Fertilization Method Does Not Appear to Influence Perinatal Outcomes Among Infants Conceived With Assisted Reproductive Technology

Differences in obstetric outcomes between intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF) appear to be driven by factors other than the method of fertilization, according to findings from a new study.

Sanaz Keyhan, MD, a fellow of the Division of Reproductive Endocrinology and Infertility at Duke University Medical Center, presented findings from the retrospective cohort study at the Scientific Congress & Expo of the American Society for Reproductive Medicine held October 15 to 19, 2016, in Salt Lake City, UT.

Preterm delivery and low birth weight (LBW) are more common among infants conceived via assisted reproductive technology than among spontaneous conceptions. Some evidence suggests that obstetric outcomes in the setting of assisted reproductive technology are improved with ICSI compared with conventional IVF. The current study assessed whether the method of fertilization contributed to differences in preterm delivery and LBW between ICSI and conventional IVF. 

Researchers examined data from first fresh autologous IVF cycles resulting in singleton births in women aged younger than 43 years that were reported to the Society for Assisted Reproductive Technology's Clinical Outcomes Reporting System database between 2004 and 2013. Cycles with any of the following features were excluded: use of preimplantation genetic diagnosis, split or second-day ICSI, mixed or unknown sperm source, missing birth weight data, and presence of more than 1 fetal heartbeat on ultrasonography.

The primary end points were preterm delivery (< 37 weeks) and LBW (< 2500 g) in the ICSI and IVF groups after controlling for factors such as male factor fertility, female factor infertility, and sperm source. Additional end points included

  • Term LBW: < 2500 g at ≥ 37 weeks
  • Preterm LBW: < 2500 g at < 37 weeks
  • Very preterm delivery: delivery at < 32 weeks
  • Very LBW: < 1500 g

In total, 90,401 cycles were included in the analysis. Of these, 60,719 (67.2%) utilized ICSI and 29,682 (32.8%) involved conventional IVF.

Multiple baseline parental characteristics were significantly different between the ICSI and IVF groups (Table 1). Male factor infertility was the most common diagnosis in the ICSI group, occurring at a rate 5 times higher than that in the conventional IVF group (57.5% vs 9.2%; P < .0001). By comparison, the most common diagnoses in the IVF group were tubal factor infertility (24.7%) and unexplained infertility (24.4%).

Table 1. Patient and Cycle Characteristics

Characteristic ICSI (n = 60,719), %

Conventional IVF
(n = 29,682), %

P Value
Partner’s sperm 96.7 96.1 < .0001
Use of ejaculated sperm 93.7 99.9 < .0001
Male factor infertility 57.5 9.2 < .0001
Unexplained infertility 11.3 24.4 < .0001
Endometriosis 10.3 14.5 < .0001
Diminished ovarian reserve 19.6 19.0 .92
Polycystic ovary syndrome 15.8 19.7 < .0001
Tubal factor infertility 12.3 24.7 < .0001
Uterine factor infertility 3.3 4.0 < .0001
Other 8.8 10.1 < .0001

ICSI = intracytoplasmic sperm injection, IVF = in vitro fertilization.

Researchers used a statistical technique called propensity-score matching to correct for baseline factors that predicted the likelihood of undergoing treatment with ICSI vs IVF. The analysis included 13,277 ICSI cycles and 11,373 conventional IVF cycles matched for baseline diagnoses and sperm source (Table 2).

Table 2. Perinatal Outcomes Following ICSI vs Conventional IVF in a Matched Data Set

Outcome OR (95% CI) P Value
Preterm delivery 1.02 (0.92-1.13) .77
Very preterm delivery 1.06 (0.78-1.43) .72
LBW 0.91 (0.81-1.02) .12
Preterm LBW 0.81 (0.68-0.97) .02
Term LBW 0.98 (0.84-1.14) .81
Very LBW 1.05 (0.74-1.49) .77

CI = confidence interval, ICSI = intracytoplasmic sperm injection, IVF = in vitro fertilization, LBW = low birth weight, OR = odds ratio.

After adjusting for these factors, the odds of preterm LBW were lower with ICSI than IVF (adjusted odds ratio 0.81; 95% confidence interval, 0.68-0.97; P = .02). However, no significant association was observed between fertilization method and any other perinatal end point. 

The lack of association between fertility method and perinatal outcomes was consistent across patient subgroups, including cycles using donor sperm and cycles with favorable-prognosis women plus unexplained fertility, tubal factor infertility, and male factor infertility. 

“Differences in adverse perinatal outcomes between ICSI and IVF may be secondary to parental characteristics and infertility diagnoses, rather than associated with the fertilization method itself,” Keyhan said. These findings may challenge the approach of selecting ICSI over IVF, all else being equal, in an effort to lessen the risk of preterm delivery or LBW.

Source: Keyhan S, Li Y, Truong T, et al. Perinatal outcomes following intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilization (IVF). Presented at: American Society for Reproductive Medicine 2016 Scientific Congress & Expo; October 15-19, 2016; Salt Lake City, UT. Abstract P-159.