Objective: To compare the screening performance of serum pregnancy-associated plasma protein-A (PAPP-A) versus placental growth factor (PlGF) in routine first trimester combined screening for preeclampsia (PE), small for gestational age (SGA) birth and trisomy 21. Methods: Retrospective study nested in pregnancy cohorts undergoing first trimester combined screening for PE and trisomy 21 using the Fetal Medicine Foundation (FMF) algorithm based on maternal characteristics, nuchal translucency, PAPP-A, free beta-human chorionic gonadotropin, blood pressure and uterine artery Doppler. Women at high-risk for preterm PE (≥1 in 50) received 150 mg aspirin, serial fetal growth scans at 28 and 36 weeks and were offered elective birth from 40 weeks of gestation. PlGF was retrospectively quantified in stored surplus first-trimester serum samples. The performance of combined first trimester screening for PE, SGA and trisomy 21 using either PAPP-A or PlGF was calculated. Results: Maternal serum PAPP-A was assayed in 1094 women including 82 with PE, 111 with SGA <10 th centile, 53 with both PE and SGA <10 th centile, and 94 with trisomy 21. PlGF levels were retrospectively obtained from 1066 out of 1094 women. Median serum PlGF MoM was significantly lower in PE (1.0, IQR=0.8-1.4, P<0.01), SGA (1.0, IQR=0.8-1.3, P<0.001) and trisomy 21 pregnancies (0.6, IQR=0.5-0.9, P<0.0001) compared to controls (1.2, IQR=0.9-1.5).There was no significant difference in the performance of first trimester screening using PAPP-A versus PlGF for either preterm PE (AUC 0.78 vs 0.79, P=0.55) or term PE (AUC 0.74 vs 0.74, P=0.60). These findings persisted even after correction for the effect of targeted aspirin use on prevalence of PE. Similarly, there were no significant differences in combined screening sensitivity or specificity for SGA or trisomy 21 when using PAPP-A versus PlGF. Conclusion:Using PlGF or PAPP-A in routine first trimester combined screening with maternal characteristics, blood pressure and uterine artery Doppler does not make an appreciable clinical difference to the detection of PE or SGA. Depending on the setting, biomarkers should be chosen to achieve a good compromise between performance and measurement requirements. This pragmatic effectiveness study suggests that combined screening for PE can be successfully implemented in public healthcare settings without changing current protocols for the assessment of PAPP-A in the first trimester.

Purpose To evaluate the efficiency of ovarian tissue treatment with Z-VAD-FMK, a broad-spectrum caspase inhibitor, to prevent follicle loss induced by ischemia/reperfusion injury after transplantation. Methods In vitro, granulosa cells were exposed to hypoxic conditions, reproducing early ischemia after ovarian tissue transplantation, and treated with Z-VAD-FMK (50 μM). In vivo, cryopreserved human ovarian fragments (n = 39) were embedded in a collagen matrix containing or not Z-VAD-FMK (50 μM) and xenotransplanted on SCID mice ovaries for 3 days or 3 weeks. Results In vitro, Z-VAD-FMK maintained the metabolic activity of granulosa cells, reduced HGL5 cell death, and decreased PARP cleavage. In vivo, no improvement of follicular pool and global tissue preservation was observed with Z-VAD-FMK in ovarian tissue recovered 3-days post-grafting. Conversely, after 3 weeks of transplantation, the primary follicular density was higher in fragments treated with Z-VAD-FMK. This improvement was associated with a decreased percentage of apoptosis in the tissue. Conclusions In situ administration of Z-VAD-FMK slightly improves primary follicular preservation and reduces global apoptosis after 3 weeks of transplantation. Data presented herein will help to guide further researches towards a combined approach targeting multiple cell death pathways, angiogenesis stimulation, and follicular recruitment inhibition.

What are the novel findings of this work? Routine contingent screening for placenta accreta spectrum disorders based on the finding of placenta previa and previous uterine surgery is effective in a public healthcare setting. What are the clinical implications of this work? A contingent screening strategy for placenta accreta spectrum disorders is feasible in an ultrasound service where placenta localization is routinely performed. When linked to a placenta accreta diagnostic and surgical management service, adoption of such a screening strategy has the potential to significantly reduce the maternal morbidity and mortality associated with this condition.

Purpose of reviewThis review aims at summarizing the latest evidence on diagnosis, natural history and management of caesarean scar pregnancy (CSP).Recent findingsCSP can result in maternal morbidity from major haemorrhage, uterine rupture, placenta accreta spectrum disorders and hysterectomy. Classification of the CSP types, presence of fetal heart activity, gestational age and residual myometrial thickness seem to influence rates of ongoing pregnancy, subsequent development of placenta accreta with expectant management, as well as success and complication rates associated with various methods of pregnancy termination. Expectant management may be appropriate in certain good prognosis cases, such as absent fetal heart activity or when the myometrial layer at the implantation site is relatively thick. Surgical treatments are typically associated with higher success rates, but seem to result in severe haemorrhage more frequently than medical treatments, which have higher failure rates. Although other treatment modalities are available, in general, the size and quality of evidence to guide care provision in CSP is very poor.SummaryCSP can be associated with severe maternal morbidity but can also lead to a livebirth. There is currently a lack of good-quality evidence to predict the outcome of CSP and provide informed and evidence-based care.

Objective Follicular granulocyte colony-stimulating factor (G-CSF) is a new biomarker of oocyte quality and embryo implantation in in vitro fertilization (IVF) cycles. Its role in reproduction is poorly understood. Our study aimed to investigate the mechanisms and cells responsible for G-CSF production in the preovulatory follicle. Design Laboratory research study. Setting Single-center study. Interventions Granulosa cells and leukocytes were isolated from the follicular fluids (FF) or the blood of women undergoing IVF and from the blood of a control group of women with spontaneous ovulatory cycles to perform cocultures. Main outcome measure G-CSF-secreted protein was quantified in the conditioned media of cocultures. Results G-CSF secretion was considerably increased in cocultures of granulosa cells and leukocytes. This effect was maximal when leukocytes were isolated from the blood of women in the late follicular phase of the menstrual cycle or from the FF of women undergoing IVF. The leukocyte population isolated from the FF samples of women undergoing IVF had a higher proportion of granulocytes than that isolated from the corresponding blood samples. Leukocytes induced the synthesis and secretion of G-CSF by granulosa cells. Among a range of other FF cytokines/chemokines, only growth-regulated oncogene alpha (GROα) was also increased. Conclusion The notable rise in G-CSF at the time of ovulation coincides with the accumulation of follicular granulocytes, which stimulate G-CSF production by granulosa cells via paracrine interactions. High follicular G-CSF concentrations may occur in follicles with optimal granulosa-leukocyte interactions, which could explain the increased implantation rate of embryos arising from these follicles.

No abstract

No abstract

No abstract