Parental Origin of the Retained X Chromosome in Monosomy X Miscarriages and Ongoing Pregnancies.

OBJECTIVE: To assess the distribution of the parental origin of the retained X chromosome in monosomy X, either in miscarriages or in ongoing pregnancies. METHOD: The parental origin of the X chromosome was determined in monosomy X pregnancies, either miscarriages or ongoing pregnancies. Microsatellite marker patterns were compared between maternal and fetal samples by quantitative fluorescence polymerase chain reaction. Distributions of maternally and paternally derived X chromosome were assessed in miscarriages and in ongoing pregnancies using two-tailed Fisher exact test. RESULTS: Forty monosomy X pregnancies were included in the study: 26 miscarried at 5-16 weeks, and 14 ongoing pregnancies were diagnosed at 11-20 weeks. The retained X chromosome was maternally derived in 67% of the cases. In miscarriages, maternal and paternal X chromosome were retained in a similar proportion (54% [95% CI: 35-73%] vs. 46% [95% CI: 27-65%]), while in ongoing pregnancies, the maternal rate was 13 times higher (93% [95% CI: 79-100%)] vs. 7% [95% CI: 0-20%]). CONCLUSIONS: The retained X chromosome in individuals with monosomy X should theoretically be maternally derived in 2/3 of the cases. Our study suggests a preferential early miscarriage in pregnancies with a retained paternally derived X chromosome. This may explain the observation that 75-90% of individuals with monosomy X retain the maternal X chromosome.

Effectiveness of ovarian age as the background risk for aneuploidy screening in an unselected pregnant population.

The aim of this study was to assess the performance of first-trimester combined screening when replacing the chronological maternal age by Anti-Müllerian hormone (AMH) and antral follicle count (AFC)-derived ovarian ages, as the background risk in trisomy risk estimation. A total of 639 pregnant women who completed first-trimester combined screening together with AMH and AFC determination were included. Trisomy risks were estimated based on three distinct 'maternal ages' as a-priori risk (chronological age, AMH- and AFC-derived ovarian age). The screening performance was assessed using three different approaches: received operator curve; detection rate and false positive rates for a fixed 1/250 threshold; and detection rates for a fixed 3% false positive rate. A non-significant trend was shown for AMH-derived age for both an increased area under the curve (0.986 versus 0.979) and an increased detection rate (from 83% to 100%) for a 1/250 risk threshold. For a 3% false-positive rate, a non-significant trend for increased detection with the use of both AMH- and AFC-derived ovarian ages was observed (from 67% to 83%). These results indicate that, although ovarian derived ages seem to potentially reflect a more precise background risk for fetal trisomies, the improvement in screening performance is only residual.

Antral follicle count as a marker of ovarian biological age to reflect the background risk of fetal aneuploidy.

STUDY QUESTION: Can antral follicle count (AFC) measured during pregnancy be used as a marker of ovarian age to assess the background risk of fetal aneuploidy? SUMMARY ANSWER: AFC was lower than expected according to maternal chronological age in trisomic pregnancies; therefore ovarian age could potentially reflect a more precise background risk of fetal aneuploidy screening. WHAT IS KNOWN ALREADY: The decline in a woman's reproductive function is determined by a decline in the ovarian follicle pool and the quality of oocytes. The quantitative status of ovarian reserve can be indirectly assessed by AFC, but the role of AFC as an aneuploidy risk marker in pregnant women has not been assessed yet. STUDY DESIGN, SIZE, DURATION: Our study comprised a prospective cohort including 1239 singleton pregnancies scanned before 14 weeks in our center during a 14-month period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reference ranges for AFC were constructed using 812 spontaneously conceived, chromosomally normal singleton ongoing pregnancies using the Lambda-Mu-Sigma method. The study population (n = 934) included 19 pregnancies with viable autosomal trisomies (trisomies 21, 18 and 13), 17 non-viable autosomal trisomies (other than 21, 18 or 13), 7 monosomies X, 1 sex trisomy and 3 triploidies (total n = 47 with chromosomal abnormalities). AFC in chromosomally abnormal pregnancies was plotted against the reference ranges. AFC multiple of the median was calculated according to the median AFC obtained by each year of age. MAIN RESULTS AND THE ROLE OF CHANCE: Sixty-eight percent of women carrying a pregnancy with viable trisomies and 65% with non-viable trisomies presented an AFC below the 50th percentile. The median ovarian age in viable trisomies and non-viable trisomies was estimated to be 3 and 6 years above than median maternal age, respectively. However, the median ovarian age in monosomies X and triploidies was not higher than median maternal age. LIMITATIONS, REASONS FOR CAUTION: We did not assess the intra- and inter-observer reliability, or use specific three-dimensional analysis which may have advantages over our two-dimensional study. In clinical practice, a drawback for assessing AFC during pregnancy is that transvaginal ultrasound is needed at the 11- to 13-week scan, when the transabdominal approach is used most commonly. Furthermore identifying ovaries by ultrasound during pregnancy could be challenging. WIDER IMPLICATIONS OF THE FINDINGS: Considering that AFC reflects ovarian aging, this 'ovarian biological age' could potentially reflect a more precise background risk of fetal aneuploidy. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by PI 11/00685. Instituto de Salud Carlos III. Fondo de Investigación Sanitaria. No competing interests declared.

