Guideline sources The following summarized guidelines for the evaluation and management of fertility preservation in patients with cancer are prepared by our editorial team based on guidelines from the Society of Obstetricians and Gynaecologists of Canada (SOGC 2023), the European Society of Human Reproduction and Embryology (ESHRE 2020), the European Society of Medical Oncology (ESMO 2020), the American Society of Clinical Oncology (ASCO 2018), and the Spanish Association of Medical Oncology (SEOM 2016). 1 2 3 4 5 6 6 7 8 Definition Fertility preservation for patients with cancer is a therapeutic option designed to maximize the reproductive future of oncological patients, including oocyte/embryo cryopreservation for female patients and sperm cryopreservation for male patients. 6 Epidemiology Fertility preservation for patients with cancer is for female and male cancer patients at risk for infertility due to anticancer treatment. 7 Disease course Fertility preservation techniques for females include embryo cryopreservation, oocyte cryopreservation, ovarian tissue cryopreservation (for pediatric and patients with hormone- dependent diseases), ovarian transposition (oophoropexy), fertoprotective adjuvant agents. Emerging techniques include activation of ovarian follicles, in vitro follicle culture, artificial https://web.pathway.md/diseases/recmUDrzahn15zOfw 1/7 6/29/23, 4:03 AM Fertility preservation in patients with cancer Pathway ovaries, and specific target tissue drugs (nanoparticles, novel fertoprotective agents). Fertility preservation techniques for males include cryopreservation of spermatozoa and cryopreservation of SSC in prepubertal children. 6 Prognosis and risk of recurrence Fertility preservation for patients with cancer is not associated with increased mortality. 8 Guidelines 1. Classification and risk stratification Risk assessment: As per ESHRE 2020 guidelines: Obtain an individual assessment of the indications and risks before fertility preservation interventions. Ensure a multidisciplinary team approach for an accurate assessment of risks. B Assess the risk of gonadotoxicity in all patients undergoing gonadotoxic treatments, taking into consideration the characteristics of the proposed treatment, the patient, and the disease. B As per ESMO 2020 guidelines, view all patients as being at potential risk of developing treatment-related gonadotoxicity, as there is no absolute threshold of exposure to anticancer therapies determining gonadal failure and infertility. B 2. Diagnostic investigations Ovarian reserve testing: obtain antral follicle count or anti-M llerian hormone level measurement for predicting high and low responses to ovarian stimulation. B Show 4 more 3. Medical management Setting of care: As per ESMO 2020 guidelines: Refer all patients with a potential interest in fertility preservation to an appropriate fertility specialist/unit. B Offer fertility preservation strategies preferably at the time of diagnosis before treatment initiation. B As per ASCO 2018 guidelines: Refer patients expressing interest in fertility preservation, as well as ambivalent patients, to a reproductive specialist. E Refer patients distressed about potential infertility to a psychosocial provider. E Fertility preservation in females, oocyte/embryo cryopreservation: https://web.pathway.md/diseases/recmUDrzahn15zOfw 2/7 6/29/23, 4:03 AM Fertility preservation in patients with cancer Pathway As per ESHRE 2020 guidelines: Offer oocyte and embryo cryopreservation as options for fertility preservation. B Offer unfertilized oocyte cryopreservation or both embryo and oocyte cryopreservation in patients having a partner. B Inform patients about the following: accurate, center-specific expertise and live birth rates with oocyte and embryo cryopreservation success rates after oocyte and embryo cryopreservation at the time of cancer diagnosis may be lower than in patients without cancer risk of losing reproductive autonomy and possible issues with ownership of stored embryos. B As per ESMO 2020 guidelines, consider offering cryopreservation of oocytes or embryos before initiating anticancer therapies if a 2-week treatment delay is feasible. B As per ASCO 2018 guidelines, consider offering cryopreservation of unfertilized oocytes as an option, particularly in patients not having a male partner, not wishing to use donor sperm, or having religious or ethical objections to embryo cryopreservation. E Show 2 more As per SEOM 2016 guidelines: Recognize that the major limitation of the embryo and mature oocyte cryopreservation is the time to complete ovarian stimulation. Recognize that immature oocyte cryopreservation is not as successful as cryopreserving oocytes or embryos that have matured in vivo and is considered experimental. Offer oocyte cryopreservation as the preferred option when embryo cryopreservation is not possible, particularly in patients without a male partner or having religious or ethical objections to embryo freezing. B Perform oocyte cryopreservation either by conventional slow freezing or by vitrification. Fertility preservation in females, ovarian tissue cryopreservation: As per ESHRE 2020 guidelines, offer ovarian tissue cryopreservation in patients undergoing moderate/high-risk gonadotoxic treatment where oocyte/embryo cryopreservation is not feasible or per patient preference. B Show 7 more As per ESMO 2020 guidelines, consider offering ovarian tissue cryopreservation as an alternative procedure when oocyte/embryo cryopreservation is not feasible. B Show 3 more As per ASCO 2018 guidelines, consider