Journal Article
. 2018 Feb; 8(1):153-158.
doi: 10.3892/mco.2017.1486.

Fertility preservation in post-pubescent female cancer patients: A practical guideline for clinicians

Amirrtha Srikanthan 1 Eitan Amir 1 Philippe Bedard 1 Meredith Giuliani 2 David Hodgson 2 Stephanie Laframboise 3 Anca Prica 1 Karen Yee 1 Ellen Greenblatt 4 Jeremy Lewin 1 Abha Gupta 1 
  • PMID: 29387409
  •     51 References
  •     1 citations


Increasing accessibility of fertility preservation (FP) options has permitted women to retain fertility following anticancer therapies. Several published guidelines have made recommendations for FP however their implementation into practice is currently unknown. In this review, we aim to provide oncology clinicians practical information about FP options for post-pubescent female cancer patients and recommendations for care delivery in order to answer preliminary questions and help triage whether FP referral is appropriate. Herein, we present a resource for oncology providers to guide them with FP discussions. Key points that are discussed in this critical review include: i) All cancer patients beginning a new plan of care should be informed of potential fertility risk. ii) If a woman requests further information on FP interventions, referral to a FP clinic should be made. iii) Given the evolving technologies in this area, patients should be informed of those which are proven and unproven, with oocyte and embryo preservation recognized as standard practice. iv) Random start (independent of menstrual cycle day) techniques are available to minimize oncologic treatment delays. v) Specific protocols for ovarian stimulation may be center-specific. vi) There is unlikely an increased cancer recurrence risk as a result of stimulation protocols in women with hormone-sensitive cancers. vii) Lastly, given the absence of consensus in the literature, routine use of GnRH analogs is not recommended for all cancer patients, however may be considered in select cases, such as high-risk women in whom definitive FP is not possible or feasible.

Keywords: cancer; females; fertility preservation; guidelines.

