Prenatal prediction of respiratory distress syndrome by multimodality approach using 3D lung ultrasound, lung-to-liver intensity ratio tissue histogram and pulmonary artery Doppler assessment of fetal lung maturity.

OBJECTIVE: Studying the correlation of different lung parameters, using three-dimensional ultrasound (3D US) with fetal lung maturity (FLM) to predict the development of neonatal respiratory distress syndrome (RDS). METHODS: Three-dimensional ultrasound was done to record the fetal lung volume (FLV), fetal lung-to-liver intensity ratio (FLLIR) and the main pulmonary artery (MPA) blood flow parameters; pulsatility index (PI), resistive index (RI) and acceleration time-to-ejection time ratio (At/Et), to 218 women between 32 and 40 weeks gestational age within 24 h from labor. RESULTS: Of 218 fetuses examined, final analysis was done for 143 fetuses. Thirty eight (26.5%) were diagnosed with RDS. The MPA PI and RI were significantly higher in fetuses diagnosed with RDS compared with those without (2.51 ± 0.33 and 0.90 ± 0.03 cm/s versus 1.96 ± 0.20 and 0.84 ± 0.01 cm/s; p value < 0.001 and <0.001 respectively). MPA At/Et was significantly lower (0.24 ± 0.04 vs 0.35 ± 0.04; p value < 0.001). FLLIR was significantly lower (1.04 ± 0.07 vs 1.18 ± 0.11; p value < 0.001), and the mean FLV was significantly smaller (28.23 ± 5.63, vs 38.87 ± 4.68 cm3; p value < 0.001). CONCLUSION: Main pulmonary artery (PI, RI, At/Et ratio), FLIIR, and mean FLV can be used as reliable predictors of neonatal RDS. ADVANCES IN KNOWLEDGE: 3D ultrasound VOCAL technique, ultrasound tissue histogram and pulmonary artery Doppler are reliable tools for prenatal prediction of fetal lung maturity.

Prenatal delineation of a distinct lethal fetal syndrome caused by a homozygous truncating KIDINS220 variant.

Kinase D-interacting substrate of 220 kDa (KIDINS220) is a transmembrane protein playing integral role in growth mediating pathways in the nervous and cardiovascular systems. KIDINS220 heterozygous truncating variants that affect the protein's C-terminus have been associated with a phenotype, so far described only in few unrelated children, including spastic paraplegia, intellectual disability, nystagmus, and obesity. More recently, a homozygous, more N-terminal truncating variant in KIDINS220 gene was suggested to be associated with enlarged cerebral ventricles and limb contractures in three fetuses from a consanguineous family. We confirm the latter finding by presenting the first detailed prenatal identification of a fetal phenotype associated with novel homozygous deleterious frameshift variant in KIDINS220 gene in a consanguineous healthy Egyptian couple. History of unexplained seven miscarriages and a similar stillbirth were recorded. Prenatal ultrasonography revealed limb contractions and ventriculomegaly; in addition to previously unreported cerebellar anomalies, cardiac anomalies and hydrops fetalis. These findings represent an expansion of clinical and molecular spectrum associated with KIDINS220 variants and broaden our understanding of genotype-phenotype relationships in lethal congenital contractures syndromes and associated severe abnormal embryological development. More generally, our study adds KIDINS220 to the rare group of genes which may cause disease by either of two distinct mutational mechanisms.

Raine syndrome: Prenatal diagnosis based on recognizable fetal facial features and characteristic intracranial calcification.

OBJECTIVE: The purpose of this study was to elucidate the facial morphology and the pattern of internal malformations in three fetuses with RS born to first cousins of Egyptian decent. METHODS: The fetal ultrasonography findings were highly suggestive of RS leading to targeted Sanger sequencing of FAM20C and postnatal assessment. RESULTS: The prenatal ultrasound findings of osteosclerotic skull, exorbitism, hypoplastic nose, midface hypoplasia, small mouth with down-curved corners, and a distinct and recognizable pattern of intracranial calcification were identified in three fetuses with RS. The calcifications were evident specifically around the corpus callosum and/or ventricular walls. Ectopic renal and hepatic calcifications, pulmonary hypoplasia, mild rhizomelic shortening of the upper limbs, intrauterine fractures, and cerebellar hypoplasia were also noted. Molecular analysis identified three novel homozygous variants, two frameshift: [c.456delC (p.Gly153Alafs*34)] in exon 1 and [c.905delT (Phe302Serfs*35)] in exon 4 and one nonsense mutation in exon 10, [c.1557C>G(p.Tyrs519*)]. The three variants were segregated with the phenotype. This is the first description of a phenotype associated with homozygous truncating variants of FAM20C. CONCLUSION: RS has characteristic prenatal ultrasound findings which can improve the prenatal identification of this condition and help in guiding the molecular diagnosis and counseling.

