Causes of Female Infertility – Cancer
Dr. Kate Dudek • May 5, 2020 • 5 min read
The impact of cancer on fertility depends not only on the type of cancer, with those affecting the reproductive organs likely to have a more detrimental effect on future fertility, but also on the treatment options selected and the age of the patient.
Dealing with a cancer diagnosis can be traumatic enough. There will be many factors to consider and decisions to make, all in a short time period. Maintaining close relationships with your spouse, your family and your friends is fundamental. One thing that may need to be considered when thinking about treatment options is fertility status and the likelihood of having or expanding a family in the future.
Chemotherapy
Chemotherapy works by killing cells in the body that divide quickly. The immature eggs (oocytes) in the ovaries tend to divide quickly, so are often affected by chemotherapy. Chemotherapy can cause temporary or permanent infertility when the drugs that are given, stop the ovaries from releasing eggs.
With temporary infertility, periods may become irregular or stop during treatment. It can take from 6 months to 2 years for the menstrual cycles to return to normal. Even if a woman is menstruating regularly after cancer treatment, she may still experience difficulties conceiving and may want to consult a specialist for advice.
The risk of permanent infertility depends on the female’s age, menstrual history, hormone levels and type of cancer; as well as the specific drugs she is given and how strong a dose she receives. With all these factors to consider, it can be difficult to predict if a woman is likely to be permanently infertile after chemotherapy. Women who are nearer to the menopause are more likely to experience permanent infertility, usually because their ovarian supply is already diminished. Chemotherapy can cause Primary Ovarian Insufficiency. It can also induce the menopause, with women typically experiencing it 5 to 10 years earlier than would normally be expected.
Chemotherapy can also cause a reduction in libido and reduced cervical secretions, making intercourse uncomfortable, difficult and/or painful.
Radiotherapy
Radiotherapy is a cancer treatment that uses high-energy rays to destroy cancer cells and shrink tumours. The impact of radiotherapy on fertility depends on the part of the body that is being treated. The types of radiotherapy that may affect fertility include:
- Radiotherapy to the pelvis. The pelvis is the lower part of the torso, located between the stomach and the legs. It contains the bladder and reproductive organs. If the ovaries or uterus are irradiated it will usually cause permanent infertility. The risk of infertility depends on the dose of radiation, age (the risk is higher the older you are), and if chemotherapy is combined with the radiotherapy. Targeting other organs in the pelvic area, also increases the risk of irreparable damage to the reproductive system. If the uterus is damaged by localised radiation, there is an increased risk of miscarriage during future pregnancies.
- Radiotherapy to the brain. This can also affect fertility if the pituitary gland is damaged. The pituitary gland normally releases gonadotropin hormones (LH and FSH), which stimulate the ovaries to release eggs. Damage to the gland can prevent normal egg release, meaning ovulation does not occur.
- Total body irradiation. This is usually given before bone marrow or stem cell transplant and will normally also cause permanent infertility.
Surgery
Surgery is used in cancer treatment to remove tumours and sometimes the surrounding tissues. It is fairly common for women with cancers of the uterus, fallopian tubes, ovaries, vagina and cervix to undergo surgery to remove the reproductive structures (hysterectomy, oophorectomy). Whilst this surgery can be lifesaving, it usually leads to complete infertility, which can be traumatic for younger women.
Where possible, for example, if the cancer is only affecting one ovary or fallopian tube, a surgeon may attempt ‘fertility conserving’ surgery. This would involve removing the affected ovary or fallopian tube, and leaving the other ovary, fallopian tube and the uterus. The remaining ovary will continue to function, releasing eggs and hormones, so there is still a chance of pregnancy.
A trachelectomy is a technique used to remove most of the cervix in cases of cervical cancer. Pregnancy is still possible, but the risk of miscarriage during subsequent pregnancies is increased.
The pituitary gland is vulnerable to damage following brain surgery. If there is a tumour in the surrounding area, the surgeon will usually endeavor to save the pituitary gland, but if damaged it will cause similar effects to those seen following radiation therapy.
Hormone Therapy
Some cancers are stimulated by, and grow rapidly in the presence of hormones. This is particularly common in some breast cancer cases, such as those that are oestrogen receptor positive (ER positive). When this happens, doctors will often prescribe drugs to reduce or suppress hormone production, examples include Goserelin and Tamoxifen. These drugs often cause periods to stop or become irregular. They also cause menopausal symptoms, such as hot flushes, difficulty sleeping, vaginal dryness and mood fluctuations.
