Advanced maternal age
{{Short description|Pregnancy at older ages}}
{{Merge from |Pregnancy over age 50 |date=November 2024 }}
{{For|effects associated with father's age|Paternal age effect}}
{{Use dmy dates|date=July 2020}}
Advanced maternal age, in a broad sense, is the instance of a woman being of an older age at a stage of reproduction, although there are various definitions of specific age and stage of reproduction.
{{cite web
|author=Fretts, Ruth C.
|date=3 December 2012
|title=Effect of advanced age on fertility and pregnancy in women
|website=UpToDate
|url=http://www.uptodate.com/contents/effect-of-advanced-age-on-fertility-and-pregnancy-in-women
|access-date=
|archive-url=https://web.archive.org/web/20160619172839/http://www.uptodate.com/contents/effect-of-advanced-age-on-fertility-and-pregnancy-in-women
|archive-date=19 June 2016
|editor1=Wilkins-Haug, Louise |editor2=Barss, Vanessa A.
}}
The variability in definitions is in part explained by the effects of increasing age occurring as a continuum rather than as a threshold effect.
Average age at first childbirth has been increasing, especially in OECD countries, among which the highest average age is 32.6 years (South Korea) followed by 32.1 years (Ireland and Spain).
{{cite web
|title=¿A qué edad tienen las madres su primer hijo? |language=es
|trans-title=At what age do mothers have their first child?
|website=El Orden Mundial (elordenmundial.com)
|date=12 August 2020
|url=https://elordenmundial.com/mapas-y-graficos/edad-madres-primer-hijo/
}}
In a number of European countries (Spain), the mean age of women at first childbirth has crossed the 30 year threshold.
{{cite report
|title=Mean age of mothers at first childbirth
|id=SF2.3
|website=oecd.org
|place=Paris, FR
|publisher=Organisation for Economic Co-operation and Development
|url=http://www.oecd.org/els/soc/SF2.3%20Mean%20age%20of%20mother%20at%20first%20childbirth%20-%20updated%20240212.pdf
|access-date=27 May 2014 |url-status=dead
|archive-url=https://web.archive.org/web/20141222133841/http://www.oecd.org/els/soc/SF2.3%20Mean%20age%20of%20mother%20at%20first%20childbirth%20-%20updated%20240212.pdf
|archive-date=22 December 2014
}}
This process is not restricted to Europe. Asia, Japan and the United States are all seeing average age at first birth on the rise, and increasingly the process is spreading to countries in the developing world such as China, Turkey and Iran. In the U.S., the average age of first childbirth was 26.9 in 2018.
{{cite report
|title=Births and natality
|website=cdc.org
|publisher=U.S. Centers for Disease Control
|url=https://www.cdc.gov/nchs/fastats/births.htm
|url-status=live |access-date=8 September 2017
|archive-url=https://web.archive.org/web/20191112144911/https://www.cdc.gov/nchs/fastats/births.htm
|archive-date=12 November 2019
}}
Advanced maternal age is associated with adverse maternal and perinatal outcomes. Possible maternal complications due to advanced maternal age include preterm labor, pre-eclampsia, gestational diabetes mellitus, stillbirth, chromosomal abnormalities, spontaneous miscarriage and cesarean delivery.{{Cite journal |last1=Glick |first1=Itamar |last2=Kadish |first2=Ela |last3=Rottenstreich |first3=Misgav |date=2021-08-10 |title=Management of Pregnancy in Women of Advanced Maternal Age: Improving Outcomes for Mother and Baby |journal=International Journal of Women's Health |language=English |volume=13 |pages=751–759 |doi=10.2147/IJWH.S283216 |doi-access=free |pmc=8364335 |pmid=34408501}} Advanced age can also increase the risk of infertility. Some of the possible fetal outcomes due to advanced maternal age include admission to neonatal intensive care units (NICU), intrauterine growth restrictions, low Apgar score, chromosomal abnormalities and infants smaller for gestational age. The corresponding paternal age effect is less pronounced.
