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Female infertility

Female infertility refers to infertility in women. It affects an estimated 48 million women,[2] with the highest prevalence of infertility affecting women in South Asia, Sub-Saharan Africa, North Africa/Middle East, and Central/Eastern Europe and Central Asia.[2] Infertility is caused by many sources, including nutrition, diseases, and other malformations of the uterus. Infertility affects women from around the world, and the cultural and social stigma surrounding it varies.

Female infertility
Cumulative percentage and average age for women reaching subfertility, sterility, irregular menstruation and menopause.[1]
SpecialtyGynecology

Cause edit

Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic, or strictly by location.

Although factors of female infertility can be classified as either acquired or genetic, female infertility is usually more or less a combination of nature and nurture. Also, the presence of any single risk factor of female infertility (such as smoking, mentioned further below) does not necessarily cause infertility, and even if a woman is definitely infertile, the infertility cannot definitely be blamed on any single risk factor even if the risk factor is (or has been) present.

Acquired edit

According to the American Society for Reproductive Medicine (ASRM), age, smoking, sexually transmitted infections, and being overweight or underweight can all affect fertility.[3]

In broad sense, acquired factors practically include any factor that is not based on a genetic mutation, including any intrauterine exposure to toxins during fetal development, which may present as infertility many years later as an adult.

Age edit

A woman's fertility is affected by her age. The average age of a girl's first period (menarche) is 12–13 (12.5 years in the United States,[4] 12.72 in Canada,[5] 12.9 in the UK[6]), but, in postmenarchal girls, about 80% of the cycles are anovulatory in the first year after menarche, 50% in the third and 10% in the sixth year.[7] A woman's fertility peaks in the early and mid 20s, after which it starts to decline, with this decline being accelerated after age 35. However, the exact estimates of a woman chances to conceive after a certain age are not clear, with research giving differing results. The chances of a couple to successfully conceive at an advanced age depend on many factors, including the general health of a woman and the fertility of the male partner.

Menopause typically occurs between 44 and 58 years of age.[8] DNA testing is rarely carried out to confirm claims of maternity at advanced ages, but in one large study, among 12,549 African and Middle Eastern immigrant mothers, confirmed by DNA testing, only two mothers were found to be older than fifty; the oldest mother being 52.1 years at conception (and the youngest mother 10.7 years old).[9]

Tobacco smoking edit

Tobacco smoking is harmful to the ovaries, and the degree of damage is dependent upon the amount and length of time a woman smokes or is exposed to a smoke-filled environment. Nicotine and other harmful chemicals in cigarettes interfere with the body's ability to create estrogen, a hormone that regulates folliculogenesis and ovulation. Also, cigarette smoking interferes with folliculogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and the uterine myometrium.[10] Some damage is irreversible, but stopping smoking can prevent further damage.[11] Smokers are 60% more likely to be infertile than non-smokers.[12] Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.[12] Also, female smokers have an earlier onset of menopause by approximately 1–4 years.[13]

Sexually transmitted infections edit

Sexually transmitted infections are a leading cause of infertility. They often display few, if any visible symptoms, with the risk of failing to seek proper treatment in time to prevent decreased fertility.[11]

Body weight and eating disorders edit

Twelve percent of all infertility cases are a result of a woman either being underweight or overweight. Fat cells produce estrogen,[14] in addition to the primary sex organs. Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control, limiting the odds of getting pregnant.[11] Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle.[11] Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate.[11] Proper nutrition in early life is also a major factor for later fertility.[15]

A study in the US indicated that approximately 20% of infertile women had a past or current eating disorder, which is five times higher than the general lifetime prevalence rate.[16]

A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs. In hypothetical groups of 1,000 women undergoing fertility care, the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women. For ovulatory women, the study counted approximately 700 live births for normal weight, 550 live births for overweight and 530 live births for obese women. The increase in cost per live birth in anovulatory overweight and obese women were, respectively, 54 and 100% higher than their normal weight counterparts, for ovulatory women they were 44 and 70% higher, respectively.[17]

Radiation edit

Exposure to radiation poses a high risk of infertility, depending on the frequency, power, and exposure duration. Radiotherapy is reported to cause infertility.[18]

the amount of radiation absorbed by the ovaries will determine if she becomes infertile. High doses can destroy some or all of the eggs in the ovaries and might cause infertility or early menopause.

Chemotherapy edit

Chemotherapy poses a high risk of infertility. Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil and chlormethine.[19] Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.[19] On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin and antimetabolites such as methotrexate, mercaptopurine and 5-fluorouracil.[19]

Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles.[20] This loss is not necessarily a direct effect of the chemotherapeutic agents, but could be due to an increased rate of growth initiation to replace damaged developing follicles.[20] Antral follicle count decreases after three series of chemotherapy, whereas follicle stimulating hormone (FSH) reaches menopausal levels after four series.[21] Other hormonal changes in chemotherapy include decrease in inhibin B and anti-Müllerian hormone levels.[21]

Women may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of ovarian tissue, oocytes or embryos.[22]

Immune infertility edit

Antisperm antibodies (ASA) have been considered as infertility cause in around 10–30% of infertile couples.[23] 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.[23][24]

Other acquired factors edit

Genetic factors edit

There are many genes wherein mutation causes female infertility, as shown in table below. Also, there are additional conditions involving female infertility which are believed to be genetic but where no single gene has been found to be responsible, notably Mayer-Rokitansky-Küstner-Hauser Syndrome (MRKH).[35] Finally, an unknown number of genetic mutations cause a state of subfertility, which in addition to other factors such as environmental ones may manifest as frank infertility.

Chromosomal abnormalities causing female infertility include Turner syndrome. Oocyte donation is an alternative for patients with Turner syndrome.[36]

Some of these gene or chromosome abnormalities cause intersex conditions, such as androgen insensitivity syndrome.

Genes wherein mutation causes female infertility[37]
Gene Encoded protein Effect of deficiency
BMP15 Bone morphogenetic protein 15 Hypergonadotrophic ovarian failure (POF4)
BMPR1B Bone morphogenetic protein receptor 1B Ovarian dysfunction, hypergonadotrophic hypogonadism and acromesomelic chondrodysplasia
CBX2; M33 Chromobox protein homolog 2; Drosophila polycomb class

Autosomal 46,XY, male-to-female sex reversal (phenotypically perfect females)

CHD7 Chromodomain-helicase-DNA-binding protein 7 CHARGE syndrome and Kallmann syndrome (KAL5)
DIAPH2 Diaphanous homolog 2 Hypergonadotrophic, premature ovarian failure (POF2A)
FGF8 Fibroblast growth factor 8 Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome (KAL6)
FGFR1 Fibroblast growth factor receptor 1 Kallmann syndrome (KAL2)
HFM1 Primary ovarian failure[38]
FSHR FSH receptor Hypergonadotrophic hypogonadism and ovarian hyperstimulation syndrome
FSHB Follitropin subunit beta Deficiency of follicle-stimulating hormone, primary amenorrhoea and infertility
FOXL2 Forkhead box L2 Isolated premature ovarian failure (POF3) associated with BPES type I; FOXL2

