{{Short description|Diminished or absent ability of a female to achieve conception}} {{Infobox medical condition (new) | name = Female infertility | synonyms = | image = Age and female fertility.svg | caption = Cumulative percentage and average age for women reaching [[subfertility]], [[Infertility|sterility]], [[irregular menstruation]] and [[menopause]]<ref>{{cite journal|last1=te Velde|first1=E. R.|title=The variability of female reproductive ageing|journal=Human Reproduction Update|volume=8|issue=2|year=2002|pages=141–154|issn=1355-4786|doi=10.1093/humupd/8.2.141|pmid=12099629|doi-access=free}}</ref> | pronounce = | field = [[Gynecology]] | symptoms = | complications = | onset = | duration = | types = | causes = | risks = | diagnosis = | differential = | prevention = | treatment = | medication = | prognosis = | frequency = | deaths = }} '''Female infertility''' refers to [[infertility]] in women, which is the inability to [[Fertilisation|conceive]] after [[sexual intercourse]]. It affects an estimated 48 million women, globally.<ref name="Mascarenhas, M.N. 2012" />
Female infertility varies widely by region, The highest rates of female infertility are found in [[Eastern Europe]] and South [[Central Asia]], followed by [[South Asia]], [[Sub-Saharan Africa]], and [[Middle East and North Africa]].<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| article-number = e1001356 | doi = 10.1371/journal.pmed.1001356 |pmid=23271957 |pmc=3525527 |doi-access=free}}</ref> Female infertility rates are lowest in [[East Asia]] and [[Latin America]].<ref name="Mascarenhas, M.N. 2012" />
Fertility is affected by a variety of factors, including [[hormone|hormones]], nutritional status, disease, and malformations of the uterus. Infertility affects women from around the world, and the social stigmas affecting infertile women may vary from region to region.<ref name="Mascarenhas, M.N. 2012" />
==Cause== Causes or factors of female infertility can be classified based on whether they are [[acquired]] or genetic, and 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) 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 that risk factor is (or has been) present.
===Hormonal dysfunction=== Ovulatory hormonal disorders are the greatest single contributing factor to female infertility.<ref name="walkerstatpearls">{{cite journal |last1=Walker |first1=Matthew H. |last2=Tobler |first2=Kyle J. |title=Female Infertility |journal=StatPearls |date=2025 |url=https://www.ncbi.nlm.nih.gov/books/NBK556033/ |publisher=StatPearls Publishing |pmid=32310493 }}</ref> [[Anovulation]], or the failure to ovulate, is primarily caused by insufficient hormone levels, including low [[estrogen]] levels, insufficient [[GnRH]] secretion, as well as insufficient levels of other hormones secreted by the [[hypothalamus]] and [[pituitary]] glands.<ref name="walkerstatpearls" /> However, women with normal estrogen levels can also suffer from low fertility, such as in the case of women with [[PCOS]].<ref name="walkerstatpearls" />
It is not understood why women with PCOS and normal estrogen levels can still be infertile. However, it is believed that imbalanced secretion of [[GnRH]] can explain why such women fail to conceive, highlighting the need for hormonal balance in women with PCOS.<ref name="walkerstatpearls" />
===Acquired=== According to the [[American Society for Reproductive Medicine]] (ASRM), age, smoking, sexually transmitted infections, and being overweight or underweight can all affect fertility.<ref>http://www.fertilityfaq.org/_pdf/magazine1_v4.pdf{{dead link|date=September 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
In a broad sense, acquired factors include any factor that is not based on a [[genetic mutation]], including any [[Environmental toxins in pregnancy|intrauterine exposure to toxins during fetal development]], which may present as infertility many years later as an adult.
