Differentiated approach to the choice of oocyte fertilization method in assisted reproductive technology programs
Bulatova V.A., Romanov A.Yu., Filimonov S.F., Dolgushina N.V., Nazarenko T.A.
In modern clinical practice, there has been an increase in the use of assisted reproductive technologies (ART). According to the 2023 report from the ART Registry of the Russian Association for Human Reproduction, the fertilization rate of oocytes using intracytoplasmic sperm injection (ICSI) is 58.3%, whereas in 2013 it was 52.1%, and in 2003 it was only 26.6%.
ICSI fertilization extends beyond indications related to male factor infertility, and is also observed among patients with borderline and normal semen parameters, despite the lack of convincing evidence of the advantage of oocyte fertilization using ICSI over conventional in vitro fertilization (IVF) in these groups, as well as the higher cost of this method.
There are currently numerous contradictory studies in the scientific literature regarding the method of oocyte fertilization in IVF programs for patients without male factor infertility. This does not make it possible to establish a standardized protocol for the management of these patients. It applies in particular to patients with unexplained infertility who are candidates for preimplantation genetic testing (PGT), women over 35 years old, and cycles in which fewer than four oocytes are retrieved, where there is no consensus on the optimal fertilization strategy.
Conclusion. The use of various fertilization techniques in ART programs in the absence of a significant male factor showed comparable embryological and clinical outcomes in women of advanced reproductive age, with a low number of retrieved oocytes, in cases of unexplained infertility, and in ART with planned PGT-A. ICSI is indicated to minimize the risk of contamination in PCR-based preimplantation genetic testing (PGT-M). Oocyte fertilization using ICSI entails additional financial costs. In the absence of improved clinical outcomes, this requires a more rigorous approach to determining indications.
Authors’ contributions. Romanov A.Yu., Nazarenko T.A., Dolgushina N.V. – developing the concept of the article and the design of the work; Bulatova V.A., Romanov A.Yu., Filimonov S.F. – analysis of the literature data; Bulatova V.A., Romanov A.Yu. – writing the text; Bulatova V.A., Romanov A.Yu., Filimonov S.F., Dolgushina N.V., Nazarenko T.A. – editing and final approval of the article.
Conflicts of interest. The authors declare no potential conflicts of interest related to the publication of this article.
Funding. The work was carried out as part of the PhD thesis by V.A. Bulatova on the topic ‘Improving the outcomes of assisted reproductive technology programs through a differentiated approach to oocyte fertilization’.
For citation: Bulatova V.A., Romanov A.Yu., Filimonov S.F., Dolgushina N.V., Nazarenko T.A.
Differentiated approach to the choice of oocyte fertilization method in assisted reproductive technology programs.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (5): 53-61 (in Russian)
https://dx.doi.org/10.18565/aig.2026.56
Keywords
References
- Meczekalski B., Szeliga A., Podfigurna A., Miechowicz I., Adashi E.Y. Assisted reproductive technology outcome in United States of America and Australia with New Zealand: comparison of annual reports 2005-2016. Gynecol. Endocrinol. 2020; 36(11): 959-67. https://dx.doi.org/10.1080/09513590.2020.1737006
- Ottun T.A., Adewunmi A.A., Jinadu F.O., Olumodeji A.M., Akinlusi F.M., Rabiu K.A. et al. A decennial cross-sectional review of assisted reproductive technology in a Tertiary Hospital in Southwest Nigeria. BMC Pregnancy Childbirth. 2023; 23(1): 680. https://dx.doi.org/10.1186/s12884-023-05964-0
- Wang S.F., Seifer D.B. Assessment of a decade of change in U.S. assisted reproductive technology cumulative live-birth rates: 2004-2009 compared with 2014-2020. Obstet Gynecol. 2024; 143(6): 839-48. https://dx.doi.org/10.1097/AOG.0000000000005598
- Корнеева И.Е., Назаренко Т.А., Перминова С.Г., Митюрина Е.В., Цыбизова Т.И., Дашиева А.Е. Медико-социальные факторы бесплодия в России. Акушерство и гинекология. 2023; 3: 65-72. [Korneeva I.Е., Nazarenko Т.А., Perminova S.G., Mityurina E.V., Cybizova T.I., Dashieva A.E. Medical and social factors of infertility in Russia. Obstetrics and Gynecology. 2023; (3): 65-72 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.279
- Beebeejaun Y., Copeland T., Duffy J.M.N., Sarris I., Showell M., Wang R. et al. Triggering oocyte maturation in in vitro fertilization treatment in healthy responders: a systematic review and network meta-analysis. Fertil. Steril. 2025; 123(5): 812-26. https://dx.doi.org/10.1016/j.fertnstert.2024.11.011
- Chen W., Bai M.Z., Yang Y., Sun D., Wu S., Sun J. et al. ART strategies in Klinefelter syndrome. J. Assist. Reprod. Genet. 2020; 37(9): 2053-79. https://dx.doi.org/10.1007/s10815-020-01818-2
- Tulek F., Kahraman A., Demirel L.C. Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin improves live birth rates in POSEIDON group 3 and 4 expected poor responders. Gynecol. Endocrinol. 2022; 38(9): 731-5. https://dx.doi.org/10.1080/09513590.2022.2101635
- Palermo G., Joris H., Devroey P., Van Steirteghem A.C. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992; 340(8810): 17-8. https://dx.doi.org/10.1016/0140-6736(92)92425-f
- Российская Ассоциация Репродукции Человека (РАРЧ). Доступно по: https://www.rahr.ru/index.php. [Russian Association for Human Reproduction (RAHR). Available at: https://www.rahr.ru/index.php (in Russian)].
