Ovulation triggering in clomiphene citrate-stimulated cycles: human chorionic gonadotropin versus a gonadotropin releasing hormone agonist
PURPOSE: To compare the use of human chorionic gonadotropin (hCG) to a gonadotropin releasing hormone (GnRH) agonist, nafarelin, in initiating ovulation and supporting the luteal phase after priming with clomiphene. METHODS: In 26 infertile women 50 mg clomiphene citrate produced a preovulatory-size follicle. Then, 11 women were randomized to receive two 400-micrograms doses of nafarelin intranasally 16 h apart, and 15 women were injected intramuscularly with 5000 IU of hCG (luteal day 0 = LD0). Starting on LD6, 7 more 400-micrograms doses of nafarelin were repeated on an every 16-h schedule or a single 2500 IU dose of hCG was given, respectively. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), progesterone (P), and hCG were measured. On LD13, endometrium was evaluated with ultrasonography and biopsy in 19 nonpregnant women. RESULTS: As judged by a threefold rise in serum LH, an LH surge was detected on LD1 in all 11 nafarelin patients, but in only 8 hCG patients (P = 0.01). LH and FSH levels were significantly higher on LD1, 7, and 8 and were significantly suppressed on LD13 in the nafarelin group. All patients had mid-luteal P levels greater than 10 ng/ml and luteal phases longer than 13 days. Significantly different luteal E2 or P levels were noted only on LD13, with lower values in the nafarelin group. Pregnancies were achieved in 3 of 11 nafarelin cycles and 2 of 15 hCG cycles. Luteal phase defects were also similar: 4 of 8 nafarelin patients and 7 of 11 hCG patients. CONCLUSION: Nafarelin or hCG in conjunction with clomiphene can result in viable pregnancies, but is associated with low pregnancy rates and a high incidence of luteal phase defects
The effect of relaxin and progesterone on rat uterine contractions
The effect of porcine relaxin on electrically stimulated in vitro contractions of isolated uterine horn segments from estrogen-pretreated immature rats was studied. Relaxin decreased the amplitude of contractions. A mean of 8.3 ng/ml of relaxin produced a 90% decrease in contraction amplitude. There was a minimal effect of 1.0 microgram/ml of progesterone on contraction amplitude. In vitro pretreatment of the isolated uterine segment with this dose of progesterone for 15 minutes did not significantly affect the dose of relaxin needed to decrease the amplitude of contractions. In contrast, pretreatment with progesterone for 45 minutes significantly decreased the concentration of relaxin needed to decrease contraction amplitude. Only 4.7 ng/ml of relaxin was needed to produce a 90% decrease in amplitude after progesterone pretreatment for 45 minutes (p less than 0.005). Relaxin and progesterone synergize in decreasing the amplitude of uterine contractions in vitro. A similar effect may occur in vivo.
Hormone secretion by monolayer cultures of human luteal cells
To be able to study the control mechanisms for human luteal function, a system was designed to maintain human luteal cells in culture. Collagenase dispersed cells of human corpora lutea of the menstrual cycle and pregnancy were maintained as monolayer cultures for 26 days. Progesterone (P) and relaxin (R) in culture media were measured by radioimmunoassay. Both menstrual cycle and pregnancy luteal cells secreted P for 26 days. hCG increased P secretion by menstrual cycle luteal cells, but not by pregnancy luteal cells. R was not detected in media of menstrual cycle luteal cell controls, nor in media of cells incubated with hCG. R was detected in media of pregnancy luteal cells for 6 days. Addition of hCG caused a significant increase in media R levels only on day 2 of culture. These studies show that human luteal cells can be maintained as viable monolayer cultures for at least 26 days and these cultures can be used to study control of human luteal function