Strengths and limitations of this study
PCOS, preeclampsia
GESTATIONAL DIABETES, OF PREGNANCY COMPLICATIONS, IUGR, PREGNANCY COMPLICATIONS, MISCARRIAGE, PREECLAMPSIA
There are several strengths of the present study including the well-characterised women with PCOS and the randomised, double-blinded placebo-controlled multi-centre study design, prospective data sampling and meticulous quality-checked diagnosis control. Some limitations should also be mentioned. There was a slight difference between the two trials regarding the metformin dose, 1700 mg and 2000 mg daily, respectively, which might have affected our results. Since maternal s-PROK1 has a dynamic course during pregnancy, timing of blood sampling for determination of s-PROK1 is crucial. Based on previous studies showing elevated s-PROK1 in the second and third trimester of preeclamptic and IUGR pregnancies, we chose to analyse s-PROK1 in gestational week 19, representing the second trimester. We did not measure the s-PROK1 in serum samples taken at inclusion (between gestational week 5 and 12), as s-PROK1 has been shown to decline remarkably within this period and patients could not have been comparable. s-PROK1 was not measured at gestational week 32 and 36 either, as these late timepoints would not hold predictive values for gestational diabetes, early onset preeclampsia or late miscarriage. However, we cannot exclude that s-PROK1 should have been determined at several timepoints to study the course of PROK1 for pregnancy complications in PCOS. Furthermore, the number of pregnancy complication cases was limited possibly leading to type II errors.