Use of in vitro fertilization programs to preserve reproductive material in patients with breast cancer
Biryukova A.M., Nazarenko T.A., Martirosyan Ya.O., Oshkina E.V.
Objective: This study aimed to refine methodologies for implementing assisted reproductive technologies (ART), specifically in vitro fertilization (IVF), to preserve reproductive material in patients diagnosed with breast cancer. A comparative analysis of various ovarian stimulation protocols was conducted along with an evaluation of the impact of incorporating aromatase inhibitors (AIs) or selective estrogen receptor modulators (SERMs) on folliculogenesis and oocyte yield.
Materials and methods: This study included 471 female patients, of whom 346 underwent IVF cycles for oocyte or embryo cryopreservation. Prior to initiating treatment, a comprehensive review of medical records provided by oncologists was conducted, detailing the oncological diagnosis, disease stage, and results of diagnostic imaging (CT, MRI, and PET-CT), as well as morphological and immunohistochemical analyses. Additionally, each patient received a consultation with an oncologist-mammologist on the day of enrollment, which included an evaluation of the patient’s reproductive health, ovarian reserve, and overall gynecological status. The data were integrated to develop a personalized treatment protocol.
Results: The mean age of patients seeking fertility preservation was 29.5 (6.8) years, with the majority (221/346 (63.9%)) being under 35 years of age. All patients exhibited preserved ovarian reserve at the time of enrollment. Of the 346 breast cancer patients, 133 (38.4%) initiated ovarian stimulation during the follicular phase using a conventional protocol, whereas 213 (61.6%) commenced stimulation in the luteal phase using a random-start protocol. This study demonstrated that treatment efficacy, as measured by the number of retrieved oocytes and mature oocytes, depended on the patient’s ovarian reserve and was independent of the menstrual cycle phase at which stimulation was initiated. The administration of letrozole at doses of 2.5 mg and 5 mg yielded comparable outcomes in oocyte retrieval; however, the 5 mg dose was associated with significantly lower preovulatory estradiol levels. In contrast, the inclusion of tamoxifen in gonadotropin-based stimulation protocols resulted in suboptimal outcomes, with a trend toward reduced oocyte yield and quality.
Conclusion: The implementation of IVF protocols in patients with breast cancer should be guided by a multidisciplinary approach that incorporates both oncological and reproductive parameters. The number of oocytes retrieved is primarily determined by the ovarian reserve and is unaffected by the timing of stimulation initiation during the menstrual cycle. Aromatase inhibitors are the preferred pharmacological agents for ovarian stimulation in this patient population, whereas the use of tamoxifen is associated with inferior outcomes, including higher preovulatory estradiol levels and reduced oocyte quantity and quality.
Authors' contributions: Biryukova A.M., Nazarenko T.A. – conception and design of the study, manuscript editing and final approval; Biryukova A.M., Martirosyan Ya.O., Oshkina E.V. – material collection, statistical analysis, drafting of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: Research 121040600410-7 Nazarenko T.A. "Solving the problem of infertility in modern conditions by developing a clinical and diagnostic model of infertile marriage and using innovative technologies in assisted reproduction programs".
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Biryukova A.M., Nazarenko T.A., Martirosyan Ya.O., Oshkina E.V. Use of in vitro fertilization programs
to preserve reproductive material in patients with breast cancer.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (4): 61-70 (in Russian)
https://dx.doi.org/10.18565/aig.2025.38
Keywords
breast cancer
fertility preservation
ovarian stimulation
aromatase inhibitors
selective estrogen receptor modulators
in vitro fertilization (IVF)
References
- Zhao J., Liu J., Chen K., Li S., Wang Y., Yang Y. et al. What lies behind chemotherapy-induced amenorrhea for breast cancer patients: a meta-analysis. Breast Cancer Res. Treat. 2014; 145(1): 113-28. https://dx.doi.org/10.1007/s10549-014-2914-x.
- Anderson R.A., Themmen A.P.N., Al-Qahtani A., Groome N.P., Cameron D.A. The effects of chemotherapy and long-term gonadotrophin suppression on the ovarian reserve in premenopausal women with breast cancer. Hum. Reprod. 2006; 21(10): 2583-92. https://dx.doi.org/10.1093/humrep/del201.
- Del Castillo L.M., Buigues A., Rossi V., Soriano M.J., Martinez J., De Felici M. et al. The cyto-protective effects of LH on ovarian reserve and female fertility during exposure to gonadotoxic alkylating agents in an adult mouse model. Hum. Reprod. 2021; 36(9): 2514-28. https://dx.doi.org/10.1093/humrep/deab165.
- Raphael J., Trudeau M.E., Chan K. Outcome of patients with pregnancy during or after breast cancer: a review of the recent literature. Curr. Oncol. 2015; 22(Suppl. 1): S8-18. https://dx.doi.org/10.3747/co.22.2338.
- Kontzoglou K., Stamatakos M., Tsaknaki S., Goga H., Kostakis A., Safioleas M. Successful pregnancy after breast cancer therapy: dream or reality? Int. Semin. Surg. Oncol. 2009; 6: 7. https://dx.doi.org/10.1186/1477-7800-6-7.
- Azim H.A., Santoro L., Pavlidis N., Gelber S., Kroman N., Azim H. et al. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur. J. Cancer. 2011; 47(1): 74-83. https://dx.doi.org/10.1016/j.ejca.2010.09.007.
