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J Balasch

Publications and source records attributed to J Balasch.

At least 37 records · Page 2Linked to original sources

Investigation of the infertile couple: investigation of the infertile couple in the era of assisted reproductive technology: a time for reappraisal.

At present, several of the elements in widespread use in basic infertility testing are in dispute, marked variability exists in the work-up among specialists, and practice patterns are influenced both by modern assisted reproductive technologies (ART) and the increasing age of couples seeking help for infertility. This article is intended to stimulate the debate on a possible (lack of) usefulness of conventional methods of infertility evaluation in relation to both the modern techniques of assisted reproduction and the woman's age.

Coitus↗

Day 3 serum inhibin B and FSH and age as predictors of assisted reproduction treatment outcome.

Recent reports investigating the value of basal inhibin B determination as a predictor of ovarian reserve and assisted reproduction treatment have led to discordant results. This study was undertaken to further assess the relative power of day 3 inhibin B and follicle stimulating hormone (FSH) (defined before treatment) and the woman's age both as single and combined predictors of ovarian response and pregnancy in an in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme. A total of 120 women undergoing their first cycle of IVF or ICSI was included. Forty consecutive cycles cancelled because of poor follicular response were initially selected. As a control group, the nearest completed IVF/ICSI cycles before and after each cancelled cycle (i.e. the closest cycles in temporal relationship to the index cycle) were used. Mean age and basal FSH concentrations were significantly higher in the cancelled than in the control group (P: < 0.01 and P: < 0.001 respectively), whereas basal inhibin B was significantly higher in the latter (P: < 0.05). The association of basal FSH (with an accuracy or predictive value of ovarian response of 79%) with cancellation rate was significant, independent of, and stronger than the effects of age and inhibin B (P: < 0.05). Any two or all three of these variables studied did not improve the predictive value of FSH alone. Woman's age was the only variable independently associated with pregnancy rate. It is concluded that the stronger predictors of success in patients undergoing their first IVF/ICSI treatment cycle are age and basal FSH rather than inhibin B. Basal FSH concentration was a better predictor of cancellation rate than age, but age was a stronger predictor of pregnancy rate.

Adult↗

Growth hormone does not increase the expression of insulin-like growth factors and their receptor genes in the pre-menopausal human ovary.

A growing body of information now supports the existence of a complete intraovarian insulin-like growth factor I (IGF-I) system. Although the precise role of IGF-I in the context of ovarian physiology remains to be determined, it is likely that IGF-I may engage in the amplification of gonadotrophin hormonal action. These facts and experiments with animals establishing the ovaries of multiple species as a site of growth hormone (GH) reception and action have led to the use of recombinant GH (rGH) as an adjunctive agent to potentiate ovulation induction by exogenous gonadotrophins. Whether intraovarian IGF-I plays an intermediary role in GH hormonal action at the ovarian level remains uncertain at present. The aim of this study was to evaluate whether rGH administration to pre-menopausal women could modify the expression of the IGF-I gene in the ovary. The expression of the IGF-I gene was examined in a time-dependent manner in normal pre-menopausal ovaries obtained from nine women treated with rGH and nine control women treated with placebo, using solution hybridization/RNase protection assays. Ovarian tissue samples were obtained 24 h (six women) and 7 days (12 women) following rGH/placebo injection. Total RNA (20 microg) from whole pre-menopausal ovaries (with or without rGH treatment) as well as from human granulosa cells was hybridized with a human IGF-I antisense RNA. IGF-I peptide, but not oestradiol, serum concentrations increased significantly 24 h after rGH injection. IGF-I gene, however, was not expressed in the luteinized granulosa cells and whole pre-menopausal ovaries irrespectively of rGH treatment in ovarian samples analysed both 1 and 7 days following rGH injection. On the contrary, IGF-II mRNA transcribed from the fetal or fetal-neonatal IGF-II promoter and IGF-I receptor mRNA (both used as hybridization control) were both found in whole pre-menopausal ovary and luteinized granulosa cells. Nevertheless, no changes in the hybridization patterns were seen in the absence or presence of rGH. These studies demonstrate that rGH administration to normal premenopausal women does not change the expression of insulin-like growth factors and their receptor genes in the pre-menopausal human ovary. Furthermore, these results provide further evidence against locally produced IGF-I as responsible for any ovarian effects seen in systemic rGH administration.

