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After repeated im courses of menopausal gonadotropins and hCG, a factor was found in a woman's serum which preferentially bound the intact hCG molecule (nanograms or milliinternational units required for 50% displacement of [125I] hCG: hCG, 9.2 ng; APL, 74 mIU; Pergonal, 400 mIU; LER 960, 900 ng; and FSH and TSH alpha-subunits, hCG beta-subunit, and LH beta-subunit, greater than 1000 ng). This factor had a low affinity (Ka = 5.8 X 10(9) liters/M) and high capacity (binding capacity, 5.5 X 10(-11) M/liter) for hCG, was isolated with the immunoglobulin G fraction of the patient's serum, and coeluted with immunoglobulin G from a Sepharose CL-6B-200 column. Preincubation of hCG with this fraction did not reduce the in vitro biological activity of the hCG in the hypophysectomized rat ventral prostate weight assay. Similarly, there was no gonadal resistance to hCG in the patient, since ovulation could still be induced with hCG, and both progesterone and 17-hydroxyprogesterone levels as well as duration of the luteal phase increased after repeated hCG injections. This serum factor prolonged the half-life of injected hCG in the patient's circulation (t 1/2 = 9.4 days in patient vs. 1.3 days in controls). The titer of the factor transiently decreased with the exogenous administration of hCG. No binding of the serum factor to human placental tissue could be demonstrated by immunohistochemical techniques. Thus, this factor behaves similarly to the antibodies frequently found after the injection of other polypeptide hormones, in that it serves as a high capacity reservoir of the hormone but does not significantly reduce its biological activity. These results also indicate that the factor requires the intact tertiary structure of the hCG molecule for immune recognition.

As used herin, the term "occult pregnancy" is defined as a pregnancy which aborts so early that no clincial suspicion of its existence arises except perhaps that there has been a few days' delay in the onset of an otherwise normal menstrual period. Sixteen Clomid-induced ovulatory cycles as evidenced by biphasic temperature charts with hyperthermic phases of 12 days or more were studied. Of these, 10 had serum luteinizing hormone values in the late luteal phase normal for that part of the cycle (6-16 mIU/ml) and six, or 37.5% showed values sufficiently elevated (more than three standard deviations) to indicate a cross reaction with human chorionic gonadotropin and hence the presence of an otherwise unsuspected pregnancy. All had clinically normal menstrual periods 12 hours to 6 days later. The clinical significance of this finding is discussed.

Serum luteinizing hormone (LH) values determined by radioimmunoassay can be of aid in evaluating patients with short-term amenorrhea. These values have proved useful in ruling out pregnancy in cases of hypothalamic amenorrhea and amenorrhea occuring during treatment with contraceptive pills and also in diagnosing early pregnancy after clomiphene therapy.