Mouse plasma progesterone levels are decreased in protease inhibitor (PI)–exposed pregnant mice and correlated with fetal weight. Mated mice were exposed to either Combivir alone (zidovudine plus lamivudine; dual nucleoside reverse transcriptase inhibitor [NRTI]), Combivir plus Kaletra (ritonavir-boosted lopinavir; PI based combination antiretroviral therapy [PI-cART]), or water as a control (Ctr) by gavage once daily starting on gestational day 1. A, The percentage of fetuses that were viable (light grey), nonviable (as assessed by pedal reflex) (white), or resorbed (dark grey) for each treatment group is shown. χ2 analysis yielded the following findings: Ctr vs PI-cART, P < .001; dual NRTI vs PI-cART, P < .01; and Ctr vs dual NRTI, P = not significant. B, Average fetal weight per litter. C, Average placenta weight per litter. D, Progesterone levels in maternal plasma. Levels normalized to the control median are shown. In panels B, C, and D, data are shown as box and whisker plots, with medians, interquartile ranges, and ranges. Statistical comparisons were assessed by the Kruskal–Wallis test with the Dunn post hoc test. Data in panels A–D were acquired from the same experiment with 10 values for the Ctr group, 8 for the PI-cART group, and 8 for the dual NRTI group. Experiments were repeated 2 times. *P < .05, **P < .01, and ***P < .001. E, Progesterone levels were plotted against the average fetal weight per litter for the PI-cART group. Correlation was assessed by Spearman r. Trend line was calculated by linear regression analysis. Data represent 17 values from 3 combined experiments.