402C --> G mutations associated with human granulosa cell tumours

FMR1 Fragile X mental retardation Premature ovarian failure (POF1) associated with premutations
GNRH1 Gonadotropin releasing hormone Normosmic hypogonadotrophic hypogonadism
GNRHR GnRH receptor Hypogonadotrophic hypogonadism
KAL1 Kallmann syndrome Hypogonadotrophic hypogonadism and insomnia, X-linked Kallmann syndrome (KAL1)
KISS1R; GPR54 KISS1 receptor Hypogonadotrophic hypogonadism
LHB Luteinizing hormone beta polypeptide Hypogonadism and pseudohermaphroditism
LHCGR LH/choriogonadotrophin receptor Hypergonadotrophic hypogonadism (luteinizing hormone resistance)
DAX1 Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 X-linked congenital adrenal hypoplasia with hypogonadotrophic hypogonadism; dosage-sensitive male-to-female sex reversal
NR5A1; SF1 Steroidogenic factor 1 46,XY male-to-female sex reversal and streak gonads and congenital lipoid adrenal hyperplasia; 46,XX gonadal dysgenesis and 46,XX primary ovarian insufficiency
POF1B Premature ovarian failure 1B Hypergonadotrophic, primary amenorrhea (POF2B)
PROK2 Prokineticin Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome (KAL4)
PROKR2 Prokineticin receptor 2 Kallmann syndrome (KAL3)
RSPO1 R-spondin family, member 1 46,XX, female-to-male sex reversal (individuals contain testes)
SRY Sex-determining region Y Mutations lead to 46,XY females; translocations lead to 46,XX males
SCNN1A Alpha subunit of Epithelial sodium channel (ENaC) Nonsense mutation leads to defective expression of ENaC in the female reproductive tract[39]
SOX9 SRY-related HMB-box gene 9
STAG3 Stromal antigen 3 Premature ovarian failure[40]
TAC3 Tachykinin 3 Normosmic hypogonadotrophic hypogonadism
TACR3 Tachykinin receptor 3 Normosmic hypogonadotrophic hypogonadism
ZP1 zona pellucida glycoprotein 1 Dysfunctional zona pellucida formation[41]

By location edit

Hypothalamic-pituitary factors edit

Ovarian factors edit

•2 of these 3 criteria: 1) Anovulation/oligoovulation 2) Hyperandrogenism 3) PCO Ultrasound •Must be excluded: o Congenital Suprarrenal hyperplasia o Androgen producer tumors o Hyperprolactinemia Some of PCOS's consequeces are:

•Insulin Resistance in 80% of PCOS women. 

•Higher incidence of spontaneus miscarriage. •Higher risk of developing diabetes mellitus type 2

- Ultrasound: antral follicle count (AFC) >6AF - Hormones: FSH, E2, AMH

Tubal (ectopic)/peritoneal factors edit

  • Endometriosis (also see endometriosis and infertility)
  • Pelvic adhesions
  • Pelvic inflammatory disease (PID, usually due to chlamydia)[44]
  • Tubal dysfunction
  • Previous ectopic pregnancy. A randomized study in 2013 came to the result that the rates of intrauterine pregnancy two years after treatment of ectopic pregnancy are approximately 64% with radical surgery, 67% with medication, and 70% with conservative surgery.[45] In comparison, the cumulative pregnancy rate of women under 40 years of age in the general population over two years is over 90%.[46]
  • Hydrosalpinx is the most frequent. This happens when there is a presence of fluid on the tubes. We have some ways to test it: Hysterosalphingography, in which we can see both the uterus (Hystero) and the tubes. Hysterosonosalphingography, in which we see only the uterus. This tests are used to check if the tubes are permeable or if there is any obstacle in the path to the uterus. We have to introduce a liquid contrast via vagina, and we check its path via x-ray. If the tube is blocked, the contrast liquid will be stopped in the tubes, but if it's not blocked, it will end in the abdominal cavity. The flow of this contrast needs peristaltic movements. This blockage can be produced by sexually transmitted infections, previous surgery, peritonitis or endometriosis.

•Permeability Hysterosalpingography (HSG) Ultrasoud + Hysterosonosalpingography (HSSG) Chlamydia serology Laparoscopy: methylene blue •Tubal examination (endoscopy): laparoscopy, faloscopy, fertiloscopy

Uterine factors edit

Previously, a bicornuate uterus was thought to be associated with infertility,[49] but recent studies have not confirmed such an association.[50]

Cervical factors edit

Vaginal factors edit

Interrupted meiosis edit

Meiosis. a special type of cell division specific to germ cells, produces egg cells in women. During meiosis, accurate segregation of chromosomes must occur during two rounds of division to create, upon fertilisation, a zygote with a proper diploid (euploid) set of chromosomes. About half of all spontaneous abortions are aneuploid, that is, have an improper set of chromosomes.[53] Human genetic variants that likely cause dysregulation of critical meiotic processes have been identified in 14 female infertility associated genes.[53]

A major cause of female infertility is premature ovarian insufficiency.[54] This insufficiency is a heterogeneous disease that affects about 1% of women who are under the age of 40.[54] Some instances of female infertility are caused by DNA repair dysregulation during meiosis.[54]

Diagnosis edit

Diagnosis of infertility begins with a medical history and physical exam. The healthcare provider may order tests, including the following:

There are genetic testing techniques under development to detect any mutation in genes associated with female infertility.[37]

Initial diagnosis and treatment of infertility is usually made by obstetrician/gynecologists or women's health nurse practitioners. If initial treatments are unsuccessful, referral is usually made to physicians who are fellowship trained as reproductive endocrinologists. Reproductive endocrinologists are usually obstetrician/gynecologists with advanced training in reproductive endocrinology and infertility (in North America). These physicians treat reproductive disorders affecting not only women but also men, children, and teens.

Usually reproductive endocrinology & infertility medical practices do not see women for general maternity care. The practice is primarily focused on helping their women to conceive and to correct any issues related to recurring pregnancy loss.

Definition edit

There is no unanimous definition of female infertility, because the definition depends on social and physical characteristics which may vary by culture and situation. NICE guidelines state 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."[46] It is recommended that a consultation with a fertility specialist should be made earlier if the woman is aged 36 years or over, or there is a known clinical cause of infertility or a history of predisposing factors for infertility.[46] According to the World Health Organization (WHO), infertility can be described as the inability to become pregnant, maintain a pregnancy, or carry a pregnancy to live birth.[57] A clinical definition of infertility by the WHO and ICMART 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."[58] Infertility can further be broken down into primary and secondary infertility. Primary infertility refers to the inability to give birth either because of not being able to become pregnant, or carry a child to live birth, which may include miscarriage or a stillborn child. [59][60] Secondary infertility refers to the inability to conceive or give birth when there was a previous pregnancy or live birth.[60][59]

Prevention edit

Acquired female infertility may be prevented through identified interventions:

  • Maintaining a healthy lifestyle. Excessive exercise, consumption of caffeine and alcohol, and smoking have all been associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh fruits and vegetables, and maintaining a normal weight, on the other hand, have been associated with better fertility prospects.
  • Treating or preventing existing diseases. Identifying and controlling chronic diseases such as diabetes and hypothyroidism increases fertility prospects. Lifelong practice of safer sex reduces the likelihood that sexually transmitted infections will impair fertility; obtaining prompt treatment for sexually transmitted infections reduces the likelihood that such infections will do significant damage. Regular physical examinations (including pap smears) help detect early signs of infections or abnormalities.
  • Not delaying parenthood. Fertility does not ultimately cease before menopause, but it starts declining after age 27 and drops at a somewhat greater rate after age 35.[61] Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions, such as premature menopause, that can be mitigated by not delaying parenthood.
  • Egg freezing. A woman can freeze her eggs preserve her fertility. By using egg freezing while in the peak reproductive years, a woman's oocytes are cryogenically frozen and ready for her use later in life, reducing her chances of female infertility.

