Zona pellucida thickness does not predict pregnancy outcomes in patients less than 38 years of age undergoing in vitro fertilization: results from a prospective, randomized trial on assisted hatching

Abstract

“Thickened zona pellucida” is a commonly cited, but poorly defined, indication for the assisted hatching (AH) procedure. We sought to determine the effect of zona pellucida (ZP) thickness on clinical pregnancy rates in younger patients undergoing in vitro fertilization (IVF), and furthermore to define a ZP thickness at which assisted hatching may be beneficial. A prospective, randomized, controlled, double-blind trial of AH in patients less than 38 years of age undergoing IVF. Between April 2004 and February 2007, 162 patients were consented and enrolled in our study. The Zona Laser Treatment System (Hamilton Thorne, Beverly, MA) was used to measure the thickness of each ZP. Patients whose embryos had a ZP thickness ≥13 microns were randomized to undergo assisted hatching or to remain unhatched; those whose embryos had a ZP thickness <13 microns were classified as “thin” and were not randomized. Each patient's mean ZP thickness was calculated for use in the final analysis. Hatching procedures were performed using acidic Tyrode's medium. To examine mean ZP thickness as a predictor of pregnancy outcomes, a receiver operator curve (ROC) was generated using a log-binomial model. A total of 98 recorded ZP measurements from 55 IVF cycles were compared. 11 embryos (11%) had a mean ZP <13 microns. The mean ZP thickness of the remaining 87 embryos was 17.36 microns ± 3.09 (SD). Among patients whose embryos did not undergo AH, there was no difference (P=0.28) between mean ZP thickness of those embryos with resultant clinical pregnancies (17.6 ± 3.3, n = 8) vs. mean ZP thickness of those without clinical pregnancies (16.8 ± 3.3, n = 5). After adjusting for assisted hatching, the ROC showed a one unit increase in mean ZP to be associated with a small increase in the odds of pregnancy, but this difference was not statistically significant (RR = 1.11, 95% CI 0.96–1.28). The area under the curve was 0.77; there was no ZP thickness that sensitively and specifically predicted the outcome of clinical pregnancy. ZP thickness is not a significant predictor of clinical pregnancy in patients less than 38 years of age undergoing IVF. Our results therefore do not support the use of “thickened ZP” as an indication for AH in this patient population. On the contrary, the evidence suggests that “thickened ZP” is not a clinically useful concept in this setting.