Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles.

To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between 1.5-2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5-2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.

Endocrine profiles of patients with testicular tumors treated with radiotherapy.

Blood samples for hormone analysis were obtained 5 to 20 years post-therapy from 12 men with testicular tumors who were originally treated by unilateral orchiectomy followed by abdominal and/or pelvic irradiation. In nine patients (75%) the levels of FSH and LH, and in one patient (8%) the testosterone values, were outside the ranges found in age- and sex-matched controls. From this retrospective study we conclude that, even when the remaining testis is kept outside the field of radiation, significant radiation damage occurs, mainly through scatter. This damage is more likely to occur if the hemiscrotum is irradiated. Methods of shielding are available to reduce the dose received by the contralateral testis.

Stimulatory effect of clebopride on human prolactin secretion.

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Follicle growth curves and hormonal patterns in patients with the luteinized unruptured follicle syndrome.

A prospective longitudinal and standardized study is presented, dealing with ultrasonographic and hormonal characteristics of the luteinized unruptured follicle (LUF) syndrome. Among 600 cycles monitored in 270 infertility patients, 40 cycles in 27 patients showed no evidence of follicle rupture, in spite of signs of luteinization, as reflected by basal body temperature recordings and progesterone determinations. In this study, 20 LUF cycles in 20 infertile patients were compared with 45 ovulatory cycles in 45 control women. During the follicular phase, no substantial difference in follicle growth was found, but after the luteinizing hormone peak, LUF follicles, instead of rupturing, showed a typical accelerated growth pattern. Both mean luteinizing hormone peak levels and midluteal progesterone levels were significantly lower in LUF cycles than in the control cycles. However, the duration of the luteal phase was not affected. Both central and local factors can be held responsible for the lack of follicle rupture. Ultrasound offers new possibilities as a noninvasive method in diagnosing the LUF syndrome.

Action of tamoxifen on folliculogenesis in the menstrual cycle of infertile patients.

Daily estimations of follicle-stimulating hormone, luteinizing hormone, prolactin, estradiol, and progesterone were made in the serum of eight infertile patients from day 1 through the follicular phase during menstrual cycles before and after tamoxifen therapy. Tamoxifen therapy was found to shorten the follicular phase from 15.4 +/- 0.8 days (mean +/- standard error of the mean) to 14.0 +/- 0.6 days (difference not significant) and to lengthen the luteal phase from 12.8 +/- 0.4 days to 14.1 +/- 0.8 days (P less than 0.05). The mean estradiol concentration in the eight patients during tamoxifen treatment cycles rose on day 8 (3 days after starting tamoxifen treatment) and increased significantly (P less than 0.05) from day 10 to midcycle. The integrated follicular phase estradiol concentration in the tamoxifen treatment cycle increased to 2450.1 +/- 208.1 pg/ml/cycle, and was significantly higher (P less than 0.025) than that in the nontreatment cycle. In contrast, the concentrations of follicle-stimulating hormone, luteinizing hormone, and prolactin during the follicular phase and at the midcycle peak of tamoxifen treatment cycles were not significantly different from those of the nontreatment cycle. These results suggest that the mechanism of tamoxifen in improving folliculogenesis may involve a direct action on the ovary without intervention of the hypothalamic-pituitary system.

Familial gonadal germinative failure: endocrine and human leukocyte antigen studies.

Two primary amenorrheic sisters were diagnosed as 46,XX pure gonadal dysgenesis. Their brother, a normal phenotypic and genotypic male, was azoospermic due to primary germinative failure. Parental consanguinity was observed, suggesting an autosomal recessive inheritance. This is the first reported family in which both an otherwise healthy male and two females were affected by gonadal germinative failure. Endocrine studies showed impaired gonadal function in the three affected siblings. The two females with gonadal dysgenesis and the azoospermic male shared one human leukocyte antigen haplotype; the second haplotype, however, was different. The common haplotype was also found in the oligomenorrheic sister whose gonadotropin-releasing hormone test was compatible with normal ovarian function, in the mother, and in one of her offspring who had a normal spermiogram. Hence, linkage between human leukocyte antigens and gonadal failure in this family had been excluded. The possible etiology of familial, chromosomally competent, gonadal failure is discussed.

