The role of men in recurrent miscarriage; a Narrative Review
Men's Health Journal,
Vol. 3 No. 1 (2019),
13 April 2019
,
Page e7
https://doi.org/10.22037/mhj.v3i1.29340
Abstract
Background and Method: Recurrent Pregnancy Loss (RPL) is defined as the occurrence of two or more consecutive miscarriages within the first 20 weeks of pregnancy. The key challenge remains to be what it is that has to be done with couples experiencing RPL. Infections, endocrine disturbances, a suboptimal uterine environment, advanced maternal age, and genetic influences are some of the factors which may increase the chances of RPL occurrence. Despite all medical and research efforts, approximately 40 percent of RPL cases are categorized as unexplained. This is while amongst all the various factors which may lead to such condition, fathers’ genetic influences have often been ignored in the past. In fact, parental chromosomal anomalies, gene mutations such as the microdeletion of chromosome Y, and/or some polymorphism of HLA-G have shown to contribute and lead to miscarriage.
Result: Furthermore, high levels of Reactive Oxygen Species (ROS) can cause DNA damage in spermatozoa. Meantime, sperm DNA damage has been closely linked with indicators such as fertilization, embryo quality, implantation, spontaneous abortion, congenital malformations, and childhood diseases. Sperm Chromatin Structure Assay (SCSA) is a test to measure DNA fragmentation. Moreover, the other SCSA parameter that needs to be considered is high DNA stainability (HDS). It is worth mentioning that HDS is associated with frequency of aneuploidy in spermatozoa. In addition, high HDS can be associated with an increased risk of early abortion in IVF and ICSI cycles.
Conclusion: Additionally, increasing paternal age and varicocele can increase the risk of miscarriage. Advanced Paternal Age (APA) can also increase the relative risk of offspring neurocognitive defects. In saying that, the microsurgical varicocelectomy effectively increases the odds of natural pregnancy, the rate of high-quality embryos, and the success rate of in vitro fertilization.
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References
Li YH, Marren A. Recurrent pregnancy loss. Australian journal of general practice. 2018;47(7):432.
Hamamah S, Fignon A, Lansac J. The effect of male factors in repeated spontaneous abortion: lesson from in-vitro fertilization and intracytoplasmic sperm injection. Human reproduction update. 1997;3(4):393-400.
Puscheck EE, Jeyendran RS. The impact of male factor on recurrent pregnancy loss. Current Opinion in Obstetrics and Gynecology. 2007;19(3):222-8.
Kaser D. The status of genetic screening in recurrent pregnancy loss. Obstetrics and Gynecology Clinics. 2018;45(1):143-54.
Kumar K, Deka D, Singh A, Mitra D, Vanitha B, Dada R. Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception. Journal of assisted reproduction and genetics. 2012;29(9):861-7.
Bronson R. Role of spermatozoa in the etiology of miscarriage. Fertility and sterility. 2016;105(1):47-8.
Kumar K, Thilagavathi J, Deka D, Dada R. Unexplained early pregnancy loss: role of paternal DNA. The Indian journal of medical research. 2012;136(2):296.
Stuppia L, Franzago M, Ballerini P, Gatta V, Antonucci I. Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health. Clinical epigenetics. 2015;7(1):120.
Rathke C, Baarends WM, Awe S, Renkawitz-Pohl R. Chromatin dynamics during spermiogenesis. Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms. 2014;1839(3):155-68.
Aston KI, Punj V, Liu L, Carrell DT. Genome-wide sperm deoxyribonucleic acid methylation is altered in some men with abnormal chromatin packaging or poor in vitro fertilization embryogenesis. Fertility and sterility. 2012;97(2):285-92. e4.
Gavriliouk D, Aitken RJ. Damage to sperm DNA mediated by reactive oxygen species: its impact on human reproduction and the health trajectory of offspring. The Male Role in Pregnancy Loss and Embryo Implantation Failure: Springer; 2015. p. 23-47.
Stringer JM, Winship A, Liew SH, Hutt K. The capacity of oocytes for DNA repair. Cellular and molecular life sciences. 2018;75(15):2777-92.
Li T, Makris M, Tomsu M, Tuckerman E, Laird S. Recurrent miscarriage: aetiology, management and prognosis. Human reproduction update. 2002;8(5):463-81.
