The associations between artificial reproductive technologies (ART) and newborn size, as well as perinatal risk factors among singleton births in Vienna, Austria.

Sylvia Kirchengast; Beda Hartmann

doi:10.52905/hbph2023.2.74

Authors

Sylvia Kirchengast Department of Evolutionary Anthropology, University of Vienna, Austria
Beda Hartmann Clinic Donaustadt, Department of Gynecology and Obstetrics, Vienna, Austria

DOI:

https://doi.org/10.52905/hbph2023.2.74

Keywords:

infertility, artificial reproductive technologies, preterm birth, newborn size, obstetric risk factors, cesarean section

Abstract

Background: The use of ssisted reproductive technologies (ART) such as fertilization (IVF) and intracytoplasmic sperm injection (ICSI) has increased markedly during the last four decades. ART, however, is still discussed critically, as there is no consensus on whether these treatments have a negative effect on fetal growth or increase the risk of preterm birth, low birth weight, and perinatal complications.

Objectives: The aim of this study is the analysis of association patterns between ART (IVF or ICSI) and newborn size, preterm birth rate, and the mode of delivery.

Sample and Methods: In this single-center medical record-based study data concerning the conception mode (spontaneous versus IVF or ICSI), preterm birth, newborn sex and size, child presentation, delivery mode, labor induction as well as parity, maternal age, body height, weight, and gestational weight gain of 5867 singleton-term births taking place in Vienna from 2015 to 2023 were included. 178 newborns (3.0%) were conceived by IVF or ICSI.

Results: ART (IVF or ICSI) increased the risk of preterm birth by a factor of 3.4, and the risk of emergency cesarean section by a factor 2.3. ART was not independently associated with newborn size as well as breech presentation. The most important factor for newborn size was the gestational week of delivery, but also maternal parameters such as body height, gestational weight gain, and age.

Conclusion: Preterm birth is a major cause of small newborn size and complications at birth. Therefore, ART can also be interpreted with caution as an indirect risk factor for small newborn size with all its long-term consequences.

References

Aboulghar, M./Aboulghar, M. (2021). Singleton birth weight and premature birth after in vitro fertilization: do we have evidence? Fertility and Sterility 116 (1), 64–65. https://doi.org/10.1016/j.fertnstert.2021.04.010.

Apgar, V. (1953). A proposal for a new method of evaluation of the newborn infant. Current Research Anesthesia & Analgesia 32, 260–267.

Bala, R./Singh, V./Rajender, S./Singh, K. (2021). Environment, lifestyle, and female infertility. Reproductive Sciences 28 (3), 617–638. https://doi.org/10.1007/s43032- 020-00279-3.

Bergholt, T./Skjeldestad, F. E./Pyykönen, A./Rasmussen, S. C./Tapper, A.-M./Bjarnadóttir, R. I./Smárason, A./Másdóttir, B. B./Klungsøyr, K./Albrechtsen, S./Käl- lén, K./Gissler, M./Løkkegaard, E. C. L. (2020). Maternal age and risk of cesarean section in women with induced labor at term-A Nordic register-based study. Acta obstetricia et gynecologica Scandinavica 99 (2), 283–289. https://doi.org/10.1111/aogs.13743.

Berntsen, S./Söderström-Anttila, V./Wennerholm, U.- B./Laivuori, H./Loft, A./Oldereid, N. B./Romundstad, L. B./Bergh, C./Pinborg, A. (2019). The health of children conceived by ART: ’the chicken or the egg?’. Human Reproduction Update 25 (2), 137–158. https://doi.org/10. 1093/humupd/dmz001.

Camarano, L./Alkon, A./Nachtigall, R. D./Schembri, M./Weiss, S./Croughan, M. S. (2012). Preterm delivery and low birth weight in singleton pregnancies conceived by women with and without a history of infertility. Fertility and Sterility 98 (3), 681–686.e1. https://doi.org/10. 1016/j.fertnstert.2012.04.033.

