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Biomedical subjects

N S Macklon

Publications and source records attributed to N S Macklon.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dynamics of the development of multiple follicles during ovarian stimulation for in vitro fertilization using recombinant follicle-stimulating hormone (Puregon) and various doses of the gonadotropin-releasing hormone antagonist ganirelix (Orgalutran/Antagon).

OBJECTIVE: To investigate relations between dose of GnRH antagonist and follicular phase characteristics. DESIGN: Randomized controlled multicenter trial. SETTING: Tertiary referral fertility centers. PATIENT(S): Three hundred and twenty-nine IVF patients. INTERVENTION(S): Ovarian stimulation for IVF with recombinant FSH starting on cycle day 2. From cycle day 7 onwards, cotreatment was provided with 0.0625, 0.125, 0.25, 0.5, 1.0, or 2.0 mg/d GnRH antagonist. MAIN OUTCOME MEASURE(S): Number of follicles, total follicular surface area, gonadotropin, and serum steroid concentrations. RESULT(S): In 311 patients, similar follicular growth was observed in all treatment groups. FSH levels increased during the follicular phase. Late follicular phase LH, androstenedione (AD), and E(2) levels showed a GnRH antagonist dose-related decrease (P<0.05). Late follicular phase E(2) levels correlated with total follicular surface area, AD, LH, and FSH (all P<0.001). Increasing GnRH antagonist doses exhibited additional suppressive action on E(2) levels. CONCLUSION(S): Follicular growth was unaffected by the dose of GnRH antagonist. A rise in follicular phase FSH serum concentrations during the follicular phase, largely related to exogenous FSH, enabled ongoing follicular growth in all treatment groups. The effect of GnRH antagonist on late follicular phase E(2) levels could not be exclusively attributed to suppression of LH.

Adolescent↗
PubMed2000

[Gonadotrophin-releasing hormone antagonists: application in ovary-stimulating and sex-steroid dependent disorders].

The hypothalamic gonadotrophin-releasing hormone (GnRH) stimulates synthesis and secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) by the gonadotrophic cells of the pituitary. The mechanisms of action of GnRH antagonists and of agonists is completely different. Due tot competitive blockage of GnRH receptors by antagonist administration, LH (and to a lesser extent FSH) levels drop rapidly. Moreover pituitary function normalizes immediately following cessation of medication. The direct and rapid action of GnRH antagonists, the dose dependent suppression of LH and FSH and the rapid restoration of hypophyseal function after cessation of the use of antagonists may shorten and simplify in-vitro fertilization, with less chance of side effects or complications. Further studies are required to decide whether antagonists can usefully be applied for other gynecological indications such as the polycystic ovary syndrome. The possibilities of profitable long term treatment will increase considerably if it proves possible to develop a sustained action formulation.

Dose-Response Relationship, Drug↗
PubMed2000

A pilot study involving minimal ovarian stimulation for in vitro fertilization: extending the "follicle-stimulating hormone window" combined with the gonadotropin-releasing hormone antagonist cetrorelix.

OBJECTIVE: To study whether minimal interference in the process of selection of the single dominant follicle may serve as the basis for a simplified ovarian stimulation regimen for IVF. DESIGN: Single-center randomized pilot study. SETTING: Tertiary referral fertility center. PATIENT(S): Fifteen normo-ovulatory patients with a regular indication for IVF. INTERVENTION(S): Ovarian stimulation for IVF was begun with 100 or 150 IU/d recombinant FSH starting on cycle day 5. From cycle day 8 or later, cotreatment was begun with 0.25 mg/d GnRH antagonist. No luteal support was provided. MAIN OUTCOME MEASURE(S): Total number of dominant follicles and characteristics of the endocrine cycle. RESULT(S): Multiple follicle development occurred in five of eight patients in the 100-IU group and in all seven women in the 150-IU group. Follicular phase and luteal phase lengths were normal, but the endocrine profile was abnormal. CONCLUSION(S): A fixed daily dose of 150 IU recombinant FSH starting in the midfollicular phase resulted in ongoing growth of a restricted number of dominant follicles and sufficient oocytes retrieved to lead to ET. A marked reduction in the total amount of gonadotropins administered compared with standard treatment was achieved. Withholding luteal support did not exclude pregnancies.

Adult↗
PubMed2000

Impact of ovarian hyperstimulation on the luteal phase.

