Female infertility: Difference between revisions

Female infertility
Female infertility
	Cumulative percentage and average age for women reaching subfertility, sterility, irregular menstruation and menopause
Specialty	Gynecology

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Revision as of 15:20, 19 June 2024

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.

Cause

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

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

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's 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

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

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

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

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

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

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

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

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

Hypothalamic-pituitary factors

Ovarian factors

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/oligovulation 2) Hyperandrogenism 3) PCO Ultrasound •Must be excluded: o Congenital Suprarenal hyperplasia o Androgen producer tumors o Hyperprolactinemia Some of PCOS's consequences are:

•Insulin Resistance in 80% of PCOS women.

•Higher incidence of spontaneous 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) >6AF - Hormones: FSH, E2, AMH

Premature menopause
Menopause
Luteal dysfunction^[43]
Gonadal dysgenesis (Turner syndrome)

Tubal (ectopic)/peritoneal factors

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, that we see only the uterus. This test is 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

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.
Myomas

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

Cervical factors

Vaginal factors

Vaginismus
Vaginal obstruction

Interrupted meiosis

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

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-Müllerian 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 & 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

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

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

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:

Ovulation induction for anovulation
In vitro fertilization in for example tubal abnormalities

Epidemiology

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

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

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

Latin America and Caribbean

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 were in the Caribbean Islands and in less developed countries.^[60]

Society and culture

Social stigma

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

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

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

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

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 do 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]

References

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^ "Archived copy" (PDF). Archived from the original (PDF) on 2018-10-09. Retrieved 2012-02-11.{{cite web}}: 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, Schürenkamp 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 > 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 Brydøy M, Fosså SD, Dahl O, Bjøro 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.; Løssl, 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 & 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.
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^ Tichelli André; Rovó 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.
^
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^ Tan Y, Bennett MJ (2007). "Urinary catheter stent placement for treatment of cervical stenosis". The Australian & New Zealand Journal of Obstetrics & Gynaecology. 47 (5): 406–9. doi:10.1111/j.1479-828X.2007.00766.x. PMID 17877600. S2CID 22467867.
^ Farhi J, Valentine A, Bahadur G, Shenfield F, Steele SJ, Jacobs HS (1995). "In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests". Hum. Reprod. 10 (1): 85–90. doi:10.1093/humrep/10.1.85. PMID 7745077.
^ ^a ^b Biswas, Leelabati; Tyc, Katarzyna; El Yakoubi, Warif; Morgan, Katie; Xing, Jinchuan; Schindler, Karen (2021). "Meiosis interrupted: The genetics of female infertility via meiotic failure". Reproduction. 161 (2): R13–R35. doi:10.1530/REP-20-0422. PMC 7855740. PMID 33170803.
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Sternke, Elizabeth A.; Abrahamson, Kathleen (2015-03-01). "Perceptions of Women with Infertility on Stigma and Disability". Sexuality and Disability. 33 (1): 3–17. doi:10.1007/s11195-014-9348-6 ISSN 1573-6717

External links

[1] 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.

[Mascarenhas,_M.N._2012-2] ^ ^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.

[3] ttps://www.fertilityfaq.org/_pdf/magazine1_v4.pdf^{[permanent dead link]}

[4] 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.

[5] Al-Sahab B, Ardern CI, Hamadeh MJ, Tamim H (2010). "Age at menarche in Canada: results from the National Longitudinal Survey of Children & Youth". BMC Public Health. 10: 736. doi:10.1186/1471-2458-10-736. PMC 3001737. PMID 21110899.

[6] "Archived copy" (PDF). Archived from the original (PDF) on 2018-10-09. Retrieved 2012-02-11.{{cite web}}: CS1 maint: archived copy as title (link)

[Apter_D_1980_107–20-7] 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.

[8] 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.

[ForsterEtAl-9] Forster P, Hohoff C, Dunkelmann B, Schürenkamp M, Pfeiffer H, Neuhuber F, Brinkmann B. (2015) "Elevated germline mutation rate in teenage fathers". Proc Biol Sci 282:20142898 [1]

[10] 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.

[asrm-risks-11] FERTILITY FACT > Female Risks Archived September 22, 2007, at the Wayback Machine By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009

[dh2009-12] Regulated fertility services: a commissioning aid - June 2009 Archived 2011-01-03 at the Wayback Machine, from the Department of Health UK

[smoking_and_infertility-13] 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.

[14] 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.

[15] 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.

[16] 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.

[17] 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.

[18] How Cancer Treatments Can Affect Fertility in Women

[Brydoy-19] Brydøy M, Fosså SD, Dahl O, Bjøro T (2007). "Gonadal dysfunction and fertility problems in cancer survivors". Acta Oncol. 46 (4): 480–9. doi:10.1080/02841860601166958. PMID 17497315. S2CID 20672988.

[Morgan2012-20] 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.

[Rosendahl-21] Rosendahl, M.; Andersen, C.; La Cour Freiesleben, N.; Juul, A.; Løssl, 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.

[22] 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.

[:0-23] 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.

[:1-24] Rao, Kamini (2013-09-30). Principles & Practice of Assisted Reproductive Technology (3 Vols). JP Medical Ltd. ISBN 9789350907368.

[Broek2012-25] 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.

[Codner2012-26] 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.

[TersigniCastellani-27] 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.

[LasaZubiaurre-28] 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.

[pmid17433901-29] Middeldorp S (2007). "Pregnancy failure and heritable thrombophilia". Semin. Hematol. 44 (2): 93–7. doi:10.1053/j.seminhematol.2007.01.005. PMID 17433901.

[pmid16835215-30] 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.

[31] 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.