Chenoweth PJ. Influence of the male on embryo quality. Theriogenology. 2007;68(3):308-15.
Mattei J. Influence of the male in embryonic mortality. Current topics in veterinary medicine and animal science. 1984.
Morel F, Roux C, Bresson J-L. FISH analysis of the chromosomal status of spermatozoa from three men with 45, XY, der (13; 14)(q10; q10) karyotype. Molecular human reproduction. 2001;7(5):483-8.
Sugiura-Ogasawara M, Ozaki Y, Sato T, Suzumori N, Suzumori K. Poor prognosis of recurrent aborters with either maternal or paternal reciprocal translocations. Fertility and sterility. 2004;81(2):367-73.
Carrell DT, Emery BR, Hammoud S. Altered protamine expression and diminished spermatogenesis: what is the link? Human reproduction update. 2007;13(3):313-27.
Ribas-Maynou J, Benet J. Single and double strand sperm DNA damage: different reproductive effects on male fertility. Genes. 2019;10(2):105.
Genesca A, Caballin M, Miro R, Benet J, Germa J, Egozcue J. Repair of human sperm chromosome aberrations in the hamster egg. Human genetics. 1992;89(2):181-6.
Shamsi MB, Imam SN, Dada R. Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility. Journal of assisted reproduction and genetics. 2011;28(11):1073-85.
Bungum M. Sperm DNA integrity assessment: a new tool in diagnosis and treatment of fertility. Obstetrics and gynecology international. 2012;2012.
Barati E, Nikzad H, Karimian M. Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cellular and Molecular Life Sciences. 2019:1-21.
Organisation WH. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction: Cambridge university press; 1999.
Lu J-C, Huang Y-F, Lü N-Q. WHO Laboratory Manual for the Examination and Processing of Human Semen: its applicability to andrology laboratories in China. Zhonghua nan ke xue= National journal of andrology. 2010;16(10):867-71.
Lewis SE, Aitken RJ, Conner SJ, De Iuliis G, Evenson DP, Henkel R, et al. The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Reproductive biomedicine online. 2013;27(4):325-37.
Loutradi KE, Tarlatzis BC, Goulis DG, Zepiridis L, Pagou T, Chatziioannou E, et al. The effects of sperm quality on embryo development after intracytoplasmic sperm injection. Journal of assisted reproduction and genetics. 2006;23(2):69-74.
Carlini T, Paoli D, Pelloni M, Faja F, Dal Lago A, Lombardo F, et al. Sperm DNA fragmentation in Italian couples with recurrent pregnancy loss. Reproductive biomedicine online. 2017;34(1):58-65.
Absalan F, Ghannadi A, Kazerooni M, Parifar R, Jamalzadeh F, Amiri S. Value of sperm chromatin dispersion test in couples with unexplained recurrent abortion. Journal of assisted reproduction and genetics. 2012;29(1):11-4.
Khadem N, Poorhoseyni A, Jalali M, Akbary A, Heydari S. Sperm DNA fragmentation in couples with unexplained recurrent spontaneous abortions. Andrologia. 2014;46(2):126-30.
Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid Á. Assessment of sperm factors possibly involved in early recurrent pregnancy loss. Fertility and sterility. 2010;94(4):1465-72.
Bellver J, Meseguer M, Muriel L, Garcia-Herrero S, Barreto M, Garda A, et al. Y chromosome microdeletions, sperm DNA fragmentation and sperm oxidative stress as causes of recurrent spontaneous abortion of unknown etiology. Human reproduction. 2010;25(7):1713-21.
Ménézo YJ, Hazout A, Panteix G, Robert F, Rollet J, Cohen-Bacrie P, et al. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reproductive biomedicine online. 2007;14(4):418-21.
Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, et al. Age-associated alteration of gene expression patterns in mouse oocytes. Human molecular genetics. 2004;13(19):2263-78.
Evenson D, Wixon R. Meta-analysis of sperm DNA fragmentation using the sperm chromatin structure assay. Reproductive biomedicine online. 2006;12(4):466-72.
Zhu X-B, Chen Q, Fan W-M, Niu Z-H, Xu B-F, Zhang A-J. Sperm DNA fragmentation in Chinese couples with unexplained recurrent pregnancy loss. Asian journal of andrology. 2019.
Evenson DP. The Sperm Chromatin Structure Assay (SCSA®) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Animal reproduction science. 2016;169:56-75.
