Comparative evaluation of embryological outcomes following conventional IVF and ICSI in couples with unexplained infertility: a single-center prospective study
Ishchuk M.P., Perminova S.G., Mityurina E.V., Filimonov S.F., Sannikova E.S.
Objective. To evaluate embryological and clinical outcomes in IVF cycles among couples with unexplained infertility following conventional in vitro fertilization (IVF) versus intracytoplasmic sperm injection (ICSI).
Materials and methods. This single-center prospective comparative study included 116 assisted reproductive technology cycles in couples with unexplained infertility, treated between January 2024 and January 2026. Conventional IVF was performed in 58 cycles and ICSI were performed in 58 cycles each. Cycles with split insemination and those involving preimplantation genetic testing for aneuploidy (PGT-A) were excluded from the analysis. The primary outcome was the normal fertilization rate. The secondary outcomes included the blastulation rate, proportion of good-quality blastocysts, implantation rate, pregnancy rate, and clinical pregnancy rate. To account for potential confounding, adjusted analyses were performed using generalized linear models, and pregnancy rates were compared using Fisher's exact test.
Results. Baseline clinical characteristics were generally comparable between the groups, although the starting gonadotropin dose was higher in the ICSI group. Sperm concentration, total motility, and proportion of mature oocytes were higher in the conventional IVF group. No statistically significant between-group differences were observed in the primary outcome, the normal fertilization rate. Likewise, no significant differences were found in the blastulation rate or the proportion of high-quality blastocysts. Implantation, pregnancy, and clinical pregnancy rates were numerically higher in the ICSI group; however, these differences were not statistically significant. After multivariable adjustment, ICSI was not associated with an increased normal fertilization rate (adjusted odds ratio [aOR] 0.96; 95% confidence interval [CI] 0.74–1.25; p=0.763), blastulation rate (aOR 0.77; 95% Cl 0.59–1.01; p=0.063), good-quality blastocyst formation (aOR 0.80; 95% Cl 0.49–1.31; p=0.370), or implantation rate (aOR 1.01; 95% CI 0.003–330; p=0.962).
Conclusion. In patients with unexplained infertility, ICSI was not associated with improved normal fertilization rates or most embryological outcomes compared with conventional IVF. These findings do not support the routine use of ICSI in couples with unexplained infertility and suggest that a selective approach to choosing a fertilization method is warranted.
Authors’ contributions. Perminova S.G., Ishchuk M.P. – conception and design of the study; Ischuk M.P., Mityurina E.V., Filimonov S.F., Sannikova E.S. – material collection and processing; Ishchuk M.P. – statistical analysis, drafting of the manuscript; Perminova S.G., Mityurina E.V. – editing of the manuscript; Filimonov S.F., Sannikova E.S. – embryological stage; Ishchuk M.P., Perminova S.G., Mityurina E.V., Filimonov S.F., Sannikova E.S. – approval of the final version of the manuscript.
Conflicts of interest. The authors have no conflicts of interest to declare.
Funding. There was no funding for this study.
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 (Ref. No. 1 from January 25, 2024).
Generative Artificial Intelligence. A generative artificial intelligence tool (ChatGPT, DoTrace) was used during manuscript preparation solely for editorial and technical formatting and for harmonizing the manuscript structure with the journal’s formatting requirements.
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: Ishchuk M.P., Perminova S.G., Mityurina E.V., Filimonov S.F., Sannikova E.S.
Comparative evaluation of embryological outcomes following conventional IVF and ICSI
in couples with unexplained infertility: a single-center prospective study.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (6): 163-171 (in Russian)
https://dx.doi.org/10.18565/aig.2026.122
Keywords
unexplained infertility
IVF
ICSI
fertilization
blastulation
implantation
assisted reproductive technology
References
- Romualdi D., Ata B., Bhattacharya S., Bosch Е., Costello М., Gersak K. et al. Evidence-based guideline: unexplained infertility. Hum. Reprod. 2023; 38(10): 1881-90. https://dx.doi.org/10.1093/humrep/dead150
- Министерство здравоохранения Российской Федерации. Клинические рекомендации. Женское бесплодие. 2021. [Ministry of Health of the Russian Federation. Clinical guidelines. Female infertility. 2021 (in Russian)].
- Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Intracytoplasmic sperm injection (ICSI) for non-male factor indications: a committee opinion. Fertil. Steril. 2020; 114(2): 239-45. https://dx.doi.org/10.1016/j.fertnstert.2020.05.032
- Zoltan M. The signal that stimulates mammalian embryo development. Front. Cell Dev. Biol. 2024; 12: 1474009. https://dx.doi.org/10.3389/fcell.2024.1474009
- Palermo G., Joris H., Devroey P. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992; 340: 17-8. https://dx.doi.org/10.1016/0140-6736(92)92425-F
- Smeenk J., Wyns C., De Geyter C., Kupka M., Bergh C., Cuevas Saiz I. et al. ART in Europe, 2019: results generated from European registries by ESHRE. Hum. Reprod. 2023; 12(38): 2321-38. https://dx.doi.org/10.1093/humrep/dead197
- 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
- Cutting E., Horta F., Dang V., van Rumste M.M., Mol B.W.J. Intracytoplasmic sperm injection versus conventional in vitro fertilisation in couples with males presenting with normal total sperm count and motility. Cochrane Database Syst. Rev. 2023; 8(8): CD001301. https://dx.doi.org/10.1002/14651858.CD001301.pub2
- Dang V.Q., Vuong L.N., Luu T.M., Pham T.D., Ho T.M., Ha A.N. et al. Intracytoplasmic sperm injection versus conventional in-vitro fertilisation in couples with infertility in whom the male partner has normal total sperm count and motility: an open-label, randomised controlled trial. Lancet. 2021; 397(10284): 1554-63. https://dx.doi.org/10.1016/S0140-6736(21)00535-3
- Wang Y., Li R., Yang R., Zheng D., Zeng L., Lian Y. et al. Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial. Lancet. 2024; 403(10430): 924-34. https://dx.doi.org/10.1016/S0140-6736(23)02416-9
- Бачурин А.В., Киракосян Е.В., Назаренко Т.А., Павлович С.В. Анализ эмбриологического этапа программ экстракорпорального оплодотворения у пациентов с бесплодием неясного генеза. Акушерство и гинекология. 2022; 9: 81-6. https://dx.doi.org/10.18565/aig.2022.9.81-86 [Bachurin A.V., Kirakosyan E.V., Nazarenko N.A., Pavlovich S.V. Analysis of the embryonic stage of in vitro fertilization programs in patients with unexplained infertility. Obstetrics and Gynecology. 2022; (9): 81-6 (in Russian). https://dx.doi.org/10.18565/aig.2022.9.81-86].
- Iwamoto A., Summers K.M., Sparks A., Mancuso A.C. Intracytoplasmic sperm injection versus conventional in vitro fertilization in unexplained infertility. F. S. Reports. 2024; 5(3): 263-71. https://dx.doi.org/10.1016/j.xfre.2024.06.003
- 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
- Somigliana E., Barbara G., Micci L.G., Di Stefano G., Paffoni A., Vigano P. ICSI for non-male infertility: from ineffectiveness to gender bias? Reprod. Biomed. Online. 2025; 50(3): 104706. https://dx.doi.org/10.1016/j.rbmo.2024.104706
- Cornelisse S., Zagers M., Kostova E., Fleischer K., van Wely M., Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilization. Cochrane Database Syst. Rev. 2020; 2020(9): CD005291. https://dx.doi.org/10.1002/14651858.CD005291.pub3
- Gleicher N., Barad D.H., Patrizio P., Orvieto R. We have reached a dead end for preimplantation genetic testing for aneuploidy. Hum. Reprod. 2022;37(Suppl. 1): 2730-4. https://dx.doi.org/10.1093/humrep/deac052
- Gardner D.K., Schoolcraft W.B. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil. Steril. 2000; 73(6): 1155-8. https://dx.doi.org/10.1016/S0015-0282(00)00518-5
- Wang X., Tian P.Z., Zhao Y.J., Lu J., Dong C.Y., Zhang C.I. The association between female age and pregnancy outcomes in patients receiving first elective single embryo transfer cycle: a retrospective cohort study. Sci. Rep. 2024; 14(1): 19216. https://dx.doi.org/0.1038/s41598-024-70249-1
- Berntsen S., Zedeler A., Grøndahl M.L., Vestergaard Gabrielsen A., Rønn Petersen M., Frøding Skipper D. et al. Early embryo developmental kinetics following IVF versus ICSI in patients without severe male factor infertility: a secondary analysis of a multicentre, randomized controlled trial (INVICSI). Hum. Reprod. 2025; 40(10): 1877-85. https://dx.doi.org/10.1093/humrep/deaf157
Received 16.04.2026
Accepted 10.06.2026
About the Authors
Maria P. Ishchuk, PhD Student, 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, marumariyaish@gmail.com,https://orcid.org/0000-0002-9577-1777
Svetlana G. Perminova, Dr. Med. Sci., Professor, Leading Researcher, 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. Oparin str., 4,
s_perminova@oparina4.ru, https://orcid.org/0000-0003-44
Elena V. Mituyrina, Dr. Med. Sci., Senior Researcher, 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. Oparin str., 4, e_mityurina@oparina4.ru, https://orcid.org/0000-0001-8830-2158
Sergey F. Filimonov, Head of the Laboratory of Clinical Embryology, 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. Oparin str., 4, s_felimonov@oparina4.ru
Elena S. Sannikova, Embryologist, 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. Oparin str., 4, el.sannikowa2013@yandex.ru,
https://orcid.org/0000-0002-9577-1777
Corresponding author: Maria P. Ishchuk, marumariyaish@gmail.com
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