Histopathology image classification: Highlighting the gap between manual analysis and AI automation

Posted on May 21, 2024 By LabLynx Journal articles

This article is about the medical condition in humans. For the soil, see Soil fertility.

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

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.

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.

Definition

"Demographers tend to define infertility as childlessness in a population of women of reproductive age," whereas the epidemiological definition refers to "trying for" or "time to" a pregnancy, generally in a population of women exposed to a probability of conception.[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]

World Health Organization

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"

United States

One definition of infertility that is frequently used in the United States by reproductive endocrinologists, doctors who specialize in infertility, to consider a couple eligible for treatment is:

  • a woman under 35 has not conceived after 12 months of contraceptive-free intercourse.
  • a woman over 35 has not conceived after six months of contraceptive-free sexual intercourse.

United Kingdom

In the UK, previous NICE guidelines defined infertility as failure to conceive after regular unprotected sexual intercourse for two years in the absence of known reproductive pathology.[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]

Other definitions

Researchers commonly base demographic studies on infertility prevalence over a five-year period.[15]

Primary vs. secondary infertility

Primary infertility is defined as the absence of a live birth for women who desire a child and have been in a union for at least 12 months, during which they have not used any contraceptives.[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]

Effects

Psychological

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]

Social

Having a child is considered to be important in most societies. Infertile couples may experience social and family pressure leading to a feeling of social isolation. Factors of gender, age, religion, and socioeconomic status are important influences.[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]

Sexual

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]

Causes

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

Iodine deficiency may lead to infertility.[30]

Natural infertility

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

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).[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]

Immune infertility

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]

Sexually transmitted infections

Infections with the following sexually transmitted pathogens have a negative effect on fertility: Chlamydia trachomatis and Neisseria gonorrhoeae. There is a consistent association of Mycoplasma genitalium infection and female reproductive tract syndromes. M. genitalium infection is associated with increased risk of infertility.[37][38]

Genetic

Main article: Genetics 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.[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.

Other causes

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

  • DNA damage
    • DNA damage reduces fertility in female ovocytes, as caused by smoking,[41] other xenobiotic DNA damaging agents (such as radiation or chemotherapy)[42] or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine[43]
    • DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage,[44] smoking,[41] other xenobiotic DNA damaging agents (such as drugs or chemotherapy)[45] or other DNA damaging agents including reactive oxygen species, fever or high testicular temperature.[46] The damaged DNA related to infertility manifests itself by the increased susceptibility to denaturation inducible by heat or acid[47] or by the presence of double-strand breaks that can be detected by the TUNEL assay.[48] 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 spermatozoas, but if the spermatozoa does not have DNA damaged, 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).[63][64][65]

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

Females

Further information: Female infertility

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:

  • 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[69]

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:

Males

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% 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]

Unexplained infertility

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.[76] Epigenetic modifications in sperm may be also be responsible for unexplaiend infertility.[77][78]

Diagnosis

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.[79]

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.[80]
  • The woman has a history of endometriosis.[81]
  • 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. 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.[citation needed]

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]

Medical treatments

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]

A depiction of the procedure of in-vitro fertilization

Tourism

Main article: Fertility tourism

Fertility tourism is the practice of traveling to another country for fertility treatments.[85]

Stem cell therapy

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]

  • Spermatogonial stem cells transplant takes places in the seminiferous tubule with the patient experiencing spermatogenesis. This therapy is sometimes used cancer patients, whose sperm have been destroyed due to the gonadotoxic treatment.[87]
  • 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.[88]

Epidemiology

Prevalence of infertility varies depending on the definition, i.e. on the time span involved in the failure to conceive.

  • Infertility rates have increased by 4% since the 1980s, mostly from problems with fecundity due to an increase in age.[89]
  • 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.[90]
  • 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.[91]
  • In people going forward for IVF in the UK, roughly half of fertility problems with a diagnosed cause are due to problems with the man, and about half due to problems with the woman. However, about one in five cases of infertility have no clear diagnosed cause.[92]
  • 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.[93]
  • In Sweden, approximately 10% of couples wanting children are infertile.[94] 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 is 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."[95]

Society and culture

Perhaps except for infertility in science fiction, films and other fiction depicting emotional struggles of assisted reproductive technology have had an upswing first in the latter part of the 2000s decade, although the techniques have been available for decades.[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

Ethics

There are several ethical issues associated with infertility and its treatment.

