High rates of aneuploidy, mosaicism and abnormal morphokinetic development in cases with low sperm concentration

Abstract

The aim of our study was to evaluate the impact of severe male infertility (SMF) on the chromosomal status of embryos and any possible correlation between chromosomal status and embryo morphokinetics in younger women using data obtained from comprehensive preimplantation genetic tests. Methods The trial was conducted in an ART and Reproductive Genetics Centre between 2011 and 2018. A total of 326 cycles in cases with SMF where the female partner's age was ≤ 35 years were evaluated. SMF is defined as sperm concentration below 5 mil/ml (million per milliliter) and divided into three subgroups according to sperm concentrations: 1-5 mil/ml, < 1mil/ml and testicular sperm. The control group of 190 cycles had normal sperm parameters. Results Significantly lower chromosomal euploidy rates were found in the testicular sperm group compared with the normal sperm controls when the female age was ≤ 35 years. In SMF, statistically significantly affected chromosomes were 2, 10, 11, 17, 21 and sex chromosomes. The mosaicism and abnormal morphokinetic development rates were higher in the SMF group than in control group, and this difference was significant when testicular sperm was used. Conclusion Lower euploidy rates, higher mosaicism rates and a higher incidence of abnormal morphokinetic development were observed in cases with testicular sperm with female partners ≤ 35 years compared with normal sperm controls. These findings suggest that PGT-A may be advisable in severe male infertility cases. Furthermore, the correlation between morphokinetics and chromosomal status was greatly reduced or absent in these most severe forms of male infertility, thus the need for new morphokinetic models.

Characteristics of the IVF Cycle that Contribute to the Incidence of Mosaicism

“…The incidence of mosaic and chaotic patterns in cleavage stage embryos from oligozoospermic and azoospermic patients ranges from 35% to 68% [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Although the incidence is lower at the blastocyst stage, two recent studies described a higher rate of mosaic blastocysts in PGT-A cycles with male factor indication compared to couples with normal sperm parameters, with the highest rate of mosaicism correlated with the severity of male infertility [ 14 , 15 ]. We also observed an increase in mosaicism with a decrease in sperm count, with the highest mosaicism rate in patients with severe oligozoospermia (7.9%) similar to the 7.7% described by Tarozzi’s group and 10.9–15.6% described by Kharaman’s group [ 14 , 15 ].…”

“…Although the incidence is lower at the blastocyst stage, two recent studies described a higher rate of mosaic blastocysts in PGT-A cycles with male factor indication compared to couples with normal sperm parameters, with the highest rate of mosaicism correlated with the severity of male infertility [ 14 , 15 ]. We also observed an increase in mosaicism with a decrease in sperm count, with the highest mosaicism rate in patients with severe oligozoospermia (7.9%) similar to the 7.7% described by Tarozzi’s group and 10.9–15.6% described by Kharaman’s group [ 14 , 15 ]. Our group of severe oligozoospermia had the highest incidence of TE biopsies with only segmental aneuploidy.…”

“…The same study, however, did not observe an effect of the ovarian response and vitrification of oocytes on mosaicism rate. Finally, the use of PGT-A in couples with compromised semen quality shows higher rates of mosaic embryos with low sperm concentrations [ 14 , 15 ].…”

Preimplantation Genetic Testing: Where We Are Today

“…Many centers started to perform PGT-A on single cells biopsied from cleavage stage embryos using FISH with chromosome-specific probes [106,107]. A study by Rubio et al [71] aimed to evaluate the role of PGT by FISH for two different indications: women <40 years with RIF and women with AMA aged 41-44 years.…”

“…Mazzilli et al [115] investigated in their study only 35 cycles in women under 35 years. Kahraman et al [107] investigated 326 cycles with 741 blastocysts biopsied and analyzed using aCGH and NGS techniques; the couples enrolled were composed of young female (≤35) with SMF partners, ranging from five million/mL to NOA.…”