Prenatal screening characteristics in Emanuel syndrome: a case series and review of the literature

Purpose

Emanuel syndrome is a rare chromosomal disorder characterized by severe mental retardation and multiple anomalies. The syndrome is caused by chromosomal imbalance due to a supernumerary derivative chromosome 22. Little is known regarding the characteristics of prenatal biochemical screening, or ultrasonographic markers in this syndrome. We aimed to identify a prenatal screening pattern characteristic of Emanuel Syndrome.

Methods

We report the prenatal characteristics of five fetuses with Emanuel syndrome, four of which were diagnosed prenatally.

Results

We found no consistent pattern of prenatal biochemical markers or other prenatal characteristics. Nevertheless, increased NT, low PAPP-A and ultrasound features such as intra uterine growth restriction, posterior fossa, cardiac and bowel abnormalities may be helpful in raising the suspicion for this rare genetic syndrome.

Conclusion

Review of the biochemical screening results, ultrasound findings, and demographic characteristics of this Emanuel syndrome case series, as well as of the relevant literature fail to suggest a characteristic prenatal pattern.     

Outcomes of patients with prenatally diagnosed agenesis of the corpus callosum in conjunction with ventriculomegaly

Purpose

We evaluated the postnatal outcomes of patients with prenatally diagnosed agenesis of the corpus callosum (ACC), in conjunction with ventriculomegaly, as a tool for parental counseling.

Materials and methods

Through a retrospective review of maternal and infant records, we evaluated the postnatal outcomes of 21 patients with prenatally diagnosed ACC and fetal ventriculomegaly.

Results

Ten of the 21 patients (48 %) were diagnosed with isolated ACC. Among these 10 patients, neurodevelopmental outcomes were normal in four, uncertain in one, and five demonstrated mild or moderate disabilities. The remaining 11 patients had ACC associated with either central nervous system (CNS) anomalies (7 of 11) or chromosomal abnormalities (4 of 11). The outcomes were estimated in nine of the 11 children; all nine had severe disabilities. The mortality rate of ACC, associated with other anomalies, was 29 % (2 of 7) in children with CNS anomalies and 75 % (3 of 4) for those with chromosomal abnormalities.

Conclusion

If ACC with fetal ventriculomegaly is associated with other malformations, a poor outcome is highly likely. Although the outcome of isolated ACC with fetal ventriculomegaly was generally better, >50 % of the patients had mild or moderate neurodevelopmental disabilities. These findings provide useful information for parental counseling.     

Three- and four-dimensional HDlive rendering images of normal and abnormal fetuses: pictorial essay

Background

Our objective is to present our experience of normal embryonic development and fetal anatomy and fetal anomalies reconstructed employing the three-dimensional (3D) and four-dimensional (4D) HDlive rendering mode.

Methods

A total of 18 normal embryos and fetuses and 21 abnormal fetuses (one case each of thoracic meningocele, thickened nuchal translucency, multicystic dysplastic kidney, gastroschisis, omphalocele, and ovarian cyst, five of hydrops fetalis, three of skeletal abnormality, three of chromosome abnormality, two of cystic hygroma, and two of amniotic band syndrome) at 7–36?weeks’ gestation were studied using the 3D/4D HDlive rendering mode.

Results

In normal fetuses, marked embryonic development with advancing gestation was clearly shown in the first trimester of pregnancy, and various realistic facial expressions were noted in the second and third trimesters. In abnormal fetuses, anatomically realistic features such as gross specimens were obtained. In particular, 3D/4D HDlive provides new, realistic sensations for the diagnosis of amniotic band syndrome, skeletal abnormalities, and facial abnormalities.

Conclusion

3D/4D HDlive rendering images seem to be more readily discernible than those obtained by conventional 3D/4D sonography. 3D/4D HDlive may be an important modality in future embryonic research, fetal neurobehavioral assessment, and the evaluation of fetal anomalies.     