  • High-cost treatments are out of financial reach for some couples.
  • Debate over whether health insurance companies (e.g. in the US) should be required to cover infertility treatment.
  • Allocation of medical resources that could be used elsewhere
  • The legal status of embryos fertilized in vitro 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 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, 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).[98][99]

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[100]
  • Regulatory bodies are also found in Canada[101] and in the state of Victoria in Australia[102]

See also

References

  1. ^ Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. (GBD 2015 Disease and Injury Incidence and Prevalence Collaborators) (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi:10.1016/S0140-6736(16)31678-6. PMC 5055577. PMID 27733282.
  2. ^ a b c d e f g h i j k l m n o p q r s t u v w x Carson, Sandra Ann; Kallen, Amanda N. (6 July 2021). "Diagnosis and Management of Infertility: A Review". JAMA. 326 (1): 65–76. doi:10.1001/jama.2021.4788. PMC 9302705. PMID 34228062.
  3. ^ Makar RS, Toth TL (June 2002). "The evaluation of infertility". American Journal of Clinical Pathology. 117 (Suppl): S95-103. doi:10.1309/w8lj-k377-dhra-cp0b. PMID 14569805.
  4. ^ Himmel W, Ittner E, Kochen MM, Michelmann HW, Hinney B, Reuter M, et al. (February 1997). "Management of involuntary childlessness". The British Journal of General Practice. 47 (415): 111–118. PMC 1312893. PMID 9101672.
  5. ^ a b c d "ART fact sheet (July 2014)". European Society of Human Reproduction and Embryology. Archived from the original on 4 March 2016.
  6. ^ a b Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. (2010). "World Health Organization reference values for human semen characteristics". Human Reproduction Update. 16 (3): 231–245. doi:10.1093/humupd/dmp048. PMID 19934213.
  7. ^ a b "Causes of infertility". National Health Service. 23 October 2017. Archived from the original on 29 February 2016. Retrieved 21 February 2016. Page last reviewed 15 July 2014
  8. ^ Stuenkel, Cynthia A.; Gompel, Anne (12 January 2023). "Primary Ovarian Insufficiency". New England Journal of Medicine. 388 (2): 154–163. doi:10.1056/NEJMcp2116488. PMID 36630623.
  9. ^ a b Gurunath S, Pandian Z, Anderson RA, Bhattacharya S (2011). "Defining infertility--a systematic review of prevalence studies". Human Reproduction Update. 17 (5): 575–588. doi:10.1093/humupd/dmr015. PMID 21493634.
  10. ^ Tamparo C, Lewis M (2011). Diseases of the Human Body. Philadelphia, PA: F.A. Davis Company. pp. 459. ISBN 9780803625051.
  11. ^ RMIA (20 October 2021). "Subfertility Or Infertility: Is It Time To Consider IVF?". Reproductive Medicine & Infertility Associates. Retrieved 3 August 2023.
  12. ^ "WHO | Infertility". Who.int. 19 March 2013. Archived from the original on 23 October 2013. Retrieved 17 June 2013.
  13. ^ Fertility: Assessment and Treatment for People with Fertility Problems (PDF). London: RCOG Press. 2004. ISBN 978-1-900364-97-3. Archived from the original (PDF) on 15 November 2010.
  14. ^ "Fertility: assessment and treatment for people with fertility problems, section: Defining infertility". NICE Clinical guidelines, CG156. February 2013. Archived from the original on 23 February 2013. Retrieved 14 February 2014.
  15. ^ "Infecundity, Infertility, and Childlessness in Developing Countries" (PDF). World Health Organization. Archived from the original (PDF) on 16 November 2020.
  16. ^ a b c "WHO | Infertility definitions and terminology". Archived from the original on 23 October 2013.
