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===Ovarian aging=== As women age, they experience a decline in reproductive performance leading to [[menopause]]. This decline is tied to a decline in the number of ovarian follicles. Although about 1 million oocytes are present at birth in the human ovary, only about 500 (about 0.05%) of these ovulate, and the rest do not ovulate. The decline in ovarian reserve appears to occur at a constantly increasing rate with age,<ref>{{cite journal | last1 = Hansen | first1 = KR | last2 = Knowlton | first2 = NS | last3 = Thyer | first3 = AC | last4 = Charleston | first4 = JS | last5 = Soules | first5 = MR | last6 = Klein | first6 = NA | year = 2008 | title = A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause | journal = Hum Reprod | volume = 23 | issue = 3| pages = 699–708 | doi = 10.1093/humrep/dem408 | pmid = 18192670 | doi-access = free | citeseerx = 10.1.1.536.1171 }}</ref> and leads to nearly complete exhaustion of the reserve by about age 52. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions. The ovarian reserve and fertility perform optimally around 20–30 years of age.<ref name=":5">{{Cite journal|last1=Amanvermez|first1=Ramazan|last2=Tosun|first2=Migraci|date=2016|title=An Update on Ovarian Aging and Ovarian Reserve Tests|journal=International Journal of Fertility & Sterility|volume=9|issue=4|pages=411–415|issn=2008-076X|pmc=4793161|pmid=26985328}}</ref> Around 45 years of age, the menstrual cycle begins to change and the follicle pool decreases significantly.<ref name=":5" /> The events that lead to ovarian aging remain unclear. The variability of aging could include environmental factors, lifestyle habits or genetic factors.<ref name=":5" /> Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely,<ref>{{cite journal | last1 = Rzepka-Górska | first1 = I | last2 = Tarnowski | first2 = B | last3 = Chudecka-Głaz | first3 = A | last4 = Górski | first4 = B | last5 = Zielińska | first5 = D | last6 = Tołoczko-Grabarek | first6 = A | year = 2006 | title = Premature menopause in patients with BRCA1 gene mutation | journal = Breast Cancer Res Treat | volume = 100 | issue = 1| pages = 59–63 | doi = 10.1007/s10549-006-9220-1 | pmid = 16773440 | s2cid = 19572648 }}</ref> suggesting that naturally occurring DNA damages in oocytes are repaired less efficiently in these women, and this inefficiency leads to early reproductive failure. The BRCA1 protein plays a key role in a type of DNA repair termed homologous recombinational repair that is the only known cellular process that can accurately repair DNA double-strand breaks. Titus et al.<ref name=Titus>{{cite journal | last1 = Titus | first1 = S | last2 = Li | first2 = F | last3 = Stobezki | first3 = R | last4 = Akula | first4 = K | last5 = Unsal | first5 = E | last6 = Jeong | first6 = K | last7 = Dickler | first7 = M | last8 = Robson | first8 = M | last9 = Moy | first9 = F | last10 = Goswami | first10 = S | last11 = Oktay | first11 = K | year = 2013 | title = Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans | journal = Sci Transl Med | volume = 5 | issue = 172| pages = 172ra21| doi = 10.1126/scitranslmed.3004925 | pmid = 23408054 | pmc=5130338}}</ref> showed that DNA double-strand breaks accumulate with age in humans and mice in primordial follicles. Primordial follicles contain oocytes that are at an intermediate (prophase I) stage of meiosis. Meiosis is the general process in eukaryotic organisms by which germ cells are formed, and it is likely an adaptation for removing DNA damages, especially double-strand breaks, from germ line DNA (see [[Meiosis]] and [[Origin and function of meiosis]]).<ref>{{Cite journal |last1=Bernstein |first1=H. |last2=Byerly |first2=H. C. |last3=Hopf |first3=F. A. |last4=Michod |first4=R. E. |date=1985-09-20 |title=Genetic damage, mutation, and the evolution of sex |journal=Science |volume=229 |issue=4719 |pages=1277–1281 |doi=10.1126/science.3898363 |pmid=3898363|bibcode=1985Sci...229.1277B }}</ref> Homologous recombinational repair is especially promoted during meiosis. Titus et al.<ref name=Titus /> also found that expression of 4 key genes necessary for homologous recombinational repair of DNA double-strand breaks (BRCA1, MRE11, RAD51 and ATM) decline with age in the oocytes of humans and mice. They hypothesized that DNA double-strand break repair is vital for the maintenance of oocyte reserve and that a decline in efficiency of repair with age plays a key role in ovarian aging. A study identified 290 genetic determinants of ovarian ageing, also found that [[DNA damage (naturally occurring)|DNA damage]] response processes are implicated and suggests that possible effects of extending fertility in women would improve bone health, reduce risk of type 2 diabetes and increase the risk of hormone-sensitive cancers.<ref>{{cite news |title=Researchers identify new genes linked to longer reproductive lifespan in women |url=https://medicalxpress.com/news/2021-08-genes-linked-longer-reproductive-lifespan.html |access-date=21 September 2021 |work=medicalxpress.com |language=en}}</ref><ref>{{cite journal |title=Genetic insights into biological mechanisms governing human ovarian ageing |journal=Nature |date=August 2021 |volume=596 |issue=7872 |pages=393–397 |doi=10.1038/s41586-021-03779-7 |language=en |issn=1476-4687|last1=Ruth |first1=Katherine S. |last2=Day |first2=Felix R. |last3=Hussain |first3=Jazib |last4=Martínez-Marchal |first4=Ana |last5=Aiken |first5=Catherine E. |last6=Azad |first6=Ajuna |last7=Thompson |first7=Deborah J. |last8=Knoblochova |first8=Lucie |last9=Abe |first9=Hironori |last10=Tarry-Adkins |first10=Jane L. |last11=Gonzalez |first11=Javier Martin |last12=Fontanillas |first12=Pierre |last13=Claringbould |first13=Annique |last14=Bakker |first14=Olivier B. |last15=Sulem |first15=Patrick |last16=Walters |first16=Robin G. |last17=Terao |first17=Chikashi |last18=Turon |first18=Sandra |last19=Horikoshi |first19=Momoko |last20=Lin |first20=Kuang |last21=Onland-Moret |first21=N. Charlotte |last22=Sankar |first22=Aditya |last23=Hertz |first23=Emil Peter Thrane |last24=Timshel |first24=Pascal N. |last25=Shukla |first25=Vallari |last26=Borup |first26=Rehannah |last27=Olsen |first27=Kristina W. |last28=Aguilera |first28=Paula |last29=Ferrer-Roda |first29=Mònica |last30=Huang |first30=Yan |pmid=34349265 |pmc=7611832 |bibcode=2021Natur.596..393R |display-authors=1 }}</ref> A variety of testing methods can be used in order to determine fertility based on maternal age. Many of these tests measure levels of hormones FSH, and GnrH. Methods such as measuring AMH ([[anti-Müllerian hormone]]) levels, and AFC (antral follicule count) can predict ovarian aging. AMH levels serve as an indicator of ovarian aging since the quality of ovarian follicles can be determined.<ref>{{Cite journal|last1=Usta|first1=Taner|last2=Oral|first2=Engin|date=June 2012|title=Is the measurement of anti-Müllerian hormone essential?|url=http://insights.ovid.com/|journal=Current Opinion in Obstetrics and Gynecology|language=en|volume=24|issue=3|pages=151–157|doi=10.1097/GCO.0b013e3283527dcf|issn=1040-872X|pmid=22487725|s2cid=24219177|url-access=subscription}}</ref>
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