Impact of sperm genome decay on Day‐3 embryo chromosomal abnormalities from advanced‐maternal‐age patients

Abstract

Infertile male patients often exhibit unconventional semen parameters, including DNA fragmentation, chromatin dispersion, and aneuploidy-collectively referred to as sperm genome decay (SGD). We investigated the correlation of SGD to embryo chromosomal abnormalities and its effect on clinical pregnancy rates in patients with advanced maternal age (AMA) (>40 years) who were undergoing intracytoplasmic sperm injection-preimplantation genetic screening (ICSI-PGS). Three groups were assessed: patients with AMA and male partners with normal sperm (AMA-N); AMA patients and male partners presenting with SGD (AMA-SGD); and young fertile female patients and male partners with SGD (Y-SGD). We found a significant increase in embryonic chromosomal abnormalities-polyploidy, nullisomy, mosaicism, and chaotic anomaly rates-when semen parameters are altered (76% vs. 67% and 66% in AMA-SGD vs. AMA-N and Y-SGD groups, respectively). Statistical analysis showed a correlation between SGD and aneuploidies of embryonic chromosomes 13, 16, 21, X, and Y, as well as negative clinical outcomes. Incorporation of molecular sperm analyses should therefore significantly minimize the risk of transmission of chromosomal anomalies from spermatozoa to embryos, and may provide better predictors of pregnancy than conventional sperm analyses. We also demonstrated that an ICSI-PGS program should be implemented for SGD patients in order to limit transmission of chromosomal paternal anomalies and to improve clinical outcome.

Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years

“…SGD results in an abnormal early embryonic development (Borini et al, ), embryo aneuploidy (Kaarouch et al, ) and affecting early embryo genome activation (EGA), that necessary for embryo genetic integrity maintaining toward genetic stability (Aitken et al, ; Benkhalifa et al, ; Emery & Carrell, ; Robertshaw et al, ; Tesarik et al, ; Simon et al, ; Zini et al, ). Whatever, there is possible sperm DNA damage repair or rescue by oocyte at fertilization stage or at later embryonic stage involving genetic repair systems generally producing embryo mosaicisms (Jaroudi et al, ; Kaarouch et al, ). However, repair failure of SGD can lead to de novo mutations and structural chromosomal alterations knowing that majority of them arise in male germline with APA.…”

“…In the other hand, we hypothesized that minimal the earlier SGD can be repaired by the oocyte (Jaroudi et al, ; Kaarouch et al, ; Ménézo, ; Perry, ) and that after the age of 40 its repair becomes difficult due to the extent of damage (Voyel et al, 2011). Our results suggest that 40 years can be considered the cutoff age for male patients undergoing IVF procedures.…”

“…The smears were stained, rinsed in distilled water, air dried, and scored using Kruger's strict criteria (Kruger et al, ). After conventional sperm parameters evaluation (volume, concentration, motility, vitality, and morphology) based on WHO (2010) recommendations, samples were divided in three aliquots to assess DNA fragmentation by TUNEL assay, chromatin condensation by aniline blue staining and chromosomes aneuploidy by FISH with specific probes to chromosome 13, 18, 21, X, and Y (Aneuvysion™, Vysis, Downers Grove, III) (Kaarouch et al, ). These three tests were used to determine SGD level.…”

“…These three tests were used to determine SGD level. Aliquots to assess DNA fragmentation by TUNEL assay chromatin decondensation by aniline blue staining as provided by (Kaarouch et al, ).…”

Couples with male infertility have an increased risk for having a child with Klinefelter syndrome

“…В сперме бесплодных мужчин также выявляются дисомии по соматическим хромосомам [8]. Вместе с тем обнаружено значительное увеличе-ние эмбриональных хромосомных аномалий (поли-плоидий, нулисомий, мозаичности и анеуплоидий в половых хромосомах) в случаях, когда у отца выявля-ется повышенный уровень фрагментации ДНК ядра или изменения в морфологии сперматозоидов [9]. Таким образом, вклад различных патологий сперма-тозоидов отца в нарушения наследственного матери-ала плода требует дальнейшего изучения.…”