New therapeutic approaches for improving the outcomes of assisted reproductive technologies

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Abstract

Infertility is a global health problem that affects up to 17.5% of the world’s population. The use of assisted reproductive technologies makes it possible to solve this problem; however, it is not adequately efficient in all observed cases. Implantation failure remains a serious and multifaceted problem faced by clinicians in reproductive technology, despite the significant advances that have been made in this area. This review highlights promising studies on medical and invasive intervention methods and their possible combinations, which potentially improve the clinical treatment of implantation failures. Nevertheless, further study is required to assess the effectiveness and safety of each therapeutic approach, which can introduce new prospects in the treatment of infertility and increase the chances of successful implantation and pregnancy.

About the authors

Sergey A. Levakov

I.M. Sechenov First Moscow State Medical University

Email: levakoff@yandex.ru
ORCID iD: 0000-0002-4591-838X
SPIN-code: 5253-2836

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Moscow

Tatyana A. Gromova

I.M. Sechenov First Moscow State Medical University

Author for correspondence.
Email: tgromova928@yandex.ru
ORCID iD: 0000-0001-6104-9842
SPIN-code: 5122-4896

MD, Cand. Sci. (Medicine), Assistant of the Department

Russian Federation, Moscow

Elizaveta A. Rudyakova

I.M. Sechenov First Moscow State Medical University

Email: doc.rudyakova@yandex.ru
ORCID iD: 0009-0006-9475-279X
SPIN-code: 1255-4654

