Is Intracytoplasmic Sperm Injection the Solution for all in Unexplained Infertility?

Abstract

Intracytoplasmic sperm injection (ICSI) was first introduced as a supplemental method to conventional in vitro fertilization (c-IVF) for couples with severe male factor infertility to overcome the poor fertilization rate, while its indications expanded in current clinical practice and gained worldwide popularity. However, ICSI is invasive and crosses all natural barriers, raising several unresolved concerns regarding procedure-dependent and procedure-independent risks, as well as the characteristic of being labor-intensive and more expensive than c-IVF. This review is aimed to draw readers' attention, to the widespread use of ICSI worldwide, with its effectiveness in different indications of infertility, especially in those with unexplained infertility, as well as the cost-effectiveness of the ICSI-for-all strategy. Also, we covered current evidence on the short- and long-term safety of children born thanks to ICSI-aided conception. Further well-designed, adequately powered, and randomized controlled clinical trials are absolutely needed to arrive at a consensus on the use of ICSI over c-IVF in different populations.

Keywords

intracytoplasmic sperm injection - unexplained infertility - assisted reproductive technology - conventional in vitro fertilization - infertility

^* These authors contributed equally to this article and are considered co-corresponding authors.

Publikationsverlauf

Artikel online veröffentlicht:
05. November 2020

• References

• 1 Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992; 340 (8810): 17-18
• 2 Hiramoto Y. Microinjection of the live spermatozoa into sea urchin eggs. Exp Cell Res 1962; 27: 416-426
• 3 Lanzendorf SE, Maloney MK, Veeck LL, Slusser J, Hodgen GD, Rosenwaks Z. A preclinical evaluation of pronuclear formation by microinjection of human spermatozoa into human oocytes. Fertil Steril 1988; 49 (05) 835-842
• 4 Ng SC, Bongso A, Ratnam SS. Microinjection of human oocytes: a technique for severe oligoasthenoteratozoospermia. Fertil Steril 1991; 56 (06) 1117-1123
• 5 Sathananthan AH, Ng SC, Trounson A, Bongso A, Laws-King A, Ratnam SS. Human micro-insemination by injection of single or multiple sperm: ultrastructure. Hum Reprod 1989; 4 (05) 574-583
• 6 Palermo GD, Cohen J, Rosenwaks Z. Intracytoplasmic sperm injection: a powerful tool to overcome fertilization failure. Fertil Steril 1996; 65 (05) 899-908
• 7 Ng SC, Bongso A, Sathananthan H, Ratnam SS. Micromanipulation: its relevance to human in vitro fertilization. Fertil Steril 1990; 53 (02) 203-219
• 8 Tournaye H, Devroey P, Liu J, Nagy Z, Lissens W, Van Steirteghem A. Microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection: a new effective approach to infertility as a result of congenital bilateral absence of the vas deferens. Fertil Steril 1994; 61 (06) 1045-1051
• 9 Devroey P, Liu J, Nagy Z, Tournaye H, Silber SJ, Van Steirteghem AC. Normal fertilization of human oocytes after testicular sperm extraction and intracytoplasmic sperm injection. Fertil Steril 1994; 62 (03) 639-641
• 10 Devroey P, Liu J, Nagy Z. et al. Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia. Hum Reprod 1995; 10 (06) 1457-1460
• 11 Boulet SL, Mehta A, Kissin DM, Warner L, Kawwass JF, Jamieson DJ. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA 2015; 313 (03) 255-263
• 12 European Society of Human Reproduction and Embryology. More than 8 million babies born from IVF since the world's first in 1978. ScienceDaily. Available at: https://www.sciencedaily.com/releases/2018/07/180703084127.htm. Accessed October 21, 2020
