HOME

TheInfoList



OR:

Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state of a human child or other young
offspring In biology, offspring are the young creation of living organisms, produced either by a single organism or, in the case of sexual reproduction, two organisms. Collective offspring may be known as a brood or progeny in a more general way. This ca ...
, because they 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 girl, the testes in a ...
, which is the body's start of reproductive capacity. In humans, infertility is the inability to become pregnant after one year of unprotected and regular sexual intercourse involving a male and female partner.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. There are many causes of infertility, including some that
medical intervention A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many different ...
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: estimates range from 12% to 28%.
Male infertility Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen ...
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 parts. In 10–20% of cases, no cause is found. The most common cause of female infertility is ovulatory problems, which generally manifest themselves by sparse or absent menstrual periods. Page last reviewed 15 July 2014 Male infertility is most commonly due to deficiencies in the
semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Sem ...
, and
semen quality Semen quality is a measure of male fertility, a measure of the ability of sperm in semen to accomplish fertilization. Semen quality involves both sperm quantity and quality Cryptorchidism, hypospadias, testicular cancer and poor semen qualit ...
is used as a surrogate measure of male fecundity. Women who are fertile experience a period of fertility before and during ovulation, and are infertile for the rest of the menstrual cycle. Fertility awareness methods are used to discern when these changes occur by tracking changes in
cervical mucus The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
or
basal body temperature Basal body temperature (BBT or BTP) is the lowest body temperature attained during rest (usually during sleep). It is usually estimated by a temperature measurement immediately after awakening and before any physical activity has been undertaken. ...
.


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 at age 24 and diminishes after 30, with pregnancy occurring rarely after age 50. A female is most fertile within 24 hours of ovulation. Male fertility peaks usually at age 25 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 jurisdictions. 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 of time (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 as the inability to conceive after a certain period of time (the length of which vary), so often the two terms overlap.


World Health Organization

The
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
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. Twelve months is the lower reference limit for ''Time to Pregnancy'' (TTP) by the World Health Organization. * a woman over 35 has not conceived after six months of contraceptive-free
sexual intercourse Sexual intercourse (or coitus or copulation) is a sexual activity typically involving the insertion and thrusting of the penis into the vagina for sexual pleasure or reproduction.Sexual intercourse most commonly means penile–vaginal pene ...
. These time intervals would seem to be reversed; this is an area where public policy trumps science. The idea is that for women beyond age 35, every month counts and if made to wait another six months to prove the necessity of medical intervention, the problem could become worse. The corollary to this is that, by definition, failure to conceive in women under 35 is not regarded with the same urgency as it is in those over 35.


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 a five-year period. Practical measurement problems, however, exist for any definition, because it is difficult to measure continuous exposure to the risk of pregnancy over a period of 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 still born child, without ever having had a live birth would present with primarily infertility'. Secondary 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 since their last live birth, during which they did not use any contraceptives. Thus the distinguishing feature is whether or not the couple have ever had a pregnancy that led to a live birth.


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" in order to appear mentally healthier than they are. It is also possible that women feel a sense of hopefulness/increased optimism prior to 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.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 and female partner 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 a 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 the infertile couples: low socioeconomic status is associated with increased chances of developing depression. In many cultures, 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; middle-class men are the most likely to respond in this way. 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.


Causes

Male infertility Male infertility refers to a sexually mature male's inability to impregnate a fertile female. In humans it accounts for 40–50% of infertility. It affects approximately 7% of all men. Male infertility is commonly due to deficiencies in the semen ...
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 parts. In 10–20% of cases, no cause is found. The most common cause of female infertility is ovulatory problems, which generally manifest themselves by sparse or absent menstrual periods. Male infertility is most commonly due to deficiencies in the
semen Semen, also known as seminal fluid, is an organic bodily fluid created to contain spermatozoa. It is secreted by the gonads (sexual glands) and other sexual organs of male or hermaphroditic animals and can fertilize the female ovum. Sem ...
, and
semen quality Semen quality is a measure of male fertility, a measure of the ability of sperm in semen to accomplish fertilization. Semen quality involves both sperm quantity and quality Cryptorchidism, hypospadias, testicular cancer and poor semen qualit ...
is used as a surrogate measure of male fecundity.