====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 |bibcode=2003Pedia.111..844A }}</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 | article-number=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 }}</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>
====Tobacco smoking==== [[File:RICO tobacco litigation corrective statement, Whitehall, PA (cropped).jpg|thumb|A [[United States v. Philip Morris|court-ordered]] corrective statement: "Smoking also causes reduced fertility, low birth weight in newborns, and cancer of the cervix" (United States, 2024).]] {{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]]. Cigarette smoking also 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==== [[Sexually transmitted infection]]s are a leading cause of infertility. They often display few, if any visible symptoms, and failing to seek proper treatment in time can decrease fertility.<ref name=asrm-risks/>
====Body weight and eating disorders==== {{See also|Obesity and fertility}} Twelve percent of all infertility cases are a result of a woman either being [[underweight]] or [[overweight]]. [[Adipocyte|Fat cells]] produce estrogen,<ref>{{cite journal |vauthors=Nelson LR, Bulun SE |title=Estrogen production and action |journal=J. Am. Acad. Dermatol. |volume=45 |issue=3 Suppl |pages=S116–24 |date=September 2001 |pmid=11511861 |doi= 10.1067/mjd.2001.117432}}</ref> in addition to the primary [[sex organ]]s. 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.<ref name=asrm-risks/> Too little body fat causes insufficient production of estrogen and disruption of the [[menstrual cycle]].<ref name=asrm-risks/> Both under and overweight women have irregular cycles, in which ovulation does not occur or is inadequate.<ref name=asrm-risks/> Proper nutrition in early life is also a major factor for later fertility.<ref>{{Cite journal | doi = 10.1093/humupd/dmq048 | last1 = Sloboda | first1 = D. M. | last2 = Hickey | first2 = M. | pmid = 20961922 | last3 = Hart | first3 = R. | title = Reproduction in females: the role of the early life environment | journal = Human Reproduction Update | volume = 17 | issue = 2 | pages = 210–227 | year = 2010| doi-access = free }}</ref>
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 was, 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==== Exposure to radiation poses a high risk of infertility, depending on the frequency, power, and exposure duration. [[Radiotherapy]] is reported to cause infertility.<ref>[https://www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/fertility-and-women-with-cancer/how-cancer-treatments-affect-fertility.html How Cancer Treatments Can Affect Fertility in Women]</ref> {{blockquote|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==== {{Main|Chemotherapy#Infertility}} [[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 |doi-access=free }}</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>
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>
==== Immune infertility ==== [[Antisperm antibodies]] (ASA) have been considered a cause of infertility in around 10–30% of infertile couples.<ref name=":0">{{Cite journal|last1=Restrepo|first1=B.|last2=Cardona-Maya|first2=W.|date=October 2013|title=Antisperm antibodies and fertility association|journal=Actas Urologicas Espanolas|volume=37|issue=9|pages=571–578|doi=10.1016/j.acuro.2012.11.003|issn=1699-7980|pmid=23428233}}</ref> ASAs 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]], impairing [[Human fertilization|fertilization]], influencing the implantation process, and impairing the 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, rape and unprotected oral or anal sex.<ref name=":0" /><ref name=":1">{{Cite book|url=https://books.google.com/books?id=QfK8AQAAQBAJ&pg=PA311|title=Principles & Practice of Assisted Reproductive Technology (3 Vols)|last=Rao|first=Kamini|date=2013-09-30|publisher=JP Medical Ltd|isbn=978-93-5090-736-8|language=en}}</ref>
====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 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 conclusion that, despite modern treatment, women with diabetes are at increased risk of female infertility, 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 | hdl = 10533/134018 | hdl-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. [[gluten-free diet|Gluten-free diets]] may reduce 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> *[[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 | url-access = subscription }} <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 a 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 | url-access = subscription }}</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=== {{See also|Genetics of infertility}} There are many [[gene]]s wherein [[mutation]] causes female infertility, as shown in table below. Also, there are 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).<ref>{{cite journal |vauthors=Sultan C, Biason-Lauber A, Philibert P |title=Mayer-Rokitansky-Kuster-Hauser syndrome: recent clinical and genetic findings |journal=Gynecol Endocrinol |volume=25 |issue=1 |pages=8–11 |date=January 2009 |pmid=19165657 |doi=10.1080/09513590802288291 |s2cid=33461252 }}</ref> 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 abnormality|Chromosomal abnormalities]] causing female infertility include [[Turner syndrome]]. Oocyte donation is an alternative for patients with Turner syndrome.<ref>{{cite journal |vauthors=Bodri D, Vernaeve V, Figueras F, Vidal R, Guillén JJ, Coll O |title=Oocyte donation in patients with Turner's syndrome: a successful technique but with an accompanying high risk of hypertensive disorders during pregnancy |journal=Hum. Reprod. |issue=3 |pages=829–832|date=March 2006 |pmid=16311294 |doi=10.1093/humrep/dei396 |volume=21|doi-access=free }}</ref>
Some of these gene or chromosome abnormalities cause [[intersexuality|intersex conditions]], such as [[androgen insensitivity syndrome]].
