Fetal Sex Prediction Research Articles

The erasure of transgender and intersex identities through fetal sex prediction and genetic essentialism.

The erasure of transgender and intersex identities through fetal sex prediction and genetic essentialism.

Performance of prenatal cfDNA screening for sex chromosomes

PurposeThe aim of this study was to assess the performance of cell-free DNA (cfDNA) screening to detect sex chromosome aneuploidies (SCAs) in an unselected obstetrical population with genetic confirmation. MethodsThis was a planned secondary analysis of the multicenter, prospective SNP-based Microdeletion and Aneuploidy RegisTry (SMART) study. Patients receiving cfDNA results for autosomal aneuploidies and who had confirmatory genetic results for the relevant sex chromosomal aneuploidies were included. Screening performance for SCAs, including monosomy X (MX) and the sex chromosome trisomies (SCT: 47,XXX; 47,XXY; 47,XYY) was determined. Fetal sex concordance between cfDNA and genetic screening was also evaluated in euploid pregnancies. ResultsA total of 17,538 cases met inclusion criteria. Performance of cfDNA for MX, SCTs, and fetal sex was determined in 17,297, 10,333, and 14,486 pregnancies, respectively. Sensitivity, specificity, and positive predictive value (PPV) of cfDNA were 83.3%, 99.9%, and 22.7% for MX and 70.4%, 99.9%, and 82.6%, respectively, for the combined SCTs. The accuracy of fetal sex prediction by cfDNA was 100%. ConclusionScreening performance of cfDNA for SCAs is comparable to that reported in other studies. The PPV for the SCTs was similar to the autosomal trisomies, whereas the PPV for MX was substantially lower. No discordance in fetal sex was observed between cfDNA and postnatal genetic screening in euploid pregnancies. These data will assist interpretation and counseling for cfDNA results for sex chromosomes.

Genetic counseling for fetal sex prediction by NIPT: Challenges and opportunities.

Non-invasive prenatal testing (NIPT) has grown in ubiquity in the last decade and is now endorsed by Society for Maternal Fetal Medicine and American College of Obstetricians and Gynecologists as a screening tool for aneuploidy in all patients. Past studies have demonstrated a tendency among obstetrics patients to focus on the ability of NIPT to predict fetal sex chromosomes; however, data on the experiences of genetic counselors (GCs) counseling on NIPT and fetal sex prediction are limited. This mixed-methods study aimed to explore how GCs counsel about NIPT and fetal sex prediction, as well as the use of gender-inclusive language in this setting. A 36-item survey with multiple choice, Likert scale, and open-ended questions was distributed to GCs who currently offer NIPT to patients. Quantitative data were analyzed using R and qualitative data were manually analyzed and coded via inductive content analysis. A total of 147 individuals completed at least some portion of the survey. A majority of participants (68.5%) reported frequent interchangeable use of the terms 'sex' and 'gender' by patients. A majority (72.9%) of participants reported that they rarely or never discuss the difference between these terms in sessions (Spearman's rho = 0.17, p = 0.052). Seventy-five respondents (59.5%) indicated that they had taken continuing education courses on inclusive clinical practices for trans and gender-diverse (TGD) patients. Several themes arose from free responses; the most frequently identified themes were the need for thorough pretest counseling that properly describes the scope of NIPT and the challenge of discrepant pretest counseling by other healthcare providers. Results from our research identified challenges and misconceptions GCs face when offering NIPT and various tactics implemented to mitigate these. Our study highlighted the need for the standardization of pretest counseling regarding NIPT, additional guidance from professional organizations, and continuing education focused on gender-inclusive language and clinical practices.

The disappearing act: diminishing Y chromosome cfDNA contribution in vanished twin pregnancies

In non-invasive prenatal screening (NIPS) via cell-free DNA (cfDNA), demise of a male co-twin may lead to discordant fetal sex prediction due to persistent chromosome Y contribution with a surviving female fetus. Despite this well-known limitation, the detection and clearance rate of chromosome Y cfDNA in vanished twin pregnancies has not been well described. Here chromosome Y contribution between serial NIPS samples is examined in 49 vanished twin pregnancies.

