Thin endometrium as a barrier to implantation and a trigger of obstetric risks: the possibilities of local enzyme therapy in assisted reproductive technology programs | Ukrainian Medical Journal

Kotlik V.V.

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Thin endometrium as a barrier to implantation and a trigger of obstetric risks: the possibilities of local enzyme therapy in assisted reproductive technology programs

Thin endometrium as a barrier to implantation and a trigger of obstetric risks: the possibilities of local enzyme therapy in assisted reproductive technology programs

June 30, 2026

102

Obstetrics and Gynecology

Kotlik V.V.

УДК: 618.177-089.888.11

DOI: 10.32471/umj.1680-3051.278311

Keywords :

ART,

chronic endometritis,

Distreptaza® Distrept,

endometrial receptivity,

enzyme therapy,

implantation window,

pathology of deep placentation,

Specialities :

Obstetrics and Gynecology

Resume

The review summarizes current data on the pathogenesis, diagnosis and treatment of thin endometrium in assisted reproductive technology programs. The role of receptivity disorders, stromal fibrosis and chronic inflammation in the formation of therapeutically refractory forms of pathology is considered, as well as their relationship with placentation defects and adverse obstetric outcomes. The feasibility of including local enzyme therapy (streptokinase + streptodornase) in comprehensive preconceptional preparation is substantiated with the aim of reducing the severity of fibrosis, improving perfusion and restoring endometrial receptivity.

