Citation Information :
Mishra S, Sahni C, Rai S, Ashish, Singh R. Genetics Insights into Recurrent Pregnancy Loss: A Comprehensive Review. J South Asian Feder Obs Gynae 2024; 16 (4):421-427.
Recurrent pregnancy loss (RPL) mainly occurs due to the disorders that cause intrauterine fetal demise or damage, such as fetal, maternal, and paternal chromosomal structural and numerical abnormalities. Approximately, 15–20% of all clinically recognized pregnancies result in the first trimester (before 20 weeks of gestational age) in spontaneous recurrent abortion. Besides all internal factors like Anatomical, immunological, and coagulation factors, genetic factors appear to be most associated with reproductive organ damage and multiple pregnancy loss. Some factors are unexplored as mentioned in the previous research articles, and there is an enormous need to research for establishing the proper etiology and prognosis. This review is all about the various factors responsible for RPL and is mainly focused on the genetic factors involving many unexplored genes associated with recurrent miscarriages. In this review, searched the articles with keywords that were published recently from various journal searches such as Google Scholar, Science Direct, and the National Center for Biotechnology Information (NCBI) platform.
Yu M, Du G, Xu Q, et al. Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy loss. EBioMedicine 2018;35:334–344. DOI: 10.1016/j.ebiom.2018.07.042.
Atik RB, Christiansen OB, Elson J, et al. ESHRE guideline: Recurrent pregnancy loss. Hum Reprod Open 2018;2018(2):hoy004. DOI: 10.1093/hropen/hoy004.
Hyde KJ, Schust DJ. Genetic considerations in recurrent pregnancy loss. Cold Spring Harb Perspect Med 2015;5(3):a023119. DOI: 10.1101/cshperspect.a023119.
Sultana S, Nallari P, Ananthapur V. Recurrent pregnancy loss (RPL): An overview. J Womens Heal Dev 2020;3(3):302–315. DOI: 10.26502/fjwhd.2644-28840038.
Pinar MH, Gibbins K, He M, et al. Early pregnancy losses: Review of nomenclature, histopathology, and possible etiologies. Fetal Pediatr Pathol 2018;37(3):191–209. DOI: 10.1080/15513815.2018.1455775.
Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure: Update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol 2018;16(1):1–18. DOI: 10.1186/s12958-018-0414-2.
Turocy JM, Rackow BW. Uterine factor in recurrent pregnancy loss. In: Seminars in Perinatology. Elsevier; 2019, pp. 74–79.
Ahmad W, Bilal S, Azhar S, et al. Puzzle Out the Reason behind Habitual Miscarriage. Journal of Pharmaceutical Research International 2020;32(32). pp. 92–98. DOI: 10.9734/jpri/2020/v32i3230938.
Maddirevula S, Awartani K, Coskun S, et al. A genomics approach to females with infertility and recurrent pregnancy loss. Hum Genet 2020;139(5):605–613. DOI: 10.1007/s00439-020-02143-5.
Sung N, Khan SA, Yiu ME, et al. Reproductive outcomes of women with recurrent pregnancy losses and repeated implantation failures are significantly improved with immunomodulatory treatment. J Reprod Immunol 2021;148:103369. DOI: 10.1016/j.jri.2021.103369.
Kim JA, Bang CH, Song GG, et al. Tumour necrosis factor alpha gene polymorphisms in women with recurrent pregnancy loss: A meta-analysis. Hum Fertil (Camb) 2020;23(3):159–169. DOI: 10.1080/14647273.2018.1543899.
Ticconi C, Pietropolli A, Di Simone N, et al. Endometrial immune dysfunction in recurrent pregnancy loss. Int J Mol Sci 2019;20(21):5332. DOI: 10.3390/ijms20215332.
Coomarasamy A, Dhillon–Smith RK, Papadopoulou A, et al. Recurrent miscarriage: Evidence to accelerate action. Lancetw 2021;397(10285):1675–1682. DOI: 10.1016/S0140-6736(21)00681-4.
