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Fertility Preservation for Pediatric and Adolescent Patients with Cancer: Medical and Ethical Considerations Sigal Klipstein, MD, FACOG,A,B Mary E

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Fertility Preservation for Pediatric and Adolescent Patients with Cancer: Medical and Ethical Considerations Sigal Klipstein, MD, FACOG,A,B Mary E CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care Fertility Preservation for Pediatric and Adolescent Patients With Cancer: Medical and Ethical Considerations Sigal Klipstein, MD, FACOG,a,b Mary E. Fallat, MD, FAAP,c Stephanie Savelli, MD, FAAP,d COMMITTEE ON BIOETHICS, SECTION ON HEMATOLOGY/ONCOLOGY, SECTION ON SURGERY Many cancers presenting in children and adolescents are curable with abstract surgery, chemotherapy, and/or radiotherapy. Potential adverse consequences of treatment include sterility, infertility, or subfertility as a result of gonad aDepartment of Obstetrics and Gynecology, Pritzker School of Medicine, removal, damage to germ cells as a result of adjuvant therapy, or damage to University of Chicago, Chicago, Illinois; bInVia Fertility Specialists, c the pituitary and hypothalamus or uterus as a result of irradiation. In recent Chicago, Illinois; Division of Pediatric Surgery, Hiram C. Polk Jr MD Department of Surgery, University of Louisville, Louisville, Kentucky; years, treatment of solid tumors and hematologic malignancies has been and dDivision of Pediatric Hematology/Oncology, Akron Children’s modified in an attempt to reduce damage to the gonadal axis. Simultaneously, Hospital, Akron, Ohio advances in assisted reproductive technology have led to new possibilities for Clinical reports from the American Academy of Pediatrics benefit from the prevention and treatment of infertility. This clinical report reviews the expertise and resources of liaisons and internal (AAP) and external reviewers. However, clinical reports from the American Academy of medical aspects and ethical considerations that arise when considering Pediatrics may not reflect the views of the liaisons or the fertility preservation in pediatric and adolescent patients with cancer. organizations or government agencies that they represent. Dr Fallat conceptualized the initial manuscript and drafted, reviewed, and revised the updated manuscript; Drs Klipstein and Savelli drafted, reviewed, and revised the updated manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. This document is copyrighted INTRODUCTION and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with Childhood cancer affects 1 of every 285 children younger than 20 years in the American Academy of Pediatrics. Any conflicts have been resolved the United States. Because of advances in treatment, survival has steadily through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any increased since the 1970s. With increasing survival rates, there are commercial involvement in the development of the content of this currently more than 375 000 survivors of childhood cancer in the United publication. 1,2 States, with 70% of them being 20 years or older. Improvements in The guidance in this report does not indicate an exclusive course of prognosis and survival have been observed for many childhood cancers, treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. including hematologic malignancies, Wilms tumor, malignant bone tumors, All clinical reports from the American Academy of Pediatrics and rhabdomyosarcomas. The relative 5-year survival rate for all fi 2 automatically expire 5 years after publication unless reaf rmed, childhood cancers combined is 83.8%. revised, or retired at or before that time. With the improved survival rate of children affected by childhood cancer DOI: https://doi.org/10.1542/peds.2019-3994 has come a growing population of adult survivors of childhood cancer who are or will be interested in having children. Past and contemporary To cite: Klipstein S, Fallat ME, Savelli S, AAP COMMITTEE ON treatments for childhood cancer, including chemotherapy, radiotherapy, BIOETHICS, AAP SECTION ON HEMATOLOGY/ONCOLOGY, AAP and hematopoietic stem cell transplant, can affect future fertility. In the SECTION ON SURGERY. Fertility Preservation for Pediatric current era, many children and adolescents who present with a new and Adolescent Patients With Cancer: Medical and Ethical Considerations. Pediatrics. 