The Lost can pick up Soul Hearts and Black Hearts despite having no health and thus can activate Immaculate Conception.
Keeper cannot encounter hearts, thus the item is useless for him.
As the short-lived Half Red Hearts dropped by Tainted Magdalene also count, it is an excellent choice for her since she will constantly be picking up hearts and gain all five familiars quickly.
Familiars spawned by the item do not affect item pools, so multiple copies of one familiar can be obtained. For example, a second Seraphim can be purchased after Immaculate Conception spawns one.
As with Cambion Conception, if this item is removed in anyway (such as with a XVII - The Stars?), the familiars from Cambion Conception will be removed upon updating familiars, including picking up items that don't add familiars but update its cache, such as Brimstone.
If the item is re-obtained after being removed (e.g. by dropping the item as Tainted Isaac), any familiars that were removed will return once familiars are updated.
Interactions
Hypercoagulation: By intentionally taking damage with something like a fire and grabbing the half-red hearts, Isaac can easily generate powerful familiars for free.
The Jar: Hearts collected in the jar do not count towards activation.