Biomedical subjects

Robert P S Jansen

Publications and source records attributed to Robert P S Jansen.

5 recordsLinked to original sources

PubMed2005

Pregnancies and live births after trophectoderm biopsy and preimplantation genetic testing of human blastocysts.

OBJECTIVE: To compare multiple-cell trophectoderm biopsy for preimplantation genetic diagnosis (PGD) from day-5 blastocysts with previously published experience with day-3 cleavage-stage embryos. DESIGN: Retrospective review of laboratory and clinical experience. SETTING: Sydney IVF, a private clinic in Australia. PATIENT(S): Preimplantation genetic diagnosis (PGD) patients age < 44 years with at least one IVF blastocyst suitable for biopsy, recruited from January 2002 through August 2004. INTERVENTION(S): Biopsy of trophectoderm from blastocysts on day 5 or 6, with same-day PGD for mutation testing, translocation testing, aneuploidy screening or sex selection. Spare, normal biopsied blastocysts were cryostored for possible later transfer. MAIN OUTCOME MEASURE(S): Fetal heart-positive pregnancy rate and accumulating live birth rate after adding results from biopsied fresh and frozen blastocysts for particular couples. RESULT(S): In 231 started PGD treatment cycles, unambiguous results were obtained from 974 of 1,050 biopsied blastocysts (93%); all blastocysts survived the biopsy procedure by reconstitution of their blastocele. One hundred nineteen women (median age, 36 years) have had 127 blastocysts transferred fresh (fetal heart-positive implantation rate, 41%). Of 146 blastocysts cryostored, 27 have been thawed (all with > 50% cell survival) and 24 transferred (implantation rate, 26%). To date, 53 pregnancies have been delivered or are ongoing, with an additional 4 clinical miscarriages (7%) and 6 subclinical miscarriages (total miscarriage rate, including biochemical pregnancies, 16%). There were no twin pregnancies. CONCLUSION(S): With technically appropriate blastocyst culture and freezing, blastocyst biopsy and cryostorage and later transfer of biopsied blastocysts is shown to be a practical and probably preferable path to preimplantation genetic testing of embryos compared with cleavage-stage embryo biopsy, being accompanied by a high implantation rate (and hence more conducive to elective single embryo transfer) and by a low rate of twinning and miscarriage.

Aneuploidy↗

PubMed2005

Elective transfer of single fresh blastocysts and later transfer of cryostored blastocysts reduces the twin pregnancy rate and can improve the in vitro fertilization live birth rate in younger women.

OBJECTIVE: To determine the extent to which embryo selection by blastulation and elective single blastocyst transfer, supported by efficient cryostorage of spare embryos, can reduce multiple pregnancies and maintain or improve on the live birth rate from IVF. DESIGN: Prospective, nonrandomized cohort study. SETTING: Sydney IVF, a private clinic in Australia. PATIENT(S): In vitro fertilization patients aged <38 years with three or more usable blastocyst, recruited from April 2000 through December 2001, with pregnancies followed up until August 2004. INTERVENTION(S): Blastocysts were cultured and cryostored with stage-specific culture medium and low oxygen conditions. MAIN OUTCOME MEASURE(S): Fetal heart-positive twin pregnancy rate and accumulating "take-home baby" rate per retrieval leading to blastocyst transfer. RESULT(S): Among 121 women who elected single fresh blastocyst transfer (but who could elect to have two frozen blastocysts transferred at once), 79 (65.3%) took home a baby, with a twin pregnancy rate of 7%. Among 285 women who chose two blastocysts for fresh transfer, 184 (64.2%) took home at least one baby, with a twin pregnancy rate of 34% and five perinatal deaths. CONCLUSION(S): With technically appropriate blastocyst culture and freezing, and elective single blastocyst transfer in the fresh cycle, the overall multiple pregnancy rate can be reduced by >75%, permitting in this series a slight increase in the chance of taking home a baby.

Adult↗

PubMed2004

Mitochondrial dysfunction in reproduction.

