OBJECTIVE:This study was designed to compare the exogenous FSH ovarian reserve test (EFORT) versus the clomiphene citrate challenge test (CCCT), basal FSH, and basal inhibin B, with respect to their ability to predict poor and/or hyperresponders in an IVF population.DESIGN:Prospective randomized controlled trial.SETTING:Fertility center of a university hospital.PATIENT(S):One hundred ten patients undergoing their first IVF cycle, randomized into two groups.INTERVENTION(S):Fifty-six patients underwent a CCCT, and 54 patients underwent an EFORT. In all patients, the test was followed by an IVF treatment.MAIN OUTCOME MEASURE(S):Ovarian response, expressed by the total number of retrieved oocytes.RESULT(S):Univariate logistic regression showed that the best predictor for poor response is the CCCT (area under receiver operator characteristic curve [ROC-AUC] = 0.87), with maximal accuracy of 0.89. Multiple logistic regression analysis did not produce a better model in terms of improving the prediction of poor response. For hyper response, univariate logistic regression showed that the best predictor is the inhibin B increment in the EFORT (ROC-AUC = 0.92) but with a low maximal accuracy of 0.78. Again, multiple logistic regression analysis did not produce a better model in terms of predicting hyper response.CONCLUSION(S):Our study, the first which compares the CCCT with the EFORT for the prediction of poor and hyperresponders, shows that the CCCT is superior for identification of low responders. The EFORT (inhibin B increment) is superior for prediction of hyper response at the cost of a high rate of false positives. Neither of the two tests seems adequate to act alone for identification of both poor and hyperresponders.

BACKGROUND: A method was previously described to measure FSH reliably in unextracted urine. The aim of the current study was to establish the course of FSH measured in urine throughout the cycle. METHOD: Daily urinary FSH (uFSH) concentrations were determined in 14 regularly menstruating volunteers aged 23-39 years during one complete menstrual cycle. RESULTS: In each subject, mean daily uFSH measured in urine, as gold standard for FSH tone, correlated significantly with FSH in early follicular phase fixed to menstruation on cycle day 3 (r = 0.75, P = 0.002), or fixed to ovulation 9 days before the pre-ovulatory FSH surge (r = 0.87, P = 0.0001), or when selected as being the highest follicular phase value (r = 0.91, P = 0.0001). Age correlated significantly with mean daily uFSH (r = 0.67, P = 0.009), highest follicular phase uFSH (r = 0.60, P = 0.024), uFSH on cycle day 3 (r = 0.80, P = 0.0006), and uFSH 9 days before FSH surge (r = 0.65, P = 0.0016). The uFSH was also measured on cycle day 3 in 104 IVF patients in a cycle prior to pituitary down-regulation. The uFSH correlated significantly with numbers of follicles (P = 0.02) and oocytes (P = 0.024). CONCLUSION: It is concluded that cycle day 3 uFSH is a good reflection of the mean uFSH of the complete cycle, and there is a highly significant correlation between uFSH and age and ovarian reserve. Measurement of FSH in urine on cycle day 3 seems to be a reliable and non-invasive tool for determining ovarian reserve in IVF.

Objective: To predict the chance of total fertilization failure (TFF) before the day of ovum pickup with known semen and female variables.Design: A statistical model was constructed to predict TFF by retrospective analysis (2,366 couples) and subsequently tested on a new IVF population (917 couples).Setting: Academic tertiary referral center.Patient(s): Three thousand three hundred eighty-three couples who underwent an IVF-ET treatment. CIntervention(s): None.Main Outcome Measure(s): The ability to predict the probability of TFF in IVF.Result(s): Two variables-postwash total progressively motile sperm cell count (postwash TPMC and number of follicles-were found to be significant. Taking a probability of 25% as an acceptable risk of TFF, we calculated that a postwash TPMC of <1.1 x 10(6) cells results in a risk of TFF of > 25%. Low responders (<4 follicles) needed a postwash TPMC of >2.2 x 10(6) cells to reduce the risk of TFF to < 25%. High responders (> 15 follicles) needed only 0.35 x 10(6) postwash progressively motile spermatozoa.Conclusion(s): When postwash TPMC and number of follicles are known and an unacceptable TFF outcome is expected, one can propose an ICSI procedure a few days before the day of ovum pick-up. (C) 2001 by American Society for Reproductive Medicine.

The aim of this study was to investigate cycle dependent changes of serum CA 125 and CA 15-3 concentrations during spontaneous ovulatory cycles. Twenty apparently healthy women with spontaneous menstrual cycles attending our infertility clinic were included. Of these women, 18 had occluded tubes as a result of sterilization. Ovulation was confirmed by luteinizing hormone test and ultrasonography and, to exclude endometriosis, a laparoscopy was performed. Serum samples for CA 125, CA 15-3, 17 beta-oestradiol and progesterone determinations were taken every second day starting on the 2nd day of the cycle until the 7th day of the next cycle. After correction for inter-individual variation in serum concentrations, highest CA 125 concentrations were found during the menstruation. During the follicular and peri-ovulatory phase CA 125 serum concentrations were lowest. For CA 15-3, serum concentrations were not statistically different throughout the cycle. CA 125 and oestradiol concentrations were negatively correlated, CA 15-3 and oestradiol concentrations were positively correlated. Absolute serum concentrations of both CA 125 and CA 15-3 vary among females. Within the female, fluctuations of CA 125 are phase related. In the population studied most of the patients had tubal obstruction and high CA 125 serum concentrations during menstruation, which revokes the theory that the menstrual rise of CA 125 is due only to retrograde menstruation.