{|class="wikitable" |+[[Gene]]s wherein [[mutation]] causes female infertility<ref name=Evian2010>Unless otherwise specified in boxes, then reference is: {{Cite journal| author1 = The Evian Annual Reproduction (EVAR) Workshop Group 2010 | last2 = Fauser | first2 = B. C. J. M. | last3 = Diedrich | first3 = K. | last4 = Bouchard | first4 = P. | last5 = Domínguez | first5 = F. | last6 = Matzuk | first6 = M. | last7 = Franks | first7 = S. | last8 = Hamamah | first8 = S. | last9 = Simón | first9 = C. | last10 = Devroey | first10 = P. | last11 = Ezcurra | first11 = D. | last12 = Howles | first12 = C. M. | title = Contemporary genetic technologies and female reproduction | journal = Human Reproduction Update | volume = 17 | issue = 6 | pages = 829–847 | year = 2011 | pmid = 21896560 | pmc = 3191938 | doi = 10.1093/humupd/dmr033}}</ref> |- ! 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 (gene)|CBX2]]; [[M33 (gene)|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]]<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 |- | [[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 |- | [[Luteinizing hormone beta polypeptide|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 (gene)|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<ref name="2018-Boggula">{{cite journal | vauthors = Boggula VR, Hanukoglu I, Sagiv R, Enuka Y, Hanukoglu A | title = Expression of the epithelial sodium channel (ENaC) in the endometrium - Implications for fertility in a patient with pseudohypoaldosteronism | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 183 | pages = 137–141 | date = October 2018 | pmid = 29885352 | doi = 10.1016/j.jsbmb.2018.06.007 | s2cid = 47010706 }}</ref> |- | [[SOX9]] || [[SRY-related HMB-box gene 9]]|| |- | [[STAG3]] || [[Stromal antigen 3]] || [[Premature ovarian failure]]<ref name="CaburetArboleda2014">{{cite journal|last1=Caburet|first1=Sandrine|last2=Arboleda|first2=Valerie A.|last3=Llano|first3=Elena|last4=Overbeek|first4=Paul A.|last5=Barbero|first5=Jose Luis|last6=Oka|first6=Kazuhiro|last7=Harrison|first7=Wilbur|last8=Vaiman|first8=Daniel|last9=Ben-Neriah|first9=Ziva|last10=García-Tuñón|first10=Ignacio|last11=Fellous|first11=Marc|last12=Pendás|first12=Alberto M.|last13=Veitia|first13=Reiner A.|last14=Vilain|first14=Eric|title=Mutant Cohesin in Premature Ovarian Failure|journal=New England Journal of Medicine|volume=370|issue=10|year=2014|pages=943–949|issn=0028-4793|doi=10.1056/NEJMoa1309635|pmid=24597867|pmc=4068824}}</ref> |- | [[TAC3]] || [[Tachykinin 3]]|| Normosmic hypogonadotrophic hypogonadism |- | [[TACR3]] || [[Tachykinin receptor 3]] || Normosmic hypogonadotrophic hypogonadism |- | [[ZP1]] || [[zona pellucida glycoprotein 1]] || Dysfunctional [[zona pellucida]] formation<ref name="HuangLv2014">{{cite journal|last1=Huang|first1=Hua-Lin|last2=Lv|first2=Chao|last3=Zhao|first3=Ying-Chun|last4=Li|first4=Wen|last5=He|first5=Xue-Mei|last6=Li|first6=Ping|last7=Sha|first7=Ai-Guo|last8=Tian|first8=Xiao|last9=Papasian|first9=Christopher J.|last10=Deng|first10=Hong-Wen|last11=Lu|first11=Guang-Xiu|last12=Xiao|first12=Hong-Mei|title=Mutant ZP1 in Familial Infertility|journal=New England Journal of Medicine|volume=370|issue=13|year=2014|pages=1220–1226|issn=0028-4793|doi=10.1056/NEJMoa1308851|pmid=24670168|pmc=4076492}}</ref> | |}
===By location===
====Hypothalamic-pituitary factors==== *[[Hypothalamic dysfunction]] *[[Hyperprolactinemia]]
====Ovarian factors==== * [[Chemotherapy]] with certain agents have a high risk of toxicity on the ovaries. *Many genetic defects also disturb ovarian function. * [[Polycystic ovary syndrome]] (also see [[infertility in polycystic ovary syndrome]]). To be considered infertile due to PCOS, a woman must meet two of the following criteria: anovulation or oligovulation; hyperandrogenism; a PCO ultrasound. The following must be excluded: congenital suprarenal hyperplasia, androgen producer tumors, and [[Hyperprolactinaemia|hyperprolactinemia]] Some of PCOS's consequences are insulin resistance in 80% of PCOS women, higher incidence of spontaneous miscarriage, and 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> *Diminished [[ovarian reserve]] (also see [[poor ovarian reserve]]), demonstrated by an [[antral follicle count]] (AFC) >6AF and measurements of the hormones FSH, E2, and AMH.
