Infertility
Inability to reproduce by natural means From Wikipedia, the free encyclopedia
Inability to reproduce by natural means From Wikipedia, the free encyclopedia
Infertility is the inability of a couple to reproduce by natural means. It is usually not the natural state of a healthy adult. Exceptions include children who have not undergone puberty, which is the body's start of reproductive capacity. It is also a normal state in women after menopause.
| Infertility | |
|---|---|
| |
| Specialty | Urology, gynecology |
| Causes | Common in females: annouvulation, blocked fallopian tube, hormonal imbalance Common in males: low sperm count, abnormal sperm morphology |
| Frequency | 113 million (2015)[1] |
In humans, infertility is 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. Many more couples, however, experience involuntary childlessness for at least one year with estimates ranging from 12% to 28%.[4]
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.[5] In 10–20% of cases, no cause is found.[5] Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.[6] 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] The most common cause of female infertility is age, which generally manifests in sparse or absent menstrual periods leading up to menopause.[7] 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.[8] 85% of infertile couples have an identifiable cause and 15% is designated unexplained infertility.[2] Of the 85% of identified infertility, 25% are due to disordered ovulation (of which 70% of the cases are due to polycystic ovarian syndrome).[2] Tubal infertility, in which there is a structural problem with the fallopian tubes is responsible for 11-67% of infertility in women of child bearing 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.
"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.[9] 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.[10]
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.[9] A couple that tries unsuccessfully to have a child after a certain period of time (often a short period, but definitions vary) is sometimes said to be subfertile, meaning less fertile than a typical couple. Both infertility and subfertility are defined 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.[11]
The World Health Organization defines infertility as follows:[12]
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 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"
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:
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.[13] 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."[14]
Researchers commonly base demographic studies on infertility prevalence over a five-year period.[15]
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.[16] The World Health Organisation also adds that 'women whose pregnancy spontaneously miscarries, or whose pregnancy results in a still born child, without ever having had a live birth would present with primarily infertility'.[16]
Secondary infertility is defined as the difficulty in conceiving a live birth in couples who previously had a child.[16]
The consequences of infertility are mainfold 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.[17] One of the main challenges in assessing the distress levels in women with infertility is the accuracy of self-report measures. It is possible that women "fake good" in order to appear mentally healthier than they are. It is also possible that women feel a sense of hopefulness/increased optimism prior to initiating infertility treatment, which is when most assessments of distress are collected. Some early studies concluded that infertile women did not report any significant differences in symptoms of anxiety and depression than fertile women. The further into treatment a patient goes, the more often they display symptoms of depression and anxiety. Patients with one treatment failure had significantly higher levels of anxiety, and patients with two failures experienced more depression when compared with those without a history of treatment. However, it has also been shown that the more depressed the infertile woman, the less likely she is to start infertility treatment and the more likely she is to drop out after only one cycle. Researchers have also shown that despite a good prognosis and having the finances available to pay for treatment, discontinuation is most often due to psychological reasons.[18] Fertility does not seem to increase when the women takes antioxidants to reduce the oxidative stress brought by the situation.[19]
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.[20] Partners may become more anxious to conceive, increasing sexual dysfunction.[21] 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.[22] Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.[23] Male and female partner respond differently to infertility problems. In general, women show higher depression levels than their male partners when dealing with infertility. A possible explanation may be that women feel more responsible and guilty than men during the process of trying to conceive. On the other hand, infertile men experience a psychosomatic distress.[20]
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.[24] Societal pressures may affect a couple's decision to approach, avoid, or experience an infertility treatment.[25] Moreover, the socioeconomic status influences the psychology of the infertile couples: low socioeconomic status is associated with increased chances of developing depression.[20] In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether.[26]
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.[27]
Couples that suffer from infertility have a higher risk than other couples to develop sexual dysfunctions. The most common sexual issue facing the couples is a decline of sexual desire and erectile dysfunction.[28]
Male infertility is responsible for 20–30% of infertility cases, while 20–35% are due to female infertility, and 25–40% are due to combined problems in both partners.[29][5] In 10–20% of cases, no cause is found.[5] The most common cause of female infertility are ovulation problems, usually manifested by scanty or absent menstrual periods.[7] Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.[6]
Iodine deficiency may lead to infertility.[30]
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)[citation needed].