Non-chimerism and chimerism pseudo dicentric Y chromosome: two case reports about azoospermia and cytogenetic/molecular genetic analysis in the Chinese population

Objective

To report the cytogenetic and molecular genetic analysis of the first two cases of non-chimerism and chimerism karyotype in Chinese male patients who suffer from azoospermia, which may be caused by pseudo dicentric Y chromosomes.

Design

Case study.

Setting

Academic reproductive medicine center.

Patients

Two male patients with azoospermia, carrying pseudo dicentric Y chromosome.

Interventions

Review the records of inquiry, testicular biopsy, pathological examination, semen routine examination, endocrine evaluation, cytogenetic chromosomal analysis, and FISH detection of peripheral blood to evaluate Y chromosome deletion.

Main outcome measures

To investigate the possible association among pseudo dicentric Y, chimeric status and azoospermia.

Results

Two patients were both diagnosed with azoospermia by a variety of andrology inspections. Further chromosomal analysis and FISH indicated their pseudo dicentric Y chromosome and different chimerism status. PCR confirmed simultaneous deletions of AZFb and AZFc regions in the Y chromosome of both patients.

Conclusions

Pseudodicentric Y chromosome affecting the long arm may lead to a male phenotype by duplicating the sex-determining region of Y chromosome (SRY) fragment and chimeric status may further impact patient's hormone levels, which obstruct spermatogenesis. However, the deletion of the azoospermia factor (AZF) is likely the key factor that causes azoospermia.     

No difference in congenital anomalies prevalence irrespective of insemination methods and freezing procedure: cohort study over fourteen years of an ART population in the south of France

Purpose

A retrospective cohort study was conducted to evaluate and compare the prevalence of congenital anomalies in babies and fetuses conceived after four procedures of assisted reproduction technologies (ART).

Methods

The prevalence of congenital anomalies was compared retrospectively between 2750 babies and fetuses conceived between 2001 and 2014 in vitro fertilization with standard insemination (IVF), IVF with intracytoplasmic sperm injection (ICSI), IVF with frozen embryo transfer (FET-IVF), and ICSI with frozen embryo transfer (FET-ICSI). Congenital anomalies were described according to European Surveillance of Congenital Anomalies (EUROCAT) classification. The parental backgrounds, biologic parameters, obstetric parameters, and perinatal outcomes were compared between babies and fetuses with and without congenital anomalies. Data were analyzed by the generalized estimating equation.

Results

Between 2001 and 2014, a total of 2477 evolutionary pregnancies were notified. Among these pregnancies, 2379 were included in the analysis. One hundred thirty-four babies and fetuses had a congenital anomaly (4.9%). The major prevalences found among the recorded anomalies were congenital heart defects, chromosomal anomalies, and urinary defects. However, the risk of congenital anomalies in babies and fetuses conceived after FET was not increased compared with babies and fetuses conceived after fresh embryo transfer, even when adjusted for confounding factors (p = 0.40).

Conclusions

There is no increased risk of congenital anomalies in babies and fetuses conceived by fresh versus frozen embryo transfer after in vitro fertilization with and without micromanipulation. Indeed, distribution of congenital anomalies found in our population is consistent with the high prevalence of congenital heart defects, chromosomal anomalies, and urinary defects that have been found by other authors in children conceived by infertile couples when compared to children conceived spontaneously.

     

Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey

Purpose

In view of the genetic risks for the next generation, the importance of careful evaluation of karyotypes and AZF microdeletions in male infertility prior to assisted reproduction is evident. In the present study, it is aimed to investigate the frequency and types of both major chromosomal abnormalities by using standard cytogenetic methods and Y chromosome microdeletions of infertile males with azoospermia and oligozoospermia to give appropriate genetic counseling before assisted reproduction techniques in southeast Turkey.

Methods

A total of 80 infertile males (52 were azoospermic, 25 oligospermic and 3 asthenospermic) were studied for the cytogenetic evaluation and molecular AZF screening program prior to use of assisted reproduction techniques. A detailed history was taken for each man. Karyotyping was performed on peripheral blood lymphocytes according to standard methods. Polymerase chain reaction (PCR) amplification by using 15 Y-specific sequence-tagged sites of AZF region was performed to screen the microdeletions in the AZF region of Y chromosome.