Cavoretto, P./Molina, F./Poggi, S./Davenport, M./Nico- laides, K. H. (2008). Prenatal diagnosis and outcome of echogenic fetal lung lesions. Ultrasound in Obstetrics & Gynecology : the official Journal of the International Society of Ultrasound in Obstetrics and Gynecology 32 (6), 769–783. https://doi.org/10.1002/uog.6218.

Chang, H.-Y./Hwu, W.-L./Chen, C.-H./Hou, C.-Y./Cheng, W. (2020). Children conceived by assisted reproductive technology prone to low birth weight, preterm birth, and birth defects: a cohort review of more than 50,000 live births during 2011–2017 in Taiwan. Frontiers in Pediatrics 8, 87. https://doi.org/10.3389/fped.2020.00087.

Chen, A. X./Hunt, R. W./Palmer, K. R./Bull, C. F./Callander, E. J. (2023). The impact of assisted reproductive technology and ovulation induction on breech presentation: a whole of populationbased cohort study. The Australian & New Zealand journal of Obstetrics & Gynaecology 63 (3), 434–440. https://doi.org/10.1111/ajo. 13663.

D’Angelo, D. V./Whitehead, N./Helms, K./Barfield, W./Ahluwalia, I. B. (2011). Birth outcomes of intended pregnancies among women who used assisted reproduc- tive technology, ovulation stimulation, or no treatment. Fertility and Sterility 96 (2), 314–320.e2. https://doi.org/ 10.1016/j.fertnstert.2011.05.073.

Dunbar, R. I. M. (1995). An interdisciplinary approach to human fertility. In: R. I. M. Dunbar (Ed.). Human reproductive decisions. London, Macmillan Education UK, 1–8.

Dunson, D. B./Colombo, B./Baird, D. D. (2002). Changes with age in the level and duration of fertility in the men- strual cycle. Human Reproduction 17 (5), 1399–1403. https://doi.org/10.1093/humrep/17.5.1399.

Fuchs, F./Monet, B./Ducruet, T./Chaillet, N./Audibert, F. (2018). Effect of maternal age on the risk of preterm birth: A large cohort study. PLOS ONE 13 (1), e0191002. https://doi.org/10.1371/journal.pone.0191002.

Gerrits, T./van Rooij, F./Esho, T./Ndegwa, W./Goossens, J./Bilajbegovic, A./Jansen, A./Kioko, B./Koppen, L./Ke- munto Migiro, S./Mwenda, S./Bos, H. (2017). Infertility in the Global South: raising awareness and generating insights for policy and practice. Facts, Views & Vision in ObGyn 9 (1), 39–44.

Graham, M. E./Jelin, A./Hoon, A. H./Wilms Floet, A. M./Levey, E./Graham, E. M. (2023). Assisted reproductive technology: short- and long-term outcomes. Devel- opmental Medicine and Child Neurology 65 (1), 38–49. https://doi.org/10.1111/dmcn.15332.

Hayashi, M./Nakai, A./Satoh, S./Matsuda, Y. (2012). Adverse obstetric and perinatal outcomes of singleton preg- nancies may be related to maternal factors associated with infertility rather than the type of assisted reproductive technology procedure used. Fertility and Sterility 98 (4), 922–928. https://doi.org/10.1016/j.fertnstert.2012.05. 049.

Helmerhorst, F. M./Perquin, D. A. M./Donker, D./Keirse, M. J. N. C. (2004). Perinatal outcome of singletons and twins after assisted conception: a systematic review

of controlled studies. BMJ (Clinical research ed.) 328 (7434), 261. https://doi.org/10.1136/bmj.37957.560278. EE.

Heo, J. S./Lee, H. J./Lee, M. H./Choi, C. W. (2019). Com- parison of neonatal outcomes of very low birth weight infants by mode of conception: in vitro fertilization versus natural pregnancy. Fertility and Sterility 111 (5), 962–970. https://doi.org/10.1016/j.fertnstert.2019.01.014.

