Performance and Diagnostic Value of Genome-Wide Noninvasive Prenatal Testing in Multiple Gestations.

OBJECTIVE: To evaluate the accuracy and diagnostic value of genome-wide noninvasive prenatal testing (NIPT) for the detection of fetal aneuploidies in multiple gestations, with a focus on dichorionic-diamniotic twin pregnancies. METHODS: We performed a retrospective cohort study including data from pregnant women with a twin or higher-order gestation who underwent genome-wide NIPT at one of the eight Belgian genetic centers between November 1, 2013, and March 1, 2020. Chorionicity and amnionicity were determined by ultrasonography. Follow-up invasive testing was carried out in the event of positive NIPT results. Sensitivity and specificity were calculated for the detection of trisomy 21, 18, and 13 in the dichorionic-diamniotic twin cohort. RESULTS: Unique NIPT analyses were performed for 4,150 pregnant women with a multiple gestation and an additional 767 with vanishing gestations. The failure rate in multiple gestations excluding vanishing gestations ranged from 0% to 11.7% among the different genetic centers. Overall, the failure rate was 4.8%, which could be reduced to 1.2% after single resampling. There were no common fetal trisomies detected among the 86 monochorionic-monoamniotic and 25 triplet cases. Two monochorionic-diamniotic twins had an NIPT result indicative of a trisomy 21, which was confirmed in both fetuses. Among 2,716 dichorionic-diamniotic twin gestations, a sensitivity of 100% (95% CI 74.12-100%) and a specificity of 100% (95% CI 99.86-100%) was reached for trisomy 21 (n=12). For trisomy 18 (n=3), the respective values were 75% (95% CI 30.06-95.44%) sensitivity and 100% (95% CI 99.86-100%) specificity, and for trisomy 13 (n=2), 100% (95% CI 20.65-100%) sensitivity and 99.96% (95% CI 99.79-99.99%) specificity. In the vanishing gestation group, 28 NIPT results were positive for trisomy 21, 18, or 13, with only five confirmed trisomies. CONCLUSION: Genome-wide NIPT performed accurately for detection of aneuploidy in dichorionic-diamniotic twin gestations.

Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test.

OBJECTIVE: We sought to determine the ability of single-nucleotide polymorphism-based noninvasive prenatal testing (NIPT) to identify triploid, unrecognized twin, and vanishing twin pregnancies. STUDY DESIGN: The study included 30,795 consecutive reported clinical cases received for NIPT for fetal whole-chromosome aneuploidies; known multiple gestations were excluded. Cell-free DNA was isolated from maternal blood samples, amplified via 19,488-plex polymerase chain reaction, and sequenced. Sequencing results were analyzed to determine fetal chromosome copy number and to identify the presence of additional fetal haplotypes. RESULTS: Additional fetal haplotypes, indicative of fetal triploidy, vanishing twin, or undetected twin pregnancy, were identified in 130 (0.42%) cases. Clinical confirmation (karyotype for singleton pregnancies, ultrasound for multifetal pregnancies) was available for 58.5% (76/130) of cases. Of the 76 cases with confirmation, 42.1% were vanishing twin, 48.7% were viable twin, 5.3% were diandric triploids, and 3.9% were nontriploid pregnancies that lacked evidence of co-twin demise. One pregnancy had other indications suggesting triploidy but lacked karyotype confirmation. Of the 5 vanishing twin cases with a known date of demise, 100% of losses occurred in the first trimester; up to 8 weeks elapsed between loss and detection by NIPT. CONCLUSION: This single-nucleotide polymorphism-based NIPT successfully identified vanished twin, previously unrecognized twin, and triploid pregnancies. As vanishing twins are more likely to be aneuploid, and undetected residual cell-free DNA could bias NIPT results, the ability of this method to identify additional fetal haplotypes is expected to result in fewer false-positive calls and prevent incorrect fetal sex calls.

First and second trimester maternal serum markers in pregnancies with a vanishing twin.

