Current Approach to Genetic Causes of Female Infertility and Genetic Counseling

Year 2022, , 56 - 62, 30.10.2022

Nıgar Shırınova , Fatma Zehra Yalçın , Sevcan Tuğ Bozdoğan

https://doi.org/10.18678/dtfd.1183278

Abstract

Infertility is a disease of the male or female reproductive system and is defined as the inability to achieve pregnancy after 12 months or more of regular and unprotected sexual intercourse. Data shows that more than 186 million people worldwide are infertile. About 10% of the women of reproductive age are unable to conceive or maintain a pregnancy. In this study, the causes of female infertility were reviewed under several headings and the importance of genetic counseling in infertility was also mentioned. There are many different causes of female infertility, including both genetic and non-genetic causes. In this review, current developments and approaches in the genetic etiology of female infertility were reviewed under six main headings, chromosomal abnormalities, female genital system disorders, hypogonadotropic hypogonadism, primary ovarian failure, polycystic ovary syndrome, and gonadal dysgenesis. Also, the role of genetic counseling in these diseases was discussed. The aim of genetic counseling is to inform people with a hereditary disease or at high risk of carrying it about the course of the disease and treatment methods, and also to guide future generations and family members about their risks. After all tests and examinations, genetic counseling has a very important place in reproductive health.

Keywords

Female, genetics, infertility, genetic counseling

Kadın İnfertilitesinin Genetik Nedenlerine Güncel Yaklaşım ve Genetik Danışmanlık

Abstract

İnfertilite, erkek veya kadın üreme sisteminin bir hastalığı olup, 12 ay veya daha uzun süre düzenli ve korunmasız cinsel ilişkiden sonra gebelik elde edilememesi olarak tanımlanır. Veriler, dünya çapında 186 milyondan fazla insanın infertil olduğunu göstermektedir. Üreme çağındaki kadınların yaklaşık %10'u gebe kalamaz veya hamileliğini sürdüremez. Bu çalışmada kadın infertilitesinin nedenleri çeşitli başlıklar altında incelenmiş ve ayrıca infertilitede genetik danışmanlığın önemine de değinilmiştir. Kadın infertilitesinin hem genetik ve hem de genetik olmayan nedenler de dahil olmak üzere birçok farklı nedeni vardır. Bu derlemede kadın infertilitesinin genetik etiyolojisindeki güncel gelişmeler ve yaklaşımlar, kromozom anomalileri, kadın genital sistem bozuklukları, hipogonadotropik hipogonadizm, primer over yetmezliği, polikistik over sendromu ve gonadal disgenezi olmak üzere altı ana başlık altında incelenmiştir. Ayrıca bu hastalıklarda genetik danışmanlığın rolü de tartışılmıştır. Genetik danışmanlığın amacı, kalıtsal bir hastalığı olan veya taşıyıcı olma riski yüksek olan kişileri hastalığın seyri ve tedavi yöntemleri hakkında bilgilendirmek, aynı zamanda gelecek nesillere ve aile bireylerine de riskleri konusunda rehberlik etmektir. Tüm test ve tetkiklerden sonra, üreme sağlığında genetik danışmanlık çok önemli bir yere sahiptir.

