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Infertility
Infertility
Infertility
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Infertility
SpecialtyUrology, gynecology
CausesCommon in females: anovulation, blocked fallopian tube, hormonal imbalance
Common in males: low sperm count, abnormal sperm morphology
Frequency113 million (2015)[1]

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, so children who have not undergone puberty, which is the body's start of reproductive capacity, are excluded. It is also a normal state in women after menopause.

In humans, infertility is defined as the inability to become pregnant after at least one year of unprotected and regular sexual intercourse involving a male and female partner.[2] There are many causes of infertility, including some that medical intervention can treat.[3] Estimates from 1997 suggest that worldwide about five percent of all heterosexual couples have an unresolved problem with infertility. That figure has been on the rise, with the World Health Organization (WHO) reporting in 2023 that about 17.5% of couples experience infertility.[4] Many more couples, however, experience involuntary childlessness for at least one year, with estimates ranging from 12% to 28%.[5]

Male infertility is responsible for 20–30% of infertility cases, while 20–35% are due to female infertility, and 25–40% are due to combined problems in both partners.[6] In 10–20% of cases, no cause is found.[6]

The most common causes of female infertility are hormonal in nature, including low estrogen, imbalanced GnRH secretion, PCOS, and aging, which generally manifests in sparse or absent menstrual periods leading up to menopause.[7][8] As women age, the number of ovarian follicles and oocytes (eggs) decline, leading to a reduced ovarian reserve.[2] Some women undergo primary ovarian insufficiency (also known as premature menopause) or the loss of ovarian function before age 40, leading to infertility.[9] 85% of infertile couples have an identifiable cause and 15% is designated unexplained infertility.[2] Of the 85% of identified infertility, 25% is due to disordered ovulation (of which 70% of the cases are due to polycystic ovarian syndrome).[2] Tubal infertility (structural issues with the fallopian tubes) is responsible for 11–67% of infertility in women of childbearing age, with the large range in prevalence due to different populations studied.[2] Endometriosis, the presence of endometrial tissue (which normally lines the uterus) outside of the uterus, accounts for 25–40% of female infertility.[2]

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 or basal body temperature.

Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.[10] Male infertility may also be due to retrograde ejaculation, low testosterone, functional azoospermia (in which sperm is not produced or not produced in enough numbers) and obstructive azoospermia in which the pathway for the sperm (such as the vas deferens) is obstructed.[2]

Definition

[edit]

"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.[11] 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.[12]

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.[11] 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.[13]

World Health Organization

[edit]

The World Health Organization defines infertility as follows:[14]

Infertility is "a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse (and there is no other reason, such as breastfeeding or postpartum amenorrhoea). Primary infertility is infertility in a couple who have never had a child. Secondary infertility is the failure to conceive following a previous pregnancy. Infertility may be caused by infection in the man or woman, but often there is no obvious underlying cause."

United States

[edit]

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.

United Kingdom

[edit]

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.[15] 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."[16]

Other definitions

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Researchers commonly base demographic studies on infertility prevalence over five years.[17]

Primary vs. secondary infertility

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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.[18] 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'.[18]

Secondary infertility is defined as the difficulty in conceiving a live birth in couples who previously had a child.[18]

Effects

[edit]

Psychological

[edit]

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.[19] 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.[20] Fertility does not seem to increase when the women takes antioxidants to reduce the oxidative stress brought by the situation.[21]

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.[22] Partners may become more anxious to conceive, increasing sexual dysfunction.[23] 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.[24] Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.[25] Male 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.[22]

Social

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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.[26] Societal pressures may affect a couple's decision to approach, avoid, or experience an infertility treatment.[27] Moreover, the socioeconomic status influences the psychology of infertile couples: low socioeconomic status is associated with increased chances of developing depression.[22] 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.[28]

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.[29]

Sexual

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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.[30]

Causes

[edit]

Male infertility is responsible for 20–30% of infertility cases, while 20–35% are due to female infertility, and 25–40% are due to combined problems in both partners.[31][6] In 10–20% of cases, no cause is found.[6] The most common cause of female infertility is abnormal ovulation, usually manifested by scanty or absent menstrual periods.[8] Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.[10]

Iodine deficiency

[edit]

Iodine deficiency may lead to infertility.[32]

Natural infertility

[edit]

Before puberty, humans are naturally infertile; their gonads have not yet developed the gametes required to reproduce: boys' testicles have not developed the sperm cells required to impregnate a female; girls have not begun the process of ovulation which activates the fertility of their egg cells (ovulation is confirmed by the first menstrual cycle, known as menarche, which signals the biological possibility of pregnancy). 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 in their brain is still underdeveloped and cannot release the hormones required to activate the gonads' gametes. Fertility in children before the ages of eight or nine is considered a disease known as precocious puberty. This disease is usually triggered by a brain tumor or other related injury.[33]

Delayed puberty

[edit]
Main article: Delayed puberty
See also: Late bloomer

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).[34] Boys are considered to have delayed puberty if they lack enlargement of the testicles by age 14.[34] Delayed puberty affects about 2% of adolescents.[35][36]

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.[34] Delay of puberty may also occur due to various causes such as malnutrition, various systemic diseases, or defects of the reproductive system (hypogonadism) or the body's responsiveness to sex hormones.[34]

Immune infertility

[edit]

Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples.[37] In both men and women, ASA production is directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. The antibodies are classified into different groups: 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, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men.[37][38]

Sexually transmitted infections

[edit]

Infections with the following sexually transmitted pathogens hurt fertility: Chlamydia trachomatis and Neisseria gonorrhoeae. There is a consistent association of Mycoplasma genitalium infection and female reproductive tract syndromes. M. genitalium infection is associated with an increased risk of infertility.[39][40]

Genetic

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Main article: Genetics of infertility

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.[41]

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.[42] See Infertility associated with small supernumerary marker chromosomes and Genetics of infertility#Small supernumerary marker chromosomes and infertility.

Other causes

[edit]

Factors that can cause male as well as female infertility are:

  • DNA damage
    • DNA damage reduces fertility in female ovocytes, as caused by smoking,[43] other xenobiotic DNA damaging agents (such as radiation or chemotherapy)[44] or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine[45]
    • DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage,[46] smoking,[43] other xenobiotic DNA damaging agents (such as drugs or chemotherapy)[47] or other DNA-damaging agents, including reactive oxygen species, fever, or high testicular temperature.[48] The damaged DNA related to infertility manifests itself by the increased susceptibility to denaturation inducible by heat or acid[49] or by the presence of double-strand breaks that can be detected by the TUNEL assay.[50] 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
  • Hypothalamic-pituitary factors
  • Environmental factors

Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).[65][66][67]

  • Body mass, the BMI (body mass index) (either being too high or too low) may be a contributor to infertility.

Females

[edit]
Further information: Female infertility

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.[69]

For women, problems with fertilization arise mainly from either structural problems in the fallopian tube 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 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.[70]

Another major cause of infertility in women may be the inability to ovulate. This is usually related to low levels of the sex hormone estrogen, as well as imbalanced GnRH secretion.[7] Ovulatory disorders make up 25% of the known causes of female infertility.[7]

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[7]

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.[citation needed]

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.[71]

Sometimes it can be a combination of factors, and sometimes a clear cause is never established.

Common causes of infertility in females include:

Males

[edit]
Further information: Male infertility

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.[2] 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 (where an infertile male has normal sperm and semen parameters) at 10% to 20%.[73]

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.[74] 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.[75] Antisperm antibodies cause immune infertility.[37][34] Cystic fibrosis can lead to infertility in men by blocking the vas deferens.[2]

Adeno-associated virus infection has been linked to poor sperm quality and may contribute to male infertility, based on small observational studies.[76]

Unexplained infertility

[edit]
Main article: Unexplained infertility

In the US, up to 15% of infertile couples have unexplained infertility, in which no identifiable cause is found.[2] polymorphisms in folate pathway genes may be a cause for fertility complications in some women with unexplained infertility.[77] Epigenetic modifications in sperm may also be responsible for unexplained infertility.[78][79]

In animals

[edit]

Many other mammals experience infertility. Hybrid animals are usually infertile, due to their odd number of chromosomes.

