S. Egozcue

Screening for abnormalities of chromosomes X, Y, and 18 and for diploidy in spermatozoa from infertile men participating in an in vitro fertilization-intracytoplasmic sperm injection program

OBJECTIVE To evaluate the frequency of disomy (for chromosomes X, Y, and 18) and of diploidy in the spermatozoa of infertile men undergoing intracytoplasmic sperm injection (ICSI). DESIGN Prospective analysis of sperm nuclei by fluorescence in situ hybridization (FISH). SETTING University-affiliated IVF-ICSI program. PATIENT(S) Semen samples from 19 patients participating in an IVF-ICSI program. INTERVENTION(S) Semen samples were analyzed and prepared for FISH. MAIN OUTCOME MEASURE(S) Semen parameters were evaluated. The frequency of disomy for chromosomes X, Y, and 18 and the frequency of diploidy were analyzed by FISH. RESULT(S) A total of 9,373 spermatozoa from 19 infertile patients were analyzed and compared with spermatozoa from a control group of 5 healthy men. No differences in the frequency of disomy 18 were found, but statistically significant differences in the incidence of sex chromosome disomy and of diploidy were observed. CONCLUSION(S) The study of sperm nuclei by FISH is useful to improve genetic counseling in infertile patients selected for ICSI.

Genetic Analysis of Sperm and Implications of Severe Male Infertility—A Review

The use of fluorescence in situ hybridization (FISH) on decondensed sperm heads has allowed to analyse the chromosome constitution of spermatozoa in different populations. In controls, the mean incidence of disomy (including all chromosomes) is about 6.7 per cent; diploidy increases with age, and some individuals may show a special tendency to nondisjunction. Carriers of numerical sex chromosome anomalies show a low incidence of sex chromosome disomies (2.54-7.69 per cent), and the need to screen ICSI candidates for these conditions has to be reconsidered. Carriers of inversions produce from 0 to 54.3 per cent abnormal sperm. Carriers of Robertsonian translocations produce from 3.4 to 36.0 per cent abnormal sperm, and carriers of reciprocal translocations produce from 47.5 to 81.0 per cent abnormal spermatozoa. However, carriers of translocations usually produce more abnormal embryos than expected from these figures. This may be partly related to interchromosomal effects induced by some structural reorganizations. Males with oligoasthenozoospermia, low motility and/or high FSH concentrations show frequent synaptic anomalies, resulting in the production of aneuploid and diploid sperm. Testicular sperm show extremely high rates of chromosomal abnormalities. The risk of recurrent abortion is increased by the presence of chromosome abnormalities in sperm.

Meiotic abnormalities in infertile males

Meiotic anomalies, as reviewed here, are synaptic chromosome abnormalities, limited to germ cells that cannot be detected through the study of the karyotype. Although the importance of synaptic errors has been underestimated for many years, their presence is related to many cases of human male infertility. Synaptic anomalies can be studied by immunostaining of synaptonemal complexes (SCs), but in this case their frequency is probably underestimated due to the phenomenon of synaptic adjustment. They can also be studied in classic meiotic preparations, which, from a clinical point of view, is still the best approach, especially if multiplex fluorescence in situ hybridization is at hand to solve difficult cases. Sperm chromosome FISH studies also provide indirect evidence of their presence. Synaptic anomalies can affect the rate of recombination of all bivalents, produce achiasmate small univalents, partially achiasmate medium-sized or large bivalents, or affect all bivalents in the cell. The frequency is variable, interindividually and intraindividually. The baseline incidence of synaptic anomalies is 6–8%, which may be increased to 17.6% in males with a severe oligozoospermia, and to 27% in normozoospermic males with one or more previous IVF failures. The clinical consequences are the production of abnormal spermatozoa that will produce a higher number of chromosomally abnormal embryos. The indications for a meiotic study in testicular biopsy are provided.

Increased Incidence of Meiotic Anomalies in Oligoasthenozoospermic Males Preselected for Intracytoplasmic Sperm Injection

AbstractPurpose: Based on data from the literature, to detect thepossible presence of an increased frequency of meiotic anomaliesin oligoasthenozoospermic (OA) patients preselectedfor intracytoplasmic sperm injection. Methods: Meiotic studies in as many successive patientswith a clinical indication for a diagnostic testicular biopsyas needed to complete at least 100 cases with a severe OA(motile sperm concentration ≤1.5 × 106/ml). Results: An increased incidence of meiotic anomalies wasfound in 102 patients with a severe OA (17.6%) comparedto the mean for 105 patients with other etiologies in theseries (5.7%) or the mean for patients reviewed in the literature(6.5%). Conclusions: Patients with a severe OA have a higher incidenceof synaptic anomalies. This may result in themalsegregation of chromosomes at meiosis I, producingabnormal sperm, and could explain the high incidence ofsterility and some cases of abortion (in two thirds of thecouples with abortions the husband had meiotic anomalies)in this group.