5th year student

Russian Federation, Moscow

References

  1. Wei D, Liu JY, Sun Y, et al. Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial. Lancet. 2019;393(10178):1310–1318. doi: 10.1016/S0140-6736(18)32843-5
  2. Shi Y, Sun Y, Hao C, et al. Transfer of fresh versus frozen embryos in ovulatory women. N Engl J Med. 2018;378(2):126–136. doi: 10.1056/NEJMoa1705334
  3. Somigliana E, Vigano P, Busnelli A, et al. Repeated implantation failure at the crossroad between statistics, clinics and over-diagnosis. Reprod Biomed Online. 2018;36(1):32–38. doi: 10.1016/j.rbmo.2017.09.012
  4. Huang C, Ye X, Ye L, et al. Platelet-rich plasma intrauterine infusion as assisted reproduction technology (ART) to combat repeated implantation failure (RIF): a systematic review and meta-analysis. Iran J Public Health. 2023;52(8):1542–1554. doi: 10.18502/ijph.v52i8.13394
  5. Li D, Zheng L, Zhao D, et al. The role of immune cells in recurrent spontaneous abortion. Reprod Sci. 2021;28(12):3303–3315. doi: 10.1007/s43032-021-00599-y
  6. Lin Y, Zhang D, Li Y, et al. Decidual NR2F2-expressing CD4+ T cells promote TH2 transcriptional program during early pregnancy. Front Immunol. 2021;12:670777. doi: 10.3389/fimmu.2021.670777
  7. Nakagawa K, Kuroda K, Sugiyama R. Helper T cell pathology and repeated implantation failures. In: Immunology of recurrent pregnancy loss and implantation failures. Cambridge, MA: Academic Press, Elsevier; 2022. Р. 273–285. doi: 10.1016/B978-0-323-90805-4.00010-9
  8. Ahmadi M, Abdolmohammadi-Vahid S, Ghaebi M., et al. Regulatory T cells improve pregnancy rate in RIF patients after additional IVIG treatment. Syst Biol Reprod Med. 2017;63(6):350–359. doi: 10.1080/19396368.2017.1390007
  9. Mukherjee N, Sharma R, Modi D. Immune alterations in recurrent implantation failure. Am J Reprod Immunol. 2023;89(2):e13563. doi: 10.1111/aji.13563
  10. Woon EV, Greer O, Shah N, et al. Number and function of uterine natural killer cells in recurrent miscarriage and implantation failure: a systematic review and meta-analysis. Hum Reprod Update. 2022;28(4):548–582. doi: 10.1093/humupd/dmac006
  11. Eberl G, Colonna M, Di Santo JP, McKenzie AN. Innate lymphoid cells: a new paradigm in immunology. Science. 2015;348(6237):aaa6566. doi: 10.1126/science.aaa6566
  12. Huhn O, Zhao X, Esposito L, et al. How do uterine natural killer and innate lymphoid cells contribute to successful pregnancy? Front Immunol. 2021;12:607669. doi: 10.3389/fimmu.2021.607669
  13. Odendaal J, Quenby S. Immunological testing in assisted reproductive technology. Semin Reprod Med. 2021;39(1-02):13–23. doi: 10.1055/s-0041-1730908
  14. Chen C, Song X, Wei W, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8(1):875. doi: 10.1038/s41467-017-00901-0
  15. Wee BA, Thomas M, Sweeney EL, et al. A retrospective pilot study to determine whether the reproductive tract microbiota differs between women with a history of infertility and fertile women. Aust N Z J Obstet Gynaecol. 2018;58(3):341–348. doi: 10.1111/ajo.12754
  16. Cicinelli E, Matteo M, Tinelli R, et al. Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy. Hum Reprod. 2015;30(2):323–330. doi: 10.1093/humrep/deu292
  17. Chen P, Chen P, Guo Y, et al. Interaction between chronic endometritis caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure. Front Immunol. 2021;12:748447. doi: 10.3389/fimmu.2021.748447
  18. Neamţu SD, Stanca L, Siminel MA, et al. The procoagulant status. Hypercoagulability as a risk factor of primary and secondary infertility. Rom J Morphol Embryol. 2021;62(3):829–834. doi: 10.47162/RJME.62.3.21
  19. Feng X, Meng X, Guo S, et al. Identification of key genes and immune cell infiltration in recurrent implantation failure: a study based on integrated analysis of multiple microarray studies. Am J Reprod Immunol. 2022;88(4):e13607. doi: 10.1111/aji.13607
  20. Franasiak JM, Alecsandru D, Forman EJ, et al. A review of the pathophysiology of recurrent implantation failure. Fertil Steril. 2021;116(6):1436–1448. doi: 10.1016/j.fertnstert.2021.09.014
  21. Budani MC, Tiboni GM. Ovotoxicity of cigarette smoke: a systematic review of the literature. Reprod Toxicol. 2017;72:164–181. doi: 10.1016/j.reprotox.2017.06.184
  22. Frederiksen Y, Farver-Vestergaard I, Skovgard NG, et al. Efficacy of psychosocial interventions for psychological and pregnancy outcomes in infertile women and men: a systematic review and meta-analysis. BMJ Open. 2015;5(1):e006592. doi: 10.1136/bmjopen-2014-006592
  23. Marchand GJ, Masoud AT, Ulibarri H, et al. Effect of a 20% intravenous fat emulsion therapy on pregnancy outcomes in women with RPL or RIF undergoing IVF/ICSI: a systematic review and meta-analysis. J Clin Transl Res. 2023;9(4):236–245.
