ReviewImplication of sperm chromosomal abnormalities in recurrent abortion and multiple implantation failure
Introduction
The analysis of chromosomes in spermatozoa is currently available for diagnosis and therapeutic orientation in cases of poor reproductive prognosis, such as repeat abortion and recurrent implantation failure. As not only embryonic or maternal factors are involved in these problems, it is pertinent to study the chromosomal constitution of the spermatozoa, that is, the paternal contribution to the future embryo.
Repeat abortion has an incidence of between 1 and 5%, and depending on the chosen definition corresponds to two or three consecutive abortions. However, this percentage would be higher if all unrecognized early gestational losses were considered. Cytogenetic studies of the remains of first trimester abortions have revealed that 50–80% of embryos are chromosomally abnormal (Pang et al., 1999). Although most numerical chromosomal abnormalities are of maternal origin, 8–12% of abortions with trisomy of chromosomes 12, 18 and 21 are of paternal origin (Nicolaidis and Petersen, 1998).
For the study of the paternal contribution to repeated abortion and implantation failure it is not enough to know only the somatic karyotype of the patient, because a normal karyotype does not exclude the presence of chromosomal abnormalities that arise de novo in the germinal line (Egozcue et al, 2000, Rubio et al, 1999). It was in the 1970s that the first studies of the chromosome constitution of spermatozoa appeared, using the technique of sperm injection into hamster oocytes. The technique that is most currently used is the application of fluorescence in-situ hybridization (FISH) on sperm nuclei.
There are few studies dealing with cytogenetic sperm analysis in the case of repeated abortion or implantation failure (Kahraman et al., 2006). Most state that the risk of these events is increased in the presence of chromosomal abnormalities in spermatozoa (Bernardini et al, 2004, Carrell et al, 2003, Rubio et al, 2001).
Despite these data, the indications for performing FISH in clinical practice and the reproductive benefits of it remain contested. As individuals with abnormalities of sperm chromosomes present an increased risk of aneuploidy in their products of conception, it is supposed that they benefit from preimplantation genetic diagnosis (PGD).
The aims of this review article are to: (i) determine the incidence of sperm aneuploidy in cases of repeated abortion and implantation failure and identify which patients would benefit most from FISH analysis of spermatozoa; and (ii) know if there is any advantage to performing FISH before or instead of PGD.
Section snippets
Materials and methods
Three bibliographical searches of the MEDLINE database were performed before 15 April 2015. In the first search, the Mesh words ‘infertility’ AND ‘spermatozoa’ AND ‘in-situ hybridization, fluorescence’ were entered into the search engine, obtaining 258 articles. In the second, the Mesh words ‘spermatozoa’ AND ‘analysis, cytogenetic’ AND ‘sperm retrieval’ resulted in 10 articles. In the third search, the following Mesh words were introduced: ‘spermatozoa’ AND ‘analysis, cytogenetic’ AND
Aneuploidy in spermatozoa and its relationship with repeated abortion and recurrent implantation failure
Rubio et al. (2001) showed that the incidence of aneuploidy is higher in men with an adverse reproductive history, such as repeat abortion or abortion after intracytoplasmic sperm injection (ICSI). In these infertile men, despite a normal 46,XY karyotype, anomalies in the meiotic germline process happen with subsequent production of spermatozoa with an aneuploid chromosomal constitution, more frequently diploid spermatozoa. The contribution of sperm aneuploidy to repeated abortion is due to the
Discussion
The aetiology of recurrent abortion is only determined in 30% of cases. In most cases, tests ordered in this context are focused on women, while men remain little investigated and sperm analysis is frequently limited to a spermogram. However, since direct genetic testing of spermatozoa is available, some studies have proved that pathologies such as recurrent pregnancy loss, repeated IVF failure, autosomal structural abnormalities (e.g. translocations and inversions) and oligozoospermia,
Ana Lara Caseiro has a Masters in Medicine, awarded in 2008 from the Faculty of Medical Sciences, New University of Lisbon; a Masters in Human Reproduction awarded in 2013 from the Faculty of Medicine, University of València and IVI – Instituto Valenciano de Infertilidad. Currently, she is a resident in the Department of Gynecology and Obstetrics at Évora's Hospital and an investigator in the Premya Study, about Esmya® (Ulipristal Acetate) and Alerta study (human contraception). She has
References (23)
- et al.
Preimplantation genetic diagnosis in patients with male meiotic abnormalities
Reprod. Biomed. Online
(2004) - et al.
Sperm aneuploidy and recurrent pregnancy loss
Reprod. Biomed. Online
(2004) - et al.
Predictive value of sperm fluorescence in situ hybridization analysis on the outcome of preimplantation genetic diagnosis for translocations
Fertil. Steril
(2003) - et al.
