Editing Infertility (section)

==Causes==
[[Male infertility]] is responsible for 20–30% of infertility cases, while 20–35% are due to [[female infertility]], and 25–40% are due to combined problems in both partners.<ref name="LMCC">Chowdhury SH, Cozma AI, Chowdhury JH. Infertility. Essentials for the Canadian Medical Licensing Exam: Review and Prep for MCCQE Part I. 2nd edition. Wolters Kluwer. Hong Kong. 2017.</ref><ref name=eshre2014>{{cite web|url=https://www.eshre.eu/guidelines-and-legal/art-fact-sheet.aspx|title=ART fact sheet (July 2014)|website=[[European Society of Human Reproduction and Embryology]]|url-status=dead|archive-url=https://web.archive.org/web/20160304060954/https://www.eshre.eu/Guidelines-and-Legal/ART-fact-sheet.aspx|archive-date=4 March 2016}}</ref> In 10–20% of cases, no cause is found.<ref name=eshre2014/> The most common cause of female infertility is abnormal ovulation, usually manifested by scanty or absent menstrual periods.<ref name="Causes of infertility"/>  Male infertility is most commonly due to deficiencies in the [[semen]], and [[semen quality]] is used as a surrogate measure of male [[fecundity]].<ref name=who2010/>

=== Iodine Deficiency ===
[[Iodine deficiency]] may lead to infertility.<ref>{{cite journal | vauthors = Mathews DM, Johnson NP, Sim RG, O'Sullivan S, Peart JM, Hofman PL | title = Iodine and fertility: do we know enough? | journal = Human Reproduction | volume = 36 | issue = 2 | pages = 265–274 | date = January 2021 | pmid = 33289034 | doi = 10.1093/humrep/deaa312 }}</ref>

=== Natural infertility ===
Before [[puberty]], humans are naturally infertile; their [[gonad]]s have not yet developed the [[gametes]] required to reproduce: boys' [[testicle]]s have not developed the [[sperm cell]]s required to impregnate a female; girls have not begun the process of [[ovulation]] which activates the fertility of their egg cells (ovulation is confirmed by the first [[menstrual cycle]], known as [[menarche]], which signals the biological possibility of pregnancy). Infertility in [[child]]ren is commonly referred to as ''[[prepubescence]]'' (or being ''prepubescent'', an adjective used to also refer to humans without [[secondary sex characteristic]]s){{citation needed|date=April 2023}}.

The absence of fertility in children is considered a natural part of [[Development of the human body|human growth]] and [[child development]], as the [[hypothalamus]] in their brain is still underdeveloped and cannot release the [[hormone]]s required to activate the gonads' gametes. Fertility in children before the ages of eight or nine is considered a disease known as ''[[precocious puberty]]''. This disease is usually triggered by a [[brain tumor]] or [[brain injury|other related injury]].<ref>{{cite web|url=http://kidshealth.org/parent/medical/sexual/precocious.html|title=Precocious Puberty|publisher=KidsHealth|access-date=2021-08-31|archive-date=23 January 2016|archive-url=https://web.archive.org/web/20160123083430/http://kidshealth.org/parent/medical/sexual/precocious.html|url-status=live}}</ref>

=== Delayed puberty ===
{{Main|Delayed puberty}}
{{See also|Late bloomer}}

[[Delayed puberty]], puberty absent past or occurring later than the average onset (between the ages of ten and fourteen), may be a cause of infertility. In the United States, girls are considered to have delayed puberty if they have not started menstruating by age 16 (alongside lacking [[breast development]] by age 13).<!-- Empty reference <ref name=":3" /--><ref name=":1" /> Boys are considered to have delayed puberty if they lack enlargement of the testicles by age 14.<ref name=":1">{{cite book | vauthors = Ferri FF |title=Ferri's clinical advisor 2019 : 5 books in 1 |isbn=9780323550765 |oclc=1040695302 |date=2018-05-26|publisher=Elsevier Health Sciences }}</ref> Delayed puberty affects about 2% of adolescents.<ref>{{cite journal | vauthors = Howard SR, Dunkel L | title = The Genetic Basis of Delayed Puberty | journal = Neuroendocrinology | volume = 106 | issue = 3 | pages = 283–291 | date = 2018 | pmid = 28926843 | doi = 10.1159/000481569 | s2cid = 4772278 | doi-access = free }}</ref><ref name=":11">{{cite journal | vauthors = Klein DA, Emerick JE, Sylvester JE, Vogt KS | title = Disorders of Puberty: An Approach to Diagnosis and Management | journal = American Family Physician | volume = 96 | issue = 9 | pages = 590–599 | date = November 2017 | pmid = 29094880 }}</ref>