Liu X, Qiu Y, Yu ED, et al. Comparison of therapeutic interventions for recurrent pregnancy loss in association with antiphospholipid syndrome: A systematic review and network meta-analysis. Am J Reprod Immunol 2020;83(4):e13219. DOI: 10.1111/aji.13219.
Sfakianoudis K, Rapani A, Grigoriadis S, et al. The role of uterine natural killer cells on recurrent miscarriage and recurrent implantation failure: From pathophysiology to treatment. Biomedicines 2021;9(10):1425. DOI: 10.3390/biomedicines9101425.
Quenby S, Gallos ID, Dhillon–Smith RK, et al. Miscarriage matters: The epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet 2021;397(10285):1658–1667. DOI: 10.1016/S0140-6736(21)00682-6.
Naeem A, Jan S, Shah BG. Association of the thyroid function disorder with recurrent pregnancy loss in women: Thyroid function disorder with recurrent pregnancy loss in women. Pakistan Biomed J 2022;5(7):274–277. DOI: 10.54393/pbmj.v5i7.687.
Kodogo V, Azibani F, Sliwa K. Role of pregnancy hormones and hormonal interaction on the maternal cardiovascular system: A literature review. Clin Res Cardiol 2019;108(8):831–846. DOI: 10.1007/s00392-019-01441-x.
Sokhadze K, Kvaliashvili S, Kristesashvili J. Reproductive function and pregnancy outcomes in women treated for idiopathic hyperprolactinemia: A non-randomized controlled study. Int J Reprod Biomed 2020;18(12):1039–1048. DOI: 10.18502/ijrm.v18i12.8025.
Amrane S, McConnell R. Endocrine causes of recurrent pregnancy loss. In: Seminars in perinatology. Elsevier; 2019, pp. 80–83.
Finley J, Hay S, Oldzej J, et al. The genomic basis of sporadic and recurrent pregnancy loss: A comprehensive in-depth analysis of 24,900 miscarriages. Reprod Biomed Online 2022;45(1):125–134. DOI: 10.1016/j.rbmo.2022.03.014.
Dimitriadis E, Menkhorst E, Saito S, et al. Recurrent pregnancy loss. Nat Rev Dis Prim 2020;6(1):1–19. DOI: 10.1038/s41572-020-00228-z.
Lucas ES, Vrljicak P, Muter J, et al. Recurrent pregnancy loss is associated with a pro-senescent decidual response during the peri-implantation window. Commun Biol 2020;3(1):1–14. DOI: 10.1038/s42003-020-0763-1.
Moghbeli M. Genetics of recurrent pregnancy loss among Iranian population. Mol Genet Genomic Med 2019;7(9):e891. DOI: 10.1002/mgg3.891.
van Dijk MM, Kolte AM, Limpens J, et al. Recurrent pregnancy loss: Diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis. Hum Reprod Update 2020;26(3):356–367. DOI: 10.1093/humupd/dmz048.
Yalçın S, Öztürk KH, Özbaş H, et al. Cytogenetic analysis in couples with recurrent pregnancy loss. J Surg Med 2021;5(5):449–452. DOI: 10.28982/josam.912521.
Bahia W, Soltani I, Abidi A, et al. Identification of genes and miRNA associated with idiopathic recurrent pregnancy loss: An exploratory data mining study. BMC Med Genomics 2020;13(1):75. DOI: 10.1186/s12920-020-00730-z.
Arias–Sosa LA, Acosta ID, Lucena–Quevedo E, et al. Genetic and epigenetic variations associated with idiopathic recurrent pregnancy loss. J Assist Reprod Genet 2018;35(3):355–366. DOI: 10.1007/s10815-017-1108-y.
