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Biomedical subjects

A H Balen

Publications and source records attributed to A H Balen.

At least 19 recordsLinked to original sources
PubMed2006

The influence of body weight on response to ovulation induction with gonadotrophins in 335 women with World Health Organization group II anovulatory infertility.

OBJECTIVE: To assess the influence of body weight on the outcome of ovulation induction in women with World Health Organization (WHO) group II anovulatory infertility. DESIGN: The combined results of two studies in which either a highly purified urinary follicle-stimulating hormone or highly purified urinary menotrophin were compared with recombinant follicle-stimulating hormone. SETTING: Thirty-six fertility clinics. POPULATION: A total of 335 women with WHO group II anovulatory infertility failing to ovulate or conceive on clomifene citrate. METHODS: Ovarian stimulation using a low-dose step-up protocol. MAIN OUTCOME MEASURES: The effects of body weight on ovarian response, ovulation rate and pregnancy rate after one treatment cycle. RESULTS: With increasing body mass index (BMI), a higher threshold dose of gonadotrophins was required and there were more days of stimulation; yet, despite a greater concentration of antral follicles, there were fewer intermediate and large follicles. There was no difference in the rates of ovulation and clinical pregnancy in relation to body weight. CONCLUSIONS: Body weight affects gonadotrophin requirements but not overall outcome of ovulation induction in women with anovulatory polycystic ovary syndrome and a BMI of less than 35 kg/m2.

Adult↗
PubMed2006

Metabolic and polycystic ovary syndromes in indigenous South Asian women with previous gestational diabetes mellitus.

OBJECTIVE: To determine the risk of metabolic syndrome (MS) and polycystic ovary syndrome (PCOS) in a cohort of indigenous South Asian women with a recent history of gestational diabetes mellitus (GDM). DESIGN: Case-control study. SETTING: Department of Obstetrics & Gynaecology, University of Colombo, Sri Lanka. SAMPLE: Two hundred and seventy-four indigenous Sri Lankan women with previous GDM and 168 ethnically matched controls. Of these, 147 with previous GDM and 67 controls not taking hormonal contraception participated in an in-depth endocrine study. METHODS: Assessing the prevalence of MS and PCOS based on clinical features, biochemistry and ovarian ultrasound examination at 3 years postpartum. MAIN OUTCOME MEASURES: Prevalence of MS and PCOS. RESULTS: Women with previous GDM and controls were studied at a mean (range) of 34.6 (13.4-84.1) and 46.5 (17.5-78) months postpartum, respectively. Those with previous GDM had a larger mean +/- 95% confidence interval waist circumference (90.9 +/- 1.3 versus 81.2 +/- 2.8 cm, P = 0.0004) and were more likely to have hypertension (17.6 versus 7.4%, P = 0.001), glucose intolerance (51.7 versus 10.4%, P = 0.00001), hypertriglyceridaemia (16.3 versus 5.9%, P = 0.02) and a lower level of high-density lipoprotein (70 versus 56.7%, P = 0.04) than the controls. Of the women who had GDM, 72 (49%) had MS, 86 (58.5%) had polycystic ovaries and 59 (40%) had PCOS, significantly more than the control women-4 (6%), 9 (13%) and 2 (3%), respectively (P = 0.00001). CONCLUSIONS: The prevalence of MS and PCOS in indigenous Sri Lankan women 3 years postpartum is significantly higher in those with previous GDM compared with ethnically matched controls. This confirms an association between GDM and subsequent PCOS and MS.

Adult↗
PubMed2006

The role of the central nervous system in the pathogenesis of polycystic ovary syndrome.

This article reviews the master gland concept and the hypothalamic-pituitary-ovarian axis with respect to embryological development and maturation through normal puberty. Intrinsic function and extrinsic modulation of the pulse generator are discussed. The neuroendocrine disturbances evident in polycystic ovary syndrome (PCOS) are reviewed and put into the context of the recent consensus definition of the syndrome. Modern theories are presented addressing a significant role for neuroendocrine dysfunction during pubertal maturation in the aetiology of PCOS.

Female↗
PubMed2005

Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women.

