Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis.

Pre-eclampsia (PE) complicates 2%-8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12), inhibin-A, pregnancy associated plasma protein A (PAPP-A), placental growth factor (PlGF) and placental protein 13 (PP-13). The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39-0.41) at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.786 (SE 0.02). When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03). In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s) can be identified in order to improve the management of women destined to develop PE.

Transplantation of cryopreserved human ovarian tissue: restoration of reproductive function after two cycles of radio- and chemo-therapeutic treatments.

BACKGROUND: Patient S. was born in 1983, developed a Ewing-Sarcoma and obtained low dose chemotherapy in 1996. In 2007, Patient S. received high-dose chemotherapy because lung-metastases were diagnosed. The aim of the study was to investigate the health of cryopreserved ovarian tissue and also to examine whether this ovarian tissue can restore the reproductive function of patient after two cycles of radio-and chemo-therapeutic treatments. METHODS: Twenty pieces of ovarian tissue (total of approximately 200 mm2) were conventionally frozen with 6% (v/v) dimethyl sulfoxide, 6% (v/v) ethylene glycol and 0.15 M sucrose and kept for five years before 8 pieces were thawed and transplanted back into the patient. Two small (1 x 2 x 1 mm) pieces of this thawed tissue were cultured in a chicken embryonic chorioallantoic membrane (CAM)-system for 5 days to assess the tissue viability. RESULTS: The ovarian tissue that was grafted re-established spontaneous menstrual bleeding within five months and serum 17-beta estradiol increased from 19 to 330 pg/mL. Ultrasound revealed a dominant follicle at the site of the transplanted tissue in the follicular phase after the menstrual bleed. Analysis of the CAM cultured tissue established that 88% of the primordial follicles had degenerated and there was limited growth of blood vessels. CONCLUSIONS: In spite of the damage caused by the cryopreservation the surviving follicles could restore ovarian function after re-transplantation.