Prometrium is the same progesterone as that which the ovary makes - so it is 'natural'. It is probably safe to take throughout the first trimester. There are some researchers who believe that there might be a very small increase in the risk of a birth defect in boy babies called hypospadias - with hypospadias the urethral opening is on the underside of the penis rather than at the tip or end. On the other hand, progesterone is used during pregnancy to prevent premature labor quite extensively. I personally do not believe the hypospadias association - of course there is always a small risk of this, but in my many years in practice using progesterone extensively I have not seen it.