Treatment edit

There is no method to reverse advanced maternal age, but there are assisted reproductive technologies for many causes of infertility in pre-menopausal women, including:

Epidemiology edit

Female infertility varies widely by geographic location around the world. In 2010, there was an estimated 48.5 million infertile couples worldwide, and from 1990 to 2010 there was little change in levels of infertility in most of the world.[2] In 2010, the countries with the lowest rates of female infertility included the South American countries of Peru, Ecuador and Bolivia, as well as in Poland, Kenya, and Republic of Korea.[2] The highest rate regions included Eastern Europe, North Africa, the Middle East, Oceania, and Sub-Saharan Africa.[2] The prevalence of primary infertility has increased since 1990, but secondary infertility has decreased overall. Rates decreased (although not prevalence) of female infertility in high-income, Central/Eastern Europe, and Central Asia regions.[2] Female infertility is prevalent across the globe.

Africa edit

Sub-Saharan Africa has had decreasing levels of primary infertility from 1990 to 2010. Within the Sub-Saharan region, rates were lowest in Kenya, Zimbabwe, and Rwanda, while the highest rates were in Guinea, Mozambique, Angola, Gabon, and Cameroon along with Northern Africa near the Middle East.[2] According to a 2004 DHS report, rates in Africa were highest in Middle and Sub-Saharan Africa, with East Africa's rates close behind.[60]

Asia edit

In Asia, the highest rates of combined secondary and primary infertility was in the South Central region, and then in the Southeast region, with the lowest rates in the Western areas.[60]

Latin America and Caribbean edit

The prevalence of female infertility in the Latin America/Caribbean region is typically lower than the global prevalence. However, the greatest rates occurred in Jamaica, Suriname, Haiti, and Trinidad and Tobago. Central and Western Latin America has some of the lowest rates of prevalence.[2] The highest regions in Latin America and the Caribbean was in the Caribbean Islands and in less developed countries.[60]

Society and culture edit

Social stigma edit

Social stigma due to infertility is seen in many cultures throughout the world in varying forms. Often, when women cannot conceive, the blame is put on them, even when approximately 50% of infertility issues come from the man .[62] In addition, many societies only tend to value a woman if she is able to produce at least one child, and a marriage can be considered a failure when the couple cannot conceive.[62] The act of conceiving a child can be linked to the couple's consummation of marriage, and reflect their social role in society.[63] This is seen in the "African infertility belt", where infertility is prevalent in Africa which includes countries spanning from Tanzania in the east to Gabon in the west.[62] In this region, infertility is highly stigmatized and can be considered a failure of the couple to their societies.[62][64] This is demonstrated in Uganda and Nigeria where there is a great pressure put on childbearing and its social implications.[63] This is also seen in some Muslim societies including Egypt[65] and Pakistan.[66] In the United States, and all over the world, infertility and women's infertility at large is an invisible yet debilitating disease that is stigmatized and looked down upon. But, in recent years many have begun to sue organizations for infertility insurance coverage, as the Americans with Disabilities Act (ADA) has recognized infertility as a disability. This however adds another stigmatization to women suffering from infertility as the word disability has a negative connotation in various world societies. [77]

Wealth is sometimes measured by the number of children a woman has, as well as inheritance of property.[63][66] Children can influence financial security in many ways. In Nigeria and Cameroon, land claims are decided by the number of children. Also, in some Sub-Saharan countries women may be denied inheritance if she did not bear any children [66] In some African and Asian countries a husband can deprive his infertile wife of food, shelter and other basic necessities like clothing.[66] In Cameroon, a woman may lose access to land from her husband and left on her own in old age.[63]

In many cases, a woman who cannot bear children is excluded from social and cultural events including traditional ceremonies. This stigmatization is seen in Mozambique and Nigeria where infertile women have been treated as outcasts to society.[63] This is a humiliating practice which devalues infertile women in society.[67][68] In the Makua tradition, pregnancy and birth are considered major life events for a woman, with the ceremonies of nthaa'ra and ntha'ara no mwana, which can only be attended by women who have been pregnant and have had a baby.[67]

The effect of infertility can lead to social shaming from internal and social norms surrounding pregnancy, which affects women around the world.[68] When pregnancy is considered such an important event in life, and considered a "socially unacceptable condition", it can lead to a search for treatment in the form of traditional healers and expensive Western treatments.[65][69] The limited access to treatment in many areas can lead to extreme and sometimes illegal acts in order to produce a child.[63][65]

Marital role edit

Men in some countries may find another wife when their first cannot produce a child, hoping that by sleeping with more women he will be able to produce his own child.[63][65][66] This can be prevalent in some societies, including Cameroon,[63][66] Nigeria,[63] Mozambique,[67] Egypt,[65] Botswana,[70] and Bangladesh,[66] among many more where polygamy is more common and more socially acceptable. In couples that are unsuccessful in conceiving, divorce rates are roughly 3.5 times higher than those of couples who are fertile. This was based on those with female infertility. [78]

In some cultures, including Botswana [70] and Nigeria,[63] women can select a woman with whom she allows her husband to sleep with in hopes of conceiving a child.[63] Women who are desperate for children may compromise with her husband to select a woman and accept duties of taking care of the children to feel accepted and useful in society.[70]

Women may also sleep with other men in hopes of becoming pregnant.[67] This can be done for many reasons including advice from a traditional healer, or finding if another man was "more compatible". In many cases, the husband was not aware of the extra sexual relations and would not be informed if a woman became pregnant by another man.[67] This is not as culturally acceptable however, and can contribute to the gendered suffering of women who have fewer options to become pregnant on their own as opposed to men.[65]

Men and women can also turn to divorce in attempt to find a new partner with whom to bear a child. Infertility in many cultures is a reason for divorce, and a way for a man or woman to increase his/her chances of producing an heir.[63][65][67][70] When a woman is divorced, she can lose her security that often comes with land, wealth, and a family.[70] This can ruin marriages and can lead to distrust in the marriage. The increase of sexual partners can potentially result with the spread of disease including HIV/AIDS, and can actually contribute to future generations of infertility.[70]

Domestic abuse edit

The emotional strain and stress that comes with infertility in the household can lead to the mistreatment and domestic abuse of a woman. The devaluation of a wife due to her inability to conceive can lead to domestic abuse and emotional trauma such as victim blaming. Women are sometimes or often blamed as the cause of a couples' infertility, which can lead to emotional abuse, anxiety, and shame.[63] In addition, blame for not being able to conceive is often put on the female, even if it is the man who is infertile.[62] Women who are not able to conceive can be starved, beaten, and may be neglected financially by her husband as if she had no child bearing use to him.[66] The physical abuse related to infertility may result from this and the emotional stress that comes with it. In some countries, the emotional and physical abuses that come with infertility can potentially lead to assault, murder, and suicide.[71]

