Pregnancy outcome and neonatal data of children born after ICSI using testicular sperm in obstructive and non-obstructive azoospermia

BACKGROUND: Registries on outcome of ICSI pregnancies obtained with testicular sperm do not differentiate between obstructive (OA) and non-obstructive azoospermia (NOA). We evaluated the pregnancy outcome and neonatal data on children born after ICSI using testicular sperm of men with histologically proven OA or NOA. METHODS: Pregnancies obtained after ICSI using testicular sperm of men with defined NOA (n = 70) were compared with those of men with OA (n = 204). RESULTS: Multiple birth rates in NOA and OA couples, respectively, were 21 versus 27% (P = NS), overall preterm delivery rates were 38 versus 26% (NS), and prematurity rates were 24 versus 13% for singletons (NS) and 86 versus 54% for twins (relative risk 1.59, 95% confidence interval 1.04-2.42). Median gestational age for singletons was 38.3 versus 39.3 weeks, respectively (P < 0.05). The low birth weight rates were 34 versus 31%, respectively (NS). The early perinatal mortality rate was 66 versus 15 per 1000 births, respectively, (NS). Major congenital malformations were observed in 4 versus 3%, respectively, of the live born babies (NS). Prenatal karyotypes showed 7% de-novo abnormalities in the NOA group versus 1% in the OA group (NS). CONCLUSIONS: Our data do not show differences between NOA and OA pregnancies except for a strong tendency towards a lower gestational age in singletons and a higher percentage of premature twins in the NOA group. Although our data are based on a limited sample, the differences observed call for further analysis. Given the low pregnancy rates after ICSI with NOA, a multicentre study, differentiating NOA and OA patients, would be recommended.     

Localisation of the gene causing diaphyseal dysplasia Camurati-Engelmann to chromosome 19q13

Camurati-Engelmann disease, progressive diaphyseal dysplasia, or diaphyseal dysplasia Camurati-Engelmann is a rare, autosomal dominantly inherited bone disease, characterised by progressive cortical expansion and sclerosis mainly affecting the diaphyses of the long bones associated with cranial hyperostosis. The main clinical features are severe pain in the legs, muscular weakness, and a waddling gait. The underlying cause of this condition remains unknown.In order to localise the disease causing gene, we performed a linkage study in a large Jewish-Iraqi family with 18 affected subjects in four generations. A genome wide search with highly polymorphic markers showed linkage with several markers at chromosome 19q13. A maximum lod score of 4.9 (theta=0) was obtained with markers D19S425 (58.7 cM, 19q13.1) and D19S900 (67.1 cM, 19q13. 2). The disease causing gene is located in a candidate region of approximately 32 cM, flanked by markers D19S868 (55.9 cM, 19q13.1) and D19S571 (87.7 cM, 19q13.4).     

Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF

BACKGROUND: Since the introduction of ICSI in 1991, medical outcome studies on ICSI children have been performed, but few have addressed developmental outcome. Hence, this outcome was assessed by performing a standard developmental test on children born after ICSI as compared with children born after IVF, at the age of 2 years. METHODS: In a prospective study, the medical and developmental outcome of 439 children born after ICSI (378 singletons, 61 twins) were compared with those of 207 children born after IVF (138 singletons, 69 twins), at the age of 24-28 months. These children were part of a cohort of children followed since birth. Of children reaching the age of 24-28 months between May 1995 and March 2002, 44.3% (2375/5356) were examined by a paediatrician who was unaware of the type of treatment used for each couple. Of all the children born, 12.2% (439/3618) in the ICSI group and 11.9% (207/1738) in the IVF group underwent a formal developmental assessment using the Bayley Scale of Infant Development (mental scale) by a paediatrician blinded to the type of treatment. RESULTS: There was no significant difference in maternal educational level, maternal age, gestational age, parity, birthweight, neonatal complication rate or malformation rate at 2 years between ICSI and IVF singletons, or between ICSI and IVF twins. No significant difference was observed in the developmental outcome using the Bayley scale at the age of 24-28 months (raw scores or test age) between ICSI children or IVF children. A multivariate regression analysis for the singleton children indicated that parity, sex (boys had lower scores than girls) and age had a significant influence on the test result, but that the fertility procedure (ICSI versus IVF) did not influence the test result. ICSI children from fathers with low sperm concentration, low sperm motility or poor morphology had a similar developmental outcome to that of children from fathers with normal sperm parameters. There were no significant differences between the initial cohort and the group lost to follow-up, nor between the psychologically tested and the non-tested group for a number of variables such as maternal educational level, birthweight in singletons and neonatal malformation rate. Although only some of the cohort of ICSI children were evaluated, a representative sample of both ICSI and IVF children was compared. CONCLUSIONS: There is no indication that ICSI children have a lower psychomotor development than IVF children. Paternal risk factors associated with male-factor infertility were found not to play a role in developmental outcome.     

