The principal way in which the promise of God threatens to be thwarted is through infertility or the barrenness of the various females that are chosen to be mothers of this great tribe and multitude that God promises Abraham will spring from his loins. This is of course the case with Sara, who famously laughs at the angels who visit her husband Abraham and promise him that he will have a multitude of descendants. This is because of her old age and the low chances of her ever conceiving again.
However, infertility is something that we see echoed again and again throughout the Biblical account. For example, in Jacob's marriage to Rachel, she is unable to conceive initially. Although his other wife, Leah, and his wife's serving-maids all give him children, Rachel initially is not able to have children until she gives birth to Joseph, who is of course Jacob's favourite son and also God's chosen one to save his brothers and family and ensure that they prosper and grow in number.