Age and female fertility

Female fertility is affected by age. Age is thus a major fertility factor for women. After puberty, female fertility increases and then decreases, with advanced maternal age causing an increased risk of female infertility. In humans, a woman's fertility peaks in the early and mid-20s, after which it starts to decline slowly, with a more dramatic drop at around 35.[1] At age 45, a woman starting to try to conceive will have no live birth in 50-80 percent of cases.[2] Menopause, or the cessation of menstrual periods, generally occurs in the 40s and 50s and marks the cessation of fertility, although age-related infertility can occur before then.[3] The relationship between age and female fertility is popularly referred to as a woman's "biological clock"; when a woman reaches an age where fertility is commonly understood to drop, it can be said that her "biological clock is ticking."[4]

Quantification of effect

Cumulative percentage and average age for women reaching subfertility, sterility, irregular menstruation and menopause.[5]

The average age of a young woman's first period (menarche) is 12 to 13 (12.5 years in the United States,[6] 12.72 in Canada,[7] 12.9 in the UK[8]) 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.[9] A woman's fertility peaks in her early and mid-20s after which it starts to decline. However, the exact estimates of the chances of a woman to conceive after a certain age are not clear, and are subject to debate.[10]

According to the National Institute for Health and Clinical Excellence about 94 out of every 100 women aged 35 who have regular unprotected sexual intercourse will get pregnant within 3 years of trying. For women aged 38, however, only 77 out of every 100 will do so.[11]

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[12]

According to a study done on a sample of 782 healthy European couples ages 19–39, fertility starts declining after age 27 and drops at a somewhat greater rate after age 35. The women were divided into four age groups: 19–26, 27–29, 30–34 and 35–39. Statistical analysis showed that the women in the 27–29 age group had significantly less chance on average of becoming pregnant than did the 19- to 26-year-olds. Pregnancy rates did not change notably between the 27–29 age group and the 30–34 age group, but dropped significantly for the 35-39 age group.[1] The age of the male partner had a significant impact on female fertility among the women who had reached their mid-30s, but not among the younger women. However, experts said the new study was too small and there were too many variables which were too difficult to sort out, for a clear conclusion to be drawn. Some experts suggested that the main change in fertility in the older women was the fact that it took them longer to conceive, not necessary that they were significantly more unlikely to eventually succeed. David Dunson, a biostatistician at the U.S. National Institute of Environmental Health Sciences, said that: "Although we noted a decline in female fertility in the late 20s, what we found was a decrease in the probability of becoming pregnant per menstrual cycle, not in the probability of eventually achieving a pregnancy."[1]

A French study found no difference between the fertility rate of women under 25 and those ages 26–30, after which fertility started to decrease. Estimating the "fertility of a woman" is quite difficult because of the male factor (quality of sperm). This French study looked at 2,193 women who were using artificial insemination because their husbands were azoospermic. The cumulative success rates after 12 cycles of insemination were 73% for women under age 25, 74% in women ages 26–30, 61% for ages 31–35, and 54% in the over 35 age group. (Note that the study is from 1982; artificial insemination techniques and success rates have evolved greatly since then.)[13]

In Hungary, a study by the Központi Statisztikai Hivatal (Central Statistics Office) estimated that 7%–12% of Hungarian women younger than 30 were infertile; 13%–22% of women age 35 were infertile; and 24%–46% of women age 40 were infertile.[14]

The below is a table containing estimates of the percentage of women who, if starting to conceive at a certain age, will fail to obtain a live birth.[2] Note that while for the young ages researchers tend to agree, for older ages there is discrepancy.

Age of woman when she starts to try to conceive % who will have no live birth according to Vincent (1950) % who will have no live birth according to Henry (1953), England % who will have no live birth according to Henry (1953), Norway % who will have no live birth according to Pittenger (1973) % who will have no live birth according to Leridon (1977) % who will have no live birth according to Trussell-Wilson (1985) % who will have no live birth according to Menken-Larsen (1986)
20 4 3.5 3.5 2.2 3 - 4
25 6 6 5 3.3 6 6 7
30 10 11 8 6.5 10 11 12
35 17 19 13 16 17 16 22
40 37 33 24 40 29 24 46
45 75 58 50 79 50 58 -

Ovarian reserve

"Percentage of ovarian reserve related to increasing age.[15] The curve describes the percentage of ovarian reserve remaining at ages from birth to 55 years, based on the ADC model. 100% is taken to be the maximum ovarian reserve, occurring at 18–22 weeks post-conception. The percentages apply to all women whose ovarian reserve declines in line with a particular model where late and early menopause are associated with high and low peak NGF populations, respectively. It is estimated that for 95% of women by the age of 30 years only 12% of their maximum pre-birth NGF population is present and by the age of 40 years only 3% remains. At birth, women have all their follicles for folliculogenesis, and they steadily decline until menopause."[15]

In terms of ovarian reserve, a typical woman has 12% of her reserve at age 30 and has only 3% at age 40.[16] 81% of variation in ovarian reserve is due to age alone,[16] making age the most important factor in female infertility.

