Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects).
|Frequency||113 million (2015)|
In humans, infertility is the inability to become pregnant or carry a pregnancy to full term. There are many causes of infertility, including some that medical intervention can treat. Estimates from 1997 suggest that worldwide about five percent of all heterosexual couples have an unresolved problem with infertility. Many more couples, however, experience involuntary childlessness for at least one year: estimates range from 12% to 28%."  20-30% of infertility cases are due to male infertility, 20-35% are due to female infertility, and 25-40% are due to combined problems in both parts. In 10-20% of cases, no cause is found. The most common cause of female infertility is ovulatory problems which generally manifest themselves by sparse or absent menstrual periods. Male infertility is most commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.
Women who are fertile experience a natural period of fertility before and during ovulation, and they are naturally 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. Currently, female fertility normally peaks at age 24 and diminishes after 30, with pregnancy occurring rarely after age 50. A female is most fertile within 24 hours of ovulation. Male fertility peaks usually at age 25 and declines after age 40. The time needed to pass (during which the couple tries to conceive) for that couple to be diagnosed with infertility differs between different jurisdictions. Existing definitions of infertility lack uniformity, rendering comparisons in prevalence between countries or over time problematic. Therefore, data estimating the prevalence of infertility cited by various sources differs significantly. A couple that tries unsuccessfully to have a child after a certain period of time (often a short period, but definitions vary) is sometimes said to be subfertile, meaning less fertile than a typical couple. Both infertility and subfertility are defined as the inability to conceive after a certain period of time (the length of which vary), so often the two terms overlap.
World Health OrganizationEdit
|“||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:
- a woman under 35 has not conceived after 12 months of contraceptive-free intercourse. Twelve months is the lower reference limit for Time to Pregnancy (TTP) by the World Health Organization.
- a woman over 35 has not conceived after 6 months of contraceptive-free sexual intercourse.
These time intervals would seem to be reversed; this is an area where public policy trumps science. The idea is that for women beyond age 35, every month counts and if made to wait another 6 months to prove the necessity of medical intervention, the problem could become worse. The corollary to this is that, by definition, failure to conceive in women under 35 isn't regarded with the same urgency as it is in those over 35.
In the UK, previous NICE guidelines defined infertility as failure to conceive after regular unprotected sexual intercourse for 2 years in the absence of known reproductive pathology. Updated NICE guidelines do not include a specific definition, but recommend that "A woman of reproductive age who has not conceived after 1 year of unprotected vaginal sexual intercourse, in the absence of any known cause of infertility, should be offered further clinical assessment and investigation along with her partner, with earlier referral to a specialist if the woman is over 36 years of age.
Researchers commonly base demographic studies on infertility prevalence on a five-year period. Practical measurement problems, however, exist for any definition, because it is difficult to measure continuous exposure to the risk of pregnancy over a period of years.
Primary vs. secondary infertilityEdit
Primary infertility is defined as the absence of a live birth for women who desire a child and have been in a union for at least 12 months, during which they have not used any contraceptives. The World Health Organisation also adds that 'women whose pregnancy spontaneously miscarries, or whose pregnancy results in a still born child, without ever having had a live birth would present with primarily infertility'.
Secondary infertility is defined as the absence of a live birth for women who desire a child and have been in a union for at least 12 months since their last live birth, during which they did not use any contraceptives.
Thus the distinguishing feature is whether or not the couple have ever had a pregnancy which led to a live birth.
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.
Infertility may have psychological effects. Partners may become more anxious to conceive, increasing sexual dysfunction. Marital discord often develops, especially when they are under pressure to make medical decisions. Women trying to conceive often have depression rates similar to women who have heart disease or cancer. Emotional stress and marital difficulties are greater in couples where the infertility lies with the man.
Older people with adult children appear to live longer. Why this is the case is unclear and may dependent in part on those who have children adopting a healthier lifestyle, support from children, or the circumstances that led to not having children.
