Cytotoxic Activity of Antineoplastic Agents on Fertility: A Systematic Review

Abstract

Objective To analyze the long-term effects of antineoplastic treatments on patient fertility.

Selection of Studies The studies were selected through the New PubMed, Scielo and Lilacs databases along with references used for the creation of the present work. For the selection of studies, articles published between the periods from January 1, 2015 to April 6, 2020 in the English, Portuguese and Spanish languages were used. As inclusion criteria: cohort studies and studies conducted in vitro. As exclusion criteria: review articles, reported cases, studies that do not address thematic reproduction, studies that do not address the cancer theme, articles that used animals, articles that address the preservation of fertility and articles in duplicate in the bases.

Data Collection The collected data included: age of the patient at the beginning of treatment, type of neoplasm, type of antineoplastic treatment, chemotherapy used, radiotherapy dosage, radiotherapy site, effect of antineoplastic agents on fertility and number of patients in the study.

Data Synthesis Thirty studies were evaluated, antineoplastic chemotherapy agents and radiotherapy modulate serum hormone levels, reduces germ cell quantities and correlated with an increase in sterility rates. The effects mentioned occur in patients in the prepubertal and postpubertal age.

Conclusion Antineoplastic treatments have cytotoxic effects on the germ cells leading to hormonal modulation, and pubertal status does not interfere with the cytotoxic action of therapies.

Resumo

Objetivo Analisar os efeitos a longo prazo dos tratamentos antineoplásicos na fertilidade de pacientes.

Fontes de dados Os estudos foram selecionados através das bases de dados New PubMed, Scielo e Lilacs, junto com as referências utilizadas para a confecção do trabalho.

Seleção dos estudos Para a seleção dos estudos, foram utilizados artigos publicados entre os períodos de 01 de janeiro de 2015 a 06 de abril de 2020 nos idiomas inglês, português e espanhol. Como critérios de inclusão: estudos de coorte e estudos realizados in vitro. Como critérios de exclusão: artigos de revisão, relatos de caso, estudos que não abordavam a temática reprodução, estudos que não abordavam a temática câncer, artigos utilizando animais, artigos que abordavam preservação da fertilidade e artigos em duplicidade nas bases.

Coleta de dados Os dados coletados incluíram: idade do paciente ao início do tratamento, tipo de neoplasia, tipo de tratamento antineoplásico, quimioterápicos utilizados, dosagem da radioterapia, local da radioterapia, efeito dos agentes antineoplásicos na fertilidade e número de pacientes dentro do estudo.

Síntese de dados Trinta estudos foram avaliados. Os agentes quimioterápicos antineoplásicos e a radioterapia modulam níveis séricos hormonais de marcadores de fertilidade, reduzem a quantidade de células germinativas e estão correlacionados com um aumento da taxa de esterilidade. Os efeitos citados anteriormente ocorreram em pacientes com idade pré-púbere e pós-púbere.

Conclusão Os tratamentos antineoplásicos possuem efeitos citotóxicos em células germinativas, levando a modulação hormonal, e o status puberal não interfere diretamente na ação citotóxica das terapias.

Keywords

oncofertility - chemotherapy - radiotherapy - neoplasm - germ tissue

Palavras-chave

oncofertilidade - quimioterapia - radioterapia - neoplasia - tecidos germinativos