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@@ Line 23: / Line 23: @@
 | deaths =
 }}
-'''Female infertility''' refers to [[infertility]] in women. It affects an estimated 48 million women,<ref name="Mascarenhas, M.N. 2012" /> 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.<ref name="Mascarenhas, M.N. 2012">{{cite journal |author1=Mascarenhas M.N. |author2=Flaxman S.R. |author3=Boerma T. |author4=Vanderpoel S. |author5=Stevens G.A. | year = 2012 | title = National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys | journal = PLOS Med | volume = 9 | issue = 12| page = e1001356 | doi = 10.1371/journal.pmed.1001356 |pmid=23271957 |pmc=3525527 |doi-access=free }}</ref> 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''' refers to [[infertility]] in women. It affects an estimated 48 million women,<ref name="Mascarenhas, M.N. 2012" /> 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.<ref name="Mascarenhas, M.N. 2012">{{cite journal |author1=Mascarenhas M.N. |author2=Flaxman S.R. |author3=Boerma T. |author4=Vanderpoel S. |author5=Stevens G.A. | year = 2012 | title = National, Regional, and Global Trends in Infertility Prevalence Since 1990: A Systematic Analysis of 277 Health Surveys | journal = PLOS Med | volume = 9 | issue = 12| page = e1001356 | doi = 10.1371/journal.pmed.1001356 |pmid=23271957 |pmc=3525527 |doi-access=free }}</ref> 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.
 ==Cause==
@@ Line 37: / Line 37: @@
 ====Age====
 {{Main|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]],<ref>{{cite journal |vauthors=Anderson SE, Dallal GE, Must A |title=Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart |journal=Pediatrics |volume=111 |issue=4 Pt 1 |pages=844–50 |date=April 2003 |pmid=12671122 |doi=10.1542/peds.111.4.844}}</ref> 12.72 in [[Canada]],<ref>{{cite journal |pmid=21110899 | doi=10.1186/1471-2458-10-736 | volume=10 | title=Age at menarche in Canada: results from the National Longitudinal Survey of Children & Youth | pmc=3001737 | year=2010 |vauthors=Al-Sahab B, Ardern CI, Hamadeh MJ, Tamim H | journal=BMC Public Health | pages=736 | doi-access=free }}</ref> 12.9 in the [[UK]]<ref>{{Cite web |url=http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics%20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf |title=Archived copy |access-date=2012-02-11 |archive-date=2018-10-09 |archive-url=https://web.archive.org/web/20181009065351/http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics%20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf |url-status=dead }}</ref>), 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.<ref name="Apter D 1980 107–20">{{cite journal |author=Apter D |title=Serum steroids and pituitary hormones in female puberty: a partly longitudinal study |journal=Clinical Endocrinology |volume=12 |issue=2 |pages=107–20 |date=February 1980 |pmid=6249519 |doi=10.1111/j.1365-2265.1980.tb02125.x|s2cid=19913395 }}</ref>  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's 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.
+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]],<ref>{{cite journal |vauthors=Anderson SE, Dallal GE, Must A |title=Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart |journal=Pediatrics |volume=111 |issue=4 Pt 1 |pages=844–50 |date=April 2003 |pmid=12671122 |doi=10.1542/peds.111.4.844}}</ref> 12.72 in [[Canada]],<ref>{{cite journal |pmid=21110899 | doi=10.1186/1471-2458-10-736 | volume=10 | title=Age at menarche in Canada: results from the National Longitudinal Survey of Children & Youth | pmc=3001737 | year=2010 |vauthors=Al-Sahab B, Ardern CI, Hamadeh MJ, Tamim H | journal=BMC Public Health | pages=736 | doi-access=free }}</ref> 12.9 in the [[UK]]<ref>{{Cite web |url=http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics%20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf |title=Archived copy |access-date=2012-02-11 |archive-date=2018-10-09 |archive-url=https://web.archive.org/web/20181009065351/http://vstudentworld.yolasite.com/resources/final_yr/gynae_obs/Hamilton%20Fairley%20Obstetrics%20and%20Gynaecology%20Lecture%20Notes%202%20Ed.pdf |url-status=dead }}</ref>), 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.<ref name="Apter D 1980 107–20">{{cite journal |author=Apter D |title=Serum steroids and pituitary hormones in female puberty: a partly longitudinal study |journal=Clinical Endocrinology |volume=12 |issue=2 |pages=107–20 |date=February 1980 |pmid=6249519 |doi=10.1111/j.1365-2265.1980.tb02125.x|s2cid=19913395 }}</ref> 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's 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.<ref>{{Cite journal |vauthors=Morabia A, Costanza MC |date=December 1998 |title=International variability in ages at menarche, first livebirth, and menopause. World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives |journal=American Journal of Epidemiology |volume=148 |issue=12 |pages=1195–205 |doi=10.1093/oxfordjournals.aje.a009609 |pmid=9867266 |doi-access=free}}</ref> 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).<ref name="ForsterEtAl">Forster P, Hohoff C, Dunkelmann B, Schürenkamp M, Pfeiffer H, Neuhuber F, Brinkmann B. (2015) "Elevated germline mutation rate in teenage fathers". ''Proc Biol Sci'' 282:20142898 [http://rspb.royalsocietypublishing.org/content/282/1803/20142898.long]</ref>
@@ Line 43: / Line 43: @@
 ====Tobacco smoking====
 {{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.<ref>{{cite journal|vauthors=Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H | title = Effects of cigarette smoking on reproduction| journal = Hum. Reprod. Update| volume = 17| issue = 1| pages = 76–95| year = 2011| pmid = 20685716| doi = 10.1093/humupd/dmq033| doi-access = free}}</ref>  Some damage is irreversible, but stopping smoking can prevent further damage.<ref name=asrm-risks>[http://www.protectyourfertility.com/femalerisks.html FERTILITY FACT > Female Risks] {{webarchive |url=https://web.archive.org/web/20070922184324/http://www.protectyourfertility.com/femalerisks.html |date=September 22, 2007 }} By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009</ref> Smokers are 60% more likely to be infertile than non-smokers.<ref name=dh2009/> Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.<ref name=dh2009>[http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_101070 Regulated fertility services: a commissioning aid - June 2009] {{Webarchive|url=https://web.archive.org/web/20110103051232/http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_101070 |date=2011-01-03 }}, from the Department of Health UK</ref> Also, female smokers have an earlier onset of [[menopause]] by approximately 1–4 years.<ref name = "smoking and infertility">{{cite journal |author=Practice Committee of American Society for Reproductive Medicine |title=Smoking and Infertility |journal=Fertil Steril |volume=90 |issue=5 Suppl |pages=S254–9 |year=2008 |pmid=19007641 |doi=10.1016/j.fertnstert.2008.08.035|doi-access=free }}</ref>
+[[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.<ref>{{cite journal|vauthors=Dechanet C, Anahory T, Mathieu Daude JC, Quantin X, Reyftmann L, Hamamah S, Hedon B, Dechaud H | title = Effects of cigarette smoking on reproduction| journal = Hum. Reprod. Update| volume = 17| issue = 1| pages = 76–95| year = 2011| pmid = 20685716| doi = 10.1093/humupd/dmq033| doi-access = free}}</ref> Some damage is irreversible, but stopping smoking can prevent further damage.<ref name=asrm-risks>[http://www.protectyourfertility.com/femalerisks.html FERTILITY FACT > Female Risks] {{webarchive |url=https://web.archive.org/web/20070922184324/http://www.protectyourfertility.com/femalerisks.html |date=September 22, 2007 }} By the American Society for Reproductive Medicine (ASRM). Retrieved on Jan 4, 2009</ref> Smokers are 60% more likely to be infertile than non-smokers.<ref name=dh2009/> Smoking reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.<ref name=dh2009>[http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_101070 Regulated fertility services: a commissioning aid - June 2009] {{Webarchive|url=https://web.archive.org/web/20110103051232/http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_101070 |date=2011-01-03 }}, from the Department of Health UK</ref> Also, female smokers have an earlier onset of [[menopause]] by approximately 1–4 years.<ref name = "smoking and infertility">{{cite journal |author=Practice Committee of American Society for Reproductive Medicine |title=Smoking and Infertility |journal=Fertil Steril |volume=90 |issue=5 Suppl |pages=S254–9 |year=2008 |pmid=19007641 |doi=10.1016/j.fertnstert.2008.08.035|doi-access=free }}</ref>