In many cultures, inability to conceive bears a stigma. In closed social groups, a degree of rejection (or a sense of being rejected by the couple) may cause considerable anxiety and disappointment. Some respond by actively avoiding the issue altogether; middle-class men are the most likely to respond in this way.
In the United States some treatments for infertility, including diagnostic tests, surgery and therapy for depression, can qualify one for Family and Medical Leave Act leave. It has been suggested that infertility be classified as a form of disability.
Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples. In both men and women, ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the female reproductive tract, inhibiting capacitation and acrosome reaction, impaired fertilization, influence on the implantation process, and impaired growth and development of the embryo. 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, accidental rape and unprotected oral or anal sex. Risk factors for the formation of antisperm antibodies in men include the breakdown of the blood‑testis barrier, trauma and surgery, orchitis, varicocele, infections, prostatitis, testicular cancer, failure of immunosuppression and unprotected receptive anal or oral sex with men.
Sexually transmitted infectionsEdit
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.
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.
Factors that can cause male as well as female infertility are:
- DNA damage
- DNA damage reduces fertility in female ovocytes, as caused by smoking, other xenobiotic DNA damaging agents (such as radiation or chemotherapy) or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine
- DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage, smoking, other xenobiotic DNA damaging agents (such as drugs or chemotherapy) or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature. The damaged DNA related to infertility manifests itself by the increased susceptibility to denaturation inducible by heat or acid  and/or by the presence of double-strand breaks that can be detected by the TUNEL assay. 
- General factors
- Hypothalamic-pituitary factors
- Environmental factors
German scientists have reported that a virus called Adeno-associated virus might have a role in male infertility, though it is otherwise not harmful. Other diseases such as chlamydia, and gonorrhea can also cause infertility, due to internal scarring (fallopian tube obstruction).
The following causes of infertility may only be found in females. For a woman to conceive, certain things have to happen: vaginal intercourse must take place around the time when an egg is released from her ovary; the system that produces eggs has to be working at optimum levels; and her hormones must be balanced.
For women, problems with fertilisation 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 and/or scar tissue. For example, endometriosis can cause infertility with the growth of endometrial tissue in the Fallopian tubes and/or around the ovaries. Endometriosis is usually more common in women in their mid-twenties and older, especially when postponed childbirth has taken place.
Another major cause of infertility in women may be the inability to ovulate. Malformation of the eggs themselves may complicate conception. For example, polycystic ovarian syndrome is when the eggs only partially developed 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.
Sometimes it can be a combination of factors, and sometimes a clear cause is never established.
Common causes of infertility of females include:
- ovulation problems (e.g. polycystic ovarian syndrome, PCOS, the leading reason why women present to fertility clinics due to anovulatory infertility.)
- tubal blockage
- pelvic inflammatory disease caused by infections like tuberculosis
- age-related factors
- uterine problems
- previous tubal ligation
- advanced maternal age
- immune infertility
The main cause of male infertility is low semen quality. In men who have the necessary reproductive organs to procreate, infertility can be caused by low sperm count due to endocrine problems, drugs, radiation, or infection. There may be testicular malformations, hormone imbalance, or blockage of the man's duct system. Although many of these can be treated through surgery or hormonal substitutions, some may be indefinite. Infertility associated with viable, but immotile sperm may be caused by primary ciliary dyskinesia. The sperm must provide the zygote with DNA, centrioles, and activation factor for the embryo to develop. A defect in any of these sperm structures may result in infertility that will not be detected by semen analysis. Antisperm antibodies cause immune infertility. 
In some cases, both the man and woman may be infertile or sub-fertile, and the couple's infertility arises from the combination of these conditions. In other cases, the cause is suspected to be immunological or genetic; it may be that each partner is independently fertile but the couple cannot conceive together without assistance.
