In Vitro Fertilization and Adverse Pregnancy Outcomes in the Elective Single Embryo Transfer Era

Abstract

Objective Our objective was to estimate the association between in vitro fertilization (IVF) pregnancy and adverse pregnancy outcomes during delivery hospital admission in a contemporary, nation-wide cohort of births in the United States.

Study Design This retrospective, population-based cohort study used the National Inpatient Sample database to identify patients discharged from the hospital following delivery from 2014 to 2019. IVF pregnancies were identified using the International Classification of Disease-Revision 9/10 codes. Crude and adjusted odds ratios of preterm birth and other clinically significant adverse pregnancy outcomes were evaluated using multivariable logistic regression models. Trends in preterm birth and multiple pregnancy were estimated over the study period. The contribution of multiple pregnancy to preterm birth in IVF pregnancy was estimated in a mediation analysis.

Results Among 4,451,667 delivery-related discharges, IVF pregnancies were associated with 3.25 times the odds of preterm birth (95% confidence interval [CI]: 3.05–3.46, p < 0.001) compared with non-IVF pregnancy deliveries. Odds of preterm birth in IVF pregnancy delivery discharges decreased over the study period (p-value for linear trend = 0.009). The proportion of multiple pregnancies decreased in IVF pregnancy delivery discharges but remained stable in non-IVF pregnancy deliveries. The proportion of the adjusted effect of IVF pregnancy on preterm birth mediated through multiple pregnancy was 67.6% (95% CI: 62.6–72.7%).

Conclusion While the odds of adverse pregnancy outcomes are increased compared with non-IVF pregnancies, the odds of preterm birth and multiple gestation have decreased among IVF pregnancies in the United States.

Key Points

• Pregnancies conceived by in vitro fertilization (IVF) are at significantly higher risk of multiple gestation, preterm birth, and other pregnancy complications.

• Recent guidelines for artificial reproductive treatments recommend single-embryo transfer in IVF.

• Using population-wide data, we demonstrate a significant gradual decline in the rates of preterm birth and other pregnancy complications following IVF in the last decade, mostly mediated by a reduction in multiple pregnancies.

Keywords

in vitro fertilization - preterm birth - multiple pregnancy - adverse pregnancy outcomes - single embryo transfer

Ethics Approval

This study received Research Ethics Board approval from REB (no.: 20210738-01H), the Committee (no.: 31360), and a determination of Not Human Subjects Research from the IRB.