*[[Premature menopause]] *[[Menopause]] *Luteal dysfunction<ref>{{EMedicine|med|1340|Luteal Phase Dysfunction}}</ref> *Gonadal dysgenesis ([[Turner syndrome]])
====Tubal (ectopic)/peritoneal factors==== {{Further|Tubal factor infertility}} *[[Endometriosis]] (also see [[endometriosis and infertility]]) *Pelvic [[Adhesion (medicine)|adhesions]] *[[Pelvic inflammatory disease]] (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 /> *[[Hydrosalpinx]] happens when there is the presence of fluid on the tubes. This can be tested by [[Hysterosalpingography|hysterosalphingography]], in which see both the uterus and the tubes are seen, or a '''[[Hysterosonosalpingiography|hysterosonosalphingography]]''', in which only the uterus is seen. This test is used to check if the tubes are permeable or if there is any obstacle in the path to the uterus. A liquid contrast is introduced via the vagina, and its path is checked with a 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 caused by sexually transmitted infections, previous surgery, peritonitis or endometriosis. •Permeability Hysterosalpingography (HSG) Ultrasoud + Hysterosonosalpingography (HSSG) Chlamydia serology Laparoscopy: methylene blue •Tubal examination (endoscopy): laparoscopy, falloposcopy, fertiloscopy
====Uterine factors==== *[[Uterine malformation]]s<ref name="pmid9402295">{{cite journal |vauthors=Raga F, Bauset C, Remohi J, Bonilla-Musoles F, Simón C, Pellicer A |title=Reproductive impact of congenital Müllerian anomalies |journal=Hum. Reprod. |volume=12 |issue=10 |pages=2277–81 |year=1997 |pmid=9402295 |doi=10.1093/humrep/12.10.2277|doi-access=free }}</ref> *[[Uterine fibroids]] *[[Asherman's Syndrome|Asherman's syndrome]]<ref name="pmid12470565">{{cite journal |author=Magos A |title=Hysteroscopic treatment of Asherman's syndrome |journal=Reprod. Biomed. Online |volume=4 |issue=Suppl 3 |pages=46–51 |year=2002 |pmid=12470565 |doi=10.1016/s1472-6483(12)60116-3}}</ref> *[[Implantation failure]] without any known primary cause. This results in a negative pregnancy test despite having performed e.g. [[embryo transfer]]. *Myomas Previously, a [[bicornuate uterus]] was thought to be associated with infertility,<ref>{{cite journal |vauthors=Shuiqing M, Xuming B, Jinghe L |title=Pregnancy and its outcome in women with malformed uterus |journal=Chin. Med. Sci. J. |volume=17 |issue=4 |pages=242–5 |year=2002 |pmid=12901513 }}</ref> but recent studies have not confirmed such an association.<ref>{{cite journal |vauthors=Proctor JA, Haney AF |title=Recurrent first trimester pregnancy loss is associated with uterine septum but not with bicornuate uterus |journal=Fertil. Steril. |volume=80 |issue=5 |pages=1212–5 |year=2003 |pmid=14607577 |doi= 10.1016/S0015-0282(03)01169-5|doi-access=free }}</ref>
====Cervical factors==== *[[Stenosis of uterine cervix|Cervical stenosis]]<ref name="pmid17877600">{{cite journal |vauthors=Tan Y, Bennett MJ |title=Urinary catheter stent placement for treatment of cervical stenosis |journal=The Australian & New Zealand Journal of Obstetrics & Gynaecology |volume=47 |issue=5 |pages=406–9 |year=2007 |pmid=17877600 |doi=10.1111/j.1479-828X.2007.00766.x|s2cid=22467867 }}</ref> *[[Antisperm antibodies]]<ref name=":1" /> *Non-receptive cervical [[mucus]]<ref name="pmid7745077">{{cite journal |vauthors=Farhi J, Valentine A, Bahadur G, Shenfield F, Steele SJ, Jacobs HS |title=In-vitro cervical mucus-sperm penetration tests and outcome of infertility treatments in couples with repeatedly negative post-coital tests |journal=Hum. Reprod. |volume=10 |issue=1 |pages=85–90 |year=1995 |pmid=7745077 |doi=10.1093/humrep/10.1.85}}</ref>
====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 [[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, they 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 /> Some instances of female infertility are caused by [[DNA repair]] dysregulation during meiosis.<ref name=Veitia2020 />
==Diagnosis== {{Main|Fertility testing}}
Diagnosis of infertility begins with a [[medical history]] and [[physical exam]]. The healthcare provider may order tests, including the following:
