A.F. MURZAKHANOVA, V.N. OSLOPOV, E.V. KHAZOVA

Kazan State Medical University of the Ministry of Health of the Russian Federation, Kazan

 Contact:

Oslopov V.N. ― MD, Professor of the Department of Propaedeutics of Internal Diseases named after Prof. S. S. Zimnitsky

Address: 49 Butlerov St., 420012, Kazan, Russian Federation, tel. +7-905-316-25-35, e-mail: kpvbol@yandex.ru

The problems of the effect of in vitro fertilization on the health of future offsprings are mainly due to infertility, age and diseases of the parents. However, the influence of technical aspects related to the procedure itself is not ruled out. It was noted that the most common are perinatal abnormalities associated with multiple pregnancy with polyembryonic implants, congenital anomalies of the nervous, genitourinary, digestive, cardiovascular and musculoskeletal systems, as well as malformations of eyes, ears, facial and cervical zones. In addition, the incidence of epigenetic disorders and oncological diseases is higher in couples using assisted reproductive technologies (ART) compared with the general population. Children with pathology make up 75% of all children born using IVF. Children who are born healthy (25%), in the future, have normal indicators of physical and sexual development, somatic and neurological health and only slightly differ from children born without the use of ART, and in school and subsequent periods of life, significant differences are not found at all.

Key words: in vitro fertilization, children’s health, congenital anomalies, oncology, somatic health, neurological outcomes.

