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Biomedical subjects

A M Salvatierra

Publications and source records attributed to A M Salvatierra.

At least 19 recordsLinked to original sources
PubMed2006

Deficient expression of monoamine oxidase A in the endometrium is associated with implantation failure in women participating as recipients in oocyte donation.

Successful implantation depends both on the quality of the embryo and on the endometrial receptivity. The latter depends on progesterone-induced changes in gene expression, a process that has been characterized by microarray analysis. One of the genes whose transcription appears to be enhanced during the receptive period is monoamine oxidase A (MAO-A). Our first objective was to confirm the increased expression of MAO-A in the endometrium during the receptive phase of spontaneous normal cycles using real time PCR and immunofluorescence. The second objective was to examine the endometrial expression of MAO-A during the receptive phase induced by exogenous estradiol (E(2)) and progesterone in patients whose endometrium was shown to have been either receptive or non-receptive to embryo implantation in repeated cycles of oocyte donation. Results showed that MAO-A transcript levels increased between the pre-receptive (LH+3) and receptive phase (LH+7) in all spontaneous cycles examined, with a median increase of 25-fold. Immunofluorescent labelling demonstrated MAO-A localization to the glandular and luminal epithelium with an increasing positive score between LH+3 and LH+7. Conversely, prior failure of embryo implantation was associated with a 29-fold decrease in MAO-A mRNA levels and a substantial reduction in MAO-A protein immunofluorescent label score. These results show a strong association between endometrial receptivity and MAO-A expression in the endometrial epithelium, suggesting an important role for this enzyme in normal implantation.

Adult↗
PubMed2006

Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study.

BACKGROUND: Levonorgestrel (LNG) consistently prevents follicular rupture only when it is given before the onset of the ovulatory stimulus. As locally synthesized prostaglandin (PG) plays a crucial role in follicular rupture and cyclooxygenase-2 (cox-2) catalyses the final step of PG synthesis, we reasoned that adding a cox-2 inhibitor to LNG would prevent follicular rupture even after the ovulatory process had been triggered by the gonadotrophin surge. METHODS: Forty-one women were divided into two groups. One was treated when the size of the leading follicle was 15-17 mm (n=10) and the other when it was >or=18 mm (n=31). Each woman contributed with one cycle treated with LNG 1.5 mg single dose plus placebo and another treated with LNG + meloxicam (Melox) 15 mg, in a randomized order. Serial blood sampling for the assay of LH and follicular monitoring by transvaginal ultrasound were performed before and after treatment. RESULTS: Follicular rupture failed to occur within the 5-day period that followed treatment in 50 and 70% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the 15-17 mm group (P=0.15) and in 16 and 39% of cycles treated with LNG + Placebo and LNG + Melox, respectively, in the >or=18 mm group (P < 0.052). The overall proportion of cycles with no follicular rupture or ovulatory dysfunction increased significantly by the addition of Melox to LNG (66 versus 88%, P < 0.012; n=41-matched pairs). CONCLUSIONS: The trend towards increased incidence of no follicular rupture when Melox was combined with LNG suggests that the addition of a cox-2 inhibitor has the potential to improve the contraceptive efficacy of LNG by a pre-fertilization effect.

Adolescent↗
PubMed2004

Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation.

We assessed to what extent the standard dose of levonorgestrel (LNG), used for emergency contraception, or a single dose (half dose), given in the follicular phase, affects the ovulatory process during the ensuing 5-day period. Fifty-eight women were divided into three groups according to timing of treatment. Each woman contributed with three treatment cycles separated by resting cycles. All received placebo in one cycle, and standard or single dose in two other cycles, in a randomized order. The diameter of the dominant follicle determined the time of treatment. Each woman had the same diameter assigned for all her treatments. Diameters were grouped into 33 categories: 12-14, 15-17 or 18-20 mm. Follicular rupture failed to occur during the 5-day period in 44%, 50% and 36% of cycles with the standard, half dose and placebo, respectively. Ovulatory dysfunction, characterized by follicular rupture associated with absent, blunted or mistimed gonadotropin surge, occurred in 35%, 36% and 5% of standard, single dose or placebo cycles, respectively. In conclusion, LNG can disrupt the ovulatory process in 93% of cycles treated when the diameter of the dominant follicle is between 12 and 17 mm. It is highly probable that this mode of action fully accounts for the contraceptive efficacy as well as the failure rate of this method. The present data suggest that half the dose may be as effective as the standard dose.

