Extended embryo culture is effective for patients of an advanced maternal age

Abstract

The aim of this study was to determine the effectiveness of extended embryo culture in advanced maternal age (AMA) patients (37-43 years). In this retrospective analysis, 21,301 normally fertilized zygotes from 4952 couples were cultured until the blastocyst stage. Blastocyst development, including kinetics and morphology, transfer rate, implantation and live birth rates, were measured. In AMA patients, the blastocyst rate was significantly decreased as compared to that in younger women. On day 5, blastocysts underwent growth retardation in AMA patients, which was highlighted by a decreased rate of full/expanded blastocysts. Organization of the cells (trophectoderm and inner cell mass) was unaffected by age. However, in AMA patients, a 'good' morphology blastocyst had a decreased probability to implant compared with an 'average' morphology blastocyst in younger women. While the rates of blastocyst transfer and useful blastocysts were similar to younger patients, in AMA patients, both implantation and live birth rates were significantly reduced. Our results support the idea that extended embryo culture is not harmful for AMA patients. However, embryo selection allowed by such culture is not powerful enough to avoid chromosomal abnormalities in the developed blastocysts and therefore cannot compensate for the effect of a woman's age.

Figure 1

Blastocyst rate by the woman’s age. The blastocyst rate is the ratio between the number of blastocysts obtained at D5 or D6 and the number of normally fertilized zygotes at D1.

Figure 2

Stage of blastocyst expansion obtained at D5 as a function of the woman's age group. The blastocyst rate is the ratio between the number of blastocysts obtained at D5 or D6 and the number of normally fertilized zygotes at D1. B1: early blastocyst (the blastocoel being less than half the volume of the embryo). B2: early blastocyst (the blastocoel being greater than half the volume of the embryo). B3: full blastocyst (the blastocoel completely filling the embryo). B4: expanded blastocyst (the blastocoel volume now being larger than that of the early embryo and the zona starting to thin). B5: hatching blastocyst (the trophectoderm starting to herniate though the zona). B6: hatched blastocyst (the blastocyst having completely escaped from the zona) (from Gardner, D. K. & Schoolcraft, W. B, 1999). Columns with the same superscript letters are not significantly different (P > 0.05).

Figure 3

Morphology of D5 blastocysts according to the woman’s age group. Morphological assessment based on the expansion of the blastocoel cavity (B1–B6) and the number and cohesiveness of the inner cell mass (ICM) and trophectoderm (TE) cells. For blastocysts graded as B3–B6, it is possible to assign independent scores to the ICM and TE. For the ICM, grade A indicated a tightly packed ICM with many cells; grade B, a loosely grouped ICM with many cells; and grade C, an ICM with very few cells. For the TE, grade A indicated a TE with many cells forming a cohesive epithelium; grade B, a TE with few cells forming a loose epithelium; and grade C, a TE with very few cells. ‘Poor’morphology: B3–B6, CC. ‘Average’ morphology: B3–B6, AC/CA/BC/CB). ‘Good’morphology (B3–B6, AA/AB/BA/BB). Data were not significantly different (p > 0.05).

Figure 4

Live birth rate (LBR) by transfer according to D5 blastocyst morphology and the woman’s age group. LBR: live birth rate. Morphological assessment based on the expansion of the blastocoel cavity (B1–B6) and the number and cohesiveness of the inner cell mass (ICM) and trophectoderm (TE) cells. For blastocysts graded as B3–B6, it is possible to assign independent scores to the ICM and TE. For the ICM, grade A indicated a tightly packed ICM with many cells; grade B, a loosely grouped ICM with many cells; and grade C, an ICM with very few cells. For the TE, grade A indicated a TE with many cells forming a cohesive epithelium; grade B, a TE with few cells forming a loose epithelium; and grade C, a TE with very few cells. ‘Poor’morphology: B3–B6, CC. ‘Average’ morphology: B3–B6, AC/CA/BC/CB). ‘Good’morphology (B3–B6, AA/AB/BA/BB).