* Lab tests ** Hormone testing, to measure levels of female hormones at certain times during a [[menstrual cycle]]. ** Day 2 or 3 measure of [[Follicle-stimulating hormone|FSH]] and [[estrogen]], to assess [[ovarian reserve]]. ** Measurements of thyroid function<ref name="pmid16842634">{{cite journal |vauthors=Wartofsky L, Van Nostrand D, Burman KD |title=Overt and 'subclinical' hypothyroidism in women |journal=Obstetrical & Gynecological Survey |volume=61 |issue=8 |pages=535–42 |year=2006 |pmid=16842634 |doi=10.1097/01.ogx.0000228778.95752.66|s2cid=6360685 }}</ref> (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.<ref name="BroerBroekmans2014">{{cite journal|last1=Broer|first1=S. L.|last2=Broekmans|first2=F. J. M.|last3=Laven|first3=J. S. E.|last4=Fauser|first4=B. C. J. M.|title=Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications|journal=Human Reproduction Update|volume=20|issue=5|year=2014|pages=688–701|issn=1355-4786|doi=10.1093/humupd/dmu020|pmid=24821925|doi-access=free}}</ref> * 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 [[Sexual intercourse|intercourse]], to check for problems with sperm surviving in cervical mucous (not commonly used now because of its 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.<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.
Usually, reproductive endocrinology & infertility medical practices do not see women for general [[maternity care]]. The practice is primarily focused on helping 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, 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 result in a miscarriage or 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">{{cite web |title=Infecundity, infertility, and childlessness in Developing Countries - DHS Comparative Reports No. 9 |url=https://www.who.int/publications/m/item/infecundity-infertility-and-childlessness-in-developing-countries---dhs-comparative-reports-no.-9 |website=www.who.int |language=en |pages=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 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. * ''Not delaying parenthood.'' Fertility does not 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 |archive-url=https://web.archive.org/web/20021107035029/http://www.sfgate.com/cgi-bin/article.cgi?file=/chronicle/archive/2002/04/30/MN182697.DTL |url-status=dead |archive-date=November 7, 2002 |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 to 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 were around 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"/>
The highest female infertility rates were found in [[Eastern Europe]], the [[Middle East and North Africa]], and southern [[Central Asia]].<ref name="Mascarenhas, M.N. 2012" /> Countries with the lowest rates of female infertility are found in [[Latin America]] and [[East Asia]].<ref name="Mascarenhas, M.N. 2012"/>
[[North Africa]], the [[Middle East]], [[Oceania]], and [[Sub-Saharan Africa]] also had high rates of female infertility.<ref name="Mascarenhas, M.N. 2012"/> The prevalence of primary infertility has increased since 1990, while secondary infertility declined. Rates declined in high-income, Central/Eastern Europe, and Central Asia regions, but the prevalence of infertility remained unchanged.<ref name="Mascarenhas, M.N. 2012"/>
===Europe=== From 1990 to 2010, [[Russia]]n and [[Ukraine|Ukrainian]] women had the highest primary infertility rate in the world, with a primary fertility rate near or exceeding 3%. Secondary infertility rates in this region were also among the highest in the world, exceeding 13%. Thirteen countries in [[Eastern Europe]] had the highest infertility rates in this region, and they were also among the highest in the world.<ref name="Mascarenhas, M.N. 2012" />
===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, and highest 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 were in southern [[Central Asia]], followed by [[Southeast Asia]].<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. The greatest rates occurred in Jamaica, Suriname, Haiti, and Trinidad and Tobago. Central and Western Latin America had 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==
===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> In addition, many societies only tend to value a woman if she is able to produce at least one child, and a marriage may 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 African 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 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 and, some Sub-Saharan countries, women may be denied [[inheritance]] if they have not born 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 be 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"/>
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 infertility is 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=978-0-253-06387-8}}</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"/>