Falling pregnant during hormone therapy is unlikely, but not impossible. As the drugs can be harmful to developing babies, it is recommended that additional contraception is used for the duration of the treatment. Unless the patient goes through the natural menopause whilst undergoing treatment, normal fertility is usually restored once drug treatment ceases. However, the duration of hormone therapy treatment may interfere with childbearing, as some women need to take hormone therapy drugs for up to 10 years.
Preserving fertility
In terms of cancer, even if the recommended treatment options are likely to cause infertility, there are options available to try and preserve fertility, including:
- Freezing embryos for In Vitro Fertilisation (IVF).
- Freezing eggs.
- Freezing ovarian tissue.
These must be done before starting treatment.
With IVF a woman gets fertility drugs to stimulate her ovaries to produce eggs. The doctors then collect the eggs and fertilise them using sperm (either belonging to her husband/partner or a donor) in a laboratory, creating embryos. The embryos are frozen until required, at which point they are transferred to the womb to grow and develop. It is a complicated process and does not always succeed.
Women can also freeze their unfertilised eggs if they do not currently have a partner, but this has a lower pregnancy rate than IVF.
Freezing ovarian tissue is another option. This involves removing ovarian tissue and freezing it before chemotherapy starts. The theory is that, once treatment is complete, the stored ovarian tissue can be transplanted back into the female’s body, restoring fertility. Freezing ovarian tissue is a relatively novel procedure that still requires optimisation.
In the case of radiotherapy to the pelvic area, it may be possible to move the ovaries out of the treatment area before radiotherapy begins. This is called ovarian transposition. Ovarian transposition can be used to prevent an early menopause and is one way of maintaining the viability of the ovarian eggs so that pregnancy after radiotherapy is possible.
These techniques are not always successful in preserving fertility, but can provide relief and hope at a time when it is most needed.
Causes of Female Infertility - Environmental/Lifestyle Factors
Nabta is reshaping women’s healthcare. We support women with their personal health journeys, from everyday wellbeing to the uniquely female experiences of fertility, pregnancy, and menopause.
Get in touch if you have any questions about this article or any aspect of women’s health. We’re here for you.
Sources:
- “How Cancer Treatment Can Affect Fertility .” Macmillan Cancer Support, 30 June 2016, www.macmillan.org.uk/information-and-support/coping/side-effects-and-symptoms/fertility-in-women/how-treatment-can-affect-fertility.html#45517.
- “How Chemotherapy Affects Women’s Fertility.” Cancer Research UK, www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/chemotherapy/fertility/women/how-chemotherapy-affects-fertility.
- “What Are Some Possible Causes of Female Infertility? .” National Institutes of Health, www.nichd.nih.gov/health/topics/infertility/conditioninfo/causes/causes-female.
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International Journal of Environmental Research and Public Health ([MDPI](https://www.mdpi.com/journal/ijerph)), 20(5), 3021.
Causes of Female Infertility – Autoimmune and Immune-Mediated Disorders
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Thus, women with the condition may want to consult a nutritionist prior to attempting to start a family. #### Auto-antibodies The production of [autoantibodies](https://nabtahealth.com/glossary/autoantibodies/) is central to autoimmune disease. One in five infertile couples are diagnosed with unexplained [infertility](https://nabtahealth.com/glossary/infertility/) (UI) in which they are unable to conceive with no obvious cause. [Autoantibodies](https://nabtahealth.com/glossary/autoantibodies/) have been found to account for some cases of UI, examples include: * Anti-[sperm](https://nabtahealth.com/glossary/sperm/) antibodies ([ASAs](https://nabtahealth.com/glossary/asas/)) * Antibodies against the [thyroid gland](https://nabtahealth.com/glossary/thyroid-gland/), or cellular components such as the nuclear membrane or the cell membrane (phospholipid) * Antiovarian antibodies. Anti-[sperm](https://nabtahealth.com/glossary/sperm/) antibodies ([ASAs](https://nabtahealth.com/glossary/asas/)) have been detected in the [cervical discharge](https://nabtahealth.com/cervical-discharge-through-the-menstrual-cycle/) of infertile women, as well as in the seminal fluid of their male partner. [ASAs](https://nabtahealth.com/glossary/asas/) bind to [](https://nabtahealth.com/everything-you-need-to-know-about-sperm/)[sperm](https://nabtahealth.com/glossary/sperm/) cells, causing them to stick together (agglutinate) resulting in [reduced movement](https://nabtahealth.com/low-sperm-motility-asthenozoospermia/) and, in many cases, reduced cervical penetration and inhibition of [implantation](https://nabtahealth.com/glossary/implantation/). However, further research is required on determining exactly how [ASAs](https://nabtahealth.com/glossary/asas/) affect fertility, as [ASAs](https://nabtahealth.com/glossary/asas/) have also been found in the cervical secretions of fertile women. The majority of studies assessing the relationship between [ASAs](https://nabtahealth.com/glossary/asas/) and [infertility](https://nabtahealth.com/glossary/infertility/) are old and have used outdated technologies which may result in false-positive results due to cross reactivity with other antibodies. The evidence of the effects of antibodies against thyroid, or cellular components such as the nuclear membrane or phospholipid and antiovarian antibodies on fertility, like [ASAs](https://nabtahealth.com/glossary/asas/) is conflicted and requires further research. Furthermore, how antibodies can cause [infertility](https://nabtahealth.com/glossary/infertility/) is not fully understood, and all studies suggesting a link are more about association with [autoantibodies](https://nabtahealth.com/glossary/autoantibodies/) rather than a cause. Anti-[oocyte](https://nabtahealth.com/glossary/oocyte/) antibodies also exist, but these seem to be a lot less common.Anti-ovarian antibodies have been detected in women with [](https://nabtahealth.com/causes-of-female-infertility-failure-to-ovulate)[POI](https://nabtahealth.com/glossary/poi/). They are associated with anti-follicle-stimulating hormone ([FSH](https://nabtahealth.com/glossary/fsh/)) antibodies. [FSH](https://nabtahealth.com/glossary/fsh/) is involved in regulating ovarian function. [Causes of Female](https://nabtahealth.com/causes-of-female-infertility-infection) [Infertility](https://nabtahealth.com/glossary/infertility/) – Infection ([PID](https://nabtahealth.com/glossary/pid/) and [HPV](https://nabtahealth.com/glossary/hpv/)) [Causes of Female](https://nabtahealth.com/causes-of-female-infertility-environmental-lifestyle-factors) [Infertility](https://nabtahealth.com/glossary/infertility/) – Environmental/Lifestyle Factors Nabta is reshaping women’s healthcare. We support women with their personal health journeys, from everyday wellbeing to the uniquely female experiences of fertility, pregnancy, and [menopause](https://nabtahealth.com/glossary/menopause/). Get in [touch](/cdn-cgi/l/email-protection#671e060b0b062709060513060f02060b130f4904080a) if you have any questions about this article or any aspect of women’s health. We’re here for you. **Sources:** * Brazdova, A, et al. “Immune Aspects of Female [Infertility](https://nabtahealth.com/glossary/infertility/).” International Journal of Fertility & Sterility , vol. 10, no. 1, 2016, pp. 1–10. * Domniz, N and Meirow, D, “Premature ovarian insufficiency and autoimmune diseases” Best Practice & Research Clinical Obstetrics & Gynaecology, vol 60, Oct 2019, pp 42-55. doi.org/10.1016/j.bpobgyn.2019.07.008. * Hickman, R A, and C Gordon. “Causes and Management of [Infertility](https://nabtahealth.com/glossary/infertility/) in Systemic [Lupus](https://nabtahealth.com/glossary/lupus/) Erythematosus .” Rheumatology, vol. 50, no. 9, Sept. 2011, pp. 1551–1558., doi:10.1093/rheumatology/ker105. * Khizroeva, J et al, “[Infertility](https://nabtahealth.com/glossary/infertility/) in women with systemic autoimmune diseases” Best Practice & Research Clinical Endocrinology & [Metabolism](https://nabtahealth.com/glossary/metabolism/), vol 33, Dec 2019, doi.org/10.1016/j.beem.2019.101369. * Kim, N Y et al. “Thyroid autoimmunity and its association with cellular and humoral immunity in women with reproductive failures.” American Journal of reproductive immunology, vol. 65, no. 1, Jan. 2011, pp. 78-87. doi: 