Patterns of maternal vascular remodeling and responsiveness in early- versus late-onset preeclampsia.

OBJECTIVE: We sought to assess vascular structure and function in early- and late-onset preeclampsia (PE) at the time of diagnosis. STUDY DESIGN: We evaluated 100 PE cases subdivided into 50 early- and 50 late-onset cases according to gestational age at onset (34 weeks), and 100 controls paired by maternal age and gestational age at scan with cases. Carotid intima-media thickness (IMT), distensibility, and circumferential wall stress together with inferior vena cava (IVC) collapsibility were assessed by ultrasound. RESULTS: Early PE was characterized by increased carotid IMT diameters, and arterial stiffness with no significant changes in IVC parameters as compared to normotensive pregnancies. Late PE was characterized by significantly increased carotid IMT and lumen diameters as compared to controls while arterial stiffness, as expressed by distensibility, did not provide pronounced changes. A significant decrease of IVC collapsibility index was also observed in late PE as compared to controls. CONCLUSION: The current data suggest that distinct vascular adaptations in early and late PE could reflect different pathophysiologic mechanisms. Future studies are warranted to further assess the complex etiologies and clinical expressions of the 2 entities.

The Cognitive Approach to Bioethical Issues in Perinatal Care in Greece.

BACKGROUND AND AIM: Current practice in prenatal diagnosis becomes challenging with new bioethics issues emerging constantly during daily clinical routine. Although fetal interventions are driven by a motivation to improve the health of the fetus, progress in fetal therapies raises issues of maternal autonomy. The objective of this article is to assess bioethics in prenatal diagnosis in Greece as well as bioethics education. METHODS: The study was conducted between October 2018 and December 2019. Two hundred and twenty eligible responders were involved in fetal and perinatal medicine in Greece. The questionnaire was developed as a Likert scale. Part 1 covered the participants' general opinion about bioethics. Part 2 covered ethical dilemmas likely to arise when routine screening presents a complicated result. RESULTS: In the study, 92.3% of the participants considered that the branch of bioethics is necessary in medical practice. Regarding challenging bioethics issues, only 86% of the participants consider that the miscarriage risk should be discussed after an invasive procedure. Furthermore, it is not clear for responders whether informed consent is a medical or legal obligation (43% vs 33%) and whether information should be provided orally or written (49% vs 46%). Finally, 32% of healthcare practitioners declare that they are not fully aware of the law concerning the rights of the fetus. CONCLUSIONS: Although healthcare professionals acknowledge the distinct role of bioethics, mismanagement of ethical dilemmas reveals that under-graduate teaching of this discipline is not addressed effectively. Identifying the parameters that would improve the learning process would make a significant contribution in the routine clinical practice.

Heterotrisomy recurrence risk: a practical maternal age-dependent approach for excess trisomy 21 risk calculation after a previous autosomal trisomy.

A new maternal age-dependent method to estimate absolute excess risks of trisomy 21, either after a previous trisomy 21 (homotrisomy) or after another trisomy (heterotrisomy), is proposed to be added to the estimated risk by conventional screening methods. Excess risk at term for a subsequent trisomy 21 was calculated from midtrimester risks reported by Morris et al., decreasing from 0.49% at 20 years to 0.01% at 46 years at the index pregnancy. Excess risk after a previous uncommon trisomy was derived from data reported by Warburton et al., decreasing from 0.37% at 20 years to 0.01% at 50 years.

Intertwin crown-rump length discordance in the prediction of fetal anomalies, fetal loss and adverse perinatal outcome.