Most commonly, puberty may be delayed for several years and still occur normally, in which case it is considered a constitutional delay of growth and puberty, a common variation of healthy physical development.<ref name=":1" /> Delay of puberty may also occur due to various causes such as [[malnutrition]], various [[systemic disease]]s, or defects of the [[reproductive system]] ([[hypogonadism]]) or the body's responsiveness to [[sex hormone]]s.<ref name=":1" />

=== Immune infertility ===
[[Antisperm antibodies]] (ASA) have been considered as infertility cause in around 10–30% of infertile couples.<ref name=":02">{{cite journal | vauthors = Restrepo B, Cardona-Maya W | title = Antisperm antibodies and fertility association | journal = Actas Urologicas Espanolas | volume = 37 | issue = 9 | pages = 571–578 | date = October 2013 | pmid = 23428233 | doi = 10.1016/j.acuro.2012.11.003 }}</ref> In both men and women, ASA production are directed against surface antigens on sperm, which can interfere with sperm motility and transport through the [[female reproductive tract]], inhibiting capacitation and [[acrosome reaction]], impaired [[Fertilisation|fertilization]], influence on the implantation process, and impaired growth and development of the [[embryo]]. The antibodies are classified into different groups: There are IgA, IgG, and IgM antibodies. They also differ in the location of the spermatozoon they bind to (head, midpiece, tail). Factors contributing to the formation of antisperm antibodies in women are disturbance of normal immunoregulatory mechanisms, infection, violation of the integrity of the mucous membranes, rape and unprotected oral or anal sex. Risk factors for the formation of antisperm antibodies in men include the breakdown of the [[blood‑testis barrier]], trauma and surgery, orchitis, [[varicocele]], infections, [[prostatitis]], [[testicular cancer]], failure of immunosuppression and unprotected receptive anal or oral sex with men.<ref name=":02" /><ref name=":2">{{cite book|url=https://books.google.com/books?id=QfK8AQAAQBAJ&pg=PA311|title=Principles & Practice of Assisted Reproductive Technology (3 Vols)| vauthors = Rao K |date=2013-09-30|publisher=JP Medical Ltd|isbn=9789350907368|language=en}}</ref>

===Sexually transmitted infections===
Infections with the following sexually transmitted pathogens hurt fertility: ''[[Chlamydia trachomatis]]'' and ''[[Neisseria gonorrhoeae]]''. There is a consistent association of ''[[Mycoplasma genitalium]]'' infection and female reproductive tract syndromes. ''M. genitalium'' infection is associated with an increased risk of infertility.<ref name="LisRowhani-Rahbar2015">{{cite journal | vauthors = Lis R, Rowhani-Rahbar A, Manhart LE | title = Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis | journal = Clinical Infectious Diseases | volume = 61 | issue = 3 | pages = 418–426 | date = August 2015 | pmid = 25900174 | doi = 10.1093/cid/civ312 | doi-access = free | hdl = 1773/26479 | hdl-access = free }}</ref><ref name=Sternak>{{cite journal | vauthors = Ljubin-Sternak S, Meštrović T | title = Chlamydia trachomatis and Genital Mycoplasmas: Pathogens with an Impact on Human Reproductive Health | journal = Journal of Pathogens | volume = 2014 | issue = 183167 | pages = 183167 | date = 2014 | pmid = 25614838 | pmc = 4295611 | doi = 10.1155/2014/183167 | doi-access = free }}</ref>

===Genetic===
{{Main|Genetics of infertility}}

Mutations to the NR5A1 gene encoding [[steroidogenic factor 1]] (SF-1) have been found in a small subset of men with non-obstructive male factor infertility, where the cause is unknown. Results of one study investigating a cohort of 315 men revealed changes within the hinge region of SF-1 and no rare [[Allele|allelic]] variants in fertile control men. Affected individuals displayed more severe forms of infertility such as [[azoospermia]] and severe [[Oligospermia|oligozoospermia]].<ref>{{cite journal | vauthors = Ferraz-de-Souza B, Lin L, Achermann JC | title = Steroidogenic factor-1 (SF-1, NR5A1) and human disease | journal = Molecular and Cellular Endocrinology | volume = 336 | issue = 1–2 | pages = 198–205 | date = April 2011 | pmid = 21078366 | pmc = 3057017 | doi = 10.1016/j.mce.2010.11.006 }}</ref>

[[Small supernumerary marker chromosome]]s are abnormal extra chromosomes; they are three times more likely to occur in infertile individuals and account for 0.125% of all infertility cases.<ref name="pmid17390076">{{cite journal | vauthors = Liehr T, Weise A | title = Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics | journal = International Journal of Molecular Medicine | volume = 19 | issue = 5 | pages = 719–731 | date = May 2007 | pmid = 17390076 | doi =  }}</ref> See [[Small supernumerary marker chromosome#sSMC-associated infertility|Infertility associated with small supernumerary marker chromosomes]] and [[Genetics of infertility#Small supernumerary marker chromosomes and infertility]].