Results

Of 80 cases, 71 had normal karyotype (46,XY). The total prevalence of chromosomal abnormalities was found to be 11.2% (9/80), including seven patients with Klinefelter syndromes and two patients with balanced autosomal rearrangements. All of the patients with Klinefelter Syndrome had azoospermia, but carriers with translocation had oligospermia. The deletions of Y chromosome were seen in one patient (1.3%) with features of normal karyotype and azoospermia. Microdeletions were seen in the AZFc and AZFd regions. Neither AZFa nor AZFb microdeletions were detected.

Conclusions

The occurrence of chromosomal anomalies and Y chromosome microdeletions among infertile males strongly suggests the need for routine genetic testing and counseling prior to employment of assisted reproduction techniques.     

Higroma quístico cervical en el primer trimestre. Resultados perinatales

Objectives

To evaluate the prenatal course and perinatal outcomes of fetuses diagnosed with cervical cystic hygroma.

Material and methods

A total of 33 pregnant women diagnosed with fetuses with cervical cystic hygroma were studied. Those who decided to continue with their pregnancies underwent a chromosome study, morphological evaluation, and follow-up of the hygroma.

Results

In our casuistics, we found a clear association with chromosome disease (seven out of the 19 fetuses with confirmed karyotype [37%]), although the number of fetuses with chromosomal abnormalities is probably higher. In contrast, 10 pregnant women (30%) with a diagnosis of cervical cystic hygroma had a satisfactory perinatal outcome.

Conclusions

Because cystic hygroma is relatively easy to diagnose, ultrasonography is widely used and an association with chromosome disease is frequent, most couples choose voluntary interruption of the pregnancy. However, if chromosomal abnormalities and malformations are absent and there is a tendency to regression, a satisfactory perinatal outcome can be considered.     

Clinical application of SNP array analysis in fetuses with ventricular septal defects and normal karyotypes

Purpose

The present study aims to evaluate the utility of high-resolution single-nucleotide polymorphism (SNP) arrays in fetuses with ventricular septal defects (VSDs) with or without other structural anomalies but with normal karyotypes and to investigate the outcomes of cases of prenatal VSDs via clinical follow-up.

Methods

We analyzed 144 fetuses with VSDs and normal karyotypes using Affymetrix CytoScan HD arrays and the analyses were carried out a year after birth.

Results

Clinically significant CNVs were detected in 12 fetuses (8.3%). The most common pathogenic CNV was a 22q11.2 deletion with a detection rate of 2.8% (4/144). Well-known microdeletion or microduplication syndromes, including Smith–Magenis, Miller–Dieker, 9q subtelomeric deletion, 1p36 microdeletion, 1q21.1 microduplication, and terminal 4q deletion syndrome, were identified in six cases. Three regions of chromosomal imbalance were also identified: microduplication at 12q24.32q24.33, microdeletion at 16p13.13p13.12 and microdeletion at Xp21.1. The genes TBX1, SKI, GJA5, EHMT1, NOTCH1 were identified as established genes and LZTR1, PRDM26, YWHAE, FAT1, AKAP10, ERCC4, and ULK1 were identified as potential candidate genes of fetal VSDs. There was no significant difference in pathogenic CNVs between isolated VSDs and VSDs with additional structural abnormalities. Ninety-five (74.8%) pregnant women with fetuses with benign CNVs chose to continue the pregnancy and had a favorable prognosis, while nine (75%) pregnant women with fetuses with pathogenic CNVs chose to terminate the pregnancy.

Conclusions

High-resolution SNP arrays are valuable tools for identifying submicroscopic chromosomal abnormalities in the prenatal diagnosis of VSDs. An excellent outcome can be expected for VSD fetuses that are negative for chromosomal anomalies and other severe anatomic abnormalities.

     

Chromosomal defects in infertile men with poor semen quality

Purpose

To assess the incidence and the type of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 76 Tunisian infertile men (54 nonobstructive azoospermia and 22 oligo-asthenospermia).