Mental and psychological impact edit

Many infertile women tend to cope with immense stress and social stigma behind their condition, which can lead to considerable mental distress.[72] The long-term stress involved in attempting to conceive a child and the social pressures behind giving birth can lead to emotional distress that may manifest as mental disease.[73] Women with infertility might deal with psychological stressors such as denial, anger, grief, guilt, and depression.[74] There can be considerable social shaming that can lead to intense feelings of sadness and frustration that potentially contribute to depression and suicide.[70] The implications behind infertility bear huge consequences for the mental health of an infertile woman because of the social pressures and personal grief behind being unable to bear children. The range of psychological issues pertaining to infertility in women is vast and can include inferiority complex, stress with interpersonal relationships, and possibly major depression and or anxiety. With the impacts of infertility on social life, cultural significance, and psychological factors, “infertility has been classified as one of the greatest stressors of life.” [76]

Emotional impact of infertility treatment edit

Many women have reported finding treatment for infertility stressful and a cause of relationship difficulties with their partners. The fear of failure was the most important barrier to treatment. Females, in studied cases, typically experience more adverse effects of infertility and treatments than to males. The psychological support is fundamental to limit the possibility to drop-out from infertility treatment and reduce the distress level which is strongly associated with lower pregnancy rates. In addition some medications (in particular clomifene citrate) used in the treatment have several side effects which may be an important risk factor for the development of depression.[75]

