Clare Meernik
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Fatigue. Hair loss. Loss of appetite, nausea, or vomiting. Constipation or diarrhea. Pain. Easy bruising. Bleeding. All common side effects of chemotherapy. Now, imagine you are a 25-year old woman, newly diagnosed with cancer–unsure if and when you may want to have children–and your oncologist tells you about another potential side effect: infertility.
Many young women diagnosed with cancer are informed that it may not be possible to have biological children in the future due to their cancer treatment. Females are born with a fixed number of primordial follicles–the “vesicles” that contain oocytes, or immature eggs. This follicle pool naturally declines with age, and when depleted below a certain threshold, will trigger the onset of menopause–signifying the loss of reproductive potential.
Pelvic radiation and certain types of chemotherapy (especially alkylating-agent based drugs that work by damaging the DNA of cells) can accelerate the depletion of primordial follicles, resulting in immediate menopause (also referred to as acute ovarian failure) or early menopause that occurs at younger than 40 years old (also referred to as premature ovarian failure or premature ovarian insufficiency). Cancer treatments like radiation or surgery can also cause functional damage to reproductive organs–like the ovaries or fallopian tubes–compromising the likelihood of becoming pregnant in the future.
So, you are that 25-year old woman, told that you have cancer and that you may never be able to have children. But you are told that you can freeze your eggs or embryos prior to fertility-impairing cancer treatment. Also known as oocyte or embryo cryopreservation, these are established methods for reproductive-age women to maintain their ability to have biological children in the future. This process generally involves stimulating the ovaries with hormones called gonadotropins to develop follicles and the oocytes within them, retrieving mature oocytes, and freezing those oocytes or fertilizing them with sperm and freezing the resulting embryos to be stored for future transfer to the woman.
But at least three major barriers stand in the way of many young women accessing and utilizing these fertility preservation methods. First is the lack of knowledge about how cancer treatment may impact their fertility and what they can do about it. National guidelines issued by organizations including the American Society of Clinical Oncology and the American Society for Reproductive Medicine advise clinicians to have these types of discussions with their reproductive-age cancer patients. Despite the guidelines, less than half of patients in a recent national assessment received fertility counseling prior to chemotherapy. The second barrier is the potential delay to initiating cancer treatment. Oocyte or embryo cryopreservation can take 2-6 weeks–that delay may not be possible for women with certain cancer types, such as hematologic malignancies, which often necessitate immediate treatment initiation. And the third barrier is the prohibitive financial burden associated with freezing one’s eggs or embryos. Only 10 states currently mandate fertility preservation insurance coverage for women facing cancer treatment-related fertility risks. Cryopreservation can cost upwards of $15,000, with additional costs for storage and eventual use to attempt pregnancy. Without insurance coverage, these costs are largely borne out-of-pocket by patients.
Research and policy initiatives are ongoing to lower the risk of treatment-related infertility and increase access to fertility preservation procedures. Strategies that reduce the toxic effect of chemotherapy drugs on the ovaries are being developed; ovarian tissue cryopreservation with later reimplantation provides a recently established method of fertility preservation for prepubertal females who do not have the option to freeze eggs or embryos; ovarian stimulation protocols are now available that can be initiated at any point during a woman’s menstrual cycle, minimizing delay to cancer treatment initiation; and there is a growing push at the federal and state level for legislation to mandate fertility preservation insurance coverage for young people with cancer who face fertility-compromising treatment. It is the hope that continued collaboration between researchers, clinicians, reproductive scientists, and policy advocates, among others, will limit the gonadotoxicity of cancer treatments and also expand fertility preservation options and accessibility for all young cancer survivors.
Edited by MaryAnn Bowyer
Figure adapted from Anderson et al. 2015
References
Anderson RA, Mitchell RT, Kelsey TW, Spears N, Telfer EE, Wallace WHB. Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults. Lancet Diabetes Endocrinol. 2015;3(7):556-567. doi:10.1016/S2213-8587(15)00039-X
Donnez J, Dolmans M-M. Fertility preservation in women. N Engl J Med. 2017;377(17):1657-1665. doi:10.1056/NEJMra1614676.
Oktay K, Harvey BE, Partridge AH, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(19):1994-2001. doi:10.1200/JCO.2018.78.1914.
Patel P, Kohn TP, Cohen J, Shiff B, Kohn J, Ramasamy R. Evaluation of reported fertility preservation counseling before chemotherapy using the quality oncology practice initiative survey. JAMA Netw Open. 2020;3(7):e2010806. doi:10.1001/jamanetworkopen.2020.10806
Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019;112(6):1022-1033. doi:10.1016/j.fertnstert.2019.09.013.
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