Adult↗

Follicular fluid concentrations of adrenomedullin, vascular endothelial growth factor and nitric oxide in IVF cycles: relationship to ovarian response.

Marked granulosa cell proliferation along with important changes in the vascular bed of the ovary characterize IVF cycles associated with multiple follicular growth and maturation. The present report investigated follicular fluid (FF) and circulating concentrations of adrenomedullin, vascular endothelial growth factor (VEGF) and nitric oxide (NO) in 70 IVF patients (14 of whom became pregnant); these three vasoactive substances may be implicated in extensive ovarian tissue remodelling. Serum and FF concentrations of oestradiol and progesterone were also measured in the 70 IVF cycles studied. Follicular fluid concentrations of VEGF and adrenomedullin but not nitrite/nitrate (the two stable oxidation products of NO metabolism) were significantly higher (P < 0.0001) than the corresponding circulating concentrations. Follicular fluid concentrations of oestradiol and progesterone were not correlated with those of adrenomedullin, VEGF or nitrite/nitrate. No relationship existed between circulating concentrations of adrenomedullin, VEGF or nitrite/nitrate on the day of oocyte aspiration and parameters of ovarian response to gonadotrophin stimulation. In contrast, FF adrenomedullin concentration showed a direct relationship with day 3 FSH serum concentration (r = 0.53, P < 0.01) and the number of ampoules of gonadotrophin administered (r = 0.36, P < 0.005), but an inverse correlation with the total number of oocytes retrieved (r = -0.29, P < 0.01) and the number of mature oocytes (r = -0.25, P < 0. 05). A positive correlation was found for FF VEGF concentration and chronological age (r = 0.29, P < 0.05) and ampoules of gonadotrophins administered (r = 0.30, P < 0.05). There was no relationship between nitrite/nitrate FF concentrations and parameters of ovarian response. Neither serum concentrations nor FF concentrations of adrenomedullin, VEGF or nitrite/nitrate were correlated with IVF outcome. This study suggested for the first time that increased FF concentrations of adrenomedullin can be a marker of decreased ovarian response in IVF. Our results also provide further evidence favouring an association between FF VEGF and patient's age, while on the basis of our findings NO measurements are not a useful marker of ovarian response.

Adrenomedullin↗

Day 5 inhibin B serum concentrations as predictors of assisted reproductive technology outcome in cycles stimulated with gonadotrophin-releasing hormone agonist-gonadotrophin treatment.

The present study investigates the usefulness of inhibin A, inhibin B and serum oestradiol concentrations obtained in the fifth day of gonadotrophin therapy in predicting ovarian response and assisted reproductive treatment outcome in women undergoing ovarian stimulation under pituitary desensitization. A total of 80 women undergoing their first cycle of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment were studied. Twenty consecutive cycles which were cancelled because of a poor follicular response were initially selected. As a control group, 60 women were randomly selected from our assisted reproductive treatment programme matching by race, age, body mass index, and indication for IVF/ICSI to those in the cancelled group. For each cancelled cycle, three IVF/ICSI women who met the matching criteria were included. Basal follicle stimulating hormone (FSH) concentrations were significantly higher in the cancelled than in the control group, whereas basal inhibin B was significantly higher in the latter. Basal oestradiol concentrations were similar in both groups of patients. On day 5 of gonadotrophin therapy serum concentrations of oestradiol, inhibin A and inhibin B were significantly lower in the cancelled group as compared with controls. Logistic regression analysis showed that the association for day 5 inhibin B (with a predictive value of ovarian response of 91.03%) with cancellation rate was significant, independent of, and stronger than, the effects of any other hormone variable investigated. In addition, day 5 inhibin B concentrations were correlated directly with parameters of ovarian response, ovum retrieval and oocyte and fertilization outcome. However, day 5 inhibin B was not a better predictor of pregnancy than the other hormone variables studied on this day. It is concluded that inhibin B concentrations obtained early in the follicular phase during ovarian stimulation under pituitary suppression for assisted reproductive treatment are highly predictive of ovarian response.

Adult↗

Serum inhibin B determination is predictive of successful testicular sperm extraction in men with non-obstructive azoospermia.