High frequency of BRCA1/2 germline mutations in 42 Belgian families with a small number of symptomatic subjects

AIM: The initial risk assessments for BRCA1/2 mutation carriers and estimates of carrier frequencies were based on extended pedigrees with a large number of symptomatic subjects. When counselling based on BRCA gene mutation analysis was initiated, we faced requests for counselling mostly from members of small families with only two or three affected members. We report on the likelihood of finding a BRCA mutation in such small families. METHODS: In the first 100 families that came for oncogenetic counselling since September 1994, a BRCA1/2 gene mutation screen was initiated if there were two or more symptomatic first degree relatives, if one of them had ovarian cancer, or if one breast cancer was diagnosed before the age of 50 years. RESULTS: BRCA gene mutations were found and confirmed by sequencing in 14 out of 42 families (33%); 10 mutations were in the BRCA1 gene and four in the BRCA2 gene. Our findings indicate an increased probability of detecting a BRCA gene mutation when ovarian cancer occurred in the family. There is no increased probability of detecting a mutation with increasing numbers of breast cancers. Only 22% of the eligible presymptomatic family members opted for testing. The presymptomatic female carriers currently prefer breast surveillance rather than prophylactic surgery. CONCLUSION: BRCA1/2 gene mutation testing can be done with reasonable efficiency in the Belgian population when there are two symptomatic family members. The availability of testing does not lead to a high frequency of requests for testing by presymptomatic family members.     

Correlation between semen parameters and sperm aneuploidy rates investigated by fluorescence in-situ hybridization in infertile men

Spermatozoa from 32 infertile patients and 13 controls with normal semen parameters were analysed using dual and triple colour fluorescence in-situ hybridization (FISH) techniques, in order to investigate the rates of aneuploidy for chromosomes 13, 18, 21, X and Y. The patients were divided into three groups according to their karyotypes or the karyotypes of their offspring: 15 were infertile men with abnormal semen parameters and normal karyotypes (group 1), 13 were infertile men with abnormal karyotypes and normal or abnormal semen (group 2) and four were infertile men with abnormal semen and normal karyotypes but whose wives conceived a child (or a fetus) with a numerical chromosomal abnormality through an intracytoplasmic sperm injection cycle (group 3). Patients with abnormal semen parameters showed a significantly higher aneuploidy rate for the investigated chromosomes in their spermatozoa compared to controls (P < 0.005). Our data suggest the presence of a correlation between poor semen parameters and an increase in aneuploidy rate of chromosomes 13, 18, 21, X and Y in spermatozoa (r = -0.81071, P < 0.002); therefore the risk of a chromosomal aneuploidy in spermatozoa seems to be inversely correlated to sperm concentration and total progressive motility. Patients with abnormal karyotypes showed a higher incidence of diploidy and chromosomal aneuploidies compared to controls (P < 0.002). This strongly suggests the presence of an interchromosomal effect of the cytogenetic rearrangement. Men who fathered a child with an abnormal karyotype through intracytoplasmic sperm injection did not present a higher aneuploidy rate for the investigated chromosomes in spermatozoa compared to patients with infertility due to a similar male factor but showed higher incidence of chromosomal aneuploidy compared to normal controls.     

Epilepsy and Canon Law

The Canon Law (Codex Iuris Canonici), promulgated in 1917, was a classification of laws and jurisprudence which ruled the early Church, governed the ecclesiastical condition of Roman Church until its reorganisation in 1983. It forbade to be ordained or to exercise orders already received to "those who are or were epileptics either not quite in their right mind or possessed by the Evil One". All the context and in particular the paragraph which treated of bodily lacks, indicated that between these three conditions, there was juxtaposition and no confusion. The texts specified the foundations of these dispositions, not in a malefic view of epilepsy inherited from Morbus Sacer of Antiquity, but in decency and on account of risk incured by Eucharist in case of fit. Some derogations could attenuate the severity of these dispositions--as jurisprudence had taken progresses of Epileptology and therapeutics into consideration. In the new Code of Canon Law (1983) physical disabilities were removed from the text and also possessed evil and epilepsy, the only impediment being "insanity or other psychic defect" appreciation of which is done by experts. Concerning poorly controlled epilepsies, we believe that experts will be allowed to express their opinion and a new jurisprudence will make up for the silence of the law.