Biomedical subjects

G De Placido

Publications and source records attributed to G De Placido.

At least 19 recordsLinked to original sources

PubMed2006

Cryptozoospermia with normal testicular function after allogeneic stem cell transplantation: a case report.

One of the most frequent consequences of allogeneic haemopoietic stem cell transplantation (allo-SCT) in both males and females is gonadal insufficiency. We report the case of a 27-year-old myelodysplastic male who developed azoospermia after allogeneic transplantation of haemopoietic stem cells from his HLA-identical sister. Post-transplant azoospermia was alternated with intermittent severe oligospermia. The patient had a normal endocrine pattern and evidence of mild chronic graft-versus-host disease (cGVHD). Normal intratesticular spermatogenesis was revealed by bilateral fine needle aspiration (FNA) cytology. Inflammation was evident at semen analysis, but no infection was detected by microbiological examination and sperm culture. These findings, together with the re-appearance of sperm cells at semen analysis after a low-dose immunosuppressive treatment, suggested the presence of cGVHD of the urogenital tract, causing a reversible obstruction of the spermatic tract and cryptozoospermia. This is the first case report documenting a severe impairment of sperm count because of a reversible obstruction of the seminal tract, likely caused by cGVHD, in a long-term survivor of allo-SCT with normal endocrine pattern. An important practical consequence of this case report is the fact that azoospermia was cured using low-dose immunosuppressive therapy, and this allowed us to avoid expensive stimulatory treatments with gonadotrophins, which remain, however, ineffective if the obstruction of spermatic tracts is not removed. A spontaneous uncomplicated pregnancy occurred in the partner of the patient 3 months after the corticosteroid treatment withdrawal.

Adult↗

PubMed2006

The use of a decremental dose regimen in patients treated with a chronic low-dose step-up protocol for WHO Group II anovulation: a prospective randomized multicentre study.

BACKGROUND: In women with chronic anovulation, the choice of the FSH starting dose and the modality of subsequent dose adjustments are critical in controlling the risk of overstimulation. The aim of this prospective randomized study was to assess the efficacy and safety of a decremental FSH dose regimen applied once the leading follicle was 10-13 mm in diameter in women treated for WHO Group II anovulation according to a chronic low-dose (CLD; 75 IU FSH for 14 days with 37.5 IU increment) step-up protocol. METHODS: Two hundred and nine subfertile women were treated with recombinant human FSH (r-hFSH) (Gonal-f) for ovulation induction according to a CLD step-up regimen. When the leading follicle reached a diameter of 10-13 mm, 158 participants were randomized by means of a computer-generated list to receive either the same FSH dose required to achieve the threshold for follicular development (CLD regimen) or half of this FSH dose [sequential (SQ) regimen]. HCG was administered only if not more than three follicles >or=16 mm in diameter were present and/or serum estradiol (E(2)) values were <1200 pg/ml. The primary outcome measure was the number of follicles >or=16 mm in size at the time of hCG administration. RESULTS: Clinical characteristics and ovarian parameters at the time of randomization were similar in the two groups. Both CLD and SQ protocols achieved similar follicular growth as regards the total number of follicles and medium-sized or mature follicles (>/=16 mm: 1.5 +/- 0.9 versus 1.4 +/- 0.7, respectively). Furthermore, serum E(2) levels were equivalent in the two groups at the time of hCG administration (441 +/- 360 versus 425 +/- 480 pg/ml for CLD and SQ protocols, respectively). The rate of mono-follicular development was identical as well as the percentage of patients who ovulated and achieved pregnancy. CONCLUSIONS: The results show that the CLD step-up regimen for FSH administration is efficacious and safe for promoting mono-follicular ovulation in women with WHO Group II anovulation. This study confirms that maintaining the same FSH starting dose for 14 days before increasing the dose in step-up regimen is critical to adequately control the risk of over-response. Strict application of CLD regimen should be recommended in women with WHO Group II anovulation.

Anovulation↗

PubMed2006

Association of pelvic endometriosis with alopecia universalis, autoimmune thyroiditis and multiple sclerosis.