 ====Sexually transmitted infections====
@@ Line 53: / Line 53: @@
 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.<ref>{{cite journal |vauthors=Freizinger M, Franko DL, Dacey M, Okun B, Domar AD |title=The prevalence of eating disorders in infertile women |journal=Fertil. Steril. |volume= 93|issue= 1|pages= 72–8|date=November 2008 |pmid=19006795 |doi=10.1016/j.fertnstert.2008.09.055 |doi-access=free }}</ref>
-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.<ref>{{cite journal  |vauthors=Koning AM, Kuchenbecker WK, Groen H, etal |title=Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care |journal=Hum. Reprod. Update |volume=16 |issue=3 |pages=246–54 |year=2010 |pmid=20056674 |doi=10.1093/humupd/dmp053 |doi-access=free }}</ref>
+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.<ref>{{cite journal |vauthors=Koning AM, Kuchenbecker WK, Groen H, et al. |title=Economic consequences of overweight and obesity in infertility: a framework for evaluating the costs and outcomes of fertility care |journal=Hum. Reprod. Update |volume=16 |issue=3 |pages=246–54 |year=2010 |pmid=20056674 |doi=10.1093/humupd/dmp053 |doi-access=free }}</ref>
 ====Radiation====
@@ Line 62: / Line 62: @@
 [[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.<ref name=Brydoy>{{cite journal |vauthors=Brydøy M, Fosså SD, Dahl O, Bjøro T |title=Gonadal dysfunction and fertility problems in cancer survivors |journal=Acta Oncol |volume=46 |issue=4 |pages=480–9 |year=2007 |pmid=17497315 |doi=10.1080/02841860601166958 |s2cid=20672988 }}</ref> Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.<ref name=Brydoy/> 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.<ref name=Brydoy/>
-Female infertility by chemotherapy appears to be secondary to [[premature ovarian failure]] by loss of [[primordial follicles]].<ref name=Morgan2012>{{Cite journal | last1 = Morgan | first1 = S. | last2 = Anderson | first2 = R. A. | last3 = Gourley | first3 = C. | last4 = Wallace | first4 = W. H. | last5 = Spears | first5 = N. | title = How do chemotherapeutic agents damage the ovary? | doi = 10.1093/humupd/dms022 | journal = Human Reproduction Update | volume = 18 | issue = 5 | pages = 525–35 | year = 2012 | pmid =  22647504| doi-access = free | hdl = 1842/9543 | hdl-access = free }}</ref> 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.<ref name=Morgan2012/> [[Antral follicle count]] decreases after three series of chemotherapy, whereas [[follicle stimulating hormone]] (FSH) reaches menopausal levels after four series.<ref name=Rosendahl/> Other hormonal changes in chemotherapy include decrease in [[inhibin B]] and [[anti-Müllerian hormone]] levels.<ref name=Rosendahl>{{Cite journal| last1 = Rosendahl | first1 = M.| last2 = Andersen | first2 = C.| last3 = La Cour Freiesleben | first3 = N.| last4 = Juul | first4 = A.| last5 = Løssl | first5 = K.| last6 = Andersen | first6 = A.| title = Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age| journal = Fertility and Sterility| volume = 94| issue = 1| pages = 156–166| year = 2010| pmid = 19342041| doi = 10.1016/j.fertnstert.2009.02.043| doi-access = free}}</ref>
+Female infertility by chemotherapy appears to be secondary to [[premature ovarian failure]] by loss of [[primordial follicles]].<ref name=Morgan2012>{{Cite journal | last1 = Morgan | first1 = S. | last2 = Anderson | first2 = R. A. | last3 = Gourley | first3 = C. | last4 = Wallace | first4 = W. H. | last5 = Spears | first5 = N. | title = How do chemotherapeutic agents damage the ovary? | doi = 10.1093/humupd/dms022 | journal = Human Reproduction Update | volume = 18 | issue = 5 | pages = 525–35 | year = 2012 | pmid = 22647504| doi-access = free | hdl = 1842/9543 | hdl-access = free }}</ref> 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.<ref name=Morgan2012/> [[Antral follicle count]] decreases after three series of chemotherapy, whereas [[follicle stimulating hormone]] (FSH) reaches menopausal levels after four series.<ref name=Rosendahl/> Other hormonal changes in chemotherapy include decrease in [[inhibin B]] and [[anti-Müllerian hormone]] levels.<ref name=Rosendahl>{{Cite journal| last1 = Rosendahl | first1 = M.| last2 = Andersen | first2 = C.| last3 = La Cour Freiesleben | first3 = N.| last4 = Juul | first4 = A.| last5 = Løssl | first5 = K.| last6 = Andersen | first6 = A.| title = Dynamics and mechanisms of chemotherapy-induced ovarian follicular depletion in women of fertile age| journal = Fertility and Sterility| volume = 94| issue = 1| pages = 156–166| year = 2010| pmid = 19342041| doi = 10.1016/j.fertnstert.2009.02.043| doi-access = free}}</ref>
 Women may choose between several methods of [[fertility preservation]] prior to chemotherapy, including [[cryopreservation]] of ovarian tissue, oocytes or embryos.<ref>{{cite journal |vauthors=Gurgan T, Salman C, Demirol A |title=Pregnancy and assisted reproduction techniques in men and women after cancer treatment |journal=Placenta |volume=29 |issue=Suppl B |pages=152–9 |date=October 2008 |pmid=18790328 |doi=10.1016/j.placenta.2008.07.007 }}</ref>
@@ Line 70: / Line 70: @@
 ====Other acquired factors====
-*[[Adhesion (medicine)|Adhesions]] secondary to [[surgery]] in the [[peritoneal cavity]] is the leading cause of acquired infertility.<ref name=Broek2012>{{Cite journal | last1 = Ten Broek | first1 = R. P. G. | last2 = Kok- Krant | first2 = N. | last3 = Bakkum | first3 = E. A. | last4 = Bleichrodt | first4 = R. P. | last5 = Van Goor | first5 = H. | title = Different surgical techniques to reduce post-operative adhesion formation: A systematic review and meta-analysis | doi = 10.1093/humupd/dms032 | journal = Human Reproduction Update | volume = 19 | issue = 1 | pages = 12–25 | year = 2012 | pmid =  22899657| doi-access = free }}</ref> 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.<ref name=Broek2012/>
+*[[Adhesion (medicine)|Adhesions]] secondary to [[surgery]] in the [[peritoneal cavity]] is the leading cause of acquired infertility.<ref name=Broek2012>{{Cite journal | last1 = Ten Broek | first1 = R. P. G. | last2 = Kok- Krant | first2 = N. | last3 = Bakkum | first3 = E. A. | last4 = Bleichrodt | first4 = R. P. | last5 = Van Goor | first5 = H. | title = Different surgical techniques to reduce post-operative adhesion formation: A systematic review and meta-analysis | doi = 10.1093/humupd/dms032 | journal = Human Reproduction Update | volume = 19 | issue = 1 | pages = 12–25 | year = 2012 | pmid = 22899657| doi-access = free }}</ref> 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.<ref name=Broek2012/>
-*[[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]].<ref name=Codner2012>{{Cite journal | last1 = Codner | first1 = E. | last2 = Merino | first2 = P. M. | last3 = Tena-Sempere | first3 = M. | doi = 10.1093/humupd/dms024 | title = Female reproduction and type 1 diabetes: From mechanisms to clinical findings | journal = Human Reproduction Update | volume = 18 | issue = 5 | pages = 568–585 | year = 2012 | pmid =  22709979| doi-access = free }}</ref> Animal models indicate that abnormalities on the molecular level caused by diabetes include defective [[leptin]], [[insulin]] and [[kisspeptin]] signalling.<ref name=Codner2012/>
+*[[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]].<ref name=Codner2012>{{Cite journal | last1 = Codner | first1 = E. | last2 = Merino | first2 = P. M. | last3 = Tena-Sempere | first3 = M. | doi = 10.1093/humupd/dms024 | title = Female reproduction and type 1 diabetes: From mechanisms to clinical findings | journal = Human Reproduction Update | volume = 18 | issue = 5 | pages = 568–585 | year = 2012 | pmid = 22709979| doi-access = free }}</ref> Animal models indicate that abnormalities on the molecular level caused by diabetes include defective [[leptin]], [[insulin]] and [[kisspeptin]] signalling.<ref name=Codner2012/>
-*[[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 [[abortion]]s, [[preterm birth|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.<ref name=TersigniCastellani>{{cite journal |vauthors=Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, Scambia G, Di Simone N |title= Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms |date= 2014 |journal= Hum. Reprod. Update |volume= 20 |issue= 4 |pages=582–93 |doi=10.1093/humupd/dmu007 |pmid= 24619876 | type= Meta-Analysis. Review|doi-access= free |hdl= 10807/56796 |hdl-access= free }}</ref><ref name=LasaZubiaurre>{{cite journal |last1= Lasa |first1= JS  |last2= Zubiaurre |first2= I |last3= Soifer |first3= LO |title= Risk of infertility in patients with celiac disease: a meta-analysis of observational studies |date= 2014 |journal= Arq Gastroenterol |volume= 51 |issue= 2 |pages=144–50 |doi=10.1590/S0004-28032014000200014 |pmid= 25003268 | type= Meta-Analysis. Review|doi-access= free }}</ref>
