Physical health of singleton children born after frozen embryo transfer using slow freezing: a 3-year follow-up study

Hum Reprod. 2015 Oct;30(10):2411-8. doi: 10.1093/humrep/dev203. Epub 2015 Aug 20.

Abstract

Study question: Are there differences in the physical health of singleton children born after frozen embryo transfer (FET) compared with children born after fresh embryo transfer (fresh ET)?

Summary answer: Register-based health indicators were similar among FET and fresh ET singletons during a 3-year follow-up.

What is known already: Large cohort studies have shown that perinatal outcomes are similar or even better in FET than fresh ET children. The early childhood morbidity among FET and fresh ET children has been shown to be quite similar, but so far these studies have been small. The short-term health outcomes of assisted reproductive technology (ART) children have been shown to be slightly worse compared with spontaneously conceived children.

Study design, size, duration: This register-based study includes women who had undergone ART treatments leading to singleton live births (n = 4758 children) in 1995-2006. A 10% random sample of women with spontaneous pregnancies from the Finnish Medical Birth Register (FMBR) served as the reference group (n = 31 137 children). The children were identified through the FMBR by using the mother's personal identification (ID) number. Children's ID numbers were linked with two nationwide registries; the Finnish Hospital Discharge Register and the Cause-of-Death Register at Statistics Finland. Information on all visits was received until 2009 using ICD-10 codes.

Participants/materials, setting, methods: The study includes 1825 children born after FET, 2933 children born after fresh ET and 31 137 children born after spontaneous pregnancies. The risk estimates for diseases were adjusted for the child's year of birth and maternal age, parity, socio-economic status and prematurity. The study focused on the differences between FET and fresh ET children.

Main results and the role of chance: Most health indicators were similar among FET and fresh ET children during the 3-year follow-up. The most common discharge diagnoses, including gastroenteritis and colitis, otitis, upper and lower respiratory diseases, asthma and allergies were similar between the ART groups. A large proportion of FET children (70.1%) and fresh ET children (69.9%) had visited a hospital at least once (P = 0.877). The risk of hospital admission did not differ between the two groups after adjusting for premature births [adjusted odds ratio (aOR) 1.01; 0.88-1.17]. Comparing with children born after spontaneously conceived pregnancies, the risk of hospital admission was slightly increased in the ART group, even after adjusting for premature births (aOR 1.10; 1.02-1.19).

Limitations, reasons for caution: Due to the study design, we were not able to control for some parental background factors, such as the cause and length of infertility. Furthermore, the health registries do not include data on the growth of the children. Our findings are generalizable only to the slow-freezing method.

Wider implications of the findings: Our study provides further evidence of the safety of embryo cryopreservation. The early physical health of FET children is similar to that of children born after fresh ET.

Study funding/competing interests: This study was funded by the University Hospital of Oulu and Helsinki, Finland. The National Institute for Health and Welfare (THL) covered the data linkages and the work of Mika Gissler. There are no competing interests to be reported.

Keywords: assisted reproductive technology; childhood morbidity; frozen embryo transfer; in vitro fertilization; infertility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child, Preschool
  • Cohort Studies
  • Cryopreservation / methods*
  • Embryo Transfer / methods*
  • Female
  • Finland
  • Follow-Up Studies
  • Health Status*
  • Humans
  • Infant
  • Infant Mortality
  • Infant, Newborn
  • Infertility / therapy
  • Live Birth
  • Patient Admission
  • Pregnancy
  • Pregnancy Outcome
  • Premature Birth
  • Registries
  • Reproductive Techniques, Assisted / adverse effects