• 13 de Mouzon J, Chambers GM, Zegers-Hochschild F. et al. International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology 2012. Hum Reprod 2020; 35 (08) 1900-1913
• 14 De Geyter C, Calhaz-Jorge C, Kupka MS. et al. European IVF-monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE). ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod Open 2020; 2020 (01) hoz038
• 15 Zagadailov P, Hsu A, Seifer DB, Stern JE. Differences in utilization of Intracytoplasmic sperm injection (ICSI) within human services (HHS) regions and metropolitan megaregions in the U.S. Reprod Biol Endocrinol 2017; 15 (01) 45
• 16 Fitzgerald O, Paul RC, Harris K, Chambers GM. Assisted reproductive technology in Australia and New Zealand 2016. The Fertility Society of Australia 2018. Available at: https://npesu.unsw.edu.au/sites/default/files/npesu/surveillances/Assisted%20Reproductive%20Technology%20in%20Australia%20and%20New%20Zealand%202016.pdf. Accessed October 19, 2020
• 17 Harris K, Fitzgerald O, Paul RC, Macaldowie A, Lee E, Chambers GM. Assisted reproductive technology in Australia and New Zealand 2014. The Fertility Society of Australia 2016. Available at: https://npesu.unsw.edu.au/sites/default/files/npesu/surveillances/Assisted%20Reproductive%20Technology%20in%20Australia%20and%20New%20Zealand%202016.pdf. Accessed on October 19, 2020
• 18 Wang YA, Chambers GM, Dieng M, Sullivan EA. Assisted reproductive technology in Australia and New Zealand 2007. The Fertility Society of Australia; 2009. Available at: https://www.aihw.gov.au/getmedia/8bd3c9bc-96ff-44dc-a8c6-baf22407273e/per-47-10753.pdf.aspx?inline=true. Accessed on October 19, 2020
• 19 Bai F, Wang DY, Fan YJ. et al. Assisted reproductive technology service availability, efficacy and safety in mainland China: 2016. Hum Reprod 2020; 35 (02) 446-452
• 20 Practice Committees of the American Society for Reproductive Medicine and Society for Assisted Reproductive Technology. Intracytoplasmic sperm injection (ICSI) for non-male factor infertility: a committee opinion. Fertil Steril 2012; 98 (06) 1395-1399
• 21 Evers JL. Santa Claus in the fertility clinic. Hum Reprod 2016; 31 (07) 1381-1382
• 22 van der Westerlaken L, Helmerhorst F, Dieben S, Naaktgeboren N. Intracytoplasmic sperm injection as a treatment for unexplained total fertilization failure or low fertilization after conventional in vitro fertilization. Fertil Steril 2005; 83 (03) 612-617
• 23 Roest J, Van Heusden AM, Zeilmaker GH, Verhoeff A. Treatment policy after poor fertilization in the first IVF cycle. J Assist Reprod Genet 1998; 15 (01) 18-21
• 24 Ruiz A, Remohí J, Minguez Y, Guanes PP, Simón C, Pellicer A. The role of in vitro fertilization and intracytoplasmic sperm injection in couples with unexplained infertility after failed intrauterine insemination. Fertil Steril 1997; 68 (01) 171-173
• 25 Hwang JL, Seow KM, Lin YH. et al. IVF versus ICSI in sibling oocytes from patients with polycystic ovarian syndrome: a randomized controlled trial. Hum Reprod 2005; 20 (05) 1261-1265
• 26 Johnson LN, Sasson IE, Sammel MD, Dokras A. Does intracytoplasmic sperm injection improve the fertilization rate and decrease the total fertilization failure rate in couples with well-defined unexplained infertility? A systematic review and meta-analysis. Fertil Steril 2013; 100 (03) 704-711