Recent work indicates that serum inhibin B is a useful marker of spermatogenesis and inhibin B production sufficient to maintain detectable serum concentrations in adults depends on spermatogenic activity. The purpose of the present study was to investigate the usefulness of serum inhibin B measurement to predict the success of testicular sperm extraction (TESE) in 17 men with nonobstructive azoospermia to be treated by intracytoplasmic sperm injection (ICSI) (group 1). Two additional groups were used as positive controls; group 2 comprised 22 infertile men having obstructive azoospermia, and group 3, which included 29 semen donors having normal seminal parameters. Follicle stimulating hormone (FSH) was significantly higher (P < 0.01) and inhibin B significantly lower (P < 0.001), in group 1 as compared with groups 2 and 3. Serum inhibin B concentrations were significantly higher (P < 0.001) among successful TESE men as compared with those having failed TESE. In contrast, no differences were detected between these two groups with respect to serum FSH or testicular size. In addition, serum inhibin B but not FSH discriminated between successful and failed TESE in group 1 subjects as compared with control groups. According to the receiver operating characteristics curve analysis, the best inhibin B value for discriminating between successful and failed TESE was >40 pg/ml (sensitivity 90%, specificity 100%). It is concluded that inhibin B measurement is a useful non-invasive predictor of spermatogenesis and thus, all azoospermic males should have serum inhibin B concentrations determined in addition to FSH measurement and karyotyping prior to undergoing TESE.

Adult↗

Prevalence and clinical significance of antiprothrombin antibodies in patients with systemic lupus erythematosus or with primary antiphospholipid syndrome.

BACKGROUND AND OBJECTIVE: Antibodies to prothrombin (aII) have been identified in patients with antiphospholipid antibodies, but their clinical significance is not well known. The aim of our study was to investigate their prevalence and association with clinical manifestations of the antiphospholipid syndrome (APS) in patients with primary APS or with systemic lupus erythematosus (SLE). DESIGN AND METHODS: A series of 177 patients with autoimmune diseases was studied: 70 with primary APS and 107 with systemic lupus erythematosus. A control group of 87 healthy volunteers were included in the study. aII were investigated in sera by an ELISA, using human prothrombin as antigen fixed in irradiated polystyrene plates. RESULTS: aII prevalence in patients with autoimmune disease was 47% (57% and 40% in patients with primary APS or with SLE, respectively) significantly higher than in controls (5%) (p<0.0001). In the whole series, thrombotic events were more prevalent in patients with aII (45% vs 28%; p=0.02). Moreover, aII was found to be an independent risk factor for arterial thrombosis (OR=2.4; p=0. 04). Similarly, in patients with SLE, aII were associated with both arterial and venous thrombosis (35% vs 14%; p=0.01), although only IgG-aII (OR=3.7; p=0.01) had an independent value as risk factor for thrombosis. However, a relationship between aII and thrombosis was not found in primary APS. aII were associated with thrombocytopenia only in patients with primary APS (OR=6.7; p=0.007). INTERPRETATION AND CONCLUSIONS: aII seem to be a serological marker of thrombosis in autoimmune diseases, mainly in SLE patients and/or in the arterial territory.

Abortion, Spontaneous↗

Circulating levels of nitric oxide in successful and unsuccessful implantation after in vitro fertilization and embryo transfer. Relationship to estradiol and progesterone.

BACKGROUND: Nitric oxide (NO) may play an important role in embryo implantation and early embryo development. This study investigated the potential role of circulating nitric oxide (NO) measurement to predict the outcome of implantation and pregnancy after IVF and ET. METHODS: Two blood samples were collected from 237 IVF patients on days 13-14 and 20-21 after ET. Serum concentration of nitrite/nitrate (the two stable oxidation products of NO metabolism), estradiol (E2), progesterone and beta-hCG were measured on days 13-14 after ET and one week later. RESULTS: No significant differences were found with respect to nitrite/nitrate serum concentrations in conception versus non-conception cycles, viable versus abnormal pregnancies, and viable pregnancy group versus non-conception cycles, respectively, despite that significant differences were observed regarding E2 and progesterone values. Nitrite/nitrate serum concentrations were similar for singleton and multiple pregnancies at both study points. In viable pregnancies, no significant change was observed for nitrite/nitrate serum concentration from days 13-14 to 20-21 after ET. No correlation was found between nitrite/nitrate serum concentration and E2 or progesterone serum levels. CONCLUSIONS: Circulating levels of nitrite/nitrate are similar in successful and unsuccessful implantation after IVF and are unrelated to the outcome of pregnancy. This precludes the use of serum NO measurement as a marker of implantation and successful pregnancy in IVF.