{{cite book
|last=Tournaye |first=Herman
|date=June 2009
|chapter=Male reproductive ageing
|editor1-last=Bewley |editor1-first=Susan
|editor2-last=Ledger |editor2-first=William
|editor3-last=Nikolaou |editor3-first=Dimitrios
|title=Reproductive Ageing
|pages=95–104
|publisher=Cambridge University Press
|isbn=978-1-906985-13-4
|chapter-url=https://books.google.com/books?id=-SlaAQAAQBAJ&pg=PA95
|access-date=24 October 2020 |url-status=live
|archive-url=https://web.archive.org/web/20201104220433/https://books.google.com/books?id=-SlaAQAAQBAJ&pg=PA95
|archive-date=4 November 2020
}}
{{cite journal
|last1=Kidd |first1=Sharon A.
|last2=Eskenazi |first2=Brenda
|last3=Wyrobek |first3=Andrew J.
|date=February 2001
|title=Effects of male age on semen quality and fertility: A review of the literature
|journal=Fertility and Sterility
|volume=75 |issue=2 |pages=237–248
|doi=10.1016/s0015-0282(00)01679-4
|pmid=11172821 |doi-access=free
}}
History
Having children later was not exceptional in the past, when families were larger and women often continued bearing children until the end of their reproductive age. What is so radical about this recent transformation is that it is the age at which women give birth to their first child, which is becoming comparatively high, leaving an ever more constricted window of biological opportunity for second and subsequent children, should they be desired. Unsurprisingly, high first-birth ages and high rates of birth postponement are associated with the arrival of low, and lowest-low fertility.
{{cite news
|title=U.S. women more likely to have children than a decade ago
|date=2018-01-18
|website=Pew Research Center's Social & Demographic Trends Project
|language=en-US
|url=https://www.pewsocialtrends.org/2018/01/18/theyre-waiting-longer-but-u-s-women-today-more-likely-to-have-children-than-a-decade-ago/
|access-date=2020-10-29
}}
This association has now become especially clear, since the postponement of first births in a number of countries has now continued unabated for more than three decades and has become one of the most prominent characteristics of fertility patterns in developed societies. A variety of authors (in particular, Lesthaeghe) have argued that fertility postponement constitutes the "hallmark" of what has become known as the "second demographic transition". {{Citation needed|date=March 2024}}
Others have proposed that the postponement process itself constitutes a separate "third transition".
{{cite journal
|last1=Kohler |first1=Hans-Peter
|last2=Billari |first2=Francesco C.
|last3=Ortega |first3=Jose Antonio
|date=December 2002
|title=The emergence of lowest-low fertility in Europe during the 1990s
|journal=Population and Development Review
|volume=28 |issue=4 |pages=641–680
|doi=10.1111/j.1728-4457.2002.00641.x
}}
On this latter view, modern developed societies exhibit a kind of dual fertility pattern, with the majority of births being concentrated either among very young or increasingly older mothers. This is sometimes known as the "rectangularisation" of fertility patterns.
Examples
In the US, the average age at which women bore their first child advanced from 21.4 years old in 1970{{cite report |last=Mathews |first=T.J. |year=2009 |title=Delayed childbearing: More women are having their first child later in life |type=databrief |url=https://www.cdc.gov/nchs/data/databriefs/db21.pdf |publisher=U.S. Centers for Disease Control |access-date=26 August 2013 |url-status=live |archive-url=https://web.archive.org/web/20171125130852/https://www.cdc.gov/nchs/data/databriefs/db21.pdf |archive-date=25 November 2017}} to 26.9 in 2018.