Wyatt MA, Baumgarten SC, Weaver AL, et al. Evaluating markers of immune tolerance and angiogenesis in maternal blood for an association with risk of pregnancy loss. J Clin Med 2021;10(16):3579. DOI: 10.3390/jcm10163579.
Ewington LJ, Tewary S, Brosens JJ. New insights into the mechanisms underlying recurrent pregnancy loss. J Obstet Gynaecol Res 2019;45(2):258–265. DOI: 10.1111/jog.13837.
Nanassy L, Carrell DT. Paternal effects on early embryogenesis. J Exp Clin Assist Reprod 2008;5(1):2. DOI: 10.1186/1743-1050-5-2.
Ibrahim Y, Johnstone E. The male contribution to recurrent pregnancy loss. Transl Androl Urol 2018;7(Suppl. 3):S317–S327. DOI: 10.21037/tau.2018.05.14.
Liu Y, Tang Y, Ye D, et al. Impact of abnormal DNA methylation of imprinted loci on human spontaneous abortion. Reprod Sci 2018;25(1):131–139. DOI: 10.1177/1933719117704906.
Neusser M, Rogenhofer N, Dürl S, et al. Increased chromosome 16 disomy rates in human spermatozoa and recurrent spontaneous abortions. Fertil Steril 2015;104(5):1130–1137. DOI: 10.1016/j.fertnstert.2015.07.1160.
McQueen DB, Zhang J, Robins JC. Sperm DNA fragmentation and recurrent pregnancy loss: A systematic review and meta-analysis. Fertil Steril 2019;112(1):54–60. DOI: 10.1016/j.fertnstert.2019.03.003.
Yin L-J, Zhang Y, Lv P-P, et al. Insufficient maintenance DNA methylation is associated with abnormal embryonic development. BMC Med 2012;10:26. DOI: 10.1186/1741-7015-10-26.
Lubinsky M. An epigenetic association of malformations, adverse reproductive outcomes, and fetal origins hypothesis related effects. J Assist Reprod Genet 2018;35(6):953–964. DOI: 10.1007/s10815-018-1197-2.
Iacobazzi V, Infantino V, Castegna A, et al. Hyperhomocysteinemia: Related genetic diseases and congenital defects, abnormal DNA methylation and newborn screening issues. Mol Genet Metab 2014;113(1–2):27–33. DOI: 10.1016/j.ymgme.2014.07.016.
Khambata K, Raut S, Deshpande S, et al. DNA methylation defects in spermatozoa of male partners from couples experiencing recurrent pregnancy loss. Hum Reprod 2021;36(1):48–60. DOI: 10.1093/humrep/deaa278.
Hedegaard S, Landersoe SK, Olsen LR, et al. Stress and depression among women and men who have experienced recurrent pregnancy loss: Focusing on both sexes. Reprod Biomed Online 2021;42(6):1172–1180. DOI: 10.1016/j.rbmo.2021.03.012.
Valero–Pacheco N, Tang EK, Massri N, et al. Maternal IL-33 critically regulates tissue remodeling and type 2 immune responses in the uterus during early pregnancy in mice. Proc Natl Acad Sci U S A 2022;119(35):e2123267119. DOI: 10.1073/pnas.2123267119.
Huppertz B. Traditional and new routes of trophoblast invasion and their implications for pregnancy diseases. Int J Mol Sci 2019;21(1):289. DOI: 10.3390/ijms21010289.
Yi Y, Lu G, Ouyang Y, et al. A logistic model to predict early pregnancy loss following in vitro fertilization based on 2601 infertility patients. Reprod Biol Endocrinol 2016;14(1):1–7. DOI: 10.1186/s12958-016-0147-z.
Wang Y, Zhang Q, Yin C, et al. Automated prediction of early spontaneous miscarriage based on the analyzing ultrasonographic gestational sac imaging by the convolutional neural network: A case–control and cohort study. BMC Pregnancy Childbirth 2022;22(1):621. DOI: 10.1186/s12884-022-04936-0.