Evidence-Based Recommendations for Fertility Preservation Options for Inclusion in Treatment Protocols for Pediatric and Adolescent Patients Diagnosed With Cancer.
Alison Fernbach, Barbara Lockart, +5 authors, Cheryl Rodgers.
J Pediatr Oncol Nurs, 2014 May 07; 31(4). PMID: 24799444    Free PMC article.
Fertility results after ovarian transposition for pelvic malignancies treated by external irradiation or brachytherapy.
P Morice, R Thiam-Ba, +5 authors, G Michel.
Hum Reprod, 1998 May 08; 13(3). PMID: 9572430
A review of 15 years of ovarian tissue bank activities.
Marie-Madeleine Dolmans, Pascale Jadoul, +5 authors, Anne Van Langendonckt.
J Assist Reprod Genet, 2013 Feb 19; 30(3). PMID: 23417329    Free PMC article.
Predicting age of ovarian failure after radiation to a field that includes the ovaries.
W Hamish B Wallace, Angela B Thomson, Frank Saran, Tom W Kelsey.
Int J Radiat Oncol Biol Phys, 2005 Jun 07; 62(3). PMID: 15936554
Experience of young women diagnosed with breast cancer who undergo fertility preservation consultation.
Kimberley A Hill, Tova Nadler, +4 authors, Ellen Warner.
Clin Breast Cancer, 2012 Mar 27; 12(2). PMID: 22444719
Laparoscopic Ovarian Transposition Before Pelvic Cancer Treatment: Ovarian Function and Fertility Preservation.
Nash S Moawad, Estefania Santamaria, Alice Rhoton-Vlasak, Judith L Lightsey.
J Minim Invasive Gynecol, 2016 Sep 11; 24(1). PMID: 27614150
A Delphi consensus study among patients and clinicians in the Netherlands on the procedure of informing young breast cancer patients about Fertility Preservation.
Mirjam M Garvelink, Moniek M Ter Kuile, +2 authors, Anne M Stiggelbout.
Acta Oncol, 2012 Oct 12; 51(8). PMID: 23050612
Fertility preservation during cancer treatment: clinical guidelines.
Kenny A Rodriguez-Wallberg, Kutluk Oktay.
Cancer Manag Res, 2014 Mar 14; 6. PMID: 24623991    Free PMC article.
Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: systematic review and meta-analysis of randomized trials.
Lucia Del Mastro, Marcello Ceppi, +10 authors, Paolo Bruzzi.
Cancer Treat Rev, 2013 Dec 24; 40(5). PMID: 24360817
Systematic Review.
Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis.
Mohamed A Bedaiwy, Ahmed M Abou-Setta, +5 authors, Tommaso Falcone.
Fertil Steril, 2010 Dec 15; 95(3). PMID: 21145541
Systematic Review.
Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy.
Halle C F Moore, Joseph M Unger, +22 authors, POEMS/S0230 Investigators.
N Engl J Med, 2015 Mar 05; 372(10). PMID: 25738668    Free PMC article.
Highly Cited.
Making hard choices easier: a prospective, multicentre study to assess the efficacy of a fertility-related decision aid in young women with early-stage breast cancer.
M Peate, B Meiser, +7 authors, M Friedlander.
Br J Cancer, 2012 Mar 15; 106(6). PMID: 22415294    Free PMC article.
Gonadatrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial.
Eman A Elgindy, Dahlia O El-Haieg, +4 authors, Ahmed M Abou-Setta.
Obstet Gynecol, 2012 Dec 25; 121(1). PMID: 23262931
Effect of luteinizing hormone-releasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study.
Bernd Gerber, Gunter von Minckwitz, +12 authors, German Breast Group Investigators.
J Clin Oncol, 2011 May 04; 29(17). PMID: 21537042
Adjuvant goserelin and ovarian preservation in chemotherapy treated patients with early breast cancer: results from a randomized trial.
A Sverrisdottir, M Nystedt, H Johansson, T Fornander.
Breast Cancer Res Treat, 2009 Jan 21; 117(3). PMID: 19153828
Chemotherapy-induced amenorrhea in patients with breast cancer with a BRCA1 or BRCA2 mutation.
Adriana Valentini, Amy Finch, +10 authors, Steven A Narod.
J Clin Oncol, 2013 Aug 28; 31(31). PMID: 23980083    Free PMC article.
Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: a prospective controlled study.
Amr A Azim, Maria Costantini-Ferrando, Kutluk Oktay.
J Clin Oncol, 2008 May 30; 26(16). PMID: 18509175
Highly Cited.
Use of hormonal protection for chemotherapy-induced gonadotoxicity.
S Samuel Kim, Jung Ryeol Lee, +4 authors, Brian Petroff.
Clin Obstet Gynecol, 2010 Nov 05; 53(4). PMID: 21048441
Educational paper: the effect of cancer therapy on fertility, the assessment of fertility and fertility preservation options for pediatric patients.
Jill P Ginsberg.
Eur J Pediatr, 2010 Dec 04; 170(6). PMID: 21127904
The positive effect of a dedicated adolescent and young adult fertility program on the rates of documentation of therapy-associated infertility risk and fertility preservation options.
Jeremy Lewin, Justin Ming Zheng Ma, +10 authors, Abha Gupta.
Support Care Cancer, 2017 Feb 06; 25(6). PMID: 28155019
Fertility preservation in reproductive-age women facing gonadotoxic treatments.
J Roberts, R Ronn, N Tallon, H Holzer.
Curr Oncol, 2015 Aug 25; 22(4). PMID: 26300680    Free PMC article.
Ovarian tissue cryopreservation: a committee opinion.
Practice Committee of American Society for Reproductive Medicine.
Fertil Steril, 2014 Apr 02; 101(5). PMID: 24684955
Highly Cited. Review.
Ovarian transposition before pelvic irradiation: indications and functional outcome.
Samer Barahmeh, Mahmoud Al Masri, +4 authors, Isam Lataifeh.
J Obstet Gynaecol Res, 2013 Jul 17; 39(11). PMID: 23855765
Grading quality of evidence and strength of recommendations.
David Atkins, Dana Best, +25 authors, GRADE Working Group.
BMJ, 2004 Jun 19; 328(7454). PMID: 15205295    Free PMC article.
Highly Cited.
Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update.
Alison W Loren, Pamela B Mangu, +7 authors, American Society of Clinical Oncology.
J Clin Oncol, 2013 May 30; 31(19). PMID: 23715580    Free PMC article.
Highly Cited. Systematic Review.
Is transplantation of cryopreserved ovarian tissue from patients with advanced-stage breast cancer safe? A pilot study.