  17. ^ Cousineau TM, Domar AD (April 2007). "Psychological impact of infertility". Best Practice & Research. Clinical Obstetrics & Gynaecology. 21 (2): 293–308. doi:10.1016/j.bpobgyn.2006.12.003. PMID 17241818.
  18. ^ Rooney KL, Domar AD (March 2018). "The relationship between stress and infertility". Dialogues in Clinical Neuroscience. 20 (1): 41–47. doi:10.31887/DCNS.2018.20.1/klrooney. PMC 6016043. PMID 29946210.
  19. ^ Showell MG, Mackenzie-Proctor R, Jordan V, Hart RJ (August 2020). "Antioxidants for female subfertility". The Cochrane Database of Systematic Reviews. 8 (11): CD007807. doi:10.1002/14651858.CD007807.pub4. PMC 8094745. PMID 32851663.
  20. ^ a b c Deka, P. K., & Sarma, S. (2010). Psychological aspects of infertility. British Journal of Medical Practitioners, 3(3), 336.
  21. ^ Donor insemination Edited by C.L.R. Barratt and I.D. Cooke. Cambridge (England): Cambridge University Press, 1993. 231 pages., page 13, citing Berger (1980)
  22. ^ Domar AD, Zuttermeister PC, Friedman R (1993). "The psychological impact of infertility: a comparison with patients with other medical conditions". Journal of Psychosomatic Obstetrics and Gynaecology. 14 (Suppl): 45–52. PMID 8142988.
  23. ^ Donor insemination Edited by C.L.R. Barratt and I.D. Cooke. Cambridge (England): Cambridge University Press, 1993. 231 pages., page 13, in turn citing Connolly, Edelmann & Cooke 1987
  24. ^ Inhorn MC, Van Balen F, eds. (2002). Infertility around the Globe: New Thinking on Childlessness, Gender, and Reproductive Technologies. Berkeley (CA): University of California Press.
  25. ^ Singh HD (2022). Infertility in a Crowded Country: Hiding Reproduction in India. Bloomington (IN): Indiana University Press. ISBN 9780253063878.
  26. ^ Schmidt L, Christensen U, Holstein BE (April 2005). "The social epidemiology of coping with infertility". Human Reproduction. 20 (4): 1044–1052. doi:10.1093/humrep/deh687. PMID 15608029.
  27. ^ Khetarpal A, Singh S (2012). "Infertility: Why can't we classify this inability as disability?". The Australasian Medical Journal. 5 (6): 334–339. doi:10.4066/AMJ.2012.1290. PMC 3395292. PMID 22848333.
  28. ^ Leeners, Brigitte; Tschudin, Sibil; Wischmann, Tewes; Kalaitzopoulos, Dimitrios Rafail (5 January 2023). "Sexual dysfunction and disorders as a consequence of infertility: a systematic review and meta-analysis". Human Reproduction Update. 29 (1): 95–125. doi:10.1093/humupd/dmac030. ISSN 1355-4786. PMID 35900268.
  29. ^ Chowdhury SH, Cozma AI, Chowdhury JH. Infertility. Essentials for the Canadian Medical Licensing Exam: Review and Prep for MCCQE Part I. 2nd edition. Wolters Kluwer. Hong Kong. 2017.
  30. ^ Mathews DM, Johnson NP, Sim RG, O'Sullivan S, Peart JM, Hofman PL (January 2021). "Iodine and fertility: do we know enough?". Human Reproduction. 36 (2): 265–274. doi:10.1093/humrep/deaa312. PMID 33289034.
  31. ^ "Precocious Puberty". KidsHealth. Archived from the original on 23 January 2016. Retrieved 31 August 2021.
  32. ^ a b c d e Ferri FF (26 May 2018). Ferri's clinical advisor 2019 : 5 books in 1. Elsevier Health Sciences. ISBN 9780323550765. OCLC 1040695302.
  33. ^ Howard SR, Dunkel L (2018). "The Genetic Basis of Delayed Puberty". Neuroendocrinology. 106 (3): 283–291. doi:10.1159/000481569. PMID 28926843. S2CID 4772278.
  34. ^ Klein DA, Emerick JE, Sylvester JE, Vogt KS (November 2017). "Disorders of Puberty: An Approach to Diagnosis and Management". American Family Physician. 96 (9): 590–599. PMID 29094880.
  35. ^ a b c Restrepo B, Cardona-Maya W (October 2013). "Antisperm antibodies and fertility association". Actas Urologicas Espanolas. 37 (9): 571–578. doi:10.1016/j.acuro.2012.11.003. PMID 23428233.
