Vol. 17 No. 1 (2024), QUALITY OF LIFE
Vol. 17 No. 1 (2024)
QUALITY OF LIFE

Pharmacological Protection of Ovaries During Program Drug Chemotherapy in Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma Patients

Published 17.05.2024
I.E. Antukh
VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997
Valeriya Olegovna Shpirko
NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian
T.A. Nazarenko
VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997
Ya.O. Martirosyan
VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997
A.M. Biryukova
VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997
S.V. Khokhlova
VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina ul., Moscow, Russian Federation, 117997
G.S. Tumyan
NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478
2024-1
PDF_2024-17-1_59-65 (Russian)

Keywords

reproductive function
gonadotropin-releasing hormone agonists
classical Hodgkin lymphoma
diffuse large B-cell lymphoma
primary mediastinal (thymic) large B-cell lymphoma
fertility in patients with hematological malignancies

How to Cite

1.
Antukh I.E., Shpirko V.O., Nazarenko T.A., et al. Pharmacological Protection of Ovaries During Program Drug Chemotherapy in Classical Hodgkin Lymphoma and Non-Hodgkin Lymphoma Patients. Клиническая онкогематология. 2024;17(1):59-65. doi:10.21320/2500-2139-2024-17-1-59-65
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Abstract

Aim. To assess the efficacy of ovarian protection and options for fertility preservation with the use of gonadotropin-releasing hormone agonists (a-GnRH) in patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphomas (NHLs) during program drug chemotherapy.

Materials & Methods. The study enrolled 247 female patients (187 with cHL and 60 with NHLs) undergoing program drug chemotherapy from 2019 to 2023. The patients were aged 13–42 years (median 24 years). Prior to chemotherapy and after it was completed, the serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol levels were measured. Besides, antral follicle count was estimated by pelvic ultrasound. To provide ovarian protection during chemotherapy, a-GnRH was administered to 67 (27 %) out of 247 patients. Ovarian reserve was assessed based on ultrasound and AMH, FSH, and estradiol levels in 2–3 months after completing the program of drug chemotherapy or after spontaneous menstrual recovery.

Results. Menstrual cycle recovered in 194 (78.5 %) out of 247 patients, regardless of lymphoid malignancy variant. Among them, there were 79.7 % (n = 149) of cHL patients and 75 % (n = 45) of NHL patients. Accordingly, ovarian function was lost in 20.3 % (n = 38) of cHL patients and 25 % (n = 15) of NHL patients. Predictors of ovarian function recovery appeared to be age ≤ 28 years and AMH level > 2.45 ng/mL. Pharmacological protection of ovaries did not impact the probability of menstrual cycle recovery. Regardless of immunomorphological variant of lymphoid malignancy, a regular menstrual cycle was completely restored in 48 (71.6 %) out of 67 a-GnRH recipients and in 146 (81.1 %) out of 180 patients without a-GnRH treatment.

Conclusion. Most of cHL and NHL patients of early reproductive age (≤ 30 years) have a fair chance of menstrual cycle recovery after completing the program drug chemotherapy similar to BEACOPP, EACODD(PP)-14, R-CHOP, R-Da-EPOCH and other regimens. Ovarian reserve cannot be preserved by means of a-GnRH administration during chemotherapy. High baseline FSH and low baseline AMH levels indirectly indicate evidence of impaired ovarian reserve. Patients belonging to this category are those who, if intensive combined cytostatic therapy regimens are planned, should undergo prior oocyte/embryo retrieval with subsequent cryopreservation due to the risk of premature loss of ovarian function.

PDF_2024-17-1_59-65 (Russian)