Methods of detection and isolation of trophoblast cells from trans-cervical specimens – a historical overview

Abstract Trophoblast cells can be detected and isolated from the cervical epithelial cells obtained via various techniques of trans-cervical samples collection such as a mucus aspiration, endocervical lavage, or standard cervical brushing in the early first trimester, even from the 5 weeks’ gestation. Isolated fetal cells can be used in the early prediction of fetal sex, prenatal diagnostics of the most common aneuploidies, and any other genetic abnormalities. Nevertheless, the collection of trophoblastic cells has limited efficacy compared to currently used methods of detection of free fetal DNA in maternal circulation or other protocols of invasive prenatal diagnostics available at later stages of pregnancy. In the past years, trans-cervical cell samples were collected mainly in women before planned pregnancy termination. The early trophoblastic cells isolation from women in ongoing pregnancies opens new perspectives for further studies focused on the elucidation of pathophysiology of numerous pregnancy-related complications.

Why the Korean Law that Prohibits Fetal Sex Prediction Must be Abolished

Why the Korean Law that Prohibits Fetal Sex Prediction Must be Abolished

Correlation of maternal concentrations of plasma testosterone with fetal sex in horses

ABSTRACT: The objectives of this study were to evaluate the correlation of fetal sex and plasma testosterone concentrations between the 5th and 8th months of pregnancy in mares and to verify the applicability of this test to predict fetal sex. Blood samples were collected from 21 mares at 30-day intervals of between 150 and 240 days of pregnancy. Plasma testosterone was determined by radioimmunoassay and the sex of the foals confirmed at birth. The levels of maternal testosterone were higher in mares carrying female fetuses at months 5 and 8 (P < 0.05). Limit values were determined by analyzing the receiver operating characteristic (ROC) estimates: 35.5 pg/mL and 40 pg/mL for the 5th and 8th month, respectively. For the mares with plasma testosterone values equal to or above the threshold, gestation of female foals was predicted, and for those with plasma testosterone below the threshold values pregnancy of male foals was predicted. In the 5th month, the predictive values for male and female fetuses were 70% and 88.9%, respectively; the detection rates were 87.5% and 72.7%, and the total accuracy of the examination was 78.9%. In the 8th month, the predictive values for male and female fetuses were 80% and 90%, respectively; the detection rates were 88.9% and 81.8%, and the total accuracy of the examination was 85%. It was concluded that there was a correlation between fetal sex and plasma testosterone concentrations in pregnant mares. Prediction of fetal sex based on plasma concentrations of maternal testosterone can be performed in months 5 and 8 with 78.9% and 85% accuracy, respectively.

Fetal sex prediction measuring yolk sac size and yolk sac-fetal pole distance in the first trimester via ultrasound screening.

The aim of the study was to determine the accuracy of fetal sex definition by measuring the yolk sac size and the yolk sac-fetal pole distance in the first trimester via ultrasound (US) screening. We enrolled 92 gestational women in this prospective study. In the first trimester of US examination, the gestational sac, the gestational sac-fetal pole distance, and the yolk sac size were measured. When the fetal pole was in the longitudinal position, the distance between the fetal pole and the yolk sac was measured in millimeters (mm). The crown-rump length (CRL) was measured in the same position. US examination at 22weeks was performed to determine whether the fetal gender was male or female. The genders of the fetuses were recorded. The sexes were also confirmed and recorded after birth. Fifty-five (59.8%) of the newborns were found to be male, while 37 (40.2%) of them were found to be female. We compared the yolk sac size and the yolk sac-fetal pole distance in both the female and male groups. We found that the genders showed a significant difference in terms of yolk sac-fetal pole distance, whereas the yolk sac size showed no significant difference between the genders. The optimal cutoff value of the yolk sac-fetal pole distance was 1.80mm, with 70% sensitivity and 67% specificity for female gender prediction. The distance also showed an independent association with gender prediction in the first trimester. Yolk sac-fetal pole distance may have the potential to predict gender in the first trimester of pregnancy.

