I was going to go into card advantage this week, a little. I consider card advantage the number of potentially active cards, so cards in the active zones: Hand and Board.

I don't see why Mothers' Seed would be a problem in this case.

Shocking Transformation needs a sacrificial lamb as well as Mothers' Seed, but MS does reduce card advantage more by taking the card from your hand instead of from your deck. MS does boost tempo a little, because it's free to play. The extra loss of card advantage of MS is mostly virtual in many cases, as usually a Ghoul Khanum is a "dead card" otherwise because of the cost of 6. Sure, you can invest in cards to reduce the cost, or just plain make more resources, but that's another investment in card advantage, depending on your resource cost curve.

Mother's Seeding a Ghoul Khanum does bring out a lot of virtual card advantage, as she's very hard to get rid off. Toughness deals with most wounding effects, Arcane does wonders against most of Yog's removal and the printed cost of 6 makes DOA a costly proposition. That combined with the fact that an unanswered Ghoul gets ugly very, very fast, and the fact that Shub can deal with the few popular choices to deal with characters (Forgotten Isle for instance) makes it so that MS generally makes the cut.

Add to this that you are likely to have more ST targets, like T-Men to deal with Yig and maybe a Rat-Thing to deal with Glimpse of the Void and you most likely want a backup plan for your ST's.

The thread mentions Mi-Go Braincases as well. Unfortunately, these don't work as well with ST or MS, since they only trigger of a "destruction" effect, not of a "sacrifice" effect.

Cost reducers generally don't help card advantage; They do a lot for tempo and help getting ahead in resource development. They cost virtual card advantage though, because they don't directly contribute to winning the game, or neutralising your opponents cards.