References

  1. Kreuser ED, Hetzel WD, Billia DO, Thiel E. Gonadal toxicity following cancer therapy in adults: significance, diagnosis, prevention and treatment. Cancer Treat Rev. 1990;17(2–3):169–75. doi: 10.1016/0305-7372(90)90043-f.
  2. Zhong Y, Lin Y, Cheng X, et al. GnRHa for Ovarian Protection and the Association between AMH and Ovarian Function during Adjuvant Chemotherapy for Breast Cancer. J Cancer. 2019;10(18):4278–85. doi: 10.7150/jca.31859.
  3. Sutcliffe SB. Cytotoxic chemotherapy and gonadal function in patients with Hodgkin’s disease. Facts and thoughts. JAMA. 1979;242(17):1898–9. doi: 10.1001/jama.1979.03300170044028.
  4. Behringer K, Thielen I, Mueller H, et al. Fertility and gonadal function in female survivors after treatment of early unfavorable Hodgkin lymphoma (HL) within the German Hodgkin Study Group HD14 trial. Ann Oncol. 2012;23(7):1818–25. doi: 10.1093/annonc/mdr575.
  5. Behringer K, Breuer K, Reineke T, et al. Secondary amenorrhea after Hodgkin’s lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin’s Lymphoma Study Group. J Clin Oncol. 2005;23(30):7555–64. doi: 10.1200/JCO.2005.08.138.
  6. Tan SJ, Lee LJ, Tzeng CR, et al. Targeted anti-apoptosis activity for ovarian protection against chemotherapy-induced ovarian gonadotoxicity. Reprod Biomed Online. 2014;29(5):612–20. doi: 10.1016/j.rbmo.2014.07.014.
  7. ISFP Practice Committee, Kim SS, Donnez J, et al. Recommendations for fertility preservation in patients with lymphoma, leukemia, and breast cancer. J Assist Reprod Genet. 2012;29(6):465–8. doi: 10.1007/s10815-012-9786-y.
  8. Broer SL, Broekmans FJ, Laven JS, Fauser BC. Anti-Mullerian hormone: ovarian reserve testing and its potential clinical implications. Hum Reprod Update. 2014;20(5):688–701. doi: 10.1093/humupd/dmu020.
  9. Martinez F, International Society for Fertility Preservation–ESHRE–ASRM Expert Working Group. Update on fertility preservation from the Barcelona International Society for Fertility Preservation-ESHRE-ASRM 2015 expert meeting: indications, results and future perspectives. Fertil Steril. 2017;108(3):407–15.e11. doi: 10.1016/j.fertnstert.2017.05.024.
  10. Leung PC, Cheng CK, Zhu XM. Multi-factorial role of GnRH-I and GnRH-II in the human ovary. Mol Cell Endocrinol. 2003;202(1–2):145–53. doi: 10.1016/s0303-7207(03)00076-5.
  11. Scaruffi P, Stigliani S, Cardinali B, et al. Gonadotropin Releasing Hormone Agonists Have an Anti-apoptotic Effect on Cumulus Cells. Int J Mol Sci. 2019;20(23):6045. doi: 10.3390/ijms20236045.
  12. Blumenfeld Z, Avivi I, Linn S, et al. Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. Hum Reprod. 1996;11(8):1620–6. doi: 10.1093/oxfordjournals.humrep.a019457.
  13. Blumenfeld Z, von Wolff M. GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy. Hum Reprod Update. 2008;14(6):543–52. doi: 10.1093/humupd/dmn022.
  14. Imai A, Sugiyama M, Furui T, et al. Direct protection by a gonadotropin-releasing hormone analog from doxorubicin-induced granulosa cell damage. Gynecol Obstet Invest. 2007;63(2):102–6. doi: 10.1159/000096062.
  15. Blumenfeld Z, Dann E. GnRH agonist for the prevention of chemotherapy-induced ovarian failure in lymphoma. J Clin Oncol. 2013;31(29):3721. doi: 10.1200/JCO.2012.47.8222.
  16. Behringer K, Wildt L, Mueller H, et al. No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase II trial from the German Hodgkin Study Group. Ann Oncol. 2010;21(10):2052–60. doi: 10.1093/annonc/mdq066.
  17. Demeestere I, Brice P, Peccatori FA, et al. 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. J Clin Oncol. 2016;34(22):2568–74. doi: 10.1200/JCO.2015.65.8864.
  18. Hasky N, Uri-Belapolsky S, Goldberg K, et al. Gonadotrophin-releasing hormone agonists for fertility preservation: unraveling the enigma? Hum Reprod. 2015;30(5):1089–101. doi: 10.1093/humrep/dev037.
  19. Harel S, Ferme C, Poirot C. Management of fertility in patients treated for Hodgkin’s lymphoma. Haematologica. 2011;96(11):1692–9. doi: 10.3324/haematol.2011.045856.
  20. Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2019. 250 с. [Kaprin AD, Starinskii VV, Petrova GV, eds. Zlokachestvennye novoobrazovaniya v Rossii v 2018 godu (zabolevaemost’ i smertnost’). (Malignant neoplasms in Russia in 2018 (incidence and mortality.) Moscow: MNIOI im. P.A. Gertsena — filial FGBU “NMITs radiologii” Publ.; 2019. 250 р. (In Russ)]
  21. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi: 10.3322/caac.21551.
  22. Bedaiwy MA, Abou-Setta AM, Desai N, et al. Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril. 2011;95(3):906–14.e144. doi: 10.1016/j.fertnstert.2010.11.017.
  23. Roness H, Spector I, Leichtmann-Bardoogo Y, et al. Pharmacological administration of recombinant human AMH rescues ovarian reserve and preserves fertility in a mouse model of chemotherapy, without interfering with anti-tumoural effects. J Assist Reprod Genet. 2019;36(9):1793–803. doi: 10.1007/s10815-019-01507-9.
  24. Von Wolff M, Montag M, Dittrich R, et al. Fertility preservation in women—a practical guide to preservation techniques and therapeutic strategies in breast cancer, Hodgkin’s lymphoma and borderline ovarian tumours by the fertility preservation network FertiPROTEKT. Arch Gynecol Obstet. 2011;284(2):427–35. doi: 10.1007/s00404-011-1874-1.
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