=== Other causes ===
Factors that can cause male as well as female infertility are:
* DNA damage
** DNA damage reduces fertility in female ovocytes, as caused by smoking,<ref name=Zenzes>{{cite journal | vauthors = Zenzes MT | title = Smoking and reproduction: gene damage to human gametes and embryos | journal = Human Reproduction Update | volume = 6 | issue = 2 | pages = 122–131 | year = 2000 | pmid = 10782570 | doi = 10.1093/humupd/6.2.122 | doi-access = free }}</ref> other [[xenobiotic]] DNA damaging agents (such as radiation or chemotherapy)<ref>{{cite journal | vauthors = Mark-Kappeler CJ, Hoyer PB, Devine PJ | title = Xenobiotic effects on ovarian preantral follicles | journal = Biology of Reproduction | volume = 85 | issue = 5 | pages = 871–883 | date = November 2011 | pmid = 21697514 | pmc = 3197911 | doi = 10.1095/biolreprod.111.091173 }}</ref> or accumulation of the oxidative DNA damage 8-hydroxy-deoxyguanosine<ref>{{cite journal | vauthors = Seino T, Saito H, Kaneko T, Takahashi T, Kawachiya S, Kurachi H | title = Eight-hydroxy-2'-deoxyguanosine in granulosa cells is correlated with the quality of oocytes and embryos in an in vitro fertilization-embryo transfer program | journal = Fertility and Sterility | volume = 77 | issue = 6 | pages = 1184–1190 | date = June 2002 | pmid = 12057726 | doi = 10.1016/s0015-0282(02)03103-5 | doi-access = free }}</ref>
** DNA damage reduces fertility in male sperm, as caused by oxidative DNA damage,<ref>{{cite journal | vauthors = Gharagozloo P, Aitken RJ | title = The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy | journal = Human Reproduction | volume = 26 | issue = 7 | pages = 1628–1640 | date = July 2011 | pmid = 21546386 | doi = 10.1093/humrep/der132 | doi-access = free }}</ref> smoking,<ref name=Zenzes /> other xenobiotic DNA damaging agents (such as drugs or chemotherapy)<ref>{{cite journal | vauthors = Nili HA, Mozdarani H, Pellestor F | title = Impact of DNA damage on the frequency of sperm chromosomal aneuploidy in normal and subfertile men | journal = Iranian Biomedical Journal | volume = 15 | issue = 4 | pages = 122–129 | year = 2011 | pmid = 22395136 | pmc = 3614247 | doi = 10.6091/ibj.990.2012 }}</ref> or other DNA-damaging agents, including reactive oxygen species, fever, or high testicular temperature.<ref>{{cite journal | vauthors = Shamsi MB, Imam SN, Dada R | title = Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility | journal = Journal of Assisted Reproduction and Genetics | volume = 28 | issue = 11 | pages = 1073–1085 | date = November 2011 | pmid = 21904910 | pmc = 3224170 | doi = 10.1007/s10815-011-9631-8 }}</ref> The damaged DNA related to infertility manifests itself by the increased susceptibility to denaturation inducible by heat or acid<ref>{{cite journal | vauthors = Evenson DP, Darzynkiewicz Z, Melamed MR | title = Relation of mammalian sperm chromatin heterogeneity to fertility | journal = Science | volume = 210 | issue = 4474 | pages = 1131–1133 | date = December 1980 | pmid = 7444440 | doi = 10.1126/science.7444440 | bibcode = 1980Sci...210.1131E }}</ref> or by the presence of double-strand breaks that can be detected by the [[TUNEL assay]].<ref>{{cite journal | vauthors = Gorczyca W, Traganos F, Jesionowska H, Darzynkiewicz Z | title = Presence of DNA strand breaks and increased sensitivity of DNA in situ to denaturation in abnormal human sperm cells: analogy to apoptosis of somatic cells | journal = Experimental Cell Research | volume = 207 | issue = 1 | pages = 202–205 | date = July 1993 | pmid = 8391465 | doi = 10.1006/excr.1993.1182 }}</ref> In this assay, the sperm's DNA will be denaturated and renatured. If DNA fragmentation occurs (double and single-strand breaks), a halo will not appear surrounding the spermatozoa, but if the spermatozoa do not have DNA damage, a halo surrounding the spermatozoa could be visualized under the microscope.
* General factors
** [[Diabetes mellitus]],<ref name= JangirJain>{{cite journal | vauthors = Jangir RN, Jain GC | title = Diabetes mellitus induced impairment of male reproductive functions: a review | journal = Current Diabetes Reviews | volume = 10 | issue = 3 | pages = 147–157 | date = May 2014 | pmid = 24919656 | doi = 10.2174/1573399810666140606111745 }}</ref><ref name= LivshitsSeidman>{{cite journal | vauthors = Livshits A, Seidman DS | title = Fertility issues in women with diabetes | journal = Women's Health | volume = 5 | issue = 6 | pages = 701–707 | date = November 2009 | pmid = 19863473 | doi = 10.2217/whe.09.47 | doi-access = free }}</ref> [[thyroid]] disorders,<ref name=Anreeva>{{cite journal | vauthors = Andreeva P | title = [Thyroid gland and fertility] | journal = Akusherstvo I Ginekologiia | volume = 53 | issue = 7 | pages = 18–23 | date = 2014 | pmid = 25675618 }}</ref> undiagnosed and untreated [[coeliac disease]],<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 | display-authors = 6 | title = Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms | journal = Human Reproduction Update | volume = 20 | issue = 4 | pages = 582–593 | date = 2014 | pmid = 24619876 | doi = 10.1093/humupd/dmu007 | quote = Physicians should investigate women with unexplained infertility, recurrent miscarriage or IUGR for undiagnosed CD. (...) CD can present with several non-gastrointestinal symptoms, and it may escape timely recognition. Thus, given the heterogeneity of clinical presentation, many atypical cases of CD go undiagnosed, leading to a risk of long-term complications. Among atypical symptoms of CD, disorders of fertility, such as delayed menarche, early menopause, amenorrhea or infertility, and pregnancy complications, such as recurrent abortions, intrauterine growth restriction (IUGR), small for gestational age (SGA) babies, low birthweight (LBW) babies or preterm deliveries, must be factored. (...) However, the risk is significantly reduced by a [[gluten]]-free diet. These patients should therefore be made aware of the potential negative effects of active CD also in terms of reproductive performance, and of the importance of a strict diet to ameliorate their health condition and reproductive health. | doi-access = free | hdl = 10807/56796 | hdl-access = free }}</ref><ref name=LasaZubiaurre>{{cite journal | vauthors = Lasa JS, Zubiaurre I, Soifer LO | title = Risk of infertility in patients with celiac disease: a meta-analysis of observational studies | journal = Arquivos de Gastroenterologia | volume = 51 | issue = 2 | pages = 144–150 | date = 2014 | pmid = 25003268 | doi = 10.1590/S0004-28032014000200014 | quote = Undiagnosed celiac disease is a risk factor for infertility. Women seeking medical advice for this particular condition should be screened for celiac disease. Adoption of a gluten-free diet could have a positive impact on fertility in this group of patients.