Methods

Karyotyping was performed on peripheral blood lymphocytes according to the standard methods. Molecular diagnosis of classical and partial Y-chromosomal microdeletions was performed by amplifying Y-specific STSs markers.

Results

Various numerical and structural chromosome abnormalities were identified in 15 patients (19.48%). The occurrence of chromosomal abnormality in the azoospermics and severe oligo-asthnospermic was 21.7% and 13.5%, respectively. The most common was Klinefelter syndrome, accounting for 10 of the 15 cytogenetic defects. The total frequency of Y chromosomal microdeletions was 17.1%, with respective frequencies in azoospermic and severe oligospermic groups, 11.1% and 31.8%. The most frequent of Y chromosomal deletions were the partial ones (11.1% in azoospermic and 27.2% in oligospermic).

Conclusion

The occurrence of chromosomal abnormalities among infertile males strongly suggests the need for routine genetic testing and counseling prior to the employment of assisted reproduction techniques.     

Pronuclear formation of freeze-dried canine spermatozoa microinjected into mouse oocytes

Purpose

The aim of the present study was to investigate the fertilizing capacity of fresh, frozen-thawed and freeze-dried canine spermatozoa.

Methods

After canine spermatozoa were injected into mouse oocytes, the rates of oocyte activation, male pronuclear formation and chromosomal aberrations were investigated.

Results

The rates of oocyte activation were comparable (90.6–100%), no matter the sperm type injected. The percentage of male pronuclear formation was higher (P?<?0.001) in the freeze-dried spermatozoa (92.3%) than the fresh (61.5%) and frozen-thawed (69.2%) spermatozoa. However, the chromosomal damage in the oocytes injected with freeze-dried spermatozoa was higher (72.9%: P < 0.001) than with fresh (26.9%) and frozen-thawed (21.4%) spermatozoa.

Conclusions

These data indicate using mouse oocytes that freeze-dried canine spermatozoa may potentially fertilize canine oocytes although chromosomal damage is frequently generated.     

Polycystic ovarian syndrome and congenital uterine anomalies: the hidden common player

Objective

To study the association between polycystic ovary syndrome (PCOS) and congenital uterine (Müllerian) anomalies in infertile patients. The ultimate aim was to check for a common factor linking both reproductive health problems.

Design

A prospective observational study.

Setting

Tertiary referral infertility center.

Subjects and methodology

3,900 infertile patients were included. The diagnoses of PCOS and uterine anomalies were made. Patients with or without PCOS were correlated to the presence or absence of uterine anomalies and statistically assessed.

Main outcome measures

Study of the prevalence of PCOS/uterine anomalies in the studied population and the ratio of coexistence.

Results

The prevalence of PCOS in the studied cohort was 10.48 %. 409 (10.48 %) patients were confirmed to have PCOS, while 204 (5.23 %) were with confirmed uterine anomalies. Of the patients with confirmed PCOS, almost one-third (n = 149, 31.4 %) had uterine anomalies, while in patients with confirmed uterine anomalies, almost three-fourths (n = 149, 73 %) had PCOS.

Conclusions

There is evident association between PCOS and uterine anomalies in infertile patients. We suggest a genetic rather than a developmental defect to be a possible common player for the development of both PCOS and uterine anomalies.     

Aneuploidy in abortuses following IVF and ICSI

Purpose

To compare aneuploidy rates in first trimester pregnancy losses following IVF ± ICSI.

Methods

A retrospective cohort analysis of karyotypes of abortuses following conventional IVF (n = 159) and ICSI (n = 196).

Results

50.1% of losses were found to be cytogenetically abnormal among all patients undergoing IVF ± ICSI. A significant increase in fetal aneuploidy rate was noted with increasing maternal age (<30 years = 26.1% vs. 31 to 34 years. = 38.2% vs. 35 to 39 years. = 51.3% vs. >39 years. = 65.9%). Aneuploidy rates were similar in the ICSI vs. conventional IVF groups (52.6% vs. 47.2% [p 0.31, RR 1.11, 95% CI 0.90, 1.38]). More sex chromosome anomalies were noted in the ICSI group.