The German Federal Institute for Population Research stated in 2015 the percentage for women with an age of at least 35 giving birth to a child was 25.9%. This figure rose from 7.6% in 1981.{{cite press release |title=Jedes vierte Neugeborene hat eine Mutter über 34 Jahre |trans-title=Every fourth newborn has a mother aged over 34 years |lang=de |website=bib-demografie.de |place=Wiesbaden, DE |publisher=Bundesinstitut für Bevölkerungsforschung [Federal Institute for Population Research] |url=http://www.bib-demografie.de/SharedDocs/Publikationen/DE/Download/Grafik_des_Monats/2017-12-20-Jedes-vierte-Neugeborene-hat-eine-Mutter-ueber-34-Jahre.pdf?__blob=publicationFile&v=4 |access-date=20 December 2017 |archive-url=https://web.archive.org/web/20171222052205/http://www.bib-demografie.de/SharedDocs/Publikationen/DE/Download/Grafik_des_Monats/2017-12-20-Jedes-vierte-Neugeborene-hat-eine-Mutter-ueber-34-Jahre.pdf?__blob=publicationFile&v=4 |archive-date=22 December 2017 |url-status=dead }}
Possible factors that influence childbearing age
There are many factors that may influence childbearing age in women, although they are mostly correlations without certain causations. For instance, older maternal age at first childbirth is associated with higher educational attainment and income.{{cite journal |last1=Shadyab |first1=Aladdin H. |last2=Gass |first2=Margery L.S. |last3=Stefanick |first3=Marcia L. |last4=Waring |first4=Molly E. |last5=Macera |first5=Caroline A. |last6=Gallo |first6=Linda C. |last7=Shaffer |first7=Richard A. |last8=Jain |first8=Sonia |last9=LaCroix |first9=Andrea Z. |display-authors=6 |date=January 2017 |title=Maternal age at childbirth and parity as predictors of longevity among women in the United States: The Women's Health Initiative |journal=American Journal of Public Health |volume=107 |issue=1 |pages=113–119 |doi=10.2105/AJPH.2016.303503 |pmid=27854529 |pmc=5308150 }}
Two studies show that generous parental leave allowances in Britain encourage young motherhood and that parental-leave allowance reduces postponement in Sweden.{{cite journal |last1=Balbo |first1=Nicoletta |last2=Billari |first2=Francesco C. |last3=Mills |first3=Melinda |title=Fertility in Advanced Societies: A Review of Research |journal=European Journal of Population |date=February 2013 |volume=29 |issue=1 |pages=1–38 |doi=10.1007/s10680-012-9277-y |pmid=23440941 |pmc=3576563 }}
Effects
= Decreased fertility =
File:Age and female fertility.svg, sterility, irregular menstruation and menopause{{cite journal |last1=te Velde |first1=E. R. |last2=Pearson |first2=PL |title=The variability of female reproductive ageing |journal=Human Reproduction Update |date=1 March 2002 |volume=8 |issue=2 |pages=141–154 |doi=10.1093/humupd/8.2.141 |pmid=12099629 |doi-access=free }}]]
{{Main|Age and female fertility}}
A woman's fertility peaks lasts during the twenties and first half of thirties, after which it starts to decline, with advanced maternal age causing an increased risk of female infertility.
According to Henri Leridon, PhD, an epidemiologist with the French Institute of Health and Medical Research, of women trying to get pregnant, without using fertility drugs or in vitro fertilization:{{cite journal |last1=Leridon |first1=H. |title=Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment |journal=Human Reproduction |date=1 July 2004 |volume=19 |issue=7 |pages=1548–1553 |doi=10.1093/humrep/deh304 |pmid=15205397 |doi-access=free }}
- At age 30, 75% will have a conception ending in a live birth within one year, and 91% will have a conception ending in a live birth within four years.
- At age 35, 66% will have a conception ending in a live birth within one year, and 84% will have a conception ending in a live birth within four years.
- At age 40, 44% will have a conception ending in a live birth within one year, and 64% will have a conception ending in a live birth within four years.
