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N Santoro

Publications and source records attributed to N Santoro.

At least 73 records · Page 4Linked to original sources
PubMed1996

Evidence for diminished midcycle ovarian androgen production in older reproductive aged women.

OBJECTIVE: To test the hypothesis that reproductive aging is associated with menstrual cycle-related decreases in androgen secretion. DESIGN: Comparison of cross-sectional data. SETTING: University teaching hospital. PATIENTS: Two groups of seven women were studied; midreproductive aged (19 to 37 years old) and older reproductive aged (43 to 47 years old). All patients were cycling regularly and had normal PRL and TSH. INTERVENTIONS: Patients underwent blood sampling during selected days of the menstrual cycle. MAIN OUTCOME MEASURE: After establishing the date of the midcycle surge, specimens were measured on selected days for androstenedione (A), total T, free T, and sex hormone-binding globulin (SHBG) using commercially available reagents. RESULTS: Sex hormone-binding concentrations did not vary across the menstrual cycle and did not differ between older and younger women. Total T did not differ significantly at any cycle stage between older and younger women. However, the midcycle rise in free T and A seen in younger women was consistently and significantly absent in the older women. CONCLUSIONS: In the absence of significant changes in SHBG associated with older reproductive age, the finding of diminished concentrations of both free T and A suggests that these hormones are produced in lesser quantity at midcycle in older women. Because the changes we noted depended on menstrual cycle stage, our findings suggest that an ovarian and not adrenal process is involved.

Adult↗
PubMed1996

Analysis of human interferon-alpha gene promoters by multiple sequence alignment.

A map of conserved motifs within 11 human interferon-alpha gene promoters was developed using multiple sequence alignment. Multiple sequence alignment revealed the highly conserved structure of the virus-response element and a second region immediately upstream of the tata box. Homolog analysis indicated six families of potential promoter elements: (1) tata boxes, (2) GTATGT motifs, (3) virus-response elements, (4) distal putative interferon regulatory factor binding sites, (5) proximal putative interferon regulatory factor binding sites, and (6) TG sequences. On the basis of conserved promoter elements, a theoretical model of human interferon-alpha gene promoter organization was advanced. Transcriptional regulation of human interferon-alpha gene expression is controlled by a tata box and four regulatory domains. Experimental verification is necessary to confirm the predicted transcriptional control sequences. Proposed experimentation will generate insight into the differential transcriptional regulation of human interferon-alpha gene expression.

Amino Acid Sequence↗
PubMed1996

Characterization of reproductive hormonal dynamics in the perimenopause.

Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.

Adult↗
PubMed1996

Myeloablative therapy and bone marrow rescue in advanced neuroblastoma. Report from the Italian Bone Marrow Transplant Registry. Italian Association of Pediatric Hematology-Oncology, BMT Group.

This study reports a large cooperative experience in myeloablative therapy and bone marrow rescue undertaken to define better the outcome of children with disseminated neuroblastoma after megatherapy. Between 1984 and 1993, 135 children underwent myeloablative therapy with bone marrow transplantation (BMT) in nine Italian Centres. One hundred and seventeen children received unpurged autologous BMT, five allogeneic BMT and 13 peripheral blood progenitor cells as rescue. Of these 135 children, 57 were in 1st CR, 11 in 2nd or subsequent CR, 42 in 1st PR, and 25 had more advanced disease. Twelve children (9%) died of toxicity, 86 relapsed or progressed at 1-68 months (median 7 months) and 80 of these subsequently died of progressive disease. Forty-three children are still alive with 37 in continuous remission at a median of 65 months (30-123 months) after BMT. Overall and disease-free survival at 8 years are 28.5% (s.e. 4.3) and 26% (s.e. 4), respectively. Disease-free survival is 34.6% (s.e. 6.7) for the patients grafted in 1st complete remission, 23.6% (s.e. 6.6) for patients grafted in 1st partial remission, 36.4% (s.e. 14.5) for patients grafted in 2nd or subsequent CR, and 8% (5.4) for patients with advanced disease. We conclude these data confirm that early toxicity of myeloablative therapy is manageable and that myeloablative therapy with bone marrow rescue may contribute to an improved long-term survival of children with disseminated neuroblastoma but the objective of cure of all patients remains distant.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Gonadal function after chemotherapy for acute lymphoblastic leukemia].