See also edit

References edit

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External links edit

female, infertility, refers, infertility, women, affects, estimated, million, women, with, highest, prevalence, infertility, affecting, women, south, asia, saharan, africa, north, africa, middle, east, central, eastern, europe, central, asia, infertility, caus. Female infertility refers to infertility in women It affects an estimated 48 million women 2 with the highest prevalence of infertility affecting women in South Asia Sub Saharan Africa North Africa Middle East and Central Eastern Europe and Central Asia 2 Infertility is caused by many sources including nutrition diseases and other malformations of the uterus Infertility affects women from around the world and the cultural and social stigma surrounding it varies Female infertilityCumulative percentage and average age for women reaching subfertility sterility irregular menstruation and menopause 1 SpecialtyGynecology Contents 1 Cause 1 1 Acquired 1 1 1 Age 1 1 2 Tobacco smoking 1 1 3 Sexually transmitted infections 1 1 4 Body weight and eating disorders 1 1 5 Radiation 1 1 6 Chemotherapy 1 1 7 Immune infertility 1 1 8 Other acquired factors 1 2 Genetic factors 1 3 By location 1 3 1 Hypothalamic pituitary factors 1 3 2 Ovarian factors 1 3 3 Tubal ectopic peritoneal factors 1 3 4 Uterine factors 1 3 5 Cervical factors 1 3 6 Vaginal factors 1 4 Interrupted meiosis 2 Diagnosis 2 1 Definition 3 Prevention 4 Treatment 5 Epidemiology 5 1 Africa 5 2 Asia 5 3 Latin America and Caribbean 6 Society and culture 6 1 Social stigma 6 2 Marital role 6 3 Domestic abuse 6 4 Mental and psychological impact 6 5 Emotional impact of infertility treatment 7 See also 8 References 9 Additional sources 10 External linksCause editCauses or factors of female infertility can basically be classified regarding whether they are acquired or genetic or strictly by location Although factors of female infertility can be classified as either acquired or genetic female infertility is usually more or less a combination of nature and nurture Also the presence of any single risk factor of female infertility such as smoking mentioned further below does not necessarily cause infertility and even if a woman is definitely infertile the infertility cannot definitely be blamed on any single risk factor even if the risk factor is or has been present Acquired edit According to the American Society for Reproductive Medicine ASRM age smoking sexually transmitted infections and being overweight or underweight can all affect fertility 3 In broad sense acquired factors practically include any factor that is not based on a genetic mutation including any intrauterine exposure to toxins during fetal development which may present as infertility many years later as an adult Age edit Main article Age and female fertility A woman s fertility is affected by her age The average age of a girl s first period menarche is 12 13 12 5 years in the United States 4 12 72 in Canada 5 12 9 in the UK 6 but in postmenarchal girls about 80 of the cycles are anovulatory in the first year after menarche 50 in the third and 10 in the sixth year 7 A woman s fertility peaks in the early and mid 20s after which it starts to decline with this decline being accelerated after age 35 However the exact estimates of a woman chances to conceive after a certain age are not clear with research giving differing results The chances of a couple to successfully conceive at an advanced age depend on many factors including the general health of a woman and the fertility of the male partner Menopause typically occurs between 44 and 58 years of age 8 DNA testing is rarely carried out to confirm claims of maternity at advanced ages but in one large study among 12 549 African and Middle Eastern immigrant mothers confirmed by DNA testing only two mothers were found to be older than fifty the oldest mother being 52 1 years at conception and the youngest mother 10 7 years old 9 Tobacco smoking edit See also Women and smoking Unique gender differences and health effects for Females Tobacco smoking is harmful to the ovaries and the degree of damage is dependent upon the amount and length of time a woman smokes or is exposed to a smoke filled environment Nicotine and other harmful chemicals in cigarettes interfere with the body s ability to create estrogen a hormone that regulates folliculogenesis and ovulation Also cigarette smoking interferes with folliculogenesis embryo transport endometrial receptivity endometrial angiogenesis uterine blood flow and the uterine myometrium 10 Some damage is irreversible but stopping smoking can prevent further damage 11 Smokers are 60 more likely to be infertile than non smokers 12 Smoking reduces the chances of IVF producing a live birth by 34 and increases the risk of an IVF pregnancy miscarrying by 30 12 Also female smokers have an earlier onset of menopause by approximately 1 4 years 13 Sexually transmitted infections edit Sexually transmitted infections are a leading cause of infertility They often display few if any visible symptoms with the risk of failing to seek proper treatment in time to prevent decreased fertility 11 Body weight and eating disorders edit Twelve percent of all infertility cases are a result of a woman either being underweight or overweight Fat cells produce estrogen 14 in addition to the primary sex organs Too much body fat causes production of too much estrogen and the body begins to react as if it is on birth control limiting the odds of getting pregnant 11 Too little body fat causes insufficient production of estrogen and disruption of the menstrual cycle 11 Both under and overweight women have irregular cycles in which ovulation does not occur or is inadequate 11 Proper nutrition in early life is also a major factor for later fertility 15 A study in the US indicated that approximately 20 of infertile women had a past or current eating disorder which is five times higher than the general lifetime prevalence rate 16 A review from 2010 concluded that overweight and obese subfertile women have a reduced probability of successful fertility treatment and their pregnancies are associated with more complications and higher costs In hypothetical groups of 1 000 women undergoing fertility care the study counted approximately 800 live births for normal weight and 690 live births for overweight and obese anovulatory women For ovulatory women the study counted approximately 700 live births for normal weight 550 live births for overweight and 530 live births for obese women The increase in cost per live birth in anovulatory overweight and obese women were respectively 54 and 100 higher than their normal weight counterparts for ovulatory women they were 44 and 70 higher respectively 17 Radiation edit Exposure to radiation poses a high risk of infertility depending on the frequency power and exposure duration Radiotherapy is reported to cause infertility 18 the amount of radiation absorbed by the ovaries will determine if she becomes infertile High doses can destroy some or all of the eggs in the ovaries and might cause infertility or early menopause Chemotherapy edit Chemotherapy poses a high risk of infertility Chemotherapies with high risk of infertility include procarbazine and other alkylating drugs such as cyclophosphamide ifosfamide busulfan melphalan chlorambucil and chlormethine 19 Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin 19 On the other hand therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine antibiotics such as bleomycin and dactinomycin and antimetabolites such as methotrexate mercaptopurine and 5 fluorouracil 19 Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles 20 This loss is not necessarily a direct effect of the chemotherapeutic agents but could be due to an increased rate of growth initiation to replace damaged developing follicles 20 Antral follicle count decreases after three series of chemotherapy whereas follicle stimulating hormone FSH reaches menopausal levels after four series 21 Other hormonal changes in chemotherapy include decrease in inhibin B and anti Mullerian hormone levels 21 Women may choose between several methods of fertility preservation prior to chemotherapy including cryopreservation of ovarian tissue oocytes or embryos 22 Immune infertility edit Antisperm antibodies ASA have been considered as infertility cause in around 10 30 of infertile couples 23 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 23 24 Other acquired factors edit Adhesions secondary to surgery in the peritoneal cavity is the leading cause of acquired infertility 25 A meta analysis in 2012 came to the conclusion that there is only little evidence for the surgical principle that using less invasive techniques introducing less foreign bodies or causing less ischemia reduces the extent and severity of adhesions 25 Diabetes mellitus A review of type 1 diabetes came to the result that despite modern treatment women with diabetes are at increased risk of female infertility such as reflected by delayed puberty and menarche menstrual irregularities especially oligomenorrhoea mild hyperandrogenism polycystic ovarian syndrome fewer live born children and possibly earlier menopause 26 Animal models indicate that abnormalities on the molecular level caused by diabetes include defective leptin insulin and kisspeptin signalling 26 Coeliac disease Non gastrointestinal symptoms of coeliac disease may include disorders of fertility such as delayed menarche amenorrea infertility or early menopause and pregnancy complications such as intrauterine growth restriction IUGR small for gestational age SGA babies recurrent abortions preterm deliveries or low birth weight LBW babies Nevertheless gluten free diet reduces the risk Some authors suggest that physicians should investigate the presence of undiagnosed coeliac disease in women with unexplained infertility recurrent miscarriage or IUGR 27 28 Significant liver or kidney disease Thrombophilia 