Adult↗

Clinical study and follow-up of 100 patients with the antiphospholipid syndrome.

OBJECTIVES: To study the clinical characteristics at diagnosis and during follow-up of patients with the antiphospholipid syndrome (APS) and to analyze the influence of treatment on their outcome. PATIENTS: One hundred patients with APS were included (86% female and 14% male; mean age, 36 years). Sixty-two percent had primary APS and 38% had APS associated with systemic lupus erythematosus (SLE). The median length of follow-up was 49 months. RESULTS: Fifty-three percent of the patients had thromboses, 52% had thrombocytopenia, and 60% of the women had pregnancy losses. Patients with APS associated with SLE had a higher prevalence of hemolytic anemia (P = .02), thrombocytopenia (platelet count lower than 100 x 10(9)/L) (P = .004), antinuclear antibodies (P = .0002), and low complement levels. Fifty-three percent of the patients with thrombosis had recurrent episodes (86% in the same site as the previous thrombotic event). Recurrences were observed in 19% of the episodes treated with long-term oral anticoagulation, in 42% treated prophylactically with aspirin, and in 91% in which anticoagulant/antiaggregant treatment was discontinued (P = .0007). Multivariate analysis showed that prophylactic treatment and older age had an independent predictive value for rethrombosis. Prophylactic treatment during pregnancy (usually with aspirin) increased the live birth rate from 38% to 72% (P = .0002). CONCLUSIONS: Patients with APS have a high risk of recurrent thromboses. Long-term oral anticoagulation seems to be the best prophylactic treatment to prevent recurrences. Prophylactic treatment with aspirin during pregnancy reduced the rate of miscarriages remarkably.

Adolescent↗

Obstetrical outcome of pregnancy in patients with systemic Lupus erythematosus. A study of 60 cases.

OBJECTIVE: To analyze the course of maternal diseases and the outcome of pregnancy in patients with systemic Lupus Erythematosus (SLE). STUDY DESIGN: During a period of 11 years we prospectively followed 60 pregnancies in 46 SLE patients in a tertiary care center in Barcelona (Spain). The management protocol included: (1) planning of conception when disease was inactive; (2) frequent follow-up visits by an internist-obstetrician team; (3) use of sequential ultrasonographic, Doppler and fetal echocardiographic examinations; (4) serial evaluations of maternal immunological condition; and (5) low dose aspirin from 1 month before attempting conception and throughout pregnancy was added in women with antiphospholipid antibodies. From 1985 until 1994 prednisone prophylaxis was used in all lupus patients during the last month of pregnancy and during the first month of the puerperium; from 1995 onwards this regime was abandoned. RESULTS: The mean (S.D.) age of patients was 28.6 (4.8) years (range 20 to 42) and the mean (S.D.) previous duration of SLE was 6.25 (4.8) years (range 0 to 17). SLE was diagnosed during the pregnancy in two cases (3.3%) and the disease was active at conception in four cases (6.7%); at that time nine patients (15%) were taking prednisone. Antiphospholipid antibodies were positive in 16 patients (30.4%) and there were 10 (16.7%) pregnancies in patients having lupus nephropathy. There were three first-trimester miscarriages (5%) and four (6.7%) voluntary abortions. Obstetric complications in the remaining 53 pregnancies included: preterm delivery, 11 cases (20.8%); intrauterine growth retardation, five cases (9.4%); hypertension, 10 patients (18.9%), five of them fulfilling the criteria of preeclampsia; premature rupture of membranes, four patients (7.5%); finally, 13 neonates had a birthweight lower than 2500 g. There were 15 lupus flares (28.3%), giving a flare rate of 0.044 per patient/month. There were five neonatal deaths (perinatal mortality rate, 94 per thousand): one because of complete heart block, three due to severe hyaline membrane disease resulting from extreme prematurity and one intrauterine death in a patient having the Leiden mutation. CONCLUSION: Pregnancy in patients with SLE should not be regarded as an unacceptable high-risk condition for the mother or her baby provided that conception is accurately planned and patients are managed according to a careful multidisciplinary treatment schedule.

