Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy

Abstract

Purpose The purpose of this study is to review recurrent pregnancy loss (RPL) due to sperm chromosomal abnormalities and discuss the genetic counseling that is required for men with sperm chromosomal abnormalities. Method The literature was reviewed, and a genetic counselor lends her expertise as to how couples with RPL and sperm chromosomal abnormalities ought to be counseled. The review of the literature was performed using MEDLINE. Results Sperm fluorescence in situ hybridization (FISH) can be used to determine if disomy or unbalanced chromosomal translocations are present. In men with aneuploidy in sperm or who carry a chromosomal translocation, pre-implantation genetic screening (PGS) combined with in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) can increase chances of live birth. In men with abnormal sperm FISH results, the degree of increased risk of abnormal pregnancy remains unclear. Genetic counselors can provide information to couples about the risk for potential trisomies and sex chromosome aneuploidies and discuss their reproductive and testing options such as PGS, use of donor sperm, and adoption. The provision of genetic counseling also allows a couple to be educated about recommended prenatal testing since pregnancies conceived with a partner who has had abnormal sperm FISH are considered to be at increased risk for aneuploidy. Conclusion We review the literature and discuss genetic counseling for couples with RPL or recurrent implantation failure due to increased sperm aneuploidy.

Meiotic nondisjunction and sperm aneuploidy in humans

“…These studies have reported a two-to seven-fold increase in sperm aneuploidy for the investigated chromosomes in these patients (Fig. 3) (Collodel et al 2009, Kohn et al 2016, Zidi-Jrah et al 2016, Esquerre-Lamare et al 2018. The majority of the aforementioned studies have focused on males with reduced semen parameters; however, a large study reported that up to 40% of male partners of RPL with normal semen parameters also had significantly increased sperm aneuploidy levels (Ramasamy et al 2015).…”

“…In reality, we are unable to test the individual sperm that will be used in ART; thus, it can only provide a generalized overview of the levels of aneuploidy in a semen sample. Perhaps one of the greatest challenges when considering the clinical relevance and utilization of sperm aneuploidy screening is the lack of a clearly established and validated sperm aneuploidy threshold (Kohn et al 2016). These need to be developed by each individual laboratory performing sperm aneuploidy testing with large numbers of individuals.…”

Impact of a mild scrotal heating on sperm chromosomal abnormality, acrosin activity and seminal alpha-glucosidase in human fertile males

“…Chromosomal aneuploidy, DNA damage rates and abnormal morphology in spermatozoa are higher in infertile individuals and may contribute to early pregnancy loss (recurrent miscarriage), birth and developmental defects or other consequences for their offspring later in life (Andreescu et al., ; Kohn, Kohn, Darilek, Ramasamy, & Lipshultz, ; Palermo et al., ; Perry et al., ). Fluorescence in situ hybridisation (FISH) analysis of sperm chromosomes was performed for patients with poor semen quality, recurrent pregnancy loss or recurrent implantation failure and spinal cord injury (anejaculation) (Andreescu et al., ; Kohn et al., ; Palermo et al., ; Perry et al., ; Qiu, Wang, Zhang, & Zhang, ; Qiu, Wang, Zhang, Li, et al., ). To date, no reports have been published about changes in sperm chromosome ploidy, sperm membrane and DNA integrity and AA under testicular heat stress.…”

The male contribution to recurrent pregnancy loss

“…With the information we currently have, testing for sperm chromosomal abnormalities and DNA fragmentation appears to be a reasonable option for male partners of women with unexplained RPL, with referral to genetic counselor if results are positive ( 69 ). Although, it remains difficult to predict the exact risk of unfavorable outcomes in the presence of positive findings from the available tests we have especially with the limitations in the methods of testing, this information provides for more detailed discussion about the risks and potential impacts on subsequent pregnancy outcomes.…”

“…In addition, Neusser et al posited that in RPL, chromosomes 1, 2, 6, 15, 16 and 21 are more relevant targets for sperm aneuploidy testing with chromosome 16 being the most promising diagnostic target ( 68 ). For these reasons, some authors suggest that until more in-depth studies are performed to explore this relationship, men with RPL should be screened for sperm aneuploidy and also referred to genetic counselors ( 69 ). At present, no intervention is known to decrease sperm aneuploidy but preimplantation genetic screening (PGS) can be used to select for euploid embryos during IVF.…”