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Cumulative conception and live birth rates after the treatment of anovulatory infertility: safety and efficacy of ovulation induction in 200 patients.

An analysis was performed on the cumulative conception rates, cumulative live birth rates and adverse effects of ovulation induction in patients with anovulatory infertility attending a single unit over an 11-year period. A total of 200 patients were included, 103 with clomiphene-resistant polycystic ovary syndrome (PCOS), 77 with hypogonadotrophic hypogonadism (HH) and 20 with weight-related amenorrhoea (WRA). Ovulation induction was performed using a number of protocols in which pulsatile luteinizing hormone-releasing hormone was administered s.c. or i.v. and gonadotrophins (human menopausal gonadotrophins or follicle-stimulating hormone) were administered i.m. The cumulative conception and live birth rates in the first course of therapy and after 12 cycles of treatment were, respectively, 73.2 and 62.4% in PCOS patients, 82.1 and 65.4% in the HH group and 95.0 and 85.3% in the WRA group. The miscarriage rates for all courses of treatment were 15.5% in PCOS patients, 22.9% in HH patients and 32.3% in WRA patients which resulted in cumulative live birth rates that were not significantly different. The median number of cycles and ovulations to achieve a pregnancy was 2 in all groups. The multiple pregnancy rate was significantly greater in women with PCOS (17.9%) than in women with HH (3.6%, P = 0.0052, 95% CI 5.12-23.36%) but not WRA (3.2%, P = 0.07, 95% CI 4.35-24.92%). The rate of multiple pregnancy fell after the introduction of monitoring by transvaginal ultrasound. Correction of anovulatory infertility by appropriately selected ovulation induction regimens results in cumulative conception and live birth rates indistinguishable from normal.

Amenorrhea↗

How are primary care organizations using financial incentives to influence prescribing?

METHODS: Primary care organizations (PCOs) in England are required to run a prescribing incentive scheme. The average payment received by general practitioners (GPs) under these schemes is not known. We conducted a longitudinal (2 year) questionnaire study of all PCOs in London and the south east of England aiming to explore the relationship between the financial incentives, the selection of prescribing indicators and success at remaining within budget. In the second year, the average reward per GP amounted to 1220 pounds (range 470 pounds-4330 pounds). Underspent PCOs made larger incentive scheme payments to their practices as did PCOs that had successfully overturned a first year overspend into a second year underspend. The size of rewards was unrelated to the selection of any particular cost- or quality-based prescribing indicator. We conclude that larger prescribing incentive scheme payments may have contributed to prescribing cost control but their effect on prescribing quality is uncertain.

Budgets↗

Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome.

Androgen receptors (AR) have been identified in human endometrium; however, their role in endometrial cyclic development and function remains poorly understood. The objective of the present study was to investigate the profile of endometrial AR in normal menstrual cycles and in the endometrium of women with polycystic ovarian syndrome (PCOS). This syndrome is characterized by chronic hyperandrogenism and oligo-ovulation, and it is often associated with poor reproductive performance. Using immunohistochemistry and reverse transcription-polymerase chain reaction, we found that women with PCOS exhibited elevated endometrial AR expression compared to normal, fertile controls. This increase was most apparent in glandular and luminal epithelium. Furthermore, when compared to endometrium from fertile women, PCOS endometrium showed other abnormalities in endometrial development, including delay or absence of the alpha(v)beta3 integrin, a well-characterized biomarker of uterine receptivity described previously (Lessey et al., JCI 1992; 90:188-195). To better understand and to gain insights regarding these findings, we used in vitro cell-culture models to study the regulation of AR in primary endometrial stromal and the well-differentiated epithelial cell line (Ishikawa). Based on Western blot analysis, epithelial AR is up-regulated by estrogens and androgens and is inhibited by progestins and epidermal growth factor (EGF). On the other hand, EGF significantly induced the expression of alpha(v)beta3, whereas estrogen and androgen treatment inhibited its expression. Collectively, these results suggest that the poor reproductive performance observed in women with PCOS may be due, in part, to the concomitant increase in both serum androgens and elevations in endometrial AR. This combination may reduce endometrial receptivity as judged by the down-regulation of alpha(v)beta3 integrin.

