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Biomedical subjects

R A Lobo

Publications and source records attributed to R A Lobo.

At least 55 records · Page 3Linked to original sources
PubMed1997

Comparing the clinical utility of GnRH antagonist to GnRH agonist in an oocyte donation program.

A potent gonadotropin-releasing hormone (GnRH) antagonist (Nal-Glu) was administered to downregulate the pituitaries of oocyte donors (n = 15) and block their midcycle luteinizing hormone surges. Donors received Nal-Glu at a dose of 50 microg/kg/day i.m., beginning when lead follicles reached a mean diameter of 14 mm. All donors had previously undergone controlled ovarian hyperstimulation cycles using GnRH agonist (leuprolide acetate) administered subcutaneously beginning during the midluteal phase. Ovarian stimulation was performed using human menopausal gonadotropin (hMG). Compared to previous stimulated cycles using agonist and hMG, cycles with antagonist and hMG demonstrated a significant decrease in the amount of hMG required for follicle stimulation (24.7 +/- 1.8 vs. 31.3 +/- 2.5 ampules; p < 0.05). There was also a significant reduction in the number of patient visits necessary per cycle (5.1 +/- 1.4 vs. 9.3 +/- 1.1; p < 0.05) and the required duration of treatment to accomplish a cycle (27.1 +/- 5.3 vs. 11.3 +/- 1.3 days; p < 0.05). However, there were no differences noted in the number of oocytes retrieved (10.7 +/- 4.5 vs. 13.0 +/- 6.3), the fertilization rate of oocytes (60.3 +/- 10.2 vs. 53.9 +/- 11.6%), or the number of embryos obtained per recipient (5.5 +/- 3.2 vs. 7.6 +/- 5.3). Clinical pregnancies occurred in 7 of 15 transfer cycles to recipients. There were no serious adverse side effects experienced by donors using antagonist. We conclude that the use of GnRH antagonist significantly reduces the amount of medication and the time required for ovarian hyperstimulation and that is a useful adjunct in cycling oocyte donors.

Adult↗
PubMed1997

5 alpha-reductase activity and prostate cancer: a case-control study using stored sera.

We report a nested case-control study of serum biomarkers of 5 alpha-reductase activity and the incidence of prostate cancer. From a cohort of more than 125,000 members of the Kaiser Permanente Medical Care Program who underwent multiphasic health examinations during 1964-1971, we selected 106 incident prostate cancer cases. A control was pair matched to each case on age, date of serum sampling, and clinic location. Serum levels of total testosterone, free testosterone, androsterone glucuronide, and 5 alpha-androstane-3 alpha,17 beta androstanediol glucuronide (3 alpha-diol G) were measured on the stored samples and scored as quartiles. Potential confounders included alcohol, smoking, and body mass index. The adjusted odds ratios and 95% confidence intervals for a one quartile score increase were 1.00 (0.75-1.34) for total testosterone, 1.14 (0.86-1.50) for free testosterone, 1.13 (0.84-1.53) for androsterone glucuronide, and 1.16 (0.86-1.56) for 3 alpha-diol G. A limitation of this study is that there are two different 5 alpha-reductase isoenzymes, only one of which is expressed in high levels within the prostate, yet both of which may affect serum biomarkers. Since the two isoenzymes are encoded on different chromosomes, variation in one would act as an independent source of measurement error in any analysis of serum biomarker effects of the other. Consequently, the odds ratios may be underestimated and the study, although negative, cannot exclude the previously hypothesized possibility that a positive relationship between intraprostatic 5 alpha-reductase activity and prostate cancer may exist. A clinical trial to test this hypothesis is under way.

Aged↗
PubMed1997

Urinary progesterone and pregnanediol. Use for monitoring progesterone treatment.

