Non-Lactobacillus dominance of the vagina is associated with reduced live birth rate following IVF/ICSI: a propensity score-matched cohort study.
In-vitro fertilization
Lactobacillus
Live birth
Propensity score
Journal
Archives of gynecology and obstetrics
ISSN: 1432-0711
Titre abrégé: Arch Gynecol Obstet
Pays: Germany
ID NLM: 8710213
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
19
10
2020
accepted:
02
08
2021
pubmed:
10
8
2021
medline:
16
3
2022
entrez:
9
8
2021
Statut:
ppublish
Résumé
Whether the dominant status of vaginal Lactobacillus is associated with IVF/ICSI outcomes. This is a propensity score-matched retrospective cohort study consists of 2285 women undergoing their first fresh autologous IVF cycles. We divided the patients into the Lactobacillus-dominant group and non-Lactobacillus-dominant group based on the abundance of Lactobacillus in Gram-stained vaginal smear examined by microscopy. We compared IVF outcomes between the two groups. We matched Lactobacillus-dominant women with non-Lactobacillus-dominant women by propensity score (PS) to reduce the impact of confounding factors. We evaluated the effect of vaginal Lactobacillus on live birth using univariate and multivariate analysis models. We also conducted interaction and stratified analyses. Compare to the Lactobacillus-dominant group, the biochemical pregnancy rate (50.12% vs. 57.61%, P = 0.03), clinical pregnancy rate (40.98% vs. 50.82%, P < 0.01), and live birth rate (31.83% vs. 41.22%, P < 0.01) were significantly lower in the non-Lactobacillus-dominant group, the preclinical pregnancy loss rate (18.22% vs. 11.79%, P = 0.05) and preterm birth rate (33.09% vs. 21.59%, P = 0.02) were significantly higher in the non-Lactobacillus-dominant group. However, the miscarriage rate (18.86% vs. 15.67%, P = 0.40) and ectopic pregnancy rate (1.41% vs.1.64%, P = 0.78) were similar between the two groups. Loss dominance of Lactobacillus in the vagina was an independent risk factor for live birth (OR 0.66, 95% CI 0.50-0.88). Loss dominance of Lactobacillus in the vagina negatively affects IVF outcomes by decreasing the chances of pregnancy and live birth, increasing risks of preclinical pregnancy loss and preterm birth.
Identifiants
pubmed: 34370072
doi: 10.1007/s00404-021-06171-y
pii: 10.1007/s00404-021-06171-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
519-528Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
Aldunate M, Srbinovski D, Hearps AC et al (2015) Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis. Front Physiol 6:164
doi: 10.3389/fphys.2015.00164
Nene NR, Reisel D, Leimbach A et al (2019) Association between the cervicovaginal microbiome, BRCA1 mutation status, and risk of ovarian cancer: a case-control study. Lancet Oncol 20(8):1171–1182
doi: 10.1016/S1470-2045(19)30340-7
Haahr T, Jensen JS, Thomsen L et al (2016) Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients. Hum Reprod 31(4):795–803
doi: 10.1093/humrep/dew026
Babu G, Singaravelu BG, Srikumar R, Reddy SV, Kokan A (2017) Comparative study on the vaginal flora and incidence of asymptomatic vaginosis among healthy women and in women with infertility problems of reproductive age. J Clin Diagn Res 11(8):DC18–DC22
pubmed: 28969122
pmcid: 5620762
Elovitz MA, Gajer P, Riis V et al (2019) Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery. Nat Commun 10(1):1305
doi: 10.1038/s41467-019-09285-9
Haahr T, Zacho J, Brauner M et al (2019) Reproductive outcome of patients undergoing in vitro fertilisation treatment and diagnosed with bacterial vaginosis or abnormal vaginal microbiota: a systematic PRISMA review and meta-analysis. BJOG 126(2):200–207
doi: 10.1111/1471-0528.15178
Ravel J, Gajer P, Abdo Z et al (2011) Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA 108(Suppl 1):4680–4687
doi: 10.1073/pnas.1002611107
Drell T, Lillsaar T, Tummeleht L et al (2013) Characterization of the vaginal micro- and mycobiome in asymptomatic reproductive-age Estonian women. PLoS One 8(1):e54379
doi: 10.1371/journal.pone.0054379