Conclusions

The aneuploidy rate in first trimester abortuses significantly increases with increasing maternal age. ICSI was not shown to significantly increase the aneuploidy rate. However, more sex chromosome anomalies were found among pregnancies resulting from ICSI.     

A novel method for detection of chromosomal integrity in cryopreserved livestock spermatozoa using artificially fused mouse oocytes

Purpose

The aim of the present study was to investigate the effect of mouse oocyte volume on the efficiency of chromosomal analysis in livestock spermatozoa.

Methods

Oocytes were injected with bull, ram, boar and dog sperm heads, and then fused with enucleated mouse oocytes.

Results

The increment of oocyte volume increased the rates of morphologically normal oocytes after sperm injection, which induced much higher rates of overall chromosome detection in bull, ram and dog spermatozoa. The recipient oocyte volume did not affect the chromosomal integrity. Furthermore, in bull, the chromosomal integrity detected by fused mouse oocytes was similar to that derived from a homologous system. On the other hand, chromosomal plates of boar spermatozoa could not be detected despite the use of fused oocytes.

Conclusion

These data indicate that fused mouse oocytes improved the efficiency of chromosome detection in bull, ram and dog spermatozoa.     

Prenatal detection and postnatal outcome of congenital talipes equinovarus in 106 fetuses

Objectives

We analyze the incidence, etiology, outcome of pregnancy and therapeutic regimes of prenatally and postnatally detected isolated and complex congenital talipes equinovarus in a tertiary referral center.

Methods

We included fetuses with at least one prenatal ultrasound examination conducted by a sub-specialized practitioner for prenatal medicine. Retrospective evaluation was made of prenatal, obstetrical and neonatal/pediatric records and where applicable pathological records or records of the involved department of pediatric surgery with a minimum follow-up of 24?months.

Results

106 children with uni- or bilateral CTEV were detected prenatally in a period of 17?years. There were 55 liveborn infants. The majority of the liveborn infants had isolated CTEV (37/55), whereas in the group of the stillborns most of the individuals suffered from complex CTEV (46/51). The gender-distribution showed a majority of male individuals in the liveborn group with isolated CTEV 22/37 and 11/18 in fetuses with non-isolated CTEV. Accordingly, 2/5 fetuses with isolated CTEV and 25/46 with complex CTEV in the group of the terminated pregnancies were males. 33/49 children were treated in a conservative manner, 16/49 needed additional surgery on the CTEV. Twenty-nine of forty-nine had excellent and 19/49 very good outcome. One of forty-nine had a good outcome. Fifteen of fifty-five liveborn children suffered from severe additional anomalies, like arthrogryposis multiplex congenita and spina bifida aperta. In the group of the stillborns all non-isolated CTEV were cases with severe additional anomalies (46/51). Mean time of prenatal diagnosis was 23^3/7 gestational weeks. Six cases with CTEV were detected postnatally only. There was one prenatal false positive diagnosis.

Conclusions

Prenatal detection of CTEV is feasible during pregnancy. The outcome of children with isolated CTEV is good. In complex CTEV outcome depends on the additional anomalies the fetus has. In isolated CTEV fetal karyotyping should be offered; in complex CTEV fetal karyotyping is mandatory. The prenatal diagnosis of an (isolated) CTEV should always include an appropriate parental counseling together with pediatric orthopedics and pediatric surgeons. Repeated ultrasound scans can confirm diagnosis and reduce the risk of misjudgement of additional fetal anomalies as those may be frequently seen in fetuses with CTEV.     

Cytogenetic abnormalities in 179 cases with male infertility in Western Region of Turkey: Report and review

Purpose

In this study we aimed to evaluate the postnatally screened karyotype results in couples who were referred because of primary infertility between 2000 and 2006 in Izmir.

Methods

The records of a total of 179 cases were evaluated retrospectively.

Results

A total of 21 cases (11.74%) showed chromosomal alteration. Thirteen (7.26%) were 47,XXY; three (1.68%) were pericentric inversion of chromosome 9; one (0.56%) 46,XY/45,XO; one (0.56%) 46,XY/47,XXY/48,XXXY; one (0.56%) 46,XY,t(X;1); one (0.56%) 46,XY/46,XY,del(Y)(q11.2) and one (0.56%) 46,XX.

