This study was conducted to determine whether the additional use of pulsed wave Doppler improves the diagnostic capacity in assessing tubal patency by hysterosalpingo contrast sonography (HyCoSy). A total of 210 women with a history of infertility were included in this study. HyCoSy was performed after intrauterine injection of Echovist 200. For the assessment of tubal patency B-mode scanning and pulsed wave Doppler ultrasound were performed in the proximal and distal tubal segments. With the combined sonographic procedure 297 tubes (74%) were rated patent, 35 (8%) incompletely obstructed and 70 (18%) completely obstructed. A total of 252 tubes were additionally examined by laparoscopy for reference purposes. Concordant results for both methods were found in 92% of tubes, nine had been rated false negative and 10 tubes appeared to have been rated false positive. The combined sonographic specificity was found to be 85% with a sensitivity of 95%. Peritubal adhesions detected by laparoscopy were found to be the reason for false positive sonographic results in 60% of cases. In conclusion, the combined B-mode and pulsed wave Doppler examination appears to be a non-invasive and low-cost test for the assessment of tubal patency, which should be performed during diagnostic work-up for infertility.

Ovarian function depends on inseparable relationship of the endocrine axis hypothalamus-pituitary-ovary. The ovary itself determines both, time of ovulation and duration of cycle. The sequences of ovarian control involve positive and negative feedback mechanisms to hypothalamus and pituitary as well as auto- and paracrine factors at the ovarian level.

In female patients gonadotropin and free alpha-subunit serum levels during GnRH-agonist (GnRH-a) treatment were investigated. Using two different immunoassays (RIA, IRMA) as well as LH in-vitro bioassay evidence was found for pituitary secretion of incomplete LH molecular forms which are detected false positive in RIA measurements but neither in IRMA nor in bioassay. In the GnRH-a induced desensitization state suppression of LH serum levels was more profound as compared to FSH. In contrast to gonadotropins free alpha-subunit serum levels were shown to increase in a biphasic course leading to ninefold higher levels persisting during GnRH-a treatment. A further increase was achieved by exogenous GnRH but not by estradiol. In conclusion these in-vivo data give evidence for a gradually different suppression of gonadotropic secretion by the use of GnRH-a. The mechanisms of inhibition are discussed to be directed to steps in the processing of beta-subunit synthesis but not of alpha-subunit.

Ovarian stimulation cycles were initiated using human menopausal gonadotropin (HMG) in 318 women (643 cycles) without pretreatment and in 341 women (525 cycles) after pituitary desensitization by pretreating with the gonadotropin-releasing hormone agonists (GnRH-A) buserelin acetate or triptorelin acetate. Significantly higher pregnancy rates were observed in the GnRH-A/HMG group (15%) as compared to the HMG group (7%) following in vitro (p less than 0.05) but not in vivo fertilization therapy (14 vs. 9%, respectively). After in vitro fertilization, the rates increased with increasing length of the active phase of follicular maturation. Gamete intrafallopian transfer, performed only in the GnRH-A/HMG group, led to a pregnancy rate of 34%. Overall, there was a clear trend to higher pregnancy rates in the GnRH-A/HMG group (16%) as compared to the HMG group (8%). Abortion rates were comparable in both groups (24 vs. 19%). The higher pregnancy rates in the GnRH-A/HMG group were attributable to enhanced follicular maturation and optimized ovarian stimulation produced by the hypogonadotropic state. However, an increased risk of the ovarian hyperstimulation syndrome was observed in these patients.

Pharmacological hypogonadotropism was induced in 167 women using the gonadotropin-releasing hormone agonists (GnRH-A) buserelin acetate or triptorelin acetate. 84 patients (group 1) began treatment using 1.2 mg/day buserelin acetate intranasally during the follicular phase (days 1-3); 41 patients (group II) began the same treatment, supported by 10 mg medroxyprogesterone acetate for 10 days, during the early luteal phase; 42 patients (group 3) received triptorelin acetate as an intramuscular depot injection, supported by 10 mg medroxyprogesterone acetate for 10 days, during the early luteal phase. Serum luteinizing hormone, follicle-stimulating hormone, oestradiol (E2), prolactin, and testosterone levels were monitored. Pituitary function was assessed by (1) measurement of endogenous luteinizing hormone fluctuation; (2) response to luteinizing hormone releasing hormone administration, and (3) response to oestradiol benzoate (E2 test). Complete pituitary desensitization was only assumed, if all three tests were negative. The LH-RH test and the E2 test were shown to be the most reliable indicator of pituitary function. E2 administration led to further reduction of gonadotropin secretion after pituitary desensitization. The desensitization time was 41.1 +/- 11.7 days in group 1 and was significantly reduced to 20.7 +/- 10.5 days in group 2 (p less than 0.01); a further, non-significant shortening to 15.1 +/- 3.0 days was observed in group 3. Changes in endocrine parameters demonstrated hypogonadotropic hypo-oestrogenism after initial pituitary stimulation.