- Rubino P., Viganò P., Luddi A., Piomboni P. The ICSI procedure from past to future: a systematic review of the more controversial aspects. Hum. Reprod. Update. 2016; 22(2): 194-227. https://dx.doi.org/10.1093/humupd/dmv050
- Boulet S.L., Mehta A., Kissin D.M., Warner L., Kawwass J.F., Jamieson D.J. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015; 313(3): 255-63. https://dx.doi.org/10.1001/jama.2014.17985
- Björndahl L. What is normal semen quality? On the use and abuse of reference limits for the interpretation of semen analysis results. Hum. Fertil. 2011; 14(3): 179-86. https://dx.doi.org/10.3109/14647273.2011.580823
- WHO laboratory manual for the examination and processing of human semen. Sixth Edition. Geneva: World Health Organization; 2021. 276 p. Available at: https://www.micropticsl.com/wp-content/uploads/2021/10/who_laboratory_manual_for_the_examination_and_processing_of_human_semen_sixth_edition.pdf
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Мужское бесплодие. 2025. [Ministry of Health of the Russian Federation. Clinical guidelines. Male infertility. 2025. (in Russian)].
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Женское бесплодие. 2024. [Ministry of Health of the Russian Federation. Clinical guidelines. Female infertility. 2024. (in Russian)].
- Киракосян Е.В., Назаренко Т.А., Бачурин А.В., Павлович С.В. Клиническая характеристика и эмбриологические показатели программ экстракорпорального оплодотворения у женщин с бесплодием неясного генеза. Акушерство и гинекология. 2022; 5: 83-90. [Kirakosyan E.V., Nazarenko T.A., Bachurin A.V., Pavlovich S.V. Clinical characteristics and embryological parameters in IVF programs for women with unexplained infertility. Obstetrics and Gynecology. 2022; (5: 83-90 (in Russian)]. https://dx.doi.org/10.18565/aig.2022.5.83-90
- Abbas A.M., Hussein R.S., Elsenity M.A., Samaha I.I., El Etriby K.A., Abd El-Ghany M.F. et al. Higher clinical pregnancy rate with in-vitro fertilization versus intracytoplasmic sperm injection in treatment of non-male factor infertility: Systematic review and meta-analysis. J. Gynecol. Obstet. Hum. Reprod. 2020; 49(6): 101706. https://dx.doi.org/10.1016/j.jogoh.2020.101706
- Geng T., Cheng L., Ge C., Zhang Y. The effect of ICSI in infertility couples with non-male factor: a systematic review and meta-analysis. J. Assist. Reprod. Genet. 2020; 37(12): 2929-45. https://dx.doi.org/10.1007/s10815-020-01970-9
- Lundin K., Sjögren A., Hamberger L. Reinsemination of one-day-old oocytes by use of intracytoplasmic sperm injection. Fertil. Steril. 1996; 66(1): 118-21. https://dx.doi.org/10.1016/S0015-0282(16)58397-6
- Chen L., Xu Z., Zhang N., Wang B., Chen H., Wang S. et al. Neonatal outcome of early rescue ICSI and ICSI with ejaculated sperm. J. Assist. Reprod. Genet. 2014; 31(7): 823-8. https://dx.doi.org/10.1007/s10815-014-0245-9
- Джусубалиева Т.М., Бекзатова К.А., Тевкин С.И., Баймурзаева Л.Г., Шишиморова М.С. ЭКО vs. ИКСИ в циклах, исключающих мужской фактор: опыт Института репродуктивной медицины. Репродуктивная медицина (Центральная Азия). 2022; 1(50): 23-35. [Jussubaliyevа T., Bekzatova K., Tevkin S., Baimurzayeva L., Shishimorova M. IVF vs. ICSI in cycles excluding the male factor infertility: experience of the Institute of Reproductive Medicine. Reproductive Medicine (Central Asia). 2022; 1(50): 23-35 (in Russian)]. https://dx.doi.org/10.37800/RM.1.2022.23-35
- Isikoglu M., Avci A., Kendirci Ceviren A., Aydınuraz B., Ata B. Conventional IVF revisited: Is ICSI better for non-male factor infertility? Randomized controlled double blind study. J. Gynecol. Obstet. Hum. Reprod. 2021; 50(7): 101990. https://dx.doi.org/10.1016/j.jogoh.2020.101990