Adult↗

Polycystic ovarian syndrome and the metabolic syndrome.

Polycystic ovarian syndrome (PCOS), first described in 1937, was defined by specific ovarian histopathology and a constellation of signs and symptoms. Through the years, the etiology remained elusive, with heated debates focusing in turn on the ovary and then the pituitary as the causative agents. In the last several decades, it has become clear that insulin resistance makes up a very important component of this syndrome. With this knowledge, new therapies have emerged along with the realization that PCOS and the metabolic syndrome are closely related through their shared insulin resistance. In this review, the diagnosis, pathophysiology, and therapy of PCOS are discussed and upon this background, those areas held in common by PCOS and the metabolic syndrome are explored.

Female↗

Polycystic ovary syndrome: clinical perspectives and management.

The polycystic ovary syndrome (PCOS) is a common hyperandrogenic disorder and is characterized by a constellation of signs and symptoms often in association with a family history of hyperandrogenism and/or PCOS. It is often associated with hyperinsulinism and insulin resistance, which puts patients at risk for possible potential complications including type 2 diabetes mellitus and cardiovascular disease. Clinical signs may be subtle, and biochemical markers most often include an elevation of free testosterone (T) and possibly dehydroepiandrosterone sulfate (DHEAS). The diagnosis should be sought in any woman with hyperandrogenic features so that appropriate treatment may be used. There is often a good therapeutic response of the hirsutism, acne, or oligomenorrhea associated with PCOS. The new modalities that increase insulin sensitivity as well as weight reduction in the obese woman with PCOS may potentially be useful in modifying the potential later complications of this common endocrinopathy of young adult women.

Female↗

Risk factors for glucose intolerance in Danish women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are reported to be at risk for glucose intolerance. The aim of the study was to describe these risk factors in a population of Danish PCOS women attending a gynecologic clinic and to identify the parameters with the strongest correlation to the fasting blood glucose levels. In addition, we studied whether the oral glucose tolerance test (OGTT) diagnosed more cases of glucose intolerance in this PCOS population than the fasting plasma glucose value (FPG) alone. METHODS: Cross-sectional study of 91 women with oligomenorrhea or amenorrhea and elevated serum testosterone, followed by an OGTT in 27 of the women. RESULTS: Women with a FPG above normal were older and had a higher body mass index (BMI), cholesterol, and triglycerides and a lower sexual hormone binding globulin (SHBG). Of the 21 women older than 34, eight (38%) had a FPG above normal. The OGTT study showed that one of five with abnormal glucose tolerance would not have been diagnosed, if the FPG alone had been performed. CONCLUSIONS: In this study, 38% of women with symptoms of PCOS over the age of 34 had abnormal blood glucose values. These women should receive blood glucose testing regardless of BMI, testosterone levels and family history of type 2 diabetes mellitus. An OGTT may be necessary to find all cases of impaired glucose intolerance.

Adolescent↗

A randomized controlled trial of laser treatment among hirsute women with polycystic ovary syndrome.

