Polyploidy in First and Second Trimester Pregnancies in Romania - a Retrospective Study.

BACKGROUND: Polyploidy is a rare lethal cytogenetic anomaly in pregnancies, generally leading to pregnancy termination. This study aims to compare first and second trimester polyploidy in pregnancies and describe the underlying mechanisms. METHODS: A retrospective study was conducted in three medical genetics laboratories, collecting cases from Eastern, Southern, and Western Romania. The period of interest was January 2008 to December 2018. Prenatal samples (chorionic villi and amniotic fluid) and miscarriage samples were tested by standard karyotyping, as well as QF-PCR or FISH as complementary or alternative techniques. RESULTS: In first trimester pregnancies, we report cytogenetic results of chorionic villi samples from miscarriages: 25 triploid cases and 13 tetraploid cases. In second trimester samples obtained by amniocentesis, cytogenetic findings were positive for 17 triploid cases. Maternal age, age of the pregnancy, and fetal gender identified by ultrasound were recorded in all cases and, additionally, data on biochemical risk and ultrasonographic findings for second trimester pregnancies. CONCLUSIONS: Cytogenetic investigations of spontaneous abortions provide valuable information on the cause of abortion. This information is crucial for genetic counseling and may also contribute to prenatal diagnosis in subsequent pregnancies.

Self-oocyte activation and parthenogenesis: an unusual outcome of a misconducted IVF cycle.

A rare cause of infertility is the lack of fertilisation with the spontaneous activation of oocytes, leading to parthenogenesis. We present such a case. The patient was a G1P0 38-year-old woman of African ethnicity, who requested an in vitro fertilisation (IVF) with donor sperm. She received a stimulation protocol of 75 IU of FSH/LH from day 3 of the cycle, which she interrupted after 2 d, and restarted with the same dosage for another 3 d from day 7, plus one administration of GnRH antagonist in day 10 of the cycle. With a follicle reaching 19 mm on day 11, estradiol of 325 ng/ml, ovulation was induced with hMG 5000 UI, and oocyte pick-up performed at 30 h. One oocyte was retrieved, and good-quality sperms were added to the insemination procedure. No fecundation occurred at 20 h, with the extruded oocyte separated from the granulosa wall. At 40 h and 64 h the aspect was of three cells, one cell with one nucleus, the others with high granulation and no visible nuclei. This case shows an unusual self-activation oocyte in a poorly managed IVF cycle. The patient will be further evaluated, to decide if a better managed stimulation protocol would prevent recurrence.

A Case of Inherited t(4;10)(q26;q26.2) Chromosomal Translocation Elucidated by Multiple Chromosomal and Molecular Analyses. Case Report and Review of the Literature.

We present a complex chromosomal anomaly identified using cytogenetic and molecular methods. The child was diagnosed during the neonatal period with a multiple congenital anomalies syndrome characterized by: flattened occipital region; slight turricephaly; tall and broad forehead; hypertelorism; deep-set eyes; down slanting and short palpebral fissures; epicanthic folds; prominent nose with wide root and bulbous tip; microstomia; micro-retrognathia, large, short philtrum with prominent reliefs; low set, prominent ears; and congenital heart disease. The GTG banding karyotype showed a 46,XY,der(10)(10pter→10q26.2::4q26→4qter) chromosomal formula and his mother presented an apparently balanced reciprocal translocation: 46,XX,t(4;10)(q26;q26.2). The chromosomal anomalies of the child were confirmed by MLPA, and supplementary investigation discovered a quadruplication of the 4q35.2 region. The mother has a triplication of the same chromosomal fragment (4q35.2). Using array-CGH, we described the anomalies completely. Thus, the boy has a 71,057 kb triplication of the 4q26-q35.2 region, a 562 kb microdeletion in the 10q26.3 region, and a 795 kb quadruplication of the 4q35.2 region, while the mother presents a 795 kb triplication of the 4q35.2 region. Analyzing these data, we consider that the boy's phenotype is influenced only by the 4q partial trisomy. We compare our case with similar cases, and we review the literature data.

Phenotypic variability in Patau syndrome.

UNLABELLED: Patau syndrome has an incidence of 1/10.000-20.000, the clinical diagnosis being suggested by the triad cleft lip and palate, microphthalmia/anophthalmia and postaxial polydactyly. Most frequent cytogenetic abnormality is free and homogeneous trisomy 13 (80.0%), rarely being detected trisomy mosaics or Robertsonian translocations. The objective of the study was to identify phenotypic features of trisomy 13. MATERIAL AND METHODS: The retrospective study was conducted on a trial group of 14 cases diagnosed cytogenetically with trisomy 13 between January 2000 and December 2012 at lasi Medical Genetics Centre. RESULTS: Of the 14 cases, 3 were evaluated pathologically (two aborted foetuses and one stillborn), 8 cases were detected in the neonatal period, and 3 in infancy. Clinical diagnosis was supported by the identification of a model of abnormal development, mainly characterized by: maxillary cleft (lip and palate--5 cases; lip--1 case), ocular abnormalities (microphthalmia/anophthalmia--7 cases; cyclopia--1 case), postaxial polydactyly (7 cases), scalp defects (6 cases), congenital heart anomalies (10 cases, 6 patients with atrial septal defect), complete holoprosencephaly (4 cases), ear abnormalities (11 cases), broad nasal root (10 cases). An important issue in confirming the phenotypic variability of Patau syndrome is that the classic clinical triad was identified only in one case. CONCLUSIONS: Patau syndrome is a disease with variable expression and is characterized by a pattern of abnormal prenatal development characterized by facial dysmorphia, polydactyly and severe birth defects (heart, brain) that generate an increased in utero and perinatal mortality.