The contemporary approach to ovarian stimulation in IVF treatment results in supraphysiological concentrations of progesterone and oestrogen in the luteal phase. These sex steroids act directly and indirectly to mature the endometrium, thus influencing its receptivity to implantation. The development of endometrial receptivity is a complex process that may be altered by inappropriate exposure to sex steroids. Alterations in the oestrogen to progesterone ratio, growth factor concentrations and cell adhesion molecule profiles may occur after ovarian stimulation, potentially affecting the receptivity of the endometrium. Recent clinical IVF studies have shown that implantation rates and corpus luteum function are influenced by oestrogen concentrations during the early luteal phase. Few comparative studies have been performed, but after ovarian stimulation there is a reduced implantation rate and a higher pregnancy loss rate before pregnancies can be detected clinically compared with natural cycle conceptions. Novel approaches to ovarian stimulation aimed at achieving a more physiological luteal phase endocrinology are now being developed. Data from a recent pilot study by our laboratory, involving minimal ovarian hyperstimulation and no luteal phase support, are discussed.

Animals↗
PubMed1999

Behavior-state-dependent changes in human fetal pulmonary blood flow velocity waveforms.

OBJECTIVE: To establish the influence of fetal behavior states on venous and arterial pulmonary blood flow velocity waveforms in the normally developing term fetus. METHODS: The relation between venous and arterial pulmonary blood flow velocity waveforms and fetal behavior states was investigated in 18 normal term fetuses. Recordings of the venous pulmonary blood flow velocity waveforms were obtained just proximal to the entrance in the left atrium, and the arterial pulmonary blood flow velocity waveforms were taken from the most proximal branch of the pulmonary artery in the same lung using color Doppler imaging. Time-averaged peak systolic, peak diastolic, and end-diastolic flow velocity; peak systolic to peak diastolic ratio; pulsatility index; and fetal heart rate were calculated from both venous and arterial Doppler recordings obtained during behavior states 1F (quiet sleep) and 2F (active sleep). Fetal behavior states were determined from combined recordings of fetal eye and body movements. RESULTS: Recordings of sufficient quality for analysis were obtained from ten fetuses. Venous pulmonary blood flow velocity waveforms demonstrated a statistically significant increase in time-averaged peak diastolic and end-diastolic velocity during fetal behavior state 2F. No behavior-state-related changes were observed for the arterial pulmonary blood flow velocity waveform. CONCLUSION: The data suggest an increased pressure gradient between the pulmonary venous system and the left atrium during behavior state 2F. Flow velocity waveforms from the proximal arterial pulmonary branch are independent of behavioral state.

Adult↗
PubMed1999

Diagnosis of deep venous thrombosis and pulmonary embolism in pregnancy.

Accurate diagnosis of deep venous thrombosis and pulmonary embolism is required because treatment can be lifesaving, although inappropriate anticoagulation exposes the mother and fetus to hemorrhage and other hazards. Clinicians must be aware of which patients are at risk, as deep venous thrombosis is frequently asymptomatic. Clinical diagnosis is unreliable for deep venous thrombosis and pulmonary thromboembolism; therefore, objective tests are required. Venography is the gold standard test for deep venous thrombosis but is invasive. It has been superseded by less invasive tests such as compression ultrasound. This test, although not yet rigorously scrutinized in pregnancy, is now the first-line investigation. Where doubt remains, venography, CT, and magnetic resonance imaging have a role. Ventilation-perfusion scanning is the pivotal test for pulmonary thromboembolism for pregnancy, and it need not expose the fetus to excess radiation. If the results of this test are unclear, deep venous ultrasound can guide management of suspected pulmonary thromboembolism, thus avoiding pulmonary angiography.

Diagnosis, Differential↗
PubMed1999

Aspects of ovarian follicle development throughout life.

The pool of primordial follicles present in the female ovary reaches its maximum number around 20 weeks of gestational age and then decreases in a logarithmic fashion throughout life until complete depletion occurs around the age of the menopause. Reproductive life is initiated when less than 10% (0.5 million) of primordial follicles are left. The entire growth trajectory of the follicle takes at least 3 months. Follicle growth up to the antral stage occurs during fetal life and infancy. While the role of gonadotropins in early follicular development remains controversial, the last 2 weeks of development are FSH dependent. The intercycle rise in FSH and decreasing levels thereafter are crucial for recruitment of a cohort of healthy, early antral follicles and subsequent single dominant selection. Following puberty, anovulation may persist for years and this may presage the development of adult anovulatory infertility. The menopause is preceded by a period of reduced fertility. The development of reliable and sensitive markers for ovarian ageing will be the challenge of the near future.

Adolescent↗
PubMed1999

Progress in ovarian stimulation.