Female↗

Recurrent empty follicle syndrome successfully treated with recombinant human chorionic gonadotrophin.

We report a case of a patient with polycystic ovary syndrome and primary infertility who was admitted to our in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programme because of her partner's severe oligozoospermia and asthenozoospermia. Ovarian stimulation was accomplished in the three treatment cycles using gonadotrophin therapy after a dual approach with ovarian suppression using oral contraceptive pills followed by gonadotrophin-releasing hormone agonist therapy. Oocyte retrieval was unsuccessful in the first two treated cycles despite the fact that human chorionic gonadotrophin (HCG) from three different batches was used. In the third treatment cycle, recombinant HCG was used and five oocytes were retrieved. This is the first report of recurrent empty follicle syndrome despite the use of different batches of commercially available urinary HCG, and of its successful treatment using recombinant HCG.

Adult↗

Human reproductive failure is not a clinical feature associated with beta(2) glycoprotein-I antibodies in anticardiolipin and lupus anticoagulant seronegative patients (the antiphospholipid/cofactor syndrome)

It has been suggested that patients with clinical features suggestive of antiphospholipid syndrome but being lupus anticoagulant (LA) and anticardiolipin (aCL) negative, should be tested for antibodies to beta(2) glycoprotein-I (abeta(2)GP-I), a protein involved in the binding of antiphospholipid antibodies (aPL) to phospholipid surfaces. This was investigated in the present study where a total of 385 women aged </=40 years were included. Of these, 175 were experimental subjects and 210 were controls. The former comprised the following two study groups: 100 spontaneous recurrent aborters (group one), and 75 patients with repeated failure of embryo transfer (group two). Controls included three groups of women: 100 normal healthy parous women with no previous abortion (group three), 60 infertile patients achieving a live birth with their first in-vitro fertilization (IVF)/embryo transfer attempt (group four), and 50 patients with recurrent abortion who tested positive for aPL (LA and/or aCL) (positive controls, group five). Only one patient among recurrent aborters (group one) tested positive for abeta(2)GP-I. All women in groups two, three and four were negative for abeta(2)GP-I screening. As expected, prevalence of patients testing positive for abeta(2)GP-I was significantly higher in group five than among the other groups of patients (P < 0.001). No differences were observed regarding the prevalence of abeta(2)GP-I positive sera in the subgroup of patients having aCL and those having the LA in group five. It is concluded that abeta(2)GP-I screening in first-trimester recurrent abortion or in failure of implantation after IVF is not warranted in patients without aPL as detected by standard antiphospholipid assays.

Abortion, Habitual↗

Long-term compliance with estrogen replacement therapy in surgical postmenopausal women: benefits to bone and analysis of factors associated with discontinuation.

OBJECTIVE: To evaluate prospectively the effects of long-term estrogen replacement therapy (ERT) on bone density in surgical postmenopausal women treated for 5 years with two different modalities and to determine the factors associated with discontinuation of ERT. DESIGN: We included in the present study 165 women (mean age, 46.8 +/- 4.6 years) who had undergone surgical menopause. ERT was prescribed immediately after surgery, and bone mineral density was measured at the lumbar spine before the women entered the study and at 12, 24, 36, 48, and 60 months after being included. Treated patients were assigned at random to one of two groups. The first group received conjugated equine estrogens 0.625 mg/day continuously, and the second group received transdermal 17beta-estradiol 50 mg/day continuously. Treated groups were compared with a nontreated control group. RESULTS: Our data showed that although ERT clearly protected against bone loss in women who had experienced surgical menopause, only one third of the treated patients continued ERT at the end of follow-up. The main reason for discontinuation was fear of cancer (36.1 % of cases). In addition, no differences were observed between oral and transdermal groups of treatment. CONCLUSIONS: Long-term ERT may have a protective effect against bone loss in surgically postmenopausal women; however, two thirds of treated patients discontinued therapy after 5 years and 43% of them presented a negative balance on bone mass in one or more bone density assessments. For this reason, enhancing compliance and monitoring treatment are mandatory.