OBJECTIVE: The aim of this study was to assess the concentration of the first and second trimester maternal serum markers in pregnancies with a vanishing twin. METHODS: This is a retrospective case-control study of pregnancies screened for Down syndrome in one Ontario center. Singleton pregnancies with ultrasound evidence of a vanishing twin were identified, and each was matched with five normal singleton controls for ethnicity, maternal age, gestational age, and blood sampling date. The median MoM of the first and second trimester serum markers was compared between cases and controls. The differences were assessed using the Mann-Whitney U-test. RESULTS: The study included 174 pregnancies that had a vanishing twin. Compared with control pregnancies, pregnancy associated plasma protein A increased by 21% (p = 0.0026), alpha-fetoprotein (AFP) increased by 10% (p < 0.0001), and dimeric inhibin A (DIA) increased by 13% (p = 0.0470) in pregnancies with a vanishing twin. Unconjugated oestriol and total human chorionic gonadotrophin were not significantly changed in these pregnancies. CONCLUSIONS: Pregnancy associated plasma protein A is not an adequate marker for pregnancies with a vanishing twin. The impact of elevated AFP on risk estimation is offset by that of DIA to certain extent. Further studies are needed to establish an adequate adjustment method for AFP and DIA to improve the accuracy of screening results for these pregnancies.

Early ß-human chorionic gonadotropin trends in vanishing twin pregnancies.

OBJECTIVE: To describe the early ß-hCG trends in vanishing twins compared with normally progressing singleton and twin pregnancies. DESIGN: Retrospective cohort study. SETTING: University-based infertility clinic. PATIENT(S): Women undergoing fresh IVF/intracytoplasmic sperm injection (ICSI) cycles between 1998 and 2010. INTERVENTION(S): Early ß-hCG level increase in vanished twin pregnancies was compared with the level increase in normally progressing singleton and twin pregnancies. MAIN OUTCOME MEASURE(S): Two-day percent increase in ß-hCG level. RESULT(S): Pregnancies with vanishing twins demonstrated a significantly lower mean 2-day percent increase in ß-hCG level than singletons and twins (114.3% vs. 128.8% and 125.4%, respectively). Vanishing twins arresting at earlier developmental stages demonstrated significantly further reduced ß-hCG level increases. Infrequently, all groups had ß-hCG level increases less than previously established clinical thresholds that led to a live birth. CONCLUSION(S): Early ß-hCG level increases are slower in vanishing twins than in singleton and twin pregnancies, with the slowest increases seen when the spontaneous fetal losses occur at earlier developmental stages. All increases, however, are within clinically accepted normal limits. Therefore, abnormal ß-hCG level increases should not be attributed to a vanishing twin. Of note, an abnormal ß-hCG level trend--even an initial decrease--does not preclude live birth, even in a singleton pregnancy.

[Diagnostic image (3). (Lithopedion)]. / Diagnose in beeld (3).

In a 62-year-old woman with aspecific symptoms in the lower abdomen a lithopaedion was diagnosed mimicking an ovarian tumour.

The vanishing twin: a review.

This article reviews the scientific literature discussing the vanishing twin phenomenon. Information pertaining to frequency, aetiology, and potential complications, as well as the impact of sonographic technology on our growing understanding of the events in early multiple pregnancy is provided.

[Ultrasonic diagnosis in abortion of one twin. The vanishing twin phenomenon]. / Ultralyddiagnostikk ved abort av en tvilling. "Vanishing twin"-fenomenet.

The article discusses the issue of the "vanishing twin" phenomenon as experienced in private practice. Out of a total of 1172 pregnancies resulting in vital babies, there were 11 pairs of twins. In addition ultrasonography in the first trimester showed 12 pregnancies with two amnion sacs where only one developed further, and the mother ultimately gave birth to a single baby. One triple pregnancy was found, where the mother gave birth to vital twins. This material included two normal/blighted ova, nine normal/missed abortions and one normal/malformed-anencephalic. Painless bleeding occurred in six patients between weeks five and fourteen. The incidental twin conception was 1:51 but only 1:106 produced vital twins.

Embryonic loss in mares. Incidence, possible causes, and diagnostic considerations.

