Serena Chen

Maternal age, morphology, development and chromosome abnormalities in over 6000 cleavage-stage embryos

Previous studies assessing the relationship between embryo development, maternal age and chromosome abnormalities were either small or analysed mostly embryos not suitable for replacement. The present study includes >6000 embryos, including many suitable for replacement. Embryos with the best morphology and development were 44% euploid in patients younger than 35, decreasing to 21% in patients 41 and older. The worst morphology group had only 30% normal embryos from patients younger than 35, and 12% in embryos from patients 41 and older. Thus morphological analysis was able to improve the population of normal embryos only from 30 to 44% in the best of cases. Regarding specific abnormalities, 20% of embryos were aneuploid, 32% aneuploid plus other abnormalities, and the rest had post-meiotic abnormalities. Of those, only aneuploidy increased with maternal age. There were no big differences in the frequency of chromosome abnormalities depending on patient indication, within a similar age group. In summary, previous trends detected in suboptimal embryos were also confirmed in the best embryos for replacement. Although dysmorphism and advanced maternal age are both related to chromosome abnormalities, these parameters can yield at most <50% euploid embryos, and other techniques such as preimplantation diagnosis are required to ensure that only euploid embryos are replaced.

The impact of LH-containing gonadotropins on diploidy rates in preimplantation embryos: long protocol stimulation

BACKGROUND The aim of this study was to evaluate the effect of ovarian stimulation with LH-containing gonadotropins (human menopausal gonadotropin, hMG), on ploidy of human cleavage-stage-embryos. METHODS A total of 104 women, at ages 27-43 years, undergoing one cycle of controlled ovarian hyperstimulation for IVF in combination with preimplantation genetic diagnosis, were eligible for enrollment in this retrospective, controlled cohort study. Ovarian stimulation included down-regulation with long agonist and stimulation with either recombinant FSH or hMG. Since the ploidy of embryos changes with female age, patients were matched for age and dosage of the respective gonadotropin. RESULTS Despite similar numbers of chromosomally normal embryos in both groups, women undergoing hMG stimulation demonstrated significantly higher percentages of diploid embryos than did the FSH-stimulated patients (69.8 versus 45.3%; P < 0.01). CONCLUSIONS Long protocol LH-containing ovarian stimulation improves embryonic ploidy in comparison to pure FSH stimulation. This observation may explain higher IVF pregnancy rates, reported for hMG stimulation in some studies.

Negligible interchromosomal effect in embryos of Robertsonian translocation carriers.

It has been suggested that translocations, and perhaps other chromosome rearrangements, disturb meiotic disjunction of chromosome pairs not involved in the translocation, resulting in non-disjunction in those chromosomes (interchromosomal effect) and predisposition to trisomy offspring. Other reports have suggested an increased risk of mosaicism and chaotic embryos in translocation carriers. This study was designed to determine if such interchromosomal effects are producing significantly more chromosome abnormalities than those expected from unbalanced gametes. For that purpose, two groups of PGD patients were compared, Robertsonian translocation carriers (RBT) and carriers of X-linked diseases (XLI), of similar age. Both groups were analysed by FISH with similar DNA probes. The results indicate that overall, the higher rate of chromosome abnormalities in the RBT group was solely due to unbalanced gametes and not to an interchromosomal effect or higher incidence of mosaicism. If unbalanced and normal were combined, this proportion was 53% in XLI and 59% in RBT. However, when specific RBT translocations were studied, only a slight increase in embryos with aneuploidy for chromosome 22 was found for the t(13;14) translocation carriers, while a higher rate of post-zygotic abnormalities was observed in the more rare RBT. In conclusion, the overall rate of non-translocation related abnormalities was not increased in the RBT group compared with the control group, but a slight interchromosomal effect may exist, as some Robertsonian translocations may be more prone to produce mosaic and chaotic embryos.

The impact of LH-containing gonadotropin stimulation on euploidy rates in preimplantation embryos: antagonist cycles.

OBJECTIVE To evaluate effects of luteinizing hormone (LH)-containing gonadotropins (human menopausal gonadotropin, hMG) on ploidy of human cleavage-stage embryos in gonadotropin releasing hormone (GnRH) antagonist cycles. DESIGN Retrospective matched cohort study. SETTING Two academically affiliated private fertility centers, private preimplantation genetics laboratory, and medical school. PATIENTS(S) One hundred four consecutive in vitro fertilization cycles (IVF) with preimplantation genetic diagnosis in women aged 30 to 45 years. INTERVENTION(S) Antagonist cycles with ovarian stimulation by either recombinant follicle stimulating hormone (FSH) alone, or in combination with human menopausal gonadotropin (FSH/hMG). MAIN OUTCOME MEASURE(S) After matching patients for age and gonadotropin dosage, embryo ploidy, pregnancy, and miscarriage rates were evaluated. RESULT(S) Euploidy rates (FSH, 29.4% vs. FSH/hMG, 25.7%) and number of euploid embryos (FSH, 2.1 +/- 1.6 vs. FSH/hMG, 1.9 +/- 1.5) were similar between both groups, although trended in favor of FSH-only stimulation. FSH-only stimulation, however, demonstrated significantly higher clinical pregnancy rates per cycle start (FSH: 34.6% vs. FSH/hMG: 11.5%) and per embryo transfer (FSH: 40% vs. FSH/hMG: 15%). CONCLUSION(S) Because this study involved mostly women of advanced reproductive age, at least in such an age category, LH-containing stimulation causes adverse effects on pregnancy rates, although whether such an adverse effect on ploidy exists in parallel requires further investigation. These observations point toward embryo-independent adverse effects on implantation (luteal phase) in antagonist cycles with hMG costimulation.