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Biomedical subjects

M C Martin

Publications and source records attributed to M C Martin.

At least 19 recordsLinked to original sources

The choice of a gonadotropin-releasing hormone analog influences outcome of in vitro fertilization treatment.

OBJECTIVE: Our purpose was to determine if there is a difference in outcome associated with choice of gonadotropin-releasing hormone analog in in vitro fertilization treatment cycles. STUDY DESIGN: A retrospective analysis of 510 consecutive in vitro fertilization cycles with patient-selected use of either nafarelin (Synarel) or leuprolide (Lupron) was performed. RESULTS: Of 510 consecutive patient cycles, 284 patients (56%) chose nafarelin and 226 (44%) chose leuprolide. In the nafarelin group 64 cycles (34% of retrievals) resulted in deliveries. In the leuprolide group 37 (24%) resulted in delivery (p < 0.05). There were 260 patients in their first cycle of treatment, with 157 (60%) choosing nafarelin, resulting in 33 deliveries (34% per retrieval). Leuprolide, used in 103 (40%) of first cycles, resulted in 12 deliveries (20% per retrieval), (p = 0.052). CONCLUSIONS: In a large population of unselected patients undergoing in vitro fertilization the choice of nafarelin was associated with a significantly better outcome in terms of successful pregnancies achieved.

Adult

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration do not predict outcome in assisted reproduction cycles.

OBJECTIVE: To determine if the level of serum P drawn on the day of hCG administration predicts assisted reproductive technology (ART) outcome in patients undergoing stimulation with hMG under GnRH agonist (GnRH-a) suppression. DESIGN: Retrospective P assay of stored serum. PATIENTS: One hundred seventy-one patients (189 cycles) who had undergone GnRH-a suppression (leuprolide acetate or nafarelin) and stimulation with hMG for an ART procedure. MAIN OUTCOME MEASURES: Progesterone RIA of serum obtained on the day of hCG administration. Measurement of sequential serum LH values by RIA in those patients with the highest P levels. RESULTS: Pregnancy rates per oocyte retrieval were not correlated with the P level before hCG administration. There were 18 of 54 (33.3%) clinical pregnancies in those cycles with P < 0.9 ng/mL (conversion factor to SI unit, 3.180) and 42 of 135 (31.1%) clinical pregnancies in cycles with a P > or = 0.9 ng/mL. Significantly higher serum E2 levels and numbers of of follicles and oocytes obtained were observed in the high P cycles. There were no differences in the number of oocytes fertilized, the number of embryos transferred, or the implantation rate. However, a significantly higher percentage of mature oocytes were fertilized in the low P cycles (73%), as compared with the high P cycles (60%). CONCLUSIONS: Serum P levels before hCG administration do not predict the outcome of ART cycles in patients suppressed with GnRH-a before hMG stimulation. Lower fertilization rates observed in the high P cycles did not have an effect on clinical outcome.

Chorionic Gonadotropin

Menopause without symptoms: the endocrinology of menopause among rural Mayan Indians.

OBJECTIVE: Our purpose was to determine the characteristics of menopause among Mayan women who did not have menopausal symptoms. STUDY DESIGN: A cross-sectional study of Mayan women from Chichimila, Mexico, was performed. Demographic information, history and physical examination, hormone concentrations, and radial bone density measurement were obtained. RESULTS: Fifty-two postmenopausal women were compared with 26 premenopausal women. Menopause occurred at 44.3 +/- 4.4 years. None of the women admitted to hot flushes and did not recall significant menopausal symptoms. Hormone levels included elevated follicle-stimulating hormone (66.6 +/- 29 mlU/ml), low estradiol and estrone (9.4 +/- 8.3 and 13.3 +/- 7.8 pg/ml), estrone greater than estradiol levels, normal levels of testosterone and androstenedione (0.17 +/- 0.14 and 0.31 +/- 0.17 ng/ml). Bone mineral density declined with age, but height did not. Clinical evidence of osteoporosis was not detected. CONCLUSIONS: Lack of symptoms during the menopausal transition is not attributable to a difference in endocrinology. Postmenopausal Mayan women are estrogen deprived and experience age-related bone demineralization but do not have a high incidence of osteoporotic fractures.

Adult

Preimplantation diagnosis.

Preimplantation embryonic biopsy and analysis offer couples at increased risk of having offspring affected with a genetic disorder the possibility of an early prenatal diagnosis. For many couples, this approach would avoid the issue of the selective termination of affected fetuses. Substantial advances have been made in the area of preimplantation diagnosis, but the possible difficulties with this approach cannot be ignored.

Animals

Lymphocytic adenohypophysitis: a pituitary mass lesion occurring in pregnancy. Proposal for medical treatment.

