https://doi.org/10.18502/ijrm.v22i5.16435
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authors
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Mina Naghi Jafarabadi
Mina Naghi Jafarabadi
Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
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Farnaz Hadavi
Farnaz Hadavi
Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
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Maedeh Ahmadi
Maedeh Ahmadi
Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
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Masoumeh Masoumi
Masoumeh Masoumi
Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
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Sara Zabihzadeh
Sara Zabihzadeh
ali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Published Date
- Jul 2, 2024
Intravaginal probiotics before embryo transfer do not improve pregnancy rates in recurrent implantation failure cases: An RCT
Abstract
Background: Considering the considerable influence of the vaginal microbiome on endometrial receptivity and embryo implantation, we hypothesized that cases of recurrent implantation failure (RIF) might benefit from the intravaginal probiotic administration.
Objective: Evaluation of the effects of intravaginal probiotic administration before frozen embryo transfer (FET) on the rates of pregnancy and the status of vaginal lactobacillary flora in cases of RIF.
Materials and Methods: This was a randomized, parallel-group, clinical trial conducted at an infertility clinic in Tehran, Iran between January 2021 and September 2022. A total of 166 reproductive-aged women with a history of unexplained RIF were randomly assigned to either the probiotic group or the control group (n = 83/each group). The probiotic group received intravaginal probiotics (LactoVag ®) daily for 2 wk from the second day of the menstrual cycle along with the routine treatment of FET. The control group received only the routine treatment of FET. The primary outcome was the chemical pregnancy rate, and the secondary outcomes were the clinical pregnancy rate and the status of vaginal lactobacillary flora.
Results: A total of 163 participants were included in the final analysis. The probiotic group had a slightly higher chemical pregnancy rate than the control group (39.02% vs. 33.33%), but the difference was not statistically significant (risk ratio: 1.71, 95% CI: 0.77–1.76; p = 0.449). The clinical pregnancy rate was also non-significantly higher in the probiotic group than the control group (37.80% vs. 33.33%; RR: 1.14, 95% CI: 0.76–1.74; p = 0.623).
Conclusion: Intravaginal probiotic administration did not significantly improve the pregnancy rates in RIF cases undergoing FET. Further studies are needed to explore the optimal dose, duration, and timing of probiotic administration, as well as the mechanisms of action and the potential adverse effects of probiotics on the vaginal microbiome and the implantation process.
Key words: Assisted reproductive technique, Probiotics, Microbiota, Pregnancy rate
References
[2] Cimadomo D, Craciunas L, Vermeulen N, Vomstein K, Toth B. Definition, diagnostic and therapeutic options in recurrent implantation failure: An international survey of clinicians and embryologists. Hum Reprod 2021; 36: 305–317.
[3] Franasiak JM, Alecsandru D, Forman EJ, Gemmell LC, Goldberg JM, Llarena N, et al. A review of the pathophysiology of recurrent implantation failure. Fertil Steril 2021; 116: 1436–1448.
[4] Chen C, Song X, Wei W, Zhong H, Dai J, Lan Z, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun 2017; 8: 875.
[5] Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol 2015; 6: 81.
[6] Sirota I, Zarek SM, Segars JH. Potential influence of the microbiome on infertility and assisted reproductive technology. Semin Reprod Med 2014; 32: 35–42.
[7] Hashimoto T, Kyono K. Does dysbiotic endometrium affect blastocyst implantation in IVF patients? J Assist Reprod Genet 2019; 36: 2471–2479.
[8] Moreno I, Garcia-Grau I, Perez-Villaroya D, Gonzalez- Monfort M, Bahçeci M, Barrionuevo MJ, et al. Endometrial microbiota composition is associated with reproductive outcome in infertile patients. Microbiome 2022; 10: 1.
[9] López-Moreno A, Aguilera M. Vaginal probiotics for reproductive health and related dysbiosis: Systematic review and meta-analysis. J Clin Med 2021; 10: 1461.
[10] De Souza SV, Monteiro PB, de Moura GA, Santos NO, Fontanezi CTB, Gomes I de A, et al. Vaginal microbioma and the presence of Lactobacillus spp. as interferences in female fertility: A review system. JBRA Assist Reprod 2023; 27: 496–506.
[11] Väinämö S, Saqib S, Kalliala I, Kervinen K, Luiro K, Niinimäki M, et al. Longitudinal analysis of vaginal microbiota during IVF fresh embryo transfer and in early pregnancy. Microbiol Spectr 2023; 11: e0165023.
[12] Favaron A, Turkgeldi E, Elbadawi M, Gaisford S, Basit AW, Orlu M. Do probiotic interventions improve female unexplained infertility? A critical commentary. Reprod Biomed Online 2024; 48: 103734.
[13] FAO. Probiotics in food: Health and nutritional properties and guidelines for evaluation. Italy: Food and agriculture organization of the united nation; 2001.
[14] Blancafort C, Llácer J. Can probiotics enhance fertility outcome? Capacity of probiotics as a single intervention to improve the feminine genital tract microbiota in non-symptomatic reproductive-aged women. Front Endocrinol 2022; 13: 1081830.
[15] Thanaboonyawat I, Pothisan S, Petyim S, Laokirkkiat P. Pregnancy outcomes after vaginal probiotic supplementation before frozen embryo transfer: A randomized controlled study. Sci Rep 2023; 13: 11892.
[16] Gilboa Y, Bar-Hava I, Fisch B, Ashkenazi J, Voliovitch I, Borkowski T, et al. Does intravaginal probiotic supplementation increase the pregnacy rate in IVFembryo transfer cycles? Reprod Biomed Online 2005; 11: 71–75.
[17] Davari Tanha F, Rahmani Z, Rezaei Z, Akbari Asbagh F, Ebrahimi M, Hosseini Quchani S, et al. The effect of normalizing vaginal microbiome using Lactovag in improving pregnancy outcomes in frozen embryo transfer cycles: A randomized clinical trial. Arch Gynecol Obstet 2023; 308: 1587–1592.
[18] Montag MHM, Morbeck DE. Principles of IVF laboratory practice: Laboratory set-up, training and daily operation. United Kingdom: Cambridge University Press; 2023.
[19] Tomusiak A, Strus M, Heczko PB, Adamski P, Stefanski G, Mikolajczyk-Cichonska A, et al. Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: A multicenter, randomized, double-blind, and placebo-controlled trial. Drug Des Devel Ther 2015; 9: 5345–5354.
[20] Balaghi Z, Azima S, Motamedifar M, Kaviani M, Poordast T, Zare N. The effect of lactofem oral probiotic capsule on lactobacilli colonization and some vaginal health parameters. Gynecol Obstet Invest 2020; 85: 245–251.
[21] Irollo AM, Gangale MF, Tartaglione A, Criscuolo C, Aiello R, Stortini E, et al. Does probiotic and prebiotic treatment in IVF cycles of infertile women with intestinal dysbiosis, affect pregnancy rate? J Siena Acad Sci 2018; 9: 44–47.
[22] Fernández L, Castro I, Arroyo R, Alba C, Beltrán D, Rodríguez JM. Application of ligilactobacillus salivarius CECT5713 to achieve term pregnancies in women with repetitive abortion or infertility of unknown origin by microbiological and immunological modulation of the vaginal ecosystem. Nutrients 2021; 13: 162.