Conclusions

The rate of gonosomal chromosomal abnormalities was nearly three times higher in our region than the rate in the literature. Chromosomal analysis is strongly suggested particularly in those who suffer fertility problems.     

Two different microarray technologies for preimplantation genetic diagnosis and screening,due to reciprocal translocation imbalances,demonstrate equivalent euploidy and clinical pregnancy rates

Purpose

To compare single nucleotide polymorphism (SNP) and comparative genomic hybridization (aCGH) microarray platforms to evaluate embryos for parental translocation imbalances and aneuploidy.

Methods

A retrospective review of preimplantation genetic diagnosis and screening (PGD/PGS) results of 498 embryos from 63 couples undergoing 75 in vitro fertilization cycles due to parental carriers of a reciprocal translocation.

Results

There was no significant difference between SNP and aCGH microarrays when comparing the prevalence of embryos that were euploid with no translocation imbalance, euploidy with a parental translocation imbalance or aneuploid with or without the parental chromosome imbalance. The clinical pregnancy rates were also equivalent for SNP (60 %) versus aCGH (65 %) microarrays. Of 498 diagnosed embryos, 45 % (226/498) were chromosomally normal without translocation errors or aneuploidy, 22 % (112/498) were euploid but had a parentally derived unbalanced chromosomal segregant, 8 % (42/498) harbored both a translocation imbalance and aneuploidy and 24 % (118/498) of embryos were genetically balanced for the parental reciprocal translocation but were aneuploid for other chromosomes. The overall clinical pregnancy rate per IVF cycle following SNP or aCGH microarray analysis was 61 % and was higher if the biopsy was done on blastocysts (65 %) versus cleavage stage embryos (59 %), although not statistically significant.

Conclusions

SNP or aCGH microarray technologies demonstrate equivalent clinical findings that maximize the pregnancy potential in patients with known parental reciprocal chromosomal translocations.     

Cancer during pregnancy: perinatal outcome after in utero exposure to chemotherapy

Objectives

To study the outcome of pregnancies complicated by malignant disease, in particular neonatal morbidity and mortality after in utero exposure to chemotherapy.

Methods

This prospective study included 118 patients diagnosed with malignant disease for the first time during pregnancy over an 8-year period (March 2003?CMarch 2011). Outcome of neonates born to mothers who received chemotherapy during pregnancy was studied and compared with a control group.

Results

The commonest cancer type diagnosed during pregnancy (56/118?=?47.45?%) was breast carcinoma followed by lymphoma/leukemia (32?=?27.12?%). Gynecological tumors (all ovarian) represented 10.16?%, soft tissue tumors 5.08?%, colorectal 4.23?%, thyroid 2.54?% and others 3.38?%. Sixty-one (51.64?%) women received chemotherapy (average 3?±?2 cycles) during the second and third trimesters. The incidence of neonatal survival, preterm birth, small for gestational age and congenital malformations was not significantly different between women who received chemotherapy during pregnancy and the control group. Five (4.23?%) women with advanced disease died during or shortly after termination of pregnancy.

Conclusion

In utero exposure to chemotherapy during the second and third trimesters of pregnancy carries minimal morbidity to the unborn fetus.     

Factors contributing to intra-uterine fetal death

Purpose

We aimed in this research to explore factors contributing to the occurrence of intra-uterine fetal death (IUFD).

Methods

The study was conducted between 1st January 2008 and 31st December 2009 in the Department of Obstetrics and Gynecology at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Patients who were diagnosed to have IUFD at ≥24?weeks of gestation and those whose dead fetuses were found to weigh ≥500?g after delivery were eligible to be included. 138 patients with IUFD and 237 controls with alive fetuses were enrolled. Data were collected from printed and computerized medical records of participants. Factors that may have contributed to the occurrence of IUFD were explored. Comparisons between various risk factors and outcomes of the two groups were done. p value was statistically significant if ≤0.05.

