Whether you’re considering having children or not, getting ahead and being in tune with your reproductive health can help you prepare for the future accordingly.
For many women, an exciting moment in life is recognising their desire to have a child. The decision to step into parenthood can come with surprising ease for some; however, for one in eight women, the hope to conceive is met by disappointing news of infertility (1). There is value in using tracking apps such as inne so you can be more in touch with your menstrual cycle throughout your reproductive lifespan. By monitoring patterns and changes, any potential issues related to fertility can be flagged up before getting to the point of trying to conceive.
Research proves that 50% of all infertility cases in both men and women are caused by genetic defects (2). For females, this can be due to a number of factors including maternal age and reproductive life span, menstrual diseases, or inherited genetic disorders. Although many scientific advancements have been discovered to help women overcome these barriers, there is still so much to be understood. In this article, we take a look at what we do know about women’s fertility and the impact of genetic defects, unpicking the details on a microscopic level.
How chromosomal abnormalities impact fertility
An essential part of fertility is dictated by chromosomes. Chromosomes can be thought of as the instruction manual for our bodies growth and development. They are composed of genes which, in turn, are made up of strands of DNA. There are 46 chromosomes paired together in every living cell; half come from the mother’s genetic information and the other half from the father’s. During conception, when a sperm fertilises an egg, a healthy foetus will contain all 23 pairs of chromosomes. The 23rd pair is extra special and labelled as X and/or Y chromosome determining the sex of the foetus; XX is female and XY is male (3). Studies show that the X chromosome in women has a significant impact on her fertility and can determine the risk of menstrual diseases (4).
The most common cause for pregnancy loss in the first trimester is due to chromosomal abnormalities, with 26% of all pregnancies ending in miscarriage (5). These studies show the majority of which are due to foetuses having missing or extra chromosomes making them abnormal. This increases the chance that the embryo will fail to implant in the uterus; something which can largely be impacted by age (6). You see, women are born with roughly 400,000 eggs in their ovaries, and that number steadily depletes throughout their reproductive lifespan. As a woman gets closer to menopause, with the average age of onset being 50-52 years old, the quality of the egg will decline, making the chances of chromosomal abnormalities even higher (7). Research also shows that between 44 - 65% of women reach menopause at the same age as their mothers, suggesting a genetic correlation between ovarian reserves (7).
The loss of ovarian function before the age of 40 is defined as premature ovarian failure (POF) or primary ovarian insufficiency. With lowering levels of estrogen, POF results in infertility at a much younger age. This is a common disease affecting 1% of the female population and has been linked to abnormalities in a woman’s X chromosome (the 23rd pair in the cell) (7). This involves either whole or partial deletions, duplications or translocations of the X chromosome. There are a number of diseases related to the X chromosome that lead to fertility issues and POF, some of which we explore below.
Common reproductive diseases affecting fertility
Polycystic ovary syndrome (PCOS) and endometriosis are two diseases known to affect fertility. Both have a direct correlation to the X chromosome and are presumed to be hereditary conditions. PCOS is a complex disease in which harmless follicles grow within the ovaries. The follicles are sacs in which eggs develop, however, they are often unable to release the egg, meaning ovulation does not occur. PCOS is considered the main cause of anovulatory infertility (the absence of ovulation) in women and is often due to elevated levels of the hormone androgen (8). Research shows that mutations and disruptions to the structure of genes within the X chromosome lead to this higher production of androgen (8). Though there are many symptoms, it is important to pay attention to signs such as irregular periods, weight gain, excessive hair growth and acne. We suggest you seek out medical advice if you find any cause for concern.
Endometriosis is a condition in which tissue, similar to the lining of the womb, grows outside of the uterus. During menstruation, the tissue will act like the uterus and try to bleed. The body responds to this by trying to heal the area resulting in the development of scar tissue. This cyclical condition affects between 8 -10% of women of reproductive age and can vary between showing no symptoms at all to causing significant and debilitating pain (9). Thirty percent of endometriosis cases result in infertility due to the tissue growing in areas such as the ovaries and the fallopian tubes, having a significant effect on ovarian reserves and function (10). This can lead to premature ovarian aging and decreasing the chances of successful conception. Studies show that severe endometriosis is 60% more likely when a relative has the disease (10).
