of aneuploidy in embryos and considered as a PGD indication in many countries. Our aim was to evaluate the gamete aneuploidy incidence in this situation in France, a country where PGD is not allowed for this indication. DESIGN: Gamete aneuploidy screening in different couples. MATERIALS AND METHODS: Population: 3 couples groups were considered: group 1 (n⫽11) control couples with pregnancy obtained after IVF with fertile sperm and female infertility, group 2 (n⫽20) couples with pregnancy obtained after IVF for male or idiopathic infertility, group 3 (n⫽32) couples with implantation failure. Methods: 1000 spermatozoa per patient were analysed by FISH (chromosome X, Y et 18 (Abbott) in the 3 groups. In group 3, 1st polar body (PB1) was also analysed by FISH with the Polar BodyTM PGT multicolour (Abbott) kit, in the 22 couples who accepted the procedure during ICSI. RESULTS: Sperm aneuploidy rate was increased in group 2 (1,6% ; p⬍0,0005) and 3 (2,1% ; p⬍0,001) in comparison to group 1 (0,6%). In group 3, 2 patients presented a very high aneuploidy rate (⬎5%) in spermatozoa (6,5% et 25%). This did not happen in group 1 and 2. 8/32 patients in group3 and 6/20 patients in group 2 exhibited a moderate but increased aneuploidy rate in sperm (between 2 and 5%). This did not happen in group 1. PB1 aneuploidy rate was high (average:35,4%) in the 127 PB1 analysed in group 3. For 3 patients, this rate was very high, more than 2/3 abnormal oocytes, analysing only 5 chromosomes! All together, 22% couples (5/22) had no particular chromosomal risk in gametes, 68% (15/22) presented an increased spermatic (⬎ 2%) or oocyte (⬎ 1/3) aneuploidy rate and 10% of couple (2/22) had both. CONCLUSION: Those results confirm that implantation failure has a heterogeneous origin and that gamete chromosome abnormality rate is one of the major factors explaining it. Genetic counselling seems to be necessary after those analyses and those results may influence the next ART attempts, and future pregnancy chance. Indeed, preconceptionnal and when possible preimplantation diagnosis can be indicated for these couple (78% in our series) with increased gamete aneuploidy risk and implantation failure. Supported by: UVSQ and Serono.
Monday, October 23, 2006 5:00 pm O-51 THE GENETIC FACTOR IN RECURRENT MISCARRIAGE. H. J. Carp. Depts of Obstetrics & Gynecology; Sheba Medical Center & Tel Aviv Univ, Tel Hashomer, Israel. OBJECTIVE: 1.) To assess the incidence of embryonic chromosomal aberrations in recurrent first trimester miscarriage, and subsequent prognosis. 2.) Whether parental karyotyping or pregestational screening (PGS) are valid substitutes. DESIGN: A computerized literature search was made of medline embase etc. using the relevant key words, and of our own database of 1800 patients. MATERIALS AND METHODS: The details of publications in the literature and of our own database were entered into a computerised database, (SPSS, Chicago, Ill.). The following questionswere asked:- 1). The prevalence of fetal chromosomal aberrations. 2). Outcome of the subsequent pregnancy. 3). Was repeat fetal aneuploidy reported. 4). Outcome of subsequent pregnancy in parental chromosomal aberrations. 5). Karyotype of the abortus in the presence of parental karyotypic aberrations. 6). Live birth rate and implantation rate in PGS and recurrent miscarriage. RESULTS: Five studies assessed fetal karyotyping in recurrent miscarriage. The mean number of miscarriages was 4.12⫾ 0.48. The incidence of fetal chromosomal aberrations varied between 25% - 57%, (mean 41.6% ⫾ 13.9). The prognosis for a subsequent pregnancy was available in two series. 62.9% (51 of 81) of pregnancies terminated in live births after aneuploidic abortions compared to only 37.9% (41 of 108) after euploid abortions (OR ⫽ 2.78, CI 1.47-5.27). Two papers provide information on repeat karyotyping. Only 11 of 73 patients (15%) aborted a second aneuploid abortion. There are three series on the prognosis in parental karyotypic aberrations. There was a 47.5% live birth rate in patients with a mean of 3.7 previous miscarriages. Additionally, one series has karyotyped the abortus in the presence of parental karyotypic aberrations. 27 of 39 (69%) abortuses were chromo-