  36. ^ Rao K (30 September 2013). Principles & Practice of Assisted Reproductive Technology (3 Vols). JP Medical Ltd. ISBN 9789350907368.
  37. ^ Lis R, Rowhani-Rahbar A, Manhart LE (August 2015). "Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis". Clinical Infectious Diseases. 61 (3): 418–426. doi:10.1093/cid/civ312. hdl:1773/26479. PMID 25900174.
  38. ^ Ljubin-Sternak S, Meštrović T (2014). "Chlamydia trachomatis and Genital Mycoplasmas: Pathogens with an Impact on Human Reproductive Health". Journal of Pathogens. 2014 (183167): 183167. doi:10.1155/2014/183167. PMC 4295611. PMID 25614838.
  39. ^ Ferraz-de-Souza B, Lin L, Achermann JC (April 2011). "Steroidogenic factor-1 (SF-1, NR5A1) and human disease". Molecular and Cellular Endocrinology. 336 (1–2): 198–205. doi:10.1016/j.mce.2010.11.006. PMC 3057017. PMID 21078366.
  40. ^ Liehr T, Weise A (May 2007). "Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics". International Journal of Molecular Medicine. 19 (5): 719–731. PMID 17390076.
  41. ^ a b Zenzes MT (2000). "Smoking and reproduction: gene damage to human gametes and embryos". Human Reproduction Update. 6 (2): 122–131. doi:10.1093/humupd/6.2.122. PMID 10782570.
  42. ^ Mark-Kappeler CJ, Hoyer PB, Devine PJ (November 2011). "Xenobiotic effects on ovarian preantral follicles". Biology of Reproduction. 85 (5): 871–883. doi:10.1095/biolreprod.111.091173. PMC 3197911. PMID 21697514.
  43. ^ Seino T, Saito H, Kaneko T, Takahashi T, Kawachiya S, Kurachi H (June 2002). "Eight-hydroxy-2'-deoxyguanosine in granulosa cells is correlated with the quality of oocytes and embryos in an in vitro fertilization-embryo transfer program". Fertility and Sterility. 77 (6): 1184–1190. doi:10.1016/s0015-0282(02)03103-5. PMID 12057726.
  44. ^ Gharagozloo P, Aitken RJ (July 2011). "The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy". Human Reproduction. 26 (7): 1628–1640. doi:10.1093/humrep/der132. PMID 21546386.
  45. ^ Nili HA, Mozdarani H, Pellestor F (2011). "Impact of DNA damage on the frequency of sperm chromosomal aneuploidy in normal and subfertile men". Iranian Biomedical Journal. 15 (4): 122–129. doi:10.6091/ibj.990.2012. PMC 3614247. PMID 22395136.
  46. ^ Shamsi MB, Imam SN, Dada R (November 2011). "Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility". Journal of Assisted Reproduction and Genetics. 28 (11): 1073–1085. doi:10.1007/s10815-011-9631-8. PMC 3224170. PMID 21904910.
  47. ^ Evenson DP, Darzynkiewicz Z, Melamed MR (December 1980). "Relation of mammalian sperm chromatin heterogeneity to fertility". Science. 210 (4474): 1131–1133. Bibcode:1980Sci...210.1131E. doi:10.1126/science.7444440. PMID 7444440.
  48. ^ Gorczyca W, Traganos F, Jesionowska H, Darzynkiewicz Z (July 1993). "Presence of DNA strand breaks and increased sensitivity of DNA in situ to denaturation in abnormal human sperm cells: analogy to apoptosis of somatic cells". Experimental Cell Research. 207 (1): 202–205. doi:10.1006/excr.1993.1182. PMID 8391465.
  49. ^ Jangir RN, Jain GC (May 2014). "Diabetes mellitus induced impairment of male reproductive functions: a review". Current Diabetes Reviews. 10 (3): 147–157. doi:10.2174/1573399810666140606111745. PMID 24919656.
  50. ^ Livshits A, Seidman DS (November 2009). "Fertility issues in women with diabetes". Women's Health. 5 (6): 701–707. doi:10.2217/whe.09.47. PMID 19863473.
  51. ^ Andreeva P (2014). "[Thyroid gland and fertility]". Akusherstvo I Ginekologiia. 53 (7): 18–23. PMID 25675618.