= Risk of birth defects =
A woman's risk of having a baby with chromosomal abnormalities increases with her age. Down syndrome is the most common chromosomal birth defect, and a woman's risk of having a baby with Down syndrome is:
{{cite web
|title=About Down syndrome
|website=ndss.org
|publisher=National Syndrome Down Society
|url=https://www.ndss.org/about-down-syndrome/down-syndrome/
}}
{{cite journal
|last1=Morris |first1=J.K.
|last2=Mutton |first2=D.E.
|last3=Alberman |first3=E.
|date=March 2002
|title=Revised estimates of the maternal age specific live birth prevalence of Down's syndrome
|journal=Journal of Medical Screening
|volume=9 |issue=1 |pages=2–6
|pmid=11943789
|doi=10.1136/jms.9.1.2 |doi-access=
}}
:;Risk of having a baby with Down syndrome
{{div col begin|colwidth=8em}}
:
style="text-align:center;"
! Age !! Risk | |
20 | {{sfrac|1| 2 000 }} |
24 | {{sfrac|1| 1 300 }} |
25 | {{sfrac|1| 1 200 }} |
29 | {{sfrac|1| 950 }} |
30 | {{sfrac|1| 900 }} |
:
style="text-align:center;"
! Age !! Risk | |
34 | {{sfrac|1| 450 }} |
35 | {{sfrac|1| 350 }} |
39 | {{sfrac|1|150}} |
40 | {{sfrac|1| 100 }} |
:
style="text-align:center;"
! Age !! Risk | |
44 | {{sfrac|1| 40 }} |
45 | {{sfrac|1| 30 }} |
49 | {{sfrac|1| 10 }} |
{{div col end}}
= Other effects =
Advanced maternal age is associated with adverse outcomes in the perinatal period, which may be caused by detrimental effects on decidual and placental development.{{cite journal |last1=Nelson |first1=S.M. |last2=Telfer |first2=E.E. |last3=Anderson |first3=R.A. |date=1 January 2013 |title=The ageing ovary and uterus: New biological insights |journal=Human Reproduction Update |volume=19 |issue=1 |pages=67–83 |doi=10.1093/humupd/dms043 |pmid=23103636 |pmc=3508627}}
The risk of the mother dying before the child becomes an adult increases by more advanced maternal age, such as can be demonstrated by the following data from France in 2007:{{cite journal |last1=Schmidt |first1=L. |last2=Sobotka |first2=T. |last3=Bentzen |first3=J.G. |last4=Nyboe Andersen |first4=A. |date=1 January 2012 |collaboration=ESHRE Reproduction and Society Task Force |title=Demographic and medical consequences of the postponement of parenthood |journal=Human Reproduction Update |volume=18 |issue=1 |pages=29–43 |doi=10.1093/humupd/dmr040 |doi-access=free |pmid=21989171}}
class="wikitable" style="text-align:center;"
! Maternal age at childbirth (years) | 20 | 25 | 30 | 35 | 40 | 45 |
Risk of mother not surviving to the child's 18th birthday (in %)
| 0.6% || 1.0% || 1.6% || 2.6% || 3.8% || 5.5% |
---|
The above table is not to be confused with maternal mortality.
Advanced maternal age continues to be associated with a range of adverse pregnancy outcomes including low birth weight, pre-term birth, stillbirth, unexplained fetal death, and increased rates of Caesarean section. However, over time, improvements in (and improvements in access to) medical services and social resources have decreased the negative association between older maternal age and low birth weight.{{cite journal |last1=Goisis |first1=Alice |last2=Schneider |first2=Daniel C. |last3=Myrskylä |first3=Mikko |title=Secular changes in the association between advanced maternal age and the risk of low birth weight: A cross-cohort comparison in the UK |journal=Population Studies |date=2 September 2018 |volume=72 |issue=3 |pages=381–397 |doi=10.1080/00324728.2018.1442584 |pmid=29582702 |s2cid=2977607 |doi-access=free }}
According to a meta analysis from 2017 of 63 cohort studies and 12 case control studies, advanced maternal age(≥35 years) increased the risk of stillbirth (OR 1.75, 95%CI 1.62 to 1.89). It also increased the risk for FGR (fetal growth restriction) (OR 1.23; 95%CI 1.01–1.52). It is suggested that the rise in the risk could be due to conditions related to placental pathology/dysfunction.{{Cite journal
| last1 = Lean
| first1 = Samantha C.