An adult Caucasian female developed a previously unreported association of pelvic endometriosis (PE) with the triad of alopecia universalis (AU), autoimmune thyroiditis (AT) and multiple sclerosis (MS). Molecular human leukocyte antigen (HLA)-tissue typing of this subject showed the presence of the DR(2) 15 and DR(3) 17 alleles, which are associated to an increased risk of MS and AT, respectively. Clinical onset of AT followed withdrawal of corticosteroid treatment for AU, whereas MS become clinically evident after withdrawal from long-term estroprogestin therapy for PE. This clinical case is presented to discuss the autoimmune origin of PE, its possible association with multiple autoimmune disorders as well as the effect of other factors, such as administration and/ or discontinuation of specific hormonal regimens, on genetic autoimmunity-prone background.

Adolescent↗

PubMed2006

Intra-follicular leptin concentration as a predictive factor for in vitro oocyte fertilization in assisted reproductive techniques.

BACKGROUND: Granulosa-cells are able to produce and store leptin, suggesting that this hormone is locally involved in the regulation of follicular growth. In this study, the role of follicular fluid (FF) leptin concentration in predicting oocyte fertilization and embryo quality was evaluated in 35 normogonadotrophic women undergoing controlled ovarian stimulation (COS) for assisted reproductive techniques. MATERIALS AND METHODS: Leptin concentration was measured in 47 consecutively collected FF in which a mature oocyte had been found during the ovum pick-up. Embryos deriving from fertilized oocytes were submitted to quality scoring systems. RESULTS: Mean leptin concentration was significantly higher in FF whose oocytes showed 2 pronuclei (no. 25) when compared with those with no evidence of fertilization (no. 22) at the 16-18 h check (26.0+/-6.1 vs 15.3+/-10.6 ng/ml, respectively, p<0.01). Follicular mean diameters were similar in the two groups (21.4+/-3.4 and 21.0+/-5.1 mm, respectively). Logistic regression analysis identified FF leptin levels as the best predictive parameter for oocyte fertilization (p<0.001). When receiving operating characteristics curve was employed, a FF leptin concentration of 20.25 ng/ml was the most reliable cut-off in predicting fertilization of oocytes. FF with leptin concentrations higher than this value (no. 27) had an oocyte fertilization rate of 85.7%. In contrast, FF levels < or =20.25 ng/ml (no. 20) were associated with a rate of 16.7% (p<0.05). No correlation emerged between FF leptin and the score attributed to 15 valuable embryos at the zygote stage (r=-0.01) and at 48 h after insemination (r=0.1). CONCLUSIONS: FF leptin levels are a better predictor of oocyte fertilization success rates than follicular diameter. These results underline the relevance of FF variables in developing methods for oocyte selection.

Adult↗

PubMed2006

Exploiting LH in ovarian stimulation.

During intermediate-late phases of human folliculogenesis, LH plays a key role in promoting steroidogenesis and growth of the leading follicle. Ovarian stimulation for assisted reproduction techniques usually consists of administering exogenous FSH in a low LH environment. Although an impairment in LH-dependent paracrine activities would be expected, multiple follicular growth is efficiently achieved in almost all patients. Thus, there appears to be a discrepancy between classical folliculogenesis models and data from IVF. This study examines the 'interface' between basic endocrinological and clinical evidence, in an attempt to answer two questions: is there an LH therapeutic window, and if there is, how can this be exploited in the practice of assisted reproduction? It also reviews the evidence that specific subgroups of women may benefit from LH supplementation during ovarian stimulation.

Adult↗

PubMed2006

Outlook: who needs LH in ovarian stimulation?