Diagnosis

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Main article: Fertility testing

If both partners are young and healthy and have been trying to conceive for one year without success, a visit to a physician 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.[80]

However, there are instances where couples should seek reproductive counseling after only 6 months of trying for a pregnancy:

  • The woman is over 35 years old.[81]
  • The woman has a history of endometriosis.[82]
  • The woman has infrequent or irregular menses.
  • 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

[edit]

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.[83] Drugs used include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) analogues, and aromatase inhibitors.[84]

Medical treatments

[edit]

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 (FSH) from the anterior pituitary. FSH and LH act on the ovaries to increase follicle growth and lead to ovulation.[2] 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.[2] Both clomiphene and letrozole have a risk of a multiple gestation pregnancy, with the risk being less than 10%.[2] Those with hypogonadotropic hypogonadism require pulsatile GnRH therapy, which is associated with a 93-100% pregnancy rate after 6 months of therapy.[2] The risk of a multiple gestation pregnancy with gonadotropins is 36%.[2] 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.[2]

Fertility treatments or medications do not increase the risk of breast, ovarian, or endometrial cancers.[2]

Metformin does not increase the rate of live births in those with infertility (including in those with PCOS), and its use is not recommended.[2]

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.[2] ICSI was first developed in 1978 by Robert Edwards and Patrick Steptoe.[85]

Ovarian stimulation (such as with clomiphene) combined with in-vitro fertilization or intra-uterine insemination has lower success rates with increasing age.[2]

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.[2]

A depiction of the procedure of in-vitro fertilization

Tourism

[edit]
Main article: Fertility tourism

Fertility tourism is the practice of traveling to another country for fertility treatments.[86]

Stem cell therapy

[edit]

Several experimental treatments related to stem 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.[87]

  • 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.[88]
  • 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.[89]

Epidemiology

[edit]

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 due to an increase in age.[90]
  • 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.[91]
  • 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.[92]
  • 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.[93]
  • 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.[94]
  • In Sweden, approximately 10% of couples wanting children are infertile.[95] 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."[96]

Society and culture

[edit]

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.[97]

Pixar's Up contains a depiction of infertility in an extended life montage that lasts the first few minutes of the film.[98]

Other individual examples are referred to individual sub-articles of assisted reproductive technology

Ethics

[edit]

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 and not transferred in vivo. (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 births, provoking ethical analysis because of the link between multiple pregnancies, premature birth, and a host of health problems.
  • Religious leaders' opinions on fertility treatments; for example, the Roman Catholic Church 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 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).[99][100]

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 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[101]
  • Regulatory bodies are also found in Canada[102] and in the state of Victoria in Australia[103]

See also

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References

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Further reading

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Infertility

View on Grokipedia
from Grokipedia
Infertility is a disease of the male or female reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. It affects both sexes, with causes including impaired gamete production, transport, or fertilization, and can be primary (no prior pregnancies) or secondary (following previous conceptions). Globally, approximately 17.5% of the adult population—roughly one in six people—experiences infertility in their lifetime, with prevalence similar across high- and low-income countries at around 17-18%. Recent studies indicate an increasing burden, with female infertility cases rising over 100% in certain age groups like 30-34 from 1990 to 2021, driven partly by delayed childbearing amid declining natural fertility with age. Causes are multifactorial: in women, ovulatory disorders account for about 25% of cases, tubal blockages around 20-36%, and endometriosis 6%; in men, low sperm count or motility contributes comparably, often 19-50% depending on cohorts; unexplained factors comprise 10-40%. Lifestyle elements like obesity, smoking, and environmental exposures exacerbate risks, while age-related oocyte quality decline in women post-35 sharply reduces conception odds, reflecting biological imperatives over modifiable factors alone. Treatments range from lifestyle interventions and medications to assisted reproductive technologies like in vitro fertilization (IVF), which has enabled over 95,000 U.S. births annually by 2023, with live birth rates per cycle around 55% for women under 35 but dropping below 25% after 40. Success often requires multiple cycles, highlighting IVF's role as a milestone achievement yet limited by maternal age and underlying pathologies. Controversies persist over access inequities and debates on whether rising rates stem more from deferred reproduction or unproven environmental claims, underscoring the need for empirical focus on causal biology.

Definition and Classification

Core Definitions and Physiological Basis

Infertility is defined medically as the failure to achieve a clinical after 12 months of regular, unprotected in couples where the is under 35 years of age, or after 6 months if she is 35 or older. This timeframe accounts for the natural monthly rate of approximately 20-25% in healthy couples during peak reproductive years, allowing for statistical differentiation between subfertility and chance. Clinical pregnancy refers to evidence of embryonic development confirmed by or histopathological examination, distinguishing it from biochemical markers alone. Physiologically, human reproduction requires synchronized gamete production, transport, fertilization, and implantation. In females, begins in fetal life with a finite pool of primordial follicles (approximately 1-2 million at birth, declining to 300,000-400,000 by ), where monthly recruitment yields one dominant via follicular development driven by pituitary gonadotropins (FSH and LH). releases the into the , where fertilization by must occur within 12-24 hours due to oocyte viability limits. capacitation—acquiring hyperactivated motility and —enables penetration, followed by pronuclear fusion and embryonic cleavage. Successful reproduction further demands transport to the (via tubal cilia and contractions), endometrial receptivity for implantation (peaking days 20-24 of a 28-day cycle, regulated by progesterone and ), and early invasion to establish . Male physiology centers on , a continuous process in seminiferous tubules yielding 100-200 million per ejaculate, with 40-60% and <15% abnormal forms deemed normal per WHO thresholds (2021 criteria). Disruptions at any stage—e.g., anovulation (affecting 25% of female infertility cases), tubal blockage (from pelvic inflammatory disease, impacting 20-30%), or oligospermia (<15 million/mL, in 40-50% of male cases)—yield infertility, often multifactorial with combined male-female contributions in 30-40% of couples.32476-6/fulltext) These processes reflect evolved efficiencies under natural selection, where age-related declines (e.g., oocyte aneuploidy rising from 20% at age 25 to 80% at 40) underscore fertility's temporal constraints.

Primary Versus Secondary Infertility

Primary infertility is defined as the inability to achieve a clinical pregnancy after 12 months or more of regular, unprotected sexual intercourse in couples who have never previously conceived. This threshold shortens to 6 months for women aged 35 or older due to age-related declines in fertility. The definition applies to both partners, though evaluation often focuses on female factors initially, as they account for approximately 40-50% of cases in primary infertility. In contrast, secondary infertility occurs when a couple has previously achieved at least one pregnancy—resulting in a live birth, miscarriage, or ectopic pregnancy—but cannot conceive again after 12 months of trying under similar conditions. Like primary infertility, the timeframe adjusts for women over 35. Secondary cases represent a distinct clinical entity, as prior fertility indicates that baseline reproductive physiology was once functional, but subsequent factors have impaired it. Key differences between primary and secondary infertility lie in etiology and psychological impact. Primary infertility often stems from congenital or longstanding issues, such as untreated ovulatory disorders, tubal blockages from pelvic inflammatory disease, or untreated male factor infertility like low sperm count. Secondary infertility, however, frequently arises from acquired changes post-pregnancy, including uterine adhesions (Asherman's syndrome) from curettage after miscarriage or delivery, age-related ovarian reserve depletion accelerating after the first birth, or complications like endometriosis progression or male age-related sperm DNA fragmentation. Hormonal disturbances, such as polycystic ovary syndrome exacerbations or thyroid dysfunction unmasked after childbirth, are more prevalent in secondary cases. Both types share overlapping causes like obesity or smoking, but secondary infertility diagnostic protocols prioritize reviewing obstetric history to identify interval-acquired pathologies. Prevalence data indicate secondary infertility may be more common globally than primary, with estimates from 1990-2010 showing primary rates at 0.6-3.4% and secondary at 8.7-32.6% across regions. In the United States, secondary infertility affects about 11% of couples, matching primary rates, yet it constitutes up to 60% of infertility clinic referrals due to underreporting among parous couples who delay seeking help. Worldwide, infertility impacts roughly 1 in 6 people of reproductive age, with secondary cases often linked to rising maternal age at subsequent pregnancies, averaging 30-35 years in developed nations. These patterns underscore that secondary infertility, while biologically similar in mechanisms, carries a higher stigma and diagnostic delay, as affected individuals may attribute failures to chance rather than pathology.