| last2 = Derricott
| first2 = Hayley
| last3 = Jones
| first3 = Rebecca L.
| last4 = Heazell
| first4 = Alexander E. P.
| year = 2017
| title = Advanced maternal age and adverse pregnancy outcomes: A systematic review and meta-analysis
| journal = PLOS ONE
| volume = 12
| issue = 10
| page = e0186287
| doi = 10.1371/journal.pone.0186287
| doi-access = free
| pmid = 29040334
| pmc = 5645107
| bibcode = 2017PLoSO..1286287L
}}
On the other hand, advanced maternal age is associated with a more stable family environment, higher socio-economic position, higher income and better living conditions, as well as better parenting practices (including better disciplinary methods{{cite journal |last1=Trillingsgaard |first1=Tea |last2=Sommer |first2=Dion |date=4 March 2018 |title=Associations between older maternal age, use of sanctions, and children's socio-emotional development through 7, 11, and 15 years |journal=European Journal of Developmental Psychology |volume=15 |issue=2 |pages=141–155 |doi=10.1080/17405629.2016.1266248 |s2cid=53061283 |url=https://pure.au.dk/ws/files/121838837/Associations_between_older_maternal_age_Accepted_manuscript_2016.pdf |url-status=live |access-date=19 July 2019 |archive-url=https://web.archive.org/web/20180719210200/https://pure.au.dk/ws/files/121838837/Associations_between_older_maternal_age_Accepted_manuscript_2016.pdf |archive-date=19 July 2018}}). A qualitative study on couples in the United States who used in-vitro fertilization to conceive their first child when the woman was aged 40 or older at the time of delivery found that 72% of the women and 57% of the men believed that they had enhanced emotional preparedness for parenting which benefitted both their children and themselves.{{cite journal |last1=Mac Dougall |first1=K. |last2=Beyene |first2=Y. |last3=Nachtigall |first3=R.D. |date=1 April 2012 |title='Inconvenient biology': Advantages and disadvantages of first-time parenting after age 40 using in vitro fertilization |journal=Human Reproduction |volume=27 |issue=4 |pages=1058–1065 |doi=10.1093/humrep/des007 |pmid=22333985 |pmc=3303492 }} In quantitative studies, mother's older age at first birth has been associated with increases in children's psychiatric health,{{cite journal |last=Goisis |first=A. |date=2 September 2015 |title=How are children of older mothers doing? Evidence from the United Kingdom |journal=Biodemography and Social Biology |volume=61 |issue=3 |pages=231–251 |doi=10.1080/19485565.2014.1001887 |pmid=26652679 |s2cid=10071445 |url=http://eprints.lse.ac.uk/60602/1/__lse.ac.uk_storage_LIBRARY_Secondary_libfile_shared_repository_Content_Goisis%2C%20A_Children%20of%20older%20mothers_Goisis_Children%20of%20older%20mothers_2015.pdf |url-status=live |access-date=19 July 2019 |archive-url=https://web.archive.org/web/20180720054256/http://eprints.lse.ac.uk/60602/1/__lse.ac.uk_storage_LIBRARY_Secondary_libfile_shared_repository_Content_Goisis%2C%20A_Children%20of%20older%20mothers_Goisis_Children%20of%20older%20mothers_2015.pdf |archive-date=20 July 2018}} language skills, cognitive ability,{{cite journal |last1=Goisis |first1=Alice |last2=Schneider |first2=Daniel C. |last3=Myrskylä |first3=Mikko |date=1 June 2017 |title=The reversing association between advanced maternal age and child cognitive ability: Evidence from three U.K. birth cohorts |journal=International Journal of Epidemiology |volume=46 |issue=3 |pages=850–859 |doi=10.1093/ije/dyw354 |pmid=28177512 |pmc=5837600 }} and fewer social and emotional difficulties. Further, a study in the United Kingdom showed that older maternal age at first birth was associated with fewer hospital admissions and fewer unintentional injuries for children up to age 5 and a greater likelihood of having had all of their immunizations by 9 months of age – all outcomes used as indicators of child wellbeing in reports from the World Health Organisation.{{cite journal |last1=Sutcliffe |first1=A.G. |last2=Barnes |first2=J. |last3=Belsky |first3=J. |last4=Gardiner |first4=J. |last5=Melhuish |first5=E. |date=21 August 2012 |title=The health and development of children born to older mothers in the United Kingdom: Observational study using longitudinal cohort data |journal=BMJ: British Medical Journal |volume=345 |issue=7876 |pages=e5116 |doi=10.1136/bmj.e5116 |pmid=22915663 |pmc=3424227}}