===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 seen in societies such as 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"/> and various societies where polygamy is more common and 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 another 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 their husband to select a woman, and accept the 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 may not be aware of the extra sexual relations and may not be informed if a woman becomes 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 is a reason for divorce in many cultures, and a way for a man or woman to increase their 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 may lose the security that often comes with land, wealth, and a family.<ref name="Mogobe, D. K. 2005"/> This can ruin marriages and lead to distrust in the marriage. The increase of sexual partners can potentially result in the spread of disease, including [[HIV/AIDS]], and can actually contribute to future generations of infertility.<ref name="Mogobe, D. K. 2005"/>
===Domestic abuse=== {{See also|Domestic abuse}} The emotional strain and stress that comes with infertility in the household can lead to the mistreatment and [[domestic abuse]] of women. The devaluation of a wife due to her inability to conceive can lead to domestic abuse and emotional trauma such as [[victim blaming]]. Women may be 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 woman, 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 their husbands, if they have no child bearing use.<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 abus that comes 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===
Many infertile women tend to experience immense stress and [[social stigma]] due to their condition, which can lead to considerable [[mental distress]].<ref name="McQuillian, J. 2003">McQuillian, J., Greil, A.L., White, L., Jacob, M.C. (2003). "Frustrated Fertility: Infertility and Psychological Distress among Women." Journal of Marriage and Family (65;4): 1007-1018.</ref> 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|mental illness]].<ref name=" Reproductive Health Outlook 2002">Reproductive Health Outlook (2002). "Infertility: Overview and lessons learned."</ref> Women with infertility might deal with psychological stressors such as denial, anger, grief, guilt, and [[Depression (mood)|depression]].<ref name="Matthews, A. M. 1986">{{cite journal |author1=Matthews A. M. |author2=Matthews R. | year = 1986 | title = Beyond the Mechanics of Infertility: Perspectives on the Social Psychology of Infertility and Involuntary Childlessness | journal = Family Relations | volume = 35 | issue = 4| pages = 479–487 | doi=10.2307/584507|jstor=584507 }}</ref> There can be considerable social shaming that can lead to intense feelings of sadness and frustration, that potentially contribute to depression and [[suicide]].<ref name="Mogobe, D. K. 2005"/> The implications behind infertility bear huge consequences for the [[mental health]] of an infertile woman, because of the social pressures and personal [[grief]] related to 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 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. Women, in studied cases, typically experience more adverse effects of infertility and treatments than men. Psychological support is fundamental, in order to limit the possibility of dropping out of 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.<ref>{{cite journal | doi=10.1192/apt.bp.112.010926 | title=Infertility and mental health | year=2014 | last1=Doyle | first1=Myles | last2=Carballedo | first2=Angela | journal=Advances in Psychiatric Treatment | volume=20 | issue=5 | pages=297–303 | doi-access=free }}</ref>
==See also== *[[Advanced maternal age]] *[[Fertility]] *[[Infertility]] *[[Male infertility]] *[[Oncofertility]]
==References== {{Reflist}}
==Additional sources== * Raval, H.; Slade, P.; Buck, P.; Lieberman, B. E. (1987-10). "The impact of infertility on emotions and the marital and sexual relationship". Journal of Reproductive and Infant Psychology. 5 (4): 221–234. {{doi|10.1080/02646838708403497}}. {{ISSN|0264-6838}}. * Khan, Ambreen Rashid (March 2019). "Impact of Infertility on Mental Health of Women" (PDF). The International Journal of Indian Psychology. 7 (1): 804–809. {{doi|10.25215/0701.089}} * 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== * https://patient.info/doctor/gynaecology/infertility-female {{Medical resources | DiseasesDB = 4786 | ICD10 = {{ICD10|N|97|0|n|80}} | ICD9 = {{ICD9|628}} | ICDO = | OMIM = | MedlinePlus = 001191 | eMedicineSubj = med | eMedicineTopic = 3535 | MeshID = D007247 }} {{Diseases of the pelvis, genitals and breasts}} {{Assisted reproductive technology}} {{Authority control}}
{{DEFAULTSORT:Female Infertility}} [[Category:Fertility medicine]] [[Category:Infertility|*]] [[Category:Fertility]] [[Category:Gynaecologic disorders]]