Progesterone in Women with Recurrent Miscarriages.

To the Editor: In summarizing their well-executed randomized trial, Progesterone in Recurrent Miscarriages (PROMISE), Coomarasamy et al. (Nov. 26 issue)1 state that there is no evidence of benefit from progesterone supplementation “in the first trimester” of pregnancy among women who have had three or more miscarriages. We wish to clarify three points. First, the trial did not address progesterone supplementation in women with coexisting subfertility. Nearly 33% of the women screened for the trial were excluded because of subfertility (515 of 1568 women). Second, because progesterone plays a key role in the implantation of the embryo, benefit from supplementation may be realized if progesterone is administered before and at the time of implantation. In women undergoing fertility treatments, it is common to administer progesterone before and at the time of implantation,2 but in the trial by Coomarasamy et al., administration began after implantation. Third, a short luteal phase (<10 days) is associated with a lower probability of clinical pregnancy, and it may also be associated with miscarriage.3,4 The correction of a lutealphase defect before implantation may improve the chance of ongoing pregnancy. The initiation of progesterone supplementation before pregnancy testing in women with subfertility, lutealphase defect, or both deserves further investigation to determine whether it would increase the chance of successful implantation and ongoing pregnancy.