Changes in interpregnancy interval
Kalberer et al.{{cite journal |last1=Kalberer |first1=Urs |last2=Baud |first2=David |last3=Fontanet |first3=Arnaud |last4=Hohlfeld |first4=Patrick |last5=de Ziegler |first5=Dominique |date=December 2009 |title=Birth records from Swiss married couples analyzed over the past 35 years reveal an aging of first-time mothers by 5.1 years while the interpregnancy interval has shortened |journal=Fertility and Sterility |volume=92 |issue=6 |pages=2072–2073 |doi=10.1016/j.fertnstert.2009.05.078 |pmid=19608170 |url=https://serval.unil.ch/resource/serval:BIB_19AEC7C94AAC.P001/REF.pdf |access-date=19 July 2019 |archive-date=19 July 2018 |archive-url=https://web.archive.org/web/20180719173543/https://serval.unil.ch/resource/serval:BIB_19AEC7C94AAC.P001/REF.pdf |url-status=live }} have shown that despite the older maternal age at birth of the first child, the time span between the birth of the first and the second child (the interpregnancy interval) decreased over the last decades. If purely biological factors were at work, it could be argued that interpregnancy interval should have increased, as fertility declines with age, which would make it harder for the woman to get a second child after postponed birth of the first one. This not being the case shows that sociologic factors (see above) prime over biological factors in determining interpregnancy interval.
With technology developments cases of post-menopausal pregnancies have occurred, and there are several known cases of older women carrying a pregnancy to term, usually with in vitro fertilization of a donor egg. A 61-year-old Brazilian woman, aided by the implantation of a donor egg, gave birth to twins in October 2012.{{cite news |title=Woman, 61, pregnant |date=27 September 2011 |newspaper=The Sydney Morning Herald |url=http://www.smh.com.au/world/woman-61-pregnant-20110926-1ktkg.html |access-date=8 February 2013 |url-status=live |archive-url=https://web.archive.org/web/20160427065626/http://www.smh.com.au/world/woman-61-pregnant-20110926-1ktkg.html |archive-date=27 April 2016}}{{cite news |last=Moreno |first=Carolina |date=26 October 2012 |title=Look: 61 year-old woman gives birth to twins |website=HuffPost (huffingtonpost.com) |url=http://www.huffingtonpost.com/2012/10/26/antonia-leticia-asti-61-year-old-mother-gives-birth-to-twins_n_2025486.html |access-date=13 October 2017 |archive-date=3 August 2016 |archive-url=https://web.archive.org/web/20160803085246/http://www.huffingtonpost.com/2012/10/26/antonia-leticia-asti-61-year-old-mother-gives-birth-to-twins_n_2025486.html |url-status=live }}
Ovarian aging
As women age, they experience a decline in reproductive performance leading to menopause.{{cite web |title=Menopause |website=medlineplus.gov |url=https://medlineplus.gov/menopause.html |url-status=live|access-date=2020-10-29 |archive-url=https://web.archive.org/web/20201016204022/https://medlineplus.gov/menopause.html |archive-date=16 October 2020}} 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 of them (about 0.05%) ovulate, and the rest do not (ovarian follicle atresia). The decline in ovarian reserve appears to occur at a constantly increasing rate with age,{{cite journal |vauthors=Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA |year=2008 |title=A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause |journal=Human Reproduction |volume=23 |issue=3 |pages=699–708 |pmid=18192670 |doi=10.1093/humrep/dem408 |doi-access=free }} and leads to nearly complete exhaustion of the reserve by about age 51. 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.
