1 Clinical Genetics Center Utrecht, 2 University Hospital Utrecht, 3 University Hospital Nijmegen, 4 Elisabeth Hospital, Tilburg, 5 Streeklaboratorium Enschede, 6 Academic Medical Center, Amsterdam, 7 University of Groningen, 8 University of Maastricht, 9 University Hospital Leiden, 10 St. Erfelijkheidsonderzoek Noord Brabant, Veldhoven, 11 University Hospital Dijkzigt, Rotterdam and 12 University Hospital, Vrije Universiteit, Amsterdam,The Netherlands
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Abstract |
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Key words: chromosome abnormality/follow-up/intracytoplasmic sperm injection (ICSI)/male infertility/oligoasthenoteratozoospermia (OAT)
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Introduction |
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Some of the chromosome abnormalities found in infertile men can also be found in fertile men. These men have a chance of transmitting such an abnormality to their children. For example, carriers of balanced translocations can produce offspring with either a normal, a chromosomally balanced or a chromosomally unbalanced karyotype. In the latter case this can result in an early developmental embryonic arrest, a spontaneous abortion, a still birth or birth of a child with a combination of (multiple) congenital anomalies and psychomotor retardation. The risk of producing such unbalanced offspring depends on which chromosomes are involved and on the extent of the chromosomal imbalance (Stengel-Rutkowski et al., 1988; Daniel et al., 1989
). Since infertile men may now take advantage of intracytoplasmic sperm injection (ICSI) to reproduce, it is assumed that the risk of producing unbalanced offspring for these men is at least as high as it is for fertile men with the same chromosome abnormality. In addition, infertile men could pass on other yet unknown genetic factors causing infertility to their offspring via the ICSI procedure. Couples asking for this treatment must be counselled carefully on the genetic risks of this technique (In't Veld et al., 1997;
Pauer et al., 1997
; Wilkins-Haug et al., 1997
; Tuerlings et al., 1998
).
The aim of the study was to assess the impact of the finding of a chromosome abnormality on the couple's decision whether or not to proceed with the ICSI procedure.
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Materials and methods |
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We determined: (i) whether the ICSI couples chose to proceed with the ICSI treatment; (ii) whether ICSI had resulted in a pregnancy: and (iii) where a pregnancy was achieved, whether they had opted for invasive prenatal diagnosis. We did not collect data on the individuals' motivation or reasons for refraining from ICSI treatment, or for proceeding and opting for prenatal diagnosis. If no prenatal karyotyping had been performed, we investigated whether postnatal karyotyping had been carried out. Results of prenatal and postnatal karyotyping were recorded. The number of treatment cycles performed in order to achieve a pregnancy was not recorded.
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Results |
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In cases of ACA, 25 (54%) of the couples proceeded with ICSI treatment, 13 (28%) refrained from it and eight (18%) are still in doubt. Of the six pregnancies, prenatal diagnosis was performed in three cases and again in one case we have no information.
Thus, in total, 23 couples (31%) have decided to refrain from further ICSI treatment, whereas 42 couples (56%) have decided to proceed. Ten couples (13%) have not yet decided. Of the couples who underwent ICSI treatment, pregnancies have resulted in 11 cases so far. In four of these, the couples opted for invasive prenatal diagnosis. In these four cases, either a cytogenetically normal or a balanced karyotype was found in the fetus: 46,XX in the case of a male with an SCA, 45,XY,der(13;15) (q10;q10) and twice 45,XY,der(13;14) (q10;q10) in cases of male Robertsonian translocations. In one case of a male with an SCA, postnatal chromosome analysis in the child revealed a normal karyotype (46,XY).
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Discussion |
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Out of a total of 75 couples, 23 (31%) of them definitively refrained from ICSI treatment and 10 (13%) are still in doubt. We thought that the option of invasive prenatal diagnosis might be an important factor for the majority of couples (42) in deciding to proceed with ICSI treatment. This does not appear to be the case, as couples opted to have prenatal diagnosis in only four of the 11 pregnancies achieved. However, we are not aware in how many of these pregnancies detailed ultrasound investigation was performed and what the influence was of the availability of ultrasound investigation on the decision whether or not to have invasive prenatal diagnosis.
Although the phenotype of a child with an ACA is expected to be more severe than that of a child with an unbalanced SCA (as was discussed with the couples prior to ICSI), there are no major differences between couples with male SCA and with male ACA as to their decision to proceed with the treatment (59% versus 54% respectively). However, it appears that the number of pregnancies in the SCA group is higher (five in 17 couples) than in the ACA group (six in 25 couples). In a study by Montag et al. (1997) significantly lower fertilization, implantation and pregnancy rates were found in eight couples with a male constitutional chromosome abnormality than in controls. Though we do not have all the data on the number of treatment cycles, fertilization and implantation rates in our patients, the number of pregnancies (11 in 42 couples) appears to be higher than that in the study by Montag et al. (one in eight couples) but still may be decreased compared with that of controls. More couples from the ACA group opted for prenatal diagnosis (three out of six versus one out of five in the SCA group). The numbers are too small to draw definitive conclusions.
All 75 couples with a karyotypically abnormal male had been extensively counselled and informed about the increased risk of having a chromosomally abnormal child. It should be noted that we have no data on the interpretation by the potential parents of the information given to them in counselling and the meaning that the risk has for them. Thus, we cannot say whether or not the couples felt that they were taking a great risk. Either way, it appears that a small majority of the infertile couples were prepared to bring about a pregnancy despite having been counselled about an increased genetic risk. Once a pregnancy was achieved, most of them were not prepared to put the pregnancy at risk by carrying out prenatal diagnosis. In our view, careful genetic counselling is needed before ICSI is considered, in order to ensure that the couples are well informed before they make a decision.
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Notes |
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References |
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Pauer, H.U., Hinney, B., Michelmann, H.W. et al. (1997) Relevance of genetic counselling in couples prior to intracytoplasmic sperm injection. Hum. Reprod., 12, 19091912.[Abstract]
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Tuerlings, J.H.A.M., De France, H.F., Hamers, A. et al. (1998) Chromosome studies in 1792 males prior to intra-cytoplasmic sperm injection: The Dutch experience. Eur. J. Hum. Genet., 6, 194200.[ISI][Medline]
Wilkins-Haug, L.E., Rein, M.S. and Hornstein, M.D. (1997) Oligospermic men: the role of karyotype analysis prior to intracytoplasmic sperm injection. Fertil. Steril., 67, 612614.[ISI][Medline]
Submitted on April 2, 1998; accepted on September 30, 1998.