offering ovarian tissue cryopreservation for future transplantation, recognizing that this method does not require ovarian stimulation or sexual maturity and restores global ovarian function. E As per SEOM 2016 guidelines, harvest and freeze ovarian tissue for ovarian tissue cryopreservation, allowing the preservation of oocytes within primordial follicles, recognizing that this procedure allows immediate initiation of cancer treatment as it does not require prior ovarian stimulation or sperm donation. B Fertility preservation in females (ovarian tissue retransplantation): ensure a multidisciplinary approach for the decision to perform ovarian tissue transplantation in patients https://web.pathway.md/diseases/recmUDrzahn15zOfw 3/7 6/29/23, 4:03 AM Fertility preservation in patients with cancer Pathway with cancer. B Show 8 more Fertility preservation in females, ovarian suppression: As per ESHRE 2020 guidelines, offer GnRH agonists during chemotherapy as an option for ovarian function protection in premenopausal patients with breast cancer. A Do not offer GnRH agonists during chemotherapy instead of cryopreservation techniques. B Show 2 more As per ESMO 2020 guidelines, offer temporary ovarian suppression with a GnRH agonist for ovarian function preservation, irrespective of tumor subtype, in premenopausal patients with breast cancer undergoing (neo)adjuvant chemotherapy. A Show 2 more As per ASCO 2018 guidelines, consider offering GnRH agonists to reduce the likelihood of chemotherapy-induced ovarian insufficiency when proven fertility preservation methods (such as oocyte, embryo, or ovarian tissue cryopreservation) are not feasible, and in young patients with breast cancer. E As per SEOM 2016 guidelines, consider offering GnRH agonists as an option in patients with early-stage receptor-negative breast cancer if embryo or oocyte cryopreservation is not feasible. Do not offer GnRH agonists to preserve fertility in patients with other types of cancer. C Fertility preservation in females (aromatase inhibitors): consider offering aromatase inhibitors to prevent supraphysiological estrogen concentrations during ovarian stimulation in female patients with estrogen-sensitive tumors. C Fertility preservation in females, ovarian transposition: As per SOGC 2023 guidelines: Consider performing ovarian transposition to improve post-treatment ovarian function in patients undergoing pelvic radiotherapy. C Consider referring patients to a reproductive endocrinologist and possible egg/embryo cryopreservation before performing ovarian transposition pelvic radiation. Recognize that transvaginal ovarian access for IVF is difficult even though unassisted pregnancies and live births are possible after ovarian transposition. Recognize that there is a high probability that pelvic radiation will result in a uterine environment incapable of carrying a pregnancy, necessitating a gestational carrier. C As per ESHRE 2020 guidelines: Consider performing ovarian transposition to prevent premature ovarian insufficiency when pelvic radiotherapy without chemotherapy is planned. C Do not perform ovarian transposition in patients with a reduced ovarian reserve and patients at risk of having ovarian metastases. D As per ESMO 2020 guidelines: Consider performing ovarian transposition to preserve ovarian function in 40 years old patients with an indication for pelvic radiotherapy. B Perform ovarian transposition by an experienced laparoscopist to minimize complications and maximize the chances of ovarian function preservation. B https://web.pathway.md/diseases/recmUDrzahn15zOfw 4/7 6/29/23, 4:03 AM Fertility preservation in patients with cancer Pathway As per ASCO 2018 guidelines, consider performing ovarian transposition (oophoropexy) when pelvic irradiation is performed as a cancer treatment. E Show 2 more Fertility preservation in females (in vitro oocyte maturation): Recognize that in vitro oocyte maturation is an innovative fertility preservation procedure B and requires specific expertise. Offer in vitro oocyte maturation only when oocyte cryopreservation is required but ovarian stimulation is not feasible. B Consider offering in vitro oocyte maturation after ex vivo extraction as an experimental procedure. C Fertility preservation in females (gonadal shielding): consider using gonadal shielding as an alternative strategy to ovarian transposition, not requiring surgical intervention. C Fertility preservation in males, sperm cryopreservation: As per ESMO 2020 guidelines, offer sperm cryopreservation before initiating anticancer treatments (chemotherapy, radiotherapy, or surgery) as a standard of care in any male patient with cancer at risk of infertility. B As per ASCO 2018 guidelines, offer sperm banking in postpubertal male patients receiving cancer treatment. E Show 2 more As per SEOM 2016 guidelines, offer sperm cryopreservation with 1-3 samples, B collected before initiating treatment. Show 2 more Fertility preservation in males, testicular tissue cryopreservation: As per ASCO 2018 guidelines, consider offering testicular tissue cryopreservation and reimplantation or grafting of human testicular tissue only as part of clinical trials or approved experimental protocols. E As per SEOM 2016 guidelines, consider offering testicular tissue or spermatogonial cryopreservation and reimplantation or grafting of human testicular tissue in prepubertal patients. Fertility preservation in males, hormonal gonadoprotection: As per ESMO 2020 guidelines, do not offer medical gonadoprotection (GnRH agonist with or without androgens, antiandrogens, or