Titus et al.{{cite journal |vauthors=Titus S, Li F, Stobezki R, Akula K, Unsal E, Jeong K, Dickler M, Robson M, Moy F, Goswami S, Oktay 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 |page=172ra21 |pmid=23408054 |doi=10.1126/scitranslmed.3004925 |pmc=5130338}} have proposed an explanation for the decline in ovarian reserve with age. They showed that as women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that normally accurately repairs DNA double-strand breaks. This repair system is referred to as homologous recombinational repair, and it is especially active during meiosis. Meiosis is the general process by which germ cells are formed in eukaryotes, and it appears to be an adaptation for efficiently removing damages in germ line DNA by homologous recombinational repair (see Origin and function of meiosis). Human primary oocytes are present at an intermediate stage of meiosis, that is prophase I (see Oogenesis). Titus et al. also showed that expression of four key DNA repair genes that are necessary for homologous recombinational repair (BRCA1, MRE11, Rad51 and ATM) decline in oocytes with age. This age-related decline in ability to repair double-strand damages can account for the accumulation of these damages, which then likely contributes to the decline in ovarian reserve.
Women with an inherited mutation in the DNA repair gene BRCA1 undergo menopause prematurely,{{cite journal |vauthors=Rzepka-Górska I, Tarnowski B, Chudecka-Głaz A, Górski B, Zielińska D, Tołoczko-Grabarek A |year=2006 |title=Premature menopause in patients with BRCA1 gene mutation |journal=Breast Cancer Res. Treat. |volume=100 |issue=1 |pages=59–63 |pmid=16773440 |doi=10.1007/s10549-006-9220-1 |s2cid=19572648 }} suggesting that naturally occurring DNA damages in oocytes are repaired less efficiently in these women, and this inefficiency leads to early reproductive failure. Genomic data from about 70,000 women were analyzed to identify protein-coding variation associated with age at natural menopause.{{cite journal |vauthors=Day FR, Ruth KS, Thompson DJ, et al. |year=2015 |title=Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair |journal=Nat. Genet. |volume=47 |issue=11 |pages=1294–303 |pmid=26414677 |pmc=4661791 |doi=10.1038/ng.3412 }} Pathway analyses identified a major association with DNA damage response genes, particularly those expressed during meiosis and including a common coding variant in the BRCA1 gene.
See also
Citations
{{reflist|25em}}
General and cited references
{{refbegin|25em|small=y}}
- {{cite journal
| last1 = Jabcosson | first1 = B.
| last2 = Ladfords | first2 = L.
| last3 = Milsom | first3 = I.
| year = 2004
| title = Advanced maternal age and adverse perinatal outcome
| journal = Obstetrics & Gynecology
| volume = 104 | issue = 4| pages = 727–733
| doi = 10.1097/01.aog.0000140682.63746.be
| pmid = 15458893 | s2cid = 8652247
}}
- {{cite journal
| last1 = Khashan | first1 = Ali S.
| display-authors = etal
| year = 2013
| title = Advanced maternal age and adverse pregnancy outcome: Evidence from a large contemporary cohort
| journal = PLOS ONE | volume = 8 | issue = 2 | pages = 1–9
| pmid = 23437176 | pmc = 3577849 | bibcode = 2013PLoSO...856583K | doi = 10.1371/journal.pone.0056583 | doi-access = free
}}
- {{cite journal
| last1 = Lorentzon | first1 = M.
| display-authors = etal
| year = 2012
| title = Advancing maternal age is associated with lower bone mineral density in young adult male offspring
| journal = Osteoporosis International
| volume = 23 | issue = 2 | pages = 475–482
| doi = 10.1007/s00198-011-1558-5
| pmid = 21350896 | pmc = 3261413
}}
- {{cite journal
| last1 = Nilsen | first1 = A.B.