Prenatal diagnosis of gonosomal anomalies: limitations of the FISH method and genetic counseling difficulties in 15 cases.

UNLABELLED: Prenatal diagnosis (PD) by FISH or cell culture is today an important tool for the prevention of chromosomal anomalies. A difficult issue is prenatal detection of gonosomal anomalies. Most gonosomal anomalies neither affect life expectancy nor cause psychomotor retardation, but sexualization disorders and the lack of reproductive potential are a constant finding. AIM: This study aimed at identifying the medical problems the specialists and the parental couple are faced with at the time of the diagnosis of fetal gonosomal anomalies. MATERIAL AND METHODS: This retrospective study (2004-2012) was conducted in the Prenatal Genetic Diagnosis Department of "CuzaVoda" Maternity by FISH technique in 1685 pregnancies. The AneuVysion probes were used for identifying and enumerating chromosomes 13, 18, 21, X, and Y via fluorescence in situ hybridization (FISH) in interphase nuclei obtained from amniotic fluid. RESULTS: Fifteen fetuses were selected in which we were faced with difficulties interpreting the number of gonosomes: monosomy X (5 cases), pseudomosaicism XX/XY (3), trisomy XXY (3 cases), trisomy XYY (1 case), 45,X/46.XX mosaicism (1 case) and triploidy XXX (2 cases). Later, by repeating the analysis, 2 cases with pseudomosaicism XX/XY were excluded. A case highlighting the limitations of the FISH test was that of a fetus in which the FISH test revealed trisomy XXY, while postnatal karyotyping showed a six cell line mosaicism (marker and ring X chromosomes). CONCLUSIONS: All parental couples received nondirective genetic counseling, respecting the individuals' dignity and rights of self-determination. Parents received information on the natural course of the disease, treatment options, and psychological support and were involved in their child's recovery.

[Performance of different methods of estimating risk screening for chromosomal anomalies]. / Performanta diferitelor metode de screening in primul trimestru de sarcina privind estimarea riscului pentru anomaliile cromozomiale.

UNLABELLED: In the last 10 years, several studies have been carried out on additional ultrasound markers in the first trimester of pregnancy in order to improve detection rate of fetal numerical chromosome abnormalities (aneuploidy) and to reduce the rate of false-positive diagnosis. The purpose of this study was to evaluate the performance of various recommendations for which amniocentesis was performed followed by FISH testing in the diagnosis of aneuploidy. These evaluations were conducted in order to determine whether ultrasound aspects are associated with fetal aneuploidy and to estimate the risk level of individual markers using probability estimation analysis. MATERIAL AND METHODS: The study has been carried out at the Clinical Hospital of Obstetrics and Gynecology "CuzaVoda" Iasi, at the Laboratory of cytogenetic--prenatal diagnosis, during January 2004-December 2011, on a target group of 1406 pregnant women. As part of this study, 1411 amniocentesis were performed. RESULTS: increased efficiency of screening for fetal aneuploidy in the first trimester of pregnancy is obtained through combined method (maternal age over 35 years, increased nuchal translucency and the presence of double test risk) which has 100% detection rate and a rate false-positive result of 0%. The efficiency of this method is provided also by the relatively high risk (RR = 17.2) and its specificity (Sp = 100%). Making the assessment following the study false positive rate, it appears that a good method of risk assessment for aneuploidy is the combined evaluation of increased nuchal translucency (NT) with maternal age over 35 years (specificity 99.5%, a detection rate of 40% false positive rate of 0.45% and a relative risk of 7.09 for the presence of aneuploidy). CONCLUSIONS: The achievement of a correct prenatal diagnosis and the increase of the method efficiency, requires a correct selection of cases with aneuploidy risk assessment, based on the results of ultrasound and biochemical (double test risk) investigations correlated with advanced maternal age or previous presence of aneuploidy of children (Down syndrome, Edwards syndrome, Patau syndrome, Klinefelter syndrome and triplo X).

[FISH technique in aneuplodies prenatal diagnosis]. / Importanta tehnicii FISH in diagnosticul prenatal al aneuploidiilor.

UNLABELLED: Chromosomal disorders are severe and affect 0.9% of the newborns. In these conditions, prenatal diagnosis should be compulsory in every public medical system. MATERIAL AND METHOD: Our study is a retrospective analysis of pregnant women investigated by amniocentesis and FISH technique. RESULTS: We analyzed 233 samples collected between 2004 and 2007 at Iasi "Cuza-Voda" Obstetrics and Gynecology Hospital. The majority of cases were investigated between 16 and 24 weeks of pregnancy. Thirty-eight abnormal cases (16.30%) were identified: 17 cases with 21 trisomy, 16 cases with 18 trisomy, 3 cases with X monosomy, and 2 cases with 13 trisomy. The main reasons for amniocentesis were: advanced maternal age (12.5% abnormal cases) ultrasound abnormalities (26.15% abnormal cases), and biochemical abnormalities (7.14% abnormal cases). CONCLUSION: Our data are in agreement with other studies, and support our results.