BACKGROUND: Aromatase catalyses the conversion of androgens to estrogens and thus variation in the aromatase gene could contribute to female syndromes of androgen excess, such as precocious pubarche (PP) and polycystic ovarian syndrome (PCOS). METHODS: Two groups, one case-control containing girls from Barcelona, Spain with PP (n = 186) or healthy controls (n = 71), and the other a population study of young women from Oxford, UK, who volunteered for a study of normal women's health (n = 109), were genotyped at four aromatase gene haplotype-tag single nucleotide polymorphisms (SNP). Clinical features and hormone concentrations relevant to hyperandrogenism were compared across haplotypes or genotypes. RESULTS: Distributions of aromatase haplotypes (P < 0.0001) and aromatase SNP_50 genotype (P = 0.001) were significantly different between PP girls and Spanish controls. The AGGG haplotype was associated with an odds ratio (95% confidence interval) of 0.5 (0.3-0.9) (P = 0.005) for the presence of PP compared to GAGG. In 84 post-pubertal PP girls, aromatase haplotype was associated with functional ovarian hyperandrogenism (P < 0.05), independently of insulin sensitivity. In the Oxford population, SNP_50 was associated with variation in PCOS symptom score (P = 0.008) and circulating testosterone concentrations (P = 0.02). CONCLUSIONS: This study suggests that common variation at the aromatase gene (and not just rare loss-of-function mutations) is associated with androgen excess in girls and young women.

Adolescent↗
PubMed2004

Prevalence of polycystic ovaries and polycystic ovary syndrome in lesbian women compared with heterosexual women.

OBJECTIVE: To determine the prevalence of polycystic ovaries (PCO) and polycystic ovarian syndrome (PCOS) in lesbian women compared with heterosexual women undergoing fertility treatment. DESIGN: A prospective observational study. SETTING: The London Women's clinic and The Hallam Medical Center. Tertiary referral fertility setup. PATIENT(S): Six hundred eighteen women undergoing ovarian stimulation with or without IUI treatment between November 2001 and January 2003. Of these, 254 were self-identified as lesbians and 364 were heterosexual women. INTERVENTION(S): Baseline pelvic ultrasound examination and blood tests conducted to measure biochemical parameters such as FSH, LH, E(2), PRL, T, androstenedione (A), sex hormone-binding globulin (SHBG), and DHEAS were performed between day 2 and 3 of each woman's menstrual cycle. Tubal patency tests were performed by hysterosalpingography or laparoscopy. MAIN OUTCOME MEASURE(S): Biochemical parameters. RESULT(S): Eighty percent of lesbian women, compared with 32% of the heterosexual women, had PCO on pelvic ultrasound examination. Thirty-eight percent of lesbian women, compared with 14% of heterosexual women, had PCOS. There were no significant differences in the androgen concentrations between lesbian and heterosexual women with normal ovaries. However, lesbian women with PCO and PCOS had significantly higher androgen concentrations compared with heterosexual women with PCO and PCOS. Tubal disease was as common in lesbian women as in heterosexual women. CONCLUSION(S): There is a significantly higher prevalence of PCO and PCOS in lesbian compared with heterosexual women. Lesbian women with either PCO or PCOS had more pronounced hyperandrogenism than did heterosexual women with either PCO or PCOS.

Adult↗
PubMed2004

Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility.