progestins) for fertility preservation in male patients with cancer. D As per ASCO 2018 guidelines, do not offer hormonal therapy as a means to preserve fertility in male patients with cancer. D As per SEOM 2016 guidelines, do not offer hormonal therapy for fertility preservation in male patients with cancer. D Fertility preservation in males (gonadal shielding): shield or remove the testes from the radiation field whenever possible to reduce radiotherapy exposure and reduce the risk of infertility. B 4. Specific circumstances https://web.pathway.md/diseases/recmUDrzahn15zOfw 5/7 6/29/23, 4:03 AM Fertility preservation in patients with cancer Pathway Pediatric patients: As per ASCO 2018 guidelines: Consider offering established methods of fertility preservation, such as sperm or oocyte cryopreservation, in postpubertal minor pediatric patients, with appropriate patient assent and parent or guardian consent. E Recognize that the only available fertility preservation options for prepubertal minor pediatric patients are ovarian and testicular tissue cryopreservation, which are considered experimental. E As per SEOM 2016 guidelines, recognize that there are no reports of live births after ovarian cortical tissue cryopreserved prepubertally and reimplanted at a later date, primarily because of the young age of the study participants. B Show 2 more Patients with gynecologic malignancies: consider performing ovarian cystectomy as a fertility-sparing treatment option in patients with early-stage ovarian cancer. E Show 2 more Patients with hereditary cancer syndromes: offer sperm cryopreservation and oocyte or embryo cryopreservation as the preferred options in newly diagnosed patients with hereditary cancer syndromes interested in fertility preservation. B Show 3 more Patients with premature ovarian insufficiency: do not offer fertility preservation in patients with overt premature ovarian insufficiency. D 5. Patient education General counseling: As per ESHRE 2020 guidelines, counsel patients with cancer eligible for fertility preservation regarding the following: impact of cancer, other diseases and their treatments on reproductive function impact of cancer, other diseases and their treatment on fertility fertility preservation options issues related to cryopreservation storage after fertility preservation infertility and fertility treatments pregnancy after gonadotoxic treatment or underlying condition other childbearing and parenting options. B Show 3 more As per ESMO 2020 guidelines, provide complete oncofertility counseling as early as possible in the treatment planning process in all patients of reproductive age with cancer, irrespective of the type and stage of the disease. B Show 2 more As per ASCO 2018 guidelines: Address the possibility of infertility in adult and pediatric patients with cancer as early as possible before treatment initiation. E https://web.pathway.md/diseases/recmUDrzahn15zOfw 6/7 6/29/23, 4:03 AM Fertility preservation in patients with cancer Pathway Encourage patients to participate in registries and clinical studies, if available, to help define the safety and efficacy of interventions and strategies to preserve fertility in patients with cancer. E As per SEOM 2016 guidelines, discuss the risk of infertility before initiating cancer treatment in patients of reproductive age. A 6. Follow-up and surveillance Pregnancy after cancer treatment: As per ESHRE 2020 guidelines, assess fitness for pregnancy, taking into account treatment late effects, the age of the patient, and the interval since treatment before the use of stored material. B Show 10 more As per ESMO 2020 guidelines, take into consideration patient/couple- and disease/treatment-related factors when counseling adult cancer survivors regarding the feasibility and safety of post-treatment pregnancies. B Show 4 more References 1. ESHRE Guideline Group on Female Fertility Preservation, Richard A Anderson, Fr d ric Amant et al. ESHRE guideline: female fertility preservation. Hum Reprod Open. 2020 Nov 14;2020 4):hoaa052. Open 2. M Mu oz, A Santaballa, M A Segu et al. SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients 2016 . Clin Transl Oncol. 2016 Dec;18 12 1229 1236. Open 3. Kutluk Oktay, Brittany E Harvey, Ann H Partridge et al. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018 Jul 1;36 19 1994 2001. Open 4. M Lambertini, F A Peccatori, I Demeestere et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2020 Dec;31 12 1664 1678. Open 5. Tarek Motan, Roland Antaki, Jinglan Han et al. Guideline No. 435 Minimally Invasive Surgery in Fertility Therapy. J Obstet Gynaecol Can. 2023 Apr;45 4 273 282.e2. Open 6. Sofia Del-Pozo-Lerida, Cristina Salvador, Fina Martinez-Soler et al. Preservation of fertility in patients with cancer Review). 2019 May;41 5 2607 2614.2019 May;41 5 2607 2614. Open 7. Kutluk Oktay, Brittany E Harvey, Ann H Partridge et al. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018 Jul 1;36 19 1994 2001. Open 8. Matteo Lambertini, Lucia Del Mastro, Maria C Pescio et al. Cancer and fertility preservation: international recommendations from an expert meeting. 2016 Jan 4;14 1.2016 Jan 4;14 1. Open 9. Matteo Lambertini, Lucia Del Mastro, Maria C. Pescio et al. Cancer and fertility preservation: international recommendations from an expert meeting. BMC Med. 2016; 14 1. Open 10. Sof a Del-Pozo-L rida, Cristina Salvador, Fina Mart nez-Soler et al. Preservation of fertility in patients with cancer Review). Oncol Rep. 2019 May;41 5 2607 2614. Open https://web.pathway.md/diseases/recmUDrzahn15zOfw 7/7