The origin of numerical chromosome abnormalities
Adv. Genet
(1995) - et al.
Preliminary FISH studies on spermatozoa and embryos in patients with variable degrees of teratozoospermia and a history of poor diagnosis
Reprod. Biomed. Online
(2006) - et al.
Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and testicular germ cells of infertile patients
Hum. Reprod
(2000) - et al.
Chromosome analysis of epididymal and testicular spermatozoa in patients with azoospermia
Eur. J. Hum. Genet
(2002) - et al.
Lower sperm aneuploidy frequency is associated with high pregnancy rates in ICSI programmes
Hum. Reprod
(2003) - et al.
Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss
Arch. Androl
(2003) - et al.
Human male infertility: chromosome anomalies meiotic disorders, abnormal spermatozoa and recurrent abortion
Hum. Reprod. Update
(2000)
A fluorescent in situ hybridization analysis of the chromosome constitution of ejaculated sperm in a 47,XYY male
Clin. Genet
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Genetics and epigenetics of healthy gametes, conception, and pregnancy establishment: Embryo, mtDNA, and disease
2022, Fertility, Pregnancy, and WellnessSperm chromosome abnormalities in patients with normal karyotype and in translocation carriers: clinical relevance for assisted reproductive technology
2020, Reproductive BioMedicine OnlineCitation Excerpt :Considering that the male factor is regularly treated by intracytoplasmic sperm injection (ICSI), an estimation of the sperm aneuploidy level in specific cases is important to identify couples at risk of producing high proportions of chromosomally abnormal embryos. Several studies have reported that increased levels of aneuploidy are detected in patients with poor reproductive prognosis, such as those with a history of repeated miscarriages and recurrent implantation failures, even in the presence of normozoospermic samples (Caseiro et al., 2015). In these specific cases, the clinical outcome could be dependent on the proportion of aneuploid sperm cells and, for this reason, sperm chromosome analysis was proposed by some investigators as an indicator of the reproductive possibilities of infertile couples (Rodrigo et al., 2019).
Recurrent implantation failure in IVF: A Canadian Fertility and Andrology Society Clinical Practice Guideline
2020, Reproductive BioMedicine OnlineCitation Excerpt :Justification: observational studies suggest that couples with RIF may have a slightly higher rate of chromosomal anomalies than fertile couples. Sperm DNA damage is associated with poor embryo development, and there is recent interest in the use of sperm DNA integrity testing in the evaluation of reproductive failure (Caseiro et al., 2015). DNA fragmentation may be associated with increased risk of miscarriage (Simon et al., 2017) but its association with RIF has not been established.
Double-stranded sperm DNA damage is a cause of delay in embryo development and can impair implantation rates
2019, Fertility and SterilityCitation Excerpt :From studies in somatic cells, it is well known that double-stranded DNA breaks trigger the initiation of DNA repair machinery and/or apoptosis (40, 41) and a misrepair of a double-strand break is the previous step to chromosome reorganizations, loss of chromosomal fragments, and/or complex reorganizations (42–46). In reproduction, these processes may occur in a similar way during gametogenesis and embryo development (47–49), as it is known that chromosome reorganizations may be present in germ cells, causing a higher risk of miscarriage and infertility (24, 50–52). Thus, we previously observed that alterations of dsSDF are related to a higher risk of recurrent pregnancy loss in couples experiencing natural pregnancy (25).
Inheritance of epigenetic dysregulation from male factor infertility has a direct impact on reproductive potential
2018, Fertility and SterilityCitation Excerpt :Likewise, ICSI circumvents fertilization failure for MF cases, but it also does not select against all possible deleterious effects arising from defective sperm DNA. Risks of implantation failure and repeated miscarriage are increased in couples with MF infertility (42–44). One study evaluating high-magnification sperm selection observed an increase in miscarriage rate from 1/12 (8.3%) in the non-MF group to 3/8 (37.5%) in the OAT (MF) group, although owing to limited sample numbers this statistic was not significant (P=.138) (45).
Ana Lara Caseiro has a Masters in Medicine, awarded in 2008 from the Faculty of Medical Sciences, New University of Lisbon; a Masters in Human Reproduction awarded in 2013 from the Faculty of Medicine, University of València and IVI – Instituto Valenciano de Infertilidad. Currently, she is a resident in the Department of Gynecology and Obstetrics at Évora's Hospital and an investigator in the Premya Study, about Esmya® (Ulipristal Acetate) and Alerta study (human contraception). She has presented multiple oral communications in national and international scientific meetings and is a member of several scientific societies: Federação das Sociedades Portuguesas de Obstetricia e Ginecologia (FSPOG), Sociedade Portuguesa de Cirurgia Minimamente Invasiva (SPCMIN) and Sociedade Portuguesa de Medicina da Reprodução (SPMR).