Publikationsverlauf

Eingereicht: 28. November 2019

Angenommen: 21. Mai 2020

Artikel online veröffentlicht:
30. November 2020

• References

• 1 Ramazzotti D, Lal A, Wang B, Batzoglou S, Sidow A. Multi-omic tumor data reveal diversity of molecular mechanisms that correlate with survival. Nat Commun 2018; 9 (01) 4453
• 2 Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144 (05) 646-674
• 3 World Health Organization. Improving affordability and effectiveness of cancer medicines [Internet]. 2018 [cited 2018 Aug 13]. Available from: http://www.who.int/medicines/areas/access/Improving-affordability-effectiveness-of-cancer-medicines/en/
• 4 Duarte AF, Sousa-Pinto B, Haneke E, Correia O. Risk factors for development of new skin neoplasms in patients with past history of skin cancer: A survival analysis. Sci Rep 2018; 8 (01) 15744
• 5 Tarín JJ, García-Pérez MA, Cano A. Obstetric and offspring risks of women's morbid conditions linked to prior anticancer treatments. Reprod Biol Endocrinol 2016; 14 (01) 37
• 6 Hassan I, Khan AA, Aman S, Qamar W, Ebaid H, Al-Tamimi J. et al Restrained management of copper level enhances the antineoplastic activity of imatinib in vitro and in vivo. Sci Rep 2018; 8 (01) 1682
• 7 Plummer C, Driessen C, Szabo Z, Mateos MV. Management of cardiovascular risk in patients with multiple myeloma. Blood Cancer J 2019; 9 (03) 26
• 8 Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Curr Opin Neurol 2015; 28 (05) 500-507
• 9 Matoso LML, Rosário SSD, Matoso MBL. As estratégias de cuidados para o alívio dos efeitos colaterais da quimioterapia em mulheres. Saúde (Santa Maria) 2015; 41 (02) 251-260
• 10 Donnez J, Dolmans MM. Fertility preservation in women. Nat Rev Endocrinol 2013; 9 (12) 735-749
• 11 De Ruysscher D, Niedermann G, Burnet NG, Siva S, Lee AWM, Hegi-Johnson F. Radiotherapy toxicity. Nat Rev Dis Primers 2019; 5 (01) 13
• 12 Katz DJ, Kolon TF, Feldman DR, Mulhall JP. Fertility preservation strategies for male patients with cancer. Nat Rev Urol 2013; 10 (08) 463-472
• 13 Bénard J, Duros S, El Hachem H, Sonigo C, Sifer C, Grynberg M. Freezing oocytes or embryos after controlled ovarian hyperstimulation in cancer patients: the state of the art. Future Oncol 2016; 12 (14) 1731-1741
• 14 MacLeod KJ, McCormick GL, Langkilde T. Glucocorticoids do not influence a secondary sexual trait or its behavioral expression in eastern fence lizards. Sci Rep 2019; 9 (01) 5229
• 15 Lenz KM, Pickett LA, Wright CL, Galan A, McCarthy MM. Prenatal allergen exposure perturbs sexual differentiation and programs lifelong changes in adult social and sexual behavior. Sci Rep 2019; 9 (01) 4837
• 16 Ramstein JJ, Halpern J, Gadzinski AJ, Brannigan RE, Smith JF. Ethical, moral, and theological insights into advances in male pediatric and adolescent fertility preservation. Andrology 2017; 5 (04) 631-639
• 17 Hisasi CS, Cortez DEA, Pomin T, Felix JS, Mesquita SFP. Alterações testiculares em rato pré-púberes após tratamento subcrônico com doxorubicina. Bol Cent Biol Reprod 2007; 26 (1/2): 66-70
• 18 Veloso EVL, Figueirêdo LCM, Menezes DJA, Sousa OB, Santos JRS. Efeitos de sulfato de vincristine sobre os testículos de ratos albinos, tratados na fase pré-púbere. Pesqui Vet Bras 2018; 38 (06) 1217-1224