somally normal. Hence, parental karyotyping does not provide a diagnosis or prognosis. Two series have shown that there is an increased prevalence of chromosomal aberrations at PGS, when the embryos of women with recurrent pregnancy loss are compared to controls (63% and 45% respectively). Although two series have shown a 74% live birth rate after PGS. The pregnancy rate was only 23%. CONCLUSION: There is no substitute for karyotyping the abortus in recurrent miscarriage, as this allows a diagnosis, and accurate prognosis to be made. Parental karyotyping is a poor substitute, as it does not make a diagnosis nor does it give a prognosis. PGS is of limited value, as some patients with recurrent miscarriage, and no infertility had been converted from miscarriage to implantation failure. However, PGS has a place in certain subgroups of patient including the older patient, and pregestational diagnosis has a place in the few patients with parental chromosomal aberrations who abort chromosomally abnormal embryos, and those with repeat embryonic aneuploidy. However, the definition of these subgroups depends on accuratel determination of the fetal karyotype. Supported by: There was no external financial support. Karyotyping of the abortus or parents was performed as part of the standaed work up of recurrent pregnancy loss.
Monday, October 23, 2006 5:15 pm O-52 THE RATE OF MOSAICISM IN PREGNANCIES FROM COUPLES WITH INFERTILITY. A. Huang, J. Adusumalli, S. Patel, L. Kao, J. Williams III, M. D. Pisarska. David Geffen School of Medicine at UCLA, Los Angeles, CA; Cedars-Sinai Medical Center, Los Angeles, CA; CedarsSinai Medical Center/David Geffen School of Medicine @ UCLA, Los Angeles, CA. OBJECTIVE: Mosaic embryos have been demonstrated in cases of preimplantation genetic diagnosis (PGD). Some embryos may develop into true mosaics, some abnormal cells may be eliminated through apoptosis resulting in a subsequent normal karyotype and others may develop into fetuses that have confined placental mosaicism (CPM). Since many cases of PGD are conducted in patients with infertility and mosaic embryos are not transferred, there is no available cytogenetic follow-up. We wanted to determine if this phenomena of mosaicism that occurs in cases of infertility and assisted reproductive technologies continues in the late first trimester and if this is unique to infertility and assisted reproductive technologies or is a normal process that occurs in all pregnancies. Thus, we set out to look at the rate of mosaicism in pregnancies from couples with infertility in the late first trimester through chorionic villus sampling (CVS) and compared them to spontaneously conceived pregnancies. DESIGN: Retrospective Case Controlled Study. MATERIALS AND METHODS: 5336 patients who underwent CVS at a single institution in the time period from 7/1999 to 12/2004. Depending on the operator’s judgment, CVS was performed either via a transabdominal or trans-vaginal approach, by one of two highly experienced perinatologists. All procedures were performed on ultrasound documented viable gestations between 9 and 12 weeks. Cytogenetic analysis was compared between groups. Data was analyzed using the Fisher’s Exact or Chi Square test with Yates correction whenever appropriate and the T-Test to compare means. RESULTS: Although the difference in age between the infertility group (39.4) and spontaneous conception group (39.1) was small, this result was statistically significant. (p ⫽ .01). When comparing spontaneous pregnancies with pregnancies achieved with fertility treatment, no difference was found in the rate of mosaicism, 1.25% vs. 1.18%, respectively (p ⫽ 1.00). Subgroup analysis of infertile couples, comparing in vitro fertilization (ART) with in vivo fertilization (other fertility treatments) revealed a rate of mosaicism of 1.62% compared to 0.41%, respectively. This was not statistically significant (p ⫽ .31). Among mosaic karyotypes, the majority were CPMs. The rates of CPMs for infertility treated pregnancies were 50% and 64% for spontaneously conceived pregnancies. Subgroup analysis of infertile patients revealed a CPM rate of 43% for in vitro fertilization and 100% for in vivo fertilization. There was no difference between the rates of true
Vol. 86, Suppl 2, September 2006