BACKGROUND: Facial hirsutism is one of the characteristic features of polycystic ovary syndrome (PCOS), and this can lead to high levels of depression and anxiety. OBJECTIVES: To evaluate the impact of laser treatment on the severity of facial hirsutism and on psychological morbidity in women with PCOS. METHODS: A randomized controlled trial of five high-fluence treatments (intervention) vs. five low-fluence treatments (control) was performed over 6 months in a National Health Service teaching hospital. Subjects were 88 women with facial hirsutism due to PCOS recruited from hospital outpatient clinics and a patient support group in 2001-2002. The main outcomes were self-reported severity of facial hair (measured on a scale of 1-10), depression, anxiety (measured on the Hospital Anxiety and Depression Scale) and quality of life (measured on the WHOQOL-BREF). RESULTS: Self-reported severity of facial hair in the intervention group (n = 51) fell from 7.3 to 3.6 over the 6-month study period; for the control group (n = 37) the corresponding scores were 7.1 and 6.1. The change was significantly greater in the intervention group [ancova F((1,83)) = 24.5, P < 0.05]. Self-reported time spent on hair removal declined from 112 to 21 min per week in the intervention group and from 92 to 56 min in the control group [F((1,80)) = 10.2, P </= 0.05]. Mean depression scores fell from 6.7 to 3.6 in the intervention group, compared with 6.1 to 5.4 in the control group [F((1,83)) = 14.7, P < 0.05]. A similar change was seen for mean anxiety scores: intervention 11.1 to 8.2, control 9.6 to 9.3 [F((1,84)) = 17.8, P < 0.05]. Psychological quality of life also improved more in the intervention group, from 49.6 to 61.2 vs. 50.1 to 51.5 in the control group [F((1,84)) = 10.9, P < 0.05]. CONCLUSIONS: Laser treatment appeared to reduce the severity of facial hair and time spent on hair removal as well as alleviating depression and anxiety in women with PCOS. These findings suggest that ways of making this method of hair removal more widely available to women with facial hirsutism should be considered.

Adult↗

Studies of prolactin secretion in polycystic ovary syndrome.

In order to investigate the postulated relationship between hyperprolactinaemia and polycystic ovary syndrome (PCOS) we have studied 62 patients with PCOS. Only two patients had persistent prolactin (PRL) concentrations greater than the normal range on both random sampling and after blood sampling from intravenous cannula over 2 hours. Twenty-eight of the remaining patients had basal PRL secretion studied in more detail. Samples were collected at 15 min intervals during a 6 h period in all 28 patients and hourly samples were collected overnight from four patients. Results failed to demonstrate differences from control subjects in mean basal PRL concentrations, in spontaneous fluctuations or in increments related to stress, food or sleep. Lactotroph response to thyrotrophin releasing hormone, luteinising hormone releasing hormone and insulin stress testing in PCOS were determined. Results confirm a previous observation that normal PRL increments occur after ovulation and a blunted response follows a period of anovulation. This study has failed to find a consistent abnormality of lactotroph function in patients with PCOS other than that associated with anovulation.

Adolescent↗

Effect of bromocriptine on LH pulsatility in the polycystic ovary syndrome.

The effects were studied of bromocriptine, 10 mg daily for 1 year, on luteinizing hormone (LH) pulse characteristics in patients with classical polycystic ovarian syndrome (PCOS). All patients were hirsute, had been oligomenorrhoeic since menarche, had LH: FSH ratios of greater than 3:1, and either elevated serum testosterone (T) or dehydroepiandrosterone sulphate (DHAS) concentrations. In 10 subjects who completed the study menstrual frequency increased from an average of 3.6 to 8 per year but few of the cycles were ovulatory. Mean (SE) serum testosterone fell from 4.4 (0.5) nmol/l pretreatment to 2.8 (0.3) nmol/l (P less than 0.01) and DHAS from 7.9 (1.1) mumol/l to 5.4 (1.1) mumol/l (P less than 0.05). Serum delta 4 androstenedione and oestradiol did not change with bromocriptine treatment. Mean serum LH fell from 17.4 (2.4) IU/l to 11.2 (1.8) IU/l (P less than 0.03) after 12 months of bromocriptine. No pattern of LH pulsatility specific to PCOS was detected during 10 min sampling for an 8 h period prior to dopamine agonist treatment. LH interpeak interval (58 (5.2) min) and peak amplitude (156 (7.2%) of mean nadir) in untreated PCOS were similar to that of the mid-follicular stage of ovulatory cycles, and bromocriptine for 1 year did not alter these variables. We conclude that while bromocriptine reduces serum androgen levels and increases menstrual frequency it has no effect centrally to modify hypothalamic GnRH secretion. The reduction in LH levels by bromocriptine may be the result of diminished gonadotroph sensitivity to GnRH or reduced pituitary stores of LH available for release. Despite the return towards normal of various hormonal characteristics of PCOS, bromocriptine has little place in the management of this condition.

