Hostname: page-component-7479d7b7d-k7p5g Total loading time: 0 Render date: 2024-07-11T07:22:39.688Z Has data issue: false hasContentIssue false

Assisted reproductive technology and long-term ophthalmic morbidity of the offspring

Published online by Cambridge University Press:  20 November 2020

Erez Tsumi*
Affiliation:
Department of Ophthalmology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva84101, Israel
Yotam Lavy
Affiliation:
Department of Ophthalmology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva84101, Israel
Eyal Sheiner
Affiliation:
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva84101, Israel
Chiya Barrett
Affiliation:
Department of Ophthalmology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva84101, Israel
Avi Harlev
Affiliation:
Fertility and IVF Unit, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva84101, Israel
Maayan Hagbi Bal
Affiliation:
Department of Ophthalmology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva84101, Israel
Tamar Wainstock
Affiliation:
Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva84101, Israel
*
Address for correspondence: Erez Tsumi, Department of Ophthalmology, Soroka University Medical Center, Ben-Gurion University, P.O.B. 151, Beer-Sheva84101, Israel. Email: ertsumi@post.bgu.ac.il

Abstract

In this study, we investigate if children born following assisted reproduction technologies (ARTs) are at an increased risk for long-term ophthalmic complications. For this purpose, a population-based cohort analysis was conducted which included all deliveries between 1991 and 2014 at a single tertiary medical center. Offspring were classified relative to conception method as ART or spontaneous pregnancies. Offspring hospitalizations up to the age of 18 years involving ophthalmic morbidities were evaluated according to a predefined set of ICD-9 codes. A Kaplan–Meier survival curve was used to compare cumulative hospitalization rates in exposed (ART) and unexposed offspring (spontaneous), and a Cox proportional hazards model was used to control for potential confounders. A total of 243,682 deliveries were included in the study. In that, 1.8% of the deliveries (4364) were of mothers who underwent fertility treatments and 98.2% (239,318) were conceived spontaneously. Offspring born to mothers who underwent fertility treatments had a significantly higher hospitalization rate involving ophthalmic morbidity, as compared to spontaneously conceived offspring (1.2% vs. 1.0%, p = 0.04). The Kaplan–Meier survival curve pointed to a significantly higher cumulative incidence of ophthalmic morbidity following ART (log rank p = 0.02). Cox proportional hazards model was adjusted for maternal age, preterm delivery, maternal hypertensive disorders, diabetes, and mode of delivery which demonstrated ART as an independent risk factor for long-term pediatric ophthalmic morbidity (adjusted hazard ratio = 1.37, CI 1.04–1.80, p-value = 0.02). We concluded that ART is an independent risk factor for long-term ophthalmic morbidity of the offspring.

Type
Original Article
Copyright
© The Author(s), 2020. Published by Cambridge University Press in association with International Society for Developmental Origins of Health and Disease

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

These two aforementioned authors have equally contributed to this article.