  52. ^ Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, et al. (2014). "Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms". Human Reproduction Update. 20 (4): 582–593. doi:10.1093/humupd/dmu007. hdl:10807/56796. PMID 24619876. 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.
  53. ^ Lasa JS, Zubiaurre I, Soifer LO (2014). "Risk of infertility in patients with celiac disease: a meta-analysis of observational studies". Arquivos de Gastroenterologia. 51 (2): 144–150. doi:10.1590/S0004-28032014000200014. PMID 25003268. 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.
  54. ^ Hozyasz K (March 2001). "[Coeliac disease and problems associated with reproduction]". Ginekologia Polska. 72 (3): 173–179. PMID 11398587. 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.
  55. ^ Sher KS, Jayanthi V, Probert CS, Stewart CR, Mayberry JF (1994). "Infertility, obstetric and gynaecological problems in coeliac sprue". Digestive Diseases. 12 (3): 186–190. doi:10.1159/000171452. PMID 7988065. 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.
  56. ^ Reichman DE, White PC, New MI, Rosenwaks Z (February 2014). "Fertility in patients with congenital adrenal hyperplasia". Fertility and Sterility. 101 (2): 301–309. doi:10.1016/j.fertnstert.2013.11.002. PMID 24355046.
  57. ^ van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, Bisschop PH (2011). "Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review" (PDF). Human Reproduction Update. 17 (5): 605–619. doi:10.1093/humupd/dmr024. PMID 21622978. Archived (PDF) from the original on 18 February 2019. Retrieved 19 September 2019.
  58. ^ Mendiola J, Torres-Cantero AM, Moreno-Grau JM, Ten J, Roca M, Moreno-Grau S, Bernabeu R (June 2008). "Exposure to environmental toxins in males seeking infertility treatment: a case-controlled study". Reproductive Biomedicine Online. 16 (6): 842–850. doi:10.1016/S1472-6483(10)60151-4. PMID 18549695.
  59. ^ Smith EM, Hammonds-Ehlers M, Clark MK, Kirchner HL, Fuortes L (February 1997). "Occupational exposures and risk of female infertility". Journal of Occupational and Environmental Medicine. 39 (2): 138–147. doi:10.1097/00043764-199702000-00011. PMID 9048320.
  60. ^ Björvang, Richelle D.; Damdimopoulou, Pauliina (2 April 2020). "Persistent environmental endocrine-disrupting chemicals in ovarian follicular fluid and in vitro fertilization treatment outcome in women". Upsala Journal of Medical Sciences. 125 (2): 85–94. doi:10.1080/03009734.2020.1727073. ISSN 0300-9734. PMC 7721012. PMID 32093529.
  61. ^ Björvang, Richelle D.; Hallberg, Ida; Pikki, Anne; Berglund, Lars; Pedrelli, Matteo; Kiviranta, Hannu; Rantakokko, Panu; Ruokojärvi, Päivi; Lindh, Christian H.; Olovsson, Matts; Persson, Sara; Holte, Jan; Sjunnesson, Ylva; Damdimopoulou, Pauliina (May 2022). "Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies". Environmental Research. 208: 112626. Bibcode:2022ER....20812626B. doi:10.1016/j.envres.2021.112626. PMID 34973191. S2CID 245581454.
  62. ^ "Regulated fertility services: a commissioning aid". Department of Health UK. June 2009. Archived from the original on 3 January 2011.
  63. ^ "Infertility & STDs - STD Information from CDC". cdc.gov. 11 January 2019. Archived from the original on 17 August 2017. Retrieved 9 September 2017.
  64. ^ Wittenberg ME. "STDs That Can Cause Infertility". LIVESTRONG.COM. Archived from the original on 24 November 2014. Retrieved 3 December 2014.
  65. ^ "5 Most Common Causes of Infertility". HowStuffWorks. 17 February 2011. Archived from the original on 14 December 2014. Retrieved 3 December 2014.
  66. ^ a b Ameratunga, Devini; Gebeh, Alpha; Amoako, Akwasi (August 2023). "Obesity and male infertility". Best Practice & Research Clinical Obstetrics & Gynaecology. 90: 102393. doi:10.1016/j.bpobgyn.2023.102393.