The mitochondrial genome passes from one generation to the next by way of the egg's cytoplasm, so ordinarily an individual's mitochondrial DNA (mtDNA) is entirely derived from his or her mother. A potential mother has a finite number of eggs, or oocytes, all of which were formed when she herself was still a fetus, many years before she can conceive. The eggs are progressively depleted through childhood and her reproductive years at a much faster rate than is accounted for by ovulation. Up to a decade before the ultimate depletion of ovarian follicles (and hence oocytes) at or soon after menopause, cytoplasmic senility of the remaining eggs leads to physiological sterility; a phenomenon that is suspected of being mitochondrially based and has been termed the oopause. When ovulation and conception occur, oxidative phosphorylation and other mitochondrial functions of the fertilized oocyte are thought to be essential to the early embryo well before it implants in the uterus. The competition between follicles to deliver the oocyte that will be fertilized and which will found a new generation could also be mitochondrially based, but the mechanism remains to be elucidated. Increasing experience with the culture of human embryos in vitro is highlighting the importance of mitochondrial metabolism generally, and the avoidance of excessive generation of reactive oxygen species in particular. Paradoxes abound in the experimental data, however. Although natural selection operates on mitochondria only in females (and in extreme cases through the survival of their offspring), reproductive disturbance from mitochondrial mutations is most obvious in males, who typically have reduced sperm motility. mtDNA point mutations such as T8993G, which is serious enough to cause the death of infants from Leigh disease in the first few years of life, can carry through the female germ line apparently unhindered; yet mtDNA deletions that cause a less severe phenotype, and which typically manifest at a later age, are effectively blocked from transmission to offspring--a phenomenon in accord with early experimental observations that deleted mtDNA species are less common in cleaving embryos than in unselected preovulatory oocytes. A mitochondrial basis for ooplasmic aging has not been convincingly established, but the novel IVF-based practice of micro-aspiration and transfer of ooplasm from younger eggs to older eggs, which includes the transfer of mitochondria, appears in preliminary studies to have some clinical efficacy in rejuvenating fertility in older women.

Journal Article↗

PubMed2004

Moving to blastocyst biopsy for preimplantation genetic diagnosis and single embryo transfer at Sydney IVF.

Developments at Sydney IVF in the successful culture of blastocysts, combined with day 5 or 6 blastocyst biopsy and blastocyst cryostorage after biopsy, permit up to five or six cells to be genetically tested, leaving the inner cell mass intact and enabling embryos to be electively transferred one at a time. These advantages can be obtained without diminishing the chance of pregnancy compared with cleavage-stage biopsy and testing.

Biopsy↗

PubMed2003

The effect of female age on the likelihood of a live birth from one in-vitro fertilisation treatment.

OBJECTIVE: To determine the chance of at least one live birth from one round of in-vitro fertilisation (IVF) treatment and the effect of the woman's age on that likelihood. DESIGN: Retrospective analysis of outcomes from IVF treatment that did not involve donated gametes, but which included embryos cryopreserved in the retrieval cycle. SETTING AND PATIENTS: All IVF patients (median age, 36 years; range, 22-48 years) who attended a private IVF clinic in Sydney for an egg retrieval between 1 January 1998 and 31 December 1998, and had embryo placements (fresh and cryostored) performed up to 30 June 2001. MAIN OUTCOME MEASURE: Independently audited live births surviving the neonatal period. RESULTS: 565 women had 648 egg retrievals during the period. The age of peak utilisation of IVF was 39 years. For women aged 34 years or less, the chance of a live birth from one round of egg retrieval and IVF treatment was 52.4% (95% CI, 47%-59%). For women aged 35-44 years, there was a linear decline in the live birth rate, and no babies were born from retrievals at age 45 years and over. There was an age-dependent rise in the frequency of miscarriages, from 10.5% (95% CI, 5%-18%) for women under 35 years, to 16.1% (95% CI, 9%-25%) for those 35-39 years, and 42.9% [95% CI, 24%-63%] for those over 40 years (P < 0.001). A third of the first births resulted from embryo transfers performed after a period of cryostorage. CONCLUSION: As fertility with IVF falls from the age of 34 years, and the age of peak IVF utilisation is 39 years, many Australian women are seeking IVF at an age when the likelihood of a live birth is reduced.

Abortion, Spontaneous↗