Serum inhibin B correlates with successful ovulation in infertile women.

PURPOSE: To investigate whether inhibin B and activin A serum and follicular fluid levels in infertile women undergoing induction of superovulation correlate with successful ovulation. METHODS: Infertile women (n = 16) (30-43 years of age) undergoing induction of superovulation for assisted reproduction were studied. A blood sample was collected before and days 3, 8, and 12 during the induction of superovulation. A follicular fluid sample at the time of ovarian pick up was also collected. Serum and follicular fluid were assayed for inhibin B, activin A, and estradiol. RESULTS: According to the successful follicular development women were divided in two groups: (A) responders (n = 10) and (B) poor responders (n = 6). Women of group A showed mean follicular fluid inhibin B levels higher than in group B (P = 0.001), while no significant difference for activin A levels was found. During induction of superovulation serum activin A levels did not change in both groups of women, while inhibin B and estradiol levels significantly increase only in responder women (P < 0.001). Serum inhibin B and estradiol levels correlated with follicles developed > or = 10 mm (P = 0.000). CONCLUSIONS: Serum inhibin B is an effective marker of follicular development in infertile women undergoing induction of superovulation, and may represent a further marker for ovarian follicular capacity.

Reduction of steps in the preparation of motile sperm for intrauterine insemination does not reduce efficacy of the procedure: simplified one-step swim-up method versus classic swim-up.

BACKGROUND: Intrauterine insemination (IUI) is a valid treatment for infertility with a cumulative pregnancy rate of >40-90% after 3-10 treatment cycles. We studied the efficacy of a simplified method for motile sperm preparation for IUI. METHODS: A prospective clinical trial was performed with 100 couples (male age 33-48 and female 28-37 years) with a 2-8 year history of primary infertility associated with slight oligozoospermia (16/100), oligomenorrhoea (32/100) or unknown (52/100). Motile sperm for IUI were prepared by: (A) the classic World Health Organization self-migration (swim-up) method which includes centrifugation, or (B) a simplified one-step swim-up procedure without centrifugation. Recombinant FSH was used for ovarian stimulation. Depending on the cause of infertility, patients were matched one-to-one at the time of IUI, so that when a total of 100 couples had been treated, 50/100 women received sperm prepared by method A and 50/100 by method B. RESULTS: A statistically significant correlation was found between the percentage motile sperm of the original semen sample and the percentage of motile sperm recovered by method A (r = 0.333, P < 0.01) and B (r = 0.400, P < 0.01). A highly significant correlation (r = 0.997, P < 0.001) was found between the two methods. CONCLUSIONS: The simplified one-step swim-up method was as effective as the classic swim-up method, but the former was easier and more economical.

Ovarian hyperstimulation-like syndrome after administration of triptorelin to a woman with endometriosis.

Ovarian hyperstimulation after a single dose of gonadotropin-releasing hormone (GnRH) analog is a rare phenomenon. A case of ovarian hyperstimulation-like syndrome after sole administration of triptorelin (Decapeptyl 3.75 mg) is reported in a woman who had undergone surgery for an endometriotic cyst. After administration of the drug, abdominal pressure increased with nausea and diffuse pelvic pain. Ultrasound examination showed bilateral enlargement of the ovaries (right 74 x 62 mm, left 62 x 53 mm), more than 10 follicles ranging in diameter from 15-25 mm, proliferative endometrium 7 mm thick and fluid in the Douglas pouch up to 25 x 23 mm thick. Estradiol plasma level was in the normal range. The syndrome spontaneously resolved in the course of treatment and a spontaneous pregnancy occurred when the triptorelin effect disappeared.

Timing of hCG administration in cycles stimulated for in vitro fertilization: specific impact of heterogeneous follicle sizes and steroid concentrations in plasma and follicle fluid on decision procedures.