Variations Across Definitions

The World Health Organization (WHO) and the International Committee for Monitoring Assisted Reproductive Technology (ICMART), in their 2017 glossary, define infertility as "a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse." This definition emphasizes physiological impairment and requires empirical evidence of failed conception attempts, distinguishing it from voluntary childlessness or transient delays in fertility. Variations arise in the temporal threshold for diagnosis, particularly with age-related adjustments. While the 12-month benchmark applies broadly, clinical guidelines from organizations like the American Society for Reproductive Medicine (ASRM) recommend initiating evaluation after 6 months for women aged 35 or older, reflecting accelerated age-related declines in oocyte quantity and quality that reduce per-cycle fecundity from approximately 20-25% in the early 30s to under 5% by age 40. This adjustment prioritizes earlier intervention without redefining the core condition, as strict adherence to 12 months could delay treatment in cases where cumulative probability of conception drops sharply after age 35. Epidemiological studies highlight how such definitional flexibility affects prevalence estimates; for instance, unprotected intercourse-based criteria classify more individuals as infertile in younger cohorts (ages 18-29) compared to older ones, potentially inflating early-life rates if not contextualized by attempt duration. Further divergence occurs in inclusivity criteria, moving beyond assumptions of heterosexual intercourse. The ASRM's 2023 committee opinion expands infertility to encompass "the need for medical intervention—including, but not limited to, in vitro fertilization—to achieve a reproductive goal, regardless of age, marital status, sexual orientation, or gender identity," framing it as a disease impairing reproductive function irrespective of partnership dynamics. This shift addresses limitations in intercourse-centric definitions, which exclude same-sex couples, single individuals, or those using donor gametes, while aligning with causal realities of reproductive barriers like gamete dysfunction or uterine factors that necessitate assisted reproduction. In contrast, the WHO definition retains a focus on natural conception attempts, potentially underrepresenting non-traditional pathways in global data. These definitional evolutions reflect ongoing debates between physiological specificity and equitable access to diagnostics, with evidence indicating that broader criteria improve early detection without diluting empirical standards.

Causes of Infertility

Female-Specific Biological Factors

Female infertility arises from disruptions in the reproductive tract's biological processes, including ovulatory dysfunction, structural abnormalities in the fallopian tubes or uterus, and age-related decline in oocyte quantity and quality. Ovulatory disorders, which prevent the release of viable eggs, constitute about 25% of diagnosed cases. These include polycystic ovary syndrome (PCOS), the most prevalent endocrine disorder affecting 6-12% of reproductive-age women, where elevated androgens and insulin resistance disrupt follicular development and lead to chronic anovulation. Hyperandrogenism in PCOS inhibits ovulation by altering gonadotropin secretion and promoting cyst formation rather than dominant follicle maturation. Hypothalamic-pituitary axis dysfunction, often from stress-induced hyperprolactinemia, further contributes by suppressing gonadotropin-releasing hormone, resulting in oligo-ovulation or amenorrhea. Age exerts a profound biological effect through diminished ovarian reserve, where the finite pool of primordial follicles—peaking at about 1-2 million at birth and declining to 1,000 by menopause—depletes progressively, accelerating after age 35. By age 40, natural fecundity drops to 5% per cycle from 20-25% in the early 20s, attributable to both quantitative loss and qualitative defects like increased aneuploidy in oocytes due to accumulated meiotic errors and mitochondrial dysfunction. (AMH) levels, a marker of follicular pool size, fall correspondingly, with women over 35 showing threefold higher infertility risk. Premature ovarian insufficiency, affecting 1% of women under 40, mirrors this process earlier via accelerated follicular atresia, often linked to genetic mutations in genes like FOXL2 or BMP15. Tubal factors account for 25-35% of female infertility, primarily from blockages or adhesions that impede sperm transport, fertilization, or embryo migration to the uterus. Proximal tubal occlusion, seen in 10-25% of such cases, often stems from inflammatory scarring post-pelvic inflammatory disease (PID), while distal hydrosalpinx results from chronic obstruction. Endometriosis, present in up to 10% of reproductive-age women, exacerbates tubal issues through ectopic endometrial tissue inducing pelvic adhesions, inflammation, and oxidative stress that impairs oocyte pickup and tubal peristalsis; infertility rates reach 30-50% in affected women, though causation involves multifactorial mechanisms beyond anatomy, including altered peritoneal fluid cytokines reducing sperm motility and embryo implantation potential. Uterine abnormalities, such as leiomyomas (fibroids) in 20-40% of women over 35, distort the endometrial cavity or alter myometrial contractility, hindering implantation; submucosal fibroids particularly elevate miscarriage risk by 20-30% via vascular disruption and inflammatory cytokine release. Congenital anomalies like unicornuate uterus, occurring in 0.1% of women, reduce implantation success by 15-20% due to reduced cavity volume and asymmetric vascular supply. Cervical factors, though rarer (less than 5%), involve hostile mucus from chronic cervicitis that blocks sperm ascent during ovulation. These biological impediments underscore the interplay of hormonal, anatomical, and cellular processes in female reproductive failure.

Male-Specific Biological Factors

Male-specific biological factors in infertility encompass disruptions to spermatogenesis, sperm quality, and ejaculatory function, detectable via semen analysis revealing oligospermia (sperm concentration <15 million/mL), asthenospermia (motility <32%), teratospermia (normal morphology <4%), or azoospermia (absence of sperm). These impairments contribute to 20% of cases where males are solely responsible and 30-50% of couples experiencing infertility overall. Spermatogenesis, the process of germ cell proliferation and maturation in the seminiferous tubules under hormonal regulation by follicle-stimulating hormone (FSH) and testosterone, fails due to intrinsic testicular defects, leading to reduced sperm output or defective gametes unable to fertilize oocytes. Varicocele, involving unilateral or bilateral dilation of the pampiniform plexus veins within the scrotum, represents the most prevalent surgically correctable biological cause, affecting 15% of adult males generally but 35-40% of those with primary infertility. Elevated scrotal temperature from venous stasis induces oxidative stress, apoptosis of germ cells, and DNA fragmentation in sperm, correlating with lower semen parameters and DNA integrity compared to normospermic men. World Health Organization data from large-scale analyses confirm significantly reduced sperm concentration in infertile men with varicocele versus those without, though causality remains debated due to observational study limitations and variable post-treatment fertility gains of 10-30% in pregnancy rates. Genetic anomalies account for 15-30% of severe cases, particularly non-obstructive or oligozoospermia, by directly impairing germ cell development or meiotic division. (47,XXY karyotype), the most common sex chromosome aneuploidy with incidence of 1:500-1:000 male births, causes progressive hyalinization of seminiferous tubules, germ cell depletion, and elevated FSH from primary hypogonadism, resulting in in 90-100% of untreated cases. Y-chromosome microdeletions in azoospermia factor (AZF) regions, detected in 10-15% of men with non-obstructive , delete multicopy genes like DAZ essential for spermatogonial proliferation, with complete AZFa or AZFb deletions yielding uniformly absent sperm retrieval while AZFc allows focal spermatogenesis in 50% of cases. These deletions arise de novo or inherit maternally but transmit paternally only if sperm is present, raising ethical concerns in assisted reproduction. Endocrine dysregulation at the testicular level, such as primary hypogonadism from Sertoli or Leydig cell failure, manifests as hypergonadotropic hypogonadism with FSH >10 IU/L and low testosterone (<300 ng/dL), signaling defective feedback and spermatogenic arrest. Idiopathic testicular failure, lacking identifiable genetic or structural etiology, predominates in 60-70% of non-obstructive azoospermia cases, potentially involving subtle microvascular or apoptotic pathways that evade routine diagnostics. Congenital conditions like cryptorchidism, if uncorrected post-puberty, reduce ipsilateral spermatogenesis by 40-50% via heat-induced damage, compounding bilateral fertility deficits.