The most common methods of checking the status of the ovarian reserve is to perform a blood test on day 3 of the menstrual cycle to measure serum FSH level, alternatively a blood test to measure the serum AMH level can give similar information. Transvaginal ultrasound can also be used to “count the number of follicles” and this procedure is called Antral Follicle Count.

The American College of Obstetricians and Gynecologists recommends ovarian reserve testing should be performed for women older than 35 years who have not conceived after 6 months of attempting pregnancy and women at higher risk of diminished ovarian reserve, such as those with a history of cancer treated with gonadotoxic therapy, pelvic irradiation, or both; those with medical conditions who were treated with gonadotoxic therapies; or those who had ovarian surgery for endometriomas.[17]

It is important to recognize that a poor result from ovarian reserve testing does not signify an absolute inability to conceive and should not be the sole criteria considered to limit or deny access to infertility treatment.[17]

Historical data

A study of a population of French women from 1670 and 1789 shows that those who married at age 20–24 had 7.0 children on average and 3.7% remained childless. Women who married at age 25–29 years had a mean of 5.7 children and 5.0% remained childless. Women who married at 30–34 years had a mean of 4.0 children and 8.2% remained childless.[18] The average age at last birth in natural fertility populations that have been studied is around 40.[19]

In 1957, a study was done on a large population that never used birth control. The investigators measured the relationship between the age of the female partner and fertility. (Infertility rates today are believed to be higher in the general population than for the population in this study from the 1950s.)

This 1957 study found that:[20]

Impact

Family planning

The inverse correlation between age and female fertility in later reproductive life is argued to motivate family planning well before having reached 35 years of age.[21] Mapping of a woman's ovarian reserve, follicular dynamics and associated biomarkers can give an individual prognosis about future chances of pregnancy, facilitating an informed choice of when to have children.[22] Notably, a higher level of anti-Müllerian hormone when tested in women in the general population has been found to have a positive correlation with natural fertility in women aged 30–44 aiming to conceive spontaneously, even after adjusting for age.[23] Thus, AMH measurement is helpful to determine which women may need to conceive at an earlier age, and which women can potentially wait.[24]

Reproductive medicine

Most in vitro fertilization (IVF) centers will attempt IVF using the female partner's own eggs until about age 43–45.[20] Michael Fox, M.D., a reproductive endocrinologist in Jacksonville, Florida states that, in regard to assisted reproduction treatment, "in general our approach to treatment of patients over age 35 is vastly more aggressive than in younger patients."[13]

Elite egg donor agencies that advertise in places such as Ivy League student newspapers offering up to $20,000 or even $50,000 for donor eggs seek donors under the age of 29.

The issues of age need to be taken up with a qualified fertility specialist such as a reproductive endocrinologist.

A review in 2012 came to the result that therapeutic interventions to halt or reverse the process of reproductive ageing in women is limited, despite recent reports of the potential existence of stem cells which may be used to restore the ovarian reserve.[22]

Common beliefs

A study commissioned by RESOLVE,[25] a non-profit patient advocacy organization, states that both three out of four men and three out of four women (in the United States) overestimate by five years the age of the onset of the rapid decline which is at 35 instead of 40 as most people commonly believe.[26] The American Society for Reproductive Medicine (ASRM) states, "...women in their 20's to early 30's are most likely to conceive."[27]