• 27 Check JH, Yuan W, Garberi-Levito MC, Swenson K, McMonagle K. Effect of method of oocyte fertilization on fertilization, pregnancy and implantation rates in women with unexplained infertility. Clin Exp Obstet Gynecol 2011; 38 (03) 203-205
• 28 Moreno C, Ruiz A, Simón C, Pellicer A, Remohí J. Intracytoplasmic sperm injection as a routine indication in low responder patients. Hum Reprod 1998; 13 (08) 2126-2129
• 29 Fishel S, Aslam I, Lisi F. et al. Should ICSI be the treatment of choice for all cases of in-vitro conception?. Hum Reprod 2000; 15 (06) 1278-1283
• 30 Harton GL, Magli MC, Lundin K, Montag M, Lemmen J, Harper JC. European Society for Human Reproduction and Embryology (ESHRE) PGD Consortium/Embryology Special Interest Group. ESHRE PGD Consortium/Embryology Special Interest Group--best practice guidelines for polar body and embryo biopsy for preimplantation genetic diagnosis/screening (PGD/PGS). Hum Reprod 2011; 26 (01) 41-46
• 31 Ho VNA, Braam SC, Pham TD, Mol BW, Vuong LN. The effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilization in women with a high antral follicle count. Hum Reprod 2019; 34 (06) 1055-1064
• 32 Vuong LN, Ho VNA, Ho TM. et al. Effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilisation in women with high antral follicle count: study protocol for a randomised controlled trial. BMJ Open 2018; 8 (12) e023413
• 33 Dieke AC, Mehta A, Kissin DM, Nangia AK, Warner L, Boulet SL. Intracytoplasmic sperm injection use in states with and without insurance coverage mandates for infertility treatment, United States, 2000-2015. Fertil Steril 2018; 109 (04) 691-697
• 34 Bhattacharya S, Hamilton MP, Shaaban M. et al. Conventional in-vitro fertilisation versus intracytoplasmic sperm injection for the treatment of non-male-factor infertility: a randomised controlled trial. Lancet 2001; 357 (9274): 2075-2079
• 35 Li Z, Wang AY, Bowman M. et al. ICSI does not increase the cumulative live birth rate in non-male factor infertility. Hum Reprod 2018; 33 (07) 1322-1330
• 36 Drakopoulos P, Garcia-Velasco J, Bosch E. et al. ICSI does not offer any benefit over conventional IVF across different ovarian response categories in non-male factor infertility: a European multicenter analysis. J Assist Reprod Genet 2019; 36 (10) 2067-2076
• 37 De Munck N, El Khatib I, Abdala A. et al. Intracytoplasmic sperm injection is not superior to conventional IVF in couples with non-male factor infertility and preimplantation genetic testing for aneuploidies (PGT-A). Hum Reprod 2020; 35 (02) 317-327
• 38 Kim JY, Kim JH, Jee BC, Lee JR, Suh CS, Kim SH. Can intracytoplasmic sperm injection prevent total fertilization failure and enhance embryo quality in patients with non-male factor infertility?. Eur J Obstet Gynecol Reprod Biol 2014; 178: 188-191
• 39 ESHRE 2020 abstract book. Available at: https://www.eshre.eu/ESHRE2020. Accessed October 11, 2020
• 40 Dang VQ, Vuong LN, Ho TM. et al. The effectiveness of ICSI versus conventional IVF in couples with non-male factor infertility: study protocol for a randomised controlled trial. Hum Reprod Open 2019; 2019 (02) hoz006
• 41 Kodama H, Fukuda J, Karube H, Matsui T, Shimizu Y, Tanaka T. High incidence of embryo transfer cancellations in patients with polycystic ovarian syndrome. Hum Reprod 1995; 10 (08) 1962-1967
• 42 Sengoku K, Tamate K, Takuma N, Yoshida T, Goishi K, Ishikawa M. The chromosomal normality of unfertilized oocytes from patients with polycystic ovarian syndrome. Hum Reprod 1997; 12 (03) 474-477