- Esteves S.C., Roque M., Bedoschi G., Haahr T., Humaidan P. Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat. Rev. Urol. 2018; 15(9): 535-62. https://dx.doi.org/10.1038/s41585-018-0051-8
- Jančar N., Mihevc Ponikvar B., Tomšič S., Vrtačnik Bokal E., Korošec S. Is IVF/ICSI an independent risk factor for spontaneous preterm birth in singletons? A population-based cohort study. Biomed. Res. Int. 2018; 2018: 7124362. https://dx.doi.org/10.1155/2018/7124362
- Davies M.J., Moore V.M., Willson K.J., Van Essen P., Priest K., Scott H. et al. Reproductive technologies and the risk of birth defects. N. Engl. J. Med. 2012; 366(19): 1803-13. https://dx.doi.org/10.1056/NEJMoa1008095
- Паскарь С.С., Калугина А.С. Рейтинговая оценка эффективности методов экстракорпорального оплодотворения и инъекции сперматозоида в цитоплазму ооцита в первом протоколе вспомогательных репродуктивных технологий у пациенток молодого репродуктивного возраста. Проблемы репродукции. 2022; 28(2): 96-101. [Paskar S.S., Kalugina A.S. Rating assessment of the effectiveness of IVF and ICSI methods in female patients of young reproductive age in the first ART protocol. Russian Journal of Human Reproduction. 2022; 28(2): 96-101 (in Russian)]. https://dx.doi.org/10.17116/repro20222802196
- Olive E., Bull C., Gordon A., Davies-Tuck M., Wang R., Callander E. Economic evaluations of assisted reproductive technologies in high-income countries: a systematic review. Hum. Reprod. 2024; 39(5): 981-91. https://dx.doi.org/10.1093/humrep/deae039
- Younes G., Tannus S., Son W.Y., Dahan M.H. When to do intracytoplasmic sperm injection: a prospective comparison. Arch. Gynecol. Obstet. 2019; 300(5): 1461-71. https://dx.doi.org/10.1007/s00404-019-05324-4
- Stimpfel M., Jancar N., Vrtacnik-Bokal E., Virant-Klun I. Conventional IVF improves blastocyst rate and quality compared to ICSI when used in patients with mild or moderate teratozoospermia. Syst. Biol. Reprod. Med. 2019; 65(6): 458-64. https://dx.doi.org/10.1080/19396368.2019.1666436
- Liu H., Zhao H., Yu G., Li M., Ma S., Zhang H. et al. Conventional in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI): which is preferred for advanced age patients with five or fewer oocytes retrieved? Arch. Gynecol. Obstet. 2018; 297(5): 1301-6. https://dx.doi.org/10.1007/s00404-018-4696-6
- Sunderam S., Boulet S.L., Kawwass J.F., Kissin D.M. Comparing fertilization rates from intracytoplasmic sperm injection to conventional in vitro fertilization among women of advanced age with non-male factor infertility: a meta-analysis. Fertil. Steril. 2020; 113(2): 354-63.e1. https://dx.doi.org/10.1016/j.fertnstert.2019.09.035
- Tannus S., Son W.Y., Gilman A., Younes G., Shavit T., Dahan M.H. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum. Reprod. 2017; 32(1): 119-24. https://dx.doi.org/10.1093/humrep/dew298
- McPherson N.O., Vincent A.D., Pacella-Ince L., Tremellen K. Comparison of in vitro fertilisation/intracytoplasmic sperm injection on live birth rates in couples with non-male factor infertility and advanced maternal age. J. Assist. Reprod. Genet. 2021; 38(3): 669-78. https://dx.doi.org/10.1007/s10815-020-02026-8
- Jiesisibieke D., Tian T., Zhu X., Fang S., Zhang N., Ma J. et al. Reproductive outcomes of conventional in vitro fertilization and intracytoplasmic sperm injection in patients with non-severe male infertility across poor and different sub-optimal ovarian response categories: a cohort study based on 30,352 fresh cycles from 2009-2019. Reprod Sci. 2024; 31(5): 1353-62. https://dx.doi.org/10.1007/s43032-023-01444-0
