The work presented in this thesis first focused on the effectiveness and safety of IUI with ovarian stimulation, in vitro fertilization (IVF) compared to expectant management in couples with unexplained subfertility. We found that in couples with unexplained subfertility, IVF and intrauterine insemination (IUI) with ovarian stimulation may result in more live births or ongoing pregnancies, but also in more multiple pregnancies in comparison with expectant management. Second, we investigated the effectiveness and safety of pharmaceutical agents in IUI within a strategy with adherence to strict cancellation criteria to reduce the risk of multiple pregnancies in couples with unexplained subfertility and a poor prognosis of natural conception. Based on the data obtained by the studies described in this part of the thesis, we conclude that in couples with unexplained subfertility and a poor prognosis of natural conception, IUI regimens with adherence to strict cancellation criteria lead to acceptable multiple pregnancy rates without compromising effectiveness. We could not identify specific subgroups of women at baseline that benefit from one or the other pharmaceutical agent and also endometrial thickness is not a valid reason to switch between pharmaceutical agents. Within a strategy with adherence to strict cancellation criteria, we therefore would suggest to perform IUI with gonadotrophins, if costs do not play a role. Otherwise, we would suggest to start with IUI with clomiphene citrate.