10.1111/j.1600-0897.2010.00911.x. * Lebovic and Naz, “Premature ovarian failure: Think ‘autoimmune disorder’”, Sexuality, Reproduction & [Menopause](https://nabtahealth.com/glossary/menopause/), vol. 2, no. 4, Dec 2004, pp.230-233. https://doi.org/10.1016/j.sram.2004.11.010. * McCulloch, F. “Natural Treatments for Autoimmune [Infertility](https://nabtahealth.com/glossary/infertility/) Concerns.” American College for Advancement in Medicine, 29 Jan. 2014, [www.acam.org/blogpost/1092863/179527/Natural-Treatments-for-Autoimmune-](http://www.acam.org/blogpost/1092863/179527/Natural-Treatments-for-Autoimmune-Infertility-Concerns)[Infertility](https://nabtahealth.com/glossary/infertility/)\-Concerns. * Romitti, M et al. “Association between [PCOS](https://nabtahealth.com/glossary/pcos/) and autoimmune thyroid disease: a systematic review and meta-analysis.” Endocrine connections, vol 7, no. 11, Oct 2018, pp 1158-1167. doi: 10.1530/EC-18-0309. * Shigesi, N et al, “The association between [endometriosis](https://nabtahealth.com/glossary/endometriosis/) and autoimmune diseases: a systematic review and meta-analysis.” Human Reproduction Update, vol. 25, no. 4, Jul 2019, pp 486-503. doi: 10.1093/humupd/dmz014. * “What Are Some Possible Causes of Female [Infertility](https://nabtahealth.com/glossary/infertility/)? .” National Institutes of Health, [www.nichd.nih.gov/health/topics/](http://www.nichd.nih.gov/health/topics/infertility/conditioninfo/causes/causes-female)[infertility](https://nabtahealth.com/glossary/infertility/)/conditioninfo/causes/causes-female.
Will Taking the Pill Increase my Risk of Developing Cancer?
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Those on combined [oestrogen](https://nabtahealth.com/glossary/oestrogen/) plus progestin therapy have a higher breast cancer risk than those who take just [oestrogen](https://nabtahealth.com/glossary/oestrogen/). Thus, the mini pill should no longer be considered a safer contraceptive option for those with an elevated risk of developing breast cancer. * **Cervical cancer**. Taking the pill for five or more years is associated with a significantly increased risk of developing cervical cancer. The duration of use increases the risk, so that women who take the pill for 5 years have a 10% increased risk, but those who take it for longer, are more than 60% more likely to be diagnosed. Ten years after stopping the pill there is no increased risk of developing cervical cancer. One important thing to note is that as a risk, oral contraceptives will always be cofactors that interact with high risk [human papillomavirus](https://nabtahealth.com/when-should-i-get-a-pap-smear/) ([HPV](https://nabtahealth.com/glossary/hpv/)) strains to induce cervical carcinogenesis. This means that oral contraceptives in isolation are not a risk factor in women who are [HPV](https://nabtahealth.com/glossary/hpv/) negative; however, for those who are [HPV](https://nabtahealth.com/glossary/hpv/) positive, the pill can exacerbate the risk. Steroid hormone receptors (mainly [progesterone](https://nabtahealth.com/glossary/progesterone/)) are found in cervical tissue and are thought to enhance the expression of high risk [HPV](https://nabtahealth.com/glossary/hpv/), contributing to cancerous changes in the [cervix](https://nabtahealth.com/glossary/cervix/). **Conclusion: the pill and cancer** ----------------------------------- It is very difficult to state conclusively whether the pill should be used or avoided based on its associations with cancer. The net effect is likely to be positive, with one long-term, UK-based study finding that taking the pill resulted in a 12% reduction in overall cancer risk. It is also challenging to assess the absolute risk posed by oral contraceptive use. Cancer can have a long latency period, meaning the time between exposure to a particular risk factor and cancer diagnosis can span many years. Most women who develop cancer will have been exposed to multiple risk factors during their lifetimes, including [parity](https://nabtahealth.com/is-pregnancy-linked-to-developing-cervical-cancer/) (the number of times she has been pregnant and carried the baby to term), [obesity](https://nabtahealth.com/the-link-between-obesity-and-cancer-in-women/) and whether or not she has breastfed (breastfeeding can exert [protective effects](https://nabtahealth.com/benefits-of-breastfeeding-for-the-mother/)). Ascertaining how