References

1. Xu S., Diao H., Xiong Y. et al. (2025) The study on the clinical efficacy of endometrial receptivity analysis and influence factors of displaced window of implantation. Sci. Rep., 15: 7326. doi.org/10.1038/s41598-025-91745-y.
2. Makrigiannakis A., Makrygiannakis F., Vrekoussis T.. (2021) Approaches to Improve Endometrial Receptivity in Case of Repeated Implantation Failures. Front. Cell Dev. Biol., 9: 613277. doi: 10.3389/fcell.2021.613277.
3. Craciunas L., Gallos I., Chu J. et al. (2019) Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum. Reprod. Update, 25(2): 202–223. doi.org/10.1093/humupd/dmy044.
4. Bulletti F.M., Sciorio R., Conforti A. et al. (2025) Causes of embryo implantation failure: a systematic review and meta-analysis of procedures to increase embryo implantation potential. Front Endocrinol., 15: 1429193. doi.org/10.3389/fendo.2024.1429193.
5. Ma J., Gao W., Li D. (2023) Recurrent implantation failure: A comprehensive summary from etiology to treatment. Front. Endocrinol. (Lausanne), 13: 1061766. doi: 10.3389/fendo.2022.
6. Gingold J.A., Lee J.A., Rodriguez-Purata J. et al. (2015) Endometrial pattern, but not endometrial thickness, affects implantation rates in euploid embryo transfers. Fertil. Steril., 104(3): 620–628. doi.org/10.1016/j.fertnstert.2015.05.036.
7. Liu K.E., Hartman M., Hartman A. et al. (2018) The impact of a thin endometrial lining on fresh and frozen-thaw IVF outcomes: an analysis of over 40000 embryotransfers. Hum. Reprod., 33(10): 1883–1888. doi.org/10.1093/humrep/dey281.
8. Bu Z., Wang K., Dai W. et al. (2016) Endometrial thickness significantly affects clinical pregnancy and live birth rates in frozen-thawed embryo transfer cycles. Gynecol. Endocrinol., 32(7): 522–525. doi.org/10.3109/09513590.2015.1136503.
9. Pérez-Milán F., Caballero-Campo M., Carrera-Roig M. et al. (2025) Spanish Fertility Society Special Interest Group on Benign Organic Reproductive Disorders. Impact of endometrial thickness on reproductive outcome in fresh and frozen-thawed embryo transfer: systematic review and meta-analysis. Ultrasound Obstet. Gynecol., 66(3): 271–281. doi: 10.1002/uog.29270.
10. Dreisler E., Kjer J.J. (2018) Asherman’s syndrome: current perspectives on diagnosis and management. Int. J. Womens Health, 10: 191–198. doi.org/10.2147/IJWH.S165474.
11. Vitagliano A., Laganà A.S., De Ziegler D. et al. (2022) Chronic Endometritis in Infertile Women: Impact of Untreated Disease, Plasma Cell Count and Antibiotic Therapy on IVF Outcome—A Systematic Review and Meta-Analysis. Diagnostics, 12(9): 2250. doi.org/10.3390/diagnostics12092250.
12. Weizel I., Lasri D., Hersko Klement A. et al. (2025) Endometrial hypoperfusion: the missing link in refractory thin endometrium. Front. Reprod. Health, 7: 1732672. doi.org/10.3389/frph.2025.1732672.
13. Cimadomo D., de los Santos M.J., Griesinger G. et al. (2023) ESHRE good practice recommendations on recurrent implantation failure. Hum. Reprod. Open, 2023(3): hoad023. doi.org/10.1093/hropen/hoad023.
14. Narayanan K.B. (2025) Enzyme-Based Anti-Inflammatory Therapeutics for Inflammatory Diseases. Pharmaceutics, 17(5): 606. doi.org/10.3390/pharmaceutics17050606.
15. Бенюк В.О., Гончаренко В.М., Кравченко Ю.В. et al. (2018) Сучасний алгоритм діагностики гіперпластичних процесів ендометрія. Збірник наукових праць Асоціації акушерів-гінекологів України, 2(42): 25–29.
16. Teh W.T., Chung J., Holdsworth-Carson S.J. et al. (2023) A molecular staging model for accurately dating the endometrial biopsy. Nat. Commun., 14(1): 6222. doi: 10.1038/s41467-023-41979-z.
17. Zhang W.B., Li J., Li Q. et al. (2024) Endometrial transcriptome profiling of patients with recurrent implantation failure during hormone replacement therapy cycles. Front. Endocrinol. (Lausanne).,14: 1292723. doi: 10.3389/fendo.2023.1292723.
18. Dankó I., Tankó A., Kelemen E. et al. (2026) Fetal growth restriction and preeclampsia as endpoints of a spectrum from the viewpoint of placental histopathology. Minerva Obstet. Gynecol., 78(3): 205–214. doi: 10.23736/S2724-606X.25.05779-3.
19. Burton G.J., Yung H.W., Cindrova-Davies T. et al. (2016) Placental endoplasmic reticulum stress and oxidative stress in the pathophysiology of unexplained intrauterine growth restriction and early onset preeclampsia. Placenta, 43: 4–8. doi.org/10.1016/j.placenta.2015.12.006.
20. Mouhayar Y., Franasiak J.M., Sharara F.I. (2019) Obstetrical complications of thin endometrium in assisted reproductive technologies: a systematic review. J. Assist. Reprod. Genet., 36(4): 607–611. doi.org/10.1007/s10815-019-01407-y.
21. Yuan X., Saravelos S.H., Wang Q. et al. (2016) Endometrial thickness as a predictor of pregnancy outcomes in 10787 fresh IVF-ICSI cycles. Reprod. Biomed. Online, 33(2): 197–205. doi.org/10.1016/j.rbmo.2016.05.002.
22. Lai S., Zhang L., Luo Y. et al. (2024) A sonographic endometrial thickness <7 mm in women undergoing in vitro fertilization increases the risk of placenta accreta spectrum. Am. J. Obstet. Gynecol., 231(5): 557.e1–557.e18. doi.org/10.1016/j.ajog.2024.02.301.
23. Jauniaux E., Ayres-de-Campos D., Langhoff-Roos J. et al. (2019) FIGO consensus guidelines on placenta accreta spectrum disorders. Int. J. Gynecol. Obstet., 146(1): 15–35. doi.org/10.1002/ijgo.12871.
24. Hong I.S. (2024) Endometrial Stem Cells: Orchestrating Dynamic Regeneration of Endometrium and Their Implications in Diverse Endometrial Disorders. Int. J. Biol. Sci., 20(3): 864–879. doi.org/10.7150/ijbs.89795.
25. Blanco-Breindel M.F., Singh M., Kahn J. (2026) Endometrial Receptivity. [Updated 2023 Jun. 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publ.
26. Li X., Lu J., Zhang J. et al. (2025) The efficacy of adjuvant therapies in improving endometrial function of women undergoing assisted reproductive technology: a systematic review and network meta-analysis. BMC Pregnancy Childbirth, 25: 1194. doi.org/10.1186/s12884-025-08296-3.
27. Hu S., Li Z., Cang Z. et al. (2020) Exosomes: A new strategy for endometrial regeneration. Front. Cell Dev. Biol., 8: 598. doi.org/10.3389/fcell.2020.00598.
28. Татарчук Т.Ф., Косей Н.В., Занько О.В. et al. (2018) Endometrial polyps: optimization of anti-inflammatory therapy. Reprod. Endocrinol., 44: 8–14. doi.org/10.18370/2309-4117.2018.44.8-14.
29. Шурпяк С.О., Пирогова В.І. (2016) Терапія хронічного ендометриту у жінок з порушеннями репродуктивного здоров’я. Бібліотека «Здоров’я України», 470–477.
30. Phaladze L. (2025) Thin endometrium: therapeutic potential of enzyme therapy. 20th World Congress on Human Reproduction, Florence, Italy.
31. Odendaal J., Fishwick K., Correia G.D.S. et al. (2026) CD138 expression in the endometrium associates with endometrial timing and inflammatory status but not microbiota composition. Hum. Reprod., 41(5): 699–711. doi.org/10.1093/humrep/deag032.
32. Coştur Filiz P., Filiz S. (2026) Endometrial receptivity: molecular mechanisms, thin endometrium subtypes, and mechanism-based therapeutic approaches. Kocaeli Üniversitesi Sağlık Bilimleri Dergisi, 12(2): 157–163. doi.org/10.30934/kusbed.1836274
33. Котлик В.В. (2019) Програмування ендометрію в циклах ДРТ: безвихідь чи перспектива? Жіночий лікар, 4: 84.
34. Котлик В.В. (2020) Підготовка до зачаття: фокус на ендометрій. Здоров’я України, 5.
35. Saad-Naguib M.H., Kenfack Y., Sherman L.S. et al. (2024) Impaired receptivity of thin endometrium: therapeutic potential of mesenchymal stem cells. Front. Endocrinol., 14: 1268990. doi.org/10.3389/fendo.2023.1268990.
36. Інструкція для медичного застосування лікарського засобу Дістрептаза Дістрепт (супозиторії ректальні). Державний реєстр лікарських засобів України.