Genetic, Immune, and Infectious Causes

Genetic causes of infertility encompass chromosomal abnormalities and monogenic mutations that disrupt gametogenesis, hormonal regulation, or structural development of reproductive organs in both sexes. In females, Turner syndrome (45,X karyotype) is a primary chromosomal cause, occurring in approximately 1 in 2,000 to 2,500 live female births and resulting in ovarian dysgenesis with streak gonads, leading to primary amenorrhea and infertility due to absent or dysfunctional oocytes. X chromosome abnormalities represent the most frequent genetic etiology of female infertility, accounting for about 10% of cases overall. In males, Klinefelter syndrome (47,XXY) affects 1 in 500 to 1,000 males and typically causes non-obstructive azoospermia through testicular dysgenesis and elevated gonadotropins. Y-chromosome microdeletions, particularly in the azoospermia factor (AZF) regions, occur in 7% of men with azoospermia or severe oligozoospermia, impairing spermatogenesis by deleting genes essential for sperm production. Monogenic causes include over 100 validated genes associated with phenotypes such as non-obstructive azoospermia or multiple morphological abnormalities of the sperm flagella, with autosomal recessive inheritance predominant; these account for roughly 4% of diagnosed male infertility cases. Immune-mediated infertility primarily involves antisperm antibodies (ASAs), which bind to sperm antigens and impair motility, capacitation, acrosome reaction, and fertilization capacity. ASAs arise from immune exposure to sperm antigens due to breaches in the blood-testis barrier, such as from testicular trauma, vasectomy (affecting 70-100% of cases), infections, or varicocele, though idiopathic origins occur. Prevalence in infertile men ranges from 2.6% to 6.6%, significantly higher than in fertile controls (0.9-2.5%), with detection via direct assays like mixed antiglobulin reaction (MAR) or immunobead tests showing binding on >50% of sperm indicating clinical relevance. In women, circulating ASAs can similarly hinder sperm transport or penetration, though male-factor immunological infertility predominates; associated conditions include autoimmune disorders like thyroiditis or celiac disease, which may indirectly exacerbate infertility through ovulatory disruption. Diagnosis requires immunological semen analysis per WHO guidelines, as ASAs correlate with reduced natural conception rates but variable IVF success. Infectious agents, particularly sexually transmitted infections (STIs), contribute to infertility via direct gonadal damage or secondary complications like pelvic inflammatory disease (PID). Chlamydia trachomatis and Neisseria gonorrhoeae are leading causes, with untreated chlamydial infections progressing to PID in 10-15% of women, resulting in tubal scarring, adhesions, and obstruction that manifest as tubal factor infertility (TFI). Globally in 2021, chlamydia accounted for 24.87% (4.76 million cases) of infection-attributable female infertility, while gonorrhea contributed 3.82% (0.73 million cases), with TFI representing 11-67% of infertility etiologies depending on region. In men, these pathogens can induce epididymitis or prostatitis, leading to obstructive azoospermia or reduced sperm quality; additionally, non-STI infections like mumps orchitis cause permanent testicular atrophy in 20-30% of post-pubertal cases. Early antibiotic treatment mitigates risks, but asymptomatic infections amplify prevalence, underscoring screening's role in prevention.

Lifestyle and Environmental Contributors

Lifestyle factors such as smoking, obesity, and excessive alcohol consumption, as well as suboptimal timing of intercourse relative to ovulation, prolong the time to natural conception by reducing per-cycle fecundity; intercourse every 1-2 days during the fertile window optimizes probabilities. Maternal age further contributes to extended conception times, as detailed in female-specific biological factors. Smoking tobacco is associated with reduced in both sexes, with meta-analyses indicating an of approximately 1.6 for infertility among female smokers compared to nonsmokers. In men, smoking correlates with lower quality and count, contributing to prolonged time to conception. Excessive alcohol consumption elevates infertility risk, with studies reporting adjusted odds ratios of 2.0 to 2.5 for moderate to high intake levels in both genders. , often measured by elevated or relative fat mass, independently increases infertility odds, particularly in women, by disrupting ovulatory function and hormonal balance; one analysis linked higher relative fat mass to significantly elevated risk in women aged 18-45. Dietary patterns and physical inactivity further compound risks, as imbalanced and sedentary behavior impair quality and reproductive levels, with systematic reviews identifying these as modifiable contributors to infertility prevalence. and poor , often tied to , may exacerbate these effects through cortisol-mediated disruptions in reproductive physiology, though causal links require further longitudinal data. Environmental exposures to endocrine-disrupting chemicals (EDCs) such as (BPA) from plastics and from consumer products are linked to impairment, with human studies showing BPA associated with altered parameters, reduced , and extended time to . residues, including organophosphates, correlate with decreased concentration and quality in exposed populations, based on epidemiological data from agricultural workers and general cohorts. Heavy metals like lead and , alongside per- and polyfluoroalkyl substances (PFAS), exhibit similar associations with ovulatory dysfunction and spermatogenic defects, as evidenced in reviews of occupational and environmental exposure studies. While some meta-analyses report inconsistent links for certain EDCs, population-level trends and mechanistic evidence from receptor interference support causal contributions, particularly for female reproductive outcomes.

Diagnosis and Assessment

Initial Evaluation and Testing

The initial evaluation of infertility involves a systematic assessment of both partners to identify treatable causes efficiently. Guidelines recommend initiating after 12 months of regular, unprotected intercourse for women under 35 years of age, or after 6 months for those 35 years or older, with earlier assessment warranted in cases of known risk factors such as irregular menses, prior pelvic , or exceeding 40 years. Concurrent of male and female partners is standard, as male factors contribute to approximately 40% of cases, female factors to another 40%, and combined issues to 20%. A comprehensive history precedes testing, encompassing medical conditions (e.g., , disorders), surgical history (e.g., , excision), reproductive details (e.g., coital frequency, prior pregnancies, length), family history of genetic disorders, and factors (e.g., , alcohol use, ). focuses on relevant systems: for women, a pelvic exam assesses uterine size, adnexal masses, and signs of ; for men, genital exam evaluates testicular (normal >15 mL per testis via ) and presence. Semen analysis serves as the cornerstone initial test for male fertility, performed after 2-5 days of ejaculatory abstinence and including measures of volume (normal ≥1.5 mL), total sperm count (≥39 million per ejaculate), concentration (≥15 million/mL), (≥40% total, ≥32% progressive), and morphology (≥4% normal forms per strict criteria). Abnormal results prompt repeat analysis or further endocrine testing (e.g., testosterone, FSH, LH) only if indicated, as routine hormonal screening lacks evidence for all men. For women, initial testing confirms through midluteal-phase serum progesterone (>3 ng/mL indicating ) or cycle tracking via or urinary kits, as underlies 25% of . Ovarian reserve assessment typically includes day-3 (FSH <10 mIU/mL optimal) and anti-Müllerian hormone (AMH) levels, with AMH providing a more reliable gauge of antral follicle count independent of cycle day. Basic screening for thyroid-stimulating hormone and prolactin occurs if history suggests endocrine disruption, given hypothyroidism's prevalence in 2-4% of reproductive-age women and its reversible impact on fertility. Transvaginal ultrasound evaluates uterine anatomy and ovarian morphology, while hysterosalpingography (HSG) or sonohysterography assesses tubal patency and intracavitary lesions if initial findings warrant. These steps prioritize cost-effective, non-invasive tests before advancing to laparoscopy or genetic karyotyping.

Advanced Diagnostic Techniques

Advanced diagnostic techniques for infertility extend beyond initial evaluations such as semen analysis, ovulation assessment, and basic imaging, employing invasive procedures and molecular analyses to pinpoint structural, genetic, or functional anomalies in reproductive organs or gametes. These methods are typically reserved for cases of unexplained infertility, suspected endometriosis, tubal factors, or severe oligospermia/azoospermia, as they carry procedural risks like infection or anesthesia complications but offer higher diagnostic precision. Evidence from systematic reviews supports their utility in improving subsequent fertility outcomes when abnormalities are identified and treated. In female patients, laparoscopy serves as the gold standard for evaluating tubal patency and pelvic pathology, involving chromopertubation to detect blockages and direct visualization of endometriosis or adhesions. Performed under general anesthesia via small abdominal incisions, it is indicated for suspected stage III/IV endometriosis or hydrosalpinx, with studies showing improved spontaneous pregnancy rates post-resection (e.g., a 2021 JAMA analysis of endometriosis treatment). Hysteroscopy, an endoscopic examination of the uterine cavity, identifies intrauterine lesions like polyps or submucosal fibroids that may impair implantation; a 2018 Cochrane review of randomized trials demonstrated higher live birth rates following polypectomy in affected women. Advanced imaging adjuncts, such as sonohysterography (saline-infused ultrasound) or 3D ultrasound/MRI, enhance detection of congenital uterine malformations (e.g., bicornuate uterus) with sensitivities up to 91% for polyps, reserved for recurrent miscarriage or abnormal bleeding. Genetic testing represents a cornerstone of advanced diagnostics across genders, targeting heritable defects contributing to gamete dysfunction or diminished reserve. For women over 35 or with family history of premature ovarian insufficiency, fragile X premutation screening (FMR1 gene, 55-200 CGG repeats) assesses ovarian reserve risks. In men, karyotyping detects chromosomal aberrations like (prevalent in 15% of azoospermic cases), while Y-chromosome microdeletion analysis via PCR identifies AZF region losses in up to 10-15% of severe oligospermia (<5 million/mL), informing surgical sperm retrieval success rates of 47% per meta-analysis. Fluorescent in situ hybridization (FISH) evaluates sperm aneuploidy rates, elevated in infertile males and predictive of IVF/ICSI outcomes. For male infertility, testicular biopsy provides histopathological insight into spermatogenesis arrest or maturation defects, particularly in obstructive or nonobstructive azoospermia, and facilitates sperm extraction for assisted reproduction; it reveals lower DNA fragmentation in testicular versus ejaculated sperm. Specialized semen assays, including sperm chromatin structure assays for DNA integrity or reactive oxygen species measurement (elevated in 40% of infertile samples), correlate with fertilization failure and embryo arrest, guiding prognosis in advanced cases. These techniques, while resource-intensive, enable causal identification over empirical treatment, though their routine application remains debated due to cost-benefit ratios in low-yield scenarios.