(...)According to our results, non-diagnosed untreated CD constitutes a risk factor significantly associated with infertility in women. When comparing studies that enrolled patients previously diagnosed with CD, this association is not as evident as in the former context. This could be related to the effect that adoption of a gluten-free diet (GFD) may have on this particular health issue. | doi-access = free }}</ref><ref name=Hozyasz>{{cite journal | vauthors = Hozyasz K | title = [Coeliac disease and problems associated with reproduction] | journal = Ginekologia Polska | volume = 72 | issue = 3 | pages = 173–179 | date = March 2001 | pmid = 11398587 | quote = Coeliac men may have reversible infertility, and as in women, if gastrointestinal symptoms are mild or absent the diagnosis may be missed. It is important to make diagnosis because the giving of gluten free diet may result in conception and favourable outcome of pregnancy. }}</ref><ref name=SherJayanthi>{{cite journal | vauthors = Sher KS, Jayanthi V, Probert CS, Stewart CR, Mayberry JF | title = Infertility, obstetric and gynaecological problems in coeliac sprue | journal = Digestive Diseases | volume = 12 | issue = 3 | pages = 186–190 | date = 1994 | pmid = 7988065 | doi = 10.1159/000171452 | quote = There is now substantial evidence that coeliac sprue is associated with infertility both in men and women. (...) In men it can cause hypogonadism, immature secondary sex characteristics and reduce semen quality. (...) Hyperprolactinaemia is seen in 25% of coeliac patients, which causes impotence and loss of libido. Gluten withdrawal and correction of deficient dietary elements can lead to a return of fertility both in men and women. }}</ref> [[adrenal]] disease<ref name=ReichmanWhite>{{cite journal | vauthors = Reichman DE, White PC, New MI, Rosenwaks Z | title = Fertility in patients with congenital adrenal hyperplasia | journal = Fertility and Sterility | volume = 101 | issue = 2 | pages = 301–309 | date = February 2014 | pmid = 24355046 | doi = 10.1016/j.fertnstert.2013.11.002 | doi-access = free }}</ref>
* Hypothalamic-pituitary factors
** [[Hyperprolactinemia]]
** [[Hypopituitarism]]
** The presence of [[anti-thyroid antibodies]] is associated with an increased risk of unexplained subfertility with an [[odds ratio]] of 1.5 and 95% [[confidence interval]] of 1.1–2.0.<ref>{{cite journal | vauthors = van den Boogaard E, Vissenberg R, Land JA, van Wely M, van der Post JA, Goddijn M, Bisschop PH | title = Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review | journal = Human Reproduction Update | volume = 17 | issue = 5 | pages = 605–619 | year = 2011 | pmid = 21622978 | doi = 10.1093/humupd/dmr024 | url = https://pure.rug.nl/ws/files/39886084/Corrigendum_Significance_of_sub_clinical_thyroid_dysfunction_and_thyroid_autoimmunity_before_conception_and_in_early_pregnancy.pdf | access-date = 19 September 2019 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20190218060751/https://pure.rug.nl/ws/files/39886084/Corrigendum_Significance_of_sub_clinical_thyroid_dysfunction_and_thyroid_autoimmunity_before_conception_and_in_early_pregnancy.pdf | archive-date = 18 February 2019 }}</ref>
* Environmental factors
** [[Toxin]]s such as glues, volatile organic [[solvents]] or [[silicone]]s, physical agents, flame retardants, chemical dusts, [[Polychlorinated biphenyl|polychlorinated biphenyls]], and [[pesticides]].<ref>{{cite journal | vauthors = Mendiola J, Torres-Cantero AM, Moreno-Grau JM, Ten J, Roca M, Moreno-Grau S, Bernabeu R | title = Exposure to environmental toxins in males seeking infertility treatment: a case-controlled study | journal = Reproductive Biomedicine Online | volume = 16 | issue = 6 | pages = 842–850 | date = June 2008 | pmid = 18549695 | doi = 10.1016/S1472-6483(10)60151-4 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Smith EM, Hammonds-Ehlers M, Clark MK, Kirchner HL, Fuortes L | title = Occupational exposures and risk of female infertility | journal = Journal of Occupational and Environmental Medicine | volume = 39 | issue = 2 | pages = 138–147 | date = February 1997 | pmid = 9048320 | doi = 10.1097/00043764-199702000-00011 }}</ref><ref>{{Cite journal |last1=Björvang |first1=Richelle D. |last2=Damdimopoulou |first2=Pauliina |date=2020-04-02 |title=Persistent environmental endocrine-disrupting chemicals in ovarian follicular fluid and in vitro fertilization treatment outcome in women |url=https://ujms.net/index.php/ujms/article/view/5630 |journal=Upsala Journal of Medical Sciences |language=en |volume=125 |issue=2 |pages=85–94 |doi=10.1080/03009734.2020.1727073 |issn=0300-9734 |pmc=7721012 |pmid=32093529}}</ref><ref>{{Cite journal |last1=Björvang |first1=Richelle D. |last2=Hallberg |first2=Ida |last3=Pikki |first3=Anne |last4=Berglund |first4=Lars |last5=Pedrelli |first5=Matteo |last6=Kiviranta |first6=Hannu |last7=Rantakokko |first7=Panu |last8=Ruokojärvi |first8=Päivi |last9=Lindh |first9=Christian H. |last10=Olovsson |first10=Matts |last11=Persson |first11=Sara |last12=Holte |first12=Jan |last13=Sjunnesson |first13=Ylva |last14=Damdimopoulou |first14=Pauliina |date=May 2022 |title=Follicular fluid and blood levels of persistent organic pollutants and reproductive outcomes among women undergoing assisted reproductive technologies |journal=Environmental Research |language=en |volume=208 |pages=112626 |doi=10.1016/j.envres.2021.112626|pmid=34973191 |s2cid=245581454 |doi-access=free |bibcode=2022ER....20812626B }}</ref> [[Tobacco smoker]]s are 60% more likely to be infertile than non-smokers.<ref name=dh2009>{{cite web | url = http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_101070 | title = Regulated fertility services: a commissioning aid | date = June 2009 | archive-url = https://web.archive.org/web/20110103051232/http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_101070 | archive-date=3 January 2011 | work = Department of Health UK }}</ref>

