A study was initiated to evaluate the prevalence of the luteinized unruptured follicle (LUF) syndrome in a group of 355 women with infertility. The diagnosis was established by carefully observing daily sonograms along with measuring estradiol, progesterone, and luteinizing hormone (LH) levels. Two distinct types of LUF syndrome were identified: mature follicle LUF, in which release of an ovum was not demonstrated after a follicle attained maturity (serum estradiol reached 200 pg/mL while serum progesterone remained less than 2.5 ng/mL), versus premature luteinization LUF, where the serum progesterone increased above 2.5 ng/mL before follicular maturation was attained. The use of either hCG alone or hCG in combination with hMG in a single injection at the time of follicular maturation successfully corrected mature follicle LUF in 21 of 46 patients (46%), whereas ovulation-inducing drugs plus hCG or hCG and hMG corrected LUF in 24 of 25 patients (96%). Clomiphene citrate proved inferior to hMG in that it corrected LUF in 3 of 25 patients (12%) versus 12 of 22 patients (95%) who had undergone hMG therapy. Thus, hMG-hCG therapy is the most efficacious for mature follicle LUF, but because release can occur spontaneously on occasion by an appropriately timed single gonadotropin injection, one could offer the less costly options first. For premature luteinization, speeding up follicular maturation with gonadotropin therapy is effective. Upon failure of this technique, the more costly endogenous gonadotropin suppression followed by hMG can be employed.

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