C.A. Long

CA 125 in tissues and amniotic fluid during pregnancy

CA 125 was assayed in amniotic fluid and tissue extracts by immunoradiometric assay, and immunohistochemical studies were performed on paraffin-embedded sections of endometrium, decidua, and fetal membranes with the monoclonal antibody OC 125 used as primary antibody. The concentration of CA 125 in amniotic fluid changes during pregnancy so that levels of 800 to 1000 U/ml are found before 12 weeks. Thereafter, levels of 4000 to 10,000 U/ml are detected routinely. As term approaches, amniotic fluid CA 125 concentrations fall to a range of 1000 to 2000 U/ml. Levels of CA 125 in tissue extracts of secretory endometrium and decidua were 65,000 and 29,500 U/gm of tissue, respectively. CA 125 was readily detected on the apical surfaces of glandular epithelium and in the secretions of endometrial glands obtained throughout the menstrual cycle. It was also detected in the lumina of decidualized glands throughout pregnancy. No antigen was detectable within glandular epithelial cells. We have previously reported high concentrations of CA 125 in chorionic tissue extracts (42,000 U/gm) and low concentrations in amniotic tissue extracts (275 U/gm). In contrast to those findings, immunohistochemical techniques detected CA 125 within the intercellular canaliculi that surround amniotic epithelial cells but not in chorion. We conclude that the likely source of amniotic fluid CA 125 is the decidua and that it gains access to the amniotic fluid via the intercellular canalicular system that traverses the amniotic epithelium.

Receiver-operator characteristic, efficiency analysis, and predictive value of serum progesterone concentration as a test for abnormal gestations

OBJECTIVE Our objective was to determine if a discriminatory progesterone concentration could be established that confidently predicted abnormal early gestations. STUDY DESIGN We analyzed differences in progesterone concentrations between normal (n = 40) and abnormal (n = 34) pregnancies during the first 49 days of gestation. The receiver-operator characteristic curve, test efficiency, and predictive value of serum progesterone to discriminate between an abnormal and normal first-trimester gestation were calculated for progesterone concentrations between 5 and 25 ng/ml. RESULTS Receiver-operator characteristic curve analysis indicated that the best discriminatory progesterone concentration was 10 ng/ml. Test efficiency was maximum between serum progesterone concentration of 9 to 14 ng/ml (80%). When progesterone was less than 10 ng/ml, the predictive value of the abnormal test result was greater than 90%. CONCLUSION Receiver-operator characteristic analysis, test efficiency, and the predictive value of an abnormal test result suggest that the best progesterone cut off point that predicts abnormal early pregnancies is 10 ng/ml.

Evaluation of patients with abnormal uterine bleeding

An accurate, efficient diagnosis of disorders responsible for abnormal uterine bleeding depends on a systematic consideration of all the possible causes. Careful history and physical and pelvic examinations provide the framework for evaluation. Many adjunctive diagnostic aids can be used to evaluate women with abnormal uterine bleeding. These tests include complete blood cell count, pregnancy test, hormone levels (estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, dehydroepiandrosterone sulfate), thyroid function tests, liver function tests, and coagulation profile. The need for these tests are individualized and based primarily on the patients presentation. In women of reproductive age a complication of pregnancy should always be ruled out. Ectopic pregnancies can be life threatening. The prognosis in women with trophoblastic disease can be altered by a delay in establishing the correct diagnosis. Ultrasonographic studies, particularly transvaginal ultrasonography and hysteroscopy, have played an increasing role in the evaluation of patients with abnormal uterine bleeding over the past decade, especially for cases of intrauterine space-occupying lesions, including endometrial polyps, submucosal myomas, and retained placental fragments. Suspicion of reproductive tract malignancies is heightened in patients > 35 years old, those with a history of oligoovulation or anovulation suggestive of long-term unopposed estrogen exposure, those who are obese, and those who do not respond to first-line medical management. Diagnostic techniques available for the evaluation of these cases include endometrial biopsy, dilatation and curettage, transvaginal ultrasonography, and hysteroscopy. These procedures not only allow accurate diagnosis but may permit immediate therapeutic measures to be taken when organic causes are discovered. In summary, the key to the evaluation of abnormal uterine bleeding is a through history and physical and pelvic examinations governed by the differential diagnosis of excessive uterine bleeding and the selected use of adjunctive diagnostic tests and procedures only when absolutely necessary.

Elevated luteinizing hormone on the day of human chorionic gonadotropin administration does not reduce cycle fecundity in a low-dose flare-up in vitro fertilization protocol**Supported in part by the Vicksburg Hospital Medical Foundation, Vicksburg, Mississippi.††Presented at the Conjoint Meeting of The American Fertility Society and the Canadian Fertility and Andrology Society, Montreal, Quebec, Canada, October 11 to 14, 1993.

OBJECTIVE To determine if elevated LH at the time of hCG administration occurs and adversely affects success in a low-dose gonadotropin-releasing hormone analogue (GnRH-a) flare-up protocol in hMG-stimulated IVF cycles. DESIGN Pearson correlation matrix analysis of hormonal, gamete, and clinical data derived from 203 consecutive IVF cycles was performed. All patients were treated with low-dose GnRH-a (250 micrograms SC leuprolide acetate) and hMG. In 203 consecutive IVF cases, serum was obtained on the day of hCG administration and assayed for E2, LH, and P. These data were correlated with peak E2, number of follicles, oocytes, embryos, and conceptions. Additionally, patients with elevated LH were compared with the nonelevated LH group. RESULTS Twenty six women had LH > 35 mIU/mL (mean +/- SEM; 51.1 +/- 1.9) and five pregnancies (cycle fecundity 19.2% per retrieval). One hundred seventy-seven patients had LH < 35 mIU/mL (16.3 +/- 0.5) and 25 pregnancies (cycle fecundity 14.1%). There were no differences in the mean P (1.0 +/- 0.1 ng/mL, conversion factor to SI unit, 3.81) and E2 (1,672 +/- 144 pg/mL, conversion factor to SI unit, 3.671) of the former group compared with the P (1.1 +/- 0.07 ng/mL) and E2 (1,456 +/- 69 pg/mL) of the latter group. There was no correlation with the number of follicles, oocytes, embryos, pregnancies, E2, or P to LH concentration (rmax = 0.132). CONCLUSION In a low-dose, GnRH-suppression, IVF induction protocol, elevated LH occurs in a small subset (13%) of women at the time of hCG administration. This event does not appear to alter cycle fecundity nor induce premature luteinization.