LH plays a key role in the intermediate-late phases of folliculogenesis. Although ovarian stimulation is efficiently achieved in most cases by the administration of exogenous FSH alone, specific subgroups of women may benefit from LH activity supplementation during ovarian stimulation. Some authors have found improved outcome with LH activity supplementation in advanced reproductive age women. Experience suggests that in about 10-12% of young normogonadotrophic patients treated with a gonadotrophin-releasing hormone agonist (GnRH-a) long protocol plus recombinant FSH human (r-hFSH), a 'steady response' is observed. In this subgroup of women, a higher number of oocytes is retrieved when daily LH activity supplementation is given from stimulation day 8, if compared with the standard FSH dose increase. Another subgroup of patients who may benefit from LH activity supplementation are those at risk for poor ovarian response treated with GnRH antagonist. Recent data demonstrate that in these women, when GnRH is administered in a flexible protocol, the concomitant addition of recombinant human LH improves the number of mature oocytes retrieved, when compared with the standard GnRH-a flare-up protocol. Thus, well calibrated LH administration improves the ovarian outcome in patients >35 years, in those showing an initial abnormal ovarian response to r-hFSH monotherapy, and in 'low prognosis' women treated with GnRH antagonists.

Adult↗

PubMed2006

Atosiban vs ritodrine used prophylactically with cerclage in ICSI pregnancies to prevent pre-term birth in women identified as being at high risk on the basis of transvaginal ultrasound scan.

Our objective was to compare the effectiveness and safety of atosiban and ritodrine, in pregnancies obtained by intracytoplasmic sperm injection (ICSI) undergoing cervical cerclage. Data from a prospective study were compared with those from a retrospective study. Sixteen ICSI pregnant women, 20-24 weeks' gestation and maternal age >18 years, received atosiban (bolus dose 6.75 mg i.v., followed by 300 microg/min i.v. for 3 h and 100 microg/min i.v. for 45 h). Cervical cerclage was performed 3 h after starting atosiban. The control group (group B) of 16 ICSI pregnant women were matched and received ritodrine hydrochloride (100-350 microg/min) for 48 h. Cervical cerclage was performed after 24 h. Pre-term rupture of membranes occurred within 48 h of cervical cerclage in one woman receiving atosiban and in four women receiving ritodrine. There was no significant difference in terms of pregnancies not delivered at 48 h (short-term tocolysis) and at 7 days (long-term tocolysis). However, there was a significantly higher incidence of maternal tachycardia with ritodrine compared with atosiban (p < 0.001). The mean gestational age at delivery was significantly higher for atosiban compared with ritodrine (36 vs 33 weeks; p < 0.001). The neonatal outcome was poorer for ritodrine than atosiban, as there were very low birth weight infants (p = 0.008), resulting in lower Apgar scores (p = 0.005) and there were more neonates requiring a long stay in the neonatal intensive care unit (p = 0.005). We conclude that atosiban is associated with a significantly lower incidence of maternal tachycardia and improved neonatal outcome compared with ritodrine.

Adult↗

PubMed2005

Acquired factor XII deficiency in a woman with recurrent pregnancy loss: working on a differential diagnosis in a single case.

BACKGROUND: Antiphospholipid syndrome (APS) has been often associated to RPL since 1980 and some reports in the Literature rarely described antibodies to factor XII in patients with APS. CASE HISTORY: We report the case history of 34-year-old caucasian women with recurrent fetal loss and persistent prolonged activated partial thromboplastin time. Haemostatic tests revealed persistent light decrease of clotting factor XII with normal values of IgG and IgM anticardiolipin antibodies and transient positivity for lupus anticoagulant (LA). Few reports in the Literature described antibodies to factor XII in patient with antiphospholipid syndrome (APS) and transient LA. So, once other causes of RPL were excluded, the patient was diagnosed an unusual form of APS associated to antibodies to factor XII, reduced factor XII plasma levels, transient LA and prolonged activated partial thromboplastin time. DISCUSSION: We suggest to consider also antibodies directed to clotting factors (e.g. factor XII in our case) as second step of thrombophilia screening in RPL, in particular if a persistent prolonged aPTT is present without an apparent cause.

Journal Article↗

PubMed2004

Recombinant human LH supplementation versus recombinant human FSH (rFSH) step-up protocol during controlled ovarian stimulation in normogonadotrophic women with initial inadequate ovarian response to rFSH. A multicentre, prospective, randomized controlled trial.