Influence of severe endometriosis on gene expression of vascular endothelial growth factor and interleukin-6 in granulosa cells from patients undergoing controlled ovarian hyperstimulation for in vitro fertilization-embryo transfer.

OBJECTIVE: To evaluate how endometriosis affects expression of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) in granulosa cells. DESIGN: Prospective study. SETTING: IVF-ET program at Osaka Medical College. PATIENT(S): Seventeen patients with revised American Fertility Society stage IV endometriosis and 17 patients with tubal infertility and no endometriosis. INTERVENTION(S): Granulosa cells obtained at oocyte retrieval were examined for VEGF and IL-6 gene expression. MAIN OUTCOME MEASURE(S): Serum E(2) and P levels at hCG administration, number of oocytes, fertilization rate, high-quality embryo rate, and pregnancy rate, and expression of VEGF and IL-6 genes. RESULT(S): Total hMG and FSH levels were statistically significantly higher in patients with endometriosis; however, the number of retrieved oocytes and the fertilization rate were lower compared with patients with tubal infertility. Serum E(2) levels and expression of VEGF in patients with tubal infertility were statistically significantly higher than those in patients with endometriosis. Interleukin-6 gene expression did not differ between the groups. CONCLUSION(S): In severe endometriosis, lower VEGF gene expression in granulosa cells may adversely affect oocyte development and maturation.

Pharmacokinetics of exogenous gonadotropin and ovarian response in in vitro fertilization.

OBJECTIVE: To assess the diffusion of gonadotropin into the follicular fluid (FF) and its relation to the results achieved in a human IVF-ET program. DESIGN: Retrospective pharmacokinetic study. SETTING: Fukuoka University Hospital, Japan. PATIENT(S): Eighty-seven infertile patients underwent 137 cycles of IVF-ET. INTERVENTION(S): Serum and FF were collected at the time of oocyte recovery. The hCG ratio (between follicular hCG and serum hCG concentrations, measured by time-resolved fluoroimmunoassay) was evaluated as an index of the diffusion of exogenous gonadotropin. MAIN OUTCOME MEASURE(S): Relation between hCG ratio and the results and outcome of the IVF-ET program. RESULT(S): The hCG ratio decreased with the total dosage of hMG and increased with the serum E2 level, the number of oocytes recovered, and the number of oocytes fertilized. Patients with a poor response showed a low hCG ratio, which was associated with a complete lack of fertilization. The mean hCG ratio in the pregnant cycles was significantly higher than that in the nonpregnant cycles. An hCG ratio > 0.46 was seen in all pregnant cycles. CONCLUSION(S): The diffusion of exogenous gonadotropin into the FF may be an important predictor of IVF outcome.

Minimal requirements for a successful outcome in anovulatory patients treated with human menopausal gonadotropins.