The timing of ovulation induction is usually decided according to estradiol plasma concentrations and follicle size. We administered human chorionic gonadotropin (hCG) when at least three follicles of 16 mm or more in diameter and adequate estradiol plasma concentrations were detected. We studied the percentage of mature oocyte-cumulus-corona radiata complexes, estradiol and progesterone concentrations in a heterogeneous sized follicle population (range 10-20 mm, n = 90) to perform a retrospective analysis of the adequacy of criteria adopted for the timing of ovulation induction. Plasma and follicular fluid were obtained from 20 normo-ovulating women (aged 28-37 years) treated with gonadotropin releasing hormone analogs (GnRH-a) and human menopausal gonadotropin (hMG) for in vitro fertilization (IVF). No correlation was found between the mean individual follicular fluid estradiol concentration (500-5640 nmol/l) and the respective maximum concentration in plasma (2-16 nmol/l). The estradiol concentration was similar in all follicles. Total follicular fluid estradiol concentration was found to be correlated with follicular fluid volume (r = 0.771, p < 0.01). On the day of hCG administration, the concentration of estradiol in the plasma but not the follicular fluid was correlated with the number of oocyte-cumulus-corona radiata complexes collected (p < 0.01) and the number of mature complexes (p < 0.01). At oocyte pick-up, the plasma concentration of progesterone was correlated (p < 0.01) with number of complexes collected and the number of mature complexes. The percentage of mature complexes collected (77.5%) was higher than suggested by the number of leading follicles. This indicates that our criteria for administering hCG were adequate and that heterogeneous follicle size does not exclude a high rate of mature oocyte-cumulus-corona radiata complexes.

Pulsatile secretion of gonadotropins and prolactin during the follicular and luteal phases of the menstrual cycle: analysis of instantaneous secretion rate and secretory concomitance.

OBJECTIVE: To characterize the pulsatile secretions of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) during the menstrual cycle and to statistically evaluate their secretory concomitance. DESIGN: Pulsatility study performed during the midfollicular and midluteal phases of a same menstrual cycle, blood samples being collected every 10 minutes for 6 hours. SETTING: Participants investigated in the Division of Endocrinology, University Hospital. PARTICIPANTS: Nine healthy women (22 to 38 years) with regular menstrual cycles. MAIN OUTCOME MEASURES: Plasma LH, FSH, and PRL values were analyzed as raw and deconvoluted data, and the specific (nonrandom) secretory concomitance was evaluated statistically. RESULTS: The pulsatile secretion of LH was confirmed, and that of FSH and PRL was clearly established during both phases of the cycle by characterization of peak frequency, period, and amplitude. A specific secretory concomitance was assessed between LH and FSH in the follicular but not the luteal phase, and a tight concomitance between LH and PRL was demonstrated during both phases. CONCLUSIONS: These results are supportive of significant pulsatile secretions of the three hormones during the menstrual cycle, and they are demonstrative of a definite copulsatility of these hormones, suggestive of common regulatory factors in the complex temporal patterns of gonadotropin and PRL secretions along the cycle.

A role for tumor markers in therapeutic decisions after chemotherapy induction of objective remission in stage III epithelial ovarian neoplasms.

The management of advanced stage ovarian carcinomas is presently based on initial surgical debulking, multiple drug chemotherapy including cisplatinum, second-look laparotomy. Such an aggressive approach has improved objective response rates and expected survival time, but no dramatic change has been demonstrated as for definitive cure percentages. Many Authors have attempted to turn an optimal objective response to chemotherapy (no residual or minimal residual disease at second-look) into a definitive cure with irradiation. Some reports show satisfactory results, but a high incidence of bowel obstructive complications has been demonstrated, probably due to multiple surgical manipulations before radiotherapy. A reliable diagnostic tool, that could help to avoid the second-look laparotomy (whose inherent role in improving survival is not assessed) should be therefore useful. The possible role of serum tumor markers determinations, for this purpose, is here discussed on the ground of a series of 20 patients affected by stage III ovarian carcinoma. Following this experience, a valuable role seems attributable to CA 125 in monitoring tumor response. Patients achieving values under 35 U/ml before second-look laparotomy showed tumor residuals in the range O-microscopic- less than 1 cm., that is, neoplastic localizations reliable for consolidation radiation therapy.

Gonadotropin, prolactin and thyrotropin pituitary secretion after exogenous dehydroepiandrosterone-sulfate administration in normal women.

The effect of exogenous dehydroepiandrosterone-sulfate (DHAS) on luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL) and thyroid-stimulating hormone (TSH) pituitary secretion was studied in 8 normal women during the early follicular phase. The plasma levels of these hormones were evaluated after gonadotropin-releasing hormone (GnRH)/thyrotropin-releasing hormone (TRH) stimulation performed after placebo or after 30 mg DHAS i.v. administration. The half-life of DHAS was also calculated on two subjects; two main components of decay were detected with half-times of 0.73-1.08 and 23.1-28.8 h. The results show an adequate response of all hormones to GnRH or TRH tests which was not significantly modified, in the case of LH, FSH and PRL, when performed in the presence of high levels of DHAS. However, the TSH response to TRH was significantly less suppressed (p less than 0.05) (39%) after DHAS administration than during repeated TRH stimulation without DHAS (51%). The data support the hypothesis that DHAS does not affect LH, FSH and PRL secretion, while TSH seemed to be partially influenced.