  67. ^ "About infertility & fertility problems". Human Fertilisation and Embryology Authority. Archived from the original on 29 August 2008.
  68. ^ Lessey BA (June 2000). "Medical management of endometriosis and infertility". Fertility and Sterility. 73 (6): 1089–96. doi:10.1016/s0015-0282(00)00519-7. PMID 10856462.
  69. ^ Walker MH, Tobler KJ (March 2020). "Female Infertility". StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. PMID 32310493.
  70. ^ "Female Infertility". Mayo Clinic. Archived from the original on 24 September 2020. Retrieved 21 September 2020.
  71. ^ Balen AH, Dresner M, Scott EM, Drife JO (February 2006). "Should obese women with polycystic ovary syndrome receive treatment for infertility?". BMJ. 332 (7539): 434–435. doi:10.1136/bmj.332.7539.434. PMC 1382524. PMID 16497735.
  72. ^ Leslie SW, Siref LE, Khan MAB. Male Infertility| Updated 2020 Oct 30| In: StatPearls [Internet]| Treasure Island (FL): StatPearls| Publishing; 2020 Jan| Available from: Leslie SW, Siref LE, Soon-Sutton TL, Khan MA (2022). "Male Infertility". Male Infertility - StatPearls - NCBI Bookshelf. StatPearls. PMID 32965929.
  73. ^ Mishail, Alek; Marshall, Susan; Schulsinger, David; Sheynkin, Yefim (May 2009). "Impact of a second semen analysis on a treatment decision making in the infertile man with varicocele". Fertility and Sterility. 91 (5): 1809–1811. doi:10.1016/j.fertnstert.2008.01.100. PMID 18384779.
  74. ^ Avidor-Reiss T, Khire A, Fishman EL, Jo KH (April 2015). "Atypical centrioles during sexual reproduction". Frontiers in Cell and Developmental Biology. 3: 21. doi:10.3389/fcell.2015.00021. PMC 4381714. PMID 25883936.
  75. ^ Kim, Chung Hyon; Kim, Jung Heon; Kim, Hyun Jung; Kim, Kun Woo; Lee, Joong Yeup; Yang, Soon Ha; Choe, Jin; Hwang, Doyeong; Kim, Ki Chul; Hwang, Eung Soo (2012). "Detection of Adeno-associated Virus from Semen Suffering with Male Factor Infertility and Having Their Conception Partners with Recurrent Miscarriages". Journal of Bacteriology and Virology. 42 (4): 339. doi:10.4167/jbv.2012.42.4.339.
  76. ^ Altmäe S, Stavreus-Evers A, Ruiz JR, Laanpere M, Syvänen T, Yngve A, et al. (June 2010). "Variations in folate pathway genes are associated with unexplained female infertility". Fertility and Sterility. 94 (1): 130–137. doi:10.1016/j.fertnstert.2009.02.025. PMID 19324355.
  77. ^ Aston KI, Uren PJ, Jenkins TG, Horsager A, Cairns BR, Smith AD, Carrell DT (December 2015). "Aberrant sperm DNA methylation predicts male fertility status and embryo quality". Fertility and Sterility. 104 (6): 1388–1397. doi:10.1016/j.fertnstert.2015.08.019. PMID 26361204.
  78. ^ Dada R, Kumar M, Jesudasan R, Fernández JL, Gosálvez J, Agarwal A (March 2012). "Epigenetics and its role in male infertility". Journal of Assisted Reproduction and Genetics. 29 (3): 213–223. doi:10.1007/s10815-012-9715-0. PMC 3288140. PMID 22290605.
  79. ^ "Infertility Help: When & where to get help for fertility treatment". Archived from the original on 25 December 2008.
  80. ^ Committee on Gynecologic Practice, American Society for Reproductive Medicine (January 2019). "Prepregnancy counseling". Fertility and Sterility. 111 (1): 32–42. doi:10.1016/j.fertnstert.2018.12.003. PMID 30611411.
  81. ^ "Endometriosis and Fertility - Brigham and Women's Hospital".
  82. ^ Baird D, Bhattacharya S, Devroey P, Diedrich K, Evers J, Fauser B, et al. (ESHRE Capri Workshop Group) (2013). "Failures (with some successes) of assisted reproduction and gamete donation programs". Human Reproduction Update. 19 (4): 354–365. doi:10.1093/humupd/dmt007. PMID 23459992.