In a double-blind, placebo-controlled, randomized study, 55 anovulatory subjects received a single s.c. injection of placebo (n = 10) or recombinant long-acting FSH [FSH-carboxy terminal peptide (CTP), ORG 36286, corifollitropin alfa; NV Organon, The Netherlands] in doses of 7.5 (n = 13), 15 (n = 10), 30 (n = 11), or 60 microg (n = 11). The injection was given 2 or 3 d after the onset of a spontaneous or progestagen-induced withdrawal bleed. After drug administration, the induced follicular response varied widely among subjects in each dose group. The percentage of subjects with a follicular response (at least one follicle > or = 10.0 mm) increased with the dose (P < 0.01) and was 10, 31, 70, 73, and 82% in the placebo and 7.5-, 15-, 30-, and 60-microg treatment groups, respectively. In responding subjects, the average maximum number of follicles was 4.0, 7.6, 13.4, and 20.0, respectively, which was reached at 6.5, 6.9, 6.6, and 8.2 d after a single dose of 7.5, 15, 30, and 60 microg FSH-CTP, respectively. The dose-response for the number of follicles was statistically significant within the dose range tested (P < 0.01). Peak serum inhibin-B levels were significantly correlated with serum estradiol (E2) levels (r = 0.84, P < 0.01), and peak concentrations of inhibin-B and E2 correlated with the number of follicles observed at the same time point (for both hormones; r = 0.47, P < 0.01). Overall per treatment group, serum E2 and inhibin B concentrations significantly increased only in the two highest FSH-CTP dose groups, reaching peak concentrations at d 3 in the 30-microg group and at d 5 in the 60-microg group. Thereafter these hormone values declined rapidly, returning to baseline within 1 wk after FSH-CTP administration. In total, nine of the 55 treated subjects (16.4%) ovulated after drug administration: one subject in the placebo group, two subjects in the 7.5-microg group, three subjects in the 15-microg group, two in the 30-microg group, and one in the 60-microg group. Three subjects had monofollicular ovulation after placebo (n = 1) and a single dose of 15 microg FSH-CTP (n = 2). In two subjects with too many preovulatory follicles, (multiple) ovulation was prevented by GnRH antagonist administration. Thus, a single low dose of long-acting FSH-CTP was able to induce one or more follicles to grow up to ovulatory sizes, but the anovulatory status was not reversed because the incidence of subsequent (mono)ovulations was low.

Adult↗
PubMed2002

No evidence for paternal mtDNA transmission to offspring or extra-embryonic tissues after ICSI.

There is a risk that ICSI may increase the transmission of mtDNA diseases to children born after this technique. Knowledge of the fate and transmission of paternal mitochondrial DNA is important since mutations in mitochondrial DNA have been described in oligozoospermic males. We have used an adaptation of solid phase mini-sequencing to exclude the presence of levels of paternal mtDNA >0.001% in ICSI families. This method is more sensitive than those used in previous studies and is sufficient to detect the likely paternal contribution (approximately 0.1-0.5% from simple calculations of expected dilution during fertilization). Using this method, we were able to detect concentrations as low as 0.001% paternal mtDNA in a maternal mtDNA background. No paternal mtDNA was detected in the embryonic (blood or buccal swabs) tissue of children born after ICSI nor in extra-embryonic tissue (placenta or umbilical cord). In conclusion, we did not detect paternal mtDNA in blood, buccal swabs, placenta or umbilical cord of children born after ICSI. We have found no evidence that ICSI increases the risk of paternal transmission of mtDNA and hence of mtDNA disorders.

DNA, Mitochondrial↗
PubMed2001

On the association between valproate and polycystic ovary syndrome.

Recent studies by Isojärvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Polycystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility. hyperandrogenemia, and menstrual disorders. From an extensive review of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyperinsulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral, and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojärvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences.

Adolescent↗
PubMed2001

The effects of female age on fecundity and pregnancy outcome.

In industrialized countries worldwide, women are delaying childbearing for a variety of reasons, including pursuit of career, greater financial independence, improved and more accessible contraception and longer life expectancy. In terms of fertility and maternity, those aged > or = 35 years are considered to be of advanced maternal age and there are usually marked reductions in both the fecundity rate for spontaneous conceptions and the success rates with assisted conception. These decreases are thought to be due mainly to oocyte ageing, and the established success of oocyte donation from younger individuals to older recipients supports this contention. For those who achieve a pregnancy at an advanced maternal age there is a greater likelihood of aneuploidy (assuming conception with the woman's own oocytes), hypertensive and other medical disorders, birth by Caesarean section and maternal mortality. However, most of the complications associated with advanced maternal age are caused by age-related confounding variables, and older premenopausal women in good health should not require special attention. The data on perinatal mortality rates are encouraging and in the absence of congenital abnormalities perinatal mortality is probably not much increased, if at all, in older mothers. Pregnancy is now possible for postmenopausal women with the application of oocyte donation, but these individuals have a significantly higher likelihood of cardiovascular ageing and should be considered at increased risk of vascular complications during pregnancy.