Fertilization rates were similar for normal and subfertile mares, and much of the difference in fertility between normal and subfertile mares was due to embryonic loss. Fertilization rate estimates for mares ranged from 71 to 96 per cent. The incidence of embryonic loss detected by ultrasonography between Days 11 and 50 was approximately 9 per cent for normal mares, and the estimated incidence of embryonic loss before Day 14 was also 9 per cent. Therefore, the estimated incidence of embryonic loss in normal mares between fertilization and Day 50 is approximately 18 per cent (Fig. 1). In subfertile mares, the corresponding estimate for embryonic loss between fertilization and Day 50 is 80 per cent, with most embryonic losses occurring before Day 14 in subfertile mares (Fig. 1). The high rate of early embryonic loss in subfertile mares could be related to embryonic defects, oviductal environment, or uterine environment. Oviductal embryos from subfertile mares were less viable than embryos from normal mares; therefore, embryonic defects were important in early embryonic losses in subfertile mares. These defects might be inherent within the embryo or might arise from the early oviductal environment. The uterine environment of subfertile mares was adequate to support normal embryos in early gestation; however, the relationship between the uterine environment and the increased metabolic demands of the conceptus in the late embryonic or early fetal periods requires further study. The uterine environment is also altered in mares with endometritis; therefore, endometritis may also be an important factor in embryonic loss in some mares. Uterine-induced luteolysis, as well as the effect of the pathogen or the resulting inflammation, may lead to embryonic loss. An increased susceptibility of some subfertile mares to endometritis could result in embryonic loss secondary to a postcoital endometritis that persists until the embryo reaches the uterus at Days 5 or 6 postovulation. Although progesterone is critical to embryonic survival, the cause-and-effect relationship between progesterone and spontaneous embryonic loss remains unclear. Reduced progesterone concentrations could be related to endometritis, failure of maternal pregnancy recognition, or luteal insufficiency. Progesterone supplementation may be indicated for some mares, but the value of exogenous progesterone for prevention of spontaneous embryonic loss has not been critically tested. A number of other factors have been associated with embryonic loss in mares.(ABSTRACT TRUNCATED AT 400 WORDS)

Outcome of the surviving cotwin of a fetus papyraceus or of a dead fetus.

Serial ultrasound examinations have demonstrated that one of two gestational sacs in a twin pregnancy may often disappear. When it disappears at an early stage of gestation, the pregnancy may advance without any disturbance and the cotwin can be delivered well developed and lively. When the intrauterine death occurs in the second trimester, the dead fetus usually results in a fetus papyraceus and the cotwin continues to be alive near term. However, when death occurs in the last trimester, the viable twin may be spontaneously delivered soon and be premature. In some cases of late fetal death, the dead fetus may induce intravascular thromboses in many organs of the surviving cotwin, so that the living infant may develop cerebral palsy later after birth.

[Fetus in fetu: report of 2 cases and analysis of the literature]. / Foetus in foetu: rapport de 2 cas et analyse de la littérature.

Foetus in foetu is a very unusual cause of abdominal mass in the infancy. Twenty cases only have been quoted in the literature. Two others cases are added, concerning two girls: a three months infant, second born from a genuine twin pregnancy, and a four weeks newborn whose the mass was discovered before the birth, on routine ultrasonography. In together, the diagnosis was made in operating room, then confirmed by pathologic studies. Literature data are recorded, and the difference between teratomas and foetus in foetu is point. The pathogeny remains obscure. It could result from the inclusion of a parasite twin in his bearer, become during embryologic stage of the delimitation.

Nonoperative management of ectopic pregnancy. A preliminary report.

The incidence of ectopic pregnancy is increasing throughout the Western world; at present it is uncertain how much of this increase is due to the disease and/or its antecedents and how much due to better means of diagnosis. That the treatment of the obvious or ruptured ectopic pregnancy should be surgical is beyond doubt. However, in view of the natural tendency of some ectopic pregnancies to terminate in tubal abortion or complete resorption, it is questionable whether surgery is always necessary in every early case or whether some patients can be monitored by means of rising or falling levels of beta subunits of human chorionic gonadotropin (HCG) until tubal abortion or resorption occurs. This may be the best means of preserving tubal function and fertility.

Reproductive failure in the pig: diagnosis and control.

An approach to reproductive failure in pigs, based on the regular collection and analysis of performance records is proposed. Inovlvement at this level gives veterinary surgeons familiarity with herd mangement and economics. The use of control charts to monitor performance is also advocated for detecting problems as they arise. When failure occurs, a stage-by-stage clinical investigation of the whole breeding programme is advisable. Post mortem studies may also be useful in detecting specific pathological changes. Diagnostic tests should only be used to confirm diagnoses. Having established the source and extent of the failure, and its likely cost, if uncorrected, appropriate measures can be considered. Three principal methods of control are discussed.