Fetal sex determination in light of interdisciplinary current studies: a forensic anthropological approach

Aim: In this study, it was aimed to highlight the situation and importance of fetal sex determination in the context of forensic anthropology. Suggestions have been made about the development of this subject with current approaches and interdisciplinary perspectives.Materials and Methods: Fetal osteology is one of the topics that needs to be developed within forensic anthropology. New techniques are needed both due to lack of sample and to the limited methods that can be applied to this age group. In this respect, a literature review was conducted within the scope of studies on fetal sex determination. It has been revealed how the applications of different disciplines in this field can be adapted to forensic anthropology.Results: The vast majority of current studies emphasize that ilium gives reliable results in fetal sex determination. Often evaluated in both clinical applications and forensic anthropological studies, this bone is subjected to morphological and morphometric analyses. Conclusion: Perspectives of interdisciplinary approaches will enable the development of fetal sex determination studies within forensic anthropology and will play an important role in identification studies. The use of technological tools such as ultrasound for fetal sex determination is thought to be useful for the development of forensic anthropological techniques as in clinical applications. Testing new techniques on fetal sex prediction is expected to contribute to many areas such as growth - development, genetics, embryology, neonatology and endocrinology.

Prediction of fetal sex by early pregnancy ultrasound localizing the implantation site lateralization

Prediction of fetal sex by early pregnancy ultrasound localizing the implantation site lateralization

An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing.

Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.

A novel approach to prenatal fetal sex diagnosis by detecting an insertion in the Y-chromosome of ovine Amelogenin gene

It is completely clarified that both intact fetal cells and cell-free fetal nucleic acids cross the placenta and circulate in the maternal blood stream during pregnancy. In the current study we employed a new approach in applying Amelogenin gene for fetal sex prediction in ovine species. The amount of fetal DNA in the maternal blood was quantified using quantitative real-time PCR technique. Peripheral blood was obtained from 45 pregnant sheep with age of pregnancy varying from 8 to 18 weeks. Optimal primers were designed on Amelogenin intron 4, a Y specific insertion region in Amelogenin gene. For 42 (93.3%) ewes, agreement was verified between fetal sex prediction using cffDNA (cffDNA) and birth outcome. The test sensitivity, specificity and accuracy of fetal sex prediction were 96.5%, 87.5% and 93.3% respectively. The result of relative quantification showed that the cell-free fetal DNA values were significantly higher in ewes with more than 3 months of pregnancy relative to those with less than it. In conclusion, an insertion part in the ovine Y-chromosome Amelogenin gene could be successfully used for fetal sex prediction in ovine species using cell-free fetal DNA.

Ultrasonographic fetometry and prenatal fetal sex assessment in camels (Camelus dromedarius)

The aims of this study were to determine the developmental patterns of some fetal parts to achieve a high accuracy level in the assessment of gestational age and to assess the feasibility and accuracy of ultrasonic prenatal fetal sex assessment in camels. Serial ultrasonographic examinations were carried out on seven pregnant dromedary camels. A total of 329 ultrasonographic examinations were conducted between the second and the 54th weeks of pregnancy. Intrauterine fluid accumulation was detected between the second and third weeks of pregnancy. The embryo proper was noticed between the third and fourth weeks. Organization of the embryo was first observed between the sixth and seventh weeks. Ossification was first detected between the seventh and ninth weeks. The accessibility during the total gestational period was 35/329 (10.6%) for crown-rump length, 35/329 (10.6%) for biparietal diameter, 42/329 (12.8%) for abdominal diameter, 42/329 (12.8%) for ruminal length, and 126/329 (38.3%) for eyeball diameter. A high correlation was found between gestational age and each of the studied parameters (P < 0.0001). The highest correlation was found with the crown-rump length and the biparietal diameter during the first trimester and with the eyeball diameter during the third trimester of pregnancy. The overall accuracy of the ultrasonic prenatal fetal sex assessment was 91.7%. The best window was found during the 11th week of pregnancy. It was concluded that sonographic fetometry can be useful for the evaluation of fetal development, the estimation of gestational age, and the prediction of prenatal fetal sex in camels.

Detection and quantification of cell-free fetal DNA in ovine maternal plasma; use it to predict fetal sex

Prediction of fetal sex in the ovine species could be useful in the management decisions, such as sex selection in breeding programs, culling decisions, and lowering the progeny test cost. In the present study detection of fetal SRY gene in maternal blood plasma using the polymerase chain reaction technique was used to predict fetal sex at different times of gestation in the ewe. The quantitative changes of fetal DNA during pregnancy were also investigated using quantitative real-time polymerase chain reaction. Fetal DNA was isolated from blood plasma of 46 pregnant ewes during the second to fifth month of gestation. The 286-base pair DNA fragment was detected in all samples with male pregnancies, but no female pregnancies. The sensitivity and specificity of tests were 100% with no false negative or false positive results. It was also determined that fetal DNA levels are significantly increased during pregnancy, up to approximately 1.65-fold in the last 2 months of pregnancy. This is the first report of fetal sex determination and circulating fetal DNA quantification by a molecular method in the ovine species.

