Prenatal phenotype of Williams-Beuren syndrome and of the reciprocal duplication syndrome.

KEY CLINICAL MESSAGE: Copy losses/gains of the Williams-Beuren syndrome (WBS) region cause neurodevelopmental disorders with variable expressivity. The WBS prenatal diagnosis cannot be easily performed by ultrasound because only few phenotypic features can be assessed. Three WBS and the first reciprocal duplication prenatal cases are described with a review of the literature.

Rapid warming increases survival of slow-frozen sibling oocytes: a step towards a single warming procedure irrespective of the freezing protocol?

Nowadays, human oocytes/embryos are cryopreserved via slow freezing or vitrification. The aim of this study was to evaluate a rapid warming protocol for slow-frozen human oocytes based on the standard warming procedure for vitrification. This was a prospective study on 216 sibling oocytes randomized for either conventional rapid thawing or rapid warming with vitrification warming solution. The primary endpoint was morphological assessment of survival at 2h. Surviving oocytes were divided into two subgroups: (i) parthenogenetically activated; and (ii) fixed and observed for spindle/chromosome configuration. Secondary endpoints were parthenogenetic development and spindle/metaphase configuration. Survival rate with rapid warming was higher (92/102, 90.2%) than with rapid thawing (85/114, 74.6%; P=0.005), and after 3d of culture the rapidly warmed parthenotes had more blastomeres compared with those rapidly thawed (P=0.042). Meiotic spindle and chromosomal configuration were not significantly influenced by rapid warming or rapid thawing. The finding of this study allows IVF centres to increase the efficiency of oocyte slow freezing, enabling survival rates comparable to vitrification protocols, and potentially to optimize costs by using the same warming protocol for both slow-frozen and vitrified reproductive cells.

Comparison of two ready-to-use systems designed for sperm-hyaluronic acid binding selection before intracytoplasmic sperm injection: PICSI vs. Sperm Slow: a prospective, randomized trial.

OBJECTIVE: To compare, in a strict, randomized way, the efficiency of two ready-to-use systems for hyaluronic acid (HA)-intracytoplasmic sperm injection (ICSI): an HA culture dish (PICSI Sperm Selection Device) and a viscous medium containing HA (Sperm Slow). DESIGN: Prospective, randomized study. SETTING: Medical center. PATIENT(S): Fifty subjects per treatment group (100 total). INTERVENTION(S): One hundred ICSI treatments were randomly carried out with PICSI or with Sperm Slow for sperm selection. Randomization was conducted with sealed envelopes. Intracytoplasmic sperm injection was performed by a single embryologist with 5 years' experience in HA-ICSI. PRIMARY OUTCOME MEASURE: good-quality embryo rate. SECONDARY OUTCOME MEASURES: oocyte fertilization, pregnancy and implantation rate, and the duration of the ICSI procedure. RESULT(S): The good-quality embryo rate was comparable between the two groups (58.5% with PICSI vs. 56% with Sperm Slow). Overall there were no statistically significant differences in secondary outcome measures except ICSI procedure duration, which was 3 minutes longer in the PICSI group. CONCLUSION(S): Both PICSI and Sperm Slow allow comparable clinical efficiency in selecting HA-bound spermatozoa. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN72668039.

Sterilization of liquid nitrogen with ultraviolet irradiation for safe vitrification of human oocytes or embryos.

OBJECTIVE: To evaluate the efficacy of ultraviolet (UV) irradiation for rapid microbial decontamination of liquid nitrogen (LN2). DESIGN: Basic research. SETTING: Private assisted reproduction center. ANIMAL(S): Microorganisms (bacteria and fungi). INTERVENTION(S): Two stainless steel open dewars containing LN2 were contaminated in a two-step experiment with high titers of cultures of bacteria (Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Escherichia coli) and fungi (Aspergillus niger). One of the two dewars was subsequently exposed to UV irradiation at 253.7 nm to obtain a rapid microbial decontamination before the complete evaporation of LN2. MAIN OUTCOME MEASURE(S): Detection of the micro-organisms in LN2 after UV sterilization through the assessment of bacterial and fungal growth in minimal and selective Petri dishes. RESULT(S): None of the contaminating micro-organisms were detected in LN2 after UV sterilization. CONCLUSION(S): Decontamination of LN2 with UV irradiation is feasible and straightforward. The fact that LN2 can be quickly and safely sterilized should encourage the wider application of human oocyte and embryo vitrification with "open carriers."