- Isikoglu M., Ceviren A.K., Cetin T., Avci A., Aydinuraz B., Akgul O.K. et al. Comparison of ICSI and conventional IVF in non-male factor patients with less than four oocytes. Arch. Gynecol. Obstet. 2022; 306(2): 493-9. https://dx.doi.org/10.1007/s00404-022-06471-x
- Wu C.Y., Huang T.J., Hwu Y.M., Kuo-Kuang Lee R., Lin M.H. Comparison of clinical outcomes between conventional in vitro fertilization and intracytoplasmic sperm injection in poor responders with only single oocyte retrieved. Taiwan J. Obstet. Gynecol. 2023; 62(1): 55-8. https://dx.doi.org/10.1016/j.tjog.2022.02.052
- American Society for Reproductive Medicine (ASRM). Available at: https://www.asrm.org/
- Society for Assisted Reproductive Technology (SART). Available at: https://www.sart.org/
- European Society of Human Reproduction and Embryology (ESHRE). Available at: https://www.eshre.eu/
- Preimplantation Genetic Diagnosis International Society (PGDIS). Available at: https://www.pgdis.org/
- De Munck N., El Khatib I., Abdala A., El-Damen A., Bayram A., Arnanz A. et al. Intracytoplasmic sperm injection is not superior to conventional IVF in couples with non-male factor infertility and preimplantation genetic testing for aneuploidies (PGT-A). Hum. Reprod. 2020; 35(2): 317-27. https://dx.doi.org/10.1093/humrep/deaa002
- Lynch C., Armstrong E., Charitou M., Gordon T., Griffin D. Investigation of the risk of paternal cell contamination in PGT and the necessity of intracytoplasmic sperm injection. Hum. Fertil. (Camb). 2023; 26(5): 958-63. https://dx.doi.org/10.1080/14647273.2022.2026498
- Thornhill A.R., DeDie-Smulders C.E., Geraedts J.P., Harper J.C., Harton G.L., Lavery S.A. et al. ESHRE PGD Consortium “Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)”. Hum. Reprod. 2005; 20(1): 35-48. https://dx.doi.org/10.1093/humrep/deh579
- Zegers-Hochschild F., Adamson G.D., Dyer S., Racowsky C., de Mouzon J., Sokol R. et al. The International glossary on infertility and fertility care, 2017. Fertil. Steril. 2017; 108(3): 393-406. https://dx.doi.org/10.1016/j.fertnstert.2017.06.005
- Wilton L., Thornhill A., Traeger-Synodinos J., Sermon K.D., Harper J.C. The causes of misdiagnosis and adverse outcomes in PGD. Hum. Reprod. 2009; 24(5): 1221-8. https://dx.doi.org/10.1093/humrep/den488
- Palmerola K.L., Vitez S.F., Amrane S., Fischer C.P., Forman E.J. Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A). J. Assist. Reprod. Genet. 2019; 36(1): 153-7. https://dx.doi.org/10.1007/s10815-018-1347-6
- Li X., Li Q., Chang Y., He S., Wang Y., Liang X. et al. Conventional in vitro fertilization enhances preimplantation genetic testing for aneuploidy outcomes in couples with non-male factor infertility. Sci. Rep. 2025; 15(1): 24904. https://dx.doi.org/10.1038/s41598-025-10300-x
- Deng J., Kuyoro O., Zhao Q., Behr B., Lathi R.B. Comparison of aneuploidy rates between conventional in vitro fertilization and intracytoplasmic sperm injection in in vitro fertilization-intracytoplasmic sperm injection split insemination cycles. F. S. Rep. 2020; 1(3): 277-81. https://dx.doi.org/10.1016/j.xfre.2020.07.006
- Bhattacharya S., Hamilton M.P., Shaaban M., Khalaf Y., Seddler M., Ghobara T. et al. Conventional in vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Lancet. 2001; 357(9274): 2075-9. https://dx.doi.org/10.1016/s0140-6736(00)05179-5
- Johnson L.N.C., Sasson I.E., Sammel M.D., Dokras A. Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis. Fertil. Steril. 2013; 100(3): 704-11. https://dx.doi.org/10.1016/j.fertnstert.2013.04.038
- Paffoni A., Vitagliano A., Corti L., Somigliana E., Viganò P. Intracytoplasmic sperm injection versus conventional in vitro insemination in couples with non-male infertility factor in the ‘real-world’ setting: analysis of the HFEA registry. J. Transl. Med. 2024; 22(1): 687. https://dx.doi.org/10.1186/s12967-024-05515-x