  24. Singh N, Davis AA, Kumar S, Kriplani A. The effect of administration of intravenous intralipid on pregnancy outcomes in women with implantation failure after IVF/ICSI with non-donor oocytes: a randomised controlled trial. Eur J Obstet Gynecol Reprod Biol. 2019;240:45–51. doi: 10.1016/j.ejogrb.2019.06.007
  25. Bespalova ON, Zhernakova TS. Experience with Intralipid in early reproductive losses. Akusherstvo i Ginekologiya. 2021;(11):194–201. doi: 10.18565/aig.2021.11.194-201
  26. Kolanska K, Bendifallah S, Cohen J, et al. Unexplained recurrent implantation failures: predictive factors of pregnancy and therapeutic management from a French multicentre study. J Reprod Immunol. 2021;145:103313. doi: 10.1016/j.jri.2021.103313
  27. Al-Zebeidi J, Agdi M, Lary S, et al. Effect of empiric intravenous intralipid therapy on pregnancy outcome in women with unexplained recurrent implantation failure undergoing intracytoplasmic sperm injection-embryo transfer cycle: a randomized controlled trial. Gynecol Endocrinol. 2020;36(2):131–134. doi: 10.1080/09513590.2019.1631280
  28. Bunk S, Ponnuswamy P, Trbic A, et al. IVIG induces apoptotic cell death in CD56(dim) NK cells resulting in inhibition of ADCC effector activity of human PBMC. Clin Immunol. 2019;198:62–70. doi: 10.1016/j.clim.2018.10.018
  29. Yamada H, Deguchi M, Saito S, et al. Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses: a double-blind, randomised, placebo-controlled trial. EClinicalMedicine. 2022;50:101527. doi: 10.1016/j.eclinm.2022
  30. Banjar S, Kadour E, Khoudja R, et al. Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss. Am J Reprod Immunol. 2023;90(2):e13737. doi: 10.1111/aji.13737
  31. Krivonos MM, Zainulina MS, Kornyushina EA, et al. Use of intravenous immunoglobulin within the ivf/icsi protocol in women with infertility and antiphospholipid antibodies. Obstetrics, Gynecology and Reproduction. 2017;11(3):11–19. EDN: ZXNQUH doi: 10.17749/2313-7347.2017.11.3.011-019
  32. Piccinni MP, Raghupathy R, Saito S, Szekeres-Bartho J. Cytokines, hormones and cellular regulatory mechanisms favoring successful reproduction. Front Immunol. 2021;12:717808. doi: 10.3389/fimmu.2021.717808
  33. Kieu V, Lantsberg D, Mizrachi Y, et al. A survey study of endometrial receptivity tests and immunological treatments in in vitro fertilisation (IVF). Aust N Z J Obstet Gynaecol. 2022;62(2):306–311. doi: 10.1111/ajo.13466
  34. Sun Y, Cui L, Lu Y, et al. Prednisone vs placebo and live birth in patients with recurrent implantation failure undergoing in vitro fertilization: a randomized clinical trial. JAMA. 2023;329(17):1460–1468. doi: 10.1001/jama.2023.5302
  35. Cicinelli E, Cicinelli R, Vitagliano A. Antibiotic therapy for chronic endometritis and its reproductive implications: a step forward, with some uncertainties. Fertil Steril. 2021;115(6):1445–1446. doi: 10.1016/j.fertnstert.2021.03.025
  36. Pantos K, Simopoulou M, Maziotis E, et al. Introducing intrauterine antibiotic infusion as a novel approach in effectively treating chronic endometritis and restoring reproductive dynamics: a randomized pilot study. Sci Rep. 2021;11(1):15581. doi: 10.1038/s41598-021-95072-w
  37. Zou Y, Ming L, Ding J, et al. Low dosage of prednisone acetate combined with doxycycline in the treatment of chronic endometritis in patients with repeated implantation failure. Am J Reprod Immunol. 2023;89(6):e13713. doi: 10.1111/aji.13713
  38. Ma N, Li J, Zhang J, et al. Combined oral antibiotics and intrauterine perfusion can improve in vitro fertilization and embryo transfer pregnancy outcomes in patients with chronic endometritis and repeated embryo implantation failure. BMC Womens Health. 2023;23(1):344. doi: 10.1186/s12905-023-02443-8
  39. Goring SM, Levy AR, Ghement I, et al. A network meta-analysis of the efficacy of belatacept, cyclosporine and tacrolimus for immunosuppression therapy in adult renal transplant recipients. Curr Med Res Opin. 2014;30(8):1473–1487. doi: 10.1185/03007995.2014.898140
  40. Nakagawa K, Kwak-Kim J, Ota K, et al. Immunosuppression with tacrolimus improved reproductive outcome of women with repeated implantation failure and elevated peripheral blood TH1/TH2 cell ratios. Am J Reprod Immunol. 2015;73(4):353–361. doi: 10.1111/aji.12338
  41. Bahrami-Asl Z, Farzadi L, Fattadhi A, et al. Tacrolimus improves the implantation rate in patients with Elevated Th1/2 helper cell ratio and repeated implantation failure (RIF). Geburtshilfe Frauenheilkd. 2020;80(8):851–862. doi: 10.1055/a-1056-3148