"Physiologic ICSI": hyaluronic acid (HA) favors selection of spermatozoa without DNA fragmentation and with normal nucleus, resulting in improvement of embryo quality.

OBJECTIVE: To evaluate the role of hyaluronic acid (HA) for sperm selection before intracytoplasmic sperm injection (ICSI). DESIGN: Three prospective studies. SETTING: Private assisted reproduction center in Italy. PATIENT(S): Study 1: 20 men. Study 2: 15 men. Study 3: 206 couples treated with ICSI on a limited number of oocytes per patient (1-3) in accordance with Italian IVF law. INTERVENTION(S): Study 1: determination of sperm DNA fragmentation of HA-bound spermatozoa versus spermatozoa in polyvinylpyrrolidone (PVP). Study 2: assessment of nuclear morphology of HA-bound spermatozoa versus spermatozoa in PVP. Study 3: randomized study comparing conventional PVP-ICSI to ICSI in which the spermatozoa are selected for their capacity to bind to HA (HA-ICSI). MAIN OUTCOME MEASURE(S): Study 1: sperm DNA fragmentation rate. Study 2: sperm nucleus normalcy rate according to motile sperm organellar morphology examination criteria. Study 3: fertilization, embryo quality and development, and implantation and pregnancy. RESULT(S): Spematozoa bound to HA show a significant reduction in DNA fragmentation (study 1) and a significant improvement in nucleus normalcy (study 2) compared with spermatozoa immersed in PVP. Furthermore, injection of HA-bound spermatozoa (HA-ICSI) significantly improves embryo quality and development (study 3). CONCLUSION(S): Hyaluronic acid may optimize ICSI outcome by favoring selection of spermatozoa without DNA fragmentation and with normal nucleus. Furthermore, HA may also be used to speed up the selection of spermatozoa with normal nucleus during intracytoplasmic morphologically selected sperm injection (IMSI).

Efficacy of low-dose human chorionic gonadotropin alone to complete controlled ovarian stimulation.

OBJECTIVE: To prove that low-dose hCG alone can be clinically used to replace FSH-containing gonadotropins to complete controlled ovarian hyperstimulation (COH). DESIGN: Controlled, prospective, randomized study. SETTING: Academic center. PATIENT(S): Infertile patients who are candidates for assisted reproduction. INTERVENTION(S): Patients received [1] recombinant FSH or hMG throughout COH (group A); [2] ovarian priming with recombinant FSH/hMG followed by low-dose hCG (200 IU/day) alone (group B). MAIN OUTCOME MEASURE(S): Medication consumption; daily serum and follicular fluid (FF) measurements of LH, FSH, hCG, E2, P, T, and androstenedione (A); number and size of follicles; intracytoplasmic sperm injection (ICSI) outcome. RESULT(S): In group B: [1] duration and dose of recombinant FSH/hMG administration were reduced; [2] preovulatory serum hCG, E2, and T were higher, whereas FSH was lower; [3] FF hCG, E2, T levels, and E2/T, E2/A, and E2/P ratios were higher, whereas A was lower; [4] small but not large preovulatory follicles were reduced; [5] fertilization rates were higher; and [6] serum and FF P levels, and ICSI outcome did not differ. CONCLUSION(S): Low-dose hCG alone in the late COH stages: [1] reduced recombinant FSH/hMG consumption whereas ICSI outcome was comparable to traditional COH regimens; [2] stimulated follicle growth and maturation independent of FSH administration; [3] was associated with a reduced number of small preovulatory follicles; [4] did not cause premature luteinization; [5] resulted in a more estrogenic intrafollicular environment.