Other diseases such as [[chlamydia infection|chlamydia]], and [[gonorrhea]] can also cause infertility, due to internal scarring ([[fallopian tube obstruction]]).<ref>{{cite web|url=https://www.cdc.gov/std/infertility/|title=Infertility & STDs - STD Information from CDC|website=cdc.gov|date=2019-01-11|access-date=9 September 2017|archive-date=17 August 2017|archive-url=https://web.archive.org/web/20170817195816/https://www.cdc.gov/std/infertility/|url-status=live}}</ref><ref>{{cite web|url=http://www.livestrong.com/article/1007744-stds-can-cause-infertility/|title=STDs That Can Cause Infertility| vauthors = Wittenberg ME |website=LIVESTRONG.COM|access-date=3 December 2014|archive-date=24 November 2014|archive-url=https://web.archive.org/web/20141124161610/http://www.livestrong.com/article/1007744-stds-can-cause-infertility/|url-status=live}}</ref><ref>{{cite web|url=http://health.howstuffworks.com/pregnancy-and-parenting/pregnancy/fertility/5-most-common-causes-of-infertility.htm#page=5|title=5 Most Common Causes of Infertility|website=HowStuffWorks|date=2011-02-17|access-date=3 December 2014|archive-date=14 December 2014|archive-url=https://web.archive.org/web/20141214051205/http://health.howstuffworks.com/pregnancy-and-parenting/pregnancy/fertility/5-most-common-causes-of-infertility.htm#page=5|url-status=live}}</ref>