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 girl, the testes in a ...
, humans are naturally infertile; their
gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sp ...
s have not yet developed the gametes required to reproduce: boys'
testicle A testicle or testis (plural testes) is the male reproductive gland or gonad in all bilaterians, including humans. It is homologous to the female ovary. The functions of the testes are to produce both sperm and androgens, primarily testoste ...
s have not developed the
sperm cell Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, ...
s 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). Infertility 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 The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus ...
in their brain is still underdeveloped and cannot release the
hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
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 occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seco ...
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 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 ...
, 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 ...
( hypogonadism) or the body's responsiveness to
sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effect ...
s.


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 spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Pro ...
, influence on the implantation process, and impaired growth and development of the
embryo An embryo is an initial stage of development of 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 spe ...
. 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 on (head, mid piece, 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 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 a ...
, failure of immunosuppression and unprotected receptive anal or oral sex with men.


Sexually transmitted infections

Infections with the following sexually transmitted pathogens have a negative effect on 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 increased risk of infertility.


Genetic

Mutations to 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 Azoospermia is the medical condition of a man whose semen contains no sperm. It is associated with male infertility, but many forms are amenable to medical treatment. In humans, azoospermia affects about 1% of the male population and may be seen ...
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 A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
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 Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) is a method for detecting DNA fragmentation by labeling the 3′- hydroxyl termini in the double-strand DNA breaks generated during apoptosis. Method TUNEL is a method for detec ...
. * General factors **
Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
,
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The ...
disorders, undiagnosed and untreated coeliac disease,
adrenal The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex which ...
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 A in the presence of B and the odds of A in the absence of B, or equivalently (due ...
of 1.5 and 95%
confidence interval In frequentist statistics, a confidence interval (CI) is a range of estimates for an unknown parameter. A confidence interval is computed at a designated ''confidence level''; the 95% confidence level is most common, but other levels, such as 9 ...
of 1.1–2.0. * Environmental factors **
Toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849 ...
s such as glues, volatile organic solvents or
silicone A silicone or polysiloxane is a polymer made up of siloxane (−R2Si−O−SiR2−, where R = organic group). They are typically colorless oils or rubber-like substances. Silicones are used in sealants, adhesives, lubricants, medicine, cookin ...
s, physical agents, chemical dusts, and pesticides. Tobacco smokers are 60% more likely to be infertile than non-smokers. German scientists have reported that a virus called
adeno-associated virus Adeno-associated viruses (AAV) are small viruses that infect humans and some other primate species. They belong to the genus ''Dependoparvovirus'', which in turn belongs to the family '' Parvoviridae''. They are small (approximately 26 nm i ...
might have a role in male infertility, though it is otherwise not harmful. Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (
fallopian tube obstruction Fallopian tube obstruction, also known as fallopian tube occlusion is a major cause of female infertility. Blocked fallopian tubes are unable to let the ovum and the sperm converge, thus making fertilization impossible. Fallopian tubes are also kno ...
). * Alimentary habits **
Obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
: Obesity can have a significant impact on male and female fertility. BMI (body mass index) may be a significant factor in fertility, as an increase in BMI in the male by as little as three units can be associated with infertility. Several studies have demonstrated that an increase in BMI is correlated with a decrease in sperm concentration, a decrease in motility and an increase in DNA damage in sperm. A relationship also exists between obesity and erectile dysfunction (ED). ED may be the consequence of the conversion of androgens to estradiol. The enzyme aromatase is responsible for this conversion and is found primarily in adipose tissue. As the number of adipose tissue increases, there is more aromatase available to convert androgens, and serum estradiol levels increase. Other hormones including inhibin B and leptin, may also be affected by obesity. Inhibin B levels have been reported to decrease with increasing weight, which results in decreased Sertoli cells and sperm production. Leptin is a hormone associated with numerous effects including appetite control, inflammation, and decreased insulin secretion, according to many studies. Obese women have a higher rate of recurrent, early miscarriage compared to non-obese women. ** Low weight: Obesity is not the only way in which weight can impact fertility. Men who are underweight tend to have lower sperm concentrations than those who are at a normal BMI. For women, being underweight and having extremely low amounts of body fat are associated with ovarian dysfunction and infertility and they have a higher risk for preterm birth. Eating disorders such as
anorexia nervosa Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
are also associated with extremely low BMI. Although relatively uncommon, eating disorders can negatively affect menstruation, fertility, and maternal and fetal well-being.


