Recurrent spontaneous abortion (RSA) affects 2%–5% of couples worldwide and remains a subject of debate regarding the effectiveness of lymphocyte immunotherapy (LIT) due to limited retrospective studies. We conducted a comprehensive Bayesian analysis to assess the impact of LIT on RSA. Using data from the Shenzhen Maternity and Child Healthcare Hospital (2001–2020, n = 2316), a Bayesian generalized linear model with predictive projection feature selection was employed. Our analysis revealed a significant improvement in live birth rates for RSA patients undergoing LIT. Notably, LIT had a greater impact compared to the other 85 factors considered. To mitigate research bias, we conducted a Bayesian meta-analysis combining our dataset with 19 previously reported studies (1985–2021, n = 4246). Additionally, we developed an empirical model high-lighting the four key factors, which are the LIT result, age, paternal blood type, and anticardiolipin antibody. Younger age (19–27), paternal blood type B, and a positive anticardiolipin antibody (IgM) were associated with better therapeutic outcomes in LIT for RSA. These findings aid clinicians in identifying suitable candidates for LIT and improving treatment outcomes.
| [1] |
Dimitriadis E, Menkhorst E, Saito S, et al. Recurrent pregnancy loss. Nat Rev Dis Primers 2020;6:1–19.
|
| [2] |
Rai R, Regan L. Recurrent miscarriage. Lancet 2006;368:601–11.
|
| [3] |
Practice Committee of the American Society for Reproductive Medicine. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril 2012;98:1103–11.
|
| [4] |
Sacha, , Krieg, , Lynn, , Westphal . Immune function and recurrent pregnancy loss. Semin Reprod Med 2015;33:305–12.
|
| [5] |
Howard Carp. Immunotherapy for recurrent pregnancy loss. Best Pract Res Clin Obstet Gynaecol 2019;60:77–86.
|
| [6] |
Mowbray JF, Liddell H, Underwood JL, et al. Controlled trial of treatment of recurrent spontaneous abortion by immunisation with paternal cells. Lancet 1985;325:941–3.
|
| [7] |
Coulam CB, Clark DA, Collins J, et al. Worldwide collaborative observational study and meta-analysis on allogenic leukocyte immunotherapy for recurrent spontaneous abortion. Am J Reprod Immunol 2013;32:55–72.
|
| [8] |
Francisco PD, Tan-Lim CSC, Agcaoili-De Jesus MSL. Efficacy of lymphocyte immunotherapy in the treatment of recurrent pregnancy loss from alloimmunity: a systematic review and meta-analysis. Am J Reprod Immunol 2022;88:e13605.
|
| [9] |
Liu Z, Xu H, Kang X, et al. Allogenic lymphocyte immunotherapy for unexplained recurrent spontaneous abortion: a meta-analysis. Am J Reproduct Immunol 2016;76:443–53.
|
| [10] |
Pan X, Jiang J, Ma Q, et al. Outbreak of HIV infection linked to nosocomial transmission, China, 2016–2017. Emerg Infect Dis 2018;24:2141.
|
| [11] |
Ticconi C, Pietropolli A, Simone ND, et al. Endometrial immune dysfunction in recurrent pregnancy loss. Int J Mol Sci 2019;20:5332.
|
| [12] |
Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2009;2:76–83.
|
| [13] |
Carp H. Immunotherapy for recurrent pregnancy loss. Best Pract Res Clin Obstetr Gynaecol 2019;60:77–86.
|
| [14] |
Dey DK, Ghosh SK, Mallick BK. Generalized Linear Models: A Bayesian Perspective. CRC Press, 2000.
|
| [15] |
Faraway JJ. Extending the Linear Model with R: Generalized Linear, Mixed Effects and Nonparametric Regression Models, 2006.
|
| [16] |
West BT. Bayesian analysis of between-group differences in variance components in hierarchical generalized linear models. JSM Proceedings, Survey Research Methods Section. Alexandria, VA: American Statistical Association, 1828, 1842.
|
| [17] |
Kruschke JK. Bayesian data analysis. Wiley Interdiscip Rev Cognit Sci 2010;1:658–76.
|
| [18] |
Kruschke, J. Doing Bayesian Data Analysis: A Tutorial with R, JAGS, and Stan, ELSEVIER, 2014.