References

Centers for Disease Control and Prevention [CDC]. Div. Reprod. Heal. Natl. Cent. Chronic Dis. Prev. Heal. Promot. 2019. https://www.cdc.gov/reproductivehealth/Infertility/ (accessed April 1, 2020).Google Scholar
Zegers-Hochschild, F, Adamson, G.D, De Mouzon, J, et al. The International Committee for Monitoring Assisted Reproductive Technology (ICMART) and the World Health Organization (WHO) Revised Glossary on ART Terminology, 2009†. Hum Reprod. 2009; 24, 26832687.CrossRefGoogle Scholar
Jackson, RA, Gibson, KA, Wu, YW, Croughan, MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol. 2004; 103, 551563.CrossRefGoogle ScholarPubMed
Boivin, J, Bunting, L, Collins, JA, Nygren, KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007; 22, 15061512.CrossRefGoogle ScholarPubMed
Silberstein, T, Levy, A, Harlev, A, Saphier, O, Sheiner, E. Perinatal outcome of pregnancies following in vitro fertilization and ovulation induction. J Matern Neonatal Med. 2014; 27, 13161319.CrossRefGoogle ScholarPubMed
Gelbaya, TA. Short and long-term risks to women who conceive through in vitro fertilization. Hum Fertil. 2010; 13, 1927.CrossRefGoogle Scholar
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, 87104.CrossRefGoogle ScholarPubMed
Wainstock, T, Sheiner, E, Yoles, I, Sergienko, R, Landau, D, Harlev, A. Fertility treatments and offspring pediatric infectious morbidities: results of a population-based cohort with a median follow-up of 10 years. Fertil Steril. 2019; 112, 11291135.CrossRefGoogle ScholarPubMed
Krieger, Y, Wainstock, T, Sheiner, E, et al. Long-term pediatric skin eruption-related hospitalizations in offspring conceived via fertility treatment. Int J Dermatol. 2018; 57, 317323.CrossRefGoogle ScholarPubMed
Wainstock, T, Walfisch, A, Shoham-Vardi, I, et al. Fertility treatments and pediatric neoplasms of the offspring: results of a population-based cohort with a median follow-up of 10 years. Am J Obstet Gynecol. 2017; 216, 314.e1314.e14.Google Scholar
Shachor, N, Wainstock, T, Sheiner, E, Harlev, A. Fertility treatments and gastrointestinal morbidity of the offspring. Early Hum Dev. 2020; 144, 105021.CrossRefGoogle ScholarPubMed
Ratson, R, Sheiner, E, Davidson, E, Sergienko, R, Beharier, O, Kessous, R. Fertility treatments and the risk for ophthalmic complications: a cohort study with 25-year follow-up. J Matern Neonatal Med. 2016; 29, 30943097.CrossRefGoogle ScholarPubMed
Yuksel, E, Yalinbas, D, Aydin, B, Bilgihan, K. Keratoconus progression induced by in vitro fertilization treatment. J Refract Surg. 2016; 32, 6063.CrossRefGoogle ScholarPubMed
Russom, M, Pradeep, B, Zeregabr, M, Fessehatzion, K, Araya, N. Blindness and retinal disorder associated with clomifene citrate: cases series assessment. Clin Med Investig. 2017; 2..CrossRefGoogle Scholar
Tunc, M. Maculopathy following extended usage of Clomiphene citrate. Eye (Lond). 2014; 28, 11441146.CrossRefGoogle ScholarPubMed
Kedar Sade, E, Wainstock, T, Tsumi, E, Sheiner, E. Prenatal exposure to preeclampsia and long-term ophthalmic morbidity of the offspring. J Clin Med. 2020; 9, 1271.CrossRefGoogle ScholarPubMed
Gur, Z, Tsumi, E, Wainstock, T, Walter, E, Sheiner, E. Association between delivery of small-for-gestational age neonate and long-term pediatric ophthalmic morbidity. Arch Gynecol Obstet. 2018; 298, 10951099.CrossRefGoogle ScholarPubMed
Walter, E, Tsumi, E, Wainstock, T, Spiegel, E, Sheiner, E. Maternal gestational diabetes mellitus: is it associated with long-term pediatric ophthalmic morbidity of the offspring? J Matern Neonatal Med. 2019; 32, 25292538.CrossRefGoogle ScholarPubMed
Norwitz, ER, Edusa, V, Park, JS. Maternal physiology and complications of multiple pregnancy. Semin Perinatol. 2005; 29, 338348.CrossRefGoogle ScholarPubMed
Su, R-N, Zhu, W-W, Wei, Y-M, et al. Maternal and neonatal outcomes in multiple pregnancy: a multicentre study in the Beijing population. Chronic Dis Transl Med. 2015; 1, 197202.Google ScholarPubMed
Sutcliffe, AG, Ludwig, M. Outcome of assisted reproduction. Lancet. 2007; 370, 351359.CrossRefGoogle ScholarPubMed
Levin, S, Sheiner, E, Wainstock, T, et al. Infertility treatments and long-term neurologic morbidity of the offspring. Am J Perinatol. 2019; 36, 949954.Google ScholarPubMed
Scherrer, U, Rexhaj, E, Allemann, Y, Sartori, C, Rimoldi, SF. Cardiovascular dysfunction in children conceived by assisted reproductive technologies. Eur Heart J. 2015; 36, 15831589.CrossRefGoogle ScholarPubMed
Carson, C, Sacker, A, Kelly, Y, Redshaw, M, Kurinczuk, JJ, Quigley, MA. Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study. Hum Reprod. 2013; 28, 471479.CrossRefGoogle ScholarPubMed
Calkins, K, Devaskar, SU. Fetal origins of adult disease. Curr Probl Pediatr Adolesc Health Care. 2011; 41, 158176.CrossRefGoogle ScholarPubMed
Ferguson-Smith, AC, Bourc’his, D. The discovery and importance of genomic imprinting. eLife. 2018; 7, e42368.Google Scholar
Katari, S, Turan, N, Bibikova, M, et al. DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet. 2009; 18, 37693778.CrossRefGoogle ScholarPubMed
Zechner, U, Pliushch, G, Schneider, E, et al. Quantitative methylation analysis of developmentally important genes in human pregnancy losses after ART and spontaneous conception. Mol Hum Reprod. 2010; 16, 704713.Google Scholar
Borghol, N, Lornage, J, Blachère, T, Sophie Garret, A, Lefèvre, A. Epigenetic status of the H19 locus in human oocytes following in vitro maturation. Genomics. 2006; 87, 417426.CrossRefGoogle ScholarPubMed
Sato, A, Otsu, E, Negishi, H, Utsunomiya, T, Arima, T, Aberrant DNA methylation of imprinted loci in superovulated oocytes. Hum Reprod. 2007; 22, 2635.CrossRefGoogle ScholarPubMed
Raatikainen, K, Kuivasaari-Pirinen, P, Hippelainen, M, Heinonen, S. Comparison of the pregnancy outcomes of subfertile women after infertility treatment and in naturally conceived pregnancies. Hum Reprod. 2012; 27, 11621169.CrossRefGoogle ScholarPubMed
Batcheller, A, Cardozo, E, Maguire, M, DeCherney, AH, Segars, JH. Are there subtle genome-wide epigenetic alterations in normal offspring conceived by assisted reproductive technologies? Fertil Steril. 2011; 96, 13061311.CrossRefGoogle ScholarPubMed
Gao, L, Shao, W, Li, N, et al. The risk of retinopathy of prematurity in the infants following assisted reproductive technology: a meta-analysis. Biomed Res Int. 2019; 2019, 111.Google ScholarPubMed
Jafarzadehpur, E, Kermani, RM, Mohhamadi, AR, Nateghi, MR, Fazeli, AS, Kashi, KM. Ocular manifestations in infants resulted from Assisted Reproductive Technology (ART). J Fam Reprod Heal. 2013; 7, 181186.Google Scholar
Anteby, I, Cohen, E, Anteby, E, BenEzra, D. Ocular manifestations in children born after in vitro fertilization. Arch Ophthalmol. 2001; 119, 1525.CrossRefGoogle ScholarPubMed
Wikstrand, MH, Strömland, K, Flodin, S, Bergh, C, Wennerholm, U-B, Hellström, A. Ophthalmological findings in children born after intracytoplasmic sperm injection. Acta Ophthalmol Scand. 2005; 84, 177181.CrossRefGoogle Scholar