Makarova K, Slesarev A, Wolf Y et al (2006) Comparative genomics of the lactic acid bacteria. Proc Natl Acad Sci U S A 103(42):15611–15616
doi: 10.1073/pnas.0607117103
Witkin SS, Linhares IM (2017) Why do lactobacilli dominate the human vaginal microbiota? BJOG 124(4):606–611
doi: 10.1111/1471-0528.14390
Bernabeu A, Lledo B, Diaz MC et al (2019) Effect of the vaginal microbiome on the pregnancy rate in women receiving assisted reproductive treatment. J Assist Reprod Genet 36(10):2111–2119
doi: 10.1007/s10815-019-01564-0
Vergaro P, Tiscornia G, Barragan M et al (2019) Vaginal microbiota profile at the time of embryo transfer does not affect live birth rate in IVF cycles with donated oocytes. Reprod Biomed Online 38(6):883–891
doi: 10.1016/j.rbmo.2018.12.019
Walker B (1998) Biodiversity and ecological redundancy. Conserv Biol 6:18–23
doi: 10.1046/j.1523-1739.1992.610018.x
Hickey RJ, Zhou X, Pierson JD, Ravel J, Forney LJ (2012) Understanding vaginal microbiome complexity from an ecological perspective. Transl Res 160(4):267–282
doi: 10.1016/j.trsl.2012.02.008
Nugent RP, Krohn MA, Hillier SL (1991) Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 29(2):297–301
doi: 10.1128/jcm.29.2.297-301.1991
Moreno I, Codoner FM, Vilella F et al (2016) Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol 215(6):684–703
doi: 10.1016/j.ajog.2016.09.075
Spandorfer SD, Neuer A, Giraldo PC, Rosenwaks Z, Witkin SS (2001) Relationship of abnormal vaginal flora, proinflammatory cytokines and idiopathic infertility in women undergoing IVF. J Reprod Med 46(9):806–810
pubmed: 11584481
Burton JP, Reid G (2002) Evaluation of the bacterial vaginal flora of 20 postmenopausal women by direct (Nugent score) and molecular (polymerase chain reaction and denaturing gradient gel electrophoresis) techniques. J Infect Dis 186(12):1770–1780
doi: 10.1086/345761
Brotman RM, Shardell MD, Gajer P et al (2018) Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 25(11):1321–1330
doi: 10.1097/GME.0000000000001236
Al-Memar M, Bobdiwala S, Fourie H et al (2020) The association between vaginal bacterial composition and miscarriage: a nested case-control study. BJOG 127(2):264–274
doi: 10.1111/1471-0528.15972
Romero R, Hassan SS, Gajer P et al (2014) The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome 2(1):4
doi: 10.1186/2049-2618-2-4
Greenbaum S, Greenbaum G, Moran-Gilad J, Weintraub AY (2019) Ecological dynamics of the vaginal microbiome in relation to health and disease. Am J Obstet Gynecol 220(4):324–335
doi: 10.1016/j.ajog.2018.11.1089
Serrano MG, Parikh HI, Brooks JP et al (2019) Racioethnic diversity in the dynamics of the vaginal microbiome during pregnancy. Nat Med 25(6):1001–1011
doi: 10.1038/s41591-019-0465-8
Tabatabaei N, Eren AM, Barreiro LB et al (2019) Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study. BJOG 126(3):349–358
doi: 10.1111/1471-0528.15299
Romero R, Hassan SS, Gajer P et al (2014) The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome 2:18
doi: 10.1186/2049-2618-2-18
Verwijs MC, Agaba SK, Darby AC, van de Wijgert J (2020) Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure. Am J Obstet Gynecol 222(2):157.e151-157.e113
doi: 10.1016/j.ajog.2019.08.008
Husain S, Allotey J, Drymoussi Z et al (2020) Effects of oral probiotic supplements on vaginal microbiota during pregnancy: a randomised, double-blind, placebo-controlled trial with microbiome analysis. Bjog 127(2):275–284
doi: 10.1111/1471-0528.15675
Bhandari P, Rishi P, Prabha V (2016) Positive effect of probiotic Lactobacillus plantarum in reversing LPS-induced infertility in a mouse model. J Med Microbiol 65(5):345–350
doi: 10.1099/jmm.0.000230
Vitali B, Cruciani F, Baldassarre ME et al (2012) Dietary supplementation with probiotics during late pregnancy: outcome on vaginal microbiota and cytokine secretion. BMC Microbiol 12:236
doi: 10.1186/1471-2180-12-236
Stojanovic N, Plecas D, Plesinac S (2012) Normal vaginal flora, disorders and application of probiotics in pregnancy. Arch Gynecol Obstet 286(2):325–332
doi: 10.1007/s00404-012-2293-7