Adolescent↗

Episodic pulsatile secretion of FSH, LH, prolactin, oestradiol, oestrone, and LH circadian variations in polycystic ovary syndrome.

Pulsatile secretion of LH, FSH, PRL, oestradiol and oestrone was studied in a group of 16 patients with micropolycystic ovary syndrome (PCOS) and compared with that of normal ovulatory women in the fifth to sixth day of the cycle. Hormone concentrations were measured at 10 min intervals for 8 h starting at 0930 h. In seven subjects, the study was prolonged for 24 h, with 20 min interval samples, in an attempt to evaluate the circadian rhythm of LH by cosinor analysis. Significant fluctuations occurred in the concentration of each hormone. Values shown are mean +/- SD. PCOS subjects had high LH mean values (27.9 +/- 5.9 IU/l) (P less than 0.005). LH pulse amplitude was higher than controls (11.6 +/- 3.7 IU/l versus 5.2 +/- 1.8 IU/l; P less than 0.005) while no consistent changes in frequency or interpulse interval (62.0 +/- 10.7 min versus 65.8 +/- 19.2 min; P = NS) were found. A mean of 4.8 +/- 1.2 pulses of FSH occurred in 8 h and the mean pulse amplitude was 2.68 +/- 1.11 with no differences from controls. All patients were normoprolactinaemic. A mean of 5.5 +/- 1.9 pulses occurred in 8 h, the interpulse interval was 76.1 +/- 14.4 min and the amplitude was 2.87 +/- 0.76 ng/ml and there were no significant differences from controls; 75% of PRL pulses showed a temporal relationship with LH pulses. Oestrone mean basal values were higher in PCOS (47.2 +/- 12.5 pg/ml) than controls (32.0 +/- 9.9 pg/ml; P less than 0.02), while no differences were observed as regards oestradiol. Oestradiol pulse amplitude was nearly the same as oestrone (43.6 +/- 18.8 pg/ml and 37.7 +/- 16.1 pg/ml, respectively); 6.0 +/- 2.2 pulses and 6.0 +/- 1.6 pulses occurred in 8 h with an interpulse interval of 81.1 +/- 27.1 min and 71.8 +/- 11.1 min, respectively. Sixty-five per cent of LH pulses were followed by an oestradiol and oestrone peak. The mean time of the appearance was 17 +/- 15 min and 25 +/- 23 min, respectively. In the PCOS group a consistent 24 h rhythm in mean plasma LH levels was found with the highest hormone values at 1720 h (P less than 0.05) unrelated to apparent sleep and different from that of adult women. Pulse frequency showed a significant slowing during the night with the longest interpulse interval at 0327 h (P less than 0.03) while no significant periodicity was observed in LH pulse amplitude.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance.

OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0-109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92-169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports of hyperinsulinaemia and insulin resistance in polycystic ovary syndrome. Furthermore, polycystic ovary syndrome subjects have a reduced postprandial thermogenesis which is related statistically to the reduced insulin sensitivity. The decreased postprandial thermogenesis may predispose women with polycystic ovary syndrome to weight gain.

Adult↗

Spontaneous follicular and luteal function in infertile women with oligomenorrhoea: role of luteinizing hormone.

