Clinical application of a contingent screening strategy for trisomies with cell-free DNA: a pilot study.

BACKGROUND: Different strategies have been designed for clinical implementation of cell-free DNA (cfDNA) testing. We aimed to evaluate the performance of a contingent strategy based on conventional screening and offering cfDNA to the intermediate-risk group, for the screening for trisomies 21, 18 and 13. Secondary objectives were to assess the uptake of cfDNA in women with intermediate-risk, to evaluate the performance of cfDNA testing, and the preferences of pregnant women with intermediate risk. METHODS: Prospective observational pilot study between February 2016 and March 2017. Singleton pregnancies with a known outcome were included in the study. At the conventional screening (first trimester combined test or second trimester quadruple test) women were classified in high (risk ≥1:250) or low risk (< 1:250). For the study, a contingent strategy was applied: following the conventional screening women were classified into three groups: high risk (risk ≥1:10 or nuchal translucency ≥3 mm), intermediate-risk (risk 1:11 to 1:1500) and low risk (< 1:1500), and a cfDNA test was offered to those at the intermediate risk. RESULTS: For the analysis, 2639 women were included, 2422 (91.8%) had a first trimester combined test and 217 (8.2%) a second trimester quadruple test. There were 5 cases of trisomy 21, 4 of trisomy 18 and none of trisomy 13. For the contingent strategy, the detection rate and false positive rates were 88.9% (8/9) and 1.3% (35/2630), respectively. For the conventional strategy, the detection rate and false positive rates were 66.7% (6/9) and 5.3% (140/2630), respectively. The cfDNA test had a detection rate for trisomy 21 of 100% (3 out of 3), and a false positive rate of 0.2% (1/466). In a survey, 81.8% (374/457) of women in the intermediate-risk group would choose cfDNA testing as the second line test, mainly due to the lack of risk for the fetus. CONCLUSION: A contingent screening strategy for trisomies 21, 18 and 13, based on conventional screening, and offering a cfDNA test to women with a risk between 1:11 to 1:1500, reduced the false positive rate and increased the detection rate for these trisomies. Moreover, this strategy is well accepted by women.

Management and outcome of pregnancies in women with red cell isoimmunization: a 15-year observational study from a tertiary care university hospital.

BACKGROUND: The aims of this study were to determine the prevalence of the different anti-erythrocytic alloantibodies, to describe pregnancy outcomes according to a low-risk and high-risk classification for fetal anemia and to determine the factors that influence adverse perinatal outcomes. METHODS: This retrospective observational study included women referred to our center following the identification of maternal anti-erythrocytic alloantibodies between 2002 and 2017. Pregnancies were classified as high risk for fetal anemia in cases with clinically significant antibodies, no fetal-maternal compatibility and titers ≥1:16 or any titration in cases of Kell system incompatibility. In high-risk pregnancies, maternal antibody titration and the fetal middle cerebral artery peak systolic velocity (MCA-PSV) were monitored. Low-risk pregnancies underwent routine pregnancy follow-up. RESULTS: Maternal antibodies were found in 337 pregnancies, and 259 (76.9%) of these antibodies were clinically significant. The most frequent antibodies were anti-D (53%) and anti-K (19%). One hundred forty-three pregnancies were classified as low risk for fetal anemia, 65 (25%) cases were classified as no fetal-maternal incompatibility, 78 had clinically nonsignificant antibodies, 4 (2.8%) resulted in first-trimester pregnancy loss, and 139 (97.2%) resulted in livebirths. Of the 194 high-risk pregnancies, 38 had titers < 1:16 (resulting in 38 livebirths), and 156 had titers ≥1:16 or anti-K antibodies. In the last group, 6 cases miscarried before 18 weeks, 93 had a MCA-PSV < 1.5 multiples of the median (MoM), resulting in 3 perinatal deaths that were unrelated to fetal anemia, one termination and 89 livebirths; and 57 had a MCA-PSV > 1.5 MoM, resulting in 3 intrauterine deaths, 6 terminations and 48 livebirths. Ninety-two intrauterine transfusions were performed in 45 fetuses (87% anti-D). Adverse outcomes were related to a MCA-PSV > 1.5 MoM (p < 0.001), hydrops (p < 0.001) and early gestational age at first transfusion (p = 0.029) CONCLUSION: Anti-D remains the most common antibody in fetuses requiring intrauterine transfusion. A low or high-risk classification for fetal anemia based on the type of antibody, paternal phenotype and fetal antigen allows follow-up of the pregnancy accordingly, with good perinatal outcomes in the low-risk group. In the high-risk group, adverse perinatal outcomes are related to high MCA-PSV, hydrops and early gestational age at first transfusion.