OBJECTIVE: To compare progesterone (P) and pregnanediol glucuronide (PDG) levels in urine with respect to their potential use for monitoring luteal activity and P treatment. STUDY DESIGN: Two different experiments were carried out. In the first experiment, each of seven normal, ovulatory women collected first morning urines daily throughout an entire menstrual cycle. The day of ovulation was determined by transvaginal ultrasound scanning. P, PDG, estrone glucuronide, luteinizing hormone and creatinine were measured in each urine specimen. In the second experiment, each of three normal, ovulatory women was given a single oral dose of 200 mg of micronized P and, 2 days later, a single intramuscular injection of 25 mg of P during days 2-5 of the cycle. Blood and urine were collected prior to each treatment and 1, 4, 8, 12 and 24 hours after treatment. P was measured in both serum and urine; PDG was quantified only in urine. RESULTS: The mean initial rises and peak days, as well as the patterns of urinary excretion of P and PDG during the menstrual cycles, were similar; however, the variability of PDG was much greater. Concentrations of PDG were 1,000-4,000 times greater than those of P. A significant correlation was observed between urinary P and PDG. Following either intramuscular or oral P treatment, serum P levels rose rapidly and reached peak levels (7.0-11.8 ng/mL) by one hour. In contrast, both urinary P and PDG peaked considerably later (4-12 hours). Twenty-four hours after intramuscular treatment, serum and urinary P and urinary PDG were still elevated. Following oral treatment the levels of these compounds decreased after peaking and were 10- to 20- fold lower at 24 hours. Also, after oral P treatment, urinary PDG levels were considerably higher and more variable as compared to urinary P levels. CONCLUSION: Urinary P appears to be as good a clinical marker of luteal activity and therapeutic P administration as PDG and may be measured in place of this metabolite. There appears to be greater variability in urinary PDG as compared to urinary P when P is administered.

Adult↗
PubMed1997

Androgens in serum and the risk of prostate cancer: a nested case-control study from the Janus serum bank in Norway.

We tested the hypothesis that serum levels of testosterone (T), dihydrotestosterone (DHT), and the DHT metabolite 3 alpha,17 beta-androstanediol glucuronide are positively associated with the risk of prostate cancer. This nested case-control study was based on the cohort of men who donated blood to the Janus serum bank at Oslo University Hospital (Oslo, Norway) between 1973 and 1994. Cancer incidence was ascertained through linkage with the Norwegian Cancer Registry. The study included sera from 59 men who developed prostate cancer (cases) subsequent to blood donation and 180 men who were free of any diagnosed cancer (controls) in 1994 and were of similar age (+/- 1 year) and had similar blood storage time (+/- 6 months) to the cases. Neither T, DHT, nor the ratio T:DHT was associated with risk of developing prostate cancer. Compared to the bottom quartile, the odds ratio (OR) associated with the top quartile of T was 0.83 [95% confidence interval (CI), 0.36-1.93]; the OR for the top (compared to the bottom) quartile of DHT was 0.83 (95% CI, 0.36-1.94), and the equivalent OR for T:DHT was 1.31 (95% CI, 0.58-2.97). Similarly, 3 alpha,17 beta-androstanediol glucuronide showed no association with prostate cancer risk; the OR for the top (compared to the bottom) quartile was 1.10 (95% CI, 0.41-2.90). These results showed no association, positive or negative, between androgens measured in serum and the subsequent risk of developing prostate cancer.

Adult↗
PubMed1996

The significance of elevated early follicular-phase follicle stimulating hormone (FSH) levels: observations in unstimulated in vitro fertilization cycles.

OBJECTIVE: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles. STUDY DESIGN: We compared cycles with elevated day 3 FSH levels (> 20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels. PATIENTS: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH. RESULTS: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E2) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies. CONCLUSIONS: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.

Blastocyst↗
PubMed1996

Rare occurrence of ovarian hyperstimulation syndrome in oocyte donors.

OBJECTIVES: To define the incidence and severity of ovarian hyperstimulation syndrome (OHSS) occurring in oocyte donors. METHODS: Women (n = 149) aged 31.3 +/- 4.8 years (mean +/- S.D., range 21-41 years) participated as designated oocyte donors and underwent 400 consecutive cycles of controlled ovarian stimulation using human menopausal gonadotropin following pituitary downregulation with gonadotropin-releasing agonist. Patients were monitored by serial transvaginal ultrasound examinations and serum estradiol (E2) determinations. Oocytes (15.6 +/- 7.5 per aspiration; range 2-57) were harvested by ultrasound-directed transvaginal follicle aspiration 36 h following the intramuscular injection of human chorionic gonadotropin (hCG). Follow-up examination occurred 1 and 2 weeks post-aspiration. RESULTS: On the day of hCG injection E2 levels ranged from 512 to 13,502 pg/ml (mean 2902.7 +/- 1486.9 pg/ml). Over the next few weeks the degree of hyperstimulation in donors was staged: mild 65% (grade I, n = 98; grade II, n = 162); moderate 33.5% (grade III, n = 120; grade IV, n = 14); severe 1.5% (grade V, n = 6; grade VI, n = 0). Associated preaspiration E2 levels were: grade I, 1120 +/- 424 pg/ml; grade II, 2084 +/- 613 pg/ml; grade III, 3785 +/- 1713 pg/ml; grade IV, 5370 +/- 1264 pg/ml; grade V, 4286 +/- 1100 pg/ml. Worsening OHSS was associated with increasing levels of E2. There were no serious complications and hospitalization was not required. All symptoms resolved within 30 days of aspiration, disappearing by the time of the first menstrual flow in women of grade-III or lower stage. CONCLUSION: Although oocyte donors commonly experienced exaggerated levels of serum E2 they rarely (< 2%) developed severe OHSS. This may be attributable to their lack of embryo transfer which avoids exacerbating the illness.