Prenatal ultrasound findings of holoprosencephaly spectrum: Unusual associations.

OBJECTIVE: The objective of this study is to evaluate the prenatal diagnosis, postnatal characteristics, and the spectrum of associated findings in fetuses with holoprosencephaly (HPE). METHODS: Fetal neurosonograms, postnatal assessment, and chromosomal analysis were performed in a cohort of 25 fetuses with HPE. RESULTS: The prevalence of HPE in high-risk pregnancies was 4.4:10 000. The alobar subtype was the most frequently encountered, with 17 cases (68%). Interestingly, among them, four cases (16%) presented with the rare agnathia-otocephaly complex. Chromosomal abnormalities were detected in 11 cases (44%), the most frequent being trisomy 13 in seven cases (five alobar, one semilobar, and one lobar HPE), followed by trisomy 18 in two cases with semilobar HPE. One case of alobar HPE had 45, XX, t(18;22) (q10;q10), -18p karyotyping, and one case of semilobar HPE was associated with triploidy. Facial malformations in HPE spectrum ranged from cyclopia, proboscis, and arrhinia that were associated with the alobar subtype to hypotelorism and median cleft that were frequent among the semilobar and lobar subtypes. Associated neural tube defects were identified in 12% of cases. CONCLUSION: Our study illustrates the clinical and genetic heterogeneity of HPE and describes different chromosomal abnormalities associated with HPE.

GnRH agonist plus vaginal progesterone for luteal phase support in ICSI cycles: a randomized study.

In this prospective randomized study, the effect of daily gonadotrophin-releasing hormone agonist (GnRHa) in the luteal phase on IVF and intracytoplasmic sperm injection (ICSI) outcomes was assessed. Women (n = 446) were counselled for IVF-ICSI, and randomized on the day of embryo transfer to group 1 (daily 0.1 mg subcutaneous GnRHa until day of beta-HCG) (n = 224) and group 2 (stopped GnRHa on day of HCG injection) (n = 222). Both groups received daily vaginal progesterone suppositories. Primary outcome was clinical pregnancy rate. Secondary outcome was ongoing pregnancy rate beyond 20 weeks. Mean age, oestradiol on day of HCG, number of oocytes retrieved, number of embryos transferred, and clinical and ongoing pregnancy rates were 28.9 ± 4.5 years, 2401 ± 746 pg/mL; 13.5 ± 6.0 oocytes; 2.6 ± 0.6 embryos, and 36.2% and 30.4% consecutively in group 1 compared with 29.7 ± 4.7 years, 2483 ± 867 pg/mL, 13.7 ± 5.5 oocytes, 2.7 ± 0.6 embryos, 30.6% pregnancy rate, and 25.7% ongoing pregnancy rate in group 2. No significant difference was found between the groups. Subcutaneous GnRHa during the luteal phase of long GnRHa protocol cycles does not increase clinical or ongoing pregnancy rates after IVF-ICSI.

Impact of antimüllerian hormone assays on the outcomes of in vitro fertilization: a prospective controlled study.

OBJECTIVE: To assess the value of routine antimüllerian hormone (AMH) assays in patients considered high risk for cancellation. DESIGN: Prospective controlled study. SETTING: A private IVF center, Cairo, Egypt. PATIENT(S): In total 4,917 patients received counseling before starting IVF/intracytoplasmic sperm injection (ICSI). They were comprised of group A1 (n = 1,335), who were considered to be at risk for cancellation after ovarian stimulation, and group A2 (n = 3,582), who were considered low risk for cancellation. A control group, B (n = 4,639), included group B1 (n = 1,248) and group B2 (n = 3,391) based on the same criteria as groups A1 and A2. INTERVENTION(S): An AMH assessment was performed for group A1. All of the patients were stimulated using the long GnRH agonist protocol. Patients with low AMH levels received the flare-up protocol. MAIN OUTCOME MEASURE(S): The cancellation of IVF/ICSI cycles before or after stimulation, as well as the pregnancy rates (PR) in relation to AMH levels. RESULT(S): The group A1 patients (6.4%) did not start IVF due to low AMH, and some (6.6%) had their cycles canceled due to poor responses, compared with 2.6% in group A2 and 13.2% in group B1. The clinical PR was 42% in patients with normal AMH and 20% in patients with low AMH. The differences among these three groups were highly significant. CONCLUSION(S): The AMH assays reduced the cancellations, cost, and stress experienced by couples.