*Body mass, the [[Body Mass Index|BMI]] (body mass index) (either being too high or too low) may be a contributor to infertility.
** [[Obesity]]: Obesity can have a significant impact on male and female fertility. In females, a BMI above 27 increases the risk of infertility 3-fold.<ref name="Carson 2021" /> Obese women have a higher rate of recurrent, early miscarriage compared to non-obese women.{{Citation needed|date=October 2024}} In males, an increase in BMI above 30 may be associated with reduced sperm quality and impaired [[spermatogenesis]] leading to infertility.<ref name="Ameratunga 2023">{{cite journal |last1=Ameratunga |first1=Devini |last2=Gebeh |first2=Alpha |last3=Amoako |first3=Akwasi |title=Obesity and male infertility |journal=Best Practice & Research Clinical Obstetrics & Gynaecology |date=August 2023 |volume=90 |pages=102393 |doi=10.1016/j.bpobgyn.2023.102393}}</ref> In males, a high BMI is also associated with low testosterone levels (secondary hypogonadism) and [[erectile dysfunction]], which contributes to infertility.<ref name="Ameratunga 2023" />
** Low weight: females with a very low BMI may have infertility. Common causes of low BMI leading to infertility include [[anorexia nervosa]] and other eating disorders, excessive exercise or [[relative energy deficiency in sport]].<ref name="Carson 2021" /> Infertility in females with a low BMI is usually due to [[functional hypothalamic amenorrhea]] due to stress-induced inhibition of the [[hypothalamic-pituitary-gonadal axis|hypothalamic pituitary ovarian axis]].<ref name="Carson 2021" />