|
| [19] |
Kruschke JK. Bayesian analysis reporting guidelines. Nat Hum Behav 2021;5:1282–91.
|
| [20] |
Brooks S, Gelman A, Jones G, Meng X-L. Handbook of Markov Chain Monte Carlo. CRC Press, 2011.
|
| [21] |
Gelman A, Carlin JB, Stern HS, Rubin DB. Bayesian Data Analysis. Chapman and Hall/CRC, 1995.
|
| [22] |
Hastings WK. Monte Carlo sampling methods using Markov chains and their applications. Biometrika, 1970;57:97–109.
|
| [23] |
Piironen J, Paasiniemi M, Vehtari A. Projective inference in high- dimensional problems: prediction and feature selection. Electron J Stat 2020;14:2155–97.
|
| [24] |
Vehtari A, Gelman A, Gabry J. Practical Bayesian model evaluation using leave-one-out cross-validation and WAIC. Stat Comput 2017;27:1413–32.
|
| [25] |
Williams DR, Rast P, Bürkner P-C. Bayesian meta-analysis with weakly informative prior distributions, PsyArXiv 2018.
|
| [26] |
Cline AM, Kutteh WH. Is there a role of autoimmunity in implantation failure after in-vitro fertilization? Curr Opin Obstet Gynecol 2009;21:291–5.
|
| [27] |
Hořejší J, Martinek J, Nováková D, et al. Autoimmune antiovarian antibodies and their impact on the success of an IVF/ET program. Ann N Y Acad Sci 2000;900:351–6.
|
| [28] |
Magnus MC, Wilcox AJ, Morken N-H, et al. Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. Bmj 2019;364:l869.
|
| [29] |
Cavalcante MB, Cavalcante CTMB, Sarno M, et al. Antinuclear antibodies and recurrent miscarriage: systematic review and meta-analysis. Am J Reprod Immunol 2020;83:e13215.
|
| [30] |
Li Y, Li X, Luo S. Effect of Recurrent Spontaneous Abortion on Pregnancy Outcomes in Sequent Successful Pregnancy Patients. Journal of Guangzhou University of Traditional Chinese Medicine 2015, 979–83.
|
| [31] |
Ruiz-Irastorza G, Crowther M, Branch W, et al. Antiphospholipid syndrome. Lancet 2010;376:1498–509.
|
| [32] |
Vinatier D, Dufour P, Cosson M, et al. Antiphospholipid syndrome and recurrent miscarriages. Eur J Obstetr Gynecol Reproduct Biol 2001;96:37–50.
|
| [33] |
Abdullahi ZG, Abdul MA, Aminu SM, et al. Antiphospholipid antibodies among pregnant women with recurrent fetal wastage in a tertiary hospital in Northern Nigeria. Ann Afr Med 2016;15:133–7.
|
| [34] |
Kiernan D. Natural resources biometrics (online book). 2021; Chapter 6.1, stats.libretexts.org/@go/page/2904.
|
| [35] |
Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions, Wiley Online Library 2008.
|
| [36] |
Team, R. C. R: A language and environment for statistical computing. MSOR Connections 2014;1:275–86.
|
| [37] |
Deeks JJ, Higgins JP. Statistical algorithms in review manager 5. Statistical Methods Group of The Cochrane Collaboration 2010;1:1–11.
|
| [38] |
Muth C, Oravecz Z, Gabry J. User-friendly Bayesian regression modeling: a tutorial with rstanarm and shinystan. Quant Methods Psychol 2018;14:99–119.
|
| [39] |
Jewson, J. RStan: Efficient MCMC in R. 2017, dokumen.tips/documents/rstan-efficient-mcmc-in-r-university-of-warwick-generated-quantities-optional.html?page=20
|
| [40] |
Cui Y, Zhong X, Ban Q, et al. Study of immunotherapy with lymphocytes in women with recurrent spontaneous abortion. Modern Prev Med 2011;38:1626–7.
|
| [41] |
Hong L, Huaixiu W, Jing W. The lymphocyte injects and treats the habitual abortion that the immune factor causes. Med Mag Shanxi 2003;32:308–9.