In the present paper we examined, whether the combined GnRH-agonist/hMG therapy implies an increased risk of the ovarian hyperstimulation syndrome (OHS). In a retrospective analysis, 525 GnRH-a/hMG cycles were compared with 643 cycles of hMG stimulation, which were simultaneously performed at the Department of Gynecology and Obstetrics of the University of Hamburg. Two different GnRH-agonists were used: Buserelin (Hoechst) given intranasally (410 cycles) and Triptorelin (Ferring) intramuscularly (115 cycles). The clinical results of hMG "only"-therapy revealed an OHS incidence of 7% for grade II and 0.2% for grade III. In contrast, significantly higher incidences were observed after GnRH-a/hMG treatment. In Buserelin/hMG cycles in 23% OHS grade II and in 1.0% OHS grade III occurred, in Triptorelin/hMG cycles in 40% OHS II and in 5.2% OHS III, respectively. The increased incidence of OHS correlated with higher ovarian estrogen production as well as a higher number of follicles following the GnRH-a/hMG stimulation. Furthermore, in GnRH-a/hMG cycles a prolonged duration of follicular maturation occurred due to an increase of the active phase; in addition the amount of hMG-ampoules needed for ovarian stimulation was higher. After GnRH-a/hMG treatment, an endogenous LH-surge was not detected, whereas in 34% of hMG stimulated cycles irregular LH-fluctuations were observed. There was a higher pregnancy rate in GnRH-a/hMG cycles (15%/525 cycles), as compared to hMG stimulation (8%/643 cycles), but the abortion rate was similar (23%, GnRH-a/hMG, versus 13%, hMG). The demonstration of an increased ovarian response leading to better pregnancy rates but also higher risks of OHS is well known from earlier data of hMG stimulation in patients with hypogonadotropic amenorrhoea (WHO group I). This implies that GnRH-agonist pre-treatment shows similar endocrine conditions in normogonadotropic patients.

We have found a significant improvement of pregnancy rates after pretreatment with an agonist of gonadotrophin releasing hormone (GnRH-a). The pregnancy rate in patients treated with HMG/HCG was 17% per patient and 5.5% per cycle, in patients treated with buserelin, 25% per patient and 15% per cycle and in the triptorelin group 25% per patient and 22% per cycle. From 740 HMG/HCG cycles without GnRH-a only 66% were sufficient according to the analytical data. In 16% we found a premature LH discharge and in 18% an irregular LH fluctuation during stimulation. It is clear that gonadotrophin stimulation during pituitary suppression provokes a more intense ovarian reaction with respect to the number of follicles, as well as the endocrine activity. There are also some important practical advantages: ovarian stimulation can be started without any respect to a definite time of menstruation or of the cycle. Of further importance is the much greater flexibility in the timing of HCG administration. Finally, it will be favourable for all patients who need ovulation induction, especially for oocyte retrieval for IVF or GIFT, because no cycle has to be cancelled.

For sensitive assessment of thyroid function a TRH stimulation test using 200 micrograms TRH i.v. was routinely performed in 304 women admitted for evaluation and treatment of infertility. In 37 cases (12.2%) the reaction of TSH 30 min after injection of TRH i.v. was enhanced (by definition of a peak TSH level greater than 25 mIU/l), according to mild or subclinical hypothyroidism. Approximately 14 (14/37 = 37.8%) of these patients were found to have slightly elevated serum PRL values (mean PRL greater than 15 ng/ml). Cycle analysis by means of basal body temperature and evaluation of progesterone and oestradiol values, supplied evidence of luteal phase deficiency in 8 and anovulation in 3 cases. Another group of 11 patients with hypothyroidism involved oligo-/amenorrhoea, hirsutism and hyperandrogenaemia. After treatment with 50-150 micrograms l-thyroxine daily for at least 4 to 6 weeks, elevated PRL values significantly decreased (mean level less than 15 ng/ml, p less than 0.01) in 9 out of 12 patients and testosterone levels slightly decreased in 5 out of 8 patients. An improvement of the cyclical ovarian function could be observed by the significant increase of the average progesterone concentration in the luteal phase. During therapy with l-thyroxine, 4 pregnancies occurred. From these results we conclude, that mild hypothyroidism may cause ovarian insufficiency. Assessment of thyroid function should be mandatory in infertile patients with elevated prolactin levels or chronic anovulation.

The induction of multiple follicular growth during ovarian stimulation for in vitro fertilization (IVF) implies follicular asynchrony. As a consequence oocytes of different quality are obtained. The maturity and fertilizability of oocytes cannot sufficiently be predicted by their morphological appearance under the light microscope. Looking for additional parameters of oocyte quality, FSH, hCG, estradiol (E2), progesterone (P), testosterone (T), prolactin (PRL) and cAMP were analysed in human follicular fluid (FF) containing a morphologically mature oocyte. The evaluation of the relationship between FF values and oocyte fertilization showed the following results: no differences of FSH, hCG, E2, P and T concentrations in FF between the group of fertilized and not fertilized ova. However, significant differences were detected for PRL and cAMP. In FF of fertilized oocytes PRL content was higher (38.8 +/- 2.2 vs 29.7 +/- 2.3 ng/ml, P less than 0.01) and cAMP level was lower (32.7 +/- 1.9 vs 59.8 +/- 7.4 pmol/ml, P less than 0.01) as compared with FF of unfertilizable oocytes. In conclusion PRL- and cAMP concentration of FF might be additional parameters of oocyte maturation and fertilizability.

Induction of ovulation in patients with functional hypothalamus and pituitary is frequently complicated by unpredictable LH discharge and premature early luteinization. The best response and highest pregnancy rate following hMG-treatment can be achieved in hypogonadotropic patients [1]. Therefore a procedure was developed for selective temporary inhibition of pituitary gonadotropin secretion with the LH/RH-analogue Buserelin [2]. In a clinical study hMG-induced follicular maturation and succeeding fertilization during pharmacologic hypogonadotropism was investigated. In 31 cycles of 26 patients hMG/hCG-stimulation for in-vitro fertilization (IVF) because of a tubal factor was started after pretreatment with Buserelin (1.2 mg/day, nasal spray) had resulted in the absence of endogenous LH-discharge to an estrogen provocation test (group I). The cycles were compared with previous hMG/hCG cycles of the same patients without Buserelin treatment (n = 18, group II) and the total of hMG-treatment cycles for IVF (n = 66, group III).