It is uncertain whether patients who do not ovulate but fail to conceive following CC therapy behave differently during gonadotropin therapy. However, if the infertile patient with PCOS is resistant to anti-estrogen therapy, gonatropin treatment administered through low dose protocols should be considered. As compared to conventional regimens, complication rates are reduced despite similar efficacy. It should be recognized that patients with PCOS constitute a very heterogeneous group. Therapy outcome may benefit from improved classification. The identification of clinical characteristics that identify those women with anovulation who are unlikely to respond to clomiphene would permit earlier use of gonadotropin therapy and potentially offer major health and economic benefits. Furthermore, if ovarian responsiveness to ovulation-induction therapy could be predicted for an individual patient, it might be possible to devise regimens that reduced the risk of ovarian hyperstimulation and multiple pregnancy.

Clomiphene↗
PubMed1998

Follicle development during the normal menstrual cycle.

An understanding of the factors which determine initiation of follicle growth, recruitment and dominant follicle selection may increase our understanding of the underlying process of ovarian aging. In this article, these aspects of the normal menstrual cycle are reviewed. The morphological and endocrinological development in the early follicle is described from the primordial follicle stage. The degree of follicle-stimulating hormone (FSH) dependency is discussed, as is the relationship of estradiol (E2) production to follicle diameter. The principles governing mono-follicular selection are outlined, and the FSH 'threshold' and 'window' concepts are highlighted. Maximum FSH levels in the early follicular phase are shown to be variable between individuals. The relevance of this and the means by which individual sensitivity to FSH may be altered at the ovary in the context of ovarian aging are discussed.

Aging↗
PubMed1998

High dose gonadotrophin-releasing hormone antagonist (ganirelix) may prevent ovarian hyperstimulation syndrome caused by ovarian stimulation for in-vitro fertilization.

This case report describes the first attempt to treat imminent ovarian hyperstimulation syndrome (OHSS) by using a gonadotrophin-releasing hormone (GnRH) antagonist. A 33 year old, normo-ovulatory woman undergoing in-vitro fertilization received daily subcutaneous injections of 150 IU of recombinant follicle-stimulating hormone (recFSH) from cycle day 2, together with GnRH antagonist (ganirelix) 0.125 mg from cycle day 7 onwards. On cycle day 10 the patient was found to have a serum oestradiol concentration of 16 500 pmol/l and, on ultrasound examination, four preovulatory (>16 mm) and nine intermediate sized (10-16 mm) follicles. RecFSH injections were discontinued, human chorionic gonadotrophin (HCG) withheld, whereas the ganirelix dose was increased to 2 mg/d. This regimen led to a rapid decrease in serum oestradiol concentrations and the decrease in ovarian size on ultrasound. Since GnRH antagonists will become clinically available for in-vitro fertilization programmes in the near future this suggested regimen might have a role in preventing severe OHSS.

Adult↗
PubMed1998

Fetal cardiac function and septal thickness in diabetic pregnancy: a controlled observational and reproducibility study.

OBJECTIVE: To determine the reproducibility of duplex Doppler waveform analysis and fetal cardiac interventricular septal thickness measurement and to compare these parameters in matched pregnancies with and without well-controlled maternal Type 1 diabetes at 18-20 weeks of gestation. DESIGN: A prospective blind twin cohort study and a blinded inter-observer and intra-observer agreement study. SETTING: A tertiary referral prenatal diagnostic unit within a university hospital. RESULTS: Good inter- and intra-observer agreement was found for the measurement of transvalvular peak flow velocities and the duration of ventricular ejection in the fetal heart. Inter-observer agreement for aortic flow acceleration rate was poor. M-mode measurement of interventricular septal thickness showed moderate reproducibility. The mean (SD) width of the interventricular septum in the fetuses of well controlled diabetic women was 2 1 mm (0.2 mm), and was significantly greater (P=0.01) when compared with the corresponding value in matched controls [1.9 mm (0.2 mm)]. No cardiac functional differences were evident. CONCLUSIONS: On-screen video analysis of Doppler cardiac flow waveforms and M-mode measurement of intraventricular septal thickness demonstrated good reproducibility. The fetuses of well controlled diabetic pregnancies demonstrated signs of altered cardiac morphology early in pregnancy, before any evident alterations in cardiac function.

Blood Flow Velocity↗
PubMed1997

Diagnosis of deep venous thrombosis and pulmonary embolism.

Accurate diagnosis of deep venous thrombosis (DVT) and pulmonary embolism (PE) is required because treatment can be life-saving, while inappropriate anticoagulation exposes the mother and fetus to haemorrhage and other hazards. Clinicians must be aware of which patients are at risk because DVT is frequently asymptomatic. Clinical diagnosis is unreliable for DVT and PE so objective tests are required. Venography is the gold standard test for DVT but is invasive and has been superseded by less invasive tests such as duplex ultrasound which is now the first-line investigation in pregnancy. However, where doubt remains, venography, CT and MRI have a role. Ventilation-perfusion scanning is the pivotal test for PE in pregnancy, and need not expose the fetus to excess radiation. If the result is unclear deep venous ultrasound can guide management of suspected PE, thus avoiding pulmonary angiography, the invasive gold standard test.