Adolescent↗
PubMed2002

Effects of the Yuzpe regimen, given during the follicular phase, on ovarian function.

This study was conducted to assess to what extent the Yuzpe regimen, or half the dose, given in the follicular phase, prevents ovulation during the ensuing 5 days. Sixty women were divided into six groups. All groups received placebo in one cycle and drug in another, in a randomized order. Groups differed by the dose and size of the leading follicle at the time of treatment (12-14, 15-17, or 18-20 mm). Ovulation was absent during the ensuing 5 days in 13 of 20 participants (65%) and in 8 of 20 participants (40%) who received the full and the half dose, respectively, when follicles were 12-17 mm. No ovulation occurred, within the critical period, in 7 of 39 placebo cycles (18%). When follicles were 18-20 mm, treatment did not prevent ovulation. In most drug-treated cycles, plasma gonadotropin and sex steroid levels were significantly depressed within the 5-day period, even when follicular rupture occurred within that period. In conclusion, the Yuzpe regimen can suppress or postpone ovulation to an extent that exceeds the fertile life of spermatozoa. Lack of ovulation within the critical period and dysfunction of the ovulatory process probably account for the contraceptive effect of this method in most cases. The present data do not warrant the use of half the dose of the Yuzpe regimen.

Contraceptives, Postcoital↗
PubMed2000

Ovarian function during use of Nestorone(R) subdermal implants.

Nestorone(R) progestin (NES) is a potent 19-nor-progesterone derivative which is biologically inactive when administered orally; however, it is an excellent option for implant contraception. The objective of this study was to evaluate ovarian function during use of either one 4-cm or two 3-cm NES implants for 24 months. A total of 60 volunteers were enrolled in each dose group. Vaginal ultrasound (VUS) and blood sampling for determinations of estradiol (E(2)), progesterone (P) and NES serum levels were carried out twice a week for 6 consecutive weeks, beginning in months 1, 6, 12, 18, and 24 of implant use. Serum levels of NES declined with time, with a more pronounced decrease during the first 18 months of implant use; thereafter, NES levels remained stable until the end of the study at 24 months. Luteal activity was very infrequent during the first year of use (<3%) but increased during the second year, occurring in 27% and 35% of the sampling periods in the 1-implant group, and 2% and 16% of the sampling periods in the 2-implant group, at months 18 and 24 of use, respectively. No luteal activity was observed with NES levels above 80 pmol/L. Serum P levels in periods of luteal activity were significantly lower than those of controls. Persistent anovulatory follicles were the most common VUS finding and this was associated with E(2) levels that remained within the normal range (101-1500 pmol/L) in the majority of the sampling periods studied. Considering that a single implant offers advantage for insertion and removal, a new single NES implant is being developed with a slightly higher release rate, to reduce effectively the incidence of ovulation and provide a greater margin of safety beyond 2 years.

Adolescent↗
PubMed1998

The expression of alpha(v) and beta3 integrin subunits in the normal human Fallopian tube epithelium suggests the occurrence of a tubal implantation window.

The co-expression of alpha1beta1, alpha4beta1 and alphavbeta3 integrins in the human endometrium coincides with the implantation window. The alphavbeta3 integrin is expressed in the apical surface of the luminal epithelium and may serve to anchor trophoblast cells in the adhesion phase of implantation. Using immunohistochemistry, we compared the expression of alphav, alpha1, alpha4 and beta3 integrin subunits in samples of normal human Fallopian tube and endometrium obtained from five women in the non-receptive period (luteal phase days 2-4) and from another five women in the receptive period (luteal phase days 6-8). The staining was quantified visually on a scale of 0 to ++, according to the intensity and density of stained cells. The alphav subunit is expressed in the Fallopian tube epithelium during both periods in a pericellular distribution. The beta3 subunit is also expressed in the same location, but it is up-regulated during the period of endometrial receptivity. The other subunits are expressed in localizations which are not relevant to trophoblast adhesion and exhibit little or no difference in the level of expression between the non-receptive and receptive periods. Based on these results we postulate that the expression of the beta3 subunit in the human tubal epithelium is under the same systemic controlling signals as in the endometrium and that the normal tubal epithelium may have an implantation window, at about the same time as the endometrium, that affords the opportunity for trophoblast attachment should a 5-7 day embryo be unduly retained in the tube.

Antigens, CD↗
PubMed1998

Contraceptive potential of a mifepristone-nomegestrol acetate sequential regimen in women.