• 43 Doldi N, Marsiglio E, Destefani A, Gessi A, Merati G, Ferrari A. Elevated serum progesterone on the day of HCG administration in IVF is associated with a higher pregnancy rate in polycystic ovary syndrome. Hum Reprod 1999; 14 (03) 601-605
• 44 Grimstad FW, Nangia AK, Luke B, Stern JE, Mak W. Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates. Hum Reprod 2016; 31 (12) 2750-2755
• 45 Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A. Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril 2008; 90 (02) 247-257
• 46 Komsky-Elbaz A, Raziel A, Friedler S. et al. Conventional IVF versus ICSI in sibling oocytes from couples with endometriosis and normozoospermic semen. J Assist Reprod Genet 2013; 30 (02) 251-257
• 47 Gleicher N, Barad D. “Ovarian age-based” stimulation of young women with diminished ovarian reserve results in excellent pregnancy rates with in vitro fertilization. Fertil Steril 2006; 86 (06) 1621-1625
• 48 Abdalla H, Thum MY. An elevated basal FSH reflects a quantitative rather than qualitative decline of the ovarian reserve. Hum Reprod 2004; 19 (04) 893-898
• 49 Fang C, Tang J, Huang R, Li LL, Zhang MF, Liang XY. Comparison of IVF outcomes using conventional insemination and ICSI in ovarian cycles in which only one or two oocytes are obtained. J Gynecol Obstet Biol Reprod (Paris) 2012; 41 (07) 650-656
• 50 Mills M, Rindfuss RR, McDonald P, te Velde E. ESHRE Reproduction and Society Task Force. Why do people postpone parenthood? Reasons and social policy incentives. Hum Reprod Update 2011; 17 (06) 848-860
• 51 Tannus S, Son WY, Gilman A, Younes G, Shavit T, Dahan MH. The role of intracytoplasmic sperm injection in non-male factor infertility in advanced maternal age. Hum Reprod 2017; 32 (01) 119-124
• 52 Farhi J, Cohen K, Mizrachi Y, Weissman A, Raziel A, Orvieto R. Should ICSI be implemented during IVF to all advanced-age patients with non-male factor subfertility?. Reprod Biol Endocrinol 2019; 17 (01) 30
• 53 Sunderam S, Boulet SL, Kawwass JF, Kissin DM. Comparing fertilization rates from intracytoplasmic sperm injection to conventional in vitro fertilization among women of advanced age with non-male factor infertility: a meta-analysis. Fertil Steril 2020; 113 (02) 354-363 .e1, e1
• 54 van der Westerlaken L, Naaktgeboren N, Verburg H, Dieben S, Helmerhorst FM. Conventional in vitro fertilization versus intracytoplasmic sperm injection in patients with borderline semen: a randomized study using sibling oocytes. Fertil Steril 2006; 85 (02) 395-400
• 55 Hamberger L, Sjögren A, Lundin K. et al. Microfertilization techniques--the Swedish experience. Reprod Fertil Dev 1995; 7 (02) 263-267 , discussion 268
• 56 Hershlag A, Paine T, Kvapil G, Feng H, Napolitano B. In vitro fertilization-intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure. Fertil Steril 2002; 77 (02) 229-232
• 57 Xie BG, Huang YH, Zhu WJ, Jin S. Comparison of the outcome of conventional in vitro fertilization and intracytoplasmic sperm injection in moderate male infertility from ejaculate. Urol Int 2015; 94 (01) 111-116
• 58 Payne D, Matthews CD. Intracytoplasmic sperm injection--clinical results from the reproductive medicine unit, Adelaide. Reprod Fertil Dev 1995; 7 (02) 219-227
• 59 Oehninger S, Veeck L, Lanzendorf S, Maloney M, Toner J, Muasher S. Intracytoplasmic sperm injection: achievement of high pregnancy rates in couples with severe male factor infertility is dependent primarily upon female and not male factors. Fertil Steril 1995; 64 (05) 977-981
• 60 Silber SJ, Nagy ZP, Liu J, Godoy H, Devroey P, Van Steirteghem AC. Conventional in-vitro fertilization versus intracytoplasmic sperm injection for patients requiring microsurgical sperm aspiration. Hum Reprod 1994; 9 (09) 1705-1709