The use of vaginal natural progesterone for prevention of preterm birth in IVF/ICSI pregnancies.

The aim of this study was to evaluate the effect of vaginal natural progesterone on the prevention of preterm birth in IVF/intracytoplasmic sperm injection (ICSI) pregnancies. A single-centre prospective placebo-controlled randomized study was performed. A total of 313 IVF/ICSI pregnant patients were randomized into two groups for either treatment with daily 400 mg vaginal natural progesterone or placebo, starting from mid-trimester up to 37 weeks or delivery. Amongst the patients, there were 215 singleton and 91 twin pregnancies. There was no significant difference in risk of preterm birth among all patients (OR 0.672, 95% CI 0.42-1.0. There was a significantly lower preterm birth rate in singleton pregnancies in the natural progesterone arm (OR 0.53, 95% CI 0.28-0.97) and no significant difference between both arms in twin pregnancies (OR 0.735, 95% CI 0.36-2). In conclusion, the administration of 400 mg vaginal natural progesterone from mid trimester reduced the incidence of preterm birth in singleton, but not in twin, IVF/ICSI pregnancies.

Prospective randomized study for hydrotubation versus no hydrotubation before intrauterine insemination in unexplained infertility.

The purpose of the study was to investigate the value of hydrotubation before intrauterine insemination (IUI). In 228 patients with the diagnosis of unexplained infertility, ovarian stimulation was performed before IUI, using 100mg of clomiphine citrate for 5 days from day 3 of the cycle and one ampoule of human menopausal gonadotrophin for 5 days from day 6 of the cycle. Folliculometry and determination of LH concentration in urine were performed daily until LH became positive, then randomization for hydrotubation before IUI versus no hydrotubation was performed. Fifteen patients were cancelled from the study due to poor response or stimulation of three or more follicles. A total of 213 patients were randomized as follows: 103 patients undergoing hydrotubation using 50 ml of saline and 110 patients with no hydrotubation. IUI was performed the following day and ongoing pregnancy occurred in 13 patients (12.6%) in the hydrotubation group and nine patients (8.2%) in the non-hydrotubation group with no significant difference (OR 1.66; 95% CI 0.62-4.63). In conclusion, hydrotubation before IUI does not improve pregnancy rate.

Ultrasound cervical measurement and prediction of spontaneous preterm birth in ICSI pregnancies: a prospective controlled study.

A prospective controlled study was performed in which transvaginal ultrasound measurement of cervical length was compared in 222 twin ICSI pregnancies, 122 singleton ICSI pregnancies and 51 spontaneous singleton pregnancies. Preterm birth was defined as

Prospective randomized study comparing luteal phase support for ICSI patients up to the first ultrasound compared with an additional three weeks.

BACKGROUND: There is a consensus that administration of progesterone to women after IVF for luteal phase support (LPS) is associated with a higher ongoing pregnancy rate. However there are few studies, including only one randomized study, which have examined the optimal duration of LPS. METHODS: A questionnaire concerning details of LPS was returned from 21 leading IVF centres. We then randomized 257 women, who were pregnant after ICSI on day of first ultrasound, into two groups: to continue LPS for three more weeks or to stop on the day of ultrasound. RESULTS: The duration of LPS in the questionnaire varied from the day of positive pregnancy test up to 12 weeks of pregnancy in different centres. In the randomized study, 132 patients in Group A continued LPS for 3 weeks after first ultrasound, whereas 125 patients in Group B stopped LPS on day of first ultrasound. After confirming pulsations, the miscarriage rate up to 20 weeks of gestation was 4.6% (6/132) in group A and 4.8% (6/125) in group B [odds ratios (OR) = 0.94; 95% confidence intervals (CI) = 0.3-3.1]. Bleeding episodes were 15.9% in Group A compared with 20.8% in group B (OR = 0.72; 95% CI = 0.38-1.36). CONCLUSIONS: There is no international consensus about the duration of LPS; our single-centre randomized trial did not support extending the LPS beyond the day of first ultrasound demonstrating echoes and pulsations. Trials registry number-ISRCTN: 88722916.

A prospective randomized study comparing coasting with GnRH antagonist administration in patients at risk for severe OHSS.