Use of Multiplanar 3-Dimensional Ultrasonography for Prenatal Sex Identification

Determination of fetal sex is an important part of detailed second-trimester ultrasonography. This task can be hindered by the fetal position, a low amniotic fluid volume, and advanced gestational age. Identification of fetal sex is further important in multiple gestations and prior histories of indeterminate-sex pregnancies. The goal of the study was to compare the effectiveness of 2-dimensional ultrasonography (2DUS) versus 3-dimensional ultrasonography (3DUS) at sex identification and to determine how genitalia measurements taken with 3DUS technology compare with measurements taken with 2DUS. A total of 111 patients at or beyond 16 weeks' gestation were recruited. Assignments of fetal sex using 2DUS and 3DUS were compared by the test of proportions. The actual neonatal sex was obtained after delivery. Given such small number of misdiagnoses by either 2DUS or 3DUS, the accuracies of the two modalities were not found to be statistically distinguishable from one another (P = .5585). The penile length, scrotal width, and bilabial diameter according to gestational age were measured and compared with previously published 2DUS data by t tests. Sexes were assigned and interpreted in 65 cases. Ranges of genitalia measurements were plotted against gestational age and were found to be comparable with published data. There was a dramatic difference between the bilabial diameter and scrotal width with advancing gestational age that made sex determination much easier in the third trimester. Although 3DUS did not have better prediction of fetal sex when compared with 2DUS, it may be a useful tool in conjunction with traditional imaging techniques in assigning fetal sex.

Prediction of Fetal Sex by Amplification of Fetal DNA Present in Cow Plasma

The aim of the present study was to predict fetal sex at different time points of gestation in cattle by detecting the fetal SRY gene in cow plasma. Plasma DNA was extracted from the blood samples of 110 pregnant cows during the gestational period of 30 to 242 days. Nested PCR was employed to detect the fetal SRY, which the male fetus carries exclusively, in cow plasma. The cows positive for SRY were predicted to carry male fetuses. The results showed that the fetal DNA from cow plasma was successfully amplified and that fetuses could be sexed with an overall accuracy rate of 100% (43/43) for males and 91.0% (61/67) for females and with accuracy rates of 100% (3/3) for males and 85.7% (12/14) for females at 30 EN 59 days of gestation and 100% (40/40) for males and 92.5% (49/53) for females at more than 2 months of gestation, respectively. This suggests that the molecular method developed here could be used in sex prediction for fetuses.

Accuracy of fetal gender detection using a conventional nested PCR assay of maternal plasma in daily practice

We have prospectively examined the diagnostic accuracy of a conventional multiplex polymerase chain reaction (PCR) analysis of maternal plasma for fetal gender determination in daily practice. Plasma DNAs were obtained from 168 pregnant women between five and 32 weeks of gestation. The 198-bp-specific sequence on Y-chromosome and the 261 bp ATL1-gene-specific sequence on X-chromosome were coamplified in a multiplex nested PCR manner. The results of fetal sex prediction were compared with routine analysis of fetal tissues and birth outcomes. The ATL1-specific sequences were detected in all cases but Y-chromosome-specific signals were observed in 95 of 97 plasma samples of women carrying male fetuses, leading to the sensitivity of 97.9, 100 and 100% for the first, second and third trimesters, respectively, and the specificity of 100% at all gestational stages. Therefore, fetal gender detection in maternal plasma with a conventional multiplex PCR assay is highly accurate in daily practice which should prove useful for non-invasive prenatal screening of sex-linked genetic disorders.