===Females===
{{Further|Female infertility}}
The following causes of infertility may only be found in females.
For a woman to conceive, certain things have to happen: vaginal intercourse must take place around the time when an egg is released from her ovary; the system that produces eggs has to be working at optimum levels; and her hormones must be balanced.<ref>{{cite web | url =http://www.hfea.gov.uk/en/802.html | title = About infertility & fertility problems | archive-url = https://web.archive.org/web/20080829125837/http://www.hfea.gov.uk/en/802.html |archive-date=29 August 2008 | work = [[Human Fertilisation and Embryology Authority]] }}</ref>

For women, problems with fertilization arise mainly from either structural problems in the [[fallopian tube]] or uterus or problems releasing eggs. Infertility may be caused by blockage of the fallopian tube due to malformations, infections such as chlamydia, or scar tissue. For example, [[endometriosis]] can cause infertility with the growth of endometrial tissue in the fallopian tubes or around the ovaries. Endometriosis is usually more common in women in their mid-twenties and older, especially when postponed childbirth has taken place.<ref name="Lessey">{{cite journal | vauthors = Lessey BA | title = Medical management of endometriosis and infertility | journal = Fertility and Sterility | volume = 73 | issue = 6 | pages = 1089–96 | date = June 2000 | pmid = 10856462 | doi = 10.1016/s0015-0282(00)00519-7 | doi-access = free }}</ref>

Another major cause of infertility in women may be the inability to [[ovulate]]. Ovulatory disorders make up 25% of the known causes of female infertility. Oligo-ovulation or anovulation results in infertility because no oocyte will be released monthly. In the absence of an oocyte, there is no opportunity for fertilization and pregnancy. The World Health Organization subdivided ovulatory disorders into four classes:
* Hypogonadotropic hypogonadal anovulation: i.e., hypothalamic amenorrhea
* Normogonadotropic normoestrogenic anovulation: i.e., polycystic ovarian syndrome (PCOS)
* Hypergonadotropic hypoestrogenic anovulation: i.e., premature ovarian failure
* Hyperprolactinemic anovulation: i.e., pituitary adenoma<ref>{{cite book | vauthors = Walker MH, Tobler KJ | chapter = Female Infertility | date = March 2020 | title = StatPearls [Internet]. | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 32310493 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK556033/}}</ref>

Malformation of the eggs themselves may complicate conception. For example, [[polycystic ovarian syndrome]] (PCOS) is when the eggs only partially develop within the ovary, and there is an excess of male hormones. Some women are infertile because their ovaries do not mature and release eggs. In this case, synthetic FSH by injection or Clomid (Clomiphene citrate) via a pill can be given to stimulate follicles to mature in the ovaries.{{citation needed|date=April 2023}}

Other factors that can affect a woman's chances of conceiving include being overweight or underweight, or her age as female fertility declines after the age of 30.<ref>{{cite web | title = Female Infertility | publisher = Mayo Clinic | url = https://www.mayoclinic.org/diseases-conditions/female-infertility/symptoms-causes/syc-20354308 | access-date = 21 September 2020 | archive-date = 24 September 2020 | archive-url = https://web.archive.org/web/20200924191639/https://www.mayoclinic.org/diseases-conditions/female-infertility/symptoms-causes/syc-20354308 | url-status = live }}</ref>

Sometimes it can be a combination of factors, and sometimes a clear cause is never established.

Common causes of infertility in females include:
* ovulation problems (e.g., PCOS, the leading reason why women present to fertility clinics due to anovulatory infertility<ref>{{cite journal | vauthors = Balen AH, Dresner M, Scott EM, Drife JO | title = Should obese women with polycystic ovary syndrome receive treatment for infertility? | journal = BMJ | volume = 332 | issue = 7539 | pages = 434–435 | date = February 2006 | pmid = 16497735 | pmc = 1382524 | doi = 10.1136/bmj.332.7539.434 }}</ref>)
* tubal blockage
* [[pelvic inflammatory disease]] caused by infections like [[tuberculosis]]
* age-related factors
* uterine problems
* previous [[tubal ligation]]
* [[endometriosis]]
* [[advanced maternal age]]
* immune infertility

===Males===
{{Further|Male infertility}}
Male infertility is defined as the inability of a male to make a fertile female pregnant, for a minimum of at least one year of unprotected intercourse. Male infertility is estimated to contribute to 35% of infertility in couples.<ref name="Carson 2021" /> There are multiple causes for male infertility including [[endocrine disorders]] (usually due to hypogonadism) at an estimated 2% to 5%, sperm transport disorders at 5%, primary testicular defects (which includes abnormal sperm parameters without any identifiable cause) at 65% to 80% and [[idiopathic]] (where an infertile male has normal sperm and semen parameters) at 10% to 20%.<ref>Leslie SW, Siref LE, Khan MAB. Male Infertility| Updated 2020 Oct 30| In: StatPearls [Internet]| Treasure Island (FL): StatPearls| Publishing; 2020 Jan| Available from: {{cite book| chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK562258/| title = Male Infertility - StatPearls - NCBI Bookshelf| chapter = Male Infertility| year = 2022| publisher = StatPearls| pmid = 32965929| vauthors = Leslie SW, Siref LE, Soon-Sutton TL, Khan MA }}</ref>