Evenson DP, LARSON KL, Jost LK. Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. Journal of andrology. 2002;23(1):25-43.
Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Human reproduction. 2006;22(1):174-9.
Lin M-H, Lee RK-K, Li S-H, Lu C-H, Sun F-J, Hwu Y-M. Sperm chromatin structure assay parameters are not related to fertilization rates, embryo quality, and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection, but might be related to spontaneous abortion rates. Fertility and sterility. 2008;90(2):352-9.
Kazerooni T, Asadi N, Jadid L, Kazerooni M, Ghanadi A, Ghaffarpasand F, et al. Evaluation of sperm’s chromatin quality with acridine orange test, chromomycin A3 and aniline blue staining in couples with unexplained recurrent abortion. Journal of assisted reproduction and genetics. 2009;26(11-12):591-6.
Jerre E, Bungum M, Evenson D, Giwercman A. Sperm chromatin structure assay high DNA stainability sperm as a marker of early miscarriage after intracytoplasmic sperm injection. Fertility and sterility. 2019.
Wyrobek AJ, Eskenazi B, Young S, Arnheim N, Tiemann-Boege I, Jabs E, et al. Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proceedings of the National Academy of Sciences. 2006;103(25):9601-6.
Lazaros L, Kaponis A, Vartholomatos G, Hatzi E, Botsari S, Plachouras N, et al. Using semen flow cytometry to evaluate association of ploidy status and chromatin condensation of spermatozoa with conventional semen parameters: clinical application in intrauterine insemination. Fertility and sterility. 2011;95(1):110-5.
Lazaros LA, Vartholomatos GA, Hatzi EG, Kaponis AI, Makrydimas GV, Kalantaridou SN, et al. Assessment of sperm chromatin condensation and ploidy status using flow cytometry correlates to fertilization, embryo quality and pregnancy following in vitro fertilization. Journal of assisted reproduction and genetics. 2011;28(10):885-91.
Buffat C, Patrat C, Merlet F, Guibert J, Epelboin S, Thiounn N, et al. ICSI outcomes in obstructive azoospermia: influence of the origin of surgically retrieved spermatozoa and the cause of obstruction. Human reproduction. 2005;21(4):1018-24.
Jia C-W, Wang L, Lan Y-L, Song R, Zhou L-Y, Yu L, et al. Aneuploidy in early miscarriage and its related factors. Chinese medical journal. 2015;128(20):2772.
Lathi RB, Milki AA. Rate of aneuploidy in miscarriages following in vitro fertilization and intracytoplasmic sperm injection. Fertility and sterility. 2004;81(5):1270-2.
Kovats S, Main EK, Librach C, Stubblebine M, Fisher SJ, DeMars R. A class I antigen, HLA-G, expressed in human trophoblasts. Science. 1990;248(4952):220-3.
Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. The FASEB Journal. 2005;19(7):681-93.
Koc A, Kirbiyik O, Kutbay YB, Ozyilmaz B, Ozdemir TR, Kaya OO, et al. Fetal HLA-G alleles and their effect on miscarriage. Advances in clinical and experimental medicine: official organ Wroclaw Medical University. 2018;27(9):1233-7.
Larsen MH, Bzorek M, Pass MB, Larsen LG, Nielsen MW, Svendsen SG, et al. Human leukocyte antigen-G in the male reproductive system and in seminal plasma. Molecular human reproduction. 2011;17(12):727-38.
Jassem RM, Shani WS, Loisel DA, Sharief M, Billstrand C, Ober C. HLA-G polymorphisms and soluble HLA-G protein levels in women with recurrent pregnancy loss from Basrah province in Iraq. Human immunology. 2012;73(8):811-7.
Apps R, Gardner L, Sharkey AM, Holmes N, Moffett A. A homodimeric complex of HLA‐G on normal trophoblast cells modulates antigen‐presenting cells via LILRB1. European journal of immunology. 2007;37(7):1924-37.
Aldrich C, Stephenson M, Karrison T, Odem R, Branch D, Scott J, et al. HLA-G genotypes and pregnancy outcome in couples with unexplained recurrent miscarriage. Molecular human reproduction. 2001;7(12):1167-72.
Vog P, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Human molecular genetics. 1996;5(7):933-43.
