Hemimegalencephaly: prenatal diagnosis and outcome.

Hemimegalencephaly (HME) is a developmental abnormality of the central nervous system (CNS) which may present as either a syndromic or isolated case. Here, we present two cases of early prenatal diagnosis of HME. Prenatal CNS ultrasound and MRI in the first case revealed ventricular asymmetry, midline shift with displacement of the occipital lobe across the midline, large dilatation mainly at the posterior horn of the left lateral ventricle, and a head circumference in the 90th percentile without involvement of the brain stem and cerebellum, as well as abdominal lymphangioma. Right hemispherectomy was performed at 3 months of age due to intractable seizures. The pathological specimen showed findings characteristic of HME, including a disorganized cytoarchitecture with lack of neuronal lamination, focal areas of polymicrogyria, and neuronal heterotopias with dysplastic cells. In the second case, 2D and 3D neurosonography demonstrated similar findings (asymmetry of cerebral hemispheres, midline shift, and dilation of the posterior horn of the left lateral cerebral ventricle). Posterior fossa structures were unremarkable. HME was diagnosed and the pregnancy was terminated. Autopsy findings confirmed the diagnosis of HME.

Preimplantation Genetic Diagnosis for Myotonic Dystrophy Type 1 and Analysis of the Effect of the Disease on the Reproductive Outcome of the Affected Female Patients.

Myotonic dystrophy type 1 (DM1) is the most common adult muscular dystrophy and presents an autosomal dominant inheritance. A reproductive option for the families affected is preimplantation genetic diagnosis (PGD). One limitation of this option is the nonoptimal response to ovarian stimulation of the women with DM1, although controversial results exist regarding this subject. In this study, we have analyzed the results of the PGD program applied to DM1 at our institution. A total of 35 couples have been included in our program since 2010, and 59 cycles have been performed. The percentage of transfers per cycle was 64.4% and the live birth rate per cycle was 18.6%. Interestingly, statistically significant differences were observed for the clinical results in the group of couples with an affected female versus the group with an affected male or versus a group of couples with different referral reasons. Specifically, both the percentage of mature oocytes out of the total oocytes retrieved and the percentage of fertilization were considerably lower in the group of DM1 females. Our findings would suggest the possibility of achieving less favourable PGD outcomes in women with DM1 in comparison with other pathologies, although the underlying mechanism remains unknown.

Clinical and Technical Overview of Preimplantation Genetic Diagnosis for Fragile X Syndrome: Experience at the University Hospital Virgen del Rocio in Spain.

Fragile X syndrome (FXS) accounts for about one-half of cases of X-linked intellectual disability and is the most common monogenic cause of mental impairment. Reproductive options for the FXS carriers include preimplantation genetic diagnosis (PGD). However, this strategy is considered by some centers as wasteful owing to the high prevalence of premature ovarian failure in FXS carriers and the difficulties in genetic diagnosis of the embryos. Here we present the results of our PGD Program applied to FXS, at the Department of Genetics, Reproduction and Fetal Medicine of the University Hospital Virgen del Rocío in Seville. A total of 11 couples have participated in our PGD Program for FXS since 2010. Overall, 15 cycles were performed, providing a total of 43 embryos. The overall percentage of transfers per cycle was 46.67% and the live birth rate per cycle was 13.33%. As expected, these percentages are considerably lower than the ones obtained in PGD for other pathologies. Our program resulted in the birth of 3 unaffected babies of FXS for 2 of the 11 couples (18.2%) supporting that, despite the important drawbacks of PGD for FXS, efforts should be devoted in offering this reproductive option to the affected families.

Experience of Preimplantation Genetic Diagnosis for Hemophilia at the University Hospital Virgen Del Rocío in Spain: Technical and Clinical Overview.