+*[[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 [[abortion]]s, [[preterm birth|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.<ref name=TersigniCastellani>{{cite journal |vauthors=Tersigni C, Castellani R, de Waure C, Fattorossi A, De Spirito M, Gasbarrini A, Scambia G, Di Simone N |title= Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms |date= 2014 |journal= Hum. Reprod. Update |volume= 20 |issue= 4 |pages=582–93 |doi=10.1093/humupd/dmu007 |pmid= 24619876 | type= Meta-Analysis. Review|doi-access= free |hdl= 10807/56796 |hdl-access= free }}</ref><ref name=LasaZubiaurre>{{cite journal |last1= Lasa |first1= JS |last2= Zubiaurre |first2= I |last3= Soifer |first3= LO |title= Risk of infertility in patients with celiac disease: a meta-analysis of observational studies |date= 2014 |journal= Arq Gastroenterol |volume= 51 |issue= 2 |pages=144–50 |doi=10.1590/S0004-28032014000200014 |pmid= 25003268 | type= Meta-Analysis. Review|doi-access= free }}</ref>
 *Significant [[liver]] or [[kidney]] disease
-*[[Thrombophilia]]<ref name="pmid17433901">{{cite journal |author=Middeldorp S |title=Pregnancy failure and heritable thrombophilia |journal=Semin. Hematol. |volume=44 |issue=2 |pages=93–7 |year=2007 |pmid=17433901 |doi=10.1053/j.seminhematol.2007.01.005}}</ref><ref name="pmid16835215">{{cite journal  |vauthors=Qublan HS, Eid SS, Ababneh HA, etal |title=Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure |journal=Hum. Reprod. |volume=21 |issue=10 |pages=2694–8 |year=2006 |pmid=16835215 |doi=10.1093/humrep/del203|citeseerx=10.1.1.544.3649 }}</ref>
+*[[Thrombophilia]]<ref name="pmid17433901">{{cite journal |author=Middeldorp S |title=Pregnancy failure and heritable thrombophilia |journal=Semin. Hematol. |volume=44 |issue=2 |pages=93–7 |year=2007 |pmid=17433901 |doi=10.1053/j.seminhematol.2007.01.005}}</ref><ref name="pmid16835215">{{cite journal |vauthors=Qublan HS, Eid SS, Ababneh HA, etal |title=Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure |journal=Hum. Reprod. |volume=21 |issue=10 |pages=2694–8 |year=2006 |pmid=16835215 |doi=10.1093/humrep/del203|citeseerx=10.1.1.544.3649 }}</ref>
-*[[Cannabis smoking]], such as of [[marijuana]] causes disturbances in the [[endocannabinoid system]], potentially causing infertility<ref>{{Cite journal | last1 = Karasu | first1 = T. | last2 = Marczylo | first2 = T. H. | last3 = MacCarrone | first3 = M. | last4 = Konje | first4 = J. C. | title = The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility | doi = 10.1093/humupd/dmq058 | journal = Human Reproduction Update | volume = 17 | issue = 3 | pages = 347–361 | year = 2011 | pmid =  21227997| doi-access = free }}</ref>
+*[[Cannabis smoking]], such as of [[marijuana]] causes disturbances in the [[endocannabinoid system]], potentially causing infertility<ref>{{Cite journal | last1 = Karasu | first1 = T. | last2 = Marczylo | first2 = T. H. | last3 = MacCarrone | first3 = M. | last4 = Konje | first4 = J. C. | title = The role of sex steroid hormones, cytokines and the endocannabinoid system in female fertility | doi = 10.1093/humupd/dmq058 | journal = Human Reproduction Update | volume = 17 | issue = 3 | pages = 347–361 | year = 2011 | pmid = 21227997| doi-access = free }}</ref>
 *Radiation, such as in [[radiation therapy]]. The radiation dose to the ovaries that generally causes permanent female infertility is 20.3 [[Gray (unit)|Gy]] at birth, 18.4 Gy at 10 years, 16.5 Gy at 20 years and 14.3 Gy at 30 years.<ref>{{cite journal |author1=Tichelli André |author2=Rovó Alicia | year = 2013 | title = Fertility Issues Following Hematopoietic Stem Cell Transplantation | url = http://www.medscape.com/viewarticle/810686_2?nlid=34365_904 | journal = Expert Rev Hematol | volume = 6 | issue = 4| pages = 375–388 | doi=10.1586/17474086.2013.816507 | pmid=23991924|s2cid=25139582 }}
-<br>In turn citing: {{cite journal |vauthors=Wallace WH, Thomson AB, Saran F, Kelsey TW | year = 2005 | title = Predicting age of ovarian failure after radiation to a field that includes the ovaries | journal = Int. J. Radiat. Oncol. Biol. Phys. | volume = 62 | issue = 3| pages = 738–744 | doi = 10.1016/j.ijrobp.2004.11.038 | pmid = 15936554 }}</ref> 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%.<ref>{{cite journal |author1=Tichelli André |author2=Rovó Alicia | year = 2013 | title = Fertility Issues Following Hematopoietic Stem Cell Transplantation | url = http://www.medscape.com/viewarticle/810686_2?nlid=34365_904 | journal = Expert Rev Hematol | volume = 6 | issue = 4| pages = 375–388 | doi=10.1586/17474086.2013.816507 | pmid=23991924|s2cid=25139582 }}</ref><ref><br>In turn citing: {{cite journal  |vauthors=Salooja N, Szydlo RM, Socie G, etal | year = 2001| title = Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey | journal = Lancet | volume = 358 | issue = 9278| pages = 271–276 | doi=10.1016/s0140-6736(01)05482-4 | pmid = 11498213| s2cid = 20198750}}</ref>
+<br>In turn citing: {{cite journal |vauthors=Wallace WH, Thomson AB, Saran F, Kelsey TW | year = 2005 | title = Predicting age of ovarian failure after radiation to a field that includes the ovaries | journal = Int. J. Radiat. Oncol. Biol. Phys. | volume = 62 | issue = 3| pages = 738–744 | doi = 10.1016/j.ijrobp.2004.11.038 | pmid = 15936554 }}</ref> 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%.<ref>{{cite journal |author1=Tichelli André |author2=Rovó Alicia | year = 2013 | title = Fertility Issues Following Hematopoietic Stem Cell Transplantation | url = http://www.medscape.com/viewarticle/810686_2?nlid=34365_904 | journal = Expert Rev Hematol | volume = 6 | issue = 4| pages = 375–388 | doi=10.1586/17474086.2013.816507 | pmid=23991924|s2cid=25139582 }}</ref><ref><br>In turn citing: {{cite journal |vauthors=Salooja N, Szydlo RM, Socie G, etal | year = 2001| title = Pregnancy outcomes after peripheral blood or bone marrow transplantation: a retrospective survey | journal = Lancet | volume = 358 | issue = 9278| pages = 271–276 | doi=10.1016/s0140-6736(01)05482-4 | pmid = 11498213| s2cid = 20198750}}</ref>
 ===Genetic factors===
@@ Line 107: / Line 107: @@
 | [[FGFR1]] || [[Fibroblast growth factor receptor 1]] || Kallmann syndrome (KAL2)
 |-
-| [[HFM1]] ||  || [[Primary ovarian failure]]<ref name="WangZhang2014">{{cite journal|last1=Wang|first1=Jian|last2=Zhang|first2=Wenxiang|last3=Jiang|first3=Hong|last4=Wu|first4=Bai-Lin|title=Mutations inHFM1in Recessive Primary Ovarian Insufficiency|journal=New England Journal of Medicine|volume=370|issue=10|year=2014|pages=972–974|issn=0028-4793|doi=10.1056/NEJMc1310150|pmid=24597873|doi-access=free}}</ref>
+| [[HFM1]] || || [[Primary ovarian failure]]<ref name="WangZhang2014">{{cite journal|last1=Wang|first1=Jian|last2=Zhang|first2=Wenxiang|last3=Jiang|first3=Hong|last4=Wu|first4=Bai-Lin|title=Mutations inHFM1in Recessive Primary Ovarian Insufficiency|journal=New England Journal of Medicine|volume=370|issue=10|year=2014|pages=972–974|issn=0028-4793|doi=10.1056/NEJMc1310150|pmid=24597873|doi-access=free}}</ref>
 |-
 | [[FSHR]] || [[FSH receptor]] || Hypergonadotrophic hypogonadism and ovarian hyperstimulation syndrome
@@ Line 169: / Line 169: @@
 * [[Polycystic ovary syndrome]] (also see [[infertility in polycystic ovary syndrome]])
 •2 of these 3 criteria:
-) Anovulation/oligoovulation
+) Anovulation/oligovulation
 ) Hyperandrogenism
 ) PCO Ultrasound
 •Must be excluded:
-o Congenital Suprarrenal hyperplasia
+o Congenital Suprarenal hyperplasia
 o Androgen producer tumors
 o Hyperprolactinemia
-Some of PCOS's consequeces are:
+Some of PCOS's consequences are:
  •Insulin Resistance in 80% of PCOS women.
-•Higher incidence of spontaneus miscarriage.
+•Higher incidence of spontaneous 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.<ref>{{cite journal |vauthors=Hull MG, Savage PE, Bromham DR |title=Anovulatory and ovulatory infertility: results with simplified management |journal=Br Med J (Clin Res Ed) |volume=284 |issue=6330 |pages=1681–5 |date=June 1982 |pmid=6805656 |pmc=1498620 |doi= 10.1136/bmj.284.6330.1681}}</ref>
@@ Line 196: / Line 196: @@