Object of this study was to verify long term effects on gonadal function in pre- and pubertal patients affected by acute lymphoblastic leukemia (ALL). The population examined was represented by 15 patients, 10 males and 5 females, who came to our Unit after a period of time ranging from 4.5 to 6.2 years. All the patients underwent combined chemotherapy without alkylating agents, such as cyclophosfamide and citosine arabinoside, and intrathecally radiotherapy for a mean period of two years. All the patients were off-therapy and without symptoms of relapse except for one case. The examination of the male and female gonadal function was done on the basis of hormonal assay, ultrasonographic examinations, Tanner's determination of the pubertal development, monitoring of the ovulation and seminal fluid evaluation. The clinical results obtained showed an absence of negative effects both on the gonadal function and on pubertal development. Combined chemotherapy for ALL during pre- and pubertal stage without alkylating agents does not alter the normal gonadal function during the following ten years. Prospective studies will establish the risk of partial follicular atresia and the incidence of premature gonadal failure.

Adolescent↗
PubMed1996

Autologous bone marrow transplantation for extramedullary relapse in childhood leukemia. The AIEOP Group and the FONOP. Italian Association of Pediatric Hemato/Oncology.

The role of autologous bone marrow transplantation (ABMT) in childhood ALL after an isolated extramedullary (IE) relapse is controversial. Between December 1984 and November 1995, 52 children underwent ABMT because of an IE relapse. The data were stored in the AIEOP-BMT Registry. Thirty four children were transplanted in 2nd CR; eighteen > 2nd CR. The median duration of 1st CR was 24 (range 3-69) and 18 (range 3-59) months, respectively. The median interval from last CR to ABMT was 6 (range 1-28) and 3 (range 1-81) months, respectively. The 5 year EFS for patients transplanted in 2nd CR was 67.7%, while the 3 year EFS for patients in > 2nd CR was 16.7%. In conclusion, ABMT was an effective treatment in early IE relapse only if performed in 2nd CR.

Adolescent↗
PubMed1995

Cyclosporine therapy for refractory Langerhans cell histiocytosis.

Optimal treatment for Langerhans Cell Histiocytosis (LCH) has not yet been established. Preliminary reports suggest some effect of cyclosporine (CSA), both alone or in combination with steroids and/or vinblastine, in untreated cases. Twelve children (6 females and 6 males, age at diagnosis 3 months to 4 years) with biopsy proven, systemic LCH received oral CSA (12 mg/kg/day in two divided doses given daily) as a second-line therapy following chemotherapy including vinblastine and/or etoposide (10 cases) or steroid alone (one case); one child was not pretreated. A total of 16 CSA courses were administered to the 12 patients: 8 were completed, 4 were interrupted as unsuccessful, and 4 are still ongoing. CSA related toxicity consisted of hypertrichosis and transient hypertension and was never limiting. Treatment was associated with a clinical response in 8/12 patients: 3 had a complete response and are off therapy, and 5 had a partial response; disease reactivation following first favorable response required additional CSA courses in 3 patients. Four patients failed to respond to CSA: two died of progressive disease, while two had a favorable response to CSA + VP16. Favorable response to CSA was not related to CSA trough and peak levels and was usually observed during the first 2 weeks of CSA therapy. CSA is effective for treatment of LCH also in pretreated children with progressive disease including life-threatening organ dysfunction. Long-lasting complete remission may be achieved after 6 to 12 months of CSA therapy. When disease reactivation occurs after treatment withdrawal, a second course may be followed by favorable response. As minimal or no adverse effects are observed during or after prolonged CSA therapy, this may also be safely used in young patients.

Child↗
PubMed1995

Isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine-activated killer cells in the treatment of in-transit metastases from limb cutaneous melanoma.