Absorptiometry, Photon↗

Ascites and liver test abnormalities during severe ovarian hyperstimulation syndrome.

OBJECTIVE: Severe ovarian hyperstimulation syndrome is an uncommon cause of ascites that is being increasingly recognized because of the high number of women undergoing assisted reproductive techniques, mainly in vitro fertilization. This prospective study investigates the clinical and biochemical characteristics of a large series of patients with this syndrome and ascites, including renal and electrolyte abnormalities, activity of neurohormonal systems participating in the regulation of extracellular fluid volume, and liver function tests. METHODS: This was a prospective longitudinal study including 50 consecutive patients with ascites due to severe ovarian hyperstimulation syndrome. Renal function, serum electrolytes, body weight, mean arterial pressure, pulse rate, plasma renin activity, plasma concentration of aldosterone, norepinephrine, antidiuretic hormone and atrial natriuretic peptide, and standard liver function tests were measured during the syndrome and 4-5 wk after recovery. A sample of ascitic fluid was obtained from eight patients for protein measurement and cell count. RESULTS: At diagnosis, patients had ascites associated with low urinary sodium excretion, oliguria, and hyponatremia. They had also markedly low arterial pressure and increased pulse rate in association with marked activation of vasoconstrictor and antinatriuretic factors. The ascitic fluid was characterized by a high protein concentration, low leukocyte count, and relatively high number of red blood cells. Fifteen (30%) patients had abnormal liver tests characterized by mild to moderate increases in AST (mean 103 +/- 17.1 IU/L) and ALT (76 +/- 8.3 IU/L), which were associated in some cases with increases in gamma-glutamyl transpeptidase or alkaline phosphatase. All abnormalities reverted to normal after the resolution of the syndrome. CONCLUSIONS: With the increasing use of assisted reproductive techniques, physicians should be aware of severe ovarian hyperstimulation syndrome as a cause of ascites. The syndrome is associated with sodium retention, hyponatremia, arterial hypotension, and marked activation of vasoconstrictor and antinatriuretic systems. In one third of patients, liver tests abnormalities are present.

Adult↗

Type-1 and type-2 cytokines in human decidual tissue and trophoblasts from normal and abnormal pregnancies detected by reverse transcriptase polymerase chain reaction (RT-PCR).

PROBLEM: Cytokine expression at the maternal fetal interface has been well documented in rodents, but data in the human are scanty and controversial. METHOD OF STUDY: We examined cytokine expression of human decidua and trophoblasts by semiquantitative visual grading of reverse transcriptase polymerase chain reaction (RT-PCR) products in five groups of patients: ten patients with uncomplicated term pregnancies undergoing elective cesarean section (Group 1); ten women having normal pregnancies at term and vaginal delivery (Group 2); ten patients having intrauterine growth-retarded infants of unknown cause after a spontaneous vaginal delivery at term (Group 3); ten childless women having their first, first-trimester spontaneous abortion (Group 4); and ten childless women with a history of one or more previous first-trimester spontaneous abortions and having a new miscarriage (Group 5). RESULTS: Results favoring the T-helper 1 (Th1)/T-helper 2 (Th2) model during pregnancy were: significantly higher expression of interferon gamma (IFN-gamma) in trophoblast samples from Group 3 versus 2 and in decidual tissue from Group 5 versus 4; stronger positivity of interleukin (IL)-10 in decidual tissue samples from Group 1 versus Groups 2 and 5; and higher expression levels of tumor necrosis factor-beta (TNF)-beta by the trophoblast in Group 5 versus 1. Against the Th1/Th2 paradigm were the following findings: the significantly increased expression of IFN-gamma by decidual or trophoblast samples in Groups 1 versus 2, 2 versus 3, and 1 versus 5; and the significantly higher expression of TNF-alpha in decidual samples from patients in Group 1 (but also Group 4) as compared with Group 5. IL-2 mRNA and IL-4 mRNA could not be detected. CONCLUSIONS: Overall, our findings suggest that there is a balance between type-1 and type-2 cytokines during pregnancy, which is mainly characterized by the expression of IFN-gamma (a type-1 cytokine) and IL-10 (a type-2 cytokine) at the maternal fetal interface.