 *[[Pelvic inflammatory disease]] (PID, usually due to [[Chlamydia infection|chlamydia]])<ref name="pmid17160569">{{cite journal |vauthors=Guven MA, Dilek U, Pata O, Dilek S, Ciragil P |title=Prevalence of Chlamydia trochomatis, Ureaplasma urealyticum and Mycoplasma hominis infections in the unexplained infertile women |journal=Arch. Gynecol. Obstet. |volume=276 |issue=3 |pages=219–23 |year=2007 |pmid=17160569 |doi=10.1007/s00404-006-0279-z|s2cid=1153686 }}</ref>
 *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.<ref>{{Cite journal | last1 = Fernandez | first1 = H. | last2 = Capmas | first2 = P. | last3 = Lucot | first3 = J. P. | last4 = Resch | first4 = B. | last5 = Panel | first5 = P. | last6 = Bouyer | first6 = J. | doi = 10.1093/humrep/det037 | title = Fertility after ectopic pregnancy: The DEMETER randomized trial | journal = Human Reproduction | volume = 28 | issue = 5 | pages = 1247–1253 | year = 2013 | pmid =  23482340| doi-access = free }}</ref> In comparison, the cumulative pregnancy rate of women under 40 years of age in the general population over two years is over 90%.<ref name=nice2013 />
+*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.<ref>{{Cite journal | last1 = Fernandez | first1 = H. | last2 = Capmas | first2 = P. | last3 = Lucot | first3 = J. P. | last4 = Resch | first4 = B. | last5 = Panel | first5 = P. | last6 = Bouyer | first6 = J. | doi = 10.1093/humrep/det037 | title = Fertility after ectopic pregnancy: The DEMETER randomized trial | journal = Human Reproduction | volume = 28 | issue = 5 | pages = 1247–1253 | year = 2013 | pmid = 23482340| doi-access = free }}</ref> In comparison, the cumulative pregnancy rate of women under 40 years of age in the general population over two years is over 90%.<ref name=nice2013 />
-*[[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.
+*[[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''', that we see only the uterus. This test is 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)
@@ Line 225: / Line 225: @@
 ===Interrupted meiosis===
-[[Meiosis]], a special type of [[cell division]] specific to germ cells, produces egg cells in women.  During meiosis, accurate [[chromosome segregation|segregation of chromosomes]] must occur during two rounds of division to create, upon [[fertilisation]], a [[zygote]] with a proper [[ploidy|diploid]] (euploid) set of chromosomes. About half of all spontaneous abortions are [[aneuploidy|aneuploid]], that is, have an improper set of chromosomes.<ref name = Biswas2021>{{cite journal | doi=10.1530/REP-20-0422 | title=Meiosis interrupted: The genetics of female infertility via meiotic failure | year=2021 | last1=Biswas | first1=Leelabati | last2=Tyc | first2=Katarzyna | last3=El Yakoubi | first3=Warif | last4=Morgan | first4=Katie | last5=Xing | first5=Jinchuan | last6=Schindler | first6=Karen | journal=Reproduction | volume=161 | issue=2 | pages=R13–R35 | pmid=33170803 | pmc=7855740 }}</ref>  Human genetic variants that likely cause dysregulation of critical meiotic processes have been identified in 14 female infertility associated [[gene]]s.<ref name = Biswas2021/>
+[[Meiosis]], a special type of [[cell division]] specific to germ cells, produces egg cells in women. During meiosis, accurate [[chromosome segregation|segregation of chromosomes]] must occur during two rounds of division to create, upon [[fertilisation]], a [[zygote]] with a proper [[ploidy|diploid]] (euploid) set of chromosomes. About half of all spontaneous abortions are [[aneuploidy|aneuploid]], that is, have an improper set of chromosomes.<ref name = Biswas2021>{{cite journal | doi=10.1530/REP-20-0422 | title=Meiosis interrupted: The genetics of female infertility via meiotic failure | year=2021 | last1=Biswas | first1=Leelabati | last2=Tyc | first2=Katarzyna | last3=El Yakoubi | first3=Warif | last4=Morgan | first4=Katie | last5=Xing | first5=Jinchuan | last6=Schindler | first6=Karen | journal=Reproduction | volume=161 | issue=2 | pages=R13–R35 | pmid=33170803 | pmc=7855740 }}</ref> Human genetic variants that likely cause dysregulation of critical meiotic processes have been identified in 14 female infertility associated [[gene]]s.<ref name = Biswas2021/>
-A major cause of female infertility is [[Primary ovarian insufficiency|premature ovarian insufficiency]].<ref name = Veitia2020>{{cite journal | doi=10.1016/j.bj.2020.03.005 | title=Primary ovarian insufficiency, meiosis and DNA repair | year=2020 | last1=Veitia | first1=Reiner A. | journal=Biomedical Journal | volume=43 | issue=2 | pages=115–123 | pmid=32381463 | pmc=7283561 }}</ref>  This insufficiency is a heterogeneous disease that affects about 1% of women who are under the age of 40.<ref name = Veitia2020/>
+A major cause of female infertility is [[Primary ovarian insufficiency|premature ovarian insufficiency]].<ref name = Veitia2020>{{cite journal | doi=10.1016/j.bj.2020.03.005 | title=Primary ovarian insufficiency, meiosis and DNA repair | year=2020 | last1=Veitia | first1=Reiner A. | journal=Biomedical Journal | volume=43 | issue=2 | pages=115–123 | pmid=32381463 | pmc=7283561 }}</ref> This insufficiency is a heterogeneous disease that affects about 1% of women who are under the age of 40.<ref name = Veitia2020/>
 Some instances of female infertility are caused by [[DNA repair]] dysregulation during meiosis.<ref name = Veitia2020/>
@@ Line 252: / Line 252: @@
 There are [[genetic testing]] techniques under development to detect any mutation in genes associated with female infertility.<ref name=Evian2010/>
-Initial diagnosis and treatment of infertility is usually made by [[obstetrician/gynecologist]]s or [[women's health nurse practitioner]]s.  If initial treatments are unsuccessful, referral is usually made to physicians who are [[Fellowship (medicine)|fellowship]] trained as [[reproductive endocrinologist]]s.  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.
+Initial diagnosis and treatment of infertility is usually made by [[obstetrician/gynecologist]]s or [[women's health nurse practitioner]]s. If initial treatments are unsuccessful, referral is usually made to physicians who are [[Fellowship (medicine)|fellowship]] trained as [[reproductive endocrinologist]]s. 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===
-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."<ref name=nice2013>[http://guidance.nice.org.uk/CG156 Fertility: assessment and treatment for people with fertility problems]. [[NICE guidelines|NICE clinical guideline]] CG156 - Issued: February 2013</ref> 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.<ref name=nice2013/>  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.<ref name="WHO, 2013 ">World Health Organization 2013.  "Health Topics: Infertility".  Available http://www.who.int/topics/infertility/en/.  Retrieved November 5, 2013.</ref>
+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."<ref name=nice2013>[http://guidance.nice.org.uk/CG156 Fertility: assessment and treatment for people with fertility problems]. [[NICE guidelines|NICE clinical guideline]] CG156 - Issued: February 2013</ref> 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.<ref name=nice2013/> 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.<ref name="WHO, 2013 ">World Health Organization 2013. "Health Topics: Infertility". Available http://www.who.int/topics/infertility/en/. Retrieved November 5, 2013.</ref>
-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."<ref name=" Zegers-Hochschild">{{cite journal |author1=Zegers-Hochschild F. |author2=Adamson G.D. |author3=de Mouzon J. |author4=Ishihara O. |author5=Mansour R. |author6=Nygren K. |author7=Sullivan E. |author8=van der Poel S. | year = 2009 | title = The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2009 | journal = Human Reproduction | volume = 24 | issue = 11| pages = 2683–2687 | doi=10.1093/humrep/dep343|pmid=19801627 |doi-access=free }}</ref>  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.
+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."<ref name=" Zegers-Hochschild">{{cite journal |author1=Zegers-Hochschild F. |author2=Adamson G.D. |author3=de Mouzon J. |author4=Ishihara O. |author5=Mansour R. |author6=Nygren K. |author7=Sullivan E. |author8=van der Poel S. | year = 2009 | title = The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2009 | journal = Human Reproduction | volume = 24 | issue = 11| pages = 2683–2687 | doi=10.1093/humrep/dep343|pmid=19801627 |doi-access=free }}</ref> 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.
