Human Reproduction – Prevalence of XXY karyotypes in human blastocysts: multicentre data from 7549 trophectoderm biopsies obtained during preimplantation genetic testing cycles in IVF

Rossella Mazzilli, Danilo Cimadomo, Laura Rienzi, Antonio Capalbo, Paolo Emanuele Levi Setti, Claudia Livi, Damiano Vizziello, Carlo Foresta, Alberto Ferlin, and Filippo Maria Ubaldi

Human Reproduction, pp. 1–9, 2018 doi:10.1093/humrep/dey110 – Submitted on February 9, 2018; resubmitted on April 17, 2018; accepted on April 27, 2018; publisched May 19, 2018


STUDY QUESTION: Which is the prevalence of a 47,XXY karyotype in human blastocysts biopsied during preimplantation genetic testing for aneuploidies (PGT-A) cycles?

SUMMARY ANSWER: The prevalence of a 47,XXY karyotype amongst male blastocysts without autosomal aneuploides is ~1%.

WHAT IS KNOWN ALREADY: The prevalence of Klinefelter syndrome is estimated as 0.1–0.2% in male newborns. However, the KS phenotype is extremely variable and there are men with a 47,XXY karyotype and less evident signs, who may go undetected. No risk factor for the 47,XXY karyotype in products of conception has been yet clearly defined, and no data are available regarding the prevalence of this karyotype among human preimplantation embryos.

STUDY DESIGN, SIZE, DURATION: This multicentre cohort study involved 7549 blastocysts obtained during 2826 PGT-A cycles per- formed between April 2013 and September 2017 at six IVF clinics in Italy.

PARTICIPANTS/MATERIALS, SETTING, METHODS: During 2826 PGT-A cycles, 7549 blastocysts underwent trophectoderm biopsy and quantitative-PCR-based comprehensive chromosomal testing to predict the karyotype of the corresponding embryos. The results were also pre- sented according to ranges of maternal and paternal age at oocyte retrieval as well as sperm factor and blastocyst quality. Univariate and multivariate logistic regression analyses were conducted to investigate the correlation of possible confounding factors with the prevalence of 47,XXY karyotype.

MAIN RESULTS, THE ROLE OF CHANCE: Overall, 62 blastocysts were 47,XXY or had an XXY karyotype associated with autosomal aneuploidies. After exclusion of the latter, the prevalence of a 47,XXY karyotype among male blastocysts without autosomal aneuploidies was 0.9% (n = 17/1794). A significant correlation was only found for maternal age and blastocyst quality (OR: 1.20, 95% CI: 1.01–1.42; P = 0.04 and OR: 1.6, 95% CI: 1.13–2.45; P = 0.01).

LIMITATIONS, REASONS FOR CAUTION: These retrospective data have been produced based on a population of infertile couples undergoing IVF and PGT-A, and the women were mainly of advanced maternal age. Moreover, the qPCR technique is validated only to detect full-chromosome uniform aneuploidies in trophectoderm biopsies.

WIDER IMPLICATIONS OF THE FINDINGS: The 0.9% prevalence of the 47,XXY karyotype among male blastocysts, when compared with the 0.1–0.2% prevalence reported in the prenatal and postnatal periods, suggests four possible scenarios that require further investiga- tions: (i) the latter prevalence is underestimated; (ii) 47,XXY blastocysts result in a lower implantation rate than euploid embryos (estimated to be ≈50%); (iii) 47,XXY blastocysts result in a higher early miscarriage rate than euploid embryos (estimated to be ≈10%); or (iv) infertile patients of advanced maternal age and referred to IVF/PGT-A produce a higher rate of 47,XXY blastocysts.



Key words: preimplantation genetic testing for aneuploidies / ICSI / Klinefelter syndrome / XXY karyotypes / sex chromosomal aneuploidies