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Objective: To determine the follicular and luteal phase impact of low-dose GnRH agonist (GnRH-a) treatment during follicular stimulation for IVF., Design: A randomized prospective study compared patients receiving low-dose GnRH-a and hMG therapy to clomiphene citrate (CC) and hMG cycles., Setting: Patients were treated through a university-based IVF-ET program., Patients: Thirty-six patients underwent follicular stimulation with low-dose GnRH-a and hMG and were compared with 34 patients undergoing ovulation induction with CC and hMG., Results: Significantly shorter luteal phase length occurred with GnRH-a and hMG therapy; however, there was no statistically significant difference in luteal P levels. Follicular parameters were the same (peak E2, number of follicles, and number of oocytes), suggesting that folliculogenesis was not altered. There were no statistical differences in pregnancy rates., Conclusions: Sustained low-dose GnRH-a therapy during follicular stimulation does not have a clinical effect on luteal function.

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.

Objective: To directly compare the ability of serum P and hCG doubling time to predict early gestational complications., Design: We analyzed differences in P concentrations and hCG doubling times between spontaneously conceived normal and abnormal pregnancies (abortions and tubal pregnancies) during the first 49 days of pregnancy. Multiple 2 x 2 contingency tables were constructed that compared pregnancy outcome within discriminatory serum P concentrations or hCG doubling time. From these tables relative operating characteristic curves were generated for P concentration and hCG doubling times. The area under the curves were estimated and compared by the critical z score., Results: Calculation of the areas under the curve for hCG doubling time and P concentration yielded values of 0.799 +/- 0.056 and 0.780 +/- 0.051 (mean +/- SEM), respectively. Critical z testing did not reveal a significant difference between the two curves., Conclusion: Serum P and hCG doubling times equally predict early gestational normalcy. Thus, a single serum P may be just as valuable in estimating risks of early pregnancy complications as repeated hCG measurements.

Objective: To determine the regulatory role of hCG on P secretion in normal and abnormal (abortive and ectopic) first trimester pregnancies., Study Design: The number of doublings of hCG per day (1/DT; reciprocal of hCG doubling time) was correlated with serum P using linear and nonlinear models in normal intrauterine pregnancies, spontaneous abortions, and ectopic pregnancies (EPs) conceived spontaneously or after clomiphene citrate (CC)., Results: Linear correlations between P and 1/DTs of hCG were poor. In contrast, nonlinear modeling with a hyperbolic curve fit the data well and allowed all of the data to be included for analysis regardless of the pregnancy type. Furthermore, this model could be used to explain the differential P concentrations seen in normal and abnormal first trimester pregnancies. The nonlinear hyperbolic model demonstrated that follicular events determine the maximal P production during early gestation. Human chorionic gonadotropin 1/DTs approximately equal to 0.5 sustain maximal P production. Progesterone production is then sustained by the rate of change of hCG., Conclusion: Nonlinear correlation analysis suggests that P production in early gestations is regulated by prior follicular events and the rate of hCG production.

Objective: To determine if a "discriminatory" P concentration could be established that predicted abnormal early pregnancies in clomiphene citrate (CC)-conceived cycles., Design: Progesterone concentrations of gestations between 28 and 49 days from last menstrual period in both spontaneously conceived and CC-stimulated cycles were analyzed using a relative-operating characteristic (ROC) curve., Interventions: Serum P concentrations were measured in 222 pregnant patients from the first 49 days of gestation. One hundred sixteen patients conceived in a spontaneous cycle and 106 patients conceived in CC-treated cycles. Two by two contingency tables were used to calculate the true-positive (sensitivity) and false-positive rates at 20 specific P at 20 specific P concentrations. A ROC curve was then generated by plotting the sensitivity of the test against the percent of normal patients incorrectly classified (false positive) at each P level. The best discriminatory value was estimated in each curve at a point of high sensitivity associated with a minimal false-positive value. The areas under the curve and SE were calculated for each group and compared by the critical ratio z-test., Results: The best discriminatory P concentration was 10 ng/mL (32 nmol/L) for spontaneously conceived pregnancies and 30 ng/mL (95 nmol/L) for CC-treated pregnancies. The area under each ROC curve was significantly predictive. Comparison of the two curves indicated that the ability of P measurements to predict gestational complications was independent of follicular stimulation., Conclusions: Follicular stimulation with CC increases the discriminatory P value that predicts gestational normalcy but does not alter the clinical utility of the test.

Moderate ovarian hyperstimulation syndrome occurred after LA was administered to control menorrhagia in an anephric woman who required hemodialysis. We postulate that women who require dialysis may be at special risk for the development of this syndrome.

A uteroglobin-like molecule was detected with a sensitive radioimmunoassay for rabbit uteroglobin in the uterine washings of women. This antigen was detectable only in small amounts in the uterine washings obtained from women in the late luteal phase or proliferative phase, but was detected in large amounts in uterine washings of women collected during the early and midluteal phases of the ovarian-menstrual cycle. Our findings suggest that antigenically similar portions of rabbit uteroglobin have been phylogenetically conserved in women, and that endometrial production and secretion of this human uteroglobin-like antigen may be hormonally regulated.

Thirty-two patients undergoing in vitro fertilization (IVF) were given bromocriptine either 1 or 12 hours before anesthesia or received no drug to determine what effect suppression of transient, anesthesia-induced hyperprolactinemia would have on peripheral and follicular fluid hormones, fertilization and cleavage rates, and pregnancy. Thirty minutes after anesthesia, there was a 120-ng/mL rise in serum prolactin (PRL) in control patients versus an insignificant change in women given bromocriptine. Levels of PRL in follicular fluid were significantly less, and estradiol (E2) levels were higher (P less than 0.05) in all bromocriptine-treated patients compared with controls, whereas follicular fluid levels of progesterone (P), inhibin activity, and midluteal serum P were unaffected. Although fertilization and pregnancy rates were similar, a greater proportion of fertilized oocytes from bromocriptine-treated patients advanced to cleaving embryos compared with controls (95% versus 63%, respectively; P less than 0.001). We conclude that bromocriptine, given before anesthesia, can suppress transient, anesthesia-induced hyperprolactinemia and dramatically alter follicular fluid concentrations of PRL and E2. Although these changes in hormonal milieu affected neither oocyte fertilization nor pregnancy rate in our IVF patients, they seemed to have a positive influence on embryonic development after IVF.

We have developed a novel semipermeable chamber for intraabdominal culture of primate gametes and embryos. Application of the egg-embryo chamber offers a unique opportunity to study fertilization and preimplantation embryogenesis. Intrinsically normal monkey embryos displayed timely cleavage and symmetric form when cultured in this intraabdominal chamber for up to 72 hours. The birth of the first normal live monkey infant derived from the egg-embryo chamber is reported.

Recent studies have demonstrated marked disparities between bioassayable (BIO) versus radioimmunoassayable concentrations of luteinizing hormone (LH) at midcycle. Other studies in intact women and monkeys have indicated that progesterone (P) may facilitate estrogen induction of the preovulatory gonadotropin surges. We have combined the study of these observations as follows: long-term castrate female monkeys were given estradiol benzoate with and without subsequent P or 17 alpha-hydroxyprogesterone (17-OHP) injections. Plasma was collected during a selected 24-hour interval via a chronic indwelling femoral vein cannula. Initially, estrogen-negative feedback decreased the pulsatility and circulating levels of gonadotropins. P and 17-OHP treatment (after estradiol) hastened initiation of the BIO-LH surge by up to 8 hours. Although estrogen-positive feedback alone enhanced the biologic activity of LH, P and 17-OHP expedited the midcycle-like BIO-LH surges.