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Recent Advances in Fertility Preservation and Counseling for Reproductive-Aged Women with Colorectal Cancer: a Systematic Review Lisa M

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Recent Advances in Fertility Preservation and Counseling for Reproductive-Aged Women with Colorectal Cancer: a Systematic Review Lisa M CURRENT STATUS REVIEWS Recent Advances in Fertility Preservation and Counseling for Reproductive-Aged Women with Colorectal Cancer: A Systematic Review Lisa M. Shandley, M.D., M.Sc.• Laurie J. McKenzie, M.D. Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia BACKGROUND: The incidence of colorectal cancer RESULTS: There are limited data regarding the impact among reproductive-aged women is increasing. Concerns of colorectal surgery on fertility. The gonadotoxic effects regarding future fertility are secondary only to concerns of chemotherapy on reproductive capacity depend regarding survival and may significantly impact quality on age at the time of chemotherapy administration, of life among reproductive-aged female cancer survivors. cumulative chemotherapy, radiation dose, type of agent, Fertility preservation counseling reduces long-term regret and baseline fertility status. Chemotherapy-induced risks and dissatisfaction among cancer survivors. Health care for colorectal cancers are considered low to moderate, providers counseling patients with colorectal cancer must whereas pelvic radiation with a dose of 45 to 50 Gray understand the impact of cancer treatment on future induces premature menopause in greater than 90% of reproductive potential. patients. Ovarian transposition may reduce but not eliminate the damaging effect of radiation on the ovaries. OBJECTIVE: This review aims to examine the effects that Embryo and oocyte cryopreservation are considered colorectal cancer treatments have on female fertility and standard of care for women desiring fertility preservation, summarize existing and emerging options for fertility with oocyte cryopreservation no longer being considered preservation. experimental. Ovarian tissue cryopreservation remains DATA SOURCES: EMBASE, National Library of Medicine experimental but may be an option for select patients. (MEDLINE)/PubMed, Cochrane Review Library were the The use of gonadotropin-releasing hormone agonists data sources for this review. remains controversial and has not been definitively shown to preserve fertility. STUDY SELECTION: A systematic literature review was performed using exploded MeSH terms to identify LIMITATIONS: The limitations of this review are the lack articles examining the effect of surgery, chemotherapy, of randomized controlled trials and high-quality studies, and radiation, as well as fertility preservation options for as well as the small sample sizes and the use of surrogate colorectal cancer on female fertility. Relevant studies were fertility markers. included. CONCLUSION: Reproductive-aged women with colorectal cancer benefit from fertility preservation counseling MAIN OUTCOME MEASURES: The primary outcome was before the initiation of cancer treatment. the effect of colorectal cancer treatment on fertility. KEY WORDS: Chemotherapy; Colectomy; Colorectal Funding/Support: None reported. cancer/neoplasm; Embryo cryopreservation; Fertility; Financial Disclosure: None reported. Fertility preservation; Infertility; Oncofertility; Oocyte cryopreservation; Ovarian tissue cryopreservation; Correspondence: Lisa Shandley, M.D., M.Sc., Emory Reproductive Ovarian transposition; Pelvic radiation. Center, 550 Peachtree St NE, Suite 1800, Atlanta, GA 30308. E-mail: Lisa. [email protected] t is estimated that 67,100 women will be diagnosed 1 Dis Colon Rectum 2019; 62: 762–771 with colorectal cancer (CRC) in 2019, making it the DOI: 10.1097/DCR.0000000000001351 Ithird most common cancer diagnosed in women an- © The ASCRS 2019 nually. Although the incidence of CRC overall is decreas- 762 DISEASES OF THE COLON & RECTUM VOLUME 62: 6 (2019) Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited. DISEASES OF THE COLON & RECTUM VOLUME 62: 6 (2019) 763 ing because of increased screening and surveillance, the treatments for CRC on female fertility and to summarize data from 2005 to 2014 indicate that the incidence among existing and emerging options for fertility preservation. those younger than 55 years of age is increasing.1 The Sur- veillance, Epidemiology, and End Results Registry demon- strates a 51% increase in CRC since 1994 in those aged MATERIALS AND METHODS 20 to 49, with 6650 women younger than 50 diagnosed A systematic review of the literature was performed to i- 2 with CRC in 2017. Younger patients with CRC commonly dentify articles examining the effect surgery, chemother- 3 present with more advanced disease at diagnosis. Fortu- apy, and radiation, as well as fertility preservation options, nately, the 5-year