BACKGROUND: Therapies of advanced melanoma patients with interleukin-2 (IL-2) and cytotoxic lymphocytes have produced interesting results, but a larger diffusion of these treatments is limited by the severe side effects due to IL-2 systemic infusion. A strictly regional administration of IL-2 and cells by an isolation perfusion (IP) in extracorporeal circulation (ECC) for the treatment of regional melanoma metastases could improve tolerability and efficacy of this specific modality of immunotherapy. METHODS: Ten patients were submitted to adoptive immunotherapy with IL-2 and lymphokine-activated killer (LAK) cells by IP in ECC. The schedule of treatment included the first course of a 5-day systemic administration of IL-2 (Proleukin, EuroCetus 9-12 x 10(6) IU/m2/day continuous infusion); autologous LAK cells were obtained via leukapheresis and after in vitro activation were given (range 8-28 x 10(9)) along with IL-2 (120-2,400 IU/ml of perfusion priming) to the affected limb by IP; IL-2 (9-12 x 10(6) IU/m2/day) was also administered by systemic continuous infusion for 5 days starting on the day after IP. RESULTS: All patients concluded the treatment without any major local or systemic toxicities. Clinical responses included one complete and six partial remissions; three patients had stable disease. All patients are alive. Follow-up after IP ranged from 12 to 35 months (median: 22). The analysis of circulating lymphocytes revealed the rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. CONCLUSIONS: IP with IL-2 and LAK cells is a new approach for the treatment of in-transit metastases due to cutaneous melanoma. The treatment appears to be feasible and reliable. Further biological and immunological studies should permit amelioration of the present modality of treatment.

Adult↗
PubMed1995

High frequency of homozygous deletions of CDK4I gene in childhood acute lymphoblastic leukaemia.

To determine the incidence of homozygous deletions of the newly identified tumour suppressor gene, CDK4I, molecular genomic DNA analyses by PCR technique were performed on primary neoplastic cells from 22 childhood acute leukaemias obtained at presentation. The blast cells derived in all the analysed cases from bone marrow. We found that none of acute myeloblastic leukaemias (four cases) showed the CDK4I alteration, whereas 6/13 (46%) common acute lymphoblastic leukaemias (ALLs) displayed homozygous deletions. Moreover, and even more important, all the blasts purified from ALLs derived from early lymphoid precursors (three early-T ALLs and two pre-B ALLs) showed the absence of CDK4I gene. When the entire coding sequence of the CDK4I gene from samples without homozygous deletions was analysed by the single-strand conformational polymorphism method, no point mutations were identified. These results demonstrate that CDK4I gene deletions are very frequent and probably early events in childhood acute leukaemias of lymphoid origin and especially in early-T and pre-B ALLs. Moreover, the molecular mechanism of the loss of function of the gene is correlated, at least in childhood ALLs, almost exclusively to deletions and not to point mutations.

Base Sequence↗
PubMed1995

Circulating tumor necrosis factor (TNF)-alpha in normally cycling women and patients with premature ovarian failure and polycystic ovaries.

PROBLEM: The purpose of this study was to investigate the levels of tumor necrosis factor (TNF)-alpha in sera of infertile patients having premature ovarian failure (POF) and polycystic ovaries (PCO), and to compare the levels with those in age-matched normally cycling women. METHOD: Levels of TNF-alpha, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) were measured in the sera of infertile and normal women by the enzyme linked immunosorbent assay (ELISA), fluorescent immunoassay and radioimmunoassay (RIA), respectively. Multiple groups comparisons were performed using Dunnet's test. Post-hoc analysis was performed using a Tukey-Kramer test. P < 0.05 was considered statistically significant. RESULTS: TNF-alpha levels were significantly (P = 0.003 to < .0001) lower in the sera of patients with POF compared to sera of controls and patients with PCO. CONCLUSIONS: TNF-alpha may have a role in ovarian function. Derangement in follicular development, luteal function and atresia results in a change of circulating TNF-alpha levels.

Adult↗
PubMed1995

Diminished function of the somatotropic axis in older reproductive-aged women.

Circulating GH and insulin-like growth factor-I (IGF-I) levels in adults generally fall with age. Studies in aging women have rarely controlled for menstrual cycle stage or status or body mass index. We hypothesized that GH and IGF-I levels in reproductive-aged women fall with age despite the stimulatory effects of endogenous estradiol (E2). Eight older reproductive-aged women (aged 42-46 yr) with regular menses, of normal weight, and in good health were compared to a group of eight young control subjects (aged 19-34 yr). Daytime frequent blood sampling was performed in the early follicular phase of the menstrual cycle to characterize pulsatile GH and LH concentrations. Pooled samples were also analyzed for IGF-I, E2, progesterone, and FSH levels. Older reproductive-aged women had lower 12-h integrated daytime GH concentrations (mean +/- SE, 171 +/- 35 vs. 427 +/- 130 micrograms min/L; P = 0.036) than younger controls and a strong trend for lower IGF-I levels (22.7 +/- 2.1 vs. 31.3 +/- 3.5 nmol/L; P = 0.055) than younger controls despite having higher circulating E2 on the day of sampling (368 +/- 51 vs. 167 +/- 20 pmol/L; P = 0.002). We conclude that older reproductive-aged women have lower daytime GH concentrations than younger controls despite having higher E2 levels on the day of sampling and overall normal gonadal hormone parameters.