Hopps C, Mielnik A, Goldstein M, Palermo G, Rosenwaks Z, Schlegel P. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Human reproduction. 2003;18(8):1660-5.
Egozcue S, Blanco J, Vendrell J, Garcia F, Veiga A, Aran B, et al. Human male infertility: chromosome anomalies, meiotic disorders, abnormal spermatozoa and recurrent abortion. Human reproduction update. 2000;6(1):93-105.
Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, et al. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. The Journal of Clinical Endocrinology & Metabolism. 2007;92(3):762-70.
Dewan S, Puscheck EE, Coulam CB, Wilcox AJ, Jeyendran RS. Y-chromosome microdeletions and recurrent pregnancy loss. Fertility and sterility. 2006;85(2):441-5.
Perrin J, Metzler-Guillemain C, Karsenty G, Grillo J-M, Mitchell MJ, Guichaoua M-R. Meiotic arrest at the midpachytene stage in a patient with complete azoospermia factor b deletion of the Y chromosome. Fertility and sterility. 2006;85(2):494. e5-. e8.
Carolan M, Frankowska D. Advanced maternal age and adverse perinatal outcome: a review of the evidence. Midwifery. 2011;27(6):793-801.
Ramasamy R, Chiba K, Butler P, Lamb DJ. Male biological clock: a critical analysis of advanced paternal age. Fertility and sterility. 2015;103(6):1402-6.
Toriello HV, Meck JM. Statement on guidance for genetic counseling in advanced paternal age. Genetics in Medicine. 2008;10(6):457.
Johnson SL, Dunleavy J, Gemmell NJ, Nakagawa S. Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis. Ageing research reviews. 2015;19:22-33.
Spanò M, Bonde JP, Hjøllund HI, Kolstad HA, Cordelli E, Leter G, et al. Sperm chromatin damage impairs human fertility. Fertility and sterility. 2000;73(1):43-50.
Ferreira RC, Braga DPdAF, de Souza Bonetti TC, Pasqualotto FF, Iaconelli Jr A, Borges Jr E. Negative influence of paternal age on clinical intracytoplasmic sperm injection cycle outcomes in oligozoospermic patients. Fertility and sterility. 2010;93(6):1870-4.
Luna M, Finkler E, Barritt J, Bar-Chama N, Sandler B, Copperman AB, et al. Paternal age and assisted reproductive technology outcome in ovum recipients. Fertility and sterility. 2009;92(5):1772-5.
Frattarelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Scott Jr RT. Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertility and sterility. 2008;90(1):97-103.
Whitcomb BW, Turzanski-Fortner R, Richter KS, Kipersztok S, Stillman RJ, Levy MJ, et al. Contribution of male age to outcomes in assisted reproductive technologies. Fertility and sterility. 2011;95(1):147-51.
Lowe X, Eskenazi B, Nelson DO, Kidd S, Alme A, Wyrobek AJ. Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome. The American Journal of Human Genetics. 2001;69(5):1046-54.
Diamond D. Adolescent varicocele: emerging understanding. BJU international. 2003;92:48-51.
Sakkas D, Moffatt O, Manicardi GC, Mariethoz E, Tarozzi N, Bizzaro D. Nature of DNA damage in ejaculated human spermatozoa and the possible involvement of apoptosis. Biology of reproduction. 2002;66(4):1061-7.
Cocuzza M, Cocuzza MA, Bragais FMP, Agarwal A. The role of varicocele repair in the new era of assisted reproductive technology. Clinics. 2008;63(3):395-404.
Ghanaie MM, Asgari SA, Dadrass N, Allahkhah A, Iran-Pour E, Safarinejad MR. Effects of varicocele repair on spontaneous first trimester miscarriage: a randomized clinical trial. Urology journal. 2012;9(2):505-13.
Mostafa T, Anis T, El‐Nashar A, Imam H, Othman I. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. International Journal of Andrology. 2001;24(5):261-5.
Sönmez MG, Haliloğlu AH. Role of varicocele treatment in assisted reproductive technologies. Arab journal of urology. 2018;16(1):188-96.
Tavalaee M, Abbasi H, Deemeh MR, Fotohi F, Gilani MAS, Esfahani MHN. Semen parameters and chromatin packaging in microsurgical varicocelectomy patients. International journal of fertility & sterility. 2012;6(3):165.
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