Adult↗
PubMed1996

Biologic effects of 17 alpha-dihydroequilin sulfate.

OBJECTIVE: To determine the independent biologic effects of 17 alpha-dihydroequilin sulfate. DESIGN: Prospective randomized study. SETTING: University of Southern California Medical Center. PATIENTS(S): Twenty-one postmenopausal women, mean age 50 +/- 2 (+/-SEM) years, and mean body mass index 27 +/- 2. INTERVENTION(S): Women were randomized to receive daily oral doses of either 1.25 mg of estrone sulfate (E1S), 0.2 mg of 17 alpha-dihydroequilin sulfate, or a combination. Three blood and urine samples were obtained before and after 30 and 90 days of treatment. RESULT(S): After 30 and 90 days of treatment, E1S alone increased sex hormone-binding globulin (SHBG) levels significantly, 19.7% +/- 6.0% and 61.3% +/- 13.0%, whereas 17 alpha-dihydroequilin sulfate reduced SHBG levels, 20.8% +/- 68% and 12.4% +/- 7.5%, respectively. Nevertheless, the combination of E1S and 17 alpha-dihydroequilin sulfate significantly increased SHBG levels, 103% +/- 27.9% and 98.2% +/- 19.1%, compared with baseline at 30 and 90 days. Fewer changes were evident with corticosteroid-binding globulin (CBG). After 90 days of treatment, CBG levels significantly increased 30.9% +/- 5.5% with E1S, decreased by 7.2% +/- 5.0% with 17 alpha-dihydroequilin sulfate, and, with the combination, significantly increased by 10.5% +/- 2.4% compared with baseline. Changes in lipids and lipoproteins were more variable. However, high-density-lipoprotein cholesterol increased significantly with E1S at 30 and 90 days compared with baseline, 96.5% +/- 39% and 91.5% +/- 22.6%, and with the combination increased 66.4% +/- 13.3% and 79.2% +/- 24.4%, respectively. Fewer changes were evident with 17 alpha-dihydroequilin sulfate alone, decreasing 4.4% +/- 22% and 2.6% +/- 21.3%. Urinary ratios of bone collagen equivalents-creatinine and calcium-creatinine decreased in all three groups. However, the combination group resulted in a significantly greater percentage decrease in bone collagen equivalents-creatinine than with E1S alone. CONCLUSIONS(S): 17 alpha-Dihydroequilin sulfate could modify some of the first-pass effects of conjugated equine estrogens and act synergistically with other conjugated equine estrogens to reduce bone resorption.

Calcium↗
PubMed1996

Oocyte donation to women of advanced reproductive age: pregnancy results and obstetrical outcomes in patients 45 years and older.

We analysed the results of oocyte donation to women of advanced reproductive age (> or = 45 years old) and followed their pregnancies through to delivery in order to assess obstetrical outcomes. Patients (n = 162) aged 45-59 years (mean +/- SD; 47.3 +/- 3.4 years) underwent 218 consecutive attempts to achieve pregnancy. Oocytes (16.2 +/- 7.2 per retrieval) were provided by donors < or = 35 years old. Cleaving embryos (8.2 +/- 4.8 zygotes/couple) were transferred transcervically (4.5 +/- 1.1 per embryo transfer) to recipients prescribed oral micronized oestradiol and intramuscular progesterone. Following oocyte aspiration there were six instances of non-fertilization (2.8%) and 212 embryo transfers. A total of 103 pregnancies was established for an overall pregnancy rate (PR) of 48.6%, which included 17 preclinical pregnancies, 12 spontaneous abortions, and 74 delivered pregnancies (clinical PR 40.6%; delivered PR 34.9%). Multiple gestations were frequent (n = 29; 39.2% of pregnancies) and included 20 twins, seven triplets, and two quadruplets. Two of the triplet and both of the quadruplet pregnancies underwent selective reduction to twins. Antenatal complications occurred in 28 women (37.8% of deliveries) and included preterm labour (n = 9), gestational hypertension (n = 8), gestational diabetes (n = 6), carpel tunnel syndrome (n = 2), pre-eclampsia (n = 2), HELLP syndrome (n = 2), and fetal growth retardation (n = 2). 48 (64.8%) deliveries were by Caesarean section. The gestational age at delivery for singletons was 38.3 +/- 1.3 weeks (range 35-41 weeks), with birth weight 3218 +/- 513 g (range 1870-4775 g); twins 35.9 +/- 2.0 weeks (range 32-39 weeks), birth weight 2558 +/- 497 g (range 1700-3450 g); and triplets 33.5 +/- 0.7 weeks (range 32-34 weeks), birth weight 1775 +/- 190 g (range 1550-2100 g). Neonatal complications (4.6% of babies born) included growth retardation (n = 2), trisomy 21 (n = 1), ventricular septal defect (n = 1), and small bowel obstruction (n = 1). There were no maternal or neonatal deaths. We conclude that oocyte donation to women of advanced reproductive age is highly successful in establishing pregnancy. However, despite careful antenatal screening, obstetrical complications are common, often secondary to multiple gestation.