Lymphocytic adenohypophysitis is a nonneoplastic, autoimmune cause of pituitary enlargement and insufficiency. Forty-eight of the 50 reported cases have occurred in women, nearly all in association with pregnancy. Left undiagnosed and untreated, it can progress to pituitary insufficiency and death. Histologic studies show characteristic changes of autoimmune disease with lymphocytic infiltration and destruction of anterior pituitary tissue with fibrotic replacement. Lymphocytic adenohypophysitis is currently diagnosed after other pituitary mass lesions are excluded and has been treated with a combination of neurosurgery and end-organ hormone replacement. However, with improved knowledge of the pathophysiologic characteristics and natural history of the disease and with the ability to make a prospective diagnosis, we believe glucocorticoids may suppress the inflammatory response and protect remaining pituitary tissue. Two previously unreported pregnancy-associated cases are described, including one prospectively diagnosed and treated without neurosurgery during pregnancy. Obstetrician-gynecologists must place lymphocytic adenohypophysitis in the differential diagnosis of pituitary enlargement associated with pregnancy, since treatment is available and the sequelae may be life-threatening.

Adult

Maturation of immature oocytes by coculture with granulosa cells.

To increase the number of embryos available for transfer, immature human oocytes were cocultured with granulosa cells from preovulatory follicles. Greater numbers of immature oocytes incubated with granulosa cells had dispersion of the cumulus and corona cells compared with immature oocytes cultured in media alone. Fifty-four percent of immature oocytes were fertilized after coculture with granulosa cells compared with 20% fertilization of immature oocytes cultured without granulosa cells. There were no cases in which only embryos developed from immature oocytes were transferred, and thus we could not determine if the immature oocytes could contribute to a pregnancy.

Cell Communication

Development of a circadian variation of plasma oxytocin concentration in the late gestation rhesus monkey.

The 24-h pattern of oxytocin (OT) concentrations in maternal plasma was investigated serially from 112-168 days gestation in four chair-restrained pregnant rhesus monkeys. No change in the mean daily plasma OT concentration was observed with advancing gestational age; there was a change in the pattern of plasma OT secretion throughout the period, however. About 21 days from delivery (150.8 +/- 1.8 days gestational age), plasma OT levels showed occasional fluctuations, distributed throughout the day. About 8 days from delivery (163.2 +/- 2.4 days gestational age), a clear circadian pattern of OT was detected, with an acrophase at 2200 h. These results suggest that there is a relationship between the pattern of OT secretion and advancing pregnancy. This may account partially for the increase in uterine activity known to occur in term rhesus monkeys.

Animals

Recent advances in the management of sexual precocity in girls.

Sexual precocity has important psychosocial implications for the prematurely developing child, as well as being associated in some cases with significant pathology. Conscientious evaluation and initiation of effective therapy can have a significant impact on improving long-term outcome. The differentiation between complete sexual precocity with activation of the hypothalamic-pituitary axis and incomplete sexual precocity without activation of the central reproductive system is of paramount importance. In incomplete sexual precocity, the sex steroids are of exogenous, adrenal, or gonadal origin. Premature adrenarche presents with the early development of pubic hair only and must be distinguished from adrenal hyperplasia or an androgen-secreting neoplasm, which may be associated with accelerated growth, advanced bone age, and virilization. When incomplete sexual precocity involves the ovary, ovarian tumors must be considered. Other causes of incomplete sexual precocity include hypothyroidism and gonadotropin-independent precocity such as McCune-Albright syndrome. Complete sexual precocity or precocious puberty of central origin is diagnosed in girls by gonadotropin-releasing hormone challenge yielding a stimulated luteinizing hormone peak greater than 15 IU/L. Radiologic evaluation of the central axis is necessary. Treatment of precocious puberty relies on the use of potent agonists of gonadotropin-releasing hormone that reversibly suppress the prematurely activated pituitary. Depot preparations are efficacious. Early initiation and careful monitoring of treatment can reduce physical signs of development, improve the likelihood for normal adult height, and postpone normal pubertal progression to a more appropriate age.

Child

Effect of previous supramaximal work on lacticaemia during supra-anaerobic threshold exercise.