Keywords

Kadın, genetik, infertilite, genetik danışmanlık

References

• Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018;62:2-10.
• Yatsenko SA, Rajkovic A. Genetics of human female infertility†. Biol Reprod. 2019;101(3):549-66.
• Johnston DR. The history of human infertility. Fertil Steril. 1963;14(3):261-72.
• Morice P, Josset P, Chapron C, Dubuisson JB. History of infertility. Hum Reprod Update. 1995;1(5):497-504.
• Yang M, Kim JW. Principles of genetic counseling in the era of next-generation sequencing. Ann Lab Med. 2018;38(4):291-5.
• Healey A. Embryology of the female reproductive tract. In: Mann GS, Blair JC, Garden AS, editors. Imaging of gynecological disorders in infants and children. Berlin, Heidelberg: Springer; 2010. p.21-30.
• Alzamil L, Nikolakopoulou K, Turco MY. Organoid systems to study the human female reproductive tract and pregnancy. Cell Death Differ. 2021;28(1):35-51.
• Hartshorne GM, Lyrakou S, Hamoda H, Oloto E, Ghafari F. Oogenesis and cell death in human prenatal ovaries: what are the criteria for oocyte selection? Mol Hum Reprod. 2009;15(12):805-19.
• Laisk T, Kukuškina V, Palmer D, Laber S, Chen CY, Ferreira T, et al. Large-scale meta-analysis highlights the hypothalamic-pituitary-gonadal axis in the genetic regulation of menstrual cycle length. Hum Mol Genet. 2018;27(24):4323-32.
• Mierla D, Malageanu M, Tulin R, Albu D. Prevalence of chromosomal abnormalities in infertile couples in Romania. Balkan J Med Genet. 2015;18(1):23-30.
• Otter M, Crins PML, Campforts BCM, Stumpel CTRM, van Amelsvoort TAMJ, Vingerhoets C. Social functioning and emotion recognition in adults with triple X syndrome. BJPsych Open. 2021;7(2):e51.
• Cui X, Cui Y, Shi L, Luan J, Zhou X, Han J. A basic understanding of Turner syndrome: Incidence, complications, diagnosis, and treatment. Intractable Rare Dis Res. 2018;7(4):223-8.
• Oktay K, Bedoschi G, Berkowitz K, Bronson R, Kashani B, McGovern P, et al. Fertility preservation in women with turner syndrome: a comprehensive review and practical guidelines. J Pediatr Adolesc Gynecol. 2016;29(5):409-16.
• Yahaya TO, Oladele EO, Anyebe D, Obi C, Bunza MDA, Sulaiman R, et al. Chromosomal abnormalities predisposing to infertility, testing, and management: a narrative review. Bull Natl Res Cent. 2021;45:65.
• Gekas J, Thepot F, Turleau C, Siffroi JP, Dadoune JP, Briault S, et al. Chromosomal factors of infertility in candidate couples for ICSI: an equal risk of constitutional aberrations in women and men. Hum Reprod. 2001;16(1):82-90.
• Innis JW. Hand-foot-genital syndrome. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, et al., editors. GeneReviews® Seattle (WA): University of Washington, Seattle; 1993-2022.
• Fontana L, Gentilin B, Fedele L, Gervasini C, Miozzo M. Genetics of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. Clin Genet. 2017;91(2):233-46.
• Connell M, Owen C, Segars J. Genetic syndromes and genes involved in the development of the female reproductive tract: a possible role for gene therapy. J Genet Syndr Gene Ther. 2013;4:127.
• Nik-Zainal S, Strick R, Storer M, Huang N, Rad R, Willatt L, et al. High incidence of recurrent copy number variants in patients with isolated and syndromic Müllerian aplasia. J Med Genet. 2011;48(3):197-204.
• Uno S, Zembutsu H, Hirasawa A, Takahashi A, Kubo M, Akahane T, et al. A genome-wide association study identifies genetic variants in the CDKN2BAS locus associated with endometriosis in Japanese. Nat Genet. 2010;42(8):707-10.
• Rahmioglu N, Nyholt DR, Morris AP, Missmer SA, Montgomery GW, Zondervan KT. Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets. Hum Reprod Update. 2014;20(5):702-16.