Jackson, R. A./Gibson, K. A./Wu, Y. W./Croughan, M.S. (2004). Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstetrics and Gynecology 103 (3), 551–563. https://doi.org/10.1097/01. AOG.0000114989.84822.51.

Kalra, S. K./Molinaro, T. A. (2008). The association of in vitro fertilization and perinatal morbidity. Seminars in reproductive Medicine 26 (5), 423–435. https://doi.org/ 10.1055/s-0028-1087108.

Kirchengast, S./Hartmann, B. (2021). Pregnancy outcome during the first COVID 19 lockdown in Vienna, Austria. International Journal of environmental Research and public Health 18 (7). https://doi.org/10.3390/ ijerph18073782.

Kocourková, J./Šídlo, L./Šťastná, A./Fait, T. (2019). Vliv věku matky na porodní hmotnost novorozenců. Casopis lekaru ceskych 158 (3–4), 118–125.

Kondapalli, L. A./Perales-Puchalt, A. (2013). Low birth weight: is it related to assisted reproductive technology or underlying infertility? Fertility and Sterility 99 (2), 303–310. https://doi.org/10.1016/j.fertnstert.2012.12.035.

Koudstaal, J./Braat, D. D./Bruinse, H. W./Naaktgeboren, N./Vermeiden, J. P./Visser, G. H. (2000). Obstetric outcome of singleton pregnancies after IVF: a matched control study in four Dutch university hospitals. Human Reproduction 15 (8), 1819–1825. https://doi.org/10.1093/ humrep/15.8.1819.

Levine, H./Jørgensen, N./Martino-Andrade, A./Mendi- ola, J./Weksler-Derri, D./Mindlis, I./Pinotti, R./Swan, S. H. (2017). Temporal trends in sperm count: a systematic review and meta-regression analysis. Human Reproduction Update 23 (6), 646–659. https://doi.org/10. 1093/humupd/dmx022.

Lieberman, E./Ginsburg, E. S./Racowsky, C. (2006). Rate of cell division and weight of neonates following IVF. Reproductive Biomedicine online 12 (3), 315–321. https://doi.org/10.1016/s1472-6483(10)61003-6.

Lodge-Tulloch, N. A./Elias, F. T. S./Pudwell, J./Gaudet, L./Walker, M./Smith, G. N./Velez, M. P. (2021). Cae- sarean section in pregnancies conceived by assisted reproductive technology: a systematic review and meta- analysis. BMC Pregnancy and Childbirth 21 (1), 244. https://doi.org/10.1186/s12884-021-03711-x.

Malchau, S. S./Loft, A./Henningsen, A.-K. A./Nyboe Andersen, A./Pinborg, A. (2014). Perinatal outcomes in 6,338 singletons born after intrauterine insemination in Denmark, 2007 to 2012: the influence of ovarian stimulation. Fertility and Sterility 102 (4), 1110–1116.e2. https://doi.org/10.1016/j.fertnstert.2014.06.034.

Mascarenhas, M. N./Flaxman, S. R./Boerma, T./Vanderpoel, S./Stevens, G. A. (2012). National, regional, and global trends in infertility prevalence since 1990: a systematic analysis of 277 health surveys. PLoS Medicine

(12), e1001356. https://doi.org/10.1371/journal.pmed. 1001356.

McDonald, S. D./Han, Z./Mulla, S./Murphy, K. E./Beyene, J./Ohlsson, A. (2009). Preterm birth and low birth weight among in vitro fertilization singletons: a systematic review and meta-analyses. European Journal of Obstetrics, Gynecology, and reproductive Biology 146 (2), 138–148. https://doi.org/10.1016/j.ejogrb.2009. 05.035.

Mogos, M./Herghelegiu, C. G./Ioan, R. G./Ionescu, C. A./Neacsu, A. (2019). Determining an umbilical cord pH cutoff value for predicting neonatal morbidity related to intrapartum hypoxia. Revista de Chimie 70 (2), 605–607. https://doi.org/10.37358/RC.19.2.6965.