Adult↗
PubMed1994

Treatment of primary or relapsing limb cancer by isolation perfusion with high-dose alpha-tumor necrosis factor, gamma-interferon, and melphalan.

BACKGROUND: Utilization of alpha-tumor necrosis factor (alpha-TNF) in clinical practice is limited by severe general side effects. Very promising results with low toxicity were reported with administration of alpha-TNF by isolation perfusion in extracorporeal circulation. METHODS: From December 1991 to November 1992, 14 patients underwent perfusion with alpha-TNF (2-4 mg, total dose), gamma-interferon (1.5 x 10(6) IU), and melphalan (10 mg/l/perfused limb). Twelve patients presented in-transit metastases of the limbs, one patient, a clear cell sarcoma of the hand, and one patient, a wide spindle cell carcinoma of the thigh. Perfusion lasted 90 minutes and was conducted in mild hyperthermia (38-40.5 degrees C, muscle temperature). RESULTS: Nine complete regressions and four stable diseases were recorded. In one case, a reliable evaluation of response was not possible for diffused tissue necrosis. Five patients relapsed or progressed locally from 3 to 4 months after surgery, five presented distant localizations from 2 to 7 months after surgery, and one died of disease 6 months after perfusion. Twelve patients are alive, seven without evidence of disease. A septic-like shock syndrome was observed in all patients and required administration of dopamine, dobutamine, or noradrenaline. One patient died 30 days after perfusion from a multiorgan-failure syndrome, likely due to alpha-TNF. The follow-up time ranges from 4 to 15 months (median, 6). CONCLUSIONS: The preliminary, impressive results reported in other series were not completely confirmed in this study adopting the same treatment scheme. Further clinical experience and biologic data are needed to state the real efficacy of the approach and to reduce the severe general toxicity consistently associated with this type of treatment.

Adult↗
PubMed1994

Relaxin secretion into human semen independent of gonadotropin stimulation.

To investigate the control of relaxin (Rlx) secretion in men, we studied seminal plasma Rlx concentrations after physiologic and supraphysiologic gonadal stimulation. In the first experiment, 14 men with idiopathic hypogonadotropic hypogonadism provided semen samples at various time points before and during therapy with pulsatile GnRH. These data were compared to seminal plasma Rlx values in 5 normal men. In a second experiment, pharmacologic doses of hCG were administered in a fashion similar to that previously shown to have stimulated Rlx secretion from the CL of women. In men with idiopathic hypogonadotropic hypogonadism, no relationship was detected by linear regression analysis between seminal plasma Rlx and testosterone, testicular volume, ejaculate volume, or the appearance of sperm in the ejaculate. Rlx concentrations varied considerably between subjects (6-120 ng/ml) but remained fairly consistent within the same individual over time. Supraphysiologic gonadal stimulation with hCG similarly failed to alter seminal plasma Rlx (n = 5, mean +/- SEM; 48 +/- 9 ng/ml, 42 +/- 7 ng/ml, and 56 +/- 9 ng/ml on Days 1, 3, and 6, respectively; p < 0.05) in normal men despite dramatic increases in serum testosterone (763 +/- 25 ng/dl, 1702 +/- 136 ng/dl, and 1494 +/- 97 ng/dl on Days 1, 3, and 6, respectively; p < 0.05 vs. Day 1). Taken together, these data suggest that Rlx in men is secreted independently from direct gonadotropin control.

Adult↗
PubMed1994

Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma.

Blood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin's, 4 Hodgkin's) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37 degrees C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients' mononuclear cells after incubation for 20 h at 37 degrees C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p < 0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p < 0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer were markedly increased in the patient's group (p < 0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.

Adolescent↗
PubMed1994

Treatment of in-transit metastases from cutaneous melanoma by isolation perfusion with tumour necrosis factor-alpha (TNF-alpha), melphalan and interferon-gamma (IFN-gamma). Dose-finding experience at the National Cancer Institute of Milan.