BACKGROUND: In approximately 12-14% of young normogonadotrophic women treated with a depot GnRH agonist long protocol, the initial ovarian response to recombinant human FSH (rFSH) can be suboptimal. We have tested the hypothesis that these women may benefit from recombinant human LH (rLH) supplementation in a multicentre, prospective, randomized trial compared with patients treated with an rFSH step-up protocol. METHODS: A total of 260 young normogonadotrophic women undergoing controlled ovarian stimulation with a GnRH agonist long protocol for IVF/ICSI were enrolled. The starting dose of rFSH was 225 IU. One hundred and thirty patients with serum estradiol levels <180 pg/ml and with at least six follicles with a mean diameter >5 mm but none >10 mm on both day 5 and day 8 of stimulation were randomly allocated to two groups. From the eighth day of stimulation, women in group A (n=65) received 150 IU of rLH in addition to rFSH, while those in group B (n=65) had an increase of 150 IU in the daily dose of rFSH (step-up protocol). One hundred and thirty normally responding women continued monotherapy with rFSH and served as a further control population (group C). RESULTS: The mean number of cumulus-oocyte complexes retrieved in group A (9.0+/-4.3) was significantly higher (P<0.01) compared with group B (rFSH 6.1+/-2.6) but significantly lower compared with group C (10.49+/-3.7, P<0.05). Implantation and pregnancy rates were significantly lower (P<0.05) in the rFSH step-up group (10.5 and 29.3% respectively) when compared with normal responders (18.1 and 47.3% respectively). CONCLUSIONS: rLH supplementation is more effective than increasing the dose of rFSH in terms of ovarian outcome in patients with an initial inadequate ovarian response to rFSH alone.

Adolescent↗

PubMed2004

Effects of recombinant LH (rLH) supplementation during controlled ovarian hyperstimulation (COH) in normogonadotrophic women with an initial inadequate response to recombinant FSH (rFSH) after pituitary downregulation.

BACKGROUND: This study was aimed to evaluate the effect of different recombinant LH (rLH) doses on the ovarian outcome of normogonadotrophic women with an initial inadequate response to recombinant FSH (rFSH) after pituitary downregulation. METHODS: Only women undergoing a 'long protocol' with a GnRH-agonist followed by rFSH administration were enrolled. On the eighth day of stimulation, 46 patients with serum E2 levels < 180 pg/ml and with no follicle > 10 mm were randomized in two groups to receive a supplementation with a daily rLH dose of 75 (group A) or 150 IU (group B), respectively. Forty-six normal responders continuing their monotherapy with rFSH formed the control group (C). RESULTS: The mean number of oocytes retrieved and the percentage of mature oocytes in the group B (9.65 +/- 2.16, 79.0%) were comparable with those observed in the group C (10.65 +/- 2.8, 82.5%) and significantly higher when compared with the group A (6.39 +/- 1.53, 65.7%). The mean number of ampoules of rLH was significantly higher in the group B (14.4 +/- 2.0 vs. 9.65 +/- 1.1), whereas these patients received a significantly lower mean number of rFSH ampoules (44.6 +/- 7.4 vs. 36.1 +/- 3.8). Seven (30.4%), 9 (39.1%) and 22 (47.8%) pregnancies were achieved in the groups A, B and C, respectively. CONCLUSIONS: These results suggest that patients with initial inadequate responses to rFSH after pituitary downregulation benefit from the addition of a daily dose of 150 IU of rLH, starting from the eighth day of stimulation.

Adult↗

PubMed2002

The effect of ease of transfer and type of catheter used on pregnancy and implantation rates in an IVF program.