- Kroman N., Jensen M.B., Melbye M., Wohlfahrt J., Mouridsen H.T. Should women be advised against pregnancy after breast-cancer treatment? Lancet. 1997; 350(9074): 319-22. https://dx.doi.org/10.1016/S0140-6736(97)03052-3.
- Blakely L.J., Buzdar A.U., Lozada J.A., Shullaih S.A., Hoy E., Smith T.L. et al. Effects of pregnancy after treatment for breast carcinoma on survival and risk of recurrence. Cancer. 2004; 100(3): 465-9. https://dx.doi.org/10.1002/cncr.11929.
- Azim H.A., Kroman N., Paesmans M., Gelber S., Rotmensz N., Ameye L. et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J. Clin. Oncol. 2013; 31(1): 73-9. https://dx.doi.org/10.1200/JCO.2012.44.2285.
- Oktay K., Harvey B.E., Partridge A.H., Quinn G.P., Reinecke J., Taylor H.S. et al. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J. Clin. Oncol. 2018; 36(19): 1994-2001. https://dx.doi.org/10.1200/JCO.2018.78.1914.
- Nye L., Rademaker A., Gradishar W.J. Breast cancer outcomes after diagnosis of hormone-positive breast cancer and subsequent pregnancy in the tamoxifen era. Clin. Breast Cancer. 2017; 17(4): e185-9. https://dx.doi.org/10.1016/j.clbc.2016.12.014.
- Lambertini M., Peccatori F.A., Demeestere I., Amant F., Wyns C., Stukenborg J.B. et al.; ESMO Guidelines Committee. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines. Ann. Oncol. 2020; 31(12): 1664-78. https://dx.doi.org/10.1016/j.annonc.2020.09.006.
- Peccatori F.A., Pup L. Del, Salvagno F., Guido M., Sarno M.A., Revelli A. et al. Fertility preservation methods in breast cancer. Breast Care. 2012; 7(3): 197-202. https://dx.doi.org/10.1159/000339671.
- Назаренко Т.А., Бурдули А.Г., Мартиросян Я.О., Джанашвили Л.Г. Криоконсервация репродуктивного материала у онкологических больных. Акушерство и гинекология. 2019; 9: 40-9. [Nazarenko T.A., Burduli A.G., Martirosyan Ya.O., Dzhanashvili L.G. Cryopreservation of reproductive material in cancer patients. Obstetrics and Gynecology. 2019; (9): 40-9. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.9.40-49.
- Bedoschi G.M., de Albuquerque F.O., Ferriani R.A., Navarro P.A. Ovarian stimulation during the luteal phase for fertility preservation of cancer patients: case reports and review of the literature. J. Assist. Reprod. Genet. 2010; 27(8): 491-4. https://dx.doi.org/10.1007/s10815-010-9429-0.
- Назаренко Т.А., Мартиросян Я.О., Бирюкова А.М., Джанашвили Л.Г., Иванец Т.Ю., Сухова Ю.В. Опыт стимуляции яичников в режиме random-start протоколов для сохранения репродуктивного материала онкологических больных. Акушерство и гинекология. 2020; 4: 52-8. [Nazarenko T.A., Martirosyan Ya.O., Biryukova A.M., Dzhanashvili L.G., Ivanets T.Yu., Sukhova Yu.V. Experience in random-start ovarian stimulation for preserving reproductive material of cancer patients. Obstetrics and Gynecology. 2020; (4): 52-8. (in Russian)]. https://dx.doi.org/10.18565/aig.2020.4.52-58.
- Корнеева И.Е., Мартиросян Я.О., Ковальчук А.И., Назаренко Т.А., Бирюкова А.М., Веюкова М.А., Иванец Т.Ю. Особенности фолликуло-стероидо-оогенеза при стимуляции яичников в лютеиновую фазу менструального цикла. Акушерство и гинекология. 2021; 7: 107-12. [Korneeva I.E., Martirosyan Ya.O., Koval’chuk A.I., Nazarenko T.A., Biryukova A.M., Veyukova M.A., Ivanets T.Yu. Characteristics of folliculogenesis, steroidogenesis, and oogenesis during ovarian stimulation in the luteal phase of the menstrual cycle. Obstetrics and Gynecology. 2021; (7): 107-12 (in Russian)]. https://dx.doi.org/10.18565/aig.2021.7.107-112.
- Cakmak H., Rosen M.P. Ovarian stimulation in cancer patients. Fertil. Steril. 2013; 99(6): 1476-84. https://dx.doi.org/10.1016/j.fertnstert.2013.03.029.
- Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol. 2022; 23(3): 382-92. https://dx.doi.org/10.1016/S1470-2045(21)00758-0.
Received 19.02.2025
Accepted 24.03.2025
About the Authors
Almina M. Biryukova, PhD, Clinical Supervisor at the F. Paulsen Research and Educational Center for ART with the Clinical Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, a_birukova@oparina4.ruTatiana A. Nazarenko, Dr. Med. Sci., Professor, Head of the Institute of Reproductive Medicine, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia,
117997, Russia, Moscow, Ac. Oparin str., 4, t_nazarenko@oparina4.ru, https://orcid.org/0000-0002-5823-1667
Yana O. Martirosyan, PhD, Junior Researcher at the F. Paulsen Research and Educational Center for ART with the Clinical Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, ya_martirosyan@oparina4.ru, https://orcid.org/0000-0002-9304-4410
Elena V. Oshkina, Oncologist at the Breast Pathology Department, V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, E_oshkina@oparina4.ru
Similar Articles