Noli, S. A./Baini, I./Parazzini, F./Mauri, P. A./Vignali, M./Gerli, S./Favilli, A./Cipriani, S. (2019). Preterm birth, low gestational age, low birth weight, parity, and other determinants of breech presentation: results from a large retrospective population-based study. BioMed Research international 2019, 9581439. https://doi.org/10. 1155/2019/9581439.

Pandey, S./Shetty, A./Hamilton, M./Bhattacharya, S./Ma- heshwari, A. (2012). Obstetric and perinatal outcomes in singleton pregnancies resulting from IVF/ICSI: a systematic review and meta-analysis. Human Reproduc- tion Update 18 (5), 485–503. https://doi.org/10.1093/ humupd/dms018.

Portal, A./Sunyach, C./Loundou, A./Lacroix-Paulmye, O./Perrin, J./Courbiere, B. (2021). Nomograms for predicting adverse obstetric outcome in IVF pregnancy: a preliminary study. Birth 48 (2), 186–193. https://doi.org/ 10.1111/birt.12528.

Prata, N. (2009). Making family planning accessible in resource-poor settings. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 364 (1532), 3093–3099. https://doi.org/10.1098/rstb.2009. 0172.

Romundstad, L. B./Romundstad, P. R./Sunde, A./Düring, V. von/Skjaerven, R./Gunnell, D./Vatten,

L. J. (2008). Effects of technology or maternal factors on perinatal outcome after assisted fertilisation: a population-based cohort study. The Lancet 372 (9640), 737–743. https://doi.org/10.1016/S0140-6736(08)61041-7.

Romundstad, L. B./Romundstad, P. R./Sunde, A./Düring, V. von/Skjaerven, R./Vatten, L. J. (2009). Assisted fertilization and breech delivery: risks and obstetric management. Human Reproduction 24 (12), 3205–3210. https://doi.org/10.1093/humrep/dep301.

Schieve, L. A./Cohen, B./Nannini, A./Ferre, C./Reynolds, M. A./Zhang, Z./Jeng, G./Macaluso, M./Wright, V. C. (2007). A population-based study of maternal and perinatal outcomes associated with assisted reproductive technology in Massachusetts. Mater- nal and Child Health Journal 11 (6), 517–525. https:// doi.org/10.1007/s10995-007-0202-7.

Slavov, S. S. (2020). Malpresentation of the fetus in singleton pregnancies after in vitro fertilization. Open Access Macedonian Journal of Medical Sciences 9 (B), 573–576. https://doi.org/10.3889/oamjms.2021.6450.

Stern, J. E./Luke, B./Tobias, M./Gopal, D./Hornstein, M. D./Diop, H. (2015). Adverse pregnancy and birth outcomes associated with underlying diagnosis with and without assisted reproductive technology treatment. Fertility and Sterility 103 (6), 1438–1445. https://doi.org/10.1016/j.fertnstert.2015.02.027.

Sullivan-Pyke, C. S./Senapati, S./Mainigi, M. A./Barn- hart, K. T. (2017). In vitro fertilization and adverse obstetric and perinatal outcomes. Seminars in Perinatology 41 (6), 345–353. https://doi.org/10.1053/j.semperi.2017. 07.001.

Sun, H./Gong, T.-T./Jiang, Y.-T./Zhang, S./Zhao, Y.- H./Wu, Q.-J. (2019). Global, regional, and national prevalence and disability-adjusted life-years for infertility in 195 countries and territories, 1990–2017: results from a global burden of disease study, 2017. Aging 11 (23), 10952–10991. https://doi.org/10.18632/aging.102497.

Sunkara, S. K./Antonisamy, B./Redla, A. C./Kamath, M. S. (2021). Female causes of infertility are associated with higher risk of preterm birth and low birth weight: analysis of 117 401 singleton live births following IVF. Human Reproduction 36 (3), 676–682. https://doi.org/10. 1093/humrep/deaa283.