The main cause of male infertility is low semen quality. In men who have the necessary reproductive organs to procreate, infertility can be caused by low sperm count due to endocrine problems, drugs, radiation, or infection.  There may be testicular malformations, hormone imbalance, or blockage of the man's duct system. Although many of these can be treated through surgery or hormonal substitutions, some may be indefinite.<ref name="Mishail">{{Cite journal |last1=Mishail |first1=Alek |last2=Marshall |first2=Susan |last3=Schulsinger |first3=David |last4=Sheynkin |first4=Yefim |date=May 2009 |title=Impact of a second semen analysis on a treatment decision making in the infertile man with varicocele |journal=Fertility and Sterility |language=en |volume=91 |issue=5 |pages=1809–1811 |doi=10.1016/j.fertnstert.2008.01.100|doi-access=free |pmid=18384779 }}</ref>
Infertility associated with viable, but immotile sperm may be caused by [[primary ciliary dyskinesia]]. The sperm must provide the zygote with [[DNA]], [[centrioles]], and activation factor for the embryo to develop. A defect in any of these sperm structures may result in infertility that will not be detected by semen analysis.<ref>{{cite journal | vauthors = Avidor-Reiss T, Khire A, Fishman EL, Jo KH | title = Atypical centrioles during sexual reproduction | journal = Frontiers in Cell and Developmental Biology | volume = 3 | pages = 21 | date = Apr 2015 | pmid = 25883936 | pmc = 4381714 | doi = 10.3389/fcell.2015.00021 | doi-access = free }}</ref> [[Antisperm antibodies]] cause immune infertility.<ref name=":02" /><ref name=":1" /> [[Cystic fibrosis]] can lead to infertility in men by blocking the vas deferens.<ref name="Carson 2021" />

[[Adeno-associated virus]] infection has been linked to poor sperm quality and may contribute to male infertility, based on small observational studies.<ref name="Kim 2012">{{cite journal |last1=Kim |first1=Chung Hyon |last2=Kim |first2=Jung Heon |last3=Kim |first3=Hyun Jung |last4=Kim |first4=Kun Woo |last5=Lee |first5=Joong Yeup |last6=Yang |first6=Soon Ha |last7=Choe |first7=Jin |last8=Hwang |first8=Doyeong |last9=Kim |first9=Ki Chul |last10=Hwang |first10=Eung Soo |title=Detection of Adeno-associated Virus from Semen Suffering with Male Factor Infertility and Having Their Conception Partners with Recurrent Miscarriages |journal=Journal of Bacteriology and Virology |date=2012 |volume=42 |issue=4 |pages=339 |doi=10.4167/jbv.2012.42.4.339}}</ref>

===Unexplained infertility===
{{Main|Unexplained infertility}}
In the US, up to 15% of infertile couples have unexplained infertility, in which no identifiable cause is found.<ref name="Carson 2021" /> [[Polymorphism (biology)|polymorphisms]] in [[folate pathway]] genes may be a cause for fertility complications in some women with unexplained infertility.<ref>{{cite journal | vauthors = Altmäe S, Stavreus-Evers A, Ruiz JR, Laanpere M, Syvänen T, Yngve A, Salumets A, Nilsson TK | display-authors = 6 | title = Variations in folate pathway genes are associated with unexplained female infertility | journal = Fertility and Sterility | volume = 94 | issue = 1 | pages = 130–137 | date = June 2010 | pmid = 19324355 | doi = 10.1016/j.fertnstert.2009.02.025 | doi-access = free }}</ref> Epigenetic modifications in sperm may also be responsible for unexplained infertility.<ref>{{cite journal | vauthors = Aston KI, Uren PJ, Jenkins TG, Horsager A, Cairns BR, Smith AD, Carrell DT | title = Aberrant sperm DNA methylation predicts male fertility status and embryo quality | journal = Fertility and Sterility | volume = 104 | issue = 6 | pages = 1388–1397 | date = December 2015 | pmid = 26361204 | doi = 10.1016/j.fertnstert.2015.08.019 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dada R, Kumar M, Jesudasan R, Fernández JL, Gosálvez J, Agarwal A | title = Epigenetics and its role in male infertility | journal = Journal of Assisted Reproduction and Genetics | volume = 29 | issue = 3 | pages = 213–223 | date = March 2012 | pmid = 22290605 | pmc = 3288140 | doi = 10.1007/s10815-012-9715-0 }}</ref>

===In Animals===
Many other [[Mammal|mammals]] experience infertility. [[Australian Cattle Dog|Red Heelers]] are known to be less fertile.{{Citation needed|date=March 2025}} [[Hybrid (biology)|Hybrid animals]] are usually infertile, due to their odd number of [[Chromosome|chromosomes]].{{Citation needed|date=March 2025}}