OBJECTIVE: There is a paucity of longitudinal endocrine studies of infertile patients with oligomenorrhoea. We have assessed the frequency and quality of spontaneous follicular development and luteal function in patients with oligomenorrhoea and infertility (PCOS), and have related the observed criteria to circulating LH activity. DESIGN: Prospective detailed investigations in a cohort of unselected patients. PATIENTS: Infertile women with oligomenorrhoea (PCOS, n = 131) presenting to the infertility clinic at the Royal Infirmary, Glasgow. MEASUREMENTS: Patients were monitored with frequent plasma oestradiol (E2) concentration assessments over a minimum period of 3 weeks, starting more than 2 weeks after a menstrual bleed. When follicular maturation was identified the patient provided daily blood samples through to her ensuing menstrual bleed, and E2, progesterone, total testosterone, FSH and LH were assessed in these samples. Luteal phase progesterone profiles were assessed between the days LH surge +2 and LH surge +6 by means of a progesterone index. RESULTS: Forty-eight per cent of the patients showed evidence of follicular development. The oestradiol profiles in the patients showing follicular growth were normal, but the progesterone curve was sub-normal in the early luteal phase, due to a high proportion of deficient luteal phases. The mean LH concentrations were elevated in the whole group, but no difference was observed between the mean LH values for those patients showing spontaneous follicular development and those who did not, and the incidence of ovulation was similar in the normal LH and elevated LH groups. Similarly, no relation was established between LH and the quantitative assessment of luteal phase progesterone profiles (progesterone index), and the distribution of progesterone indices was similar in the normal LH and elevated LH groups. Testosterone concentrations were positively correlated with LH (p = 0.008) but not with the incidence of spontaneous follicular growth. There was no significant difference in the incidence of spontaneous ovulation between the patients with elevated or normal mean follicular phase testosterone concentrations. CONCLUSION: The data indicate that both LH and testosterone secretion in PCOS were closely linked, but that neither was directly linked to the incidence or inhibition of spontaneous follicular development in PCOS, or to the disturbance in luteal phase progesterone profiles.

Adult↗

Differential effects of endothelin-1 on the vasorelaxant properties of benzopyran and non-benzopyran potassium channel openers.

1. The effects of endothelin-1 (ET-1) on the vasorelaxant properties of structurally different potassium channel openers (PCOs), BRL-38227, Ro 31-6930, SDZ PCO 400, EMD-52692, RP-49356 and pinacidil, were studied. 2. All PCOs evoked concentration-related relaxations of ET-1 (10 nM) or KCl (20 mM) contracted rat isolated aortic rings denuded of endothelium. BRL-38227, EMD 52692, SDZ PCO 400 and Ro 31-6930 were 11-42 times less potent in relaxing contractions to ET-1 than KCl. In contrast, this differential potency was not observed with RP-49356 or pinacidil. 3. BRL-38227 (0.06-3.0 microM), RP-49356 (0.3-3.0 microM) and pinacidil (0.3-3.0 microM) displaced KCl concentration-response curves to the right of controls, without modifying the maximum response. A subcontractile concentration of ET-1 (0.1 nM) prevented the inhibitory effects of low concentrations of BRL-38227 (0.06-0.1 microM) on KCl responses, but failed to modify those to RP-49356, pinacidil or high concentrations of BRL-38227 (0.3-3.0 microM). The inhibitory effects of BRL-38227 (0.1 microM) were also not changed by ET-3 (1.0 nM) or angiotensin II (0.1 nM). 4. In anaesthetized spontaneously hypertensive rats (SHR), cumulative bolus intravenous administrations of BRL-38227 (1-1000 micrograms kg-1, i.v.), Ro 31-6930 (1-1000 micrograms kg-1, i.v.), RP-49356 (10-1000 micrograms kg-1, i.v.) or nitrendipine (0.1-30 micrograms kg-1, i.v.) produced dose-dependent falls in diastolic blood pressure (DBP).ET-1 (i.v.) evoked a transient fall in DBP (1 pg kg- = 58 + 1 mmHg) which returnedto pre-administration levels within 4 min.5. Pretreatment of anaesthetized SHR with ET-l (1 pg kg-', i.v.) significantly increased the ED,5 (dose to evoke a 15% fall in DBP) values for BRL-38227 and Ro 31-6930. However, ET-l failed to modify the ED,5 values for RP-49356 or nitrendipine. The ED50 values for all of the vasodilators studied were not modified by ET-1.6. Infusion of BRL-38227 (2 pgkg-'min-', i.v.) or RP-49356 (4 pgkg-'min', i.v.) to anaesthetized SHR evoked dose-related falls in DBP, with a corresponding increase in descending aortic blood flow (DABF) and a decrease in total lower body vascular resistance (TLBVR). Pretreatment with ET-1 (1 ptg kg-', i.v.) significantly attenuated the decreases in DBP and TLBVR observed with low doses of BRL-38227, but not RP-49356 or high doses of BRL-38227. In contrast, ET-3 (3 pig kg-, i.v.) failed to modify the effects of BRL-38227 on DBP or TLBVR.7. In conscious SHR, the fall in DBP to BRL-38227 (30 pgkg-', p.o.) was significantly reduced following ET-1 (1 pig kg-', i.a.) treatment. ET-1 (1 pg kg-', i.a.) pretreatment, however, failed to modify the decrease in DBP induced by an equieffective oral dose of RP-49356 (1001pgkg-1).8. In conclusion, ET-1 selectively attenuated the vasorelaxant effects of the potassium channel opener,BRL-38227 and other substituted benzopyrans. The results are compatible with the hypothesis that benzopyran PCOs and ET-1 have affinity for a site that does not recognise RP-49356 or pinacidil. Thus,ET-l can differentiate between structurally unrelated potassium channel openers. The cardiovascular effects of some, but not all, PCOs might be radically modified in the clinical setting by elevated endogenous levels of ET-1 associated with certain diseased states.

