Elvire Van Assche

Embryo implantation after biopsy of one or two cells from cleavage-stage embryos with a view to preimplantation genetic diagnosis

Preimplantation genetic diagnosis (PGD) can be offered as an alternative to prenatal diagnosis (PND) to couples at risk of having a child with a genetic disease. The affected embryos are detected before implantation by fluorescent in situ hybridisation (FISH) for sexing (X‐linked diseases) and chromosomal disorders (numerical and structural) or by polymerase chain reaction (PCR) for monogenic disorders (including some X‐linked diseases). The accuracy and reliability of the diagnosis is increased by analysing two blastomeres of the embryo. However, the removal of two blastomeres might have an effect on the implantation capacity of the embryo. We have evaluated the implantation of embryos after the removal of one, two or three cells in 188 PGD cycles where a transfer was done. The patients were divided into five groups: a first group which received only embryos from which one cell had been removed, a second group which received only embryos from which two cells had been removed, a third group which received a mixture of embryos from which one and two cells had been taken, a fourth group where two and three cells had been removed, and a fifth group where three cells had been removed. The overall ongoing pregnancy rate per transfer was 26.1%, the overall implantation rate per transfer was 15.2% and the overall birth rate was 14.2%. Although pregnancy rates between the groups cannot be compared because the second group (two cells removed) contains more rapidly developing and therefore ‘better quality’ embryos, an ongoing pregnancy rate of 29.1% and an implantation rate of 18.6% per transferred embryo in this group is acceptable, and we therefore advise analysing two cells from a ≥7‐cell stage embryo in order to render the diagnosis more accurate and reliable. Copyright

An excess of chromosome 1 breakpoints in male infertility.

In a search for potential infertility loci, which might be revealed by clustering of chromosomal breakpoints, we compiled 464 infertile males with a balanced rearrangement from Mendelian Cytogenetics Network database (MCNdb) and compared their karyotypes with those of a Danish nation-wide cohort. We excluded Robertsonian translocations, rearrangements involving sex chromosomes and common variants. We identified 10 autosomal bands, five of which were on chromosome 1, with a large excess of breakpoints in the infertility group. Some of these could potentially harbour a male-specific infertility locus. However, a general excess of breakpoints almost everywhere on chromosome 1 was observed among the infertile males: 26.5 versus 14.5% in the cohort. This excess was observed both for translocation and inversion carriers, especially pericentric inversions, both for published and unpublished cases, and was significantly associated with azoospermia. The largest number of breakpoints was reported in 1q21; FISH mapping of four of these breakpoints revealed that they did not involve the same region at the molecular level. We suggest that chromosome 1 harbours a critical domain whose integrity is essential for male fertility.

Genetic Problems and Congenital Malformations in 1987 ICSI Children

When assisted fertilization and intracytoplasmic sperm injection (ICSI) were introduced, there was major concern about the safety of the newly introduced technique. Intracytoplasmic sperm injection is indeed a more invasive procedure than routine IVF because one spermatozoon is injected through the oo-cyte membrane and because fertilization can be obtained from sperm that could never have been used before in fertility treatment. Even more questions arose and concern was again expressed when ICSI with nonejaculated spermatozoa, either epidididymal or testicular, was introduced. Emphasis was put on the fact that because more chromosomal aberrations are found in azoospermic males and more in particular in case of nonobstructive azoosper-mia, the risk for chromosomal aberrations in the offspring might even be higher. Other heritable genetic causes might also be involved. On the other hand, it was suspected that imprinting may be less complete at the time of fertilization if testicular sperm is used. If this were so, then it would be unlikely to impair fertilization and early development, but anomalies might become manifest at birth or only later in life.