The effectiveness of a sequential regimen consisting of mifepristone, 10 mg/day for 15 days, followed by nomegestrol acetate (NOMA), 5 mg/day for the next 13 days, for inhibiting ovulation and maintaining regular bleeding cycles was assessed in 10 surgically sterilized volunteers who were followed for one pretreatment and three treated cycles. Hormonal determinations in blood and urine, ovarian ultrasonography, bleeding records in all cycles and an endometrial biopsy taken on day 22-25 of the third treatment cycle were used to monitor the effects of treatment. During treatment, 24 monophasic (no sustained progesterone rise above 12 nmol/l) and six biphasic cycles were recorded. Nine follicular ruptures were detected echographically in these 30 treated cycles, five of which occurred in monophasic cycles. All follicular ruptures occurred on days 1-7 of NOMA treatment. Echographic and endocrine features of ovulatory cycles were both present in only four treated cycles (13.3%). Development of a secretory endometrium was achieved in all cases, but it was always irregular. Regular withdrawal bleeding occurred in all subjects and no adverse reactions were recorded. The ovarian and endometrial effects of this regimen justify testing its contraceptive effectiveness in phase 2 clinical trials.

Adult↗
PubMed1998

Effects of long-term low-dose mifepristone on reproductive function in women.

Low-dose antiprogestin administration has been proposed as a new contraceptive modality to interference with endometrial receptivity without disturbing ovarian function. The effects of 1 mg/day mifepristone for 150 days on the menstrual cycle were assessed in 21 surgically sterilized women. The aim was to study each woman for one control cycle and during months 1, 3 and 5 of treatment. Ovulation, endometrial thickness, serum oestradiol and progesterone, urinary luteinizing hormone, endometrial morphology and cervical mucus were assessed. Luteal phase progesterone concentrations were observed in 36 of the 60 treated months assessed and less frequently as treatment progressed. The bleeding pattern was regular in most biphasic cycles, while prolonged interbleeding intervals or no bleeding were associated with monophasic cycles. Altered endometrial morphology was found in all cases irrespective of the occurrence of luteal activity. Increased endometrial thickness and dilated glands were observed in 25 and 34% respectively of the monophasic cycles. Mifepristone, 1 mg/day, interferes with endometrial development while allowing the occurrence of biphasic ovarian cycles and regular bleeding. However, it also prevents ovarian cyclicity in a high proportion of treated months, and this is associated with increased endometrial growth in some women, which may be of concern.

Adult↗
PubMed1997

Colposcopic evaluation of a vaginal gel formulation of iota-carrageenan.

There is an urgent need to develop safe, effective, and acceptable vaginal products for the prevention of sexually transmitted infections. Preliminary in vitro results suggest that vaginal formulations of sulfated polysaccharides, including iota-carrageenan, have the potential to block mucosal transmission of human immunodeficiency virus (HIV). Twenty-five women in five sites participated in Phase I trials to evaluate the safety of a formulation containing iota-carrageenan (PC 213). The results of this study indicate that a 5 mL 2% gel formulation of iota-carrageenan is not associated with significant irritation of the female reproductive tract when administered once daily in the absence of sexual intercourse. Given the small number of participants in this initial study, careful observation for potential irritation must also be included in larger studies of this and other vaginal formulations.

Administration, Intravaginal↗
PubMed1996

Effects of a sequential regimen of mifepristone-medroxyprogesterone acetate on ovarian function, endometrial development and hormonal parameters.

The efficacy of a low dose of mifepristone, 5 mg/day for the first 15 days of the menstrual cycle, followed by medroxy-progesterone acetate (MPA), 10 mg/day for the next 13 days, for inhibiting ovulation was assessed in ten volunteers who were treated for three successive cycles. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on day 21-24 of the third treatment cycle were used to monitor the cycles. Ovulation was confirmed in 11 of the 30 treated cycles and, in these 11, the LH peak and follicular rupture occurred during MPA treatment periods. Out of 19 anovulatory cycles, 16 had no increase in progesterone levels and another 3 developed a luteinized unruptured follicle. Progestin administration induced secretory changes in the endometrium, but irregular or delayed development was found. Regular withdrawal bleeding occurred in all subjects. These data indicate that the sequential regimen can suppress ovulation while maintaining regular bleeding but increased efficacy is needed for phase II clinical trials.