Abortion, Spontaneous↗
PubMed1996

Plasma lipids and desogestrel and ethinyl estradiol: a meta-analysis.

OBJECTIVE: To review the literature to determine the magnitude of the effect of 150 micrograms desogestrel-30 micrograms ethinyl E2, an oral contraceptive (OC) formulation, on plasma lipid concentrations in healthy women using meta-analysis techniques. DATA SOURCES: All English-language published reports (1981 to 1991) on lipid parameters in women taking 150 micrograms desogestrel and 30 micrograms ethinyl E2 for up to 6 months obtained via an Embase database search and via a subsequent review of the reference lists. METHODS OF STUDY SELECTION: Of 98 articles, 18 met eligibility criteria and were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS: Data on total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were extracted. The change in each parameter from baseline to cycle 6 was estimated as a weighted mean of changes reported in each study; a standard error of the estimate was calculated. This procedure was validated by goodness-of-fit tests. RESULTS: The following statistically significant changes from baseline to cycle 6 were estimated (mean +/- SE): HDL-C: 0.15 +/- 0.02 mmol/L (5.80 +/- 0.62 mg/dL); triglycerides: 0.28 +/- 0.03 mmol/L (24.49 +/- 2.59 mg/dL); and LDL: - 0.12 +/- 0.04 mmol/L (-4.53 +/- 1.55 mg/dL). There was a nonsignificant trend toward an increase in total cholesterol. CONCLUSION: When given in combination with 30 micrograms ethinyl E2, desogestrel increased HDL-C and triglycerides and decreased LDL-C. The positive impact on HDL-C and LDL-C suggests that a potential cardioprotective benefit (rather than an atherosclerosis risk) may occur with prolonged use of such an OC, but this hypothesis will be difficult to prove.

Cholesterol↗
PubMed1996

Evidence for heterogeneous etiologies of adrenal dysfunction in polycystic ovary syndrome.

OBJECTIVE: To examine the hypothesis that, in polycystic ovary syndrome (PCOS), ovarian steroids induce adrenal enzyme dysfunction or adrenal androgen hyperresponsiveness to ACTH. DESIGN: Prospective controlled clinical study. SETTING: Reproductive endocrinology unit of an academic medical center. PATIENTS: Twelve women with PCOS who had adrenal androgen excess were compared with five weight-matched ovulatory women. In half of the women with PCOS, prestudy screening was suggestive of mild 3 beta-hydroxysteroid dehydrogenase (HSD) deficiency. INTERVENTIONS: Basal and adrenal dynamic blood sampling before and after GnRH agonist (GnRH-a) administration for 6 months. MAIN OUTCOME MEASURES: Basal E2 and androgen levels as well as dexamethasone-suppressed, ACTH-stimulated 17 alpha-hydroxyprogesterone, 17 alpha-hydroxypregnenolone, and androgen levels before and after ovarian suppression. RESULTS: Although none of the subjects with PCOS proved to have mild 3 beta-HSD deficiency, the majority of them (58%) met the criteria for 17,20 lyase hyperactivity before and after GnRH-a therapy. As a group, the remaining subjects with PCOS exhibited an elevated DHEAS response to ACTH before GnRH-a treatment, which may have normalized after GnRH-a treatment. CONCLUSION: Adrenal androgen excess in PCOS may be heterogeneous in etiology, whereas 17,20 lyase hyperactivity appears to be an intrinsic adrenal disorder, adrenal androgen hyperresponsiveness to ACTH may be ovarian induced. Reliance on historical controls may lead to overdiagnosis of mild 3 beta-HSD deficiency.