PURPOSE: To test the effects of type of embryo transfer catheter, transfer difficulty, and observations after the transfer procedure on pregnancy and implantation rates in an IVF programme. METHODS: Patients were prepared for IVF using standard protocols. Embryo transfer was performed using either Edwards-Wallace or TDT catheter. The difficulty of transfer was graded by a clinician and biologist. Blood observed inside the catheter after the transfer procedure was scored as endometrial damage. Pregnancy and implantation rates were scored. RESULTS: Type of embryo transfer catheter and the observation of blood did not significantly affect pregnancy and implantation rates when transfer was performed by a single operator. CONCLUSIONS: In the hands of experienced, skilled operators, neither choice of transfer catheter and difficulty of transfer nor observations of blood on the transfer catheter caused any significant reduction in outcome to the patient.

Adult↗

PubMed2001

Mitochondrial aggregation patterns and activity in human oocytes and preimplantation embryos.

Mitochondria play a vital role in the metabolism of energy-containing compounds in the oocyte cytoplasm to provide adenosine trisphosphate for fertilization and preimplantation embryo development. In this study, ratiometric confocal microscopy with the mitochondrion-specific membrane potential-sensitive fluorescence dye JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide) was used to measure the activity of mitochondria in human oocytes and developing preimplantation embryos. Mitochondria in oocytes and embryos were characterized by distinct localized aggregation patterns. These patterns however did not determine localized regions of heterogeneity in mitochondrial activity. Mitochondrial activity was analysed during oocyte maturation and after fertilization. The activity of mitochondria in fresh metaphase II oocytes was negatively correlated with maternal age. This trend continued when the activity of developing embryos was analysed. Mitochondrial activity was strongly correlated with the rate of embryo development on day 3 after fertilization, but not on day 2. Partial regression analysis showed that the rate of cleavage of preimplantation embryos was more highly correlated with embryo mitochondrial activity than maternal age. These data suggest that the efficiency of mitochondrial respiration in oocytes and preimplantation embryos is closely correlated with the programmed rate of embryo development, and suggest that maternal age further influences this factor. The loss of mitochondrial activity in oocytes obtained from ageing couples may therefore contribute to lower embryo development and pregnancy rates observed during cycles of IVF.

Benzimidazoles↗

PubMed2001

The peritoneal fluid concentration of leptin is increased in women with peritoneal but not ovarian endometriosis.

This study was designed to measure leptin concentrations in the peritoneal fluid (PF) of women with different aspects of pelvic endometriosis. Among 36 consecutive women undergoing laparoscopy, nine were diagnosed as having minimal-mild endometriosis (stage I-II). Among nine other subjects with advanced stage (III-IV) disease, six showed one or more ovarian endometriotic cysts as the only operative finding. The remaining 18 unaffected women constituted the control group. Patients with endometriosis had significantly higher PF leptin concentrations (32.6 +/- 16.2 versus 17.1 +/- 6.6 ng/ml, P = 0.002); this difference remained significant when corrected for body mass index (BMI) (PF leptin/BMI ratio 1.41 +/- 0.67 versus 0.76 +/- 0.28, P = 0.001). Furthermore, the PF leptin/BMI ratio was significantly higher in women with peritoneal implants than in those in whom no implant was found at laparoscopy (1.6 +/- 0.7 versus 0.83 +/- 0.33, P = 0.007). Conversely, patients with one or more ovarian endometriomata as the only finding, had a PF leptin/BMI ratio comparable with that in women where no cyst was found (1.05 +/- 0.4 versus 1.1 +/- 0.65). In women with stage I-II endometriosis, a higher mean PF leptin/BMI ratio was found compared with those affected by stage III-IV (1.78 +/- 0.68 versus 1.05 +/- 0.43, P = 0.01). These results show that during endometriosis the presence of peritoneal disease, and not of ovarian endometriotic cysts, influences leptin concentrations in PF. The data suggest that leptin may play a role in the development of peritoneal endometriosis, and that different biochemical phenomena might be involved in the pathogenesis of the ovarian form of the disease.

Adult↗

PubMed2001

Pregnancy after cytoplasmic transfer in a couple suffering from idiopathic infertility: case report.