Evaluation of tumor-associated trypsin inhibitor (TATI) in women with benign and malignant gynecological disease.

Tumor-associated trypsin inhibitor (TATI) was assayed in healthy subjects and in women with benign and malignant gynecological diseases. Significantly lower levels were found in boys than in healthy adult subjects. No variations in level were evident over the course of a 24 h period. At a cut-off level of 20 micrograms/l elevated concentrations were found in 42%, 11.4% and 19% of women with ovarian, endometrial and cervical neoplasia, respectively. In patients with ovarian tumors TATI level were elevated both in mucinous and serous tumors. TATI does not seem to be useful for diagnosis of uterine tumors, but could have a specific place in the study and management of ovarian tumors, in which serum concentrations can reach levels 100-200 micrograms/l. In the other gynecological diseases maximum levels of 30-40 micrograms/l were observed.

Different dopaminergic control of plasma luteinizing hormone, follicle-stimulating hormone and prolactin in ovulatory and postmenopausal women: effect of ovariectomy.

The main aim of this study was to evaluate the effect of dopamine infusion on plasma luteinizing hormone (LH), follicle-stimulating hormone, (FSH) and prolactin (PRL) after acute (1 week postovariectomy) and chronic (postmenopausal women) estrogen withdrawal. We also studied the same group of postmenopausal women after ovariectomy to evaluate the possible influence of other gonadal factors on the endocrine effects of dopamine. In order to have a further indication of neuroendocrine dopamine activity on pituitary secretions, we measured the change in plasma LH, FSH and PRL after the administration of metoclopramide, a dopamine receptor antagonist. Our findings confirm that in fertile women dopamine infusion inhibits plasma LH and FSH levels and show that 1 week after ovariectomy the LH decrease during dopamine administration is still present whereas the FSH decrease is not. In all groups of patients, dopamine significantly inhibited plasma PRL levels. Metoclopramide increased plasma LH levels in reproductive-age women before ovariectomy, but not in postmenopausal women. Plasma FSH levels did not change in any group and PRL levels increased after metoclopramide administration in all subjects. The present findings show that dopamine regulation of LH is impaired in long-term menopause, but not shortly after ovariectomy. These changes in LH control are not followed by similar changes in PRL secretion, which remains under tonic inhibitory regulation by dopamine. The different behavior of LH and FSH after ovariectomy and in postmenopause shows the independence of LH and FSH regulation.

CA 125 and CA 19-9 in peritoneal, cyst and amniotic fluids.

The concentrations of the tumour markers CA 125 and CA 19-9 were determined in peritoneal, cyst and amniotic fluids, with particular attention being paid to certain reliability criteria of the assay methods. The antigens were measured in undiluted samples and after several dilutions. A recovery test was also performed and protein content evaluated. The results show high levels of CA 125 in all fluids; in descending order of concentration: amniotic (2376-3891 U ml-1), peritoneal (379-4040 U ml-1) and cyst fluid (124-466 U ml-1). Amniotic, peritoneal and cyst fluid concentrations of CA 19-9 were found to be 314-1008 U ml-1, 26.7-2182 U ml-1 and 226-2988 U ml-1, respectively. Recovery was between 80 and 100% for all fluids. CA 125 was easily assayable in all fluids, except amniotic and peritoneal which required dilution even of the samples which fell within the range of the standard curve before dilution. The presence of CA 125 and CA 19-9 in amniotic and cyst fluids emphasizes the non-specificity of these molecules and suggests caution in the interpretation of the results.

Plasma and cyst fluid levels of delta 5 and delta 4 steroid hormones in women with gross cystic breast disease.

delta 5 and delta 4 steroid levels were studied in the plasma and cyst fluid of women with gross cystic breast disease (GCBD). In luteal phase a significant increase in plasma levels (mean +/- SEM) of DHA (11.2 +/- 2.4 ng/ml), DHAS (1.45 +/- 0.6 micrograms/ml) and cortisol 277 +/- 15.7 ng/ml) was found; in follicular phase the mean levels were 4.09 +/- 0.47 ng/ml for DHA, 0.65 +/- 0.08 microgram/ml for DHAS and 190 +/- 46.3 micrograms/ml for cortisol. The DHA/DHAS and cortisol/androstenedione ratios were significantly higher in the plasma and lower in the cyst fluid of GCBD patients, than in the plasma of controls; the androstenedione/DHA ratio was higher in the cyst fluid than in the plasma of controls. The hormonal situation of the GCBD patients thus differed from that of the controls both in the plasma and cyst fluid, particularly as regards the delta 5 steroids.