This work evaluated possible advantages of gonadotrophin-releasing hormone (GnRH) antagonist administration as an alternative to coasting in prevention of severe ovarian hyperstimulation syndrome (OHSS) in women undergoing IVF/ intracytoplasmic sperm injection. A prospective randomized study comparing coasting (group A) (n = 96) and GnRH antagonist administration (group B) (n = 94) in patients at risk of OHSS was performed. The primary outcome measure was high quality embryos. The secondary outcome measures were days of intervention, number of oocytes, pregnancy rate, number of cryopreserved embryos and incidence of severe OHSS. There were significantly more high quality embryos (2.87 +/- 1.2 versus 2.21 +/- 1.1; P < 0.0001), and more oocytes (16.5 +/- 7.6 versus 14.06 +/- 5.2; P = 0.02), in group B as compared with group A. There were more days of coasting as compared with days of antagonist administration (2.82 +/- 0.97 versus 1.74 +/- 0.91; P < 0.0001). In conclusion, GnRH antagonist was superior to coasting in producing significantly more high quality embryos and more oocytes as well as reducing the time until HCG administration. There was no significant difference in pregnancy rate between the two groups. No OHSS developed in either group.

Among women undergoing embryo transfer, is the probability of pregnancy and live birth improved with ultrasound guidance over clinical touch alone? A systemic review and meta-analysis of prospective randomized trials.

OBJECTIVE: To investigate the theory that ultrasound guidance during ET improves clinical outcomes. DESIGN: Systematic review of prospective, randomized, controlled trials comparing ultrasound with clinical touch methods of embryo catheter guidance. SETTING: Infertility centers. PATIENT(S): 5,968 ET cycles in women. INTERVENTION(S): Embryo transfer with or without ultrasound guidance. MAIN OUTCOME MEASURE(S): Meticulous electronic (e.g., PubMed, EMBASE, CENTRAL) and hand searches were performed to locate trials. Primary outcome measures were the live-birth, ongoing pregnancy, and clinical pregnancy rates. Secondary outcome measures were the implantation, multiple pregnancies, and miscarriage rates. In addition, the incidences of ectopic pregnancies and difficult transfers were evaluated. RESULT(S): Twenty-five studies were retrieved, of which five were excluded. Meta-analysis of the remaining studies (5,968 ET cycles in women) was conducted by using the Mantel-Haenszel method (fixed-effect model). There was a significantly increased chance of a live birth (odds ratio [OR] = 1.78, 95% confidence interval [CI] = 1.19 to 2.67), ongoing pregnancy (OR = 1.51, 95% CI = 1.31 to 1.74), clinical pregnancy (OR = 1.50, 95% CI = 1.34 to 1.67), embryo implantation (OR = 1.35, 95% CI = 1.22 to 1.50), and easy transfer rates after ultrasound guidance (OR = 0.68, 95% CI = 0.58 to 0.81). There was no difference in multiple pregnancy, ectopic pregnancy, or miscarriage rates. CONCLUSION(S): Ultrasound-guided ET significantly increases the chance of live birth and ongoing and clinical pregnancy rates compared with the clinical touch method.

Pregnancy rate is not improved by delaying embryo transfer from days 2 to 3.

OBJECTIVE: To compare the outcome of assisted reproduction in day 2 versus day three embryo transfer. DESIGN: Prospective study. PARTICIPANTS: A total of 927 consecutive embryo transfers for IVF and ICSI cycles including 626 embryo transfers on day 2 and 301 on day 3. INTERVENTION: IVF and ICSI. OUTCOME MEASURE: Clinical pregnancy rate. RESULTS: There is no significant difference in the pregnancy rate between ET on day 2 (50.9%) and ET on day 3 (50.5%). CONCLUSION: Embryo transfer could be done on days 2 or 3 according to the convenience of the patient and the medical team. CONDENSATION: Embryo transfer could be done on days 2 or 3 according to the convenience of the medical team with similar results.

The outcome of in vitro fertilization in advanced endometriosis with previous surgery: a case-controlled study.

OBJECTIVE: This study was undertaken to evaluate the outcome of in vitro fertilization (IVF) in patients with advanced pelvic endometriosis and previous surgical treatment. STUDY DESIGN: A case controlled study was performed. RESULTS: Patients with the diagnosis of stage IV endometriosis with previous surgical treatment were treated by IVF (group A = 85). An age-matched group of patients (group B = 177) with tubal factor infertility were treated with the same protocol of IVF. In group A, cycle cancellation because of poor response occurred in 29.7% compared with 1.1% in the control group (relative risk 26.03, 95% CI 6.02-112.45). There were 13 (15.3%) clinical pregnancies per stimulated cycle in group A compared with 93 (52.5%) clinical pregnancies in the control group, P <.0001 (odds ratio 0.29, 95% CI 0.15-0.55). CONCLUSION: The outcome of IVF in stage IV endometriosis with previous surgery was significantly lower compared with an age-matched group of tubal factor infertility.