Couples suffering from idiopathic infertility are among the most difficult to treat in IVF cycles due to the unknown cause of failure to reproduce. This can lead to years of unsuccessful attempts to conceive and often the abandonment of treatment. In some couples, the only observable problem is the development of poor quality embryos. In this case report, we describe the successful use of cytoplasmic donation in a couple where the high level of embryo fragmentation and poor embryo development was thought to be the unique cause of failure to conceive after intracytoplasmic sperm injection (ICSI). We noted a strong reduction in embryo fragmentation and a consequent increase in embryo quality after the treatment. Transfer of four of the embryos receiving donor cytoplasm led to a pregnancy with two gestational sacs and the birth of healthy twins.

Adult↗

PubMed2001

Rescue of IVF cycles by HMG in pituitary down-regulated normogonadotrophic young women characterized by a poor initial response to recombinant FSH.

BACKGROUND: The aim of this study was to investigate the effects of adding human menopausal gonadotrophin (HMG) during controlled ovarian stimulation in normoovulatory normogonadotrophic patients showing an initial suboptimal response to a standardized long protocol therapy with recombinant FSH (rFSH) (300 IU/day). METHODS: A total of 43 such patients were randomized in two groups. In Group A, 150 IU rFSH was substituted by 150 IU HMG after day 8 of stimulation. The stimulation protocol of Group B involved a simple increase of the daily rFSH dose to 375 IU after day 8. A total of 40 BMI and age matched patients with an optimal ovarian response formed the control group (Group C). RESULTS: The mean Group A serum concentration of oestradiol on the day of HCG administration and average number of oocytes retrieved were significantly higher than Group B (P < 0.001) and equivalent to Group C. A total of 10 pregnancies (50%) in Group A, 8 (34.8%) in Group B and 19 (47.5%) in the control group were achieved. CONCLUSIONS: The data suggest that LH supplementation improves the ovarian outcome in patients characterized by an inadequate initial response to rFSH therapy in a long protocol.

Adult↗

PubMed2000

Effects of hormone replacement therapy on postmenopausal uterine myoma.

OBJECTIVES: To evaluate the effects of sequential continuous hormone replacement therapy (HRT) on myoma size and on pulsatility index (PI) of uterine arteries and to verify the correlation between uterine artery flow impedance and the growth rate of myoma in women receiving HRT. METHODS: In a prospective 1-year study 60 postmenopausal women were enrolled into three study-groups to receive continuous transdermal 17beta-oestradiol 0.05 mg/day plus nomegestrolo acetate 5 mg/day sequentially added: 20 patients (group A) unaffected by uterine myomas, 20 patients (group B) with single asymptomatic myoma <3 cm/14 cm3, 20 patients (group C) with single asymptomatic myoma >3 cm/14 cm3. The changes in myoma volume and in PI were assessed by means of transvaginal ultrasonographic scan every 3 months. The patients with myoma were divided into two subgroups: quiescent myoma (B1, C1) and growing myoma (B2, C2). RESULTS: No significant increase of uterine fibroids volume was found after 1-year HRT (24.14+/-20.02-->28.81+/-30.02 cm3). Six out of eight myomas growing during HRT belonged to group C. The uterine artery basal PI value of group A was significantly higher (P<0.01) than the corresponding PI in group B and C. At 3 months follow-up, uterine artery PI was significantly higher (P<0.01) than the basal value in both group B (1.70+/-0.22-->1.88+/-0.16) and C (1.59+/-0.28-->1.92+/-0.21). The baseline PI values in group B1 and C1 were significantly higher than the baseline values observed in group B2 and C2 (1.76+/-0.17 vs. 1.32+/-0.02, 1.76+/-0.16 vs. 1.24+/-0.08) and significantly lower than those observed in group A (2.39+/-0.47). After 3 months of HRT, the PI values were not significantly higher than the baseline values in groups B1 and C2 (1.76+/-0.17-->1.90+/-0.17; 1.24+/-0.08-->1.74+/-0.16), while they were significantly higher in group C1 (1.76+/-0.16-->2.01+/-0.17). CONCLUSIONS: Sequential continuous HRT does not increase the volume of the uterine myoma. The findings of very low resistance index in the uterine arteries of women with growing myoma may indicate the risk of growth of the neoplasia during HRT. The assessment of PI in the uterine arteries could be helpful in predicting the growth rate of the myomas before starting HRT.

