Review
Implication of sperm chromosomal abnormalities in recurrent abortion and multiple implantation failure

https://doi.org/10.1016/j.rbmo.2015.07.001Get rights and content

Abstract

Currently, some infertility treatment centres provide sperm karyotype analysis, although the impact of sperm chromosomal abnormalities on fertility is not yet fully understood. Several studies using fluorescence in-situ hybridization (FISH) to analyse sperm chromosomal constitution discovered that the incidence of aneuploidy is increased in individuals with a history of repeated abortion or implantation failure and is even higher in cases of oligoasthenoteratozoospermia (OAT), abnormal somatic karyotype or in spermatozoa retrieved directly from the testis or epididymis, showing that the application of FISH in these cases may be of some benefit for improving the reproductive outcome. This article presents the results of clinical trials of FISH analysis on spermatozoa, the medical indications for performing this examination, its results in infertile patients and the advantages when performing genetic counselling prior to treatment. Also discussed is the possibility of applying the latest techniques of genetic analysis in these cases and the potential benefits for improving the prognosis of male infertility.

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

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    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).

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