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.[31]
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).[32] Boys are considered to have delayed puberty if they lack enlargement of the testicles by age 14.[32] Delayed puberty affects about 2% of adolescents.[33][34]
Most commonly, puberty may be delayed for several years and still occur normally, in which case it is considered constitutional delay of growth and puberty, a common variation of healthy physical development.[32] 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.[32]
Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples.[35] In both men and women, ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, 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 on (head, mid piece, tail). Factors contributing to the formation of antisperm antibodies in women are disturbance of normal immunoregulatory mechanisms, infection, violation of the integrity of the mucous membranes, rape and unprotected oral or anal sex. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men.[35][36]
Infections with the following sexually transmitted pathogens have a negative effect on fertility: Chlamydia trachomatis and Neisseria gonorrhoeae. There is a consistent association of Mycoplasma genitalium infection and female reproductive tract syndromes. M. genitalium infection is associated with increased risk of infertility.[37][38]
Mutations to NR5A1 gene encoding steroidogenic factor 1 (SF-1) have been found in a small subset of men with non-obstructive male factor infertility where the cause is unknown. Results of one study investigating a cohort of 315 men revealed changes within the hinge region of SF-1 and no rare allelic variants in fertile control men. Affected individuals displayed more severe forms of infertility such as azoospermia and severe oligozoospermia.[39]
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.[40] See Infertility associated with small supernumerary marker chromosomes and Genetics of infertility#Small supernumerary marker chromosomes and infertility.
Factors that can cause male as well as female infertility are:
Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).[63][64][65]
The following causes of infertility may only be found in females. For a woman to conceive, certain things have to happen: vaginal intercourse must take place around the time when an egg is released from her ovary; the system that produces eggs has to be working at optimum levels; and her hormones must be balanced.[67]
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.[68]
Another major cause of infertility in women may be the inability to ovulate. Ovulatory disorders make up 25% of the known causes of female infertility. Oligo-ovulation or anovulation results in infertility because no oocyte will be released monthly. In the absence of an oocyte, there is no opportunity for fertilization and pregnancy. World Health Organization subdivided ovulatory disorders into four classes:
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.[70]
Sometimes it can be a combination of factors, and sometimes a clear cause is never established.
Common causes of infertility of females include:
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% 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%.[72]
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.[73] 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.[74] Antisperm antibodies cause immune infertility.[35][32] 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.[75]
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.[76] Epigenetic modifications in sperm may be also be responsible for unexplaiend infertility.[77][78]
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.[79]
However, there are instances where couples should seek reproductive counseling after only 6 months of trying for a pregnancy:
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 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.[82] 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.[83]
Clomiphene is a selective estrogen receptor modulator used for induction of ovulation. It works by blocking the negative feedback from estrogen, creating a gonadotropin releasing hormone (GnRH) increase, which causes release of leutenizing 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 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.[84]
Ovarian stimulation (such as with clomiphene) combined with in-vitro fertilization or intra-uterine insemination have 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 which make pregnancy dangerous or precluding pregnancy, those with severe infertility or females with a non-functioning uterus.[2]
Fertility tourism is the practice of traveling to another country for fertility treatments.[85]
There are several experimental treatments related to stem cell therapy not yet routinely used in reproductive medicine. These treatments may provide the opportunity for a live birth for people who lack of 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.[86]
Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive.
Perhaps except for infertility in science fiction, films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing first in the latter part of the 2000s decade, although the techniques have been available for decades.[96] Yet, the number of people that can relate to it by personal experience in one way or another is ever-growing, and the variety of trials and struggles is huge.[96]
Pixar's Up contains a depiction of infertility in an extended life montage that lasts the first few minutes of the film.[97]
Other individual examples are referred to individual sub-articles of assisted reproductive technology
There are several ethical issues associated with infertility and its treatment.
Many countries have special frameworks for dealing with the ethical and social issues around fertility treatment.
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