Publikationsverlauf

Eingereicht: 06. Juli 2022

Angenommen: 07. November 2022

Accepted Manuscript online:
16. November 2022

Artikel online veröffentlicht:
26. Dezember 2022

• References

• 1 Shevell T, Malone FD, Vidaver J. et al. Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 2005; 106 (5, pt. 1): 1039-1045
• 2 Reddy UM, Wapner RJ, Rebar RW, Tasca RJ. Infertility, assisted reproductive technology, and adverse pregnancy outcomes: executive summary of a National Institute of Child Health and Human Development workshop. Obstet Gynecol 2007; 109 (04) 967-977
• 3 Frey HA, Klebanoff MA. The epidemiology, etiology, and costs of preterm birth. Semin Fetal Neonatal Med 2016; 21 (02) 68-73
• 4 Waitzman NJ, Jalali A, Grosse SD. Preterm birth lifetime costs in the United States in 2016: an update. Semin Perinatol 2021; 45 (03) 151390
• 5 Roque M, Lattes K, Serra S. et al. Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis. Fertil Steril 2013; 99 (01) 156-162
• 6 Evans J, Hannan NJ, Edgell TA. et al. Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence. Hum Reprod Update 2014; 20 (06) 808-821
• 7 Harbottle S, Hughes C, Cutting R, Roberts S, Brison D. Association Of Clinical Embryologists & The (ACE) British Fertility Society (BFS). Elective single embryo transfer: an update to UK Best Practice Guidelines. Hum Fertil (Camb) 2015; 18 (03) 165-183
• 8 Mancuso AC, Boulet SL, Duran E, Munch E, Kissin DM, Van Voorhis BJ. Elective single embryo transfer in women less than age 38 years reduces multiple birth rates, but not live birth rates, in United States fertility clinics. Fertil Steril 2016; 106 (05) 1107-1114
• 9 Stillman RJ, Richter KS, Jones Jr HW. Refuting a misguided campaign against the goal of single-embryo transfer and singleton birth in assisted reproduction. Hum Reprod 2013; 28 (10) 2599-2607
• 10 Practice Committee of the American Society for Reproductive Medicine., Practice Committee of the Society for Assisted Reproductive Technology. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril 2017; 107 (04) 901-903
• 11 Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Criteria for number of embryos to transfer: a committee opinion. Fertil Steril 2013; 99 (01) 44-46
• 12 Meczekalski B, Szeliga A, Podfigurna A, Miechowicz I, Adashi EY. Assisted reproductive technology outcome in United States of America and Australia with New Zealand: comparison of annual reports 2005-2016. Gynecol Endocrinol 2020; 36 (11) 959-967
• 13 Sabban H, Zakhari A, Patenaude V, Tulandi T, Abenhaim HA. Obstetrical and perinatal morbidity and mortality among in-vitro fertilization pregnancies: a population-based study. Arch Gynecol Obstet 2017; 296 (01) 107-113
• 14 Healthcare Cost and Utilization Project. NIS database documentation. 2021 Accessed January 9, 2022 at: https://www.hcup-us.ahrq.gov/db/nation/nis/nisdbdocumentation.jsp
• 15 Khera R, Angraal S, Couch T. et al. Adherence to methodological standards in research using the National Inpatient Sample. JAMA 2017; 318 (20) 2011-2018
• 16 Sarayani A, Wang X, Thai TN, Albogami Y, Jeon N, Winterstein AG. Impact of the transition from ICD–9–CM to ICD–10–CM on the identification of pregnancy episodes in US health insurance claims data. Clin Epidemiol 2020; 12: 1129-1138
• 17 Kuklina EV, Whiteman MK, Hillis SD. et al. An enhanced method for identifying obstetric deliveries: implications for estimating maternal morbidity. Matern Child Health J 2008; 12 (04) 469-477
• 18 Purisch SE, Gyamfi-Bannerman C. Epidemiology of preterm birth. Semin Perinatol 2017; 41 (07) 387-391
• 19 Martin JA, Hamilton BE, Osterman MJ, Curtin SC, Matthews TJ. Births: final data for 2013. Natl Vital Stat Rep 2015; 64 (01) 1-65
• 20 Kulkarni AD, Jamieson DJ, Jones Jr HW. et al. Fertility treatments and multiple births in the United States. N Engl J Med 2013; 369 (23) 2218-2225
• 21 Sunderam S, Kissin DM, Crawford SB. et al. Assisted reproductive technology surveillance—United States, 2015. MMWR Surveill Summ 2018; 67 (03) 1-28
• 22 Katler QS, Kawwass JF, Hurst BS. et al. Vanquishing multiple pregnancy in in vitro fertilization in the United States-a 25-year endeavor. Am J Obstet Gynecol 2022; 227 (02) 129-135
• 23 Practice Committee of the American Society for Reproductive Medicine and the Practice Committee for the Society for Assisted Reproductive Technologies. Electronic address: [e-mail]. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril 2021; 116 (03) 651-654
• 24 Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med 2008; 359 (03) 262-273
• 25 Wang Y, Shi H, Chen L. et al. Absolute risk of adverse obstetric outcomes among twin pregnancies after in vitro fertilization by maternal age. JAMA Netw Open 2021; 4 (09) e2123634
• 26 Litwinska E, Syngelaki A, Cimpoca B, Frei L, Nicolaides KH. Outcome of twin pregnancy with two live fetuses at 11-13 weeks' gestation. Ultrasound Obstet Gynecol 2020; 55 (01) 32-38
• 27 Healthcare Cost and Utilization Project. HCUP Quality Control Procedures. February 23, 2021. Accessed February 18, 2022 at: https://www.hcup-us.ahrq.gov/db/quality.jsp#procedures