Conventional ovarian stimulation vs. delayed single dose corifollitropin alfa ovarian stimulation in oocyte donors: a prospective randomized study. Tail trial.

The present study compares two protocols for ovarian controlled stimulation in terms of number of cumulus-oocyte complexes and metaphase II oocytes. We employed a single injection of 150mcg of corifollitropin alfa after a 7-day oral contraceptive pill-free interval for TAIL group and a conventional administration of corifollitropin alfa after a 5-day OCP-free interval with additional rFSH from 8th of ovarian controlled stimulation. Prospective, randomized, comparative, non-inferiority, opened and controlled trial carried out in 180 oocyte donors 31 were excluded, 81 were randomized to the control group and 68 to the TAIL group. No differences were found in the number of follicles larger than 14 and 17 mm at triggering day. However, a lower number of cumulus-oocyte complexes and metaphase II oocytes were obtained in TAIL group compared to the control group, expressed as median (interquartile range): 10.5 (5.5-19) vs. 14 [11-21] and 9 (4-13) vs. 12 (9-17) respectively. Additionally, the incidence of failed retrieval or metaphase II oocytes = 0 was higher in TAIL group 7(10.3%) vs. 1(1.2%) p = 0.024. The use of a single injection of corifollitropin alfa after a 7-day oral contraceptive pill-free interval in oocyte donors resulted in a lower number of cumulus-oocyte complexes and metaphase II oocytes. No additional rFSH was administered in this group. Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-001343-44/results.

Impact of endometrial compaction on reproductive outcomes after cryotransfer of euploid embryos in a modified natural cycle: protocol for a prospective cohort study.

Introduction: Embryo implantation is a complex and poorly understood process. Most studies to date have focused on the analysis of the endometrium at the end of the estrogenic phase, while the available data on its importance after secretory transformation are limited and inconsistent. Current evidence does not allow for a conclusive interpretation of the changes observed in the pre-implantation endometrium, whether in the natural or replacement cycle, and their relevance in the development of a pregnancy or the implications for clinical practice. Methods: Multicenter prospective observational cohort study. Based on our sample size calculation, the study group will consist of 206 women (exposed or "compaction" group: 103 women with a decrease of ≥ 5% in endometrial thickness between the estrogenic phase and the day of embryo transfer; non-exposed "non-compaction" group: 103 women with similar or greater endometrial thickness between these time points). The main objective of this study is to compare the ongoing pregnancy rates in natural cycles for euploid embryo transfer in patients who present endometrial compaction at the time of transfer versus those who with a stable or greater endometrial thickness with respect to the estrogenic phase. The estimated duration of the study is 30 months. Inclusion criteria are: 18 to 50 years of age, with primary or secondary infertility, subjected to endometrial preparation in a modified natural cycle for transfer of a genetically euploid blastocyst, from their own oocyte or oocyte donation, with a normal uterine cavity. Exclusion criteria are: uterine or endometrial disease (e.g., multiple myomatosis, severe adenomyosis, Asherman syndrome, refractory endometrium), conditions that prevent correct ultrasound assessment (tilted uterus), or a history of recurrent implantation failure or repeated miscarriages. Discussion: The findings from this study will provide valuable insights into the potential influence of the "endometrial compaction" phenomenon on reproductive outcomes during natural cycle endometrial preparation. By examining this aspect, we aim to contribute to a better understanding of the factors that may impact successful outcomes in fertility treatments.