Estradiol↗

PubMed2000

A phase I study of gemcitabine and epirubicin for the treatment of platinum-resistant or refractory advanced ovarian cancer.

BACKGROUND: Gemcitabine is active in patients with otherwise resistant or refractory ovarian cancer. As the drug is well tolerated, studies using gemcitabine combined with other antineoplastic agents are needed. The aim of the study was to determine the maximum tolerated dose (MTD) of epirubicin combined with gemcitabine, with and without support of G-CSF. PATIENTS AND METHODS: Patients with platinum-resistant or refractory ovarian cancer were eligible. Gemcitabine (G) (starting dose 800 mg/m2 day 1 and 8; 200 mg/m2 escalation per level) and epirubicin (E) (starting dose 60 mg/m2 day 1; 15 mg/m2 escalation per level) were given every 21 days for four to six cycles. G-CSF (filgrastim 5 microg/kg/die) was given in case of grade 4 neutropenia (levels without support) or from day 9 up to leukocyte count > 10.000/mm3 after nadir (levels with support). Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered. MTD was determined first without and then with G-CSF. RESULTS: Four levels were studied (G 800 + E 60; G 1000 + E 60; G 1000 + E 75; G 1000 + E 75 + G-CSF) with four, four, three and three patients enrolled, respectively. DLT (grade 4 febrile neutropenia) was observed in two patients at level 3. Thus, G1000 + E 60 mg/m2 was the MTD without G-CSF. The addition of prophylactic G-CSF did not allow a further increase of the dose and grade 4 thrombocytopenia was the DLT at level 4. Non-hematological toxicity was mild. Grade 2 mucositis was reported in four patients. Among the 13 patients with measurable or evaluable disease, 3 partial responses were observed for an overall response rate of 23.1%. CONCLUSIONS: The combination of gemcitabine 1000 mg/m2 (day 1, 8) and epirubicin at 60 mg/m2 (day 1) is a feasible therapy. Grade 4 neutropenia is frequent and G-CSF support is often required. With prophylactic support of G-CSF, the DLT is thrombocytopenia.

Adult↗

PubMed2000

Recombinant follicle stimulating hormone is effective in poor responders to highly purified follicle stimulating hormone.

Ovarian stimulation in cases of poor ovarian responsiveness is an important challenge in in-vitro fertilization (IVF) programmes. Despite improvements in oocyte number and quality, an ideal ovarian stimulation strategy has yet to be defined. Here, the results of ovarian stimulation with recombinant follicle stimulating hormone (rFSH) in 28 poor responders to highly purified FSH (FSH-HP) with high basal concentrations of FSH are reported. The protocols used on the FSH-HP and rFSH cycles were identical with the sole exception of the FSH preparation: triptorelin 0.1 mg/day (gonadotrophin-releasing hormone, GnRH-agonist short protocol) and the starting FSH dose of 300 IU/day were administered from day 2 of the menstrual cycle. Ovarian outcome was classified as 'normal', 'intermediate' and 'poor', depending on the number of mature oocytes retrieved and the peak serum oestradiol concentration. Nine of the 28 subjects had an intermediate ovarian response to re-stimulation with rFSH. In the 26 patients who received human chorionic gonadotrophin on both cycles, re-stimulation resulted in a significant increase (P < 0.05) in the mean number of mature oocytes (2.4 +/- 1.4 versus 1.7 +/- 0.8), mean peak oestradiol concentration (606 +/- 252 versus 443 +/- 32 pg/ml) and fertilization rate (73.0 versus 53.3%). Four pregnancies were achieved. It is concluded that rFSH in a GnRH-agonist short protocol improves the ovarian outcome in poor responders to FSH-HP with high basal concentrations of FSH.

Estradiol↗