Female↗
PubMed1997

An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy.

OBJECTIVE: To investigate gestational and postural changes in diameter and blood flow in the proximal deep leg veins during pregnancy. DESIGN: A longitudinal, prospective observational study. SETTING: The ultrasound department of a teaching maternity hospital. POPULATION: Twenty-four healthy women with uncomplicated singleton pregnancies. METHODS: Real-time and duplex Doppler ultrasound assessments of the vessel diameter, flow velocity and respiratory flow fluctuation in the proximal deep leg veins of women serially measured from the first trimester of pregnancy to six weeks postnatally. MAIN OUTCOME MEASURES: The effects of increasing gestation and the adoption of the left lateral position on the above parameters. RESULTS: An increase in vessel diameter and a fall in flow velocity with increasing gestation was observed. However, no change in venous flow variation was observed. Delivery had reverse effects. Flow velocity was slower in the left than right legs, but on adoption of the left lateral position an increase in flow velocity and venous flow variation was observed in both legs during pregnancy. CONCLUSIONS: These data are consistent with the observed increase in incidence and pattern of deep venous thrombosis in pregnancy and may aid interpretation of duplex Doppler ultrasound examinations for deep venous thrombosis in pregnancy. Postural changes should be part of this evaluation. The gravid uterus may not be the sole cause for postural changes in deep venous flow velocity.

Blood Flow Velocity↗
PubMed1997

The deep venous system in the puerperium: an ultrasound study.

OBJECTIVE: To study the vessel wall diameter and blood flow velocity within the proximal deep venous system of the leg in the puerperium and to compare these measures with respect to the left versus right leg, 4th versus 42nd postnatal day, and vaginal versus caesarean delivery. DESIGN: A combined longitudinal and cross-sectional observational study. SETTING: The ultrasound department of a teaching maternity hospital. RESULTS: A reduction in vessel diameter and an increase in flow velocity was observed between the 4th and 42nd postnatal day. Vessel diameter was greater and flow velocity was reduced in the left compared to the right leg. In those delivered by caesarean section, a trend towards reduced flow velocity in the proximal deep leg veins was observed when compared with those delivered vaginally. CONCLUSIONS: These data suggest possible physiological mechanisms behind previous clinical observations relating to the period of greatest risk of deep vein thrombosis in the puerperium, the relative preponderance of left sided deep vein thrombosis and the risk of deep vein thrombosis associated with caesarean section.

Blood Flow Velocity↗
PubMed1996

Venous thromboembolic disease in obstetrics and gynaecology: the Scottish experience.

The incidence and pattern of thromboembolic complications in obstetric and gynaecological patients in Scotland between 1981 and 1992 was investigated by analysing ICD coded data retrieved from the SMR1 and SMR2 database. The effect of mode of delivery and maternal age over 35 on risk of thromboembolism in pregnancy was also assessed. 0.076% of gynaecological episodes were subsequently complicated by thromboembolic events. Nineteen percent of those suffering thromboembolic complications within two weeks of discharge were referred back to gynaecology. The incidence of deep venous thrombosis (DVT) in those under 35 years and over 35 years was 0.615/1000 maternities and 1.216/1000 maternities respectively. Respective figures for postnatal DVT were 0.304/1000 and 0.720/1000 and for pulmonary thromboembolism (PTE), 0.108/ 1000 and 0.405/1000. In both age groups, emergency caesarean section was associated with a higher incidence of DVT than elective caesarean section and vaginal delivery.

Adult↗
PubMed1995

Thrombocytopenia, antithrombin deficiency and extensive thromboembolism in pregnancy: treatment with low-molecular-weight heparin.

Pregnancy limits the therapeutic options for managing thrombocytopenia which occurs in 5% of patients on heparin. We describe a case of extensive thromboembolism associated with antithrombin (AT) deficiency complicated by thrombocytopenia which resolved when low-molecular-weight heparin was instituted. A primigravid woman presented at 11 weeks gestation with bilateral femoral occlusive thrombi extending above the renal veins. Investigations revealed AT deficiency, thrombocytopenia and renal infarction. After low-molecular-weight heparin was substituted for unfractionated heparin, the thrombocytopenia resolved and although the pregnancy was lost, the patient made a full recovery.

Adult↗