies cause immune infertility. Cystic fibrosis
Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...
can lead to infertility in men by blocking the vas deferens.
Adeno-associated virus infection has been linked to poor sperm quality and may contribute to male infertility, based on small observational studies.
Unexplained infertility
In the US, up to 15% of infertile couples have unexplained infertility, in which no identifiable cause is found. polymorphisms in folate pathway genes may be a cause for fertility complications in some women with unexplained infertility. Epigenetic modifications in sperm may also be responsible for unexplained infertility.
In Animals
Many other mammals
A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...
experience infertility. Red Heelers are known to be less fertile. Hybrid animals are usually infertile, due to their odd number of chromosomes.
Diagnosis
If both partners are young and healthy and have been trying to conceive for one year without success, a visit to a physician
A physician, medical practitioner (British English), medical doctor, or simply doctor is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through the Medical education, study, Med ...
or women's health nurse practitioner (WHNP) could help to highlight potential medical problems earlier rather than later. The doctor or WHNP may also be able to suggest lifestyle changes to increase the chances of conceiving.
However, there are instances where couples should seek reproductive counseling after only 6 months of trying for a pregnancy
Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins.
Conception (biology), Conception usually occurs ...
:
*The woman is over 35 years old.
*The woman has a history of endometriosis
Endometriosis is a disease in which Tissue (biology), tissue similar to the endometrium, the lining of the uterus, grows in other places in the body, outside the uterus. It occurs in women and a limited number of other female mammals. Endomet ...
.
*The woman has infrequent or irregular menses
Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and Mucous membrane, mucosal tissue from the endometrium, inner lining of the uterus through the vagina. The menstrual cycle is characterized ...
.
*There is a male factor involved.
A doctor or WHNP takes a medical history and gives a physical examination. They can also carry out some basic tests on both partners to see if there is an identifiable reason for not having achieved a pregnancy. Among these tests, blood tests are common and may include serologies to detect infections such as hepatitis B (HBV), hepatitis C (HCV), HIV, syphilis, and rubella. Optional tests like karyotypes can also be performed. For females, specific tests might include measuring antimüllerian hormone (AMH) to assess ovarian reserve, thyroid-stimulating hormone (TSH), prolactin (PRL), and vitamin D levels, which can influence fertility. If necessary, they refer patients to a fertility clinic or local hospital for more specialized tests. The results of these tests help determine the best fertility treatment.
Treatment
Treatment depends on the cause of infertility, but may include counselling, fertility treatments, which include in vitro fertilization. According to ESHRE recommendations, couples with an estimated live birth rate of 40% or higher per year are encouraged to continue aiming for a spontaneous pregnancy. Drugs used include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...
(FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone
Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and rele ...
(GnRH) analogues, and aromatase inhibitors.
Medical treatments
Clomiphene is a selective estrogen receptor modulator used to induce ovulation. It works by blocking the negative feedback from estrogen, creating a gonadotropin releasing hormone (GnRH) increase, which causes release of luteinizing hormone (LH) and follicle-stimulating hormone
Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...
(FSH) from the anterior pituitary. FSH and LH act on the ovaries to increase follicle growth and lead to ovulation. Letrozole is an aromatase inhibitor which reduces estradiol levels and increases levels of FSH and LH, which can stimulate ovarian follicle maturation and ovulation. Letrozole is the preferred treatment in those with infertility due to PCOS and is associated with a higher pregnancy rate than other treatments. Both clomiphene and letrozole have a risk of a multiple gestation pregnancy, with the risk being less than 10%. Those with hypogonadotropic hypogonadism require pulsatile GnRH therapy, which is associated with a 93-100% pregnancy rate after 6 months of therapy. The risk of a multiple gestation pregnancy with gonadotropins is 36%. Ovarian stimulation with clomiphene, aromatase inhibitors, or gonadotropins (especially when combined with intrauterine insemination) have a risk of ovarian hyperstimulation syndrome which may occur in 1-5% of cycles and presents as ascites, electrolyte abnormalities and blood clots.