OBJECTIVE:To determine the presence of FSH in unextracted urine of perimenopausal women using a microparticle enzyme immunoassay kit on an AxSYM random access immunoassay analyzer. DESIGN:Controlled descriptive study. SETTING:A large teaching hospital and infertility clinic. PATIENT(S):Forty perimenopausal women aged 32-55 years admitted to our clinic for a gynecological operation. INTERVENTION(S):None. MAIN OUTCOME MEASURE(S):Mean serum FSH level and urinary FSH in early-morning urine, in a random void urine sample, and in 24-hour urine on the same day. FSH in urine on the day of excretion and 1 and 4 weeks thereafter, stored under various conditions. FSH in urine before and after extraction. RESULT(S):The Pearson's correlation coefficient between mean serum FSH levels and urinary FSH in early morning urine was 0.904, in a random void 0.915, and in 24-hour urine 0.857. Determination of optimal storage conditions revealed that urine was best kept at 4 degrees C without any additive. The correlation between FSH in extracted and unextracted urine was 98.9%. CONCLUSION(S):In perimenopausal women, FSH can be reliably measured in unextracted urine. The correlation between urinary FSH and a random void urine sample and mean FSH from a serial serum sample is very high. Urine can be stored for 4 weeks at 4 degrees C without loss of FSH immunoreactivity.

A literature review is given on the pulsedose, the pulse interval, the route of administration and the complications of pulsatile GnRH therapy in hypogonadotropic patients. It is concluded that the treatment regimen should be as follows: 1. Start first treatment cycle with a pulsedose of 5 μg/pulse and a pulse interval of 120 min. 2. Regardless the outcome of the first treatment cycle, during the second cycle either the dose should be increased to 10 μg/pulse or the interval should be reduced to 60 min. 3. Only if insufficient results are obtained with this pulsedose should the dose be increased to a maximum of 20 μg/pulse. With respect to the route of administration it is concluded that the choice of the i.v. versus the s.c. route of administration is mainly one of personal preference. Complications are mainly local inflammatory reactions. All other side effects and complications are rare and of minor importance.

Objective: Does an exogenously administered regimen of luteinizing hormone-releasing hormone (LH-RH) pulses override endogenous LH-RH?Design: Pulses of LH-RH were given intravenously during 1 week with intervals of 90 (n = 5) or 120 minutes (n = 5). Before, during, and after treatment serial plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) patterns and pituitary responsiveness to LH-RH were estimated.Patients: Women with virtual absence of gonadal function (postmenopause, gonadal dysgenesis, and premature menopause).Results: During treatment with the 90-minute interval, no LH pulses that were not related to injections of LH-RH were observed. Two spontaneous LH pulses were observed during treatment with the 120-minute interval. Immediately after treatment, a lowered incidence of spontaneous LH pulses was seen of 3 pulses/6 h if LH-RH had been given every 90 minutes and to 1.5 pulses/6 h after the 120-minute interval treatment. Gonadotropin responses to 100-mu-g of LH-RH were attenuated during treatment but recovered within 48 hours after discontinuation of treatment.Conclusions: (1) Exogenously administered LH-RH can override endogenous LH-RH or its effects on the release of LH in women with hypergonadotropic hypogonadism; (2) during pulsatile LH-RH treatment desensitization of the pituitary occurs to some degree; and (3) immediately after cessation of treatment with pulsatile LH-RH, spontaneous LH pulses are present but with a significantly lower incidence.

Forty-seven hyperprolactinaemic patients with serum prolactin (PRL) concentrations persistently above 1500 mU/l were treated with the new dopamine agonist CV 205-502 or bromocriptine in a prospective, randomized and double-blind fashion during a 24-week period. Two women had to be excluded because of poor compliance in the first month. Therefore 45 patients remained for evaluation. 81% of the patients in the CV 205-502 group and 70% of the patients in the bromocriptine group normalized their prolactin levels within the study period with a treatment dose as permitted in this protocol. In general serum prolactin normalized within 8 to 12 weeks of treatment. There were no differences between the two tested drugs regarding restoration of the menstrual cycle or disappearance of galactorrhoea. Both drugs gave rise to adverse reactions, especially during the initiation of therapy. However, the adverse reactions reported during CV 205-502 treatment were less severe and persistent than those attributed to bromocriptine. Patient acceptance of the new drug with regard to tolerability was judged by 90% of the women in that treatment group as very good or good, while 75% of those treated with bromocriptine evaluated its tolerability as very good or good. We conclude that CV 205-502 is highly effective in the treatment of hyperprolactinaemia with concomitant restoration of gonadal function and prevention of galactorrhoea. The tolerability of the drug seems better than of bromocriptine and therefore this drug is of value in the treatment of hyperprolactinaemic patients.

