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Biomedical subjects

G Bettendorf

Publications and source records attributed to G Bettendorf.

At least 19 recordsLinked to original sources

Induction of pharmacological hypogonadotropism using gonadotropin-releasing hormone agonists in patients undergoing controlled ovarian stimulation.

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.

Adult

Ovarian response and pregnancy rates in in vitro fertilization, gamete intrafallopian transfer, and in vivo fertilization therapies after combined gonadotropin-releasing hormone agonist/human menopausal gonadotropin stimulation.

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.

Adult

[GnRH agonist/hMG stimulation in gamete intrafallopian transfer (GIFT)].

During a period of 17 months 61 couples without pathological tubal factors were treated by follicular puncture and gamete intra-Fallopian transfer (GIFT) at the department of Obstretrics and Gynaecology, University of Hamburg. The combination GnRH-antagonist (GnRH-A)/hMG was administered in 69 stimulation cycles. Two different GnRH-A application forms were used (daily intranasal spray/monthly depot injection). In all cases mature oocytes were collected after ovulation induction, and gamete transfer was performed. None of the cycles had to be cancelled. Twenty-two clinical pregnancies were achieved (32% by stimulation cycle). The highest pregnancy rate was observed in the group of cervical infertility (58%), lowest rate in cases of pathological male factors (15%). In addition, pregnancy rate correlated with the number and maturity of transfered oocytes. The combined GnRH-A/hMG stimulation therapy allows for a prolonged active follicular development without the occurrence of endogenous, premature luteinization. Besides a more flexible and effective strategy of ovarian stimulation, the number of follicles/oocytes was L, increased which provided a better condition for GIFT.

Administration, Intranasal

[Increased incidence of ovarian hyperstimulation syndrome following combined GnRH agonist/hMG therapy].

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.

Buserelin

[Preclinical hypothyroidism and disorders of ovarian function].

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.

Adult

Endocrine profiles and luteal function during GnRH-analogue/HMG therapy.

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.

Anovulation

Endocrine parameters of human follicular fluid and fertilization capacity of oocytes.

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.

Adult

[Gonadotropin stimulation and in vitro fertilization following selective hypophyseal suppression by LH/RH analogs].

Out of 109 hMG stimulations for in vitro fertilization (IVF) 41 cycles (38%) had to be cancelled because of premature endogenous luteinization. Pretreatment with the LH/RH-agonist Buserelin induces selective pituitary suppression and prevents spontaneous LH-surge during hMG stimulation. The pharmacologic hypogonadotropism allows considerable flexibility with respect to the timing of starting gonadotropin stimulation and ovulation induction. In 74 Buserelin/hMG/IVF-cycles no premature luteinization occurred and all started stimulations yielded in follicular puncture. In addition increased oocyte recovery rate, significant higher fertilization rate and significant better pregnancy rate could be achieved as compared with hMG/IVF-cycles. In conclusion pharmacologic hypogonadotropism by administration of LH/RH-analogue reliably prevents endogenous luteinization and improves gonadotropin stimulation as well as IVF results.

Adult

Radioreceptor assay for lactogenic hormones based on membranes from rat mammary tumour.

A highly sensitive radioreceptor assay (RRA) for human prolactin (hPRL) based on membrane preparations obtained from chemically induced rat mammary tumour is described. The binding of 125I-labelled, highly purified pituitary human prolactin was specific for lactogenic hormones and depending on time, temperature, and concentration of receptor protein. Optimal specific receptor binding (18-20%) was obtained by incubation at 21 degrees C for 18 h. The prolactin receptor was shown to have a single "class" of binding sites with an affinity constant (Ka) of 6.0 X 10(10) mol-1. The binding capacity was 8-33 fmol/mg membrane protein. The sensitivity of the radioreceptor assay was 0.5 ng/ml ovine prolactin (NIH-PS-10) or 0.84 ng/ml human prolactin (NIH-VLS-4). The receptor binding activity of various purified prolactin preparations from different species was comparable to the biological hormone activities, indicating that this in vitro assay system measures values which are biologically relevant.

Animals

[Gonadotropin stimulation during LH/RH analog-induced inhibition of pituitary function].

Ovarian stimulation with hMG/hCG is most effective in hypogonadotropic patients. In normogonadotropic/estrogen-positive patients in whom gonadotropin therapy is also indicated after failure of other forms of treatment, it is much more difficult and considerably less effective. The objective of this study was to change the endocrine status in patients from a normogonadotropic and estrogen-positive status, by administration of a GNRH analogue, to a hypogonadotropic, estrogen-negative status, in order to create better conditions for gonadotropin stimulation. For this purpose Buserilin was administered either intranasally or intravenously and the endocrine reaction was observed. The endocrine changes observed were very varied. In the majority of cycles a fall in plasma FSH concentrations resulted (20 out of 28), in 2 a rise, while in 6 of the 28 there was no change. In 12 out of 28 cycles the plasma LH concentration decreased; it rose in 3 and was unchanged in 13. The LH fluctuation was suppressed or irregular in all cases. Estrogen secretion was unaffected in 16 cycles; it increased continuously in 6 cycles and temporarily in a further 6. The reaction to the hMG injections did not show the hoped-for improvement with simultaneous administration of an RH analogue. A complete and constant suppression of pituitary function, and thus the creation of a hypogonadotropic state, could not be achieved by medication with 8 X 300 micrograms Buserilin or intravenous injection of 5 and 10 micrograms every 90 minutes.

Adult

[Gonadotropin treatment in ovarian insufficiency, stimulation of follicle maturation with human urinary FSH].

Thirty-two infertile patients with basal FSH/LH ratios of less than 0.5 were treated with a pure human urinary FSH preparation in various doses, in 57 cycles. With initially low FSH doses and increase in the dose according to the individual reaction (analogous to hMG therapy) ovulation and a normal luteal phase were achieved in 22 out of 25 cycles, and 6 pregnancies. In one cycle there was a clinical overstimulation syndrome in early pregnancy. Treatment with high doses of FSH at the beginning of the cycle proved unsuitable: normal follicle stimulation, ovulation and luteal phase only occurred in 12 out of 23 cycles, and there was no pregnancy. The combination of FSH therapy with initially high doses and subsequent stimulation with hMG resulted in ovulation in 9 out of 10 cycles without ensuing pregnancy. The behaviour of the endogenous LH under FSH therapy varied: with an initially high dose of FSH there was a clear drop in serum LH concentrations in 8 out of 23 cycles, and with an initially low dose in 5 out of 25 cycles. In 5 cycles the serum LH concentrations rose under FSH therapy. The results of the investigation confirm earlier observations that ovarian stimulation with FSH is possible in cases with low endogenous FSH/LH ratios, and that it is best accomplished by individualized therapy with an initially low dose. However, because of the different reaction of endogenous LH secretion, a better ovarian reaction than with hMG therapy could not be achieved with regard to ovulation and pregnancy rate, course of the luteal phase and overstimulation.

Adult