Further Effects of Nonsteroidal Anti-inflammatory Compounds on Blastocyst Hatching in vitro and Implantation Rates in the Mouse1

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Abstract
When tested in protein-free medium NCTC 109, mouse blastocytes hatching in vitro was inhibited by low doses (< 50 .mu.M) of indomethacin, meclofenamic acid, mefenamic acid and naproxen [prostaglandin inhibitors]. Ketoprofen was not inhibitory within the same concentration range. In medium supplemented with 10% fetal calf serum, meclofenamic acid inhibited hatching above 100 .mu.M but in contrast naproxen had no effect at 500 .mu.M. With ultrafiltration plus high performance liquid chromatography analysis, 92-83% of meclofenamic acid over the range 100-200 .mu.M was bound to 10% fetal calf serum. Cinemicrographic recording of supplemented cultures containing 100-150 .mu.M meclofenamic acid revealed that the principal reason for the inhibition of hatching was the prevention of adequate blastocyst expansion which is a normal prerequisite to hatching in vitro. Intrauterine administration of 160 .mu.M meclofenamic acid to 1 horn of pregnant mice on day 4 significantly reduced the rate of implantation.