29 30 Cannabis smoking such as of marijuana causes disturbances in the endocannabinoid system potentially causing infertility 31 Radiation such as in radiation therapy The radiation dose to the ovaries that generally causes permanent female infertility is 20 3 Gy at birth 18 4 Gy at 10 years 16 5 Gy at 20 years and 14 3 Gy at 30 years 32 After total body irradiation recovery of gonadal function occurs in 10 14 of cases and the number of pregnancies observed after hematopoietic stem cell transplantation involving such as procedure is lower than 2 33 34 Genetic factors edit See also Genetics of infertility There are many genes wherein mutation causes female infertility as shown in table below Also there are additional conditions involving female infertility which are believed to be genetic but where no single gene has been found to be responsible notably Mayer Rokitansky Kustner Hauser Syndrome MRKH 35 Finally an unknown number of genetic mutations cause a state of subfertility which in addition to other factors such as environmental ones may manifest as frank infertility Chromosomal abnormalities causing female infertility include Turner syndrome Oocyte donation is an alternative for patients with Turner syndrome 36 Some of these gene or chromosome abnormalities cause intersex conditions such as androgen insensitivity syndrome Genes wherein mutation causes female infertility 37 Gene Encoded protein Effect of deficiencyBMP15 Bone morphogenetic protein 15 Hypergonadotrophic ovarian failure POF4 BMPR1B Bone morphogenetic protein receptor 1B Ovarian dysfunction hypergonadotrophic hypogonadism and acromesomelic chondrodysplasiaCBX2 M33 Chromobox protein homolog 2 Drosophila polycomb class Autosomal 46 XY male to female sex reversal phenotypically perfect females CHD7 Chromodomain helicase DNA binding protein 7 CHARGE syndrome and Kallmann syndrome KAL5 DIAPH2 Diaphanous homolog 2 Hypergonadotrophic premature ovarian failure POF2A FGF8 Fibroblast growth factor 8 Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome KAL6 FGFR1 Fibroblast growth factor receptor 1 Kallmann syndrome KAL2 HFM1 Primary ovarian failure 38 FSHR FSH receptor Hypergonadotrophic hypogonadism and ovarian hyperstimulation syndromeFSHB Follitropin subunit beta Deficiency of follicle stimulating hormone primary amenorrhoea and infertilityFOXL2 Forkhead box L2 Isolated premature ovarian failure POF3 associated with BPES type I FOXL2 402C gt G mutations associated with human granulosa cell tumoursFMR1 Fragile X mental retardation Premature ovarian failure POF1 associated with premutationsGNRH1 Gonadotropin releasing hormone Normosmic hypogonadotrophic hypogonadismGNRHR GnRH receptor Hypogonadotrophic hypogonadismKAL1 Kallmann syndrome Hypogonadotrophic hypogonadism and insomnia X linked Kallmann syndrome KAL1 KISS1R GPR54 KISS1 receptor Hypogonadotrophic hypogonadismLHB Luteinizing hormone beta polypeptide Hypogonadism and pseudohermaphroditismLHCGR LH choriogonadotrophin receptor Hypergonadotrophic hypogonadism luteinizing hormone resistance DAX1 Dosage sensitive sex reversal adrenal hypoplasia critical region on chromosome X gene 1 X linked congenital adrenal hypoplasia with hypogonadotrophic hypogonadism dosage sensitive male to female sex reversalNR5A1 SF1 Steroidogenic factor 1 46 XY male to female sex reversal and streak gonads and congenital lipoid adrenal hyperplasia 46 XX gonadal dysgenesis and 46 XX primary ovarian insufficiencyPOF1B Premature ovarian failure 1B Hypergonadotrophic primary amenorrhea POF2B PROK2 Prokineticin Normosmic hypogonadotrophic hypogonadism and Kallmann syndrome KAL4 PROKR2 Prokineticin receptor 2 Kallmann syndrome KAL3 RSPO1 R spondin family member 1 46 XX female to male sex reversal individuals contain testes SRY Sex determining region Y Mutations lead to 46 XY females translocations lead to 46 XX malesSCNN1A Alpha subunit of Epithelial sodium channel ENaC Nonsense mutation leads to defective expression of ENaC in the female reproductive tract 39 SOX9 SRY related HMB box gene 9STAG3 Stromal antigen 3 Premature ovarian failure 40 TAC3 Tachykinin 3 Normosmic hypogonadotrophic hypogonadismTACR3 Tachykinin receptor 3 Normosmic hypogonadotrophic hypogonadismZP1 zona pellucida glycoprotein 1 Dysfunctional zona pellucida formation 41 By location edit Hypothalamic pituitary factors edit Hypothalamic dysfunction HyperprolactinemiaOvarian factors edit Chemotherapy as detailed previously with certain agents have a high risk of toxicity on the ovaries Many genetic defects as also detailed previously also disturb ovarian function Polycystic ovary syndrome also see infertility in polycystic ovary syndrome 2 of these 3 criteria 1 Anovulation oligoovulation 2 Hyperandrogenism 3 PCO Ultrasound Must be excluded o Congenital Suprarrenal hyperplasia o Androgen producer tumors o Hyperprolactinemia Some of PCOS s consequeces are Insulin Resistance in 80 of PCOS women Higher incidence of spontaneus miscarriage Higher risk of developing diabetes mellitus type 2 Anovulation Female infertility caused by anovulation is called anovulatory infertility as opposed to ovulatory infertility in which ovulation is present 42 Diminished ovarian reserve also see Poor Ovarian Reserve Ultrasound antral follicle count AFC gt 6AF Hormones FSH E2 AMH Premature menopause Menopause Luteal dysfunction 43 Gonadal dysgenesis Turner syndrome Tubal ectopic peritoneal factors edit Further information Tubal factor infertility Endometriosis also see endometriosis and infertility Pelvic adhesions Pelvic inflammatory disease PID usually due to chlamydia 44 Tubal dysfunction Previous ectopic pregnancy A randomized study in 2013 came to the result that the rates of intrauterine pregnancy two years after treatment of ectopic pregnancy are approximately 64 with radical surgery 67 with medication and 70 with conservative surgery 45 In comparison the cumulative pregnancy rate of women under 40 years of age in the general population over two years is over 90 46 Hydrosalpinx is the most frequent This happens when there is a presence of fluid on the tubes We have some ways to test it Hysterosalphingography in which we can see both the uterus Hystero and the tubes Hysterosonosalphingography in which we see only the uterus This tests are used to check if the tubes are permeable or if there is any obstacle in the path to the uterus We have to introduce a liquid contrast via vagina and we check its path via x ray If the tube is blocked the contrast liquid will be stopped in the tubes but if it s not blocked it will end in the abdominal cavity The flow of this contrast needs peristaltic movements This blockage can be produced by sexually transmitted infections previous surgery peritonitis or endometriosis Permeability Hysterosalpingography HSG Ultrasoud Hysterosonosalpingography HSSG Chlamydia serology Laparoscopy methylene blue Tubal examination endoscopy laparoscopy faloscopy fertiloscopy Uterine factors edit Uterine malformations 47 Uterine fibroids Asherman s syndrome 48 Implantation failure without any known primary cause It results in negative pregnancy test despite having performed e g embryo transfer MyomasPreviously a bicornuate uterus was thought to be associated with infertility 49 but recent studies have not confirmed such an association 50 Cervical factors edit Cervical stenosis 51 Antisperm antibodies 24 Non receptive cervical mucus 52 Vaginal factors edit Vaginismus Vaginal obstructionInterrupted meiosis edit Meiosis a special type of cell division specific to germ cells produces egg cells in women During meiosis accurate segregation of chromosomes must occur during two rounds of division to create upon fertilisation a zygote with a proper diploid euploid set of chromosomes About half of all spontaneous abortions are aneuploid that is have an improper set of chromosomes 53 Human genetic variants that likely cause dysregulation of critical meiotic processes have been identified in 14 female infertility associated genes 53 A major cause of female infertility is premature ovarian insufficiency 54 This insufficiency is a heterogeneous disease that affects about 1 of women who are under the age of 40 54 Some instances of female infertility are caused by DNA repair dysregulation during meiosis 54 Diagnosis editMain article Fertility testing Diagnosis of infertility begins with a medical history and physical exam The healthcare provider may order tests including the following Lab tests Hormone testing to measure levels of female hormones at certain times during a menstrual cycle Day 2 or 3 measure of FSH and estrogen to assess ovarian reserve Measurements of thyroid function 55 a thyroid stimulating hormone TSH level of between 1 and 2 is considered optimal for conception Measurement of progesterone in the second half of the cycle to help confirm ovulation Anti Mullerian hormone to estimate ovarian reserve 56 Examination and imaging An endometrial biopsy to verify ovulation and inspect the lining of the uterus Laparoscopy which allows the provider to inspect the pelvic organs Fertiloscopy a relatively new surgical technique used for early diagnosis and immediate treatment Pap smear to check for signs of infection Pelvic exam to look for abnormalities or infection A postcoital test which is done soon after intercourse to check for problems with sperm surviving in cervical mucous not commonly used now because of test unreliability Hysterosalpingography or sonosalpingography to check for tube patency Sonohysterography to check for uterine abnormalities There are genetic testing techniques under development to detect any mutation in genes associated with female infertility 37 Initial diagnosis and treatment of infertility is usually made by obstetrician gynecologists or women s health nurse practitioners If initial treatments are unsuccessful referral is usually made to physicians who are fellowship trained as reproductive endocrinologists Reproductive endocrinologists are usually obstetrician gynecologists with advanced training in