-<ref name="WHO terminology, 2013">World Health Organization 2013."Sexual and reproductive health: Infertility definitions and terminology".  Available [https://web.archive.org/web/20131023231051/http://www.who.int/reproductivehealth/topics/infertility/definitions/en/] . Retrieved November 5, 2013.</ref><ref name="Rutstein 2004">Rutstein, Shea O., and Iqbal H. Shah. "Infecundity, Infertility, and Childlessness in Developing Countries." DHS Comparative Reports No. 9 (2004): 1-57.</ref>  [[Secondary infertility]] refers to the inability to conceive or give birth when there was a previous pregnancy or live birth.<ref name="Rutstein 2004" /><ref name="WHO terminology, 2013" />
+<ref name="WHO terminology, 2013">World Health Organization 2013."Sexual and reproductive health: Infertility definitions and terminology". Available [https://web.archive.org/web/20131023231051/http://www.who.int/reproductivehealth/topics/infertility/definitions/en/]. Retrieved November 5, 2013.</ref><ref name="Rutstein 2004">Rutstein, Shea O., and Iqbal H. Shah. "Infecundity, Infertility, and Childlessness in Developing Countries." DHS Comparative Reports No. 9 (2004): 1-57.</ref> [[Secondary infertility]] refers to the inability to conceive or give birth when there was a previous pregnancy or live birth.<ref name="Rutstein 2004" /><ref name="WHO terminology, 2013" />
 ==Prevention==
 Acquired female infertility may be prevented through identified interventions:
-* ''Maintaining a healthy lifestyle.''  Excessive exercise, consumption of [[caffeine]] and [[alcohol (drug)|alcohol]], and [[smoking]] have all been  associated with decreased fertility.  Eating a well-balanced, nutritious diet, with plenty of fresh [[fruit]]s and [[vegetable]]s, and maintaining a normal weight, on the other hand, have been associated with better fertility prospects.
+* ''Maintaining a healthy lifestyle.'' Excessive exercise, consumption of [[caffeine]] and [[alcohol (drug)|alcohol]], and [[smoking]] have all been associated with decreased fertility. Eating a well-balanced, nutritious diet, with plenty of fresh [[fruit]]s and [[vegetable]]s, 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 infection]]s will impair fertility; obtaining prompt treatment for sexually transmitted infections reduces the likelihood that such infections will do significant damage.  Regular [[physical examination]]s (including pap smears) help detect early signs of infections or abnormalities.
+* ''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 infection]]s will impair fertility; obtaining prompt treatment for sexually transmitted infections reduces the likelihood that such infections will do significant damage. Regular [[physical examination]]s (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.<ref name="titleStudy speeds up biological clocks / Fertility rates dip after women hit 27">{{cite news |url=http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2002/04/30/MN182697.DTL |title=Study speeds up biological clocks / Fertility rates dip after women hit 27 |access-date=2007-11-21 |work=The San Francisco Chronicle | first=Carl T. | last=Hall |date=April 30, 2002}}</ref>  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.
+* ''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.<ref name="titleStudy speeds up biological clocks / Fertility rates dip after women hit 27">{{cite news |url=http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2002/04/30/MN182697.DTL |title=Study speeds up biological clocks / Fertility rates dip after women hit 27 |access-date=2007-11-21 |work=The San Francisco Chronicle | first=Carl T. | last=Hall |date=April 30, 2002}}</ref> 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.
 * ''[[oocyte cryopreservation|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.
@@ Line 274: / Line 274: @@
 ==Epidemiology==
-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.<ref name="Mascarenhas, M.N. 2012"/>
+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.<ref name="Mascarenhas, M.N. 2012"/>
-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.<ref name="Mascarenhas, M.N. 2012"/>  The highest rate regions included Eastern Europe, North Africa, the Middle East, Oceania, and Sub-Saharan Africa.<ref name="Mascarenhas, M.N. 2012"/>  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.<ref name="Mascarenhas, M.N. 2012"/> Female infertility is prevalent across the globe.
+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.<ref name="Mascarenhas, M.N. 2012"/> The highest rate regions included Eastern Europe, North Africa, the Middle East, Oceania, and Sub-Saharan Africa.<ref name="Mascarenhas, M.N. 2012"/> 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.<ref name="Mascarenhas, M.N. 2012"/> Female infertility is prevalent across the globe.
 ===Africa===
-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.<ref name="Mascarenhas, M.N. 2012"/>  According to a 2004 DHS report, rates in Africa were highest in Middle and Sub-Saharan Africa, with East Africa's rates close behind.<ref name="Rutstein 2004" />
+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.<ref name="Mascarenhas, M.N. 2012"/> According to a 2004 DHS report, rates in Africa were highest in Middle and Sub-Saharan Africa, with East Africa's rates close behind.<ref name="Rutstein 2004" />
 ===Asia===
-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.<ref name="Rutstein 2004" />
+In Asia, the highest rates of combined secondary and primary infertility were in the South Central region, and then in the Southeast region, with the lowest rates in the Western areas.<ref name="Rutstein 2004" />
 ===Latin America and Caribbean===
-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.<ref name="Mascarenhas, M.N. 2012"/>  The highest regions in Latin America and the Caribbean was in the Caribbean Islands and in less developed countries.<ref name="Rutstein 2004" />
+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.<ref name="Mascarenhas, M.N. 2012"/> The highest regions in Latin America and the Caribbean were in the Caribbean Islands and in less developed countries.<ref name="Rutstein 2004" />
 ==Society and culture==
@@ Line 293: / Line 293: @@
 ===Social stigma===
 {{main|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 .<ref name="WHO 2010">{{cite journal | author = WHO  | year = 2010 | title = Mother or nothing: the agony of infertility | journal = Bulletin of the World Health Organization | volume = 88 | issue = 12| pages = 881–882 | doi = 10.2471/BLT.10.011210 | pmid = 21124709 | pmc = 2995184}}</ref>
+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.<ref name="WHO 2010">{{cite journal | author = WHO | year = 2010 | title = Mother or nothing: the agony of infertility | journal = Bulletin of the World Health Organization | volume = 88 | issue = 12| pages = 881–882 | doi = 10.2471/BLT.10.011210 | pmid = 21124709 | pmc = 2995184}}</ref>
-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 [[Human fertilization|conceive]].<ref name="WHO 2010"/> The act of conceiving a child can be linked to the couple's consummation of marriage, and reflect their social role in society.<ref name="Araoye, M. O. 2003"/> 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.<ref name="WHO 2010"/>  In this region, infertility is highly stigmatized and can be considered a failure of the couple to their societies.<ref name="WHO 2010"/><ref name="Leke 1993 ">Robert J. Leke, Jemimah A. Oduma, Susana Bassol-Mayagoitia, Angela Maria Bacha, and Kenneth M. Grigor.  "Regional and Geographical Variations in Infertility: Effects of Environmental, Cultural, and Socioeconomic Factors" Environmental Health Perspectives Supplements (101) (Suppl. 2): 73-80 (1993).</ref>  This is demonstrated in [[Uganda]] and [[Nigeria]] where there is a great pressure put on [[childbearing]] and its social implications.<ref name="Araoye, M. O. 2003"/>  This is also seen in some Muslim societies including [[Egypt]]<ref name="Inhorn, M. C. 2003"/> and Pakistan.<ref name="Dyer, S. J. 2012"/> 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]