The Lancet Global Health (2022). Infertility-why the silence? The Lancet Global Health 10 (6), e773. https:// doi.org/10.1016/S2214-109X(22)00215-7.

Tough, S. C./Greene, C. A./Svenson, L. W./Belik, J. (2000). Effects of in vitro fertilization on low birth weight, preterm delivery, and multiple birth. The Jour- nal of Pediatrics 136 (5), 618–622. https://doi.org/10. 1067/mpd.2000.105132.

Valenzuela-Alcaraz, B./Crispi, F./Manau, D./Cruz-Lem- ini, M./Borras, A./Balasch, J./Gratacós, E. (2016). Differential effect of mode of conception and infertility treatment on fetal growth and prematurity. The Journal of maternal-fetal & neonatal Medicine 29 (23), 3879–3884. https://doi.org/10.3109/14767058.2016.1151868.

Wang, Y. A./Sullivan, E. A./Black, D./Dean, J./Bryant, J./Chapman, M. (2005). Preterm birth and low birth weight after assisted reproductive technology-related pregnancy in Australia between 1996 and 2000. Fertility and Sterility 83 (6), 1650–1658. https://doi.org/10.1016/j. fertnstert.2004.12.033.

Wang, Y./Shi, H./Chen, L./Zheng, D./Long, X./Zhang, Y./Wang, H./Shi, Y./Zhao, Y./Wei, Y./Qiao, J. (2021). Absolute risk of adverse obstetric outcomes among twin pregnancies after in vitro fertilization by maternal age. JAMA Network open 4 (9), e2123634. https://doi.org/10. 1001/jamanetworkopen.2021.23634.

Wennerholm, U.-B./Bergh, C. (2020). Perinatal outcome in children born after assisted reproductive technologies. Upsala Journal of medical Sciences 125 (2), 158–166. https://doi.org/10.1080/03009734.2020.1726534.

WHO (2004). International statistical classification of diseases and related health problems. 10th ed. Geneva.

WHO (2023). Infertility prevalence estimates, 1990–2021. Available online at https://iris.who.int/ bitstream/handle/10665/366700/9789240068315-eng. pdf?sequence=1&isAllowed=y (accessed 10/10/2023).

Wyns, C./Geyter, C. de/Calhaz-Jorge, C./Kupka, M. S./Motrenko, T./Smeenk, J./Bergh, C./Tandler-Schneider, A./Rugescu, I. A./Goossens, V. (2022). ART in Europe, 2018: results generated from European registries by ESHRE. Human Reproduction open 2022 (3), hoac022. https://doi.org/10.1093/hropen/hoac022.

Yu, H./Liang, Z./Cai, R./Jin, S./Xia, T./Wang, C./Kuang, Y. (2022). Association of adverse birth outcomes with in vitro fertilization after controlling infertility factors based on a singleton live birth cohort. Scientific Reports 12 (1), 4528. https://doi.org/10.1038/s41598-022-08707-x.

Zádori, J./Kozinszky, Z./Orvos, H./Katona, M./Pál, A./Kovács, L. (2003). Dilemma of increased obstetric risk in pregnancies following IVF-ET. Journal of assisted Reproduction and Genetics 20 (6), 216–221. https://doi. org/10.1023/a:1024103427374.

Zheng, Z./Chen, L./Yang, T./Yu, H./Wang, H./Qin, J. (2018). Multiple pregnancies achieved with IVF/ICSI and risk of specific congenital malformations: a metaanalysis of cohort studies. Reproductive Biomedicine online 36 (4), 472–482. https://doi.org/10.1016/j.rbmo. 2018.01.009.

Zhu, L./Zhang, Y./Liu, Y./Zhang, R./Wu, Y./Huang, Y./Liu, F./Li, M./Sun, S./Xing, L./Zhu, Y./Chen, Y./Xu, L./Zhou, L./Huang, H./Zhang, D. (2016). Maternal and live-birth outcomes of pregnancies following assisted reproductive technology: a retrospective cohort study. Scientific Reports 6, 35141. https://doi.org/10.1038/ srep35141.