OBJECTIVE: To determine the minimal requirements for achieving a full-term singleton pregnancy in hMG-treated patients. METHODS: One hundred and ninety-two pregnancy cycles resulting from hMG therapy in infertile patients were retrospectively studied to determine the minimal requirements for the occurrence of a pregnancy in those women. The cycles were divided into five groups: pregnancies ending in miscarriage, ectopic pregnancies, pregnancies ending in preterm delivery, full-term singleton pregnancies, and full-term multiple pregnancies. The number of hMG ampules, the number of preovulatory follicles reaching 18 mm or more in diameter, the cervical mucus score (Insler), the number of living spermatozoa per high-power field (HPF) observed in the cervical mucus on the day of hCG administration, and the midluteal plasma progesterone concentration were determined and correlated with the outcome of the pregnancy in the five groups studied. The minimal requirements for the occurrence of a full-term singleton pregnancy were also determined. RESULTS: In this cohort of 192 women, the mean number of hMG ampules administered was 25.38 (1903.5 IU), the mean number of preovulatory follicles reaching 18 mm was 2.1, the mean cervical mucus score (Insler) was 9.48, and the mean number of motile spermatozoa per HPF in the cervical mucus on the day of hCG administration was 19.3. There were no statistically significant differences between the five groups studied regarding these four variables. The mean midluteal plasma progesterone concentration was 29.07 ng/mL and there was no statistically significant difference in midluteal plasma progesterone concentration between the cycles resulting in full-term deliveries and those ending in miscarriage. However, a statistically significant difference in midluteal plasma progesterone concentration was found between the cycles resulting in full-term singleton pregnancies and those resulting in full-term multiple pregnancies. CONCLUSIONS: The minimal requirements for achieving a full-term singleton pregnancy were 9 ampules of hMG (675 IU), one 18-mm follicle, a cervical mucus score (Insler) of 6 on the day of hCG administration, and a midluteal plasma progesterone concentration of 10.83 ng/mL. The presence of motile spermatozoa in the cervical mucus was a reassuring sign in 92.7% of instances but was not an absolute necessity for a successful outcome.

[Hormonal and functional parameters in hyperprolactinaemia (author's transl)]. / Hormon- und Funktionsprofile bei Hyperprolaktinämie.

58 women with raised serum prolactin levels and normal hypophyseal-X-ray parameters were subdivided into three groups according to the serum prolactin level (16 to 40, 41 to 80, greater than 80 ng/ml). In addition to the determination of LH, FSH, oestradiol, progesterone and testosterone in the serum and thyroid diagnostic procedures the following hormonal tests were performed: 1. response to gestagen; 2. response to clomiphene; 3. Gn-RH-test for hypophyseal function; 4. ovarian response to administered gonadotropins (only in cases with prolactin levels greater than 80 ng/ml). The grade of menstrual cycle disorders depends on the severity of the observed hyperprolactinaemia. Slight disorders like luteal phase insufficiency, anovulatory cycle and oligomenorrhoea are associated with low- or medium-grade hyperprolactinaemia. Mainly secondary, but also primary amenorrhoea is found in cases with higher serum prolactin levels (greater than 80 ng/ml). In these cases the hypophyseal response to Gn-RH is frequently found (61%) to be negative and, moreover, the ovarian response to administered gonadotropins seems to be diminished. Increasing HPRL levels often appear to be associated with a negative response to the other above-mentioned tests.

Fluctuating ovarian function in a perimenopausal women.

Plasma follicle stimulating hormone (FSH) and luteinising hormone (LH) concentrations, and pregnanediol and oestrogen excretion rates, were measured in a perimenopausal woman from the first appearance of oligomenorrhoea until the onset of severe and persistent hot flushes two years later. Postmenopausal episodes characterised by hot flashes, amenorrhoea, high FSH levels (greater than or equal to 5IU/L) and low urinary oestrogens (less than or equal to 50 nmol/24hr), were followed by menstrual cycles in which the FSH levels were low (less than 5 IU/L) and there was an ovulatory pattern of oestrogen and pregnanediol excretion. An unusual association of high urinary oestrogens (greater than or equal to 50 nmol/24hr) with high gonadotrophin levels was observed on several occasions. The transient postmenopausal episodes were biochemically and symptomatically indistinguishable from the permanent amenorrhoea of postmenopausal women.

Endocrine changes and follicular development in patients during ovulation induction using Goserelin and different gonadotropin treatments.

The aim of this study was to compare endocrine changes and the follicular development in patients receiving pure FSH alone or in association with LH after desensitization with an LH-RH agonist depot. Thirty four cycles were selected for this prospective randomized study. Desensitization was obtained using Goserelin the cycle before the stimulation. Induction of ovulation for IUI was carried out with 225 IU/day of pure FSH or with 225 IU/day of hMG. The number of days and ampules required for follicular maturation were equivalent in the two groups. The same number of follicles were developed, while different, but not significant, pregnancy rates were obtained. Estradiol values at the end of stimulation were significantly lower for FSH group. In conclusion the contemporary administration of LH with FSH does not exert any effect on follicular development, but it seems to facilitate E2 synthesis, probably providing more substrate for the aromatization process.