Adult↗
PubMed1996

Sucking pressure and its relationship to milk transfer during breastfeeding in humans.

Breast sucking pressure has been only partially characterized in humans and its quantitative relationships with milk transfer and endocrine maternal responses are unknown. A method to record sucking pressure and milk transfer during complete sucking episodes is described. A tubing connected at one end to a pressure transducer was attached to the nipple so that the baby sucked both the nipple and the catheter during breastfeeding. The transducer's signals were fed into a commercial computer system designed to digitize and analyse physiological signals. A total of 27 recordings, 13 of which were from a single breast and 14 from both breasts were evaluated. Average values for the mean and maximum sucking pressures were -50 and -197 mmHg, respectively; the median intersuck interval was 0.7 s; and duration of the sucking episode was 7 min. Diverse sucking pressure patterns were observed due to different mixes of sucking bursts with steady sucking and stable versus decreasing pressure and frequency throughout each sucking episode. The amount of milk transferred to the baby was estimated from the difference in body weight immediately before and after each episode. Milk transfer from the second breast was 58% lower than from the first; this was associated with a significant decrease in grams of milk transferred per suck or per minute without significant changes in sucking pressure. The data suggest that there is a change in the maternal physiological response to sucking between the first and second breast. This report shows the feasibility of measuring the sucking pressure developed by human babies during complete nursing episodes, and offers great potential to explore the relationships between the physical parameters of sucking and maternal physiological responses, such as hormonal changes, milk yield and duration of lactational amenorrhoea.

Breast Feeding↗
PubMed1995

Effects of intermittent antiprogestin RU486 combined with cyclic medroxyprogesterone acetate on folliculogenesis and ovulation.

The results of several studies have suggested an inhibitory effect of the antiprogestin RU486 on late stages of folliculogenesis and ovulation. To assess the feasibility of using this property to inhibit ovulation without losing cycle control, an intermittent administration of RU486 alternated with medroxyprogesterone acetate (MPA) was tested in a phase I study. RU486 at a dose of 50 mg/day was given on menstrual cycle days 9-11 and 27-29, and 10 mg/day of MPA was given on cycle days 17-26 for three consecutive cycles to six Finnish and five Chilean women. Blood samples were collected two to three times a week for serum progesterone and oestradiol assays in three treatment cycles. One control cycle and one post-treatment recovery cycle were also monitored by serum samplings. Ultrasonography was carried out to measure follicular diameters in the treatment cycles. In 29 of 32 cycles, bleeding commenced within 3 days after the last MPA pill intake. Out of 32 treatment cycles, 20 were without luteal activity (serum progesterone < 9 nmol/l). Although 12 treatment cycles showed luteal activity (serum progesterone > or = 9 nmol/l), a clear rupture of a pre-ovulatory follicle > 15 mm, verified by ultrasonography, was seen in only one treatment cycle. During the treatment cycles with luteal activity (serum progesterone levels > or = 9 nmol/l), serum oestradiol concentrations were significantly higher on cycle days 9-18 and significantly lower at the end of the cycle compared with the cycles without luteal activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Follicle stimulating hormone-granulosa cell axis involvement in the antifolliculotrophic effect of low dose mifepristone (RU486).

This study was designed to assess the involvement of follicle stimulating hormone (FSH)-granulosa and luteinizing hormone (LH)-theca axes in the antifolliculotrophic effect of mifepristone. Plasma gonadotrophins, including plasma LH bioactivity and pulsatility, oestradiol, testosterone and inhibin concentrations, and follicular growth were monitored in volunteer women treated with placebo or mifepristone in two consecutive cycles. Mifepristone was given either as a single dose of 5 mg (n = 7) when the leading follicle had reached a diameter between 12 and 14 mm, or as a multiple dose of 5 mg/day for 3 days, beginning when the leading follicle had reached a diameter between 14 and 16 mm (n = 5) or between 6 and 11 mm (n = 5). Following the single dose of mifepristone, follicular growth and the accompanying increase in plasma oestradiol were arrested at 12 and 36 h respectively without changes in gonadotrophin or testosterone serum concentrations. The 3 day regimen arrested follicular growth and oestradiol rise and decreased plasma inhibin concentrations when follicles were larger than 12 mm at the onset of treatment. These results indicate that the antifolliculotrophic action of mifepristone is associated with a selective compromise of the FSH-granulosa axis of dominant follicles that have passed a critical stage of growth.