Twelve male and female subjects (eight trained, four untrained) exercised for 30 min on a treadmill at an intensity of maximal O2 consumption (% VO2max) 90.0%, SD 4.7 greater than the anaerobic threshold of 4 mmol.l-1 (Than = 83.6% VO2max, SD 8.9). Time-dependent changes in blood lactate concentration [( lab]) during exercise occurred in two phases: the oxygen uptake (VO2) transient phase (from 0 to 4 min) and the VO2 steady-state phase (4-30 min). During the transient phase, [lab] increased markedly (1.30 mmol.l-1.min-1, SD (0.13). During the steady-state phase, [lab] increased slightly (0.02 mmol.l-1.min-1, SD 0.06) and when individual values were considered, it was seen that there were no time-dependent increases in [lab] in half of the subjects. Following hyperlacticaemia (8.8 mmol.l-1, SD 2.0) induced by a previous 2 min of supramaximal exercise (120% VO2max), [lab] decreased during the VO2 transient (-0.118 mmol.l-1.min-1, SD 0.209) and steady-state (-0.088 mmol.l-1.min-1, SD 0.103) phases of 30 min exercise (91.4% VO2max, SD 4.8). In conclusion, it was not possible from the Than to determine the maximal [lab] steady state for each subject. In addition, lactate accumulated during previous supramaximal exercise was eliminated during the VO2 transient phase of exercise performed at an intensity above the Than. This effect is probably largely explained by the reduction in oxygen deficit during the transient phase. Under these conditions, the time-course of changes in [lab] during the VO2 steady state was also affected.

Adult

Neuromodulatory regulation of gonadotropin-releasing hormone pulsatile discharge in women.

The pulsatile release of gonadotropin-releasing hormone and the consequent secretion of gonadotropins are regulated by a complex interplay of steroids, neuropeptides, catecholamines, and environmental factors. Estrogen and progesterone influence the amplitude and frequency of luteinizing hormone pulsatile secretion. These effects lead to both a diurnal variation in pulse frequency, with a lower frequency at night, and variation during the menstrual cycle, with a lower frequency and increased amplitude during the luteal phase. Opioid peptides inhibit the pulsatile discharge of gonadotropin-releasing hormone and luteinizing hormone. The opioid antagonist, naloxone, causes an increase in luteinizing hormone secretion, particularly during the luteal phase. The administration of opioid receptor agonists, such as beta-endorphin, results in a decline in serum luteinizing hormone during the early follicular phase. Corticotropin-releasing factor, which is increased during stress, inhibits pulsatile luteinizing hormone secretion, and this effect can be blocked by the simultaneous administration of naloxone. These observations suggest that corticotropin-releasing factor exerts its effects on luteinizing hormone through an opioidergic intermediary. Endogenous catecholamines such as dopamine inhibit pulsatile luteinizing hormone release; however, the mechanism involved is not clear.

Adult

Insulin-like growth factor I (IGF-I) levels in follicular fluid from human preovulatory follicles: correlation with serum IGF-I levels.

Insulin-like growth factor I (IGF-I) levels were measured in both serum and fluid of preovulatory follicles (n = 156) in 43 women undergoing in vitro fertilization (IVF). The mean IGF-I level in follicular fluid (FF) was significantly lower than in serum (0.52 +/- 0.02 IU/L versus 0.66 +/- 0.23 IU/L), and FF levels were significantly correlated with individual serum IGF-I levels as well as with follicular size and FF volume but not with oocyte maturity, granulosa cell appearance, or IVF. This suggests that FF IGF-I levels cannot serve as a clinical indicator for the degree of oocyte/granulosa cell differentiation or a predictor for IVF. Serum IGF-I levels were inversely correlated with the number of human menopausal gonadotropin ampules administered during treatment, suggesting that IGF-I might enhance ovarian gonadotropic stimulation.

Estradiol

Maintenance of cell proliferation and steroidogenesis in cultured human fetal adrenal cells chronically exposed to adrenocorticotropic hormone: rationalization of in vitro and in vivo findings.

Previous studies indicated that acute exposure of adrenal cells to adrenocorticotropic hormone (ACTH) markedly stimulates steroidogenic capacity in vitro but also inhibits cell proliferation. However, in vivo, ACTH is known to stimulate adrenal cell growth. To address this discrepancy, we determined the effect of long-term (9-11 days) continuous or intermittent exposure to ACTH on human fetal adrenal cell proliferation and steroidogenesis. Adrenal glands from fetuses 18-22 wk gestation were studied. Fetal zone cells were plated either on plastic or on an extracellular matrix (ECM) in the presence and absence of basic fibroblast growth factor (bFGF) (0.5 ng/ml) and 1 or 10 nM ACTH. As determined by cell counting, bFGF stimulated cell proliferation during 9 days in culture. In the presence of bFGF, the average doubling time decreased from 44 to 30 h on plastic and from 37 to 26 h on ECM. Under these conditions, ACTH did not inhibit cell proliferation. Proliferation of fetal adrenal corticosteroid-producing cells in the ACTH-treated cultures also was assessed by histochemical staining for 3 beta-hydroxysteroid dehydrogenase (3 beta HSD). The number of positive cells increased more than 4-fold between Days 5 and 9 in culture. Continuous treatment with 1 nM ACTH increased dehydroepiandrosterone sulfate (DHAS) production 5- to 10-fold during the first 5 days in culture. Thereafter, the stimulated hormone production decreased over time, although there was still a difference of almost 100-fold between the control and ACTH-treated cultures at the end of 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases

Polypronuclear embryos after in vitro fertilization.