V Luyckx, J F Durant, +7 authors, M M Dolmans.
J Assist Reprod Genet, 2013 Aug 31; 30(10). PMID: 23989997    Free PMC article.
Female reproductive health after childhood, adolescent, and young adult cancers: guidelines for the assessment and management of female reproductive complications.
Monika L Metzger, Lillian R Meacham, +8 authors, Daniel M Green.
J Clin Oncol, 2013 Feb 06; 31(9). PMID: 23382474    Free PMC article.
Safety considerations for transplanting cryopreserved ovarian tissue to restore fertility in female patients who have recovered from Ewing's sarcoma.
Stine D Sørensen, Tine Greve, +2 authors, Claus Yding Andersen.
Future Oncol, 2014 Feb 05; 10(2). PMID: 24490613
Successful surrogate pregnancy after ovarian transposition, pelvic irradiation and hysterectomy.
Michael Zinger, James H Liu, Nader Husseinzadeh, Michael A Thomas.
J Reprod Med, 2004 Aug 13; 49(7). PMID: 15305832
Oophoropexy: a relevant role in preservation of ovarian function after pelvic irradiation.
Monica Terenziani, Luigi Piva, +3 authors, Marina Merola.
Fertil Steril, 2008 Oct 28; 91(3). PMID: 18951125
American Society of Clinical Oncology recommendations on fertility preservation in cancer patients.
Stephanie J Lee, Leslie R Schover, +7 authors, American Society of Clinical Oncology.
J Clin Oncol, 2006 May 03; 24(18). PMID: 16651642
Highly Cited. Systematic Review.
Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer.
Pamela N Munster, Amy P Moore, +6 authors, Susan E Minton.
J Clin Oncol, 2012 Jan 11; 30(5). PMID: 22231041    Free PMC article.
Random-start ovarian stimulation in patients with cancer.
Hakan Cakmak, Mitchell P Rosen.
Curr Opin Obstet Gynecol, 2015 Apr 29; 27(3). PMID: 25919235
Laparoscopic oophoropexy and ovarian function in the treatment of Hodgkin disease.
R S Williams, R D Littell, N P Mendenhall.
Cancer, 1999 Nov 26; 86(10). PMID: 10570443
Fertility Preservation for the Young Breast Cancer Patient.
Shari B Goldfarb, Sabrina A Kamer, +6 authors, Mary L Gemignani.
Ann Surg Oncol, 2016 Jan 23; 23(5). PMID: 26790670    Free PMC article.
Ovarian stimulation protocols for onco-fertility patients.
Juliette Koch, William Ledger.
J Assist Reprod Genet, 2013 Feb 19; 30(2). PMID: 23417355    Free PMC article.
Autotransplantation of cryopreserved ovarian tissue in cancer survivors and the risk of reintroducing malignancy: a systematic review.
L Bastings, C C M Beerendonk, +5 authors, R Peek.
Hum Reprod Update, 2013 Jul 03; 19(5). PMID: 23817363
Systematic Review.
No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial.
Isabelle Demeestere, Pauline Brice, +9 authors, Yvon Englert.
J Clin Oncol, 2016 May 25; 34(22). PMID: 27217453
Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women.
Hengxi Chen, Jinke Li, Tao Cui, Lina Hu.
Cochrane Database Syst Rev, 2011 Nov 11; (11). PMID: 22071842
Systematic Review.
SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016).
M Muñoz, A Santaballa, +7 authors, A Blasco.
Clin Transl Oncol, 2016 Nov 30; 18(12). PMID: 27896641    Free PMC article.
Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study.
Ahmed Badawy, Aboubakr Elnashar, Mohamed El-Ashry, May Shahat.
Fertil Steril, 2008 Aug 05; 91(3). PMID: 18675959
Fertility preservation in women.
Jacques Donnez, Marie-Madeleine Dolmans.
Nat Rev Endocrinol, 2013 Oct 30; 9(12). PMID: 24166000
Highly Cited. Review.
Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial.
Lucia Del Mastro, Luca Boni, +14 authors, Marco Venturini.
JAMA, 2011 Jul 21; 306(3). PMID: 21771987
Fertility preservation in children, adolescents, and young adults with cancer: Quality of clinical practice guidelines and variations in recommendations.
Anna Font-Gonzalez, Renée L Mulder, +10 authors, PanCareLIFE Consortium.
Cancer, 2016 May 14; 122(14). PMID: 27175973
Physician perceptions and practice patterns regarding fertility preservation in hematopoietic cell transplant recipients.
A W Loren, R Brazauskas, +22 authors, N S Majhail.
Bone Marrow Transplant, 2013 Feb 20; 48(8). PMID: 23419436    Free PMC article.
Anti-Müllerian hormone and assessment of ovarian reserve after ovarian toxic treatment: a systematic narrative review.
Akira Iwase, Tomoko Nakamura, +2 authors, Fumitaka Kikkawa.
Reprod Sci, 2014 Sep 18; 22(5). PMID: 25228631
Systematic Review.
Concurrent treatment with gonadotropin-releasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: a meta-analysis of randomized controlled trials.
Bo Yang, Weiwei Shi, +4 authors, Shunchang Jiao.
Breast, 2013 Jan 10; 22(2). PMID: 23298851
Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis.
Megan E B Clowse, Millie A Behera, +4 authors, Lori A Bastian.
J Womens Health (Larchmt), 2009 Mar 14; 18(3). PMID: 19281314    Free PMC article.
Systematic Review.
Does a dedicated program for young breast cancer patients affect the likelihood of fertility preservation discussion and referral?
Amirrtha Srikanthan, Eitan Amir, Ellen Warner.
Breast, 2016 May 24; 27. PMID: 27212696
Age-specific probability of live birth with oocyte cryopreservation: an individual patient data meta-analysis.
Aylin Pelin Cil, Heejung Bang, Kutluk Oktay.
Fertil Steril, 2013 May 28; 100(2). PMID: 23706339    Free PMC article.
New methods to improve the safety assessment of cryopreserved ovarian tissue for fertility preservation in breast cancer patients.
Beatriz Rodríguez-Iglesias, Edurne Novella-Maestre, +3 authors, Antonio Pellicer.
Fertil Steril, 2015 Sep 15; 104(6). PMID: 26364839
Developing a Web-Based Shared Decision-Making Tool for Fertility Preservation Among Reproductive-Age Women With Breast Cancer: An Action Research Approach.
Ling-Ming Tseng, Pei-Ju Lien, +3 authors, Sheng-Miauh Huang.
J Med Internet Res, 2021 Mar 18; 23(3). PMID: 33729164    Free PMC article.