Adult↗
PubMed2001

A postal survey of embryo transfer practice in the UK.

In this postal survey a questionnaire was sent to all unit directors in the UK to determine their attitudes to the factors influencing embryo transfer practice. They were requested to rate each step on a scale of 1-10, where 1 was irrelevant and 10 very important. A total of 80 practitioners from 40 units replied. Over 50% of the corresponding practitioners were consultants, 33% were middle-grade clinicians, and 12% were infertility nurse specialists. The factor that got the highest rating was the need for a standardized protocol for all unit staff regarding embryo transfer technique. The second critical factor voted by the respondents was the presence of blood on the embryo transfer catheter. Not touching the uterine fundus was deemed to be the third most important factor while the type of embryo transfer catheter used was a very close fourth. Prolonged bed rest following embryo transfer was voted the least important factor to influence the outcome. The wide variations in practice and choice of catheters encountered in this survey are indications of the divided opinion and lack of concrete evidence on which to base any firm decisions. The need for large clinical studies to assess clearly whether higher pregnancy rates will result from modifications in embryo transfer practice is highlighted.

Data Collection↗
PubMed2001

Polycystic ovaries and eating disorders: Are they related?

A cross-sectional observational study was used to investigate the reported association between polycystic ovarian syndrome and bulimia nervosa in a group of young, post-menarcheal women in the normal population. Volunteers aged 18-25 years were recruited from two universities and two general practice surgeries in Oxford. A total of 230 women completed an interviewer-based eating disorder examination, which was used to diagnose bulimia nervosa and its variants, and to assess eating behaviour. Transabdominal ultrasound was used to diagnose the presence or absence of polycystic ovaries. Symptoms of polycystic ovarian syndrome were assessed using menstrual history, anthropometric measurements, clinical observation of acne and hirsutism, and biochemical analysis of a fasting blood sample. A total of 30% of all participants described episodes of overeating and 4% had used extreme methods of weight control. Two women were diagnosed with bulimia nervosa, and five women with binge-eating disorder; however, these diagnoses were not associated with polycystic ovaries. Scores for dieting and overall eating disorder symptoms in the polycystic ovary groups were not significantly higher than those for women with normal ovaries, and therefore the suggestion that polycystic ovaries predispose towards the development of eating disorders is not supported by this study.

Adolescent↗
PubMed2001

Appropriate design of biochemistry request cards can promote the use of protocols and reduce unnecessary investigations.

Attempts to control laboratory workload in the past always proved to be short-lived. We designed a request card based on clinical conditions for a gynaecology out-patient clinic to help clinical staff to adhere to agreed investigation protocols. Each request card had a tick-box associated with a clinical condition. The tests performed for each condition were advertised on a poster in the clinic. The workload was assessed for a 2-year period before and after the introduction of these cards. The numbers of all endocrine tests, except progesterone and sex hormone binding globulin, fell by 19% (P<0.0001) whereas the clinical cases seen remained steady at 227 per month. This report demonstrates that agreed protocols can be implemented but that a persistent aide-mémoire is necessary.

Biomarkers, Tumor↗
PubMed2000

New concepts in superovulation strategies for assisted conception treatments.

Controlled ovarian stimulation for in-vitro fertilization treatment using preparations that contain follicle-stimulating hormone has been routinely performed since the 1980s. The early preparations were urinary human menopausal gonadotrophins, containing follicle-stimulating hormone and luteinizing hormone. In the early 1990s, highly purified follicle-stimulating hormone preparations were introduced because of a desire to provide drugs for subcutaneous administration with a lower risk of allergic reactions. Intensive research resulted in the discovery of recombinant follicle-stimulating hormone, which is more potent that the highly purified follicle-stimulating hormone, resulting in significantly higher clinical pregnancy rates. The two recombinant follicle-stimulating hormone preparations available appear to be equally effective and provide comparable results. Gonadotrophin-releasing hormone antagonists, which have recently been introduced, appear to be effective in preventing a premature rise in luteinizing hormone during ovarian stimulation for in-vitro fertilization, as well as improved response to lower doses of gonadotrophins. It is envisaged that the availability of recombinant gonadotrophins and gonadotrophin-releasing hormone antagonists will ultimately lead to shorter, cheaper and safer treatments, using reduced dosages.