Results

Patients who did not receive antenatal care (ANC) services are at 70?% increased risk for developing IUFD (OR 0.31, p?<?0.0001). Risk of IUFD increases 25-fold with the occurrence of abruption placenta (OR 25.81, p?≤?0.0001), tenfolds with the occurrence of intra-uterine growth restrictions (OR 10.78, p?=?0.04) and threefolds with the presence of hypertensive disorder in pregnancy (OR 3.17, p?=?0.04). Finally, patients carrying IUFD fetuses are at higher risk to develop labor complications compared with their controls (p?≤?0.0001).

Conclusion

Despite the difficulty in predicting IUFD occurrence, it appears that carefully implemented ANC and timely management of at risk patients may contribute to its prevention.     

Postnatal neuro-development of fetuses with absent end-diastolic flow in the umbilical artery and/or fetal descending aorta

Objective

To determine whether absence of end-diastolic flow in the umbilical artery and/or fetal aorta impacts postnatal neuro-development in preterm-born children.

Methods

The study group, consisting of 43 fetuses with absent end-diastolic flow in the umbilical artery and/or fetal aorta, was compared with a control group, consisting of 30 fetuses, matching for gestational age but with normal doppler-flow results. The children’s neuro-developmental status was assessed using the ‘Munich functional developmental diagnostics’ (MFDD), between the 2nd and 3rd year of life.

Results

Gestational age at birth was 33?+?6?weeks in the study group and 34?+?4?weeks in the control group. A brain-sparing effect was observed in 37.3% of fetuses in the study group compared with 10.0% in the control group (p?=?0.014). For all seven MFDD domains, the number of children with deficiencies was higher in the study group. For the domains perception, active speech and comprehension this effect was statistically significant (p?<?0.05). Overall, 30.2% of children in the study group and 16.7% of the control group had pathologic test results (p?<?0.013).

Conclusion

Pathological doppler-flow in the umbilical artery and/or fetal descending aorta in preterm born children is associated with neuro-developmental deficiencies. Intensive pediatric care is recommended to mitigate these deficiencies during early childhood.     

Präimplantationsdiagnostik weltweit

Background

Globally preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS) are a rapidly advancing diagnostic approaches incorporating current testing technologies and covering an increasing number of conditions. In some countries, however, PGD and PGS remain highly controversial.

Objective

To assess the number of tests and indications in international registers in order to track current clinical trends in PGD and PGS.

Method

A total of 6 registers from the following organizations were compared: the Consortium for Preimplantation Genetic Diagnosis (Europe), European IVF Monitoring (EIM), the Australian and New Zealand Assisted Reproduction Database (ANZARD), the Society for Assisted Reproductive Technology (SART, USA), the Center for Disease Control (CDC, USA) and the International Committee for Monitoring Assisted Reproductive Technology (ICMART).

Results

In Europe PGD was reported in 44?% of all countries using in vitro fertilization (IVF) treatment in 2009 and worldwide in 47?% for 2006. In Europe over 5000 (USA for 2012 over 8000) tests were performed in 2009 and worldwide over 11,000 in 2006. This corresponds to 1?% (USA 5?%) of all IVF treatments reported worldwide. In Europe 42?% (USA 28?%) of all tests were for familial chromosome anomalies or monogenic conditions and 58?% for aneuploidy screening with PGS (USA 52?% and an additional 20?% for social sexing). The main indications included reciprocal translocations and autosomal dominant conditions for classical PGD and advanced maternal age for PGS. In 2009 the biopsy of eight cell embryos by laser, PGD with genetic analysis after the polymerase chain reaction (PCR) and PGS with fluorescence in situ hybridization (FISH) were the predominating methods. The clinical pregnancy rate per oocyte retrieval was 26?% (range 24–33?%) in Europe and 33?% worldwide.

Discussion

In about approximately half of all the countries reporting IVF data PGD was performed. The results are acceptable for classical PGD, i. e. it was embryologically and genetically reliable and the pregnancy rates were sufficiently high, but PGS is controversial because the clinical benefits were not clear.