Fertility treatments or medications do not increase the risk of breast, ovarian, or endometrial cancers.
Metformin does not increase the rate of live births in those with infertility (including in those with PCOS), and its use is not recommended.
In some cases, in vitro fertilization (IVF) is used, in which induced ovarian follicle stimulation is followed by the extraction of oocytes from the ovaries. The oocytes are then fertilized in vitro by sperm using Intracytoplasmic sperm injection (ICSI) and the fertilized eggs are re-introduced into the uterus in a procedure called embryo transfer
Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy. This technique - which is often used in connection with in vitro fertili ...
. ICSI was first developed in 1978 by Robert Edwards and Patrick Steptoe.
Ovarian stimulation (such as with clomiphene) combined with in-vitro fertilization or intra-uterine insemination has lower success rates with increasing age.
Sperm or oocyte donors with in vitro fertilization and gestational carriers are sometimes used for gay couples, those with severe medical conditions that make pregnancy dangerous or preclude pregnancy, those with severe infertility, or females with a non-functioning uterus.
Tourism
''Fertility tourism'' is the practice of traveling to another country for fertility treatments.
Stem cell therapy
Several experimental treatments related to stem cell
In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...
therapy are not yet routinely used in reproductive medicine. These treatments may provide the opportunity for a live birth for people who lack gametes and also for same-sex couples and single people who want to have offspring. Theoretically, with this therapy, artificial gametes can be produced ''in vitro''.
* Spermatogonial stem cells transplant takes place in the seminiferous tubule, with the patient experiencing spermatogenesis. This therapy is sometimes used in cancer patients, whose sperm have been destroyed due to the gonadotoxic treatment.
* Ovarian stem cells may be used to generate new oocytes, which can then be implanted in the uterus after in vitro fertilization. This therapy is still in the experimental phase.
Epidemiology
Prevalence of infertility varies depending on the definition, i.e., on the period involved in the failure to conceive.
* Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity
Fecundity is defined in two ways; in human demography, it is the potential for reproduction of a recorded population as opposed to a sole organism, while in population biology, it is considered similar to fertility, the capability to produc ...
due to an increase in age.
* Fertility problems affect one in seven couples in the UK. Most couples (about 84%) who have regular sexual intercourse (that is, every two to three days) and who do not use contraception get pregnant within a year. About 95 out of 100 couples who are trying to get pregnant do so within two years.
* Women become less fertile as they get older. For women aged 35, about 94% who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only about 77%. The effect of age upon men's fertility is less clear.
* In people going forward for IVF in the UK, roughly half of fertility problems with a diagnosed cause are due to problems with the man, and about half due to problems with the woman. However, about one in five cases of infertility has no diagnosed cause.
* In Britain, male factor infertility accounts for 25% of infertile couples, while 25% remain unexplained. 50% are female causes, with 25% being due to anovulation and 25% tubal problems/other.
* In Sweden, approximately 10% of couples wanting children are infertile. In approximately one-third of these cases, the man is the factor, in one-third the woman is the factor, and in the remaining third the infertility is a product of factors on both parts.
* In many lower-income countries, estimating infertility is difficult due to incomplete information and infertility and childlessness stigmas.
* Data on income-limited individuals, male infertility, and fertility within non-traditional families may be limited due to traditional social norms. Historical data on fertility and infertility are limited, as any form of study or tracking only began in the early 20th century. Per one account, "The invisibility of marginalised social groups in infertility tracking reflects broader social beliefs about who can and should reproduce. The offspring of privileged social groups are seen as a boon to society. The offspring of marginalised groups are perceived as a burden."
Society and culture
Perhaps except for infertility in science fiction, films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing first in the latter part of the 2000s, although the techniques have been available for decades.
Pixar
Pixar (), doing business as Pixar Animation Studios, is an American animation studio based in Emeryville, California, known for its critically and commercially successful computer-animated feature films. Pixar is a subsidiary of Walt Disney ...