• Painter JN, Anderson CA, Nyholt DR, Macgregor S, Lin J, Lee SH, et al. Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nat Genet. 2011;43(1):51-4.
• De Conto E, Matte Ú, Bilibio JP, Genro VK, Souza CA, Leão DP, et al. Endometriosis-associated infertility: GDF-9, AMH, and AMHR2 genes polymorphisms. J Assist Reprod Genet. 2017;34(12):1667-72.
• Qin Y, Jiao X, Simpson JL, Chen ZJ. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update. 2015;21(6):787-808.
• Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med. 2009;360(6):606-14.
• Rafique M, AlObaid S, Al-Jaroudi D. 47, XXX syndrome with infertility, premature ovarian insufficiency, and streak ovaries. Clin Case Rep. 2019;7(6):1238-41.
• Sugawara N, Maeda M, Manome T, Nagai R, Araki Y. Patients with 47, XXX karyotype who experienced premature ovarian failure (POF): two case reports. Reprod Med Biol. 2013;12(4):193-5.
• Tang R, Lin L, Guo Z, Hou H, Yu Q. Ovarian reserve evaluation in a woman with 45,X/47,XXX mosaicism: A case report and a review of literature. Mol Genet Genomic Med. 2019;7(7):e00732.
• Goswami R, Goswami D, Kabra M, Gupta N, Dubey S, Dadhwal V. Prevalence of the triple X syndrome in phenotypically normal women with premature ovarian failure and its association with autoimmune thyroid disorders. Fertil Steril. 2003;80(4):1052-4.
• Smits MAJ, Janssens GE, Goddijn M, Hamer G, Houtkooper RH, Mastenbroek S. Longevity pathways are associated with human ovarian ageing. Hum Reprod Open. 2021;2021(2):hoab020.
• Yang X, Zhang X, Jiao J, Zhang F, Pan Y, Wang Q, et al. Rare variants in FANCA induce premature ovarian insufficiency. Hum Genet. 2019;138(11-12):1227-36.
• Bednarska S, Siejka A. The pathogenesis and treatment of polycystic ovary syndrome: What's new? Adv Clin Exp Med. 2017;26(2):359-67.
• McAllister JM, Legro RS, Modi BP, Strauss JF 3rd. Functional genomics of PCOS: from GWAS to molecular mechanisms. Trends Endocrinol Metab. 2015;26(3):118-24.
• Breehl L, Caban O. Genetics, gonadal dysgenesis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022.
• Chen B, Xu P, Wang J, Zhang C. The role of MiRNA in polycystic ovary syndrome (PCOS). Gene. 2019;706:91-6.
• Costa-Barbosa FA, Balasubramanian R, Keefe KW, Shaw ND, Al-Tassan N, Plummer L, et al. Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes. J Clin Endocrinol Metab. 2013;98(5):E943-53.
• Culha C, Ozkaya M, Serter R, Sahin I, Aydin B, Aral Y. Swyer's syndrome: in a fifty-year-old female. J Obstet Gynaecol India. 2012;62(5):571-4.
• Beke A. Genetic causes of female infertility. In: Igaz P, Patócs A, editors. Genetics of endocrine diseases and syndromes. Cham: Springer; 2019. p.367-83.
• Dey M, Sharma S, Aggarwal S. Prenatal screening methods for aneuploidies. N Am J Med Sci. 2013;5(3):182-90.
• Ramos ES. Turner syndrome: counseling prior to oocyte donation. Sao Paulo Med J. 2007;125(2):112-4.
• Cariati F, D'Argenio V, Tomaiuolo R. The evolving role of genetic tests in reproductive medicine. J Transl Med. 2019;17(1):267.
• Kyei-Barffour I, Margetts M, Vash-Margita A, Pelosi E. The embryological landscape of Mayer-Rokitansky-Kuster-Hauser syndrome: genetics and environmental factors. Yale J Biol Med. 2021;94(4):657-72.
• Butz H, Nyírő G, Kurucz PA, Likó I, Patócs A. Molecular genetic diagnostics of hypogonadotropic hypogonadism: from panel design towards result interpretation in clinical practice. Hum Genet. 2021;140(1):113-34.
• Barasoain M, Barrenetxea G, Huerta I, Télez M, Criado B, Arrieta I. Study of the genetic etiology of primary ovarian insufficiency: FMR1 gene. Genes (Basel). 2016;7(12):123.