In a retrospective international study 223 pregnancies induced with pulsatile hormone-releasing hormone (LH-RH) were evaluated. In patients with hypothalamic amenorrhea (HA) and polycystic ovarian disease (PCOD) the abortion rate was similar (10% vs 8.7%). The premature delivery rate was significantly higher, however, in the patients with HA, but this could be explained by the higher incidence of multiple pregnancies in this group. Thirty multiple pregnancies were observed in the HA group (n = 174) compared with none in the PCOD group (n = 24; p less than 0.05). The incidence of multiple pregnancies in the HA group correlated to the pulse dose (p less than 0.05). The 1st treatment cycle resulted in more multiple pregnancies than did subsequent cycles (p less than 0.05). Difference in pulse interval did not affect the incidence of multiple pregnancies, nor did the route of administration (intravenous or subcutaneous). The incidence of congenital anomalies was comparable to that with spontaneously achieved pregnancies.

The influence of luteinizing hormone-releasing hormone (LH-RH) pulse frequency on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was studied in hypogonadotropic hypogonadal women. They received three regimens of 5 days of pulsatile LH-RH (5 micrograms/pulse) given at 30-, 90-, or 180-minute intervals, with at least 6 weeks between treatments. On day 1, LH and FSH increased in proportion to the LH-RH pulse frequency. After 5 days of treatment with the 30- and 90-minute intervals, LH was still elevated, but FSH had returned to pretreatment levels together with a decline of the FSH response. The LH response only declined during treatment with the 30-minute pulse interval. During each treatment, estradiol (E2) increased. Explanations for dissociation between LH and FSH secretion during treatment with higher LH-RH pulse frequencies could be: (1) desensitization of FSH rather than LH secretion on LH-RH; (2) a differential effect of E2 on LH and FSH; (3) nonsteroidal ovarian factors selectively regulating LH and/or FSH release.

We analyzed the importance of 3 factors derived from the HSG (nature of the mucosal pattern, diameter of the hydrosalpinx, expandability of the ampulla) and of four factors from the findings at laparoscopy (extent of adhesions, nature of adhesions, thickness of tubal wall and diameter of the hydrosalpinx) for predicting the pregnancy outcome in 98 patients with bilateral hydrosalpinx. Each factor was categorized into 3 scores and each patient was scored for both the right and the left tube, resulting in 6 score-combinations. An association between the pregnancy prospects based on the score-combinations and the actual pregnancy outcome seemed to be present for all factors evaluated, except for the extent of adhesions and the diameter of the hydrosalpinx (laparoscopy). The results further indicate that a favourable score on the nature of mucosal pattern in one or both tubes concurs with good pregnancy prospects. In contrast, the presence of an unfavourable score for most of the other factors in at least one tube is associated with a poor fertility prognosis, regardless of the condition of the other tube.

In order to test gonadotropic function 30 prepubertal and 2 early pubertal girls and boys were treated with LH-releasing hormone (LRH) in a pulsatile fashion for 7 days. LRH was administered iv either in a dose of 10 micrograms every 90 min or in a dose of 20 micrograms/1.73 m2 every 96 min. On days 1 and 7, just before as well as at the end of LRH treatment, a LRH test (100 micrograms/m2 iv) was performed. In 27 patients a LRH test was repeated 4 (day 11) or 7 days (day 14) after LRH withdrawal as well. Plasma LH, FSH, and estradiol or testosterone levels were estimated during the LRH tests on days 1, 7, and 11/14. The patients were divided into 4 groups: group 1 consisted of 2 girls and 1 boy with gonadal failure, group 2 of 1 girl and 2 boys with intact pituitary and gonadal function, group 3 of 11 girls and 13 boys with various central endocrine disorders, and group 4 of 1 girl and 1 boy with pubertal arrest of unknown origin. In group 1 LRH treatment elicited an increase of both gonadotropins into the castrate range, whereas gonadal steroids did not increase. In group 2 baseline LH as well as the response to LRH increased on day 7. In the boys FSH changed similarly. In the girl baseline FSH increased, but the high FSH response of day 1 decreased. Estradiol and testosterone levels were elevated on day 7. These changes during LRH treatment are similar to those during normal pubertal development. When the LRH test was repeated on day 11/14 basal levels had returned into the prepubertal range and a high response of LH especially was found in all 3 subjects. Patients of group 3 were separated into two subgroups: group 3a, those with, and group 3b, those without an increase of gonadal steroids on day 7 of LRH treatment. Since an increment must be the result of increased gonadotropin stimulation, this probably indicates intact gonadotropic function. Group 3a had a pattern of gonadotropin secretion similar to group 2. In group 3b basal and peak LH levels were lower on day 7 compared to group 3a, whereas FSH levels did not differ. Four or 7 days after LRH discontinuation (day 11/14) basal gonadotropin levels were in the original low range. In the LRH test mean LH peak level of group 3a was 43.7 U/liter, of group 3b 13.1 U/liter (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)