REFERENCES

1. Pis’mo Minzdrava Rossii ot 05.03.2019 N 15-4/I/2-1913 «O napravlenii klinicheskikh rekomendatsiy (protokola lecheniya) «Zhenskoe besplodie (sovremennye podkhody k diagnostike i lecheniyu)» [Letter of the Ministry of Health of Russia dated 05.03.2019 N 15-4/I/2-1913 “On the direction of clinical recommendations (treatment protocol)“ Female infertility (modern approaches to diagnosis and treatment) ”], avaialble at: http://www.consultant.ru/document/cons_doc_LAW_322996/ (accessed on: 24.05.2020).
2. Orazov M.R. Radzinskiy V.E., Lokshin V.N. Besplodnyy brak. Versii i kontraversii [Barren marriage. Versions and contraverses]. Moscow: GEOTAR-Media, 2019. 404 p.
3. Baranov A.A. Spravka o sostoyanii zdorov’ya detey, rodivshikhsya v rezul’tate ispol’zovaniya vspomogatel’nykh reproduktivnykh tekhnologiy, v tom chisle EKO, 2012 [Information on the health status of children born as a result of using assisted reproductive technologies, including IVF], available at: https://web.archive.org/web/20140418182237/http://www.pediatr-russia.ru:80/node/124
4. Kalinina E.A., Smol’nikova V.Yu., Leonov B.V. The use of the drug Utrozhestan after transfer of embryos into the uterine cavity. Probl. Reprod., 1998, no. 2, pp. 12-14 (in Russ.).
5. Zdanovskiy V.M., Vityazeva I.I. The course and outcome of pregnancies after infertility treatment using assisted reproduction (MVR) methods. Problemy reproduktsii, 2000, no. 3, pp. 55–56 (in Russ.).
6. Kalinina E.A., Alieva K.U., Strel’chenko M.B. Scientific and clinical analysis of the work of the department of assistive technologies in the treatment of infertility in 2011. Akusherstvo i ginekologiya, 2013, no. 1, pp. 81-84 (in Russ.).
7. Prosyanik V.A. Real statistics of in vitro fertilization protocols. Studencheskiy: elektron. nauchn. zhurnal, 2019, no. 2(46) (in Russ.), available at: https://sibac.info/journal/student/46/129036
8. Zhirnov V.A., Dmitrieva M.V., Rustyanova D.R. Analiz somaticheskogo statusa novorozhdennykh detey, zachatykh posredstvom ekstrakorporal’nogo oplodotvoreniya [Analysis of the somatic status of newborns conceived through in vitro fertilization]. Molodoy uchenyy: vyzovy i perspektivy: materialy VI Mezhdunarodnoy nauchno-prakticheskoy konferentsii. Moscow, 2016. Pp. 67-71.
9. Korsak V.S., Vasil’eva O.V., Isakova E.V. Endometriosis and ART (literature review). Problemy reproduktsii, 2006, no. 3, pp. 41-46 (in Russ.).
10. Saidova R.A., Guseynova Z.S. The significance of pregravid preparation in the prevention of fetal loss syndrome in patients with hyperandrogenism. Problemy zhenskogo zdorov’ya, 2011, vol. 6, no. 1, pp. 25-30 (in Russ.).
11. Krasnopol’skaya K.V., Kabanova D.I., Kalugina A.S. The effectiveness of in vitro fertilization in patients with polycystic ovary syndrome and ovarian hyperandrogenism. Akusherstvo i ginekologiya, 2003, no. 1, pp. 57-61 (in Russ.).
12. Maslyanyuk N.A. Sostoyanie novorozhdennykh detey i ikh dal’neyshee razvitie pri mnogoplodnoy beremennosti posle ekstrakorporal’nogo oplodotvoreniya: avtoref. dis. … kand. med. nauk [The condition of newborn children and their further development in multiple pregnancy after in vitro fertilization. Synopsis of dis. PhD med. sciences]. Saint Petersburg, 2005. 24 p.
13. Kinsht D.A., Soboleva M.K., Ayzikovich I.V. The health of newborns from a singleton induced pregnancy: own experience of observing MC Avicenna. Reproduktivnaya meditsina, 2014, vol. 20, no. 3-4, pp. 18-23 (in Russ.).
14. Vartanyan E.V. Possibilities for overcoming repeated failures in assisted reproductive technology procedures. Vestnik Ural’skoy meditsinskoy akademicheskoy nauki, 2013, vol. 45, no. 3, pp. 56-62 (in Russ.).
15. Helmerhorst F.M., Perquin D.A., Donker D. et al. Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies. BMJ, 2004; 328: 7434: 261.
16. Jackson R.A., Gibson K.A., Wu Y.W. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet. Gynecol, 2004, no. 103 (3), pp. 551-563.
17. McDonald S.D., Han Z., Mulla S. et al. Knowledge Synthesis Group. Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. Eur J Obstet Gynecol Reprod Biol, 2009, no. 146 (2), pp. 138-148.
18. Nygren K.G., Finnström O., Källén B. et al. Population-based Swedish studies of outcomes after in vitro fertilization. Acta Obstet Gynecol Scand, 2007, no. 86 (7), pp. 774-782.
19. Savel’eva G.M., Kurtser M.A., Karachunskaya E.M. The health of children born after IVF. Akusherstvo i ginekologiya, 2010, no.5, pp. 49-54 (in Russ.).
20. Davies M.J., Moore V.M., Willson K.J. Reproductive technologies and the risk of birth defects. N. Engl. J. Med, 2012, no. 366 (19), pp. 1803-1813.
21. Wen J., Jiang J., Ding C. Birth defects in children conceived by in vitro fertilization and in tracytoplasmic sperm injection: a meta-analysis. Fertil. Steril,  2012, no.97 (6), pp. 1331–1337.