reproductive endocrinology and infertility in North America These physicians treat reproductive disorders affecting not only women but also men children and teens Usually reproductive endocrinology amp infertility medical practices do not see women for general maternity care The practice is primarily focused on helping their women to conceive and to correct any issues related to recurring pregnancy loss Definition edit There is no unanimous definition of female infertility because the definition depends on social and physical characteristics which may vary by culture and situation NICE guidelines state 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 46 It is recommended that a consultation with a fertility specialist should be made earlier if the woman is aged 36 years or over or there is a known clinical cause of infertility or a history of predisposing factors for infertility 46 According to the World Health Organization WHO infertility can be described as the inability to become pregnant maintain a pregnancy or carry a pregnancy to live birth 57 A clinical definition of infertility by the WHO and ICMART 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 58 Infertility can further be broken down into primary and secondary infertility Primary infertility refers to the inability to give birth either because of not being able to become pregnant or carry a child to live birth which may include miscarriage or a stillborn child 59 60 Secondary infertility refers to the inability to conceive or give birth when there was a previous pregnancy or live birth 60 59 Prevention editAcquired female infertility may be prevented through identified interventions Maintaining a healthy lifestyle Excessive exercise consumption of caffeine and alcohol and smoking have all been associated with decreased fertility Eating a well balanced nutritious diet with plenty of fresh fruits and vegetables and maintaining a normal weight on the other hand have been associated with better fertility prospects Treating or preventing existing diseases Identifying and controlling chronic diseases such as diabetes and hypothyroidism increases fertility prospects Lifelong practice of safer sex reduces the likelihood that sexually transmitted infections will impair fertility obtaining prompt treatment for sexually transmitted infections reduces the likelihood that such infections will do significant damage Regular physical examinations including pap smears help detect early signs of infections or abnormalities Not delaying parenthood Fertility does not ultimately cease before menopause but it starts declining after age 27 and drops at a somewhat greater rate after age 35 61 Women whose biological mothers had unusual or abnormal issues related to conceiving may be at particular risk for some conditions such as premature menopause that can be mitigated by not delaying parenthood Egg freezing A woman can freeze her eggs preserve her fertility By using egg freezing while in the peak reproductive years a woman s oocytes are cryogenically frozen and ready for her use later in life reducing her chances of female infertility Treatment editThere is no method to reverse advanced maternal age but there are assisted reproductive technologies for many causes of infertility in pre menopausal women including Ovulation induction for anovulation In vitro fertilization in for example tubal abnormalitiesEpidemiology editFemale infertility varies widely by geographic location around the world In 2010 there was an estimated 48 5 million infertile couples worldwide and from 1990 to 2010 there was little change in levels of infertility in most of the world 2 In 2010 the countries with the lowest rates of female infertility included the South American countries of Peru Ecuador and Bolivia as well as in Poland Kenya and Republic of Korea 2 The highest rate regions included Eastern Europe North Africa the Middle East Oceania and Sub Saharan Africa 2 The prevalence of primary infertility has increased since 1990 but secondary infertility has decreased overall Rates decreased although not prevalence of female infertility in high income Central Eastern Europe and Central Asia regions 2 Female infertility is prevalent across the globe Africa edit Sub Saharan Africa has had decreasing levels of primary infertility from 1990 to 2010 Within the Sub Saharan region rates were lowest in Kenya Zimbabwe and Rwanda while the highest rates were in Guinea Mozambique Angola Gabon and Cameroon along with Northern Africa near the Middle East 2 According to a 2004 DHS report rates in Africa were highest in Middle and Sub Saharan Africa with East Africa s rates close behind 60 Asia edit In Asia the highest rates of combined secondary and primary infertility was in the South Central region and then in the Southeast region with the lowest rates in the Western areas 60 Latin America and Caribbean edit The prevalence of female infertility in the Latin America Caribbean region is typically lower than the global prevalence However the greatest rates occurred in Jamaica Suriname Haiti and Trinidad and Tobago Central and Western Latin America has some of the lowest rates of prevalence 2 The highest regions in Latin America and the Caribbean was in the Caribbean Islands and in less developed countries 60 Society and culture editSocial stigma edit Main article Infertility and childlessness stigmas Social stigma due to infertility is seen in many cultures throughout the world in varying forms Often when women cannot conceive the blame is put on them even when approximately 50 of infertility issues come from the man 62 In addition many societies only tend to value a woman if she is able to produce at least one child and a marriage can be considered a failure when the couple cannot conceive 62 The act of conceiving a child can be linked to the couple s consummation of marriage and reflect their social role in society 63 This is seen in the African infertility belt where infertility is prevalent in Africa which includes countries spanning from Tanzania in the east to Gabon in the west 62 In this region infertility is highly stigmatized and can be considered a failure of the couple to their societies 62 64 This is demonstrated in Uganda and Nigeria where there is a great pressure put on childbearing and its social implications 63 This is also seen in some Muslim societies including Egypt 65 and Pakistan 66 In the United States and all over the world infertility and women s infertility at large is an invisible yet debilitating disease that is stigmatized and looked down upon But in recent years many have begun to sue organizations for infertility insurance coverage as the Americans with Disabilities Act ADA has recognized infertility as a disability This however adds another stigmatization to women suffering from infertility as the word disability has a negative connotation in various world societies 77 Wealth is sometimes measured by the number of children a woman has as well as inheritance of property 63 66 Children can influence financial security in many ways In Nigeria and Cameroon land claims are decided by the number of children Also in some Sub Saharan countries women may be denied inheritance if she did not bear any children 66 In some African and Asian countries a husband can deprive his infertile wife of food shelter and other basic necessities like clothing 66 In Cameroon a woman may lose access to land from her husband and left on her own in old age 63 In many cases a woman who cannot bear children is excluded from social and cultural events including traditional ceremonies This stigmatization is seen in Mozambique and Nigeria where infertile women have been treated as outcasts to society 63 This is a humiliating practice which devalues infertile women in society 67 68 In the Makua tradition pregnancy and birth are considered major life events for a woman with the ceremonies of nthaa ra and ntha ara no mwana which can only be attended by women who have been pregnant and have had a baby 67 The effect of infertility can lead to social shaming from internal and social norms surrounding pregnancy which affects women around the world 68 When pregnancy is considered such an important event in life and considered a socially unacceptable condition it can lead to a search for treatment in the form of traditional healers and expensive Western treatments 65 69 The limited access to treatment in many areas can lead to extreme and sometimes illegal acts in order to produce a child 63 65 Marital role edit Men in some countries may find another wife when their first cannot produce a child hoping that by sleeping with more women he will be able to produce his own child 63 65 66 This can be prevalent in some societies including Cameroon 63 66 Nigeria 63 Mozambique 67 Egypt 65 Botswana 70 and Bangladesh 66 among many more where polygamy is more common and more socially acceptable In couples that are unsuccessful in conceiving divorce rates are roughly 3 5 times higher than those of couples who are fertile This was based on those with female infertility 78 In some cultures including Botswana 70 and Nigeria 63 women can select a woman with whom she allows her husband to sleep with in hopes of conceiving a child 63 Women who are desperate for children may compromise with her husband to select a woman and accept duties of taking care of the children to feel accepted and useful in society 70 Women may also sleep with other men in hopes of becoming pregnant 67 This can be done for many reasons including advice from a traditional healer or finding if another man was more compatible In many cases the husband was not aware of the extra sexual relations and would not be informed if a woman became pregnant by another man 67 This is not as culturally acceptable however and can contribute to the gendered suffering of women who have fewer options to become pregnant on their own as opposed to men 65 Men and women can also turn to divorce in attempt to find a new partner with whom to