Animals↗

The impact of ethnicity on the presentation of polycystic ovarian syndrome.

The effect of ethnicity on the prevalence and presentation of polycystic ovarian syndrome (PCOS) was examined in a cross-sectional study of women with clinical - and ultrasound - diagnosed PCOS. European, Maori and Pacific Island women were seen in proportion to the general population, whereas Indian women were over-represented and Chinese women under-represented. European and Maori women were more likely to present with hirsutism than other ethnic groups (43% versus 25%, p < 0.05), while European women were less likely to present with infertility (46% versus 68%, p < 0.01). The Pacific Island women had little or no acne but other signs of PCOS were similar among ethnic groups. Although less than 10% of patients were referred with obesity, the majority of PCOS women were overweight on examination. Maori and Pacific Island women were more obese and had the highest rates of insulin resistance and lipid abnormalities. The adverse metabolic profile of many of these women, particularly the Maori and Pacific Islanders, is very likely to predispose them to early cardiovascular disease.

Adolescent↗

Polycystic ovaries and polycystic ovary syndrome in epilepsy: evidence for neurogonadal disease.

Polycystic ovary syndrome (PCOS) is a mysterious reproductive disorder that results in subfertility. The underlying causes are not known, and even the definition is a moving target. Women with epilepsy have features of PCOS at a higher than expected rate, and polycystic ovaries (PCO) also are present at high rates in this population. Valproate is associated with weight gain and increased androgen levels, two features of PCOS. This review proposes that epilepsy, with its known adverse effects on luteinizing hormone pulsatility, could be a cause of PCOS and that valproate could be an imitator, if not also a cause of the syndrome.

Journal Article↗

An overview of the diagnostic considerations in polycystic ovarian syndrome.

The past ten years have been particularly exciting with regard to the elucidation of the pathophysiology of PCOS. It appears that PCOS is about to yield some of its mysteries and to have some of its discrete subsets defined, as Cushing syndrome did 50 years ago. However, future studies of PCOS will require a complex interplay of clinical investigation, molecular and genetic probes, increasingly refined anatomic observations, and fundamental neuroendocrine studies. Each observer has a bias, which must be acknowledged in his/her studies. However, a true synthesis of the abnormalities characteristic of PCOS must continually be sought, for only through a comprehensive view of this syndrome will we come to understand its true pathophysiology; and only then can rational therapies be designed.