much of a role each of these factors plays in a later cancer diagnosis is likely to be extremely difficult. One final thing to consider is that the pill has changed in formulation over the decades since it was first utilised as a type of contraception. The specific synthetic hormones in use have changed, as has their concentration. Today, a triphasic pill is commonly used, whereby the hormone concentration changes across the month. This is designed to more closely mimic the normal ovulatory cycle. These different formulations will have differing risks and benefits. The consequence of this is that women who were prescribed the pill in its infancy, in the 1950s and 1960s should certainly not be compared to those taking it today in the 21st Century. Perhaps the advent of the mini pill came with initial optimism that the risks associated with the combined pill would be alleviated by removing the [oestrogen](https://nabtahealth.com/glossary/oestrogen/) component. Unfortunately, it appears that women taking this form of contraceptive have a comparable cancer risk to those taking the more commonly prescribed combined oral contraceptive pill. Nabta is reshaping women’s healthcare. We support women with their personal health journeys, from everyday wellbeing to the uniquely female experiences of fertility, pregnancy, and [menopause](https://nabtahealth.com/glossary/menopause/). Get in [touch](/cdn-cgi/l/email-protection#5f263e33333e1f313e3d2b3e373a3e332b37713c3032) if you have any questions about this article or any aspect of women’s health. We’re here for you. **Sources:** * Brynhildsen, Jan. “Combined Hormonal Contraceptives: Prescribing Patterns, Compliance, and Benefits versus Risks.” Therapeutic Advances in Drug Safety, vol. 5, no. 5, Oct. 2014, pp. 201–213., doi:10.1177/2042098614548857. * “Does the Contraceptive Pill Increase Cancer Risk?” Cancer Research UK, 4 Mar. 2019, [https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/hormones-and-cancer/does-the-contraceptive-pill-increase-cancer-risk](https://www.cancerresearchuk.org/about-cancer/causes-of-cancer/hormones-and-cancer/does-the-contraceptive-pill-increase-cancer-risk). * Gierisch, J. M., et al. “Oral Contraceptive Use and Risk of Breast, Cervical, Colorectal, and Endometrial Cancers: A Systematic Review.” Cancer Epidemiology Biomarkers & Prevention, vol. 22, no. 11, Nov. 2013, pp. 1931–1943., doi:10.1158/1055-9965.epi-13-0298. * Knowlden, Hilary A. “The Pill and Cancer: a Review of the Literature. A Case of Swings and Roundabouts?” Journal of Advanced Nursing, vol. 15, no. 9, Sept. 1990, pp. 1016–1020., doi:10.1111/j.1365-2648.1990.tb01981.x. * Li, Li, et al. “Association between Oral Contraceptive Use as a Risk Factor and Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.” Molecular and Clinical Oncology, vol. 7, no. 1, 12 May 2017, pp. 76–80., doi:10.3892/mco.2017.1259. * Murphy, Neil, et al. “Reproductive and Menstrual Factors and Colorectal Cancer Incidence in the Women’s Health Initiative Observational Study.” British Journal of Cancer, vol. 116, no. 1, 29 Nov. 2016, pp. 117–125., doi:10.1038/bjc.2016.345. * Mørch, L S, et al. “Contemporary Hormonal Contraception and the Risk of Breast Cancer.” New England Journal of Medicine, vol. 377, no. 23, 7 Dec. 2017, pp. 2228–2239., doi:10.1056/NEJMoa1700732. * “Oral Contraceptives (Birth Control Pills) and Cancer Risk.” National Cancer Institute, [https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet](https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/oral-contraceptives-fact-sheet). * Roura, Esther, et al. “The Influence of Hormonal Factors on the Risk of Developing Cervical Cancer and Pre-Cancer: Results from the EPIC Cohort.” Plos One, vol. 11, no. 1, 25 Jan. 2016, doi:10.1371/journal.pone.0147029. * Schairer, Catherine. “Menopausal Estrogen and Estrogen-Progestin Replacement Therapy and Breast Cancer Risk.” Jama, vol. 283, no. 4, 26 Jan. 2000, pp. 485–491., doi:10.1001/jama.283.4.485. * Smith, Jennifer S, et al. “Cervical Cancer and Use of Hormonal Contraceptives: a Systematic Review.” The Lancet, vol. 361, no. 9364, 5 Apr. 2003, pp. 1159–1167., doi:10.1016/s0140-6736(03)12949-2. * Soroush, Ali, et al. “The Role of Oral Contraceptive Pills on Increased Risk of Breast Cancer in Iranian Populations: A Meta-Analysis.” Journal of Cancer Prevention, vol. 21, no. 4, 30 Dec. 2016, pp. 294–301., doi:10.15430/jcp.2016.21.4.294.