Carles Giménez

In vitro fertilization plus preimplantation genetic diagnosis in patients with recurrent miscarriage: an analysis of chromosome abnormalities in human preimplantation embryos

OBJECTIVE To analyze the incidence of numeric chromosomal abnormalities in preimplantation embryos from women with unexplained recurrent miscarriage (RM) so as to seek an etiology and to determine whether the use of IVF may be indicated to treat these cases. DESIGN Prospective controlled study. SETTING University laboratory of reproductive genetics and a tertiary referral center for infertility. PATIENT(S) Nine women with a mean (+/-SD) of 3.9 +/- 0.6 RMs who were undergoing IVF and preimplantation genetic diagnosis, and a control group of young (n = 10) and older (n = 6) patients who were undergoing preimplantation genetic diagnosis because of sex-linked diseases. INTERVENTION(S) In vitro fertilization, embryo culture for 72 hours, blastomere biopsy, and analysis of chromosomes 13, 16, 18, 21, 22, X, and Y with the use of fluorescent in situ hybridization. Transfer of chromosomally normal embryos into the uterus. MAIN OUTCOME MEASURE(S) Numeric chromosomal abnormalities in human embryos. RESULT(S) Sixty-six embryos from patients with RM were compared with 62 embryos from young patients and 41 embryos from older patients. There was a significant increase in the rate of abnormal embryos in the patients with RM and the older patients compared with the controls. Abnormalities in most of the chromosomes studied were higher in the RM group than in the control group, especially those affecting chromosome 13. CONCLUSION(S) There was an increase in numeric chromosomal abnormalities in preimplantation embryos from women with RM that could be the cause of infertility in many couples with unexplained RM. The use of IVF in such circumstances may be indicated if successful preimplantation genetic diagnosis is added to the procedure.

FISH preimplantation diagnosis of chromosome aneuploidy in recurrent pregnancy wastage.

Purpose:Our purpose was to detect aneuploidy for chromosomes 13, 16,18, 21, 22, X, and Y in preimplantation embryos from patients with a history of unexplained recurrent miscarriage.Methods:Three patients with a history of unexplained recurrent spontaneous abortion were included in this study. Embryos were biopsied at the eight-cell stage, individually fixed on slides, and processed for fluorescent in situ hybridization (FISH). A multiple FISH protocol for seven chromosomes pairs (13, 16, 18, 21, 22, X, and Y) has been developed.Results:A total of 39 embryos was studied with the multiple FISH protocol developed. Successful analysis of the biopsied embryos was achieved within the time limits usually allowed in a preimplantation diagnosis program. Analysis of the blastomeres showed that 17 embryos were chromosomally normal for the probes used, 16 embryos were aneuploid, and in 6 embryos no informative results were obtained.Conclusions:In the patients studied, a large proportion of embryos (41%) exhibited chromosomal abnormalities for the probes used. Preimplantation diagnosis to screen for chromosome abnormalities could be a feasible approach to improve the possibility of successful pregnancy in these couples.

The importance of good practice in preimplantation genetic screening: critical viewpoints

ger association between prenatal depressive symptoms and the risk of preterm delivery. With regard to the subtypes of preterm delivery, unfortunately, we did not have such information for that study. However, as with the potential misclassification of depressive symptoms, the effect of potential misclassification of outcomes (i.e. assuming that depression during pregnancy is only related to certain subtype(s) of preterm delivery) is to attenuate the observed association. In other words, had we only included the subtypes that are associated with depressive symptoms during pregnancy, the observed association would have been stronger.

Preimplantation genetic screening and human implantation

In recent years, preimplantation genetic screening (PGS) has been used and recommended to increase the implantation rate in older women or in couples with previous assisted reproduction (ART) failures, to try to increase pregnancy rates in couples with recurrent abortions, to prevent the transmission of chromosome anomalies to the offspring of carriers of balanced chromosomal rearrangements, or even to try to decrease the incidence of trisomic births in older women. So far, PGS has contributed to increase the implantation rate in older women; however, the rate of clinical pregnancies has not increased, either in older women or in couples with previous ART failures. In couples with recurrent abortions, the pregnancy rate seems to increase, but only when the woman is young (< or =35). In carriers of balanced reorganizations, the prognosis is poor. Attempts to decrease the birth of trisomic children to older women are difficult to evaluate. This absence of relevant results is not related to the technique itself, which is quite safe, but to other still largely unknown factors.

Preimplantation genetic diagnosis.

Preimplantation genetic diagnosis (PGD) includes a variety of techniques that have been developed to detect the transmission to the offspring of genetic diseases or of chromosome abnormalities by couples at risk before a pregnancy is established, to avoid these couples the risk of recurrent abortions and/or of repeated terminations of pregnancy. Candidate couples are carriers of gene mutations or of structural chromosome rearrangements, or with recurrent spontaneous abortions of unknown origin. Diagnostic procedures include different modalities of gene amplification using the polymerase chain reaction (PCR) or of fluorescent in situ hybridization (FISH). Embryo biopsies are carried out at the 6-8 cell stage. Healthy embryos are transferred on day 4 or at the blastocyst stage. By now, several hundred healthy children have been born using PGD, and only one diagnostic error has been reported.

The decision to cancel a preimplantation genetic diagnosis cycle.

It has been suggested that a minimum number (six) of cumulus‐oocyte complexes (COCs) should be retrieved for fertilization to offer enough chances to ensure a pregnancy after a preimplantation genetic diagnosis (PGD) procedure. Therefore a decision to cancel a PGD cycle should be adequately weighted to offer the patients the highest chances to obtain a pregnancy. We describe a case where, after retrieving only three COCs suitable for fertilization, a triplet pregnancy was obtained. This case suggests that, although low numbers of COCs can reduce the effectiveness of the PGD procedure, other factors are involved in its final result. Thus, the opportunity of routinely cancelling such cycles should be reconsidered. In addition, this is, to our knowledge, the first case where sex selection was carried out to prevent the birth of carriers of the abnormal gene, and not of affected offspring. Copyright

Pregnancy outcome after preimplantation genetic diagnosis in an affected couple with X-linked adrenoleukodystrophy

OBJECTIVE To achieve a pregnancy free of X-linked adrenoleukodystrophy (X-ALD) by intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis (PGD). DESIGN Case report. SETTING Clínica FIV Recoletos, a private IVF center. PATIENT(S) A couple in which the man had X-ALD. INTERVENTION(S) The ICSI protocol and PGD of the obtained embryos. MAIN OUTCOME MEASURE(S) Blastomeres were analyzed by fluorescence in situ hybridization using sex selection techniques. Embryos were transferred and pregnancy was diagnosed by hCG analysis and ultrasonographic examination. RESULT(S) Ten embryos were obtained by ICSI. A biopsy was taken from eight embryos to perform PGD and two male embryos were transferred resulting in a twin pregnancy. CONCLUSION(S) This is the first registered gestation in which PGD has been used to prevent X-ALD transmission.