45,X/46,XY Mosaicism and Normozoospermia in a Patient with Male Phenotype

Abstract

The phenotypic spectrum of 45,X/46,XY mosaic males varies greatly. Previous reports have only described cases with either oligozoospermia, growth retardation, or elevated gonadotropins. However, the present case presented with normozoospermia, and normal height, sperm DNA fragmentation index (DFI), and gonadotropins. The male and his spouse were referred to The Fertility Clinic, Skive Regional Hospital, due to 2 years of infertility. After failure of several attempts of assisted reproductive treatment (ART), the male underwent genetic analysis. Conventional karyotyping in peripheral lymphocytes yielded a low-grade 45,X/46,XY mosaicism, confirmed by fluorescence in situ hybridization (FISH) showing 6% 45,X cells. A FISH test performed on interphase nuclei from buccal mucosal cells yielded one cell with only one X-signal (0.6%), explaining the normal phenotype of the patient, but not the infertility. FISH test for sperm aneuploidy showed normal range parameters, except for a 10-fold elevated gonosomal nullisomy rate (2.1%). Hence, germinal mosaicism may be an explanation of the infertility of the case. Increased sex nullisomy levels may reflect an aberrant testicular environment compromising fertility even though sperm euploidy rates and other sperm parameters do not preclude a successful treatment with ART. Based on these results, the couple decided to use donor semen for their subsequent intrauterine insemination treatment and obtained a successful pregnancy.

Sperm nullisomy is not associated with routine semen parameters but it negatively impacts on ICSI outcomes

“…In line with this finding, higher frequencies of nullisomy of chromosomes 21, 22 and sex chromosomes (Fowler et al., 2019; Ioannou et al., 2019) than of other chromosomes have been reported due to the high risk of nondisjunction produced by a single recombination site in these chromosomes (Hassold et al., 2000; Ioannou et al., 2019). However, our results show that nullisomy of chromosome 22 and other chromosomes was not associated with basic semen parameters or pathologies, which is consistent with a recent case report, in which it has been described a patient with normal semen parameters and a 10‐fold higher sex chromosome nullisomy rate (2.1%) who experienced recurrent ART failure (Ketheeswaran et al., 2019). Our study also confirms a negative impact of sperm nullisomy on ART outcomes, with significant decreases in fertilisation, blastocyst and pregnancy and implantation rates during ICSI treatments.…”