+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 [[Human fertilization|conceive]].<ref name="WHO 2010"/> The act of conceiving a child can be linked to the couple's consummation of marriage, and reflect their social role in society.<ref name="Araoye, M. O. 2003"/> 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.<ref name="WHO 2010"/> In this region, infertility is highly stigmatized and can be considered a failure of the couple to their societies.<ref name="WHO 2010"/><ref name="Leke 1993 ">Robert J. Leke, Jemimah A. Oduma, Susana Bassol-Mayagoitia, Angela Maria Bacha, and Kenneth M. Grigor. "Regional and Geographical Variations in Infertility: Effects of Environmental, Cultural, and Socioeconomic Factors" Environmental Health Perspectives Supplements (101) (Suppl. 2): 73-80 (1993).</ref> This is demonstrated in [[Uganda]] and [[Nigeria]] where there is a great pressure put on [[childbearing]] and its social implications.<ref name="Araoye, M. O. 2003"/> This is also seen in some Muslim societies including [[Egypt]]<ref name="Inhorn, M. C. 2003"/> and Pakistan.<ref name="Dyer, S. J. 2012"/> 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.<ref name="Araoye, M. O. 2003"/><ref name="Dyer, S. J. 2012">Dyer, S. J. (2012). "The economic impact of infertility on women in developing countries – a systematic review." FVV in ObGyn: 38-45.</ref>  Children can influence financial security in many ways.  In Nigeria and [[Cameroon]], [[land claim]]s 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 <ref name="Dyer, S. J. 2012"/>  In some African and Asian countries a husband can deprive his infertile wife of food, shelter and other basic necessities like clothing.<ref name="Dyer, S. J. 2012"/>  In Cameroon, a woman may lose access to land from her husband and left on her own in old age.<ref name="Araoye, M. O. 2003"/>
+Wealth is sometimes measured by the number of children a woman has, as well as inheritance of property.<ref name="Araoye, M. O. 2003"/><ref name="Dyer, S. J. 2012">Dyer, S. J. (2012). "The economic impact of infertility on women in developing countries – a systematic review." FVV in ObGyn: 38-45.</ref> Children can influence financial security in many ways. In Nigeria and [[Cameroon]], [[land claim]]s 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 <ref name="Dyer, S. J. 2012"/> In some African and Asian countries a husband can deprive his infertile wife of food, shelter and other basic necessities like clothing.<ref name="Dyer, S. J. 2012"/> In Cameroon, a woman may lose access to land from her husband and left on her own in old age.<ref name="Araoye, M. O. 2003"/>
-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.<ref name="Araoye, M. O. 2003"/> This is a humiliating practice which devalues infertile women in society.<ref name="Gerrits, T. 1997"/><ref name="Whiteford, L. M. 1995">Whiteford, L. M. (1995). "STIGMA: THE HIDDEN BURDEN OF INFERTILITY." Sot. Sci. Med. (40;1): 27-36.</ref> In the [[Makua people|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.<ref name="Gerrits, T. 1997"/>
+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.<ref name="Araoye, M. O. 2003"/> This is a humiliating practice which devalues infertile women in society.<ref name="Gerrits, T. 1997"/><ref name="Whiteford, L. M. 1995">Whiteford, L. M. (1995). "STIGMA: THE HIDDEN BURDEN OF INFERTILITY." Sot. Sci. Med. (40;1): 27-36.</ref> In the [[Makua people|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.<ref name="Gerrits, T. 1997"/>
 The effect of infertility can lead to social shaming from internal and [[social norms]] surrounding pregnancy, which affects women around the world.<ref name="Whiteford, L. M. 1995"/> 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.<ref name="Inhorn, M. C. 2003"/><ref>{{cite book |last1=Singh |first1=Holly Donahue |title=Infertility in a Crowded Country: Hiding Reproduction in India |date=2022 |publisher=Indiana University Press |location=Bloomington (IN) |isbn=9780253063878}}</ref> The limited access to treatment in many areas can lead to extreme and sometimes illegal acts in order to produce a child.<ref name="Araoye, M. O. 2003"/><ref name="Inhorn, M. C. 2003"/>
@@ Line 304: / Line 304: @@
 ===Marital role===
-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.<ref name="Araoye, M. O. 2003">Araoye, M. O. (2003). "Epidemiology of infertility: social problems of the infertile couples." West African journal of medicine (22;2): 190-196.</ref><ref name="Inhorn, M. C. 2003">Inhorn, M. C. (2003). "Global infertility and the globalization of new reproductive technologies: illustrations from Egypt." Social Science & Medicine (56): 1837 - 1851.</ref><ref name="Dyer, S. J. 2012"/> This can be prevalent in some societies, including Cameroon,<ref name="Araoye, M. O. 2003"/><ref name="Dyer, S. J. 2012"/> Nigeria,<ref name="Araoye, M. O. 2003"/>  Mozambique,<ref name="Gerrits, T. 1997"/> Egypt,<ref name="Inhorn, M. C. 2003"/> Botswana,<ref name="Mogobe, D. K. 2005"/> and Bangladesh,<ref name="Dyer, S. J. 2012"/> 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]
+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.<ref name="Araoye, M. O. 2003">Araoye, M. O. (2003). "Epidemiology of infertility: social problems of the infertile couples." West African journal of medicine (22;2): 190-196.</ref><ref name="Inhorn, M. C. 2003">Inhorn, M. C. (2003). "Global infertility and the globalization of new reproductive technologies: illustrations from Egypt." Social Science & Medicine (56): 1837 - 1851.</ref><ref name="Dyer, S. J. 2012"/> This can be prevalent in some societies, including Cameroon,<ref name="Araoye, M. O. 2003"/><ref name="Dyer, S. J. 2012"/> Nigeria,<ref name="Araoye, M. O. 2003"/> Mozambique,<ref name="Gerrits, T. 1997"/> Egypt,<ref name="Inhorn, M. C. 2003"/> Botswana,<ref name="Mogobe, D. K. 2005"/> and Bangladesh,<ref name="Dyer, S. J. 2012"/> 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 <ref name="Mogobe, D. K. 2005"/> and Nigeria,<ref name="Araoye, M. O. 2003"/> women can select a woman with whom she allows her husband to sleep with in hopes of conceiving a child.<ref name="Araoye, M. O. 2003"/> 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.<ref name="Mogobe, D. K. 2005">Mogobe, D. K. (2005). "Denying and Preserving Self: Batswana Women's Experiences of Infertility." African Journal of Reproductive Health (9;2): 26-37.</ref>
-Women may also sleep with other men in hopes of becoming pregnant.<ref name="Gerrits, T. 1997">Gerrits, T. (1997). "Social and cultural aspects of infertility in Mozambique." Patient Education and Counseling (31): 39-48.</ref> 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.<ref name="Gerrits, T. 1997"/> 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.<ref name="Inhorn, M. C. 2003"/>
+Women may also sleep with other men in hopes of becoming pregnant.<ref name="Gerrits, T. 1997">Gerrits, T. (1997). "Social and cultural aspects of infertility in Mozambique." Patient Education and Counseling (31): 39-48.</ref> 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.<ref name="Gerrits, T. 1997"/> 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.<ref name="Inhorn, M. C. 2003"/>
-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.<ref name="Araoye, M. O. 2003"/><ref name="Inhorn, M. C. 2003"/><ref name="Gerrits, T. 1997"/><ref name="Mogobe, D. K. 2005"/> When a woman is divorced, she can lose her security that often comes with land, wealth, and a family.<ref name="Mogobe, D. K. 2005"/> 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.<ref name="Mogobe, D. K. 2005"/>
+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.<ref name="Araoye, M. O. 2003"/><ref name="Inhorn, M. C. 2003"/><ref name="Gerrits, T. 1997"/><ref name="Mogobe, D. K. 2005"/> When a woman is divorced, she can lose her security that often comes with land, wealth, and a family.<ref name="Mogobe, D. K. 2005"/> 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.<ref name="Mogobe, D. K. 2005"/>
 ===Domestic abuse===
 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.<ref name="Araoye, M. O. 2003"/>  In addition, blame for not being able to conceive is often put on the female, even if it is the man who is infertile.<ref name="WHO 2010"/> 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.<ref name="Dyer, S. J. 2012"/> 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]].<ref name="Omberlet, W. 2012">Omberlet, W. (2012). "Global access to infertility care in developing countries: a case of human rights, equity and social justice " FVV in ObGyn: 7-16.</ref>
+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.<ref name="Araoye, M. O. 2003"/> In addition, blame for not being able to conceive is often put on the female, even if it is the man who is infertile.<ref name="WHO 2010"/> 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.<ref name="Dyer, S. J. 2012"/> 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]].<ref name="Omberlet, W. 2012">Omberlet, W. (2012). "Global access to infertility care in developing countries: a case of human rights, equity and social justice " FVV in ObGyn: 7-16.</ref>
 ===Mental and psychological impact===