In the US, up to 20% of infertile couples have unexplained infertility. In these cases abnormalities are likely to be present but not detected by current methods. Possible problems could be that the egg is not released at the optimum time for fertilization, that it may not enter the fallopian tube, sperm may not be able to reach the egg, fertilization may fail to occur, transport of the zygote may be disturbed, or implantation fails. It is increasingly recognized that egg quality is of critical importance and women of advanced maternal age have eggs of reduced capacity for normal and successful fertilization. Also, polymorphisms in folate pathway genes could be one reason for fertility complications in some women with unexplained infertility. However, a growing body of evidence suggests that epigenetic modifications in sperm may be partially responsible.
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.
Women over the age of 35 should see their physician or WHNP after six months as fertility tests can take some time to complete, and age may affect the treatment options that are open in that case.
A doctor or WHNP takes a medical history and gives a physical examination. They can also carry out some basic tests on both partners to see if there is an identifiable reason for not having achieved a pregnancy. If necessary, they refer patients to a fertility clinic or local hospital for more specialized tests. The results of these tests help determine the best fertility treatment.
Treatment 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. Treatment methods for infertility may be grouped as medical or complementary and alternative treatments. Some methods may be used in concert with other methods. Drugs used for both women and men include clomiphene citrate, human menopausal gonadotropin (hMG), follicle-stimulating hormone (FSH), human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) analogues, aromatase inhibitors, and metformin.
Medical treatment of infertility generally involves the use of fertility medication, medical device, surgery, or a combination of the following. If the sperm are of good quality and the mechanics of the woman's reproductive structures are good (patent fallopian tubes, no adhesions or scarring), a course of ovarian stimulating medication maybe used. The physician or WHNP may also suggest using a conception cap cervical cap, which the patient uses at home by placing the sperm inside the cap and putting the conception device on the cervix, or intrauterine insemination (IUI), in which the doctor or WHNP introduces sperm into the uterus during ovulation, via a catheter. In these methods, fertilization occurs inside the body.
If conservative medical treatments fail to achieve a full term pregnancy, the physician or WHNP may suggest the patient undergo in vitro fertilization (IVF). IVF and related techniques (ICSI, ZIFT, GIFT) are called assisted reproductive technology (ART) techniques.
ART techniques generally start with stimulating the ovaries to increase egg production. After stimulation, the physician surgically extracts one or more eggs from the ovary, and unites them with sperm in a laboratory setting, with the intent of producing one or more embryos. Fertilization takes place outside the body, and the fertilized egg is reinserted into the woman's reproductive tract, in a procedure called embryo transfer.
In vitro fertilizationEdit
IVF is the most commonly used ART. It has been proven useful in overcoming infertility conditions, such as blocked or damaged tubes, endometriosis, repeated IUI failure, unexplained infertility, poor ovarian reserve, poor or even nil sperm count.
Intracytoplasmic sperm injectionEdit
ICSI technique is used in case of poor semen quality, low sperm count or failed fertilization attempts during prior IVF cycles. This technique involves an injection of a single healthy sperm directly injected into mature egg. The fertilized embryo is then transferred to womb.
Fertility tourism is the practice of traveling to another country for fertility treatments. It may be regarded as a form of medical tourism. The main reasons for fertility tourism are legal regulation of the sought procedure in the home country, or lower price. In-vitro fertilization and donor insemination are major procedures involved.
Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive.
- Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity due to an increase in age.
- Fertility problems affect one in seven couples in the UK. Most couples (about 84%) who have regular sexual intercourse (that is, every two to three days) and who do not use contraception get pregnant within a year. About 92 out of 100 couples who are trying to get pregnant do so within two years.
- Women become less fertile as they get older. For women aged 35, about 94% who have regular unprotected sexual intercourse get pregnant after three years of trying. For women aged 38, however, only about 77%. The effect of age upon men's fertility is less clear.
- In people going forward for IVF in the UK, roughly half of fertility problems with a diagnosed cause are due to problems with the man, and about half due to problems with the woman. However, about one in five cases of infertility has no clear diagnosed cause.