Spermatogenic Patterns and Early Embryo Development After Intracytoplasmic Sperm Injection in Severe Oligoasthenozoospermia

AbstractPurpose: Evaluate the influence of different baseline spermatogenic patterns [meiotic pattern (normal or abnormal), sperm concentration ( > 1 × 106/mL or ≤1 × 106/mL), and the combined meiosis–sperm concentration pattern] on early embryo development in severe oligoasthenozoospermia. Methods: Embryo outcomes (fertilization rate, cleavage rate, and ≥4-cell stage embryo division rate on day 2) after IVF–ICSI in 75 oligoasthenozoospermia and 79 normozoospermic males. Results: The embryo division rate was significantly lower in oligoasthenozoospermia compared to normozoospermia (50.43% vs. 58.72%, p < 0.01) and in the oligoasthenozoospermia group for meiotic anomalies (43.40%), sperm concentration ≤1 × 106/mL (44.35%), and the combined pattern ≤ 1 × 106/mL with meiotic anomalies (37.17%). Logistic regression analysis showed a synergic effect (OR = 2.00; 95% CI = 1.28–3.12) when the two spermatogenic patterns predictive of slow embryo development [meiotic anomalies (OR = 1.49; 95% CI = 1.03–2.15) and sperm concentration ≤ 1 × 106/mL (OR = 1.53; 95% CI = 1.09–2.13)] were present. Conclusions: The data suggest that the early embryonic developmental capacity is inversely related to the severity of spermatogenic impairment (meiotic anomalies and/or sperm concentration ≤ 1 × 106/mL).

Outcome of intracytoplasmic sperm injection in relation to the meiotic pattern in patients with severe oligoasthenozoospermia

OBJECTIVE The aim of the study was to evaluate the intracytoplasmic sperm injection outcome in a selected group of patients with oligoasthenozoospermia in relation to the results obtained from their meiotic analysis. DESIGN Retrospective clinical study. SETTING An assisted reproduction service and a university department. PATIENT(S) One hundred thirty-seven men with oligoasthenozoospermia grouped in relation to their meiotic pattern. INTERVENTION(S) Two hundred twenty-four intracytoplasmic sperm injection cycles from 137 men with oligoasthenozoospermia in whom diagnostic meiotic analyses had been performed. MAIN OUTCOME MEASURE(S) Fertilization, pregnancy, implantation, and abortion rates. RESULT(S) There were no significant statistical differences in fertilization, pregnancy, implantation, or abortion rates among the three groups studied. CONCLUSION(S) No statistically significant differences in fertilization, pregnancy, implantation, or abortion rates were found in patients with oligoasthenozoospermia in relation to the meiotic pattern.

Estimación del riesgo de aneuploidías para los cromosomas sexuales en un paciente 46,XY/47,XXY candidato a fecundación in vitro con microinyección intracitoplasmática espermática

Resumen Se presenta un embarazo conseguido tras microinyeccion intracitoplasmatica de espermatozoides del eyaculado de un paciente con sindrome de Klinefelter mosaico. El mosaicismo observado en celulas germinales premeioticas estaba invertido con respecto al observado en sangre periferica. A partir de los estudios meioticos y de hibridacion in situ (FISH) en espermatozoides, se estimo que el riesgo genetico del paciente para la transmision de gonosomopatias a la descendencia era equivalente a la de la poblacion control, aconsejandose un ciclo de fecundacion in vitro con microinyeccion intracitoplasmatica espermatica y posterior diagnostico prenatal en caso de gestacion Por desgracia, el embarazo no llego a termino. Los pacientes con sindrome de Klinefelter deben ser estudiados con detalle antes de realizar un ciclo de fecundacion in vitro con microinyeccion intracitoplasmatica espermatica. En estos pacientes se recomiendan los estudios meioticos y de FISH en espermatozoides eyaculados o testiculares, asi como diagnostico prenatal. El diagnostico genetico preimplantacional puede recomendarse solo en casos de alto riesgo genetico