Does PGT for aneuploidy increase live births?

(©NicoElNino/shutterstock.com)

In women of advanced maternal age (36 to 40 years) undergoing intracytoplasmic sperm injection (ICSI), preimplantation genetic testing (PGT) did not increase the live birth rate at one year, according to results of the Evaluation of oocyte Euploidy by Microarray analysis (ESTEEM) trial. ESTEEM was a multinational, randomized clinical trial that enrolled 396 participants between August 2012 and December 2016 in seven countries. It was designed to reflect clinical practice, one of the major strengths of the trial. Although it was the largest study to date to address this question, recruitment was less than expected due to potential participants’ reluctance to be randomized still, the researchers were able to enroll enough women to power the study at 90% to detect the proposed targeted increase. Results were published in Human Reproduction.

Two hundred and five women were randomly assigned to comprehensive chromosomal screening for aneuploidy (PGT-A) as part of their ICSI treatment cycle and 191 were assigned to ICSI treatment without PGT. Embryos from women in the PGT-A group were analyzed for 23 chromosomes in polar bodies 1 and 2 to select euploid embryos for transfer. PGT-A was performed between six and nine hours after ICSI, and between 42 and 49 hours after injection of human chorionic gonadotropin. Both the women and their clinicians were blinded to their group assignment from enrollment until the day after the intervention. 

Among other things, women were excluded from the study if they had undergone three or more failed in vitro fertilization (IVF) or ICSI cycles with their current partner, had poor ovarian response during previous IVF/ICSI attempts, irregular menstrual periods, three or more miscarriages, were using certain drugs, or if their partners required sperm retrieval or had other sperm abnormalities. Women in both the intervention and control groups had normal body mass indices (23.2 kg/m²).

Use of polar bodies in trial

The rationale for using polar bodies rather than the more commonly used trophectoderm biopsy was that they are the initial non-functional byproduct cells found in a fertilized egg as it prepares to divide for the first time. Although polar bodies contain only genetic material from mothers, they represent the full chromosomal content of the egg and can detect 90% of meiotic errors, reported the authors. In addition, polar body analysis was the only type of PGT-A allowed in Italy and Germany, two of the countries included in the analysis, at the time the study was initiated. However, it does not capture meiotic errors contributed by fathers, and it misses mosaicism that occurs during later stages of embryo development. 

Results confirm previous findings

The results revealed no difference in terms of the primary endpoint of the study in that both groups had a live birth rate within one year of 24% (difference = 0.83%, 95% CI -7.60 to 9.18%) after one cycle of treatment. There were 50 live births in the intervention group and 45 in the control group. Thus, the results confirmed findings from other studies, reported the authors.

In terms of secondary outcomes, however, there were significantly fewer miscarriages in the PGT-A group (7% versus 14%, P= 0.02). There were also fewer embryo transfers in the intervention group. The researchers noted that it is unclear if these benefits will outweigh the invasive nature and substantial costs of PGT-A, greater workload for IVF lab staff members, and potential negative impact on the children born of this intervention.