Many couples attempt to get pregnant but experience recurrent miscarriage, also referred to as recurrent pregnancy loss. It has become difficult to understand the reason even after numerous investigations and hence, it can be difficult for both patients and clinicians. It has been studied that the most frequent reason for spontaneous loss is spontaneous foetal aneuploidies, especially in the first stage of pregnancy. To prevent tests or treatments that are unnecessary or have not been proven to be beneficial, studies show that it is critical to use a methodical and evidence-based strategy to testing and management. A crucial component of the management of couples with recurrent miscarriage is the specialized clinic services and psychological assistance. Also, there are many case studies which show that losses caused by de novo foetal aneuploidies happen to women who experience sporadic and recurrent losses at about the same rates, some couples who experience recurrent pregnancy loss have additional genetic factors that are linked with them, while others have nongenetic causes. Genetic testing of the foetuses from couples who have experienced two or more miscarriages could help identify the root cause and inform patients about their chances of having a healthy baby in the future. The present review emphasizes on the various aspects of recurrent pregnancy loss. It also deals with the factors which aid in causing the same. In addition, it is an examination of the relation between pregnancy and immune factors.

1. Eshre Guideline Group on RPL, Bender Atik, R., Christiansen, O. B., Elson, J., Kolte, A. M., Lewis, S., ... &Goddijn, M. (2018). ESHRE guideline: recurrent pregnancy loss. Human reproduction open, 2018(2), hoy004.
2. Wang, X. H., Xu, S., Zhou, X. Y., Zhao, R., Lin, Y., Cao, J., & Zhao, J. Y. (2021). Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk. Nature Communications, 12(1), 3428.
3. Chaithra, P. T., Malini, S. S., & Kumar, C. S. (2011). An overview of genetic and molecular factors responsible for recurrent pregnancy loss. International journal of human genetics, 11(4), 217-225.
4. Toth, B., Vomstein, K., Togawa, R., Böttcher, B., Hudalla, H., Strowitzki, T., ... & Kuon, R. J. (2019). The impact of previous live births on peripheral and uterine natural killer cells in patients with recurrent miscarriage. Reproductive Biology and Endocrinology, 17, 1-8.
5. Hyde, K. J., & Schust, D. J. (2015). Genetic considerations in recurrent pregnancy loss. Cold Spring Harbor perspectives in medicine, 5(3), a023119.
6. Zhao, X., Jiang, Y., Wang, L., Li, Z., Li, Q., & Feng, X. (2018). Advances in understanding the immune imbalance between T-lymphocyte subsets and NK cells in recurrent spontaneous abortion. Geburtshilfe und Frauenheilkunde, 78(07), 677-683.
7. Meka, A., & Reddy, B. M. (2006). Recurrent spontaneous abortions: an overview of genetic and non-genetic backgrounds. International Journal of Human Genetics, 6(2), 109-117.
8. Muyayalo, K. P., Li, Z. H., Mor, G., & Liao, A. H. (2018). Modulatory effect of intravenous immunoglobulin on Th17/Treg cell balance in women with unexplained recurrent spontaneous abortion. American Journal of Reproductive Immunology, 80(4), e13018.
9. Dimitriadis, E., Menkhorst, E., Saito, S., Kutteh, W. H., &Brosens, J. J. (2020). Recurrent pregnancy loss. Nature reviews disease primers, 6(1), 98.
10. Hennessy, M., Dennehy, R., Meaney, S., Linehan, L., Devane, D., Rice, R., & O'Donoghue, K. (2021). Clinical practice guidelines for recurrent miscarriage in high-income countries: a systematic review. Reproductive Bio Medicine Online, 42(6), 1146-1171.
11. Park, D. W., Lee, H. J., Park, C. W., Hong, S. R., Kwak‐Kim, J., & Yang, K. M. (2010). Peripheral blood NK cells reflect changes in decidual NK cells in women with recurrent miscarriages. American Journal of Reproductive Immunology, 63(2), 173-180.
12. Toth, B., Vomstein, K., Togawa, R., Böttcher, B., Hudalla, H., Strowitzki, T., & Kuon, R. J. (2019). The impact of previous live births on peripheral and uterine natural killer cells in patients with recurrent miscarriage. Reproductive Biology and Endocrinology, 17, 1-8.
13. Warburton, D. O. R. O. T. H. Y., Kline, J., Stein, Z., Hutzler, M., Chin, A., &Hassold, T. (1987). Does the karyotype of a spontaneous abortion predict the karyotype of a subsequent abortion? Evidence from 273 women with two karyotyped spontaneous abortions. American journal of human genetics, 41(3), 465.
14. Ogasawara, M., Aoki, K., Okada, S., & Suzumori, K. (2000). Embryonic karyotype of abortuses in relation to the number of previous miscarriages. Fertility and sterility, 73(2), 300-304.
15. Carp, H., Toder, V., Aviram, A., Daniely, M., Mashiach, S., &Barkai, G. (2001). Karyotype of the abortus in recurrent miscarriage. Fertility and sterility, 75(4), 678-682.
16. Teklenburg, G., Salker, M., Heijnen, C., Macklon, N. S., &Brosens, J. J. (2010). The molecular basis of recurrent pregnancy loss: impaired natural embryo selection. Molecular human reproduction, 16(12), 886-895.
17. Evans, J., Catalano, R. D., Brown, P., Sherwin, R., Critchley, H. O., Fazleabas, A. T., & Jabbour, H. N. (2009). Prokineticin 1 mediates fetal-maternal dialogue regulating endometrial leukemia inhibitory factor. The FASEB Journal, 23(7), 2165.
18. Hochner-Celnikier, D., Ron, M., Eldor, A., Segal, S., Palti, Z., Fuks, Z., &Vlodavsky, I. (1984). Growth characteristics of human first trimester decidual cells cultured in serum-free medium: production of prolactin, prostaglandins and fibronectin. Biology of reproduction, 31(4), 827-836.
19. Brosens, J. J., Hayashi, N., & White, J. O. (1999). Progesterone receptor regulates decidual prolactin expression in differentiating human endometrial stromal cells. Endocrinology, 140(10), 4809-4820.
20. Cloke, B., Huhtinen, K., Fusi, L., Kajihara, T., Yliheikkilä, M., Ho, K. K.,&Brosens, J. J. (2008). The androgen and progesterone receptors regulate distinct gene networks and cellular functions in decidualizing endometrium. Endocrinology,149(9), 4462-4474.
21. Lynch, V. J., Tanzer, A., Wang, Y., Leung, F. C., Gellersen, B., Emera, D., & Wagner, G. P. (2008). Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals. Proceedings of the National Academy of Sciences, 105(39), 14928-14933.

Ranjana Rawat

Department of Biochemistry Rama Medical College, Hospital & Research Centre Mandhana, Kanpur, Uttar Pradesh, India