Can You Hear Your Biological Clock Ticking?

By: Morgan Ivens-Duran

            In the centuries preceding the Industrial Revolution, teenage pregnancy was something to be celebrated, and the more children a woman gave birth to during her lifetime, the better. Of course, at that time life expectancy was a great deal shorter than it is today, and the risk of infant mortality was around 25%.

            In our modern era, as women have begun to seek higher education and employment outside of the “traditional” housewife model, it is perhaps unsurprising that women have begun to delay childbearing. It can seem easier to put having a family on hold than finishing school, finding secure employment, or getting that next promotion. After all, magazines and talk shows are full of stories of women in their late 30’s or even 40’s who successfully have children. With all of our medical advancements, haven’t we figured out a way to beat the biological clock?

Halle Berry (41) on the cover of InStyle, February 2008. Image from  http://tinyurl.com/asuepam

            Unfortunately, waiting that long before having children isn’t always an option. Fertility begins to decline well before the onset of menopause (after which women cease monthly menstruation), and many physicians consider 35 to be the tipping point, after which pregnancy is both dangerous to the mother and unlikely to be successful. After 45, the probability of conception through natural methods, sometimes called “spontaneous conception”, is so low that most pregnancies are only possible with a combination of medically assisted fertilization and the use of either eggs frozen at a younger age or eggs from a donor in her 20’s – 30’s.

            The real-life implications of a woman’s biological clock got an unusual airing in the public forum on an episode of Fox’s “New Girl” just after Thanksgiving. Check out the clip below:

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            While Jess’s (played by Zoe Deschanel) ignorance may seem comedic, she’s not alone. Studies in Sweden, Israel, Canada, and the US have shown that most while most people understand that fertility decreases as women get older, they often underestimate the influence of maternal age on successful pregnancies, overestimate the rate of spontaneous conception, and overestimate the success of fertility treatments such as IVF (in vitro fertilization) to promote conception. Many women assume that because medical advances and better nutrition have extended life expectancy beyond the 27 years one could expect in Europe during the late 18^th century, the age at which fertility begins to decline has moved upwards as well. But while genetic manipulations to combat the natural decline in fertility are a possibility, at the moment they are more science fiction than scientific fact.           

            This begs the question of what causes this decline in female fertility, and why we don’t see the same magnitude of a decline in men of a similar age. Current research points to increasing aneuploidy, the failure of chromosomes to separate properly during meiosis, as the culprit. Aneuploidy most often results in spontaneous abortions, in which the fetus dies prior to completing development, and those babies that do survive are often born with severe developmental disabilities. Meiosis is the process of cellular division that produces eggs or sperm, depending on the sex of the individual in question. In males, once an individual has reached puberty he continually produces new sperm via meiosis. In females, the process of meiosis begins as the fetus develops in her mother’s womb, and then is put on hold. After the onset of puberty, each month one of the immature eggs, or oocytes, completes meiosis. If it is not fertilized, the egg is discarded through menstruation and the following month, another oocyte completes meiosis.

The phases of meiosis in males and females. Image from http://tinyurl.com/aoafpcb

            The lengthy period of time an oocyte spends in the interval between the initiation and completion of meiosis in females (also known as “prophase arrest”), is likely a major factor underlying the high rate of aneuploidy in older women, but the exact mechanism is not yet fully understood and likely involves multiple factors and processes. Some studies have shown that as maternal age increases, the integrity of proteins known as “cohesins”, which are crucial to proper chromosome separation, decreases. Work on other organisms that exhibit similar declines in female fertility suggests that hormones such as TGF-b and IGF, which are also involved in regulating physical growth, may also play an important role.

            But while the exact mechanisms underlying decreased female fertility with aging are of great interest to scientists and medical professionals, the average woman simply wants to know what she should do about it. When should she start trying to have kids? What medical options are available if she has trouble conceiving?

        While by no means an in-depth look at the huge variety of maternal age-related fertility treatments available today, there are essentially two main precursors: use of a donor egg or use of eggs frozen earlier in life (ie with a younger maternal age than the biological mother’s age now). Modern methods of egg freezing, also known as vitrification, address many of the issues associated with older methods of egg freezing, such as ice crystallization that renders the oocyte non-viable. Vitrification seems to represent a promising avenue for women to set aside “younger” eggs and thus preserve their fertility. However, even though vitrification is no longer considered an “experimental” treatment, there has been a great deal of push back from the medical community, insisting that vitrification should not be available to women without immediate medical concerns that threaten their fertility, and many insurance companies still refuse to cover the cost of elective egg freezing.

            As the ethical debates over techniques such as vitrification play out, I hope that we as a society will come down on the side of hopeful parents who are struggling to cope with a biological clock who’s timing was fixed millennia ago, when living to 100 was pie in the sky rather than reality. And I hope that we continue to educate ourselves about the science of infertility and the risk of involuntary childlessness, whether by combing scientific literature, talking with your doctor, or watching surprisingly educational television episodes.

References

Bretherick, K.L., N. Fairbrother, L. Avila, S.H.A. Harbord, W.P. Robinson. 2010. Fertility and aging: do reproductive-aged Canadian women know what they need to know? Fertility and Sterility 93(7):2162 – 2168.

Chiang, T., F.E. Duncan, K. Schindler, R.M. Schultz, M.A. Lampson. 2012. Evidence that Weakened Centromere Cohesion is a Leading Cause of Age-Related Aneuploidy in Oocytes. Current Biology 20:1522-1528.

Hasholoni-Delev, Y., A. Kaplan, S. Shkedi-Rafid. 2011. The fertility myth: Israeli students’ knowledge regarding age-related fertility decline and late pregnancies in an era of assisted reproduction technology. Human Reproduction 26(11): 3045-3053.

Homburg, R., F. van der Veen, S.J. Silber. 2009. Oocyte vitrification – Women’s emancipation set in stone. Fertility and Sterility 91(4): 1319 – 1320.

Hunt, P. and T. Hassold. 2008. Female Meiosis: Coming Unglued with Age. Current Biology 20(17): R669 – R702.

Knapp, Vincent J. 1998. Infant Mortality and Malnutrition in Preindustrial Europe: A Contemporary Explanation. Nutrition and Health 12(89):89 – 95.

Lampic, C., A.S. Svanberg, P. Karlström, T. Tydén. 2006. Fertility awareness, intentions concerning childbearing, and attitudes towards parenthood among female and male academics. Human Reproduction 21(2):558 – 564.

Mac Dougall, K., Y. Beyene, R.D. Nachtigall. 2013. Age shock: misperceptions of the impact of age on fertility before and after IVF in women who conceived after age 40. Human Reproduction 28(2):350 – 356.

NPR. 2012. Egg Freezing Moves Out of Experimental Realm. http://www.npr.org/2012/10/24/163558294/egg-freezing-moves-out-of-experimental-realm

Tatar, M. 2010. Reproductive aging in invertebrate genetic models. Annals of the New York Academy of Sciences 1204:149 – 155.