TY - JOUR

T1 - Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection

T2 - a Nordic study from the CoNARTaS group

AU - Henningsen, Anna Karina Aaris

AU - Opdahl, Signe

AU - Wennerholm, Ulla Britt

AU - Tiitinen, Aila

AU - Rasmussen, Steen

AU - Romundstad, Liv Bente

AU - Bergh, Christina

AU - Gissler, Mika

AU - Forman, Julie Lyng

AU - Pinborg, Anja

N1 - Publisher Copyright: © 2023 American Society for Reproductive Medicine

PY - 2023

Y1 - 2023

N2 - Objective: To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with in vitro fertilization (IVF)? Design: Nordic register-based cohort study. Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. Patient(s): All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Intervention(s): Different in vitro conception methods, and cryopreservation of embryos. Main Outcome Measure(s): Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Result(s): Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryo-ICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01–1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23–1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99–1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03–332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period. Conclusion(s): In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility.

AB - Objective: To investigate whether the risk of major congenital malformations is higher in live-born singletons conceived with intracytoplasmic sperm injection (ICSI) compared with in vitro fertilization (IVF)? Design: Nordic register-based cohort study. Setting: Cross-linked data from Medical Birth Registers and National ART and Patient Registers in Denmark, Norway and Sweden. Data were included from the year the first child conceived using ICSI was born: Sweden, 1992; Denmark, 1994; and Norway, 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden. Patient(s): All live-born singletons conceived using fresh ICSI (n = 32,484); fresh IVF (n = 47,178); without medical assistance (n = 4,804,844); and cryo-ICSI (n = 7,200) during the study period. Intervention(s): Different in vitro conception methods, and cryopreservation of embryos. Main Outcome Measure(s): Risk of major congenital malformations on the basis of International Classification of Diseases codes. The European Concerted Action on Congenital Anomalies and Twins was used to differentiate between major and minor malformations. Result(s): Among singletons conceived using fresh ICSI, 6.0% had a major malformation, compared with 5.3% of children conceived using fresh IVF; 4.2% of children conceived without medical assistance; and 4.9% of children conceived using cryo-ICSI; adjusted odds ratio (AOR) 1.07 (95% confidence interval [CI] 1.01–1.14) in ICSI vs. IVF; and AOR 1.28 (95% CI, 1.23–1.35) in ICSI vs. no medical assistance; and AOR 1.11 (95% CI, 0.99–1.26) in ICSI fresh vs. cryo-ICSI. When malformations were grouped by different organ systems, children conceived using ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived using IVF, but there were very few cases in each group. When categorizing children conceived using ICSI according to treatment indication (male factor infertility only vs. other indications), we found a higher risk of hypospadias when ICSI was performed because of male factor infertility only (AOR 1.85 [95% CI 1.03–332]). The indications for ICSI changed over time, as male factor infertility did not remain the primary indication for ICSI throughout the study period. Conclusion(s): In this large cohort study, we found the risk of major malformations in live-born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing the assisted reproductive technology method for couples without male factor infertility.

KW - assisted reproduction

KW - congenital malformations

KW - ICSI

KW - Intracytoplasmic sperm injection

KW - male infertility

U2 - 10.1016/j.fertnstert.2023.07.003

DO - 10.1016/j.fertnstert.2023.07.003

M3 - Journal article

C2 - 37442533

AN - SCOPUS:85173020431

VL - 120

SP - 1033

EP - 1041

JO - Sexuality, Reproduction and Menopause

JF - Sexuality, Reproduction and Menopause

SN - 1546-2501

IS - 5

ER -