22. Reefhuis J., Honein M.A., Schieve L.A. Assisted reproductive technology and major structural birth defects in the United States. The National Birth Defects Prevention Study. Hum. Reprod, 2009, no.24, pp. 360-366.
23. Anteby I. et al. Ocular manifestations in children born after in vitro fertilization. Arch. Ophthalmol, 2001, no.119 (10), pp. 1525-1529.
24. Riebeling P. et al. Are screening examinations necessary in ruling out ocular malformations after reproduction treatment? Klin. Monatsbl. Augenheilkd, 2007, no.224 (5), pp. 417-421.
25. Watts P. In vitro fertilization and stage 3 retinopathy of prematurity. Eye, 2000, no.14 (3A), pp. 330-333.
26. Jennifer J. Kurinczuk Safety issues in assisted reproduction technology. Human reproduction, 2003, no.18 (5), pp. 925-931.
27. Theses of the XVI World Congress on Fertility and Sterility, transl. by. P. Gogolevsky and R. Nersyan. Problemy reproduktsii, 1999, no.2 (in Russ.).
28. Barashnev Yu. I., Nikitina I.V. Chastota i struktura vrozhdennykh porokov razvitiya u novorozhdennykh, rodivshikhsya v rezul’tate ispol’zovaniya vspomogatel’nykh reproduktivnykh tekhnologiy. Materialy VI Rossiyskogo foruma «Mat’ i ditya» [Frequency and structure of congenital malformations in newborns born as a result of using assisted reproductive technologies. Materials of the VI Russian Forum “Mother and Child”]. Moscow, 2004. Pp. 549–550.
29. Sutcliffe A., D’Souza S., Cadman J., Richards B.et al. Minor congenital anomalies, major congenital malformations and development in children conceived from cryopreserved embryos. Human Reproduction, 1995, vol. 10, pp. 3332-3337.
30. Lie R., Lyngstadaas A., Bakketeig L., Jacobsen G. et al. Birth defects in children conceived by ICSI compared with children conceived by other IVF-methods; a meta-analysis. Int. J. Epidemiol, 2005, 34:696-701.
31. Wennerholm U.-B., Albertsson-Wikland K., Bergh C., Hamberger L. et al. Postnatal growth and health in children born after cryopreservation as embryos. Lancet, 1998;351:1085-90.
32. Nelissen E., van Montfoort A., Dumoulin J., Evers J. Epigenetics and the placenta. Human Reproduction Update, 2011;17:397-417.
33. Hiura H., Okae H., Chiba H. et al. Imprinting methylation errors in ART. Reprod Med Biol., 2014; 13 (4): 193-202.
34. Simpson J.L. Birth defects and assisted reproductive technologies. Semin Fetal Neonatal Med., 2014; 19 (3): 177-82.
35. Tomizawa S., Sasaki H. Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell. J Hum Genet., 2012; 57: 2: 84-91.