• 61 Tournaye H. Male factor infertility and ART. Asian J Androl 2012; 14 (01) 103-108
• 62 Cissen M, Bensdorp A, Cohlen BJ, Repping S, de Bruin JP, van Wely M. Assisted reproductive technologies for male subfertility. Cochrane Database Syst Rev 2016; 2: CD000360
• 63 Zheng JF, Chen XB, Zhao LW. et al. ICSI treatment of severe male infertility can achieve prospective embryo quality compared with IVF of fertile donor sperm on sibling oocytes. Asian J Androl 2015; 17 (05) 845-849
• 64 Pisarska MD, Casson PR, Cisneros PL. et al. Fertilization after standard in vitro fertilization versus intracytoplasmic sperm injection in subfertile males using sibling oocytes. Fertil Steril 1999; 71 (04) 627-632
• 65 Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril 1988; 49 (01) 112-117
• 66 Menkveld R, Stander FS, Kotze TJ, Kruger TF, van Zyl JA. The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Hum Reprod 1990; 5 (05) 586-592
• 67 Fan W, Li SW, Li L. et al. Outcome of conventional IVF and ICSI on sibling oocytes in the case of isolated teratozoospermia. J Assist Reprod Genet 2012; 29 (09) 905-910
• 68 World Health Organization. Laboratory Manual for the Examination of Human Semen and Semen–Cervical Mucus Interaction. 3rd ed.. 1993
• 69 Tournaye H, Verheyen G, Albano C. et al. Intracytoplasmic sperm injection versus in vitro fertilization: a randomized controlled trial and a meta-analysis of the literature. Fertil Steril 2002; 78 (05) 1030-1037
• 70 Plachot M, Belaisch-Allart J, Mayenga JM, Chouraqui A, Tesquier L, Serkine AM. Outcome of conventional IVF and ICSI on sibling oocytes in mild male factor infertility. Hum Reprod 2002; 17 (02) 362-369
• 71 Elizur SE, Levron J, Seidman DS, Kees S, Levran D, Dor J. Conventional in vitro fertilization versus intracytoplasmic sperm injection for sibling oocytes in couples with mild oligoteratoasthenozoospermia and couples with normal sperm. Fertil Steril 2004; 82 (01) 241-243
• 72 Shuai HL, Ye Q, Huang YH, Xie BG. Comparison of conventional in vitro fertilisation and intracytoplasmic sperm injection outcomes in patients with moderate oligoasthenozoospermia. Andrologia 2015; 47 (05) 499-504
• 73 Xie BG, Zhu WJ, Huang YH. Outcome of conventional IVF and ICSI on sibling oocytes in moderate ligoasthenozoospermia. Pak J Med Sci 2013; 29 (05) 1221-1224
• 74 Kastrop PM, Weima SM, Van Kooij RJ, Te Velde ER. Comparison between intracytoplasmic sperm injection and in-vitro fertilization (IVF) with high insemination concentration after total fertilization failure in a previous IVF attempt. Hum Reprod 1999; 14 (01) 65-69
• 75 Zheng D, Zeng L, Yang R. et al. Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilisation (IVF) in couples with non-severe male infertility (NSMI-ICSI): protocol for a multicentre randomised controlled trial. BMJ Open 2019; 9 (09) e030366
• 76 Ray A, Shah A, Gudi A, Homburg R. Unexplained infertility: an update and review of practice. Reprod Biomed Online 2012; 24 (06) 591-602
• 77 Smith S, Pfeifer SM, Collins JA. Diagnosis and management of female infertility. JAMA 2003; 290 (13) 1767-1770
• 78 Bungum L, Bungum M, Humaidan P, Andersen CY. A strategy for treatment of couples with unexplained infertility who failed to conceive after intrauterine insemination. Reprod Biomed Online 2004; 8 (05) 584-589
• 79 Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohí J, Simón C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 1998; 70 (03) 425-431