  42. Shen P, Zhang T, Han R, et al. Co-administration of tacrolimus and low molecular weight heparin in patients with a history of implantation failure and elevated peripheral blood natural killer cell proportion. J Obstet Gynaecol Res. 2023;49(2):649–657. doi: 10.1111/jog.15500
  43. Cavalcante MB, Tavares ACM, Rocha CA, et al. Calcineurin inhibitors in the management of recurrent miscarriage and recurrent implantation failure: Systematic review and meta-analysis. J Reprod Immunol. 2023;160:104157. doi: 10.1016/j.jri.2023.104157
  44. Huang W, Lu W, Li Q, et al. Effects of cyclosporine a on proliferation, invasion and migration of HTR-8/SVneo human extravillous trophoblasts. Biochem Biophys Res Commun. 2020;533(4):645–650. doi: 10.1016/j.bbrc.2020.09.072
  45. Liao Z, Liu C, Cai L, et al. The effect of endometrial thickness on pregnancy, maternal, and perinatal outcomes of women in fresh cycles after IVF/ICSI: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2022;12:814648. doi: 10.3389/fendo.2021.814648
  46. Mouanness M, Ali-Bynom S, Jackman J, et al. Use of intra-uterine injection of platelet-rich plasma (PRP) for endometrial receptivity and thickness: a literature review of the mechanisms of action. Reprod Sci. 2021;28(6):1659–1670. doi: 10.1007/s43032-021-00579-2
  47. Zabrodina YuV, Akhmediyanova GU, Khamidullina ZG. Use of platelet-rich autoplasma in the assisted reproductive technology programs. Akusherstvo i Ginekologiya. 2023;(7):5–11. EDN: UTSAIA doi: 10.18565/aig.2023.63
  48. Kim MK, Yoon JA, Yoon SY, et al. Human platelet-rich plasma facilitates angiogenesis to restore impaired uterine environments with asherman's syndrome for embryo implantation and following pregnancy in mice. Cells. 2022;11(9):1549. doi: 10.3390/cells11091549
  49. Savina VA, Samoilovich YaA, Isakova EV. Experience with intrauterine plateletrich plasma infusions for endometrial preparation in thawed embryo transfer programs in patients with an unfavorable prognosis of treatment outcomes. Akusherstvo i Ginekologiya. 2020;(11):168–173. EDN: HQMURL doi: 10.18565/aig.2020.11.168-173
  50. Shaulov T, Sierra S, Sylvestre C. Recurrent implantation failure in IVF: a Canadian fertility and andrology society clinical practice guideline. Reprod BioMed Online. 2020;41(5):819–833. doi: 10.1016/j.rbmo.2020.08.007
  51. Hou Z, Jiang F, Yang J, et al. What is the impact of granulocyte colony-stimulating factor (G-CSF) in subcutaneous injection or intrauterine infusion and during both the fresh and frozen embryo transfer cycles on recurrent implantation failure: a systematic review and meta-analysis? Reprod Biol Endocrinol. 2021;19(1):125. doi: 10.1186/s12958-021-00810-4
  52. Kalem Z, Namli Kalem M, Bakirarar B, et al. Intrauterine G-CSF administration in recurrent implantation failure (RIF): An Rct. Sci Rep. 2020;10(1):5139. doi: 10.1038/s41598-020-61955-7
  53. Fan L, Sha M, Li W, et al. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves embryo implantation in mice by regulating local Treg/Th17 cell balance. J Reprod Dev. 2021;67(6):359–368. doi: 10.1262/jrd.2021-006
  54. Nikolaeva MA, Arefieva AS, Stepanova EO, et al. Time to pregnancy after pre-gestational allogeneic immunotherapy and peripheral blood cell cytokine profile in women with a history of recurrent spontaneous abortion. Akusherstvo i Ginekologiya. 2021;(1):79–87. EDN: XPFBLC doi: 10.18565/aig.2021.1.79-87
  55. Liu X, Ma D, Wang W, et al. Intrauterine administration of human chorionic gonadotropin improves the live birth rates of patients with repeated implantation failure in frozen-thawed blastocyst transfer cycles by increasing the percentage of peripheral regulatory T cells. Arch Gynecol Obstet. 2019;299(4):1165–1172. doi: 10.1007/s00404-019-05047-6299
  56. Gao M, Jiang X, Li B, et al. Intrauterine injection of human chorionic gonadotropin before embryo transfer can improve in vitro fertilization-embryo transfer outcomes: a meta-analysis of randomized controlled trials. Fertil Steril. 2019;112(1):89–97.e1. doi: 10.1016/j.fertnstert.2019.02.027
  57. Simon C, Gomez C, Cabanillas S, et al. A 5-year multicentre randomized controlled trial comparing personalized, frozen and fresh blastocyst transfer in IVF. Reprod BioMed Online. 2020;41(3):402–415. doi: 10.1016/j.rbmo.2020.06.002
  58. Semenchenko SI, Kasparova AE, Chegus LA, Chernaya EE. Effectiveness of endometrial scratching in infertility treatment with assisted reproductive technologies. Medical Council. 2022;16(23):224–230. EDN: JXXSYF doi: 10.21518/2079-701X-2022-16-23-224-230
  59. Lensen SF, Armstrong S. Gibreel A, et al. Endometrial injury in women undergoing in vitro fertilisation (IVF). Cochrane Database Syst Rev. 2021;6(6):CD009517. doi: 10.1002/14651858.CD009517.pub4

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