  83. ^ Sabanegh Jr ES (20 October 2010). Male Infertility: Problems and Solutions. Springer Science & Business Media. pp. 82–83. ISBN 978-1-60761-193-6.
  84. ^ Steptoe, P. C.; Edwards, R. G. (12 August 1978). "Birth after the reimplantation of a human embryo". The Lancet. 2 (8085): 366. doi:10.1016/s0140-6736(78)92957-4. PMID 79723. Retrieved 27 June 2024.
  85. ^ Bergmann S (2011). "Fertility tourism: circumventive routes that enable access to reproductive technologies and substances". Signs. 36 (2): 280–288. doi:10.1086/655978. PMID 21114072. S2CID 22730138. Archived from the original on 27 July 2021. Retrieved 27 July 2021.
  86. ^ Vassena R, Eguizabal C, Heindryckx B, Sermon K, Simon C, van Pelt AM, et al. (September 2015). "Stem cells in reproductive medicine: ready for the patient?". Human Reproduction. 30 (9): 2014–2021. doi:10.1093/humrep/dev181. PMID 26202914.
  87. ^ Hermann BP, Sukhwani M, Winkler F, Pascarella JN, Peters KA, Sheng Y, et al. (November 2012). "Spermatogonial stem cell transplantation into rhesus testes regenerates spermatogenesis producing functional sperm". Cell Stem Cell. 11 (5): 715–726. doi:10.1016/j.stem.2012.07.017. PMC 3580057. PMID 23122294.
  88. ^ Kim, Hye Kyeong; Kim, Tae Jin (19 February 2024). "Current Status and Future Prospects of Stem Cell Therapy for Infertile Patients with Premature Ovarian Insufficiency". Biomolecules. 14 (2): 242. doi:10.3390/biom14020242. PMC 10887045. PMID 38397479.
  89. ^ Maheshwari A (2008). Human Reproduction. pp. 538–542.
  90. ^ Taylor A (August 2003). "ABC of subfertility: extent of the problem". BMJ. 327 (7412): 434–436. doi:10.1136/bmj.327.7412.434. PMC 188498. PMID 12933733.
  91. ^ Zitzmann M (August 2013). "Effects of age on male fertility". Best Practice & Research. Clinical Endocrinology & Metabolism. 27 (4): 617–628. doi:10.1016/j.beem.2013.07.004. PMID 24054934.
  92. ^ "HFEA Chart on reasons for infertility". Archived from the original on 30 May 2008. Retrieved 2 June 2008.
  93. ^ Khan K, Gupta JK, Mires G (2005). Core clinical cases in obstetrics and gynaecology: a problem-solving approach. London: Hodder Arnold. p. 152. ISBN 978-0-340-81672-1.
  94. ^ "Till spermadonator" [To sperm donators] (PDF). Sahlgrenska University Hospital (in Swedish). Archived from the original (PDF) on 26 June 2008. Cirka 10% av alla par har problem med ofrivillig barnlöshet. [About 10% of all couples have problems with involuntary childlessness.])
  95. ^ Barnes, Liberty; Fledderjohann, Jasmine (7 December 2017). "The invisible infertile: how cultural beliefs can shape statistics". theconversation.com. Retrieved 13 April 2023.
  96. ^ a b Mastony C (21 June 2009). "Heartache of infertility shared on stage, screen". Chicago Tribune. Archived from the original on 3 July 2012.
  97. ^ O'Neill D (2009). "Up with ageing". BMJ. 339: b4215. doi:10.1136/bmj.b4215. S2CID 73118359.
  98. ^ Deomampo D (2016). Transnational Reproduction: Race, Kinship, and Commercial Surrogacy in India. New York: New York University Press.
  99. ^ Singh HD (2014). "The World's Back Womb?: Commercial Surrogacy and Infertility Inequalities in India". American Anthropologist. 116 (4): 824–828. doi:10.1111/aman.12146. hdl:2027.42/109636.
  100. ^ "Europa". europa.eu. Archived from the original on 21 May 2008.
  101. ^ "Assisted Human Reproduction Canada". Archived from the original on 23 May 2008.
  102. ^ "Independent Theatre Association". Archived from the original on 28 August 2021. Retrieved 2 June 2008.

Further reading

source: https://en.wikipedia.org/wiki/Infertility

    by LabLynx

    Website

    Related Posts