Prevalence of premature urinary luteinizing hormone surges in women with regular menstrual cycles and its effect on implantation of frozen-thawed embryos.

OBJECTIVE: To determine the frequency and effect of premature luteinizing hormone (LH) surges on pregnancy rates in women with regular menstrual cycles. DESIGN: Retrospective cohort study. SETTING: Assisted Reproductive Technology Program at private medical college. PATIENT(S): Regularly menstruating women undergoing frozen embryo transfer (ET). INTERVENTION(S): Detection of urinary LH surges with an RIA kit during natural-cycle frozen-embryos transfer. MAIN OUTCOME MEASURE(S): Incidence of premature LH surges and pregnancy outcomes. RESULT(S): Eighty-eight (46.8%) of 188 regularly menstruating women had premature LH surges and 33 (37%) of those 88 had multiple premature LH surges. Pregnancy rates per ET are similar between women with and without premature LH surges. CONCLUSION(S): A high percentage of normally cycling women demonstrate premature urinary LH surges without an effect on outcome of frozen-thawed ETs.

Algorithm to predict assisted reproductive technology pregnancy outcome reveals minimal embryo synergy.

A mathematical model was developed to calculate the implantation probability for individual embryos based on the pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cases with multiple embryos transferred. This model was used to calculate implantation probabilities of embryos of 31 morphological types using the outcome of 1,200 IVF/ICSI cases. The algorithm was validated by comparing the calculated pregnancy probability and multiple pregnancy probability with the actual outcome of 281 separate IVF/ICSI cases. Finally, an estimation of embryo synergy was calculated.

Preimplantation genetic diagnosis (PGD) for heritable neoplasia.

UNLABELLED: Especially applicable for heritable neoplasia, preimplantation genetic diagnosis (PGD) is possible for any Mendelian disorder whose gene has been localized, whether the molecular basis is known or not. METHODS AND RESULTS: PGD requires DNA from gametes (oocytes) or embryos before 6 days postconception, when implantation occurs. Approaches include 1) polar body biopsy, 2) blastomere biopsy (aspiration of one or two cells from the six- to eight-cell embryos at 2 or 3 days), and 3) trophectoderm biopsy, which allows recovery of 20 or more cells (20-50) from 125- to 150-cell, 5- to 6-day blastocysts. Of some 6000 PGD cycles worldwide, approximately 1500 have been performed for Mendelian indications. The approximately 25% live birth rates following PGD parallel the general U.S. experience for assisted reproductive technology. PGD has been accomplished for both cancer-specific disorders like adenomatous polyposis coli (APC), BRCA1, retinoblastoma, Li-Fraumeni syndrome, and von Hippel-Lindau syndrome (VHL), as well as disorders predisposing to neoplasia (Fanconi anemia, Wiskott-Aldrich syndrome). PGD also makes possible the identification and, hence, transfer of embryos of specific HLA genotypes. This allows cord blood harvesting for stem cell implantation into a moribund child, often an older sibling of the fetus. CONCLUSIONS: PGD is a complex, but achievable, approach especially applicable to Mendelian forms of neoplasia. PGD is an attractive addition to the prenatal diagnostic armamentarium, especially relevant to heritable neoplasia. PGD also makes possible novel indications having special relevance to heritable neoplasia.

Pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection with profound teratospermia.

OBJECTIVE: To assess the pregnancy outcome of IVF with intracytoplasmic sperm injection (ICSI) in couples with profound teratospermia (Kruger's strict criteria of zero). DESIGN: Retrospective analysis of 545 consecutive cycles of IVF/ICSI performed between January 2000 and January 2003. SETTING: Tertiary care center. PATIENT(S): Of 545 IVF/ICSI cycles, 45 patients were identified with a semen strict morphology of 0 using Kruger's strict criteria. INTERVENTION(S): Ovarian down-regulation (Lupron) was followed by controlled ovarian stimulation exclusively with hMG. Embryo transfer was performed 2 days after transvaginal aspiration/ICSI. MAIN OUTCOMES MEASURE(S): Pregnancy outcomes and newborn/infant status. RESULT(S): Of 45 patients undergoing 54 treatment cycles, 21 patients were positive for pregnancy (38.9% pregnancy/cycle). No birth defects were noted at time of delivery and all infants had obtained appropriate developmental milestones at 1 year of age. CONCLUSION(S): Men with profound teratospermia (Kruger's strict criteria of zero) may achieve acceptable pregnancy rates after IVF/ICSI thereby alleviating the use of donor sperm in this group. Furthermore, no increased risk of birth defects is apparent in this small series.

Nuclear chromosomal localization in human preimplantation embryos: correlation with aneuploidy and embryo morphology.

BACKGROUND: Spatial organization of chromosomes is hypothesized to reflect transcriptional activity and regulatory protein function. Preimplantation genetic diagnosis allows assessment of the spatial relationship of chromosomes in human blastomeres. We thus examined the localization of chromosomes 13, 16, 18, 21, 22, X and Y in blastomeres from 6-8-cell stage embryos, correlating localization to aneuploidy and embryo morphology. METHODS: Following fluorescence in situ hybridization to enumerate chromosomes 13, 16, 18, 21, 22, X and Y, signal positions were localized within one of four concentric shells. Statistical analysis compared chromosome localization between euploid and aneuploid blastomeres as well as morphologically normal and abnormal embryos. RESULTS: Of 98 embryos, 109 blastomeres were evaluated. Within chromosomally normal blastomeres, no difference in the location of all seven chromosomes (P

Paternal gonadal mosaicism detected in a couple with recurrent abortions undergoing PGD: FISH analysis of sperm nuclei proves valuable.

Many couples are now seeking preimplantation genetic diagnosis (PGD) and fluorescence in-situ hybridization (FISH) as an alternative approach to avoid spontaneous abortion by ensuring transfer of presumed chromosomally normal embryos. This case report describes unexpected findings in a couple having three spontaneous abortions and two failed IVF cycles. In two IVF PGD cycles, four of 13 (30.8%) embryos (blastomeres) demonstrated duplication involving the Down syndrome critical region, detectable by a locus specific chromosome 21 probe. The same duplication was subsequently detected by FISH in 66 of 1002 (6.6%) sperm nuclei, demonstrating paternal gonadal mosaicism. Cytogenetic studies of peripheral blood revealed normal karyotypes in both the male and female partners. This identification of paternal germ cell or gonadal mosaicism suggests that analysis of sperm nuclei prior to undergoing IVF with PGD may be of value in patients with recurrent spontaneous abortions or multiple failed IVF.