- In Britain, male factor infertility accounts for 25% of infertile couples, while 25% remain unexplained. 50% are female causes with 25% being due to anovulation and 25% tubal problems/other.
- In Sweden, approximately 10% of couples wanting children are infertile. In approximately one third of these cases the man is the factor, in one third the woman is the factor, and in the remaining third the infertility is a product of factors on both parts.
Society and cultureEdit
Perhaps except for infertility in science fiction, films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing first in the latter part of the 2000s decade, although the techniques have been available for decades. Yet, the number of people that can relate to it by personal experience in one way or another is ever growing, and the variety of trials and struggles is huge.
Other individual examples are referred to individual subarticles of assisted reproductive technology
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).
- Pro-life opposition to the destruction of embryos not transferred in vivo.
- IVF and other fertility treatments have resulted in an increase in multiple births, provoking ethical analysis because of the link between multiple pregnancies, premature birth, 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, and/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.
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 
- Regulatory bodies are also found in Canada  and in the state of Victoria in Australia 
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Infertility is often not seen (by the West) as being an issue outside industrialized countries. This is because of assumptions about overpopulation problems and hyper fertility in developing countries, and a perceived need for them to decrease their populations and birth rates. The lack of health care and high rates of life-threatening illness (such as HIV/AIDS) in developing countries, such as those in Africa, are supporting reasons for the inadequate supply of fertility treatment options. Fertility treatments, even simple ones such as treatment for STIs that cause infertility, are therefore not usually made available to individuals in these countries.
Despite this, infertility has profound effects on individuals in developing countries, as the production of children is often highly socially valued and is vital for social security and health networks as well as for family income generation. Infertility in these societies often leads to social stigmatization and abandonment by spouses. Infertility is, in fact, common in sub-Saharan Africa. Unlike in the West, secondary infertility is more common than primary infertility, being most often the result of untreated STIs or complications from pregnancy/birth.
Due to the assumptions surrounding issues of hyper-fertility in developing countries, ethical controversy surrounds the idea of whether or not access to assisted reproductive technologies should comprise a critical aspect of reproductive health or at least, whether or not the distribution and access of such technologies should be subject to greater equity. However, as highlighted by Inhorn  the overarching conceptualisation of infertility, to a great extent, disguises important distinctions that can be made within a local context, both demographically and epidemiological and moreover, that these factors are highly significant in the ethics of reproduction. An important factor, argues Inhorn, is the positioning of men within the paradigm of reproductive health, whereby because rates of general infertility mask differences between male and female infertility, men remain a largely invisible facet within the theorisation and discourse surrounding infertility, as well as the related treatments and biotechnologies. This is particularly significant given that male infertility accounts for more than half of all cases of infertility  and moreover, it is evident that the attitudes and behaviours of men have profound implications for the reproductive health of both individuals and couples. For example, Inhorn  notes that when couples in Egypt are faced with seemingly intractable infertility problems - due to a range of family and societal pressures that centre around the place of children in constituting the gender identity of men and women - it is often the women who is forced to seek continued treatment; this continues to occur, even in known instances of male infertility and that the constant seeking of treatment frequently becomes iatrogenic for the women. Inhorn states that infertility often leads to “marital demise, physical violence, emotional abuse, social exclusion, community exile, ineffective and iatrogenic therapies, poverty, old age insecurity, increased risk of HIV/AIDS, and death” Significantly, Inhorn demonstrates that this phenomenon can not simply be explained by a lack of knowledge, rather it occurs in a complex interaction between the centrality of children in the male gender identity as a symbol of maturity and the relative lack of power of women in Egyptian society, whereby they effectively become scapegoats for a culturally accepted narrative as a site of blame for the lack of childlessness. It should be emphasised that this is not simply an issue of “women oppressed by men” but rather, that men and women both share the burden of this narrative, but in different, unequal and highly complex ways. Therefore, while the notion that reproductive health is a ‘women’s issue’, may have powerful social currency, especially within popular discourse and indigenous systems of meaning, the reality of infertility suggests that medical and health paradigms have a significant part to play in challenging the validity of this entrenched belief . Moreover, the effectiveness of any therapeutic intervention, medical or otherwise will be contingent on such outcomes and has an important part to play in the alleviation of gendered suffering, especially the burden imposed on women, who continue to suffer disproportionately from the effects of infertility.