bear a child Infertility in many cultures is a reason for divorce and a way for a man or woman to increase his her chances of producing an heir 63 65 67 70 When a woman is divorced she can lose her security that often comes with land wealth and a family 70 This can ruin marriages and can lead to distrust in the marriage The increase of sexual partners can potentially result with the spread of disease including HIV AIDS and can actually contribute to future generations of infertility 70 Domestic abuse edit The emotional strain and stress that comes with infertility in the household can lead to the mistreatment and domestic abuse of a woman The devaluation of a wife due to her inability to conceive can lead to domestic abuse and emotional trauma such as victim blaming Women are sometimes or often blamed as the cause of a couples infertility which can lead to emotional abuse anxiety and shame 63 In addition blame for not being able to conceive is often put on the female even if it is the man who is infertile 62 Women who are not able to conceive can be starved beaten and may be neglected financially by her husband as if she had no child bearing use to him 66 The physical abuse related to infertility may result from this and the emotional stress that comes with it In some countries the emotional and physical abuses that come with infertility can potentially lead to assault murder and suicide 71 Mental and psychological impact edit Many infertile women tend to cope with immense stress and social stigma behind their condition which can lead to considerable mental distress 72 The long term stress involved in attempting to conceive a child and the social pressures behind giving birth can lead to emotional distress that may manifest as mental disease 73 Women with infertility might deal with psychological stressors such as denial anger grief guilt and depression 74 There can be considerable social shaming that can lead to intense feelings of sadness and frustration that potentially contribute to depression and suicide 70 The implications behind infertility bear huge consequences for the mental health of an infertile woman because of the social pressures and personal grief behind being unable to bear children The range of psychological issues pertaining to infertility in women is vast and can include inferiority complex stress with interpersonal relationships and possibly major depression and or anxiety With the impacts of infertility on social life cultural significance and psychological factors infertility has been classified as one of the greatest stressors of life 76 Emotional impact of infertility treatment edit Many women have reported finding treatment for infertility stressful and a cause of relationship difficulties with their partners The fear of failure was the most important barrier to treatment Females in studied cases typically experience more adverse effects of infertility and treatments than to males The psychological support is fundamental to limit the possibility to drop out from infertility treatment and reduce the distress level which is strongly associated with lower pregnancy rates In addition some medications in particular clomifene citrate used in the treatment have several side effects which may be an important risk factor for the development of depression 75 See also editAdvanced maternal age Fertility Infertility Male infertility OncofertilityReferences edit te Velde E R 2002 The variability of female reproductive ageing Human Reproduction Update 8 2 141 154 doi 10 1093 humupd 8 2 141 ISSN 1355 4786 PMID 12099629 a b c d e f g h Mascarenhas M N Flaxman S R Boerma T Vanderpoel S Stevens G A 2012 National Regional and Global Trends in Infertility Prevalence Since 1990 A Systematic Analysis of 277 Health Surveys PLOS Med 9 12 e1001356 doi 10 1371 journal pmed 1001356 PMC 3525527 PMID 23271957 http www fertilityfaq org pdf magazine1 v4 pdf permanent dead link Anderson SE Dallal GE Must A April 2003 Relative weight and race influence average age at menarche results from two nationally representative surveys of US girls studied 25 years apart Pediatrics 111 4 Pt 1 844 50 doi 10 1542 peds 111 4 844 PMID 12671122 Al Sahab B Ardern CI Hamadeh MJ Tamim H 2010 Age at menarche in Canada results from the National Longitudinal Survey of Children amp Youth BMC Public Health 10 736 doi 10 1186 1471 2458 10 736 PMC 3001737 PMID 21110899 Archived copy PDF Archived from the original PDF on 2018 10 09 Retrieved 2012 02 11 a href Template Cite web html title Template Cite web cite web a CS1 maint archived copy as title link Apter D February 1980 Serum steroids and pituitary hormones in female puberty a partly longitudinal study Clinical Endocrinology 12 2 107 20 doi 10 1111 j 1365 2265 1980 tb02125 x PMID 6249519 S2CID 19913395 Morabia A Costanza MC December 1998 International variability in ages at menarche first livebirth and menopause World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives American Journal of Epidemiology 148 12 1195 205 doi 10 1093 oxfordjournals aje a009609 PMID 9867266 Forster P Hohoff C Dunkelmann B Schurenkamp M Pfeiffer H Neuhuber F Brinkmann B 2015 Elevated germline mutation rate in teenage fathers Proc Biol Sci 282 20142898 1 Dechanet C Anahory T Mathieu Daude JC Quantin X Reyftmann L Hamamah S Hedon B Dechaud H 2011 Effects of cigarette smoking on reproduction Hum Reprod Update 17 1 76 95 doi 10 1093 humupd dmq033 PMID 20685716 a b c d e FERTILITY FACT gt Female Risks Archived September 22 2007 at the Wayback Machine By the American Society for Reproductive Medicine ASRM Retrieved on Jan 4 2009 a b Regulated fertility services a commissioning aid June 2009 Archived 2011 01 03 at the Wayback Machine from the Department of Health UK Practice Committee of American Society for Reproductive Medicine 2008 Smoking and Infertility Fertil Steril 90 5 Suppl S254 9 doi 10 1016 j fertnstert 2008 08 035 PMID 19007641 Nelson LR Bulun SE September 2001 Estrogen production and action J Am Acad Dermatol 45 3 Suppl S116 24 doi 10 1067 mjd 2001 117432 PMID 11511861 Sloboda D M Hickey M Hart R 2010 Reproduction in females the role of the early life environment Human Reproduction Update 17 2 210 227 doi 10 1093 humupd dmq048 PMID 20961922 Freizinger M Franko DL Dacey M Okun B Domar AD November 2008 The prevalence of eating disorders in infertile women Fertil Steril 93 1 72 8 doi 10 1016 j fertnstert 2008 09 055 PMID 19006795 Koning AM Kuchenbecker WK Groen H et al 2010 Economic consequences of overweight and obesity in infertility a framework for evaluating the costs and outcomes of fertility care Hum Reprod Update 16 3 246 54 doi 10 1093 humupd dmp053 PMID 20056674 How Cancer Treatments Can Affect Fertility in Women a b c Brydoy M Fossa SD Dahl O Bjoro T 2007 Gonadal dysfunction and fertility problems in cancer survivors Acta Oncol 46 4 480 9 doi 10 1080 02841860601166958 PMID 17497315 S2CID 20672988 a b Morgan S Anderson R A Gourley C Wallace W H Spears N 2012 How do chemotherapeutic agents damage the ovary Human Reproduction Update 18 5 525 35 doi 10 1093 humupd dms022 hdl 1842 9543 PMID 22647504 a b Rosendahl M Andersen C La Cour Freiesleben N Juul A Lossl K Andersen A 2010 Dynamics and mechanisms of chemotherapy induced ovarian follicular depletion in women of fertile age Fertility and Sterility 94 1 156 166 doi 10 1016 j fertnstert 2009 02 043 PMID 19342041 Gurgan T Salman C Demirol A October 2008 Pregnancy and assisted reproduction techniques in men and women after cancer treatment Placenta 29 Suppl B 152 9 doi 10 1016 j placenta 2008 07 007 PMID 18790328 a b 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 ISSN 1699 7980 PMID 23428233 a b Rao Kamini 2013 09 30 Principles amp Practice of Assisted Reproductive Technology 3 Vols JP Medical Ltd ISBN 9789350907368 a b Ten Broek R P G Kok Krant N Bakkum E A Bleichrodt R P Van Goor H 2012 Different surgical techniques to reduce post operative adhesion formation A systematic review and meta analysis Human Reproduction Update 19 1 12 25 doi 10 1093 humupd dms032 PMID 22899657 a b Codner E Merino P M Tena Sempere M 2012 Female reproduction and type 1 diabetes From mechanisms to clinical findings Human Reproduction Update 18 5 568 585 doi 10 1093 humupd dms024 PMID 22709979 Tersigni C Castellani R de Waure C Fattorossi A De Spirito M Gasbarrini A Scambia G Di Simone N 2014 Celiac disease and reproductive disorders meta analysis of epidemiologic associations and potential pathogenic mechanisms Hum Reprod Update Meta Analysis Review 20 4 582 93 doi 10 1093 humupd dmu007 hdl 10807 56796 PMID 24619876 Lasa JS Zubiaurre I Soifer LO 2014 Risk of infertility in patients with celiac disease a meta analysis of observational studies Arq Gastroenterol Meta Analysis Review 51 2 144 50 doi 10 1590 S0004 28032014000200014 PMID 25003268 Middeldorp S 2007 Pregnancy failure and heritable thrombophilia Semin Hematol 44 2 93 7 doi 10 1053 j seminhematol 2007 01 005 PMID 17433901 Qublan HS Eid SS Ababneh HA et al 2006 Acquired and inherited thrombophilia implication in recurrent IVF and embryo transfer failure Hum Reprod 21 10 2694 8 CiteSeerX 10 1 1 544 3649 doi 10 1093 humrep del203 PMID 16835215 Karasu T Marczylo T H MacCarrone M Konje J C 2011 The role of sex steroid hormones cytokines and the endocannabinoid system in female fertility Human Reproduction Update 17 3 347 361 doi 10 1093 humupd dmq058 PMID 21227997 Tichelli Andre Rovo Alicia 2013 Fertility Issues Following Hematopoietic Stem Cell Transplantation Expert Rev Hematol 6 4 375 388 doi 10 1586 17474086 2013 816507 PMID 23991924 S2CID 25139582 In turn citing Wallace WH Thomson AB Saran F Kelsey TW 2005 Predicting age of ovarian failure after radiation to a field that includes the ovaries Int J Radiat Oncol Biol Phys 62 3 738 744 doi 10 1016 j ijrobp 2004 11 038 PMID 15936554 Tichelli Andre Rovo Alicia 2013 Fertility Issues Following Hematopoietic Stem Cell Transplantation Expert Rev Hematol 6 4 375 388 doi 10 1586 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