See also

References

  1. 1 2 3 Hall, Carl T. (2002-04-30). "Study speeds up biological clocks / Fertility rates dip after women hit 27". The San Francisco Chronicle. Retrieved 2007-11-21.
  2. 1 2 Leridon, Henri (2005). "The biological obstacles to late childbearing and the limits of ART" (PDF). Ined-Inserm, Paris. Retrieved 2012-08-26.
  3. ↑ A.D.A.M. Editorial Board (2011-09-13), "Menopause", PubMed Health (A.D.A.M. Medical Encyclopedia), retrieved Jul 17, 2014
  4. ↑ Pasqualotto, Fabio Firmbach; Borges Júnior, Edson; Pasqualotto, Eleonora Bedin (May 2008), "The male biological clock is ticking: a review of the literature", Sao Paulo Medical Journal 126 (3): 197–201, doi:10.1590/S1516-31802008000300012, ISSN 1516-3180, retrieved Jul 17, 2014
  5. ↑ te Velde, E. R. (2002). "The variability of female reproductive ageing". Human Reproduction Update 8 (2): 141–154. doi:10.1093/humupd/8.2.141. ISSN 1355-4786.
  6. ↑ Anderson SE, Dallal GE, Must A (April 2003). "Relative weight and race influence average age at menarche: results from two nationally representative surveys of US girls studied 25 years apart". Pediatrics 111 (4 Pt 1): 844–50. doi:10.1542/peds.111.4.844. PMID 12671122.
  7. ↑ Al-Sahab B1, Ardern CI, Hamadeh MJ, Tamim H. (2010). "Age at menarche in Canada: results from the National Longitudinal Survey of Children & Youth". BMC Public Health 28 (10): 736. doi:10.1186/1471-2458-10-736.
  8. ↑ Hamilton-Fairley, Diana (2004). "Obstetrics and Gynaecology: Lecture Notes (2nd ed.)" (PDF). Blackwell Publishing. Retrieved 2012-08-26.
  9. ↑ Apter D (February 1980). "Serum steroids and pituitary hormones in female puberty: a partly longitudinal study". Clinical Endocrinology 12 (2): 107–20. doi:10.1111/j.1365-2265.1980.tb02125.x. PMID 6249519.
  10. ↑ http://www.bbc.com/news/magazine-24128176
  11. ↑ CG11 Fertility: information for the public
  12. 1 2 Leridon, H. (2004). "Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment". Human Reproduction 19 (7): 1548–1553. doi:10.1093/humrep/deh304. PMID 15205397.
  13. 1 2 Fox M (May 2000). "Age And Infertility: The Biological Clock: Fact Or Fiction?". Jacksonville Medicine 51 (5).
  14. ↑ Balázs, Kapitány (February 2010). "A kései gyermekvállalás kockázatai" (PDF). KorFa on-line. Archived from the original (PDF) on 2012-03-13. Retrieved 2012-08-26.
  15. 1 2 Wallace, W. Hamish B.; Thomas W. Kelsey (2010-01-27). Vitzthum, Virginia J., ed. "Human Ovarian Reserve from Conception to the Menopause". PLoS ONE 5 (1): e8772. doi:10.1371/journal.pone.0008772. PMC 2811725. PMID 20111701.
  16. 1 2 Wallace WHB, Kelsey TW (2010). "Human Ovarian Reserve from Conception to the Menopause". PLoS ONE 5 (1): e8772. doi:10.1371/journal.pone.0008772. PMC 2811725. PMID 20111701.
  17. 1 2 "Committee Opinion No. 618: Ovarian Reserve Testing". Obstetrics and Gynecology 125: 268–273. January 2015. doi:10.1097/01.AOG.0000459864.68372.ec.
  18. ↑ Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment
  19. ↑ Fertility, Biology, and Behavior: An Analysis of the Proximate Determinants (Studies in Population), by John Bongaarts, Robert E. Potter. pp 42 - 43. "The average of these estimates is 40 years, which, as expected, is slightly below the mean age at onset of sterility. The data in Table 2.4 indicate that the mean age at last birth is remarkably invariant. With few exceptions the means fall in the 39–41 year range."
  20. 1 2 Age and Female Infertility, Fertility Tests of Egg Supply
  21. ↑ Infertility, Economics, and Common Sense. By Paul E. Visneski. The Journal of Lancaster General Hospital.
  22. 1 2 Nelson, S. M.; Telfer, E. E.; Anderson, R. A. (2012). "The ageing ovary and uterus: New biological insights". Human Reproduction Update 19 (1): 67–83. doi:10.1093/humupd/dms043. PMC 3508627. PMID 23103636.
  23. ↑ Broer, S. L.; Broekmans, F. J. M.; Laven, J. S. E.; Fauser, B. C. J. M. (2014). "Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications". Human Reproduction Update 20 (5): 688–701. doi:10.1093/humupd/dmu020. ISSN 1355-4786. PMID 24821925.
  24. ↑ Broer, S. L.; Broekmans, F. J. M.; Laven, J. S. E.; Fauser, B. C. J. M. (2014). "Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications". Human Reproduction Update 20 (5): 688–701. doi:10.1093/humupd/dmu020. ISSN 1355-4786. PMID 24821925.
    In turn citing:
  25. ↑ RESOLVE : The National Infertility Association
  26. ↑ Section: Age, Timing of Decline
  27. ↑ http://dl.dropbox.com/u/8256710/ASRM_Age.pdf

External links

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