[Gonadotropins in amenorrhea]. / Die gonadotropiene in amenoree.

Serum gonadotrophin values were measured in 410 patients with amenorrhoea. These patients were grouped into five groups in order to determine diagnostic gonadotrophin values, since the latter are most often implicated in the diagnostic investigation of patients with amenorrhoea. Statistically significant differences were noted. To differentiate between hypergonadotrophin amenorrhoea and polycystic ovarian disease, determination of both gonadotrophins, namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH), is necessary. Because of overlapping of values in the polycystic ovarian disease group and the normogonadotrophic group, the LH:FSH ratio is important.

[Serum appearance kinetics of human menopausal gonadotropin (HMG) after intramuscular administration in women]. / Cinétique d'apparition sérique de la gonadotrophine ménopausique humaine (HMG) après administration intra-musculaire chez la femme.

Intramuscularly administered HMG in women induces an increase of serum FSH after 2 hours. Maximal values are reached between the 6 th and the 24 th hour and remain statistically increased until the 48 th hour. An important individual variability is however observed. The modifications of serum LH are inconstant.

[A diagnostic oriented approach to amenorrhea]. / 'n diagnosties-georiënteerde benadering van amenoree.

A practical approach to the diagnosis of amenorrhea is presented. By utilizing a flow-chart 410 patients with amenorrhea were categorized in the following groups: (i) polycystic ovarian disease; (ii) hypergonadotrophic amenorrhoea; (iii) hyperprolactinaemic amenorrhoea; (iv) normogonadotrophic amenorrhoea; and (v) hypergonadotrophic amenorrhoea. This approach helps the practising physician to come to a logical aetiological diagnosis in each category and saves time as well as money. This approach depends on clinical as well as appropriate laboratory examinations, most of which can be done by the private practitioner. Only a minority of patients need sophisticated and costly examinations.

[Thyrotropic reserve in Sheehan's syndrome. Study in 36 patients (author's transl)]. / La réserve thyréotrope au cours syndrome de Sheehan. Etude chez 36 malades.

Thyrotropic involvement is considered to be constant in Sheehan's syndrome. In this study, plasma thyroid stimulating hormone (TSH) levels were similar to those of normal women (respectively: 1.01 +/- 0.54 ng/ml and 0.54 +/- 0.27 ng/ml). The pituitary response to the administration of TRH was nul in 63.8% of cases. In one patient, thyrotrophic function was normal. Twelve patients had a minimal or moderate reserve of TRH. By order of prevalence, thyrotrophic involvement succeeds that of the somatotrophic and lactotrophic axes. There is no correlation with involvement of other axes which would make it possible to define a sequential course of pituitary lesions. These results are discussed in the light of the existing literature. The TRH test does not offer certain evidence of hypothalamic involvement.

[Treatment of ovarian polycystic syndrome in vitro. Physiopathogenetic considerations]. / Traitement des dystrophies ovariennes polykystiques au cours de fécondation in vitro. Considerations physiopathogeniques.

More than 60% of patients with polycystic ovary disease (PCO) cannot conceive after repeated ovulation inductions with Clomifene citrate although there is ovulation or more frequently follicle luteinization. Because of hyperstimulation, therapy with hMG has been superseded by low doses of purified FSH with variable results according to authors. It has been even claimed that there was no benefit to replace hMG with FSH. However, on the basis of the PCO physico-pathology, namely LH hypersecretion and androgen hyperproduction, it would be rational to associate the desensitization of the pituitary with LH-RH agonist and the ovary stimulation with variable doses of hMG or purified FSH. In the series where such therapy associating LH-RH agonists with purified FSH was applied, the results concerning suppression of LH and androgen secretion, and the occurrence of pregnancy were interesting. However, the risk of hyperstimulation still occurred. Thus, the first part concerns the critical review of these results while, in the second part, our experience in in vitro fecundation will be reported.