• 19 Cabral REL, Mendes TB, Vendramini V, Miraglia SM. Carnitine partially improves oxidative stress, acrosome integrity, and reproductive competence in doxorubicin-treated rats. Andrology 2018; 6 (01) 236-246
• 20 Pati D, Lorusso LN. How to write a systematic review of the literature. HERD 2018; 11 (01) 15-30
• 21 PRISMA. PRISMA Statement [Internet]. 2009 [cited 2018 Aug 13]. Available from: http://www.prisma-statement.org/PRISMAStatement/
• 22 Gini G, Annibali O, Lupasco D, Bocci C, Tomarchio V, Sampaolo M. et al. Gonadal function recovery and fertility in women treated with chemo-and/or radiotherapy for Hodgkin's and non-Hodgkin lymphoma. Chemotherapy 2019; 64 (01) 36-41
• 23 Shandley LM, Fothergill A, Spencer JB, Mertens AC, Cottrell HN, Howards PP. Impact of cancer treatment on risk of infertility and diminished ovarian reserve in women with polycystic ovary syndrome. Fertil Steril 2018; 109 (03) 516-525.e1
• 24 Sinha N, Letourneau JM, Wald K, Xiong P, Imbar T, Li B. et al. Antral follicle count recovery in women with menses after treatment with and without gonadotropin-releasing hormone agonist use during chemotherapy for breast cancer. J Assist Reprod Genet 2018; 35 (10) 1861-1868
• 25 Al-Rawi SA, Saleh BO, Al-Naqqash MA. Serum anti-müllerian hormone levels in evaluation of chemotherapy effect on ovarian reserve in women with breast cancer. A follow-up study. Saudi Med J 2018; 39 (07) 733-735
• 26 Anderson RA, Remedios R, Kirkwood AA, Patrick P, Stevens L, Clifton-Hadley L. et al. Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin's lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial. Lancet Oncol 2018; 19 (10) 1328-1337
• 27 D'Avila AM, Capp E, Corleta HVE. Antral follicles count and anti-Müllerian hormone levels after gonadotoxic chemotherapy in patients with breast cancer: cohort study. Rev Bras Ginecol Obstet 2017; 39 (04) 162-168
• 28 Chang X, Zhou L, Chen X, Xu B, Cheng Y, Sun S. et al. Impact of imatinib on the fertility of male patients with chronic myelogenous leukaemia in the chronic phase. Target Oncol 2017; 12 (06) 827-832
• 29 Creux H, Monnier P, Son WY, Tulandi T, Buckett W. Immature oocyte retrieval and in vitro oocyte maturation at different phases of the menstrual cycle in women with cancer who require urgent gonadotoxic treatment. Fertil Steril 2017; 107 (01) 198-204
• 30 Wenners A, Grambach J, Koss J, Maass N, Jonat W, Schmultzer A, Mundhenke C. Reduced ovarian reserve in young early breast cancer patients: preliminary data from a prospective cohort trial. BMC Cancer 2017; 17 (01) 632
• 31 Perdrix A, Saint-Ghislain M, Degremont M. et al. Influence of adjuvant chemotherapy on anti-Müllerian hormone in women below 35 years treated for early breast cancer. Reprod Biomed Online 2017; 35 (04) 468-474
• 32 McLaughlin M, Kelsey TW, Wallace WH, Anderson RA, Telfer EE. Non-growing follicle density is increased following adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy in the adult human ovary. Hum Reprod 2017; 32 (01) 165-174
• 33 Abir R, Ben-Aharon I, Garor R. et al. Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy. Hum Reprod 2016; 31 (04) 750-762
• 34 Hamy AS, Porcher R, Eskenazi S, Cuvier C, Giacchetti S, Coussy F. et al. Anti-Müllerian hormone in breast cancer patients treated with chemotherapy: a retrospective evaluation of subsequent pregnancies. Reprod Biomed Online 2016; 32 (03) 299-307