Female↗
PubMed2000

Trends in the incidence of ectopic pregnancy in England and Wales from 1966 to 1996.

OBJECTIVE: To examine the incidence of ectopic pregnancy over the period 1966 to 1996. SETTING: England and Wales. DESIGN: Use of official statistics on hospital discharges, maternities, legal abortions and estimated populations of women aged 15-44 years. MAIN OUTCOME MEASURES: Incidence rates of ectopic pregnancies. RESULTS: Between 1966 to 1970 and 1994 to 1996 the recorded incidence increased 4.5-fold from 3.45 to 15.5 per 1000 maternities, 3.8-fold from 3.25 to 12.4 per 1000 pregnancies and 3.1-fold from 30.2 to 94.8 per 100,000 women aged 15-44. The rate of increase was not uniform. Incidence approximately doubled between 1966 and 1985, when the official data collection system changed. By 1989, when data from the new system became available, there had been a further almost doubling of recorded incidence. Subsequently, the upward trend appears to have continued until 1991 to 1992 and has remained stable in the last four years of the study. The trends were similar in each of three 10-year age groups. CONCLUSIONS: The recorded incidence of ectopic pregnancy has increased markedly over the last three decades. This may be partly due to artefacts of data recording and more sensitive diagnostic tests, but it is likely that the actual incidence has increased, probably due to a sexually transmitted agent.

Adolescent↗
PubMed2000

Definition and measurement of follicle stimulating hormone.

FSH has a key role in the development and function of the reproductive system and is widely used both diagnostically and therapeutically in developmental and reproductive medicine. The accurate measurement of FSH levels, in patients for diagnosis and monitoring and in therapeutic preparations for clinical use, is essential for safe and successful treatment. Historically, FSH was defined on the basis of classical in vivo endocrine activity, and early therapeutic preparations were calibrated using in vivo bioassays. There was early recognition that reference preparations were required for calibration if the results from different laboratories were to be comparable. In response to the perceived need, the World Health Organization established the first standard for such preparations in 1959. Subsequent developments in biotechnology have led to recognition that there is no single molecule that can be uniquely defined as FSH, and that FSH can induce a range of biological activities. Several highly purified standards for FSH are now available, but discontinuity and heterogeneity of estimates of FSH activity in terms of these standards made using in vitro assays and binding assays have been noted. It is thus essential that any measurement of FSH include specification both of the standard with which the measured FSH is compared and the assay method used for that comparison.

Animals↗
PubMed1999

Induction of ovulation with the use of a starting dose of 50 units of recombinant human follicle-stimulating hormone (Puregon).

OBJECTIVE: To determine whether a starting dose of 50 units of recombinant FSH (follitropin beta, Puregon; Organon Laboratories Limited, Cambridge, United Kingdom) produces a follicular response in patients with clomiphene citrate-resistant polycystic ovary syndrome (PCOS). DESIGN: Prospective observational study. SETTING: Routine clinical practice in a teaching hospital fertility unit. PATIENT(S): Patients with clomiphene citrate-resistant PCOS who wanted to become pregnant. INTERVENTION(S): Low-dose step-up protocol of SC recombinant FSH administration, monitored prospectively by transvaginal ultrasonography and retrospectively by serum endocrine assays taken at each monitoring visit. MAIN OUTCOME MEASURE(S): Rate and size of follicular growth, recombinant FSH requirement, E2 response, ovulation, cycle cancellation, and pregnancy. RESULT(S): All patients exhibited a follicular response: Six patients ovulated, of whom two conceived and four had their cycles cancelled because of overstimulation. One patient did not ovulate despite the development of a follicle. CONCLUSION(S): Recombinant FSH can be used successfully to stimulate follicular growth at a starting dose of 50 IU.

Adult↗