Treatment Options

Medical and Surgical Interventions

Evidence from systematic reviews and meta-analyses supports several non-invasive fertility enhancement methods, primarily lifestyle interventions and nutritional supplements. Weight loss in overweight or obese individuals improves fertility markers and outcomes, such as ovulation and pregnancy rates, though evidence is mixed and often insufficient for strong clinical recommendations. Adherence to healthy diets, such as the Mediterranean diet, benefits fertility parameters in both men and women. For male infertility, supplements like L-carnitine combined with micronutrients and antioxidants significantly improve sperm parameters, including motility and concentration, and may enhance pregnancy rates. Coenzyme Q10 (CoQ10) supplementation increases clinical pregnancy rates in women undergoing assisted reproductive technology (ART), though it does not significantly affect live birth rates. These approaches represent evidenced non-invasive options distinct from more established medical or surgical interventions. Medical interventions for female infertility primarily target ovulation disorders, which account for approximately 25% of cases. Clomiphene citrate, an oral selective estrogen receptor modulator, induces ovulation by blocking estrogen receptors in the hypothalamus, leading to increased gonadotropin secretion; it has been used for over 40 years and achieves ovulation rates of 60-80% in anovulatory women without polycystic ovary syndrome (PCOS). Letrozole, an aromatase inhibitor, suppresses estrogen production to promote follicular development and has demonstrated comparable live birth rates to clomiphene in women with PCOS, with ovulation rates exceeding 60% in randomized trials. Injectable gonadotropins, such as follicle-stimulating hormone (FSH), are reserved for clomiphene-resistant cases and yield higher multiple pregnancy risks but superior ovulation induction in severe anovulation. Surgical interventions for female infertility address structural issues like tubal blockages or endometriosis. Laparoscopic tubal anastomosis for sterilization reversal restores patency in suitable candidates, with pregnancy rates of 55-75% and live birth rates around 53% reported in retrospective series, influenced by tubal length and patient age under 35. For endometriosis-associated infertility, laparoscopic excision of endometriotic lesions improves spontaneous pregnancy rates by 10-25% compared to diagnostic laparoscopy alone, particularly in mild to moderate stages, though evidence is limited by small trials and potential selection bias. Tubal surgery remains viable when fallopian tube patency is confirmed and IVF is not preferred, but success diminishes with advanced maternal age or severe adhesions. In male infertility, pharmacological options focus on hypogonadotropic hypogonadism or idiopathic oligozoospermia, though evidence for broad efficacy is inconsistent. Clomiphene citrate off-label use elevates endogenous testosterone and improves sperm concentration and motility in meta-analyses of hypogonadal men, with pregnancy rates increasing by 10-20% in select cohorts, but routine application lacks strong support due to variable semen parameter improvements. Exogenous testosterone replacement therapy is contraindicated as it suppresses spermatogenesis via negative feedback on the hypothalamic-pituitary-gonadal axis, reducing sperm counts in up to 90% of users; alternatives like human chorionic gonadotropin (hCG) are preferred for fertility preservation. Surgical treatments for male infertility emphasize varicocele correction, present in 15-20% of infertile men. Microsurgical varicocelectomy improves semen parameters in 60-80% of cases, with spontaneous pregnancy rates of 40-70% at 1-2 years post-procedure, outperforming embolization in recurrence rates (under 1%) and supported by meta-analyses showing odds ratios for conception up to 2.65. Vasectomy reversal via microsurgical vaso-vasostomy achieves patency rates of 90-95% and pregnancy rates of 50-70% within 2 years, declining with obstruction duration over 10 years due to antisperm antibody formation. These interventions prioritize natural conception attempts before advancing to assisted technologies, with outcomes contingent on baseline semen quality and partner fertility.

Assisted Reproductive Technologies

Assisted reproductive technologies (ART) encompass medical procedures that handle human eggs, sperm, or embryos outside the body to achieve pregnancy, with in vitro fertilization (IVF) as the predominant method. IVF involves ovarian stimulation to produce multiple eggs, transvaginal oocyte retrieval, laboratory fertilization of eggs with sperm, embryo culture for 3-5 days, and transfer of one or more embryos into the uterus. (ICSI), a variant used in about 60% of U.S. IVF cycles, directly injects a single sperm into an egg to address severe male factor infertility or prior fertilization failure. Less common procedures include gamete intrafallopian transfer (GIFT), where eggs and sperm are placed into the fallopian tube, and zygote intrafallopian transfer (ZIFT), involving transfer of a fertilized zygote to the tube, though these have declined due to the efficacy and simplicity of uterine embryo transfer in IVF. Success rates for ART vary significantly by maternal age, underlying infertility causes, and cycle specifics like fresh versus frozen embryo transfer. In the United States, CDC data from 2021 indicate live birth rates per intended egg retrieval of approximately 54% for women under 35 using their own eggs in fresh cycles, dropping to 41% for ages 35-37, 25% for 38-40, and 7% for over 42. For frozen embryo transfers, rates are often higher, reaching 50-60% in younger women due to improved embryo selection and endometrial preparation. Overall, ART resulted in 95,860 live births in the U.S. in 2023, up from 91,771 in 2022, reflecting increased utilization amid rising infertility rates. Preimplantation genetic testing (PGT) for aneuploidy enhances outcomes by selecting euploid embryos, reducing miscarriage rates, though it does not universally improve live birth rates across all patients.
Maternal Age GroupLive Birth Rate per Retrieval (Own Eggs, Fresh Cycles, 2021 CDC Data)
<35 years~54%
35-37 years~41%
38-40 years~25%
>40 years~7%
Complications of ART include (OHSS), affecting up to 20% of stimulated cycles mildly and 1-2% severely, characterized by ovarian enlargement, fluid shifts, and potential or renal failure, largely mitigated by using GnRH agonists for trigger and elective single . Multiple pregnancies, historically a major risk from transferring multiple embryos, have decreased with single embryo transfer policies, reducing twin rates from over 30% in the early to under 10% recently, though they still elevate and risks compared to singletons. Evidence on birth defects shows a modest 1.3- to 2-fold increased risk in ART-conceived children versus spontaneous conceptions, potentially attributable to epigenetic alterations, parental infertility factors, or subfertility rather than the procedures themselves, as risks diminish after adjusting for confounders like multiple gestation. Long-term health outcomes for ART offspring, including cardiovascular and neurodevelopmental risks, require further study but do not indicate widespread deficits beyond those linked to prematurity or .