's '' Up'' contains a depiction of infertility in an extended life montage that lasts the first few minutes of the film.
''Other individual examples are referred to individual sub-articles of assisted reproductive technology''
Ethics
There are several ethical issues associated with infertility and its treatment.
* High-cost treatments are out of financial reach for some couples.
* Debate over whether health insurance companies (e.g., in the US) should be required to cover infertility treatment.
* Allocation of medical resources that could be used elsewhere
* The legal status of embryos fertilized in vitro
''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...
and not transferred in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
. (See also beginning of pregnancy controversy).
* Opposition to the destruction of embryos not transferred in vivo.
* IVF and other fertility treatments have increased by multiple birth
A multiple birth is the culmination of a multiple pregnancy, wherein the mother gives birth to two or more babies. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such births ...
s, provoking ethical analysis because of the link between multiple pregnancies, premature birth
Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is betwee ...
, and a host of health problems.
* Religious leaders' opinions on fertility treatments; for example, the Roman Catholic Church
The Catholic Church (), also known as the Roman Catholic Church, is the List of Christian denominations by number of members, largest Christian church, with 1.27 to 1.41 billion baptized Catholics Catholic Church by country, worldwid ...
views infertility as a calling to adopt or to use natural treatments (medication, surgery, or cycle charting), and members must reject assisted reproductive technologies.
* Infertility caused by DNA defects on the Y chromosome is passed on from father to son. If natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
is the primary error correction mechanism that prevents random mutations on the Y chromosome, then fertility treatments for men with abnormal sperm (in particular ICSI) only defer the underlying problem to the next male generation.
* Specific procedures, such as gestational surrogacy, have led to numerous ethical issues, particularly when people living in one country contract for surrogacy in another (transnational surrogacy).
Many countries have special frameworks for dealing with the ethical and social issues around fertility treatment.
* One of the best known is the HFEA – The UK's regulator for fertility treatment and embryo research. This was set up on 1 August 1991 following a detailed commission of enquiry led by Mary Warnock
Helen Mary Warnock, Baroness Warnock, (née Wilson; 14 April 1924 – 20 March 2019) was an English philosopher of ethics, morality, philosophy of education, education, and philosophy of mind, mind, and a writer on existentialism. She is best ...
in the 1980s
* A similar model to the HFEA has been adopted by the rest of the countries in the European Union. Each country has its own body or bodies responsible for the inspection and licensing of fertility treatment under the EU Tissues and Cells directive
* Regulatory bodies are also found in Canada and in the state of Victoria in Australia
See also
* Advanced maternal age
* Age and female fertility
* Antinatalism
* Birth control
Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth control only be ...
* Childlessness
* Conception device
* Kallmann Syndrome
* Klinefelter Syndrome
* Mossman–Pacey paradox
* Oncofertility, fertility in cancer patients
* Pentasomy X
* Population control
* Sterility
* Surrogate marriage
* Trisomy X
Trisomy X, also known as triple X syndrome and characterized by the karyotype 47,XXX, is a chromosome disorder in which a female has an extra copy of the X chromosome. It is relatively common and occurs in 1 in 1,000 females, but is rarely diagn ...
* Turner Syndrome
* Voluntary childlessness
Voluntary childlessness or childfreeness is the active choice not to have children and not to Adoption, adopt children. Use of the word ''childfree'' was first recorded in 1901 and entered common usage among Feminism, feminists during the 1970s. ...
References
Further reading
*
* Lock, Margaret and Vinh-Kim Nguyen. 2011. An anthropology of biomedicine: Wiley-Blackwell.
*
*
*
*
*
RCOG clinical guidelines for infertility
(concise guidelines)
Fertility: Assessment and Treatment for People with Fertility Problems
2004 (extensive guidelines)
GeneReviews/NCBI/NIH/UW entry on CATSPER-Related Male Infertility
Infertility not just a Female Problem
Assisted Reproduction in Judaism
{{Authority control
Fertility medicine
Gynaecological endocrinology
Women's health
Mycoplasma