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Recommendations for Surveillance of Premature Ovarian Insufficiency in Female Survivors of CAYA Cancers

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Harmonized recommendations for surveillance of premature ovarian insufficiency in female survivors of childhood, adolescent, and young adult (CAYA) cancers have been published by van Dorp et al in the Journal of Clinical Oncology on behalf of the International Late Effects of Childhood Cancer Guideline Harmonization Group in Collaboration with the PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Consortium (PanCareSurFup). The recommendations, formulated by an international multidisciplinary panel using an evidence-based approach, are meant to harmonize the several existing North American and European guidelines. Key recommendations are summarized/reproduced here.

General Recommendation

Survivors treated with one or more potentially gonadotoxic treatments, and their providers, should be aware of the risk of premature ovarian insufficiency and its implications for future fertility (level A and level C evidence).

Who Needs Surveillance?

Counseling regarding the risk of premature ovarian insufficiency and its implications for future fertility is recommended for survivors treated with:

  • Alkylating agents in general (level A evidence)
  • Cyclophosphamide and procarbazine (level C evidence)
  • Radiotherapy potentially exposing the ovaries (level A evidence)

What Surveillance Modality Should Be Used for Pre- and Peripubertal Survivors?

Monitoring of growth (height) and pubertal development and progression (Tanner stage) is recommended for prepubertal survivors treated with potentially gonadotoxic chemotherapyor radiotherapy potentially exposing the ovaries (expert opinion/no literature search).

Follicle-stimulating hormone (FSH) and estradiol are recommended for evaluation of premature ovarian insufficiency in prepubertal survivors treated with potentially gonadotoxic chemotherapy or radiotherapy potentially exposing the ovaries who fail to initiate or progress through puberty (expert opinion/no literature search).

What Surveillance Modality Should Be Used for Postpubertal Survivors?

A detailed history and physical examination with specific attention for premature ovarian insufficiency symptoms (eg, amenorrhea and irregular cycles) are recommended for postpubertal survivors treated with potentially gonadotoxic chemotherapy or radiotherapy potentially exposing the ovaries (expert opinion/no literature search).

FSH and estradiol are recommended for evaluation of premature ovarian insufficiency in postpubertal survivors treated with potentially gonadotoxic chemotherapy or radiotherapy potentially exposing the ovaries who present with menstrual cycle dysfunction suggesting premature ovarian insufficiency or who desire assessment about the potential for future fertility. Hormone replacement therapy should be discontinued prior to laboratory evaluation when applicable (expert opinion/no studies).

Anti-Müllerian hormone (AMH) is not recommended as the primary surveillance modality for evaluation of premature ovarian insufficiency in survivors treated with potentially gonadotoxic chemotherapy or radiotherapy potentially exposing the ovaries who desire assessment about the potential for future fertility (expert opinion/no studies).

AMH may be reasonable in conjunction with FSH and estradiol for identification of premature ovarian insufficiency in survivors treated with potentially gonadotoxic chemotherapy or radiotherapy potentially exposing the ovaries aged ≥ 25 years who present with menstrual cycle dysfunction suggesting premature ovarian insufficiency or who desire assessment about the potential for future fertility (expert opinion/no studies).

When Should Pre- and Peripubertal Survivors Be Referred?

Referral to pediatric endocrinology/gynecology is recommended for any survivor who has (expert opinion/no literature search):

  • No signs of puberty by 13 years of age
  • Primary amenorrhea by 16 years of age
  • Failure of pubertal progression

When Should Postpubertal Survivors Be Referred?

Referral to gynecology/reproductive medicine/endocrinology (according to local referral pathways) is recommended for postpubertal survivors treated with potentially gonadotoxic chemotherapy or radiotherapy potentially exposing the ovaries who present with menstrual cycle dysfunction suggesting premature ovarian insufficiency (expert opinion/no literature search).

What Should Be Done When Abnormalities Are Identified in Pre-, Peri-, and Postpubertal Survivors?

Consideration of sex steroid replacement therapy is recommended for pre-, peri- and postpubertal survivors diagnosed with premature ovarian insufficiency by referral to gynecology/endocrinology (expert opinion/no literature search).

What Should Be Done When the Potential for Future Fertility Is Questioned?

Referral to gynecology/reproductive medicine/endocrinology (according to local referral pathways) is recommended for postpubertal females treated with potentially gonadotoxic chemotherapy or ovarian irradiation without signs and symptoms of premature ovarian insufficiency who desire assessment about the potential for future fertility (expert opinion/no literature search).

The authors concluded: “The harmonized set of premature ovarian insufficiency surveillance recommendations is intended to be scientifically rigorous, to positively influence health outcomes, and to facilitate the care for female survivors of CAYA cancer.”

The work was supported by the Pediatric Oncology Centre Society for Research, Rotterdam, Dutch Cancer Society, Cancer Center Support grant to St. Jude Children’s Research Hospital and American Lebanese Syrian Associated Charities, and the 7th Framework Programme of the European Union, PanCareSurfUp.

W. Hamish Wallace, MD, of the University of Edinburgh & Royal Hospital for Sick Children, is the corresponding author of the Journal of Clinical Oncology article. Dr. Wallace and Riccardo Haupt, MD, of Istituto Giannina Gaslini, Genoa, contributed equally to this work.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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