• 80 Guzick DS, Sullivan MW, Adamson GD. et al. Efficacy of treatment for unexplained infertility. Fertil Steril 1998; 70 (02) 207-213
• 81 Reindollar RH, Regan MM, Neumann PJ. et al. A randomized clinical trial to evaluate optimal treatment for unexplained infertility: the fast track and standard treatment (FASTT) trial. Fertil Steril 2010; 94 (03) 888-899
• 82 Eijkemans MJ, Lintsen AM, Hunault CC. et al. Pregnancy chances on an IVF/ICSI waiting list: a national prospective cohort study. Hum Reprod 2008; 23 (07) 1627-1632
• 83 Stewart JD, Pasternak MC, Pereira N, Rosenwaks Z. Contemporary management of unexplained infertility. Clin Obstet Gynecol 2019; 62 (02) 282-292
• 84 Gunn DD, Bates GW. Evidence-based approach to unexplained infertility: a systematic review. Fertil Steril 2016; 105 (06) 1566-1574 .e1, e1
• 85 McClamrock HD, Jones Jr HW, Adashi EY. Ovarian stimulation and intrauterine insemination at the quarter centennial: implications for the multiple births epidemic. Fertil Steril 2012; 97 (04) 802-809
• 86 Gürgan T, Urman B, Yarali H, Kişnişçi HA. The results of in vitro fertilization-embryo transfer in couples with unexplained infertility failing to conceive with superovulation and intrauterine insemination. Fertil Steril 1995; 64 (01) 93-97
• 87 Aboulghar MA, Mansour RT, Serour GI, Sattar MA, Amin YM. Intracytoplasmic sperm injection and conventional in vitro fertilization for sibling oocytes in cases of unexplained infertility and borderline semen. J Assist Reprod Genet 1996; 13 (01) 38-42
• 88 Takeuchi S, Minoura H, Shibahara T, Shen X, Futamura N, Toyoda N. In vitro fertilization and intracytoplasmic sperm injection for couples with unexplained infertility after failed direct intraperitoneal insemination. J Assist Reprod Genet 2000; 17 (09) 515-520
• 89 Foong SC, Fleetham JA, O'Keane JA, Scott SG, Tough SC, Greene CA. A prospective randomized trial of conventional in vitro fertilization versus intracytoplasmic sperm injection in unexplained infertility. J Assist Reprod Genet 2006; 23 (03) 137-140
• 90 Buckett W, Sierra S. The management of unexplained infertility: an evidence-based guideline from the Canadian Fertility and Andrology Society. Reprod Biomed Online 2019; 39 (04) 633-640
• 91 Bonduelle M, Van Assche E, Joris H. et al. Prenatal testing in ICSI pregnancies: incidence of chromosomal anomalies in 1586 karyotypes and relation to sperm parameters. Hum Reprod 2002; 17 (10) 2600-2614
• 92 Wisborg K, Ingerslev HJ, Henriksen TB. In vitro fertilization and preterm delivery, low birth weight, and admission to the neonatal intensive care unit: a prospective follow-up study. Fertil Steril 2010; 94 (06) 2102-2106
• 93 Bonduelle M, Bergh C, Niklasson A, Palermo GD, Wennerholm UB. Collaborative Study Group of Brussels, Gothenburg and New York. Medical follow-up study of 5-year-old ICSI children. Reprod Biomed Online 2004; 9 (01) 91-101
• 94 Lazaraviciute G, Kauser M, Bhattacharya S, Haggarty P, Bhattacharya S. A systematic review and meta-analysis of DNA methylation levels and imprinting disorders in children conceived by IVF/ICSI compared with children conceived spontaneously. Hum Reprod Update 2014; 20 (06) 840-852
• 95 Berntsen S, Söderström-Anttila V, Wennerholm UB. et al. The health of children conceived by ART: ‘the chicken or the egg?’. Hum Reprod Update 2019; 25 (02) 137-158
• 96 Pinborg A, Wennerholm UB, Romundstad LB. et al. Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis. Hum Reprod Update 2013; 19 (02) 87-104