2020;145(3):e20193994 cancer diagnosis can benefit from fertility-preserving modalities initiated Downloaded from www.aappublications.org/news by guest on September 29, 2021 PEDIATRICS Volume 145, number 3, March 2020:e20193994 FROM THE AMERICAN ACADEMY OF PEDIATRICS before cancer treatment. Individuals or other diseases requiring treatment pregnancy after 12 months or more of whose previous treatment of with gonadotoxic therapies to regular unprotected intercourse. childhood cancer led to infertility or understand the potential deleterious Earlier evaluation and treatment may sterility can often benefit from effects of the various treatments on be justified on the basis of medical fertility treatment options such as egg male and female fertility and to be history, such as anovulation or and sperm donation and gestational familiar with the American Society of erectile dysfunction. For women surrogacy. Clinical Oncology (ASCO) guidelines 35 years and older, a fertility for fertility preservation in children. evaluation is recommended after fi Although not speci cally addressed in Recognizing the risks associated with 6 months of unsuccessful attempts at this report, the same strategies of both radiation and chemotherapy, the conception.4 Although fertility fertility preservation apply to ASCO recommends that oncologists declines with age for both men and children facing gonadotoxic therapies (1) use established methods of women, this decline is much more for treatment of nonmalignant fertility preservation (semen profound in women. At age 40, half of diseases such as juvenile idiopathic cryopreservation and oocyte women will have trouble conceiving. arthritis and Fanconi anemia. cryopreservation) for postpubertal If in vitro fertilization (IVF) is Infertility resulting from the minor children, with patient assent as required, the chance of pregnancy per treatment of differences of sexual appropriate, and parent or guardian cycle is only 13.9% in women at age development and as a result of consent; (2) present information on 40 and under and 4% in women older hormonal or surgical gender- additional methods that are available than 42 years.5 For men at age 45, the fi af rming therapies for transgender for children but are still chance of achieving a pregnancy is individuals are beyond the scope of investigational; and (3) refer for much higher, and for these older men, this document. experimental protocols when the age of their female partner is the available.3 Establishing relationships most significant determinant of Although this document focuses on 6 adolescents and young adults under with centers and physicians who have outcome. The risk of infertility after the age of 18 years, many individuals expertise in counseling and treating cancer treatment depends on the type fi fi who received a cancer diagnosis in children who may bene t from of malignancy and its speci c childhood continue to be seen by fertility preservation will help treatment as well as the age of the their pediatric providers well into oncologists better streamline care individual both at the time of for their patients who are interested diagnosis and at the time that they adulthood. As such, these guidelines 7 are generalizable beyond the age of in fertility preservation. Oncologists wish to initiate a pregnancy. In men, majority and apply to decision- can refer families for consultation treatments can lead to a complete making for adult survivors of to discuss both the effects of therapy absence of spermatogenesis, childhood cancers as well. Complex and potential fertility preservation a decreased sperm count, or sexual ethical considerations arise when options in a timely manner, as dysfunction. In women, there can be counseling families confronting long as any delay will not negatively a complete depletion of viable egg a cancer diagnosis regarding fertility affect the success of their treatment. production or diminished ovarian preservation options. The difficulty of In so doing, they will prevent reserve, leading to subfertility and such decision-making is often missed opportunities for information a shortened fertile window. A compounded by the frequently and interventions related to fertility hysterectomy or insult to the uterus limited time available to make care. may lead to the inability to gestate a pregnancy. decisions that can affect fertility. The Recognizing that older adolescents differences between male and female and even young adults may develop reproductive physiology affect the cancers that fall under the umbrella NORMAL PHYSIOLOGY AND FERTILITY range of options available to boys and of childhood malignancies, this POTENTIAL girls. Options in adolescents who clinical report will include options have undergone puberty are broader Differences in the male and female that may be more appropriate for the reproductive systems influence than those in prepubertal children. patient who is older than 18 years The ideal time to consider fertility available options for fertility after but is still being cared for in cancer treatment.8,9 In general, there preservation is before the initiation of a children’s hospital. therapies that may decrease fertility is a lack of proven options for or cause sterility,
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