Emerging and Experimental Therapies

In vitro gametogenesis (IVG) represents a pioneering approach to address gamete shortages in infertility cases, involving the derivation of functional eggs or sperm from induced pluripotent stem cells (iPSCs) sourced from skin or blood. As of September 2025, researchers successfully generated human eggs containing genetic material from adult skin cells, marking a milestone toward clinical application for infertile individuals or same-sex couples, though full maturation and fertilization in humans remain preclinical. IVG could bypass age-related oocyte decline by producing unlimited gametes, but ethical debates persist regarding safety, epigenetic risks, and potential for non-reproductive uses, with human trials not yet approved. Stem cell therapies aim to rejuvenate ovarian tissue and restore folliculogenesis in conditions like premature ovarian insufficiency (POI). A July 2025 study demonstrated that mesenchymal stem cell injections activated dormant oocytes in 70% of women with ovarian failure, correlating with improved hormone levels and potential conception rates, though long-term efficacy and risks like tumorigenesis require further validation through ongoing trials. Clinical trials, such as those evaluating stem cell-derived exosomes for gonadal failure, have enrolled participants since 2023, reporting preliminary safety but variable fertility restoration, with peak trial activity noted in 2018-2020 before stabilizing at 3-5 annually. These interventions leverage stem cells' regenerative potential but face challenges in scalability and integration with existing IVF protocols. Mitochondrial replacement therapy (MRT), or "three-parent IVF," targets mitochondrial dysfunction contributing to age-related infertility and disease transmission by transferring nuclear DNA from a patient's to a donor with healthy mitochondria. In July 2025, the reported the birth of eight healthy babies via pronuclear transfer MRT, confirming embryo viability and absence of carryover above 2%, though U.S. regulatory approval lags due to modification concerns. MRT enhances oocyte quality without altering nuclear genetics but is limited to mitochondrial carriers and requires rigorous preimplantation testing. CRISPR/Cas9 gene editing holds promise for correcting monogenic causes of infertility, such as spermatogenesis defects in non-obstructive azoospermia. Preclinical models as of September 2025 show restoration of fertility via targeted edits in animal germ cells, but human applications remain experimental, confined to research on embryo editing for disease prevention rather than direct infertility resolution, amid debates over off-target effects and ethical germline alterations. No infertility-specific human trials have advanced beyond proof-of-concept, prioritizing safety assessments.

Global and Regional Prevalence

Approximately 17.5% of the global adult population—equating to roughly 1 in 6 people of reproductive age—experiences infertility over their lifetime, according to a 2023 (WHO) analysis of 133 population-based studies encompassing 2.6 million participants across 48 countries. This lifetime prevalence reflects the proportion unable to achieve a clinical after of regular unprotected intercourse or achieve a live birth via medically assisted , with rates derived from self-reported and clinically verified data. The WHO emphasizes that these figures underscore infertility as a significant issue, though measurement challenges persist due to varying definitions (e.g., primary vs. secondary infertility) and underreporting in regions with limited healthcare access. Lifetime infertility shows minimal disparity by income level, at 17.8% in high-income countries and 16.5% in low- and middle-income countries, per the same WHO report, challenging assumptions of uniformly higher burdens in resource-poor settings. However, 12-month rates—focusing on current inability to conceive—reveal contrasts: 3.5% to 16.7% in more developed nations, often tied to delayed childbearing and age-related ovarian decline, versus 6.9% to 9.3% in less-developed regions, where infectious etiologies like untreated sexually transmitted infections contribute disproportionately. In the United States, Centers for Disease Control and Prevention (CDC) data from 2015–2019 indicate that 13.4% of women aged 15–49 report impaired ability to get pregnant or carry to term, with 16.3% of married women in that age group exhibiting impaired . Regionally, exhibits elevated secondary infertility (post-first birth), with rates up to 20–30% in some areas attributable to tubal blockages from secondary to or , as documented in demographic health surveys from countries like (prevalence 2% primary, 19% secondary across sampled nations). In contrast, and report 12-month infertility around 8–12%, predominantly primary and linked to , male factor issues, or lifestyle factors, with national registries like those in the UK showing 1 in 7 couples seeking fertility treatment. displays variability, with lower reported rates in (e.g., 10–15% lifetime) influenced by cultural delays in family formation, while sees higher infectious burdens in rural areas. These differences arise from causal factors rather than inherent biology, with developing regions facing amplified rates from inadequate antenatal care and STIs, per a 2021 global burden analysis projecting sustained or rising trends without intervention.
Income/Region GroupLifetime Prevalence (%)12-Month Prevalence Range (%)Primary Causes Noted
High-Income (e.g., Europe, North America)17.83.5–16.7Age, lifestyle, endometriosis
Low/Middle-Income (Global Aggregate)16.56.9–9.3Infections, untreated STIs
Sub-Saharan AfricaNot specified (elevated secondary)Up to 19 (secondary)Pelvic inflammatory disease
Infertility prevalence has historically varied by region and measurement, with limited reliable data prior to the mid-20th century due to inconsistent definitions and underreporting. , surveys from the indicated that approximately 8.4% of women aged 15-44 were infertile, defined as unable to conceive after one year of unprotected intercourse, rising to 10.2% by 1995 amid projections of further increases driven by delayed childbearing and factors. Globally, estimates from less-developed nations in earlier decades ranged from 6.9% to 9.3%, while developed regions saw wider variability from 3.5% to 16.7%, reflecting differences in diagnostic access and environmental exposures rather than uniform temporal shifts. In recent decades, absolute numbers of infertility cases have risen substantially, even as age-standardized prevalence rates in some populations have plateaued. A 2022 analysis of U.S. data confirmed that infertility rates among women aged 15-49 stabilized around 10-12% from the early onward, with higher rates among older women (over 35), non-Hispanic Black women, and those lacking , attributing persistence to age-related ovarian decline rather than broad epidemiological surges. Globally, the reported in 2023 that 17.5% of adults—approximately one in six—experience infertility over their lifetime, a figure consistent with prior estimates but highlighting increased case burdens from and . For , global cases in the 30-34 age group doubled from 13.3 million in 1990 to 26.9 million in 2021, a 102% increase, while cases rose 75% over the same period, linked to rising incidences of conditions like and endocrine disruptions. Contemporary trends, particularly from 2020 to 2025, show heightened impacts on women in their late 30s, with surges attributed to deferred , industrial pollutants, and potential epigenetic factors, though biological remains tied more to age than novel epidemics. U.S. Centers for Control and Prevention data indicate that 13.8% of women aged 15-49 report inability to conceive after , with impaired affecting 16.3% of married women in this group, figures stable since the but amplified by broader declines to 1.6 births per woman in 2023. These patterns underscore that while core infertility rates have not dramatically escalated, societal delays in family formation exacerbate effective by compressing reproductive windows against natural declines after age 30.

Societal and Lifestyle Influences on Rates

Societal shifts toward delayed childbearing, driven by increased , career , and economic pressures, have contributed to rising infertility rates. In high-income countries, the average age of first birth has risen to 30-35 years, correlating with a decline in natural as diminishes after age 35, with infertility risk increasing by approximately 3-5% per year thereafter. Global data indicate that surged 84% from 1990 to 2021, affecting over 110 million women, with the sharpest rises in the 30-34 age group (103.68% increase in ). This trend stems from socioeconomic factors like and women's workforce participation, which delay family formation despite awareness of age-related declines. Lifestyle factors, modifiable through personal choices, significantly impact infertility rates by altering hormonal balance, quality, and reproductive organ function. Obesity, defined as BMI ≥30, elevates infertility risk by 10-20% in women via mechanisms like and ovulatory dysfunction, with similar effects in men through reduced . accelerates ovarian aging, increasing (FSH) levels by 30-35% in women consuming 10+ cigarettes daily and reducing parameters in men by up to 20%. Excessive alcohol intake (>14 units/week) impairs and , contributing to a dose-dependent fertility reduction, while combined adverse habits like and heavy compound risks additively. Recent studies highlight cumulative effects: adherence to multiple healthy behaviors (e.g., normal BMI, non-, moderate alcohol) lowers infertility odds by 20-50% compared to poor lifestyles, yet rising (global prevalence ~13% in adults) and persistent smoking rates (8-10% among reproductive-age women) drive upward trends. These influences interact with societal ones, as delayed childbearing amplifies age-related vulnerabilities exacerbated by suboptimal habits, underscoring the need for evidence-based interventions over narrative-driven policies.