OBJECTIVE: To assess the risks of fetal anomalies, fetal loss and adverse perinatal outcome in a cohort of first-trimester intertwin crown-rump length (CRL) discordant twins, stratified by chorionicity and the degree of CRL discordance. METHOD: Four-hundred-and-seventy-one twin pregnancies were scanned during an 8-year period at 11-14 weeks, and those with an intertwin CRL discordance ≥10% were compared with concordant twins. Outcomes were also compared between monochorionic and dichorionic twins and between moderate (10-16%) and severe (>16%) discordance. RESULTS: Four-hundred-and-five twin pregnancies, 65 discordant and 340 concordant, were follow-up. Discordant twin pregnancies were at significant higher risk of chromosomal (OR = 11.42; 95% CI: 2.78-46.94) and structural anomalies (OR = 5.91; 95% CI: 2.25-15.54), spontaneous fetal loss (OR = 4.23; 95% CI: 1.79-10.01), birthweight discordance (OR = 2.8; 95% CI: 1.48-5.65) and small-for-gestational age (OR = 3.48; 95% CI: 1.78-6.79). Similar differences (except for birthweight discordance) were observed among dichorionic twins. Among monochorionic, increased frequencies were only seen for structural anomalies, birthweight discordance and small newborns. Severe CRL discordance presented with higher rates of structural anomalies, stillbirth, birthweight discordance and small newborns. CONCLUSION: Intertwin CRL discordance (≥10%) results in an increased risk of fetal anomalies and growth restriction that increases in severe CRL discordance (≥16%).

Transcervical chorionic villus sampling: a practical guide.

First trimester screening for fetal aneuploidies has made the implementation of diagnostic techniques essential. Chorionic villus sampling (CVS) is the method of choice for obtaining chorionic villi for molecular and cytogenetic analysis in the first trimester. Two techniques have been developed, a transcervical and a transabdominal. The selection criteria have been based historically on factors, such as placental location, parity, maternal weight and preference of the operator. In our institution, we developed an elevated level of expertise in the field of transcervical approach, resulting in good quality of samples and comparable fetal loss rate to other approaches. Despite three decades of transcervical CVS performance, little consensus in terms of its technique and clinical guidelines exists. Considering the expertise and the volume of procedures performed at our center, we suggest a practical clinical guideline for transcervical CVS.

Role of ovarian reserve markers, antimüllerian hormone and antral follicle count, as aneuploidy markers in ongoing pregnancies and miscarriages.

OBJECTIVE: To assess the role of two ovarian reserve markers, antimüllerian hormone (AMH) and antral follicle count (AFC), as markers of the background risk for fetal trisomy. DESIGN: Prospective study. SETTING: Tertiary referral hospital. PATIENT(S): Assessment was carried out either in ongoing pregnancies or miscarriages in our center. INTERVENTION(S): AFC was assessed transvaginally during a routine (11-13 weeks) or referral scan. AMH was determined either during the first-trimester maternal serum markers assessment or in cases referred for chorionic villi sampling after the invasive procedure. MAIN OUTCOME MEASURE(S): AMH reference ranges were constructed according to maternal age, and AMH- and AFC-derived ovarian ages were compared among three different cytogenetic groups (normal karyotype, autosomal trisomies, and other chromosomal anomalies) in both ongoing pregnancies and miscarriages. RESULT(S): In autosomal trisomies, the median AFC-derived ovarian age was 3-5 years above the median maternal age. No differences were observed between AMH-derived ovarian age and maternal age. CONCLUSION(S): AFC-derived ovarian biologic age reflects a more precise background risk for fetal aneuploidy that is not observed for AMH-derived age.

The use of atosiban and ritodrine in external cephalic version.

OBJECTIVE: To compare the efficacy of atosiban and ritodrine as tocolytic agents for successful external cephalic version (ECV). Factors affecting the success of ECV, as well as maternal and perinatal outcomes are reviewed. METHOD: A retrospective review of women who underwent ECV with either atosiban (2004) or ritodrine (2002). RESULTS: Atosiban and ritodrine were similarly effective (28 versus 41%, p>0.05). Side effects were more common with ritodrine. No significant adverse maternal and perinatal outcomes were recorded following procedures with either tocolytic. CONCLUSION: Atosiban is a safe choice for ECV with less maternal side effects. However, it is no more effective than ritodrine and the benefit of safety has to be balanced against that of cost.