Cytokines↗

Two-year prospective and comparative study on the effects of tibolone on lipid pattern, behavior of apolipoproteins AI and B.

OBJECTIVE: To investigate long-term lipid and lipoprotein changes in postmenopausal women treated with tibolone in a prospective study using appropriate control groups. DESIGN: Seventy-six of 105 postmenopausal women initially selected for this study completed the 2-year follow-up. Patients were allocated into three groups. The first received 2.5 mg/day tibolone continuously (n = 27; group T), the second received 0.625 mg/day conjugated equine estrogen plus 2.5 mg/day of medroxyprogesterone (group E-P) continuously (n = 25), and a third group contained an additional 24 women who did not receive replacement therapy; these constituted the untreated control group (group C). Plasma lipids and lipoproteins were determined in all patients before joining the study and also at 12 and 24 months after being included. RESULTS: Women treated with tibolone experienced the greatest decreases in cholesterol, both total and high density lipoprotein (HDL), and triglycerides (TG), whereas the highest increase in HDL was observed in the group E-P. A decrease in low density lipoprotein levels was detected in both therapy groups, whereas a significant increase was observed in the control group. TG were increased after E-P therapy. In all the groups, apolipoprotein AI showed parallel trends to HDL and apolipoprotein B to low density lipoprotein. CONCLUSIONS: Both therapy groups, tibolone and E-P, induced changes in levels of plasma lipids, lipoproteins and apolipoproteins. Long-term tibolone treatment is associated with a marked and significant decrease in HDL apolipoprotein AI and TG, an effect that defines the major difference with standard HRT. Clearly, further studies are necessary to establish the definite risk/benefit ratio of tibolone with respect to its overall effect on lipid metabolism.

Anabolic Agents↗

Adrenomedullin and nitric oxide in menstrual and in vitro fertilization cycles. Relationship to estradiol.

BACKGROUND: Estradiol has marked systemic vasodilator effects which may be partially mediated by nitric oxide. Recently, a new vasodilator peptide, adrenomedullin, having potent vasodilatory action which is mediated at least in part by nitric oxide, has been isolated. This study investigated whether a relationship exists between circulating levels of estradiol, adrenomedullin, and nitrite/nitrate (the two stable oxidation products of NO metabolism) both in the spontaneous menstrual cycle and IVF cycles. METHODS: Ten normal ovulatory infertile patients were included in this prospective longitudinal study. Circulating levels of estradiol, adrenomedullin, and nitrite/nitrate were investigated. Follicular fluid concentrations of adrenomedullin and nitrite/nitrate, as well as estradiol, were also determined in IVF cycles. RESULTS: Serum nitrite/nitrate levels were significantly elevated in the late follicular phase compared to cycle day 3 of the spontaneous menstrual cycle thus paralleling plasma estradiol. However, no significant change in serum nitrite/nitrate concentration was found associated to multifollicular development and supraphysiological levels of estradiol in IVF cycles. Adrenomedullin plasma levels did not show significant variation either in menstrual or IVF cycles. No correlation was found between plasma estradiol levels and nitrite/nitrate serum concentrations or adrenomedullin plasma levels nor between circulating adrenomedullin and nitrite/nitrate both in menstrual and IVF cycles. Follicular fluid concentrations of estradiol and adrenomedullin but not nitrite/nitrate were significantly higher than those found in plasma or serum. Neither estradiol follicular fluid concentration correlated with those of adrenomedullin or nitrite/nitrate nor a relationship was observed between adrenomedullin and nitrite/nitrate. CONCLUSIONS: Circulating levels of nitrite/nitrate show a significant increase during the late follicular phase in the normal menstrual cycle which is unrelated to adrenomedullin. In addition, this does not necessarily indicate a cause and effect relationship between nitrite/nitrate and estradiol levels given that no increase in nitrite/nitrate was observed from a hypoestrogenic to a hyperestrogenic state during IVF cycles. Further studies are necessary to clarify this subject. Also, the biological and clinical significance of the presence of adrenomedullin in the human follicular fluid remains to be elucidated.

Adrenomedullin↗