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 (singular salpinx), are paired tubes in the human female that stretch from the uterus to the ovaries. The fallopian tubes are part of the female reproductive system. In o ...
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 of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, fa ...
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. 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. 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 (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 of females include: * ovulation problems (e.g. PCOS, the leading reason why women present to fertility clinics due to anovulatory infertility) * tubal blockage *
pelvic inflammatory disease Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be ...
caused by infections like
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...
* age-related factors * uterine problems * previous tubal ligation *
endometriosis Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, fa ...
* 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. There are multiple causes for male infertility. These include
endocrine disorders Endocrine diseases are disorders of the endocrine system. The branch of medicine associated with endocrine disorders is known as endocrinology. Types of disease Broadly speaking, endocrine disorders may be subdivided into three groups: # Endocrin ...
(usually due to hypogonadism) at an estimated 2% to 5%, sperm transport disorders (such as vasectomy) at 5%, primary testicular defects (which includes abnormal sperm parameters without any identifiable cause) at 65% to 80% and idiopathic (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.Mishail, A., et al. (2009) ''Impact of a second semen analysis on a treatment decision making in the infertile man with varicocele: 1809-1811'' Infertility associated with viable, but immotile sperm may be caused by primary ciliary dyskinesia. The sperm must provide the zygote with DNA, centrioles, 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 can lead to infertility in men.


Combined infertility

In some cases, both the man and woman may be infertile or sub-fertile, and the couple's infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance.


Unexplained infertility

In the US, up to 20% of infertile couples have unexplained infertility. In these cases, abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. However, a growing body of evidence suggests that epigenetic modifications in sperm may be partially responsible.


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 (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...
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. Women over the age of 35 should see their physician or WHNP after six months as fertility tests can take some time to complete, and age may affect the treatment options that are open in that case. 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. 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 Pregnancy rate is the success rate for getting pregnant. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simp ...
of 40% or higher per year are encouraged to continue aiming for a spontaneous pregnancy. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for both women and men include clomiphene citrate,
human menopausal gonadotropin Menotropin (also called human menopausal gonadotropin or hMG) is a hormonally active medication for the treatment of fertility disturbances. Frequently the plural is used as the medication is a mixture of gonadotropins. Menotropins are extracted ...
(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, pubertal maturation, ...
(FSH),
human chorionic gonadotropin Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantatio ...
(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 released ...
(GnRH) analogues, aromatase inhibitors, and metformin.


Medical treatments

Medical treatment of infertility generally involves the use of
fertility medication Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options a ...
, medical device, surgery, or a combination of the following. If the sperm is of good quality and the mechanics of the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring), a course of ovulation induction may be used. The physician or WHNP may also suggest using a conception cap
cervical cap The cervical cap is a form of barrier contraception. A cervical cap fits over the cervix and blocks sperm from entering the uterus through the external orifice of the uterus, called the ''os''. Terminology The term ''cervical cap'' has been ...
, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor or WHNP introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body. If conservative medical treatments fail to achieve a full-term pregnancy, the physician or WHNP may suggest the patient to undergo in vitro fertilization (IVF). IVF and related techniques ( ICSI, ZIFT, GIFT) are called
assisted reproductive technology Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gamet ...
(ART) techniques. ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer. Other medical techniques are e.g.
tuboplasty Tuboplasty refers to a number of surgical operations that attempt to restore patency and functioning of the fallopian tube(s) so that a pregnancy could be achieved. As tubal infertility is a common cause of infertility, tuboplasties were commonly p ...
, assisted hatching, and preimplantation genetic diagnosis.