Triploidy occurs in 1% to 3% of recognized conceptions in vivo. In vitro fertilization (IVF), which places large numbers of sperm in proximity to the oocyte, may increase the risk of triploidy. The risk also could be influenced by stimulation protocols that differentially affect egg quality. We found no significant difference in triploidy when cycles were stimulated with clomiphene citrate/human menopausal gonadotropin (3.2%) compared with gonadotropin-releasing hormone analog/human menopausal gonadotropin stimulation (4.4%). Triploidy was less common with male factor infertility (0.7%) compared with other causes of infertility (3.4% to 3.8%). Triploid embryos can develop to cleavage stages indistinguishable from those generated by diploid embryos. Thus, identifying and discarding embryos with greater than 2 pronuclei is a vital function of an IVF laboratory.

Cell Nucleus

Type II hyperprolinaemia in a pedigree of Irish travellers (nomads).

We describe a study of 312 subjects in 71 families near related to a proband with type II hyperprolinaemia. The subjects were Irish travellers (nomads) among whom consanguineous marriage and high fertility are common. Thirteen additional cases of type II hyperprolinaemia were discovered; all were offspring of consanguineous unions. A further 50 subjects were found to have mild hyperprolinaemia. We found a strong association between type II hyperprolinaemia and seizures during childhood but no significant association with mental handicap. Most adults with type II hyperprolinaemia enjoyed normal health and there was no evidence that maternal hyperprolinaemia compromised fetal development. The documented association between type II hyperprolinaemia and seizures may be related to the neuromodulatory or reducing-oxidising effects of proline and pyrroline-5-carboxylate, respectively, that has been shown in vitro. Alternatively, another genetic defect closely linked to the type II hyperprolinaemia allele could be the explanation.

1-Pyrroline-5-Carboxylate Dehydrogenase

Pelvic endometriosis: MR imaging.

The value of magnetic resonance (MR) imaging at 0.35 T in detecting, characterizing, and staging pelvic endometriosis was prospectively investigated in 30 consecutive women in whom this disease was clinically suspected. MR findings were correlated with the results of laparoscopy (13 women) and laparotomy (17 women). Surgical examination revealed a normal pelvis in five patients and endometriosis in 25. Three of the five normal cases and 16 of the 25 cases of endometriosis were correctly identified with MR imaging (sensitivity, 64%; specificity, 60%; accuracy, 63%). MR imaging demonstrated seven of eight endometriomas but only 14 of 29 adhesions and only six of 45 endometrial implants. While MR imaging demonstrated endometriomas, ovarian adhesions, and extraperitoneal endometrial implants, it could not accurately depict extraovarian endometrial adhesions and intraperitoneal endometrial implants. In addition, MR imaging findings did not correlate with the surgically determined severity of the disease. These limitations indicate that MR imaging cannot be used as the primary modality in the detection, characterization, and staging of endometriosis; laparoscopy remains the procedure of choice.

Adult

An enzyme-linked immunosorbent assay to study human relaxin in human pregnancy and in pregnant rhesus monkeys.

A sensitive and specific double-antibody enzyme-linked immunoassay, using a synthetic analogue of human relaxin for standard and immunogen, was developed for the measurement of human relaxin (hRLX) in serum and plasma. No cross-reactivity was observed for human insulin, human insulin-like growth factor-I, hGH, human chorionic gonadotropin, hFSH, hLH or human prolactin. The assay was used to monitor RLX concentrations in samples from men, non-pregnant and pregnant women, and in pregnant rhesus monkeys infused with hRLX. RLX was not detected in serum from men nor from non-pregnant women, while a concentration of 600 ng/l was measured in pooled sera from two pregnant women (pregnancies achieved by in-vitro fertilization). Immunoreactive RLX (1.1 micrograms/g) was found in human corpora lutea taken from ectopic pregnancies at 7 weeks. In an experiment with a pregnant rhesus monkey infused with human RLX analogue, less than 1.5% of the maternal concentration was measured in the fetal circulation. Even though preliminary, these data suggest a low level of transfer of human analogue relaxin across the placenta in a rhesus monkey. Further studies of the physiology of RLX in human pregnancy will be facilitated by the availability of this immunoassay.

Amino Acid Sequence