Hemophilia A and B are the most common hereditary hemorrhagic disorders, with an X-linked mode of inheritance. Reproductive options for the families affected with hemophilia, aiming at the prevention of the birth of children with severe coagulation disorders, include preimplantation genetic diagnosis (PGD). Here we present the results of our PGD Program applied to hemophilia, at the Department of Genetics, Reproduction and Fetal Medicine of the University Hospital Virgen del Rocío in Seville. A total of 34 couples have been included in our program since 2005 (30 for hemophilia A and 4 for hemophilia B). Overall, 60 cycles were performed, providing a total of 508 embryos. The overall percentage of transfers per cycle was 81.7% and the live birth rate per cycle ranged from 10.3 to 24.1% depending on the methodological approach applied. Although PGD for hemophilia can be focused on gender selection of female embryos, our results demonstrate that methodological approaches that allow the diagnosis of the hemophilia status of every embryo have notorious advantages. Our PGD Program resulted in the birth of 12 healthy babies for 10 out of the 34 couples (29.4%), constituting a relevant achievement for the Spanish Public Health System within the field of haematological disorders.

Experience of preimplantation genetic diagnosis with HLA matching at the University Hospital Virgen del Rocío in Spain: technical and clinical overview.

Preimplantation genetic diagnosis (PGD) of genetic diseases, combined with HLA matching (PGD-HLA), is an option for couples at risk of transmitting a genetic disease to select unaffected embryos of an HLA tissue type compatible with that of an existing affected child. Here we present the results of our PGD-HLA program at the Department of Genetics, Reproduction and Fetal Medicine of the University Hospital Virgen del Rocío in Seville. Seven couples have participated in our program because of different indications. Overall, 26 cycles were performed, providing a total of 202 embryos. A conclusive molecular diagnosis and HLA-typing could be assured in 96% of the embryos. The percentage of transfers per cycle was 26.9% and the birth rate per cycle was 7.7% per transfer. Our PGD-HLA program resulted in the birth of 2 healthy babies, HLA-identical to their affected siblings, with successful subsequent haematopoietic stem cell (HSC) transplantations. Both HSC-transplanted children are currently doing well 48 and 21 months following transplantation, respectively. All the procedures, including HSCs umbilical cord transplantation, were performed in our hospital.

Novel one-step multiplex PCR-based method for HLA typing and preimplantational genetic diagnosis of ß-Thalassemia.

Preimplantation genetic diagnosis (PGD) of single gene disorders, combined with HLA matching (PGD-HLA), has emerged as a tool for couples at risk of transmitting a genetic disease to select unaffected embryos of an HLA tissue type compatible with that of an existing affected child. Here, we present a novel one-step multiplex PCR to genotype a spectrum of STRs to simultaneously perform HLA typing and PGD for ß-thalassemia. This method is being routinely used for PGD-HLA cycles in our department, with a genotyping success rate of 100%. As an example, we present the first successful PGD-HLA typing in Spain, which resulted in the birth of a boy and subsequent successful HSC transplantation to his affected brother, who is doing well 4 years following transplantation. The advantage of our method is that it involves only a round of single PCR for multiple markers amplification (up to 10 markers within the HLA and 6 markers at the ß-globin loci). This strategy has allowed us to considerably reduce the optimization of the PCR method for each specific PGD-HLA family as well as the time to obtain molecular results in each cycle.

Two sets of monozygotic twins after intracytoplasmic sperm injection and transfer of two embryos on day 2.

OBJECTIVE: To report a case of quadruple gestation (two sets of monozygotic twins) after intracytoplasmic sperm injection (ICSI) and transfer of two embryos. DESIGN: Case report. SETTING: Tertiary clinical and academic medical center. PATIENT(S): Thirty-four-year-old patient who underwent an ICSI cycle. INTERVENTION(S): After 7 years of primary sterility for andrologic subfertility, the patient underwent an ICSI cycle, with transfer of two embryos on day 2. MAIN OUTCOME MEASURE(S): Transvaginal sonogram performed at the 36th day of gestational age showed a quadruple gestation (dichorionic-quadramniotic). RESULT(S): After receiving extensive counseling, the couple decided to proceed to a nonselective reduction of a set of monozygotic twins. Final outcome was complete loss of pregnancy. CONCLUSION(S): Several factors have been involved in the etiopathogenesis of monozygotic twins in assisted reproductive technology: maternal age, extended embryo culture and in vitro culture condition, blastocyst-stage transfer, ICSI, and assisted hatching. One of the most important objectives in assisted reproductive technology is to reduce the multiple-gestation rate; therefore, it is necessary to determine the optimum number of embryos to be transferred in each case. In addition, couples must be informed that monozygotic-twin pregnancies could be an important complication in IVF-ICSI cycles.