Psychological and Social Impacts

Mental Health Consequences

Infertility is associated with significantly elevated rates of psychiatric morbidity, including depression, anxiety, and stress, among affected individuals. Systematic reviews indicate that infertile women experience higher levels of these conditions compared to fertile women and to infertile men, with meta-analyses reporting standardized mean differences in depression scores of approximately 0.5 to 1.0 standard deviations higher in infertile populations. Overall of anxiety and depression in infertile couples ranges from 25% to 60%, exceeding general rates where global depression is around 4.4%. Women undergoing infertility or treatment report depression rates of 35% to 44% and anxiety rates up to 86.8%, often linked to perceived loss of control, in outcomes, and repeated treatment failures. In contrast, men exhibit lower overt depression but higher psychosomatic symptoms, with anxiety and stress levels still elevated relative to fertile counterparts; one study found 18.7% of female partners and lower but unspecified rates in males experiencing these disorders. Gender disparities persist longitudinally, with women showing greater distress over time, potentially exacerbated by biological factors like hormonal fluctuations during treatments and sociocultural expectations of motherhood. The grief associated with infertility and IVF treatments is often framed through the Kübler-Ross model of five stages: denial, anger, bargaining, depression, and acceptance. These stages are not strictly linear and frequently recur amid the cyclical nature of infertility, involving repeated hopes and disappointments from monthly cycles or treatment attempts. Manifestations include denial of the diagnosis or negative test results; anger directed at the perceived unfairness of infertility or at others' successful pregnancies; bargaining through lifestyle adjustments or high expectations for interventions; depression stemming from sustained hopelessness; and acceptance of paths like adoption or child-free living. These burdens extend to reduced , with infertile individuals scoring lower on domains such as emotional and social functioning in validated scales. During assisted reproductive technologies like IVF, anxiety and depression peak, correlating with lower success rates in some cohorts, though causality remains debated as distress may both precede and result from unsuccessful cycles. Infertility-related stress also manifests as marital strain and isolation, compounding risks for severe outcomes like , though longitudinal data on incidence rates are limited and primarily drawn from cross-sectional studies. underscores the need for integrated psychological screening in fertility care, as untreated distress can perpetuate a cycle impairing treatment adherence and outcomes.

Effects on Relationships and Family Structures

Infertility often imposes significant strain on marital relationships, manifesting as increased conflict, reduced intimacy, and emotional distress due to the shared over unfulfilled reproductive goals. Studies indicate that infertile couples experience higher levels of infertility-related stress, which correlates with diminished marital satisfaction and heightened risk of emotional disconnection, including behaviors akin to emotional . For instance, among infertile individuals, this stress directly undermines relational harmony, exacerbating tensions around treatment decisions and future planning. Evidence on divorce rates presents a nuanced picture, with outcomes varying by treatment success and cultural context. A 2014 analysis of Danish women undergoing treatments found that those remaining childless after intervention faced a threefold higher likelihood of or separation compared to fertile counterparts. However, a more recent 2023 of Norwegian couples revealed that women utilizing treatments exhibited a lower risk—up to 20 years post-marriage—than those not seeking such interventions, suggesting that the pursuit of parenthood may foster relational resilience in some cases. These divergent findings underscore the role of biological parenthood achievement in stabilizing unions, as persistent amplifies relational vulnerabilities. Regarding family structures, infertility disrupts conventional formation, compelling couples toward alternative pathways such as , , or , which can reshape intergenerational dynamics and support networks. Permanent infertility, affecting approximately 4-5% of individuals in fertile ages, limits biological lineage continuity and often leads to non-traditional configurations, with adoptive parents reporting lingering marital instability traceable to pre-adoption infertility experiences. In regions with limited access to assisted reproduction, this may result in smaller or absent units, contributing to broader demographic shifts toward delayed or foregone childbearing. Couples navigating these alternatives frequently encounter altered power dynamics and redefined roles, where infertility's unresolved trauma influences and extended interactions. Infertility stigma manifests globally as a social penalty tied to cultural expectations of , often disproportionately affecting women despite infertility arising equally from factors in approximately 40-50% of cases each, with the remainder combined or unexplained. In pronatalist societies, where childbearing defines familial and social roles, infertile individuals face exclusion, ridicule, or accusations of personal failing, exacerbating isolation. This stigma permeates self-perception, with affected persons internalizing that correlates with diminished and identity disruption. Cross-culturally, perceptions vary but converge on infertility as a deviation from normative adulthood. In sub-Saharan African communities, such as those in Ghana's Talensi and Nabdam districts, infertility links to or ancestral curses, prompting social ostracism, , or for men while women endure blame and abandonment. A of African experiences highlights how entrenched norms amplify stigma, leading to or economic dependence loss for women. In , infertile women report heightened stigma from familial pressures, with surveys indicating factors like rural residence and low intensifying feelings of inferiority. Western contexts show attenuated but persistent stigma, influenced by , yet surveys reveal 49% of respondents citing social concerns as barriers to treatment. Gender disparities amplify stigma, with women bearing disproportionate blame across cultures due to associations with and motherhood. Studies indicate infertile women experience more severe psychological distress, including lower and higher depression rates than men, as societal narratives frame infertility as a "woman's problem." Globally, 53-64% of infertile women report stigma, often manifesting in relational strain or secrecy to avoid judgment. Men, while affected, disclose less due to norms, though shared couple stigma persists in high-fertility expectation settings. Religious frameworks further shape stigma, viewing infertility variably as divine test, punishment, or trial of . In Catholic traditions, biblical accounts of barren women like underscore sorrow but affirm life's sanctity, potentially framing assisted reproduction as conflicting with natural procreation. Islamic and Christian perspectives in some regions endorse treatments for married couples but stigmatize infertility through pronatalist theology, correlating with coping via or heightened guilt. Qualitative analyses reveal devout women interpreting infertility as spiritual challenge, yet stigma intensifies when linked to moral failing, prompting secrecy or alternative pursuits. These dimensions underscore how cultural and religious lenses, while providing resilience for some, often entrench stigma absent empirical intervention.

Historical Context

Pre-Modern Perspectives and Treatments

In ancient Egyptian medicine, documented as early as the Ebers Papyrus around 1550 BCE, infertility was primarily attributed to women and addressed through diagnostic tests such as the barley and emmer wheat germination method, where urine from a suspected infertile woman was poured over the grains; sprouting indicated potential fertility. Treatments included herbal concoctions, fumigations with incense, and spells invoking deities like Hathor for conception, reflecting a blend of empirical observation and supernatural intervention, though efficacy remained unproven. In from the 5th century BCE, physicians like shifted toward naturalistic explanations, viewing infertility as an imbalance of bodily humors—excess or coldness obstructing —rather than solely divine , marking an early conceptualization of it as a medical condition affecting both sexes. Recommended remedies encompassed dietary adjustments to warm the body, purgatives, vaginal suppositories of honey and cedar oil, and coital positioning to facilitate semen retention, with some rituals persisting from earlier Mycenaean practices. Roman adaptations, as in Soranus of Ephesus's 2nd-century CE writings, emphasized similar humoral therapies, including exercise, baths, and emmenagogues to induce as a precursor to , while acknowledging male seminal deficiencies through urine analysis for turbidity. Medieval European perspectives, influenced by Galenic humoral theory and from the 5th to 15th centuries, often framed infertility as a divine trial or sin's consequence, yet medical texts like the () prescribed remedies such as weasel blood baths or pig testicle powders mixed with wine to stimulate arousal and conception. Prayer to saints, including St. Anne as patron of infertile women, was widespread, sometimes combined with pilgrimages or amulets, while elite women sought empirical aids like regulated intercourse timing based on lunar cycles. Socially, infertility disproportionately stigmatized women, serving as grounds for in , though rare male-focused treatments addressed "sterile seed" via purgatives. These approaches yielded negligible success rates, constrained by absent diagnostic tools like , and persisted until anatomical discoveries in the .

Development of Modern Infertility Management

The foundations of modern infertility management emerged in the early with advancements in , including the isolation of key hormones like in 1929 and progesterone in 1934, enabling diagnostic hormone assays and early therapeutic interventions. Surgical techniques, such as tubal repair via salpingostomy, were refined in the 1920s by physicians like Emil Novak, though success rates remained low at under 20% due to limited understanding of underlying . By the mid-century, diagnostic tools advanced with the introduction of in for assessing tubal patency and in the 1950s for visualizing pelvic , allowing more precise identification of causes like or adhesions. Ovulation induction marked a pivotal shift, beginning with gonadotropin extracts from pregnant mare serum in the 1930s, but achieving clinical viability with human menopausal gonadotropin (hMG) in the 1960s and clomiphene citrate, which underwent first trials in 1960 and yielded the initial reported pregnancy in 1961. Clomiphene, approved by the U.S. Food and Drug Administration in 1967, induced ovulation in approximately 70-80% of anovulatory women, particularly those with polycystic ovary syndrome, often combined with intrauterine insemination (IUI) to enhance conception rates to 10-20% per cycle. IUI itself evolved from early artificial insemination practices, with modern protocols incorporating ovarian stimulation emerging in the 1970s, bypassing cervical barriers and concentrating motile sperm directly into the uterus for mild male factor or unexplained infertility cases. In vitro fertilization (IVF) revolutionized treatment with the birth of on July 25, 1978, the first human conceived via IVF, developed by and Edwards after decades of animal research starting in the . Initial IVF cycles used natural-cycle protocols without stimulation, achieving low success rates of about 5-10% per transfer, but with gonadotropins from the early 1980s increased egg yield and live birth rates to over 30% by the . The first U.S. IVF birth occurred in 1981, and cryopreservation of embryos followed with the initial live birth in 1984, enabling deferred transfers and reducing the need for repeated egg retrievals. Subsequent innovations addressed specific barriers, including (ICSI), first successfully applied in humans in 1992, which directly injects a single spermatozoon into the , achieving fertilization rates of 70-80% in severe male factor infertility where conventional IVF failed. (PGD), introduced in 1990, allowed embryo screening for chromosomal abnormalities, reducing risks and improving outcomes in recurrent implantation failure cases. By the , refinements like culture and for further boosted cumulative live birth rates per retrieval to 50-60% in younger patients, though overall success varies by age and etiology, with global ART cycles exceeding 2 million annually by 2018.