- Human Fertilisation and Embryology Authority (HFEA). Available at: https://www.hfea.gov.uk/
- Song J., Liao T., Fu K., Xu J. ICSI does not improve live birth rates but yields higher cancellation rates than conventional IVF in unexplained infertility. Front. Med. 2020; 7: 614118. https://dx.doi.org/10.3389/fmed.2020.614118
- Singh N., Malhotra N., Mahey R., Kumari S., Saini M., Nisha. Should we be offering intracytoplasmic sperm injection to all couples with unexplained infertility: a cohort study. J. Hum. Reprod. Sci. 2025; 18(1): 9-15. https://dx.doi.org/10.4103/jhrs.jhrs_157_24
- Мартиросян Я.О., Кадаева А.И., Большакова А.С., Назаренко Т.А., Бирюкова А.М., Аскералиева А.Н. Клиническое использование расширенного генетического обследования в тактике ведения пар с бесплодием неясного генеза. Акушерство и гинекология. 2024; 12: 50-8. [Martirosyan Ya.O., Kadaeva A.I., Bolshakova A.S., Nazarenko T.A., Biryukova A.M., Askeralieva A.N. Clinical use of expanded genetic testing in the management of couples with unexplained infertility. Obstetrics and Gynecology. 2024; (12): 50-8 (in Russian)]. https://dx.doi.org/10.18565/aig.2024.274
- Moolenaar L.M., Cissen M., de Bruin J.P., Hompes P.G.A., Repping S., van der Veen F. et al. Cost-effectiveness of assisted conception for male subfertility. Reprod. Biomed. Online. 2015; 30(6): 659-66. https://dx.doi.org/10.1016/j.rbmo.2015.02.006
- Leusder M., van Elten H.J., Ahaus K., Hilders C.G.J.M., van Santbrink E.J.P. Patient-level cost analysis of subfertility pathways in the Dutch healthcare system. Eur. J. Heal. Econ. 2025; 26(6): 927-43. https://dx.doi.org/10.1007/s10198-024-01744-5
- Vitek W.S., Galárraga O., Klatsky P.C., Robins J.C., Carson S.A., Blazar A.S. Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection. Fertil. Steril. 2013; 100(5): 1381-8.e1. https://dx.doi.org/10.1016/j.fertnstert.2013.06.035
- Bouwmans C.A.M., Lintsen B.M.E., Eijkemans M.J.C., Habbema J.D.F., Braat D.D.M., Hakkaart L. A detailed cost analysis of in vitro fertilization and intracytoplasmic sperm injection treatment. Fertil. Steril. 2008; 89(2): 331-41. https://dx.doi.org/10.1016/j.fertnstert.2007.03.003
- Venson R., Maheshwari A., Nelson S.M., Boyd K.A. Setting a tariff for IVF and ICSI treatment: a cost analysis. Hum. Fertil. (Camb). 2023; 26(3): 519-26. https://dx.doi.org/10.1080/14647273.2023.2204409
Received 16.02.2026
Accepted 16.04.2026
About the Authors
Viktoriya A. Bulatova, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(909)066-15-95, viktoria_bulatova98@mail.ru, https://orcid.org/0000-0003-2992-4381Andrey Yu. Romanov, PhD, Head of the Department of Planning and Support of Scientific Projects, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(903)158-94-00, a_romanov@oparina4.ru,
https://orcid.org/0000-0003-1821-8684
Sergey F. Filimonov, Embryologist at the F. Paulsen Research and Educational Center for ART with the Clinical Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(962)080-82-14,
s_filimonov@oparina4.ru
Nataliya V. Dolgushina, Professor, Dr. Med. Sci., Deputy Director for Research, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(495)438-49-77, n_dolgushina@oparina4.ru, https://orcid.org/0000-0003-1116-138X
Tatiana A. Nazarenko, Professor, Dr. Med. Sci., Director of the Institute of Reproductive Medicine, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparina str., 4, +7(495)531-44-44, t_nazarenko@oparina4.ru,
https://orcid.org/0000-0003-4414-9942
Corresponding author: Andrey Yu. Romanov, a_romanov@oparina4.ru