• 97 Esteves SC, Roque M, Bedoschi G, Haahr T, Humaidan P. Intracytoplasmic sperm injection for male infertility and consequences for offspring. Nat Rev Urol 2018; 15 (09) 535-562
• 98 Sfontouris IA, Nastri CO, Lima ML, Tahmasbpourmarzouni E, Raine-Fenning N, Martins WP. Artificial oocyte activation to improve reproductive outcomes in women with previous fertilization failure: a systematic review and meta-analysis of RCTs. Hum Reprod 2015; 30 (08) 1831-1841
• 99 Wen J, Jiang J, Ding C. et al. Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril 2012; 97 (06) 1331-7.e1 , 4
• 100 Davies MJ, Moore VM, Willson KJ. et al. Reproductive technologies and the risk of birth defects. N Engl J Med 2012; 366 (19) 1803-1813
• 101 Bay B, Lyngsø J, Hohwü L, Kesmodel US. Childhood growth of singletons conceived following in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta-analysis. BJOG 2019; 126 (02) 158-166
• 102 Belva F, Bonduelle M, Roelants M. et al. Semen quality of young adult ICSI offspring: the first results. Hum Reprod 2016; 31 (12) 2811-2820
• 103 Belva F, Roelants M, De Schepper J, Van Steirteghem A, Tournaye H, Bonduelle M. Reproductive hormones of ICSI-conceived young adult men: the first results. Hum Reprod 2017; 32 (02) 439-446
• 104 Belva F, Roelants M, Vloeberghs V. et al. Serum reproductive hormone levels and ultrasound findings in female offspring after intracytoplasmic sperm injection: first results. Fertil Steril 2017; 107 (04) 934-939
• 105 Sonntag B, Eisemann N, Elsner S. et al. Pubertal development and reproductive hormone levels of singleton ICSI offspring in adolescence: results of a prospective controlled study. Hum Reprod 2020; 35 (04) 968-976
• 106 Balayla J, Sheehy O, Fraser WD. et al. Neurodevelopmental outcomes after assisted reproductive technologies. Obstet Gynecol 2017; 129 (02) 265-272
• 107 Bay B, Mortensen EL, Kesmodel US. Assisted reproduction and child neurodevelopmental outcomes: a systematic review. Fertil Steril 2013; 100 (03) 844-853
• 108 Spangmose AL, Malchau SS, Schmidt L. et al. Academic performance in adolescents born after ART-a nationwide registry-based cohort study. Hum Reprod 2017; 32 (02) 447-456
• 109 Norrman E, Petzold M, Bergh C, Wennerholm UB. School performance in children born after ICSI. Hum Reprod 2020; 35 (02) 340-354
• 110 Spaan M, van den Belt-Dusebout AW, van den Heuvel-Eibrink MM. OMEGA-Steering Group. Risk of cancer in children and young adults conceived by assisted reproductive technology. Hum Reprod 2019; 34 (04) 740-750
• 111 Kissin DM, Zhang Y, Boulet SL. et al. Association of assisted reproductive technology (ART) treatment and parental infertility diagnosis with autism in ART-conceived children. Hum Reprod 2015; 30 (02) 454-465
• 112 Rumbold AR, Sevoyan A, Oswald TK, Fernandez RC, Davies MJ, Moore VM. Impact of male factor infertility on offspring health and development. Fertil Steril 2019; 111 (06) 1047-1053
• 113 Chen E. Why socioeconomic status affects the health of children - a psychosocial perspective. Curr Dir Psychol Sci 2004; 13 (03) 112-115
• 114 Hollingsworth B, Harris A, Mortimer D. The cost effectiveness of intracytoplasmic sperm injection (ICSI). J Assist Reprod Genet 2007; 24 (12) 571-577
• 115 Moolenaar LM, Cissen M, de Bruin JP. et al. Cost-effectiveness of assisted conception for male subfertility. Reprod Biomed Online 2015; 30 (06) 659-666
• 116 Vitek WS, Galárraga O, Klatsky PC, Robins JC, Carson SA, Blazar AS. Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection. Fertil Steril 2013; 100 (05) 1381-1388