High costs may also be a factor and research by the Genk Institute for Fertility Technology, in Belgium, claimed a much lower cost methodology (about 90% reduction) with similar efficacy, which may be suitable for some fertility treatment. At the 1994 United Nations International Conference on Population and Development (ICPD) in Cairo, the prevention and treatment of infertility was accepted into the program of action for reproductive healthcare. Infertility has shown to have a greater effect on developing nations than on birth rates or population control, but also on a social level as well. Reproduction is a large aspect of life for many cultures within developing nations, and infertility can lead to social and familial problems such as rejection or abandonment as well as personal psychological issues. Currently, fertility treatment options and programs are only available through private health sectors in developing nations and little-to-no treatment is available through public health sectors. The fertility treatment options offered through the private sectors are often costly or not easily accessible. Additionally, counseling is considered an essential aspect of fertility treatment, and due to lack of education and resources such forms of therapy remain scarce as well. While quality fertility care is not readily available in developing nations (such as sub-Saharan African countries), a standard procedure of care could be easily implemented for a low cost as a basic intervention. The lack of fertility treatment is problematic, and high birth and population rates are every reason to implement treatment options rather than reject them.
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Physicians should investigate women with unexplained infertility, recurrent miscarriage or IUGR for undiagnosed CD. (...) CD can present with several non-gastrointestinal symptoms and it may escape timely recognition. Thus, given the heterogeneity of clinical presentation, many atypical cases of CD go undiagnosed, leading to a risk of long-term complications. Among atypical symptoms of CD, disorders of fertility, such as delayed menarche, early menopause, amenorrhea or infertility, and pregnancy complications, such as recurrent abortions, intrauterine growth restriction (IUGR), small for gestational age (SGA) babies, low birthweight (LBW) babies or preterm deliveries, must be factored. (...) However, the risk is significantly reduced by a gluten-free diet. These patients should therefore be made aware of the potential negative effects of active CD also in terms of reproductive performances, and of the importance of a strict diet to ameliorate their health condition and reproductive health.
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Undiagnosed celiac disease is a risk factor for infertility. Women seeking medical advice for this particular condition should be screened for celiac disease. Adoption of a gluten-free diet could have a positive impact on fertility in this group of patients.(...)According to our results, non-diagnosed untreated CD constitutes a risk factor significantly associated with infertility in women. When comparing studies that enrolled patients previously diagnosed with CD, this association is not as evident as in the former context. This could be related to the effect that adoption of a gluten-free diet (GFD) may have on this particular health issue.
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Coeliac men may have reversible infertility, and as in women, if gastrointestinal symptoms are mild or absent the diagnosis may be missed. It is important to make diagnosis because the giving of gluten free diet may result in conception and favourable outcome of pregnancy.
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There is now substantial evidence that coeliac sprue is associated with infertility both in men and women. (...) In men it can cause hypogonadism, immature secondary sex characteristics and reduce semen quality. (...) Hyperprolactinaemia is seen in 25% of coeliac patients, which causes impotence and loss of libido. Gluten withdrawal and correction of deficient dietary elements can lead to a return of fertility both in men and women.
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|Wikimedia Commons has media related to Infertility.|
- RCOG clinical guidelines for infertility (concise guidelines)
- Fertility: Assessment and Treatment for People with Fertility Problems, 2004 (extensive guidelines)
- GeneReviews/NCBI/NIH/UW entry on CATSPER-Related Male Infertility
- Infertility not just a Female Problem
- Assisted Reproduction in Judaism
- Facing Life Without Children When It Isn’t by Choice
- Patient Voices – Infertility