Early identification in maternal blood of fetal sex in the presence of fetal DNA from previous pregnancies

The presence of cell-free fetal DNA in maternal plasma allows for the noninvasive identification of fetal sex. It was recently suggested, however, that fetal-cell DNA can persist in the maternal circulation from one pregnancy to the next [1], thereby severely hampering prenatal diagnostic analysis of fetal DNA from maternal plasma. A method for clearing fetal-cell DNA from a previous pregnancy in maternal plasma was developed to facilitate the identification of cell-free fetal DNA from the current pregnancy. Thirty-three of the 73 recruited women were pregnant, and the 40 who were not been pregnant with at least 1 male child. Characteristics of the entire sample are shown in Table 1. Blood samples were collected in ethylene diamine tetra-acetic acid (EDTA) tubes with 4% formaldehyde [2]. Samples from nonpregnant women underwent 3 different protocols. The first protocol consisted in centrifugation at 200 ×g for 10 min; the second protocol consisted of the first protocol, followed by centrifugation at 1600 ×g for 10 min, followed by centrifugation at 13,000 ×g for 10 min. The third protocol consisted in the second protocol plus a plasma filtration through 0.22 μm filters (Millex-GS, Millipore, Bedford, MA, USA). All samples from pregnant women were processed using the third protocol. DNA was extracted from 400 μL of plasma using aQIAampDNABloodMini Kit (Qiagen, Hilden, Germany). Real-time polymerase chain reaction with an ABI Prism 7700 (Applied Biosystems, Foster City, CA, USA)was used to amplify SRY and GAPDH gene sequences. Of the extracted plasma DNA, 5 μL was amplified to a final volume of 25 μL under the following cycling conditions: 50 °C for 2min, 95 °C for 10min, 40 cycles of 95 °C for 15 s, and 60 °C for 1 min. The study findings are shown in Table 2. When the third protocol was used, fetal-cell DNA from previous pregnancies was entirely cleared out from the plasma of nonpregnant women. For this reason, the third protocol was also used in pregnant women. The GAPDH gene was detected in all samples and the SRY gene only in the samples of women carrying male fetuses. Sensitivity and specificity were 100% for the prediction of fetal sex. By the time recruitment for the present study was completed and DNA extracted using formaldehyde, finding that formaldehyde increased the amounts of cell-free fetal DNA in maternal plasma in [2] was no longer held accurate [3]. Nevertheless, this study's findings confirm and expand on recently published results regarding the diagnosis of fetuses at risk for X-linked diseases [4]. Clearing maternal plasma from fetal-cell DNA from previous pregnancies further enhances the potential of

Early detection of cell-free fetal DNA in maternal plasma

Objectives We aimed to establish the earliest gestational age at which fetal DNA in maternal plasma could be detected and whether this was reliable at 12–13 weeks' gestation. Study design A prospective observational cohort study of 32 pregnancies either after IVF or before prenatal diagnosis by CVS. Maternal blood was taken and RT-PCR was carried out to detect the multi-copy Y chromosome associated DSY14 gene. The end point was gender as assessed at delivery or on karyotype. Results Y signal was obtained as early as 14 days post conception (4 weeks' gestation) and has a good prediction rate by 12 weeks' gestation. Conclusion Free fetal DNA allows very early prediction of fetal sex in some cases and could be useful for clinical use for X-linked conditions by the end of the first trimester.

Identification of fetal gender in maternal blood is a helpful tool in the prenatal diagnosis of haemophilia

Fetal DNA identification in maternal circulation has provided a new approach for non-invasive prenatal diagnosis. However, fetal DNA can persist in maternal blood long after the delivery, severely hampering this possibility. We addressed the issue of fetal DNA persistence in maternal blood. Thus, we investigated cell-free fetal DNA as a reliable approach in prenatal diagnosis of haemophilia. Forty non-pregnant women, who had had at least a male fetus, 29 control pregnant women, and 14 pregnant women, carriers of hemophilia A or B. The assessment of Y-chromosomal sequences was performed by analysing SRY and amelogenin genes using PCR-based techniques. A protocol consisting of double centrifugation at full speed followed by plasma filtration hampered the detection of Y chromosome-specific sequence in non-pregnant women. In 29 control pregnant women, blinded determination of fetal sex confirmed the specificity and sensitivity of the method applied. In 14 pregnant carriers of hemophilia, the investigation revealed a male fetus in nine pregnancies. Excluding the three cases in which a spontaneous miscarriage occurred, the sensitivity and specificity of fetal sex prediction by SRY and amelogenin gene analyses were both 100% as compared with the invasive approach and the fetal sex outcome at birth (six males and five females). Because of its high accuracy in prediction, fetal gender determination with cell-free fetal DNA in maternal plasma may be a useful tool in prenatal diagnosis of haemophilia allowing for the avoidance of invasive procedures for female fetuses.