Fertility and Genetic diseases
Studies show that approximately 15% of all genetic disorders are associated with infertility (11). One such disorder is Turner Syndrome when a woman is missing all or part of the X chromosome determining her sex. In the most severe form, women will be born with only 45 chromosomes and a single X chromosome. Turner Syndrome is known to affect 1 in 2000 females, many of whom will only be diagnosed in their teenage years or when they are trying to conceive (12). Due to the genetic abnormality, many women with Turner Syndrome will experience difficulty conceiving and be subject to a significantly faster decline in ovarian function, leading to POF and infertility.
Similarly, fragile X syndrome has been related to POF. Affecting 1 in 200 women, fragile X syndrome occurs when a critical gene found in the X chromosome (FMR1) is fully mutated (2). The change in the gene causes a range of developmental issues for the embryo and may result in a child being born with learning disabilities. Research shows that fragile X syndrome is a hereditary disease, with 16% of women experiencing POF carrying the critical gene related to this condition (7).
Stay Aware of Your Fertilities Health
Whether you’re considering having children or not, getting ahead and being in tune with your reproductive health can help you prepare for the future accordingly. All genetic diseases vary from person to person with studies showing a clear correlation between chromosomal abnormalities and environmental factors including stress, diet and substance misuse (2). As we wait for research to uncover more about the behaviour of genetic defects, there are multiple ways for you to check in with your own body's fertility health. Identifying any genetic diseases or predispositions that run in the family can be a great start, alongside addressing issues such as heavy, absent or painful periods. By using inne’s tracking app, you can map the length of your cycle, and check to see if any changes occur between and during menstruation. As always, we suggest you seek medical advice should you have any cause for concern.
1. J. Datta, M.J. Palmer, C. Tanton, L.J. Gibson, K.G. Jones, W. Macdowall, A. Glasier, P. Sonnenberg, N. Field, C.H. Mercer, A.M. Johnson, K. Wellings, Prevalence of infertility and help seeking among 15 000 women and men, Human Reproduction, Volume 31, Issue 9, September 2016, Pages 2108–2118
2. Zorrilla M, Yatsenko AN. The Genetics of Infertility: Current Status of the Field. Curr Genet Med Rep. 2013;1(4):10.1007/s40142-013-0027-1. doi:10.1007/s40142-013-0027-1
3. Deakin JE, Potter S, O'Neill R, et al. Chromosomics: Bridging the Gap between Genomes and Chromosomes. Genes (Basel). 2019;10(8):627. Published 2019 Aug 20. doi:10.3390/genes10080627
4. Venkatesh T, Suresh PS, Tsutsumi R. New insights into the genetic basis of infertility. Appl Clin Genet. 2014;7:235-243. Published 2014 Dec 1. doi:10.2147/TACG.S40809
5. Dugas C, Slane VH. Miscarriage. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan
6. Dugas C, Slane VH. Miscarriage. [Updated 2020 Nov 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.
7. Chapman C, Cree L, Shelling AN. The genetics of premature ovarian failure: current perspectives. Int J Womens Health. 2015;7:799-810. Published 2015 Sep 23. doi:10.2147/IJWH.S64024
8. Khan MJ, Ullah A, Basit S. Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives. Appl Clin Genet. 2019;12:249-260. Published 2019 Dec 24. doi:10.2147/TACG.S200341
9. Nina Shigesi, Marina Kvaskoff, Shona Kirtley, Qian Feng, Hai Fang, Julian C Knight, Stacey A Missmer, Nilufer Rahmioglu, Krina T Zondervan, Christian M Becker, The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis, Human Reproduction Update, Volume 25, Issue 4, July-August 2019, Pages 486–503,
10. Pedro Acién, Irene Velasco, "Endometriosis: A Disease That Remains Enigmatic", International Scholarly Research Notices, vol. 2013, Article ID 242149, 12 pages, 2013.
11. Cariati F, D'Argenio V, Tomaiuolo R. The evolving role of genetic tests in reproductive medicine. J Transl Med. 2019;17(1):267. Published 2019 Aug 14. doi:10.1186/s12967-019-2019-8
12. Doğer E, Çakıroğlu Y, Ceylan Y, Ulak E, Özdamar Ö, Çalışkan E. Reproductive and obstetric outcomes in mosaic Turner's Syndrome: a cross-sectional study and review of the literature. Reprod Biol Endocrinol. 2015;13:59. Published 2015 Jun 10. doi:10.1186/s12958-015-0055-7