Classification	D ICD-10: N97.0 ICD-9-CM: 628 MeSH: D007247 DiseasesDB: 4786
External resources	MedlinePlus: 001191 eMedicine: med/3535 Patient UK: Female infertility

v t e Assisted reproductive technology
Infertility	Female Male LGBT Fertility clinic Fertility testing Fertility tourism Male infertility crisis
Fertility medication	Estrogen antagonists aromatase inhibitor clomifene FSH GnRH agonists Gonadotropins menotropins hCG
In vitro fertilisation (IVF) and expansions	Assisted zona hatching Autologous endometrial coculture Cytoplasmic transfer Embryo transfer Gestational carrier In vitro maturation Intracytoplasmic sperm injection Oocyte selection Ovarian hyperstimulation Partner-assisted reproduction Preimplantation genetic diagnosis Transvaginal ovum retrieval Zygote intrafallopian transfer
Other methods	Artificial insemination Ovulation induction Cryopreservation embryos oocyte ovarian tissue semen Gamete intrafallopian transfer Reproductive surgery Vasectomy reversal Selective reduction Sex selection Surrogacy
Donation	Donor registration Donor Sibling Registry Egg donation Embryo Sperm Semen collection Sperm bank Ova bank
Ethics	Accidental incest Fertility fraud Genetic diagnosis of intersex Religious response to ART Mitochondrial donation Sex selection
Related	Reproduction and pregnancy in speculative fiction