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Biomedical subjects

Jan Gerris

Publications and source records attributed to Jan Gerris.

6 recordsLinked to original sources

Human granulosa cells after ovulation induction show caspase-independent cell death.

It has become clear that apoptosis is an essential part of normal folliculogenesis and that granulosa cells in particular demonstrate intense cellular activity as well as programmed cell death. Although the entire mechanism of apoptosis appears to be conserved through many species, it now becomes clear that different cells may use different pathways within this system. We examined human granulosa cells after ovulation induction during an in vitro fertilization procedure to study apoptosis in this particular situation. We demonstrated a loss of cytokeratin staining as granulosa cells differentiate. We also detected that granulosa cells with apoptotic morphology did not stain for terminal deoxy-UTP nick end labeling and we showed the absence of immunoreactivity for caspase-cleaved cytokeratin, caspase-cleaved poly-ADP-ribose polymerase and caspase-cleaved caspase-3 in apoptotic granulosa cells. These data provide strong arguments for a caspase-independent cell death mechanism in human granulosa-lutein cells.

Apoptosis↗

Partial DAZ deletions in a family with five infertile brothers.

OBJECTIVE: To study the genetic cause of infertility in a family with five infertile brothers. DESIGN: Case report. SETTINGS: Center for reproductive medicine at a university medical center. PATIENT(S): Five brothers presenting with primary infertility due to severely impaired spermatogenesis; also, their parents and two other paternally related family members. INTERVENTION(S): Fluorescence in situ hybridization and sequence family variant analysis was performed in leukocyte DNA to determine the number of deleted in azoospermia (DAZ) genes. Linkage analysis was performed for X chromosome inheritance, and mitochondrial DNA (mtDNA) was screened for mutations. MAIN OUTCOME MEASURE(S): DAZ gene copy number, X chromosome linkage, and mtDNA sequence. RESULT(S): With conventional polymerase chain reaction (PCR) analysis, no deletions of the AZFc region were found, but with fluorescence in situ hybridization and sequence family variant analysis, only two DAZ genes instead of four were detected in all individuals tested. The five brothers did not share an identical X chromosomal locus, and no mutations were found in the mtDNA of the index patient. CONCLUSION(S): A reduced copy number of the DAZ genes is found in five infertile brothers with severely impaired spermatogenesis, as well as in their normospermic father and in two other fertile paternally related family members. This illustrates that the phenotype associated with a reduced copy number of the DAZ genes can be extremely variable.

Adult↗

Multinucleation in cleavage stage embryos.

BACKGROUND: The aim was to analyse multinucleation in relation to its incidence in time and in the population, and its correlation with clinical variables, with other morphological characteristics and with the implantation rate of cleavage stage embryos. METHODS: Retrospective analysis of 10 388 cleaved embryos from 1395 consecutive IVF/ICSI cycles in 700 patients between January 1, 1999 and June 30, 2002. RESULTS: Multinucleation was observed in 3491 (33.6%) embryos in 1107 cycles (79.4%) of 609 (87%) patients, more frequently on day 2 than on day 3: 2848 (27.4%) versus 1567 (15.1%) [relative risk (RR) = 1.82; 95% confidence interval (CI) = 1.72-1.92]. Its incidence increased with fragmentation: 31.0, 34.4 and 36.5% for fragmentation </=10%, 10-20% or 20-30%. It was increased in stimulation cycles that were shorter (34.9 versus 32.0%, RR = 1.09; 95% CI = 1.03-1.15), required a higher FSH dose (34.6 versus 32.0%, RR = 1.08; 95% CI = 1.02-1.14) and yielded more oocytes (34.5 versus 29.7%, RR = 1.16; 95% CI = 1.08-1.25). Four-cell embryos on day 2 showed minimal multinucleation (16.8%) as well as 8-cell embryos on day 3 (15.5%). Embryos counting both 4 blastomeres on day 2 and 8 on day 3 showed minimal multi nucleation (11.6%). Multinucleated embryos had a decreased implantation rate: 4.3% in single and 5.7% in double embryo transfers. CONCLUSIONS: Multinucleation is a frequently observed phenomenon. It is associated with impaired cleavage and increased fragmentation and is compromising the ongoing implantation rate. Multinucleation should be part of embryo assessment.

Adult↗

Elective single day 3 embryo transfer halves the twinning rate without decrease in the ongoing pregnancy rate of an IVF/ICSI programme.

BACKGROUND: Data on the effect of elective single embryo transfer (eSET) on the total and multiple pregnancy rates of an IVF/ICSI programme are reported. METHODS AND RESULTS: A retrospective cohort analysis of eSET was carried out over a 4 year period. A total of 1559 cycles resulted in 1464 transfers; 299 transfers of one top quality embryo (20.4%) and 86 of one non-top quality embryo (5.9%) yielded 149 conceptions (49.8%) with 105 ongoing pregnancies (35.1%) and 26 conceptions (30.2%) with 19 ongoing implantations (22.1%) respectively; 1079 transfers of two (n = 853; 58.3%) or more than two (n = 226; 15.4%) embryos yielded 366 ongoing pregnancies (33.9%). The ongoing pregnancy rates for the years between 1998 and 2001 were 35.9, 27.9, 31.9 and 31.0% per oocyte retrieval and 38.5, 29.4, 34.1 and 33.2% per transfer. There were no differences in pregnancy rates between any of the years. The average ongoing pregnancy rate (>12 weeks) over the 4 years was 31.5% per started cycle and 33.5% per transfer; the average number of embryos transferred decreased from 2.26 (1998) to 1.79 (2001); the multiple pregnancy and twinning rates dropped from 33.6 and 29.5% (1998) to 18.6 and 16.3% (2001) respectively. CONCLUSIONS: Judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate.

Adult↗

A health-economic decision-analytic model comparing double with single embryo transfer in IVF/ICSI.

BACKGROUND: Single embryo transfer (SET) is the sole strategy with which to reduce the incidence of twins following assisted reproductive technology (ART), but SET may increase the number of ART cycles needed per live-born child. Its cost-effectiveness compared with double embryo transfer (DET) is therefore unknown. METHODS: A decision-analytic model comparing SET with DET was developed. Estimates were obtained from literature, national pregnancy registers and local hospital records. A sensitivity analysis was performed, using pregnancy rates from four published studies. The outcome measure was the cost per child born, calculated from IVF procedure-related, pregnancy-related and neonatal care costs. Neonatal mortality and long-term morbidity costs were not taken into account. RESULTS: Independently of the pregnancy rates used, the SET cost per child born was in all instances the same as with DET, varying from EURO= 9520 (SET) versus EURO= 9511 (DET) to EURO= 12254 (SET) versus EURO= 12934 (DET). CONCLUSIONS: More ART cycles are required to obtain the same numbers of children born following SET compared with DET. Because SET allows the avoidance of twins and thus diminishes pregnancy-related and neonatal care costs, there is no difference in the cost per child born between SET and DET. The real advantage of SET is the avoidance of the very high long-term costs resulting from the increased morbidity of twins after birth.

Cost-Benefit Analysis↗