36. Kitsui S., Xaidaru A., Giannikou K. De novo interstitial duplication of the 15q11.2–q14 PWS/AS region of maternal origin. Am. J. Med. Genet., 2010; 152 (8): 1925–1932.
37. Kallen B., Finnstrom O., Nygren K.G. In vitro fertilization in Sweden: child morbidity including cancer risk. Fertil. Steril., 2005; 84 (3): 605–610.
38. Jaques A.M., Amor D.J., Baker H.V. et al. Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies. Fertil Steril., 2014; 94 (7): 2674-9.
39. Zhang Y., Cui Y., Zhou Z. et al. Altered global gene expressions of human placentae subjected to assisted reproductive technology treatments. Placenta, 2010; 31: 4: 251-258.
40. Kallen B., Finnstrom O., Lindam A., Nilsson E. et al. Cancer risk in children and young adults conceived by in vitro fertilization. Pediatrics, 2010;126:270-276.
41. Källén B., Finnstrom O., Nygren K.G. et al. In vitro fertilization in Sweden: maternal characteristics. Acta Obstet Gynecol Scand., 2005; 84: 1185-1191.
42. Belva F., Henriet S., Van den Abbeel E., Camus M. et al. Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles. Human Reproduction, 2008; 23:2227-2238.
43. Knoester M., Helmerhorst F.M., van der Westerlaken L.A. et al. Artificial Reproductive Techniquesf Follow-up Project (L-artFUP). Matched follow-up study of 5-8-year-old ICSI singletons: child behaviour, parenting stress and child (health-related) quality of life. Hum Reprod., 2007; 22: 12: 3098-3107.
44. Koivurova S., Hartikainen A.L., Sovio U. et al. Growth, psychomotor development and morbidity up to 3 years of age in children born after IVF. Hum Reprod., 2003; 18: 2328-2336.
45. Makhoul I.R., Tamir A., Bader D. et al. In vitro fertilisation and use of ovulation enhancers may both influence childhood height in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed., 2009; 94: 5: 355-359.
46. Belva F., Roelants M., Painter R. et al. Pubertal development in ICSI children. Hum Reprod., 2012; 27: 4: 1156-1161.
47. Belva F., Bonduelle M., Painter R.C. Serum inhibin B concentrations in pubertal boys conceived by ICSI: first results. Hum. Reprod., 2010; 25 (11): 2811–2814.
48. Romundstad L.B., Romundstad P.R., Sunde A. Effects of technology or maternal factors on perinatal outcome after assisted fertilization: a population based cohort study. Lancet, 2008; 372: 737–743.
49. Kleshchenko E.I., Zhdanova I.A., Lukisha A.I. Sostoyanie zdorov’ya detey pri mnogoplodnoy beremennosti posle EKO. Materialy pervogo mezhdunarodnogo kongressa po perinatal’noy meditsine i VI ezhegodnogo kongressa RASPM [The health status of children with multiple pregnancy after IVF. Materials of the first international congress on perinatal medicine and the VI annual congress of RASPM]. Moscow, 2011. 94 p.
50. Beydoun H.A., Sicignano N., Beydoun M.A. et al. A crosssectional evaluation of the first cohort of young adults conceived by in vitro fertilization in the United States. Fertil Steril., 2010; 94: 6: 2043-2049.
51. Bonduelle M., Wennerholm U.B., Loft A. et al. A multi-centre cohort study of the physical health of 5-year-old children conceived after intracytoplasmic sperm injection, in vitro fertilization and natural conception. Hum Reprod., 2005; 20: 413-419.
52. Finnstrom O., Kallen B., Lindam A. Maternal and child outcome after in vitro fertilization – a review of 25 years population based data from Sweden. Acta Obstet. Gynecol. Scand., 2011; 90 (5): 494-500.
53. Ceelen M., van Weissenbruch M.M., Vermeiden J.P. et al. Cardiometabolic differences in children born after in vitro fertilization: follow-up study. J Clin Endocrinol Metab., 2008; 93: 5: 1682-1688.
54. Hart R., Norman R.J. The longer-term health outcomes for children born as a result of IVFtreatment. Part II-Mental health and development outcomes. Hum Reprod Update 2013, 19: 3: 244-250.
55. Strömberg B., Dahlquist G., Ericson A. Neurological sequelae in children born after in-vitro fertilisation: a population based study. Lancet, 2002; 359: 9305: 461-465.
56. Hvidtjørn D., Grove J., Schendel D.E. et al. Cerebral palsy among children born after in vitro fertilization: the role of preterm delivery-population-based, cohort study. Pediatrics, 2006; 118: 2: 475-482.
57. Kopylova I.V., Vityazeva I.I. Health and endocrine status of children born using assisted reproductive technologies. Problemy endokrinologii, 2012; 1: 54-60 (in Russ.).
58. Wagenaar K., van Weissenbruch M.M., van Leeuwen F.E. et al. Self-reported behavioral and socioemotional functioning of 11- to 18-year-old adolescents conceived by in vitro fertilization. Fertil Steril., 2011; 95: 2: 611-616.
59. Leunens L., Celestin-Westreich S., Bonduelle M. Follow-up of cognitive and motor development of 10-year-old singleton children born after ICSI compared with spontaneously conceived children. Hum Reprod., 2008; 23: 1: 105-111.
60. Middelburg K.J., Heineman M.J., Bos A.F. et al. Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI-a systematic review. Hum Reprod Update., 2008; 14: 3: 219-231.
61. Sazonova A., Kallen B., Thurin-Kjellberg A. Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos. Hum. Reprod., 2012; 27 (5): 1343-1350.
62. Wagenaar K., van Weissenbruch M.M., van Leeuwen F.E. et al. Behavior and socioemotional functioning in 9–18-year-old children born after in vitro fertilization. Fertil Steril., 2009; 92: 6: 1907-1914.
63. Xing L.F., Qu F. Qian Y.L. et al. The social adaptation of children born after ICSI compared with IVF-conceived children: a study from China. J Obstet Gynaecol., 2011; 31: 8: 751-753.
64. Hvidtjørn D., Grove J., Schendel D. et al. Risk of autism spectrum disorders in children born after assisted conception: a population-based follow-up study. J Epidemiol Community Health, 2011; 65: 6: 497-502.
65. Sandin S., Nygren K.G. Iliadou A. et al. Autism and mental retardation among offspring born after in vitro fertilization. JAMA, 2013; 310: 1: 75-84.
66. Lysenko I.M. et al. Fertile marriage and the health of children born as a result of assisted reproductive technologies. Vestnik Smolenskoy gosudarstvennoy meditsinskoy akademii, 2019, vol. 18, no. 3, pp. 211-216 (in Russ.).
67. Podzolkova N.M. Besplodie. Diagnostika, sovremennye metody lecheniya [Infertility. Diagnosis, modern treatment methods]. Moscow: GEOTAR-Media, 2019. 144 p.
68. Ismaylova M.K. The significance of preimplantation genetic diagnosis in the program of in vitro fertilization. Meditsinskiy vestnik Bashkortostana, 2018, vol. 13, no. 6, pp. 28-32 (in Russ.).