|
| [42] |
Mowbray J, Liddell H, Underwood JL, et al. Controlled trial of treatment of recurrent spontaneous abortion by immunisation with paternal cells. Lancet 1985;325:941–3.
|
| [43] |
Lin S, Yan S, Shan E. Analysis the efficacy of immunotherapy with lymphocytes for recurrent spontaneous abortion. Jilin Med 2012;33:1822–3.
|
| [44] |
Pandey MK, Agrawal S. Induction of MLR-Bf and protection of fetal loss: a current double blind randomized trial of paternal lymphocyte immunization for women with recurrent spontaneous abortion. Int Immunopharmacol 2004;4:289–98.
|
| [45] |
Chen J-L, Yang J-M, Huang Y-Z, et al. Clinical observation of lymphocyte active immunotherapy in 380 patients with unexplained recurrent spontaneous abortion. Int Immunopharmacol 2016;40:347–50.
|
| [46] |
Liu S, Gu X, Weng R. Clinical effect of lymphocyte immunotherapy on patients with unexplained recurrent spontaneous abortion. Immun Inflammation Dis 2021;9:1272–8.
|
| [47] |
Carp H et al. Allogenic leukocyte immunization after five or more miscarriages Recurrent Miscarriage Immunotherapy Trialists Group. Hum Reprod 1997;12:250–5.
|
| [48] |
Illeni MT, Marelli G, Parazzini F, et al. Immunology: immunotherapy and recurrent abortion: a randomized clinical trial. Hum Reprod 1994;9:1247–9.
|
| [49] |
Sarno M, Cavalcante MB, Niag M, et al. Gestational and perinatal outcomes in recurrent miscarriages couples treated with lymphocyte immunotherapy. Eur J Obstetr Gynecol Reproduct Biol 2019;3:100036.
|
| [50] |
Aiwu W, Mingzhu L, Runzhi W. Preventive treatment of unexplained recurrent spontaneous abortion and effect on pregnancy outcome by lymphocytes immunotherapy. China J Chin Med 2013;28:876–8.
|
| [51] |
Bin T, Kaishu H, Wenquan Z. Analysis of lymphocytes immunotherapy for recurrent spontaneous abortion. Chin Med Treat Works 2013;21:171–2.
|
| [52] |
Ho HN, Gill TJ, Hsieh HJ, et al. Immunotherapy for recurrent spontaneous abortions in a Chinese population. Am J Reproduct Immunol 1991;25:10–5.
|
| [53] |
Group RMIT. Worldwide collaborative observational study and meta-analysis on allogenic leukocyte immunotherapy for recurrent spontaneous abortion 1. Am J Reprod Immunol 1994;32:55–72.
|
| [54] |
Gatenby PA, Cameron K, Simes RJ, et al. Treatment of recurrent spontaneous abortion by immunization with paternal lymphocytes: results of a controlled trial. Am J Reproduct Immunol 1993;29:88–94.
|
| [55] |
Daya S, Gunby J; Group RMIT. The effectiveness of allogeneic leukocyte immunization in unexplained primary recurrent spontaneous abortion. Am J Reprod Immunol 1994;32:294–302.
|
| [56] |
Clark DA, Daya S. Trials and tribulation in the treatment of recurrent spontaneous abortion. Am J Reproduct Immunol 1991;25:18–24.
|
| [57] |
Cauchi M, Lim D, Young D, et al. Treatment of recurrent aborters by immunization with paternal cells—controlled trial. Am J Reprod Immunol 1991;25:16–7.
|
| [58] |
Christiansen OB, Mathiesen O, Husth M, et al. Placebo-controlled trial of active immunization with third party leukocytes in recurrent miscarriage. Acta Obstet Gynecol Scand 1994;73:261–8.
|
| [59] |
Bandyopadhyay AR, Chatterjee D, Chatterjee M, et al. Maternal fetal interaction in the ABO system: a comparative analysis of healthy mother and couples with spontaneous abortion in Bengalee population. Am J Human Biol 2011;23:76–9.
|
| [60] |
Guzzo RA, Jackson SE, Katzell RA. Meta-analysis analysis. Res Organ Behav 1987;9:407–42.
|
| [61] |
Sutton AJ, Abrams KR. Bayesian methods in meta-analysis and evidence synthesis. Stat Methods Med Res 2001;10:277–303.
|
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