| display-authors = etal
| year = 2012
| title = Characteristics of women who are pregnant with their first baby at an advanced age
| journal = Acta Obstetricia et Gynecologica Scandinavica
| volume = 91 | issue = 3 | pages = 353–362
| s2cid = 38149716 | pmid = 22150020
| doi = 10.1111/j.1600-0412.2011.01335.x
| doi-access = free
}}
{{refend}}
Further reading
- {{cite magazine
|author=Charlemagne
|date=9 February 2006
|title=The Fertility Bust
|department=Europe
|magazine=The Economist
|url=http://www.economist.com/world/europe/displaystory.cfm?story_id=5494593
|url-access=subscription
}}
- {{cite journal
|last1=Gavrilov |first1=L.A.
|last2=Gavrilova |first2=N.S.
|year=1997
|title=Parental Age at Conception and Offspring Longevity
|journal=Reviews in Clinical Gerontology
|volume=7 |pages=5–12
|doi=10.1017/S0959259897000026
}}
- {{cite book
|last1=Gavrilov |first1=L.A.
|last2=Gavrilova |first2=N.S.
|year=2000
|chapter=Human Longevity and Parental Age at Conception
|editor1-first=J.-M. |editor1-last=Robine
|editor2-first=T.B.L. |editor2-last=Kirkwood
|editor3-first=M. |editor3-last=Allard
|title=Sex and Longevity: Sexuality, Gender, Reproduction, Parenthood
|location=Berlin / Heidelberg, DE
|publisher=Springer-Verlag
|pages=7–31
|isbn=3-540-67740-2
}}
- {{cite book
|last1=Hofmeister |first1=Heather
|last2=Mills |first2=Melinda
|last3=Blossfeld |first3=Hans-Peter
|year=2006
|chapter=Globalization, Uncertainty and Women's, Mid-Career Life Courses: A Theoretical Framework
|title=Globalization, Uncertainty, and Women's Careers : An international comparison
|editor1-first=Hans-Peter |editor1-last=Blossfeld
|editor2-first=Heather |editor2-last=Hofmeister
|location=Cheltenham
|publisher=Edward Elgar Publishing
|pages=3–31
|isbn=1-84542-664-9
|chapter-url=https://fis.uni-bamberg.de/handle/uniba/13816
}}
- {{cite book
|last1=Kohler |first1=Hans-Peter
|last2=Billari |first2=Francesco C.
|last3=Ortega |first3=José Antonio
|year=2006
|chapter=Low Fertility in Europe: Causes, Implications and Policy Options
|editor1-last=Harris |editor1-first=Fred R.
|title=The Baby Bust: Who will do the work? Who will pay the taxes?
|pages=48–109
|publisher=Rowman & Littlefield
|isbn=978-0-7425-3855-9
|chapter-url=https://books.google.com/books?id=75alsu8U9QAC&pg=PA48
}}
- {{cite journal
|author1=Lesthaeghe, R.
|author2=Neels, K.
|year=2002
|title=From the First to the Second Demographic Transition: An Interpretation of the Spatial Continuity of Demographic Innovation in France, Belgium and Switzerland
|journal=European Journal of Population
|volume=18 |issue=4 |pages=325–360
|doi=10.1023/A:1021125800070 |s2cid=878879
}}
- {{cite thesis
|last=Sobotka |first=Tomás
|date=25 Nov 2004
|title=Postponement of Childbearing and Low Fertility in Europe
|lang=en
|degree=Ph.D.
|department=Faculty of Spatial Sciences
|publisher=University of Groningen
|place=Groningen, DE
|hdl=11370/7fe0743c-9766-4ae9-befe-3edae1006c6e
|isbn=9036191025
}}
External links
- {{cite AV media
|first=Tomás |last=Sobotka
|title=Postponement of childbearing and low fertility in Europe |medium=PowerPoint presentation
|url=http://www.ilcuk.org.uk/downloads/2%20Tomas%20Sobotka.ppt
}}
- [http://www.inciid.org/ InterNational Council on Infertility Information Dissemination] (inciid.org)