Other. That/this is pretty personal for me, Lucillle. But for you, I will answer that question.
It would be close between four.
1) When I was 15 y/o, I caught my father with the town whore, all drunk and naked and in a human double-pretzel configuration...and was left scarred by it. He made me promise not to tell, or else, told me he was glad it was me and not my mom who caught him, and told me that I would be doing the same thing in another 15 years. Yes.....he did.
I promised myself that I would not hurt a wife, a son, a family, or do anything of the kind....and I have kept that promise to myself.
But 'infidelity' hurts, destroys lives, and injures the human spirit. I know.
2) Deciding not to finish medical school, halfway through, caused some friends, and family, who I thought loved me for just being me....to drop me like a hot potato and never speak to me again.
3) Divorce-like. On September 9, 1994, I had a life partner (or so I thought) of four years, that moved out when I was working the 11pm-7am shift. Took the furniture, the dog, the cat, the dishes, the contents of the joint bank account, etc.,....and left me a spineless 'dear john' letter. I have remained partnerless since that very morning that I got home, and with a keyturn...my life changed. I found out later that he had been cheating on me (yes, the 'infidelity' theme again), with various people, and would just order me another double vodka on the rocks when the waiter asked him, "...weren't you just in here the other day with a so-and-so with so-and-so hair?....".
4) Over the past 20 or so years, almost all of my gay male friends from the early 80's college years and party years...have one by one died of AIDS. I have no long time gay male friends my age. I was kind of prudish in the sexual domain---so I guess that is why I'm still here---I realized very early that what I wanted with another human being went beyond just the sexual act. Sometimes I feel very alone, literally, generationally,...a number of ways.
5) The day in the summer of 2006 when my baby sister called and told me she'd been diagnosed with Multiple Sclerosis.
Gosh, I don't know which is worse, the instantaneous shocks...or the prolonged...
I think that's about it, Lucille.