Access Disparities and Equity Issues

Access to infertility treatments, particularly assisted reproductive technologies (ART) such as in vitro fertilization (IVF), exhibits significant disparities influenced by socioeconomic status, race, ethnicity, geography, and national policies. Globally, infertility affects approximately 17.5% of adults, or 1 in 6 people, yet affordable, high-quality care remains limited, especially in low- and middle-income countries where over 180 million couples experience primary or secondary infertility compounded by social stigma and inadequate infrastructure. In developing regions, cultural, religious, and political factors further restrict access, with ART utilization concentrated in wealthier nations despite its practice in over 100 countries as of 2018. Even in countries with public subsidies for IVF in about 64% of cases, socioeconomic gradients persist; for instance, in France, where national health insurance fully covers ART, lower-income and minority groups show reduced uptake due to opportunity costs and indirect barriers like travel or lost wages. In the United States, economic barriers are pronounced, as infertility treatments often cost $12,000–$15,000 per IVF cycle without , leading to lower utilization among low-income households despite infertility of about 16% among married women aged 15–49. Only 21 states plus the District of Columbia mandate some form of infertility coverage in private as of 2024, with variations in scope—some require only diagnostics, while others cover limited IVF cycles—leaving federal employees and those on employer plans without mandates at a disadvantage. Racial and ethnic disparities exacerbate these issues: face roughly twofold higher infertility odds than women but comprise just 4% of IVF live births, compared to 53.8% for , partly due to lower treatment initiation rates and longer travel distances (median 10 miles for and women versus 5 miles for Whites and Asians). and Asian patients also underutilize ART relative to their infertility burdens, with factors including discontinuous , clinic proximity, and cultural mistrust contributing beyond pure economic constraints. Geographic inequities compound access challenges, as fertility clinics cluster in urban areas, forcing rural or underserved populations to incur high travel and accommodation costs; in the , this affects treatment completion rates, with economic analyses showing that out-of-pocket expenses deter 40–50% of potential patients from pursuing care. Equity debates highlight tensions between expanding —which could strain resources given ART's modest success rates (e.g., 30–40% live birth per cycle for women under 35)—and prioritizing basic reproductive health needs in under-resourced communities. Internationally, contrasts are stark: European nations like and the provide subsidized IVF (up to three cycles), enabling broader access than in the , though wait times and eligibility restrictions (e.g., age or ) introduce new inequities. These disparities not only limit family-building opportunities but also perpetuate cycles of socioeconomic disadvantage, as untreated infertility correlates with delayed childbearing and reduced lifetime .

Moral and Bioethical Concerns in Reproduction

Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) raise profound bioethical questions regarding the moral status of human embryos, as procedures typically involve creating multiple embryos via fertilization of oocytes with sperm outside the body, with only a subset implanted and the remainder often discarded, cryopreserved indefinitely, or used for research. The Catholic Church, in documents like Donum Vitae (1987) and the Catechism of the Catholic Church (paragraph 2377), deems IVF intrinsically immoral because it dissociates procreation from the conjugal act, treats gametes and embryos as commodities, and results in the destruction of nascent human life, equating excess embryos to moral equivalents of early abortions. This stance prioritizes the principle that human life begins at fertilization, rendering embryo selection and disposal ethically impermissible, though some Protestant denominations permit IVF under conditions preserving embryo dignity. Preimplantation genetic diagnosis (PGD), integrated with IVF to screen embryos for genetic disorders like or chromosomal anomalies before implantation, intensifies debates over and the value of . While proponents argue PGD upholds parental and prevents —aligning with utilitarian principles of maximizing welfare—critics contend it fosters a "" by enabling selection against disabilities, potentially devaluing lives deemed imperfect and pressuring society toward genetic uniformity, as evidenced by historical precedents where state-mandated screening led to discriminatory outcomes. Empirical data from clinics show PGD reduces implantation of affected embryos by up to 90% for single-gene disorders, but ethical frameworks emphasize that voluntary parental choice does not negate broader societal risks, such as reduced tolerance for natural variation in traits like . Surrogacy, particularly commercial forms, elicits concerns over exploitation and , as gestational carriers—often from economically disadvantaged backgrounds—gestate and relinquish children for payment, raising questions of whether this treats women's reproductive capacity and infants as marketable goods. Studies document cases in developing countries where face inadequate compensation, health risks without recourse, and psychological distress post-delivery, with bans in nations like and reflecting fears of trafficking-like dynamics; for instance, India's 2018 surrogacy ban followed reports of among poor women. Altruistic surrogacy mitigates some issues by avoiding payment, yet even non-commercial arrangements provoke debates on whether gestation undermines maternal bonds and child welfare, with first-principles reasoning highlighting the causal inseparability of gestation from . Gamete donation introduces ethical tensions between donor anonymity and the offspring's right to genetic origins, as anonymous sperm or egg provision—common in the U.S., affecting over 90% of donor-conceived individuals in some cohorts—can lead to identity crises and health risks from undisclosed hereditary conditions. Countries like the UK and Sweden have shifted to identity-release systems since 2005, allowing adult offspring access to donor information, supported by evidence that non-disclosure correlates with higher rates of psychological distress; the American Society for Reproductive Medicine advocates balancing donor privacy with offspring interests, arguing anonymity erodes trust in family narratives. Non-medical uses, such as sex selection via PGD, further complicate ethics, with autonomy defenses clashing against risks of reinforcing gender imbalances, as seen in cultural contexts favoring sons. Overall, these concerns underscore a core bioethical divide: individual reproductive liberty versus collective duties to safeguard human dignity from technological overreach.

Broader Demographic and Societal Implications

Rising infertility rates, affecting an estimated 17.5% of the global adult or roughly 1 in 6 individuals, compound other drivers of low to produce sub-replacement total fertility rates (TFR) in most countries, undermining natural replenishment. The worldwide TFR has fallen from approximately 5 children per woman in 1950 to 2.2 in 2021, with infertility—particularly age-related declines in from delayed childbearing—exacerbating this trend by reducing realized births among those intending to reproduce. By 2050, over 75% of countries are projected to have TFRs insufficient to sustain sizes without , rising to more than 95% by 2100, leading to absolute declines in many regions. These dynamics precipitate profound demographic imbalances, including accelerated shrinkage and aging. Without net migration, numerous countries face projected declines exceeding 50% from 2017 levels by 2100, shifting age structures toward fewer youth and a burgeoning elderly cohort. The resulting increase in old-age dependency ratios—where fewer working-age individuals support more retirees—intensifies pressures on labor markets, with shrinking cohorts reducing participation and potential. Healthcare and social security systems face heightened burdens, as extended lifespans amid low birth rates amplify demand for elder care while diminishing the tax base funding it. Economically, infertility-driven fertility declines yield mixed outcomes: short-term demographic dividends from reduced child dependency may boost savings, female labor force entry, and per capita growth, as observed in post-transition economies. However, sustained TFRs below 1.4 trigger rapid depopulation and structural stagnation, curtailing consumption, investment, and productivity gains from scale. Societies with entrenched patterns of late reproduction, often tied to extended education and career prioritization, encounter heightened involuntary , further entrenching these cycles and challenging policies aimed at reversal through incentives like subsidies or family leave.

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