From December 1991 to July 1993, 22 consecutive patients with grade IIIA-IIIAB melanoma underwent isolation perfusion with TNF-alpha (0.5-4 mg), melphalan (10 mg/l perfused limb) and, in the first 12 cases, IFN-gamma (1.5 x 10(6) U). The first series of 12 patients received a total dosage TNF-alpha of 2-4 mg, and the second series of 10 cases received an escalating dosage of TNF-alpha (1.5-1.0-0.5 mg) and no IFN-gamma before or during surgery. The perfusion lasted 90 min and was conducted in mild hyperthermia (39-39.5 degree C muscle temperature). The results of the first series included seven patients in complete remission, four with stable disease and one case not evaluable for local toxicity. Fifty per cent of cases developed a regional relapse from 3 to 4 months after surgery. Presently with a median follow up of 10 months, five patients of this group have no evidence of disease, four are alive with disease, two died from melanoma and one died of complications likely due to treatment (multi-organ failure syndrome). In the second series, the immediate responses included seven patients in complete remission and three in partial remission; with a median follow up of 3 months, two patients developed a regional relapse, respectively, 3 and 5 months after surgery. So far our experience of perfusion with TNF-alpha has not reproduced the data reported by other investigators. Further clinical and biological findings and a longer follow-up period are needed to draw any conclusion, and a decreasing TNF-alpha dose should be carefully evaluated.

Adult↗
PubMed1994

Time-resolved immunofluorometric assay and specimen storage conditions for measuring urinary gonadotropins.

We optimized storage conditions and validated a sensitive immunofluorometric assay (IFMA) for urinary gonadotropins. Assay linearity and parallelism for luteinizing hormone (LH) and follicle-stimulating hormone (FSH) was observed to 0.04 IU/L. Urinary LH and FSH were unaffected by changes of osmolarity from 0.5 to 3.0 mOsm/kg, and from pH 4.5 to 10.5. Serum and urine measurements of the hormones correlated well over a wide range of values: for LH, R2 = 0.94, P < 0.01; for FSH, R2 = 0.71, P < 0.01 (n = 304). Preservation of urine with glycerol (70 mL/L) and storage at -20 degrees C yielded > 80% recovery of LH and FSH after 51 weeks; this was comparable with recovery for acetone extracts of urine. Untreated urine showed loss of activity by 4 weeks of storage. Preserving urine specimens with glycerol is a simple method of storage for longitudinal study and compares favorably with acetone extraction. IFMAs can measure urinary gonadotropins reproducibly over a wide range of pH and osmotic conditions.

Adult↗
PubMed1994

Benefits of continuous physiological pulsatile gonadotropin-releasing hormone therapy in women with polycystic ovarian syndrome.

OBJECTIVE: Can continuous pulsatile GnRH from one ovulatory cycle to another enhance the endocrine milieu of women with polycystic ovarian syndrome (PCOS)? DESIGN: Five women with well-characterized, clomiphene citrate (CC)- and hMG-resistant PCOS were treated with a 100 ng/kg per bolus of IV pulsatile GnRH (Lutrepulse; Ortho Pharmaceutical Corporation, Raritan, NJ) every 90 minutes for two consecutive ovulatory cycles. Weekly vaginal ultrasonography and daily blood sampling for LH (mIU/mL), FSH (mIU/mL), E2 (pg/mL), and P (ng/mL) were performed. These data were compared with a control group of normally cycling women. RESULTS: First ovulatory cycles on therapy were characterized by significantly increased mean follicular phase LH = 88 (arbitrary units area under the curve [AUC]) compared with second cycles (28 mean AUC units) and controls (13 mean AUC units). Luteal phase E2 (3,081 mean AUC units) was significantly increased in first cycles compared with second cycles (880 mean AUC units) and controls (1,562 mean AUC units in PCOS). Luteal phase E2 secretion was elevated in second cycles when compared with normal but not significantly. The changes occurring between the first and second ovulatory cycles in women with PCOS resulted in a more physiological overall pattern of gonadotropin and sex steroid secretion in the second cycles. Two singleton pregnancies were achieved in the second cycle. CONCLUSIONS: Low-dose pulsatile IV GnRH can successfully induce ovulation in women with PCOS who have failed to conceive on all previous conventional therapy (CC, hMG, and/or GnRH agonist, and hMG). Continuous cycle-to-cycle physiological GnRH replacement normalized the endocrine parameters of second cycles. Women with PCOS, even when ovulatory on pulsatile GnRH, do not display entirely normal gonadotropin and sex steroid dynamics.

Adult↗