Circulating levels of immunoreactive peptides and steroid hormones in bronchogenic carcinoma.

Plasma levels of immunoreactive parathormone (iPTH), immunoreactive calcitonin (iCT) and prostaglandins (PGE2) were measured by RIA in 115 patients with bronchogenic carcinoma. In 37 of these cases the following hormones were also assayed: adrenocorticotropic hormone (ACTH), cortisol, plasma renin activity (PRA), aldosterone, prolactin, human growth hormone (HGH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH) human chorionic gonadotropin (HCG), progesterone (P), androstenedione (A), testosterone (T), estradiol (E2) and dehydroepiandrosterone sulphate (DHAS). High serum levels of many hormone-like substances and hormones were found and the levels of certain hormones varied in some cases according to the clinical evolution of the disease and the response to therapy.

Estrogen receptor content in breast cancer: correlation between biochemical and immunohistochemical methods.

Estrogen receptor content of 26 consecutive cases of ductal breast carcinoma was evaluated by using both biochemical and immunohistochemical methods. Agreement was present in 20/26 cases (76.9%). The analysis of discordant cases shows that in 5 cases disagreement is due to sampling error or to prolonged storage before biochemical evaluation. Such cases may reasonably be excluded when correlating results. Linear regression of the remaining 21 cases shows a significant relationship (r = 0.931; p less than 0.001) between biochemical and immunohistochemical values. Results show that immunohistochemical and biochemical assays are largely comparable, and stress the important role of the pathologist in tumor sampling.

[Changes in plasma concentrations of adrenal androgens in patients with chronic renal insufficiency]. / Alterate concentrazioni plasmatiche degli androgeni surrenalici in pazienti con insufficienza renale cronica (IRC).

The present study points out that the CHRONIC RENAL FAILURE (CRF) represents a situation of decreased adrenal function: at least for delta 5 Steroids which are markedly reduced when compared with normal subjects. Peripheral plasma levels of Pregnenolone (delta 5 P) ranged in CRF between 190 and 860 pg/ml; Dehydroepiandrosterone-sulphate (DHA-S) 0.1-2.2 ng/ml and Dehydroepiandrosterone (DHA) 200-3100 pg/ml. Cortisol was in the normal range or slightly elevated (70-175 ng/ml). A significant correlation between basal concentration and the time of dialysis was observed. It is interesting to notice how the phase levels of delta 5 P, DHA-S and DHA are reduced ad from the beginning of the haemodialysis treatment and that during such a treatment a further progressive decrease occurs reaching concentrations with are similar to those found in pre-puberty. This phenomenon appears to be the evidence of a progressive metabolic involution of the adrenal gland due to the exhaustion of enzymatic activities and of receptorial structures. Furthermore, these results suggest speculation on interrelationship between adrenal and gonadal activity in these patients.

[Hyperprolactinemia in chronic renal insufficiency: an interesting model of hypothalamo-hypophyseal dysfunction]. / L'iperprolattinemia nella insufficienza renale cronica (IRC): un interessante modello di disfunzione ipotalamo - ipofisaria.

It is note that hyperprolactinemia is frequently associated to chronic renal failure (CRF). The etiopathogenesis of this endocrine disorder is not clearly understood, trying to evaluate the possible hypothalamic-pituitary cause we have evaluated the Prl levels under some pharmacological tests: TRH (200 mcg i.v.),Domperidone (DOM)(10 mg i.v.),Nomifensine (NOM)(200 mg p.o.)and Bromocriptine (BRC)(2.5 mg p.o.) in 3 groups of patients: CRF(8 cases), dysfunctional (8 cases) and tumoral (9 cases) hyperPrl. Prl plasma levels have been evaluated by RIA (kits,Biodata,Roma). In patients affected by CRF either direct (BRC) than indirect (NOM) agonist acting dopaminergic drugs failed to induce a reduction in Prl plasma levels, like to tumoral patients for NOM, and in contrast to the significant decrease after BRC (-70%) in tumoral and (-74%) in dysfunctional and NOM (-50%) observed in dysfunctional patients. CRF and dysfunctional patients showed significant response to TRH and DOM, being prolactinoma bearing patients unresponsive to these tests. These results show an hyporesponsivity of pituitary Prl secreting cells to dopaminergic control suggesting the existence of central etiopathological factor in inducing hyperprolactinemia in CRF patients.