Androgens↗

Effects of switching to wen-jing-tang (unkei-to) from preceding herbal preparations selected by eight-principle pattern identification on endocrinological status and ovulatory induction in women with polycystic ovary syndrome.

The objective of this study was to investigate the effects of switching therapy to wen-jing-tang (unkei-to) from previous selected herbal preparations on endocrine levels and induction of ovulation in women with polycystic ovary syndrome (PCOS). Sixty-four anovulatory women diagnosed with PCOS were enrolled in the study. After Kampo diagnosis, subjects received matched Kampo preparations (43 cases: dang-gui-shao-yao-san, 21 cases: gui-zhi-fu-ling-wan) selected by the matching theory of eight-principle pattern identification and Kampo diagnosis based on concepts of the qi, blood, and fluids as the physiologic activity. Fifty-four women who failed to ovulate after an 8-week treatment were randomly allocated to continuation of treatment with the preceding Kampo prescription (continuation group, n = 27) or treatment with wen-jing-tang (switching group, n = 27). Plasma FSH, LH and estradiol levels were measured and ovulation rates were determined at the beginning and after an 8-week treatment with the preceding Kampo prescription, as well as after the subsequent 8-week treatment with the same preparation or wen-jing-tang. No decrease in mean plasma LH level was observed in the 54 women who failed to ovulate among the 64 treated with a Kampo preparation. After the 8-week treatment with wen-jing-tang, plasma LH levels were decreased by 58.2% (p < 0.0001) and 49.4% (p = 0.0005) in the groups switched from dang-gui-shao-yao-san and gui-zhi-fu-ling-wan, respectively. In the group switched from dang-gui-shao-yao-san, a tendency towards increase in plasma estradiol level was observed (1.51-fold, p = 0.055), which was significant compared with that in the group switched from gui-zhi-fu-ling-wan (p = 0.032). The ovulation rate with switching of treatment to wen-jing-tang was significantly higher (59.3%) than that with continued use of the same preparation (7.4%, p = 0.0036). This study confirmed that wen-jing-tang was effective in improving endocrine condition in the treatment of disturbances of ovulation in patients with PCOS without taking eight-principle pattern identification into consideration. This finding indicates that wen-jing-tang is appropriate for use in treating PCOS in women with various constitutions (as determined by the matching theory of eight-principle pattern identification) in clinical practice and may prove to be a potent therapeutic agent with a wide therapeutic spectrum.

Adolescent↗

The relationship of recurrent spontaneous miscarriage with reproductive failure.

OBJECTIVE: To investigate the reproductive performance of non-pregnant women with recurrent spontaneous miscarriage (RSM) and the association between RSM and polycystic ovary syndrome (PCOS) in reproductive failure. SUBJECTS AND METHODS: Fifty non-pregnant women with 3 or more consecutive RSM attending our RSM clinic were evaluated prospectively. Detailed history and physical examination were completed. Extensive laboratory investigations, ultrasonographic, radiological and specialized procedures/tests were performed. Those patients who did not achieve pregnancy within the first 6 months of follow-up had appropriate treatment options implemented. The outcome of any subsequent pregnancies was analyzed. RESULTS: The mean age of the patients was 33.8 +/- 4.6 years (range 22-43 years). The aetiological factors associated with RSM were chromosome anomaly, uterine abnormality, antiphospholipid syndrome, PCOS and infections; 40% were 'unexplained'. Thirty patients (60%) were able to achieve viable pregnancies which progressed to term, resulting in live births. Fourteen of the other 20 patients had high body mass index (BMI) >30 and evidence of PCOS. Of these 20 patients, 13 eventually achieved pregnancies which ended again in first-second-trimester abortions (cause undetermined). The remaining 7 patients (4 with high BMI) who had a combination of male factor/protracted PCOS/ovarian failure did not achieve pregnancies. CONCLUSION: The association of RSM with PCOS resulted in poor reproductive performance, which may progress to reproductive failure.

Abortion, Habitual↗