In vitro fertilization

IVF is the most commonly used ART. It has been proven useful in overcoming infertility conditions, such as blocked or damaged tubes, endometriosis, repeated IUI failure, unexplained infertility, poor ovarian reserve, poor or even nil sperm count.


Intracytoplasmic sperm injection

ICSI technique is used in case of poor semen quality, low sperm count or failed fertilization attempts during prior IVF cycles. This technique involves an injection of a single healthy sperm directly injected into mature egg. The fertilized embryo is then transferred to womb.


Tourism

''Fertility tourism'' is the practice of traveling to another country for fertility treatments. It may be regarded as a form of
medical tourism Medical tourism refers to people traveling abroad to obtain medical treatment. In the past, this usually referred to those who traveled from less-developed countries to major medical centers in highly developed countries for treatment unavailable a ...
. The main reasons for fertility tourism are legal regulation of the sought procedure in the home country, or lower price. In-vitro fertilization and donor insemination are major procedures involved.


Stem cell therapy

Nowadays, there are several treatments (still in experimentation) related to
stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of ...
therapy. It is a new opportunity, not only for partners with lack of gametes, but also for same-sex couples and single people who want to have offspring. Theoretically, with this therapy, we can get artificial gametes ''in vitro''. There are different studies for both women and men. * Spermatogonial stem cells transplant: it takes places in the seminiferous tubule. With this treatment, the patient experience spermatogenesis, and therefore, it has the chance to have offspring if he wants to. It is specially oriented for cancer patients, whose sperm is destroyed due to the gonadotoxic treatment they are submitted to. * Ovarian stem cells: it is thought that women have a finite number of follicles from the very beginning. Nevertheless, scientists have found these stem cells, which may generate new oocytes in postnatal conditions. Apparently there are only 0.014% of them (this could be an explanation of why they were not discovered until now). There is still some controversy about their existence, but if the discoveries are true, this could be a new treatment for infertility. Stem cell therapy is really new, and everything is still under investigation. Additionally, it could be the future for the treatment of multiple diseases, including infertility. It will take time before these studies can be available for clinics and patients.


Epidemiology

Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive. * Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity 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 have no clear 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 stigma.


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 decade, although the techniques have been available for decades. Yet, the number of people that can relate to it by personal experience in one way or another is ever-growing, and the variety of trials and struggles is huge. Pixar'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 Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), cryopreservation of gamet ...
''


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'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...
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, and p ...
. (See also beginning of pregnancy controversy). * Opposition to the destruction of embryos not transferred in vivo. * IVF and other fertility treatments have resulted in an increase in multiple births, 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 between ...
, 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 largest Christian church, with 1.3 billion baptized Catholics worldwide . It is among the world's oldest and largest international institutions, and has played a ...
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 heritable traits characteristic of a population over generations. Cha ...
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 Human Fertilisation and Embryology Authority (HFEA) is an executive non-departmental public body of the Department of Health and Social Care in the United Kingdom. It is a statutory body that regulates and inspects all clinics in the Unite ...
– 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 morality, education, and mind, and a writer on existentialism. She is best known for chairing an inquiry whose report formed th ...
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 Female fertility is affected by age and is a major fertility factor for women. A woman's fertility peaks between the late teens and late-20s, after which it starts to decline slowly. While many sources suggest a more dramatic drop at around 35, ...
* Antinatalism *
Birth control Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...
* Childlessness * Conception device * Mossman–Pacey paradox * Oncofertility, fertility in cancer patients *
Population control Population control is the practice of artificially maintaining the size of any population. It simply refers to the act of limiting the size of an animal population so that it remains manageable, as opposed to the act of protecting a species from ...
* Sterility * Surrogate marriage * Voluntary childlessness


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 Women's health Mycoplasma