• 35 Paoli D, Rizzo F, Fiore G, Pallotti F, Pulsoni A, Annechini G. et al. Spermatogenesis in Hodgkin's lymphoma patients: a retrospective study of semen quality before and after different chemotherapy regimens. Hum Reprod 2016; 31 (02) 263-272
• 36 Even-Or E, Ben-Haroush A, Yahel A, Yaniv I, Stein J. Fertility after treatment with high dose melphalan in women with acute myelogenous leukemia. Pediatr Blood Cancer 2016; 63 (02) 334-336
• 37 Jacobson MH, Mertens AC, Spencer JB, Manatunga AK, Howards PP. Menses resumption after cancer treatment-induced amenorrhea occurs early or not at all. Fertil Steril 2016; 105 (03) 765-772.e4
• 38 Gupta AA, Lee Chong A, Deveault C, Traubici J, Maloney AM, Knight S. et al. Anti-Müllerian hormone in female adolescent cancer patients before, during, and after completion of therapy: a pilot feasibility study. J Pediatr Adolesc Gynecol 2016; 29 (06) 599-603
• 39 Ruddy KJ, Guo H, Barry W, Dang CT, Yardley DA, Moy B. et al. Chemotherapy-related amenorrhea after adjuvant paclitaxel-trastuzumab (APT trial). Breast Cancer Res Treat 2015; 151 (03) 589-596
• 40 Huser M, Smardova L, Janku P, Crha I, Zakova J, Stourac P. et al. Fertility status of Hodgkin lymphoma patients treated with chemotherapy and adjuvant gonadotropin-releasing hormone analogues. J Assist Reprod Genet 2015; 32 (08) 1187-1193
• 41 Levi M, Hasky N, Stemmer SM, Shalgi R, Ben-Aharon I. Anti-Müllerian hormone is a marker for chemotherapy-induced testicular toxicity. Endocrinology 2015; 156 (10) 3818-3827
• 42 Thomas-Teinturier C, Allodji RS, Svetlova E, Frey M-A, Obertlin O, Millischer A-E. et al. Ovarian reserve after treatment with alkylating agents during childhood. Hum Reprod 2015; 30 (06) 1437-1446
• 43 Meissner J, Tichy D, Katzke V, Kuhn T, Dietrich S, Schmitt T. et al. Long-term ovarian function in women treated with CHOP or CHOP plus etoposide for aggressive lymphoma. Ann Oncol 2015; 26 (08) 1771-1776
• 44 Duhil de Bénazé G, Pacquement H, Faure-Conter C, Patte C, Orbach D, Corradini N. et al. Paediatric dysgerminoma: Results of three consecutive French germ cell tumours clinical studies (TGM-85/90/95) with late effects study. Eur J Cancer 2018; 91: 30-37
• 45 Fernandez-Pineda I, Davidoff AM, Lu L, Rao BN, Wilson CL, Srivastava DK. et al. Impact of ovarian transposition before pelvic irradiation on ovarian function among long-term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study. Pediatr Blood Cancer 2018; 65 (09) e27232
• 46 Rives N, Walschaerts M, Setif V, Hennebicq S, Saias J, Brugnon F. et al. Sperm aneuploidy after testicular cancer treatment: data from a prospective multicenter study performed within the French Centre d'Étude et de Conservation des Oeufs et du Sperme network. Fertil Steril 2017; 107 (03) 580-588.e1
• 47 Green DM, Zhu L, Wang M, Chemaitilly W, Srivastava D, Kutteh WH. et al. Effect of cranial irradiation on sperm concentration of adult survivors of childhood acute lymphoblastic leukemia: a report from the St. Jude Lifetime Cohort Study. Hum Reprod 2017; 32 (06) 1192-1201
• 48 Chemaitilly W, Li Z, Krasin MJ. et al. Premature ovarian insufficiency in childhood cancer survivors: a report from the St. Jude Lifetime Cohort. J Clin Endocrinol Metab 2017; 102 (07) 2242-2250
• 49 Chow EJ, Stratton KL, Leisenring WM, Oeffinger KC, Sklar CA, Donaldson SS. et al. Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort. Lancet Oncol 2016; 17 (05) 567-576