survival rate from CRC is improving, for CRC on female fertility. Literature repositories re- with nearly 65% of those diagnosed with CRC surviving viewed included EMBASE, the National Library of Med- 4 at least 5 years from diagnosis. icine (MEDLINE)/PubMed, and the Cochrane Review As survival rates improve, there is an increased focus Library. Exploding MeSH terms and combinations thereof on the complex issues surrounding cancer survivorship, were used, including: colorectal neoplasms, colorectal sur- in particular, for younger women of reproductive age. gery, colectomy, laparoscopy, chemotherapy, radiation, Among young women diagnosed with cancer, concerns fertility, fertility preservation, infertility, ovarian trans- regarding future fertility are secondary only to concerns 5,6 position, uterine transposition, oocyte cryopreservation, regarding survival. One study found that, among child- ovarian reserve testing, embryo preservation, gonadotro- less cancer survivors, over 75% endorsed wanting children pin-releasing hormone, pregnancy, and birth outcomes. in the future, yet only 6% had undergone infertility treat- 7 Citations from the articles found through search terms ment. Another study found that among those with GI were examined for additional relevant articles. cancers, including colorectal, over half desired a(nother) The search was limited to the English language. In- child after treatment.8 Guidelines from the American Soci- cluded studies were limited to those involving primary ety of Clinical Oncology and American Society for Repro- data collection (randomized-controlled trials, cohort ductive Medicine state that health care providers should studies, case-control studies, case series or reports) or re- discuss the possibility of infertility and fertility preserva- view articles (systematic reviews, meta-analyses). tion options with all reproductive-age patients diagnosed with cancer.9,10 Although the majority of men diagnosed with cancer receive information regarding treatment im- RESULTS pact on fertility, 40% to 62% of reproductive-age women diagnosed with cancer have reported not receiving fer- Counseling tility counseling at diagnosis or report unmet fertility When caring for a reproductive-aged female patient with needs.11–14 For individuals with newly diagnosed CRC, a a new diagnosis of CRC, a multidisciplinary approach is i- fertility discussion was documented with only 33.9% of deal to balance both the need for urgent initiation of treat- patients.15 One qualitative study exploring survivor pref- ment and the patient’s potential desire for future fertility. erence surrounding fertility concerns asked women how Gamete cryopreservation is the first-line approach for fer- they would like to learn about fertility issues; one identi- tility preservation; however, it necessitates an approximate fied theme was that survivors wanted their doctors or an- 2-week delay in initiation of cancer therapy. Oocyte and other health care provider to initiate a discussion about embryo cryopreservation are not recommended during their options.16 Unaddressed fertility concerns may sig- chemotherapy because of the low yield of oocytes and the nificantly impact quality of life among reproductive-aged potential increased risk of birth defects.21,22 female cancer survivors.12 Receipt of counseling regarding Before the initiation of cancer therapy, obtaining a fertility preservation has been shown to reduce long-term baseline fertility evaluation may be useful. Ovarian reserve regret and dissatisfaction among cancer survivors, and is best measured in this population via anti-Müllerian may be associated with both improved physical and psy- hormone (AMH) testing. AMH is a glycoprotein prod- chological quality of life.8,17,18 uct of small antral and preantral follicles and estimates an Treatment for CRC often includes a mix of surgery, individual’s ovarian reserve.23,24 Anti-Müllerian hormone radiation therapy, and chemotherapy.19 Various treatment may also be utilized as a marker of ovarian recovery fol- modalities appear to have a differential effect on fertility.20 lowing the insult of gonadotoxic agents.24,25 Individuals Other factors, such as age at the time of cancer treatment, with higher pretreatment AMH values may be more likely cumulative chemotherapy or radiation dosing, and the in- to regain ovarian function following cancer treatment.25–28 dividual’s baseline fertility status, will affect future repro- An AMH greater than 1.0 ng/mL in an adult female pa- ductive capacity. It is essential that health care providers tient indicates good ovarian reserve, whereas values less counseling patients with CRC have an understanding of than 1.0 ng/mL suggest a suboptimal ovarian reserve. the impact of cancer treatment on future reproductive po- There is scant research on pregnancy outcomes, par-
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