17-alpha-Hydroxypregnenolone↗
PubMed1995

Triplet pregnancy in a 51-year-old woman after oocyte donation.

A triplet pregnancy occurred in a 51-year-old menopausal women after oocyte donation. Three of the four transferred embryos implanted, and the patient elected to carry the pregnancy. She delivered three viable infants weighing between 1500 and 2100 gm at 33 weeks' gestation by cesarean section.

Female↗
PubMed1995

Recipient's age does not adversely affect pregnancy outcome after oocyte donation.

OBJECTIVE: Our purpose was to examine the effect of the recipient's age on pregnancy and miscarriage rates after oocyte donation. STUDY DESIGN: A retrospective analysis of 307 consecutively performed donor oocyte cycles was undertaken. Recipients were divided into two groups: younger group < or = 42 years old (165 cycles) versus older group > 42 years old (145 cycles). Pregnancy outcomes between groups were compared. Confounding variables such as donor and cycle characteristics, recipient characteristics, and male parameters were also examined. RESULTS: Both groups had the same incidence (6%) of failed fertilization cycles. At least one embryo was transferred in the remaining 286 cycles. Ongoing or delivered pregnancy rates per embryo transfer were similar for younger and older groups (30.2% vs 30.6%). Differences in miscarriage rates were not statistically significant (9.8% vs 16.3%). There were no differences in the cycle parameters related to donor age, number of oocytes aspirated, number of oocytes fertilized, and number of embryos transferred. Donor sperm was more frequently utilized in the older group (19 vs 4 cycles, p = 0.0002). In the remaining cycles male partners of older recipients were significantly older (37.9 +/- 0.5 years vs 43.9 +/- 0.6 years, p < 0.0001), but there were no differences in semen parameters or fertilization rates. Older recipients were more likely to be parous but also to have experienced a previous miscarriage. CONCLUSION: Recipient age does not adversely affect cycle outcome with donor oocytes. This implies that aging of the uterus is not of clinical significance to patients electing this method of infertility treatment.

Abortion, Spontaneous↗
PubMed1995

Benefits and risks of estrogen replacement therapy.

Estrogen replacement therapy (ERT) has been shown to reduce the risk of cardiovascular disease (CVD) and osteoporosis in postmenopausal women. Studies also indicate a reduced risk of stroke and its consequent mortality among estrogen users, and ERT may also have a role in reducing the risk of Alzheimer's disease and increasing a woman's overall quality of life. On the negative side, some studies show a small duration-related risk of breast cancer with estrogen use and a significant increase in endometrial cancer; the latter is virtually eliminated with the addition of a progestin to the regimen. Although the definitive answer is not yet available, recent epidemiologic data suggest no reduction in protection against CVD and bone fracture with the addition of progestin, which is referred to as hormone replacement therapy, as opposed to using estrogen alone. A woman's potential risks associated with ERT or hormone replacement therapy must be weighed against her lifetime risks of developing CVD, stroke, and bone fracture. The reduction in mortality and morbidity rates with hormone use is generally viewed to be substantial and cost-effective. Health care professionals have an important role in shaping their patients' attitudes. Patients need more information from their physicians about the risks and benefits of estrogen therapy.

Administration, Oral↗
PubMed1995

Insulin sensitivity is unaltered by the use of the Norplant subdermal implant contraceptive.

Prior evaluations of carbohydrate metabolism in Norplant implant users, using the oral glucose tolerance test, have shown mild but clinically insignificant deterioration of insulin sensitivity. Using the more sensitive insulin tolerance test, the effects of the Norplant implant system on insulin sensitivity was studied in normal women. Insulin tolerance tests were performed before Norplant implant insertion in ten ovulatory female volunteers and repeated after 12 weeks of use. Both fasting glucose and fasting insulin values were similar before and after the use of Norplant implants. There was no significant difference in either the Kitt glucose value or the Kitt insulin value at baseline and at 3 months of use. Furthermore, the insulin-to-glucose ratio did not differ before and after the use of Norplant implants. There was a significant correlation with BMI and Kitt glucose value (r = -0.45, p < .05), as well as between fasting insulin and BMI (r = 0.6, p = 0.006). In the first three months of use, the levonorgestrel-containing implant system, Norplant, does not affect sensitivity to insulin or glucose in normal, nondiabetic women.

Administration, Cutaneous↗