• 50 Boltežar L, Pintarić K, Jezeršek Novaković B. Fertility in young patients following treatment for Hodgkin's lymphoma: a single center survey. J Assist Reprod Genet 2016; 33 (03) 325-333
• 51 Sonigo C, Seroka A, Cédrin-Durnerin I, Sermondade N, Sifer C, Grynberg M. History of ABVD alters the number of oocytes vitrified after in vitro maturation in fertility preservation candidates. Future Oncol 2016; 12 (14) 1713-1719
• 52 Xiao S, Zhang J, Romero MM, Smith KN, Shea LD, Woodruff TK. In vitro follicle growth supports human oocyte meiotic maturation. Sci Rep 2015; 5: 17323
• 53 Woodruff TK. The Oncofertility Consortium--addressing fertility in young people with cancer. Nat Rev Clin Oncol 2010; 7 (08) 466-475
• 54 Laronda MM, Rutz AL, Xiao S, Whelan KA, Duncan FE, Roth EW. et al. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat Commun 2017; 8: 15261
• 55 Xu M, Pavone ME, Woodruff T. Fruitful progress to fertility: preserving oocytes from chemodestruction. Nat Med 2011; 17 (12) 1562-1563
• 56 Carvalho B, Caetano J, Cavagna M, Marinho M, Silva A, Nakagawa M. Indução de ovulação em pacientes com tumor estrogênio-dependente: diretrizes clínicas da Sociedade Brasileira de Reprodução Humana. Reprod Clim 2017; 32 (01) 31-38
• 57 Huddart RA, Norman A, Moynihan C, Horwich A, Parker C, Nicholls E, Dearnaley DP. Fertility, gonadal and sexual function in survivors of testicular cancer. Br J Cancer 2005; 93 (02) 200-207
• 58 Madhu P, Reddy KP, Reddy PS. Role of melatonin in mitigating chemotherapy-induced testicular dysfunction in Wistar rats. Drug Chem Toxicol 2016; 39 (02) 137-146
• 59 Liang S, Kinghorn AB, Voliotis M, Prague JK, Veldhuis JD, Tsaneva-Atanasova K. et al. Measuring luteinising hormone pulsatility with a robotic aptamer-enabled electrochemical reader. Nat Commun 2019; 10 (01) 852
• 60 Chang ZL, Li BX, Liu B, , Yao Lu, Yu, Jie, Jiang GM, Tan J-H. Effects of FSH and the weather during induced ovulation and timed artificial insemination to increase jenny conception rates. Sci Rep 2019; 9 (01) 3220
• 61 Pergialiotis V, Koutaki D, Christopoulos-Timogiannakis E, Kotrogianni P, Perrea DN, Daskalakis G. Anti-Müllerian Hormone Levels in Preeclampsia: A Systematic Review of the Literature. J Family Reprod Health 2017; 11 (04) 179-184
• 62 Brandão HN, David JP, Couto RD, Nascimento JAP, David JM. Química e farmacologia de quimioterápicos antineoplásicos derivados de plantas. Quim Nova 2010; 33 (06) 1359-1369
• 63 Martinez RM, Hauser R, Liang L, Mansur A, Adir M, Dioni L. et al. Urinary concentrations of phenols and phthalate metabolites reflect extracellular vesicle microRNA expression in follicular fluid. Environ Int 2019; 123: 20-28
• 64 Park J, Park Y, Lee SU, Kim T, Choi YK, Kim JY. Differential dosimetric benefit of proton beam therapy over intensity modulated radiotherapy for a variety of targets in patients with intracranial germ cell tumors. Radiat Oncol 2015; 10: 135
• 65 Isaksson S, Eberhard J, Ståhl O, Cavallin-Ståhl E, Cohn-Cedermark G, Arver S. et al. Inhibin B concentration is predictive for long-term azoospermia in men treated for testicular cancer. Andrology 2014; 2 (02) 252-258
• 66 Paoli D, Gallo M, Rizzo F. et al. Testicular cancer and sperm DNA damage: short- and long-term effects of antineoplastic treatment. Andrology 2015; 3 (01) 122-128