Adult↗
PubMed1994

Effect of the antiprogestin onapristone on follicular growth in women.

The effects of the antiprogestin onapristone on the menstrual cycle were assessed in surgically sterilized volunteer women. The steroid was given orally at the dose of 5, 15 or 50 mg/day, from day 5 to day 11 of the cycle. Ovarian ultrasonography and hormonal determinations in plasma and urine were used to monitor the pre-treatment, treated and post-treatment cycles. Onapristone, given at a dose of 5 mg/day, affected follicular growth inconsistently. The dose of 15 or 50 mg/day arrested follicular growth and oestradiol increase and delayed gonadotrophin surge, extending the length of the follicular phase in five of seven women in each group. After discontinuation of treatment the leading follicle resumed its growth and ovulation occurred as judged by the elevation of plasma progesterone, preceded in most but not all cases by an echographic image of follicular collapse. The ensuing luteal phases were not significantly altered in length or plasma progesterone concentration. Cortisol concentrations were unaffected and no serious side-effects were recorded. The antifolliculotrophic effect of onapristone demonstrated here, together with previous reports of similar activity of mifepristone in women, indicate that this may be a general property of compounds that interfere with progesterone receptor function.

Adult↗
PubMed1993

Effects of continuous treatment with low dose mifepristone throughout one menstrual cycle.

The effects of continuous low dose mifepristone (RU 486) 10, 5 or 1 mg/day on the menstrual cycle were assessed in groups of five volunteers, who were treated for 30 days from the beginning of the cycle. Hormonal determinations in blood and urine samples, ovarian ultrasonography and an endometrial biopsy taken on day 22-29 of treatment were used to monitor the cycle. Pre- and post-treatment cycles presented a normal profile. During treatment, concentrations of RU 486 in plasma ranged from 65 nmol/l with 1 mg/day to 1000 nmol/l with 10 mg/day. With 10 or 5 mg/day, all treated cycles were prolonged as a result of arrested or slower follicular growth during treatment. Gonadotrophins, sex steroids and their urinary metabolites remained at early follicular phase levels throughout treatment, whereas androstenedione, prolactin and cortisol were unaffected. Follicular maturation resumed after discontinuation of treatment and several days later a luteinizing hormone surge followed by a luteal phase was observed in all cases. Ovulation was suppressed during treatment only in one of the five cycles treated with 1 mg/day. Endometrial maturation was disturbed by all doses. These data demonstrate a differential threshold of the follicle and the endometrium to mifepristone. This finding has potential application in the contraceptive field.

Adult↗
PubMed1993

Response to intermittent RU486 in women.

OBJECTIVE: To determine the effects of intermittent administration of the antiprogestin RU486 on ovarian function. DESIGN: Three different regimens of RU486 were tested. PARTICIPANTS: Nine healthy regularly menstruating volunteers protected by an intrauterine device or surgical sterilization. INTERVENTIONS: Two groups of three women each received 10 mg or 50 mg RU486 at weekly intervals for 5 weeks. Another three women received 50 mg RU486 for 3 consecutive days at 10-day intervals for 80 days. MAIN OUTCOME MEASURES: Serum E2, P and RU486 levels. Ovarian ultrasound (US) and serum LH and FSH in select subjects. RESULTS: The predominant effect was partial inhibition of E2 secretion and suppressed P levels. During a total aggregate of 16 treatment months, there were seven episodes of elevated P levels; however, US did not always indicate the occurrence of normal ovulation. CONCLUSION: Intermittent RU486 administration can interfere with normal follicular development and function, but its clinical application may require a more effective dose and/or timing of administration.

Administration, Oral↗
PubMed1992

Serum osteocalcin in normal menstrual cycle.

Serum osteocalcin (OC) was serially measured along an ovulatory menstrual cycle in 4 healthy unmedicated volunteers (age 33-38 years). During the study the women maintained their normal diet and daily physical activity. Starting at days 4-5 of the cycle, blood samples were taken between 09-11 AM every 2 or 3 days for OC, FSH, LH, E2 and P determinations. Daily ultrasound assessment of ovulation was performed in all subjects between days 7-18 of the cycle. Hormone determinations and OC were performed by RIA. While blood levels of FSH, LH, E2 and P changed during the cycle, according to the expected ovulatory pattern, serum OC concentrations remained stable during the cycle in each subject. In conclusion, serum OC is independent of the gonadotropin and ovarian steroid variations during the normal menstrual cycle.

Adult↗