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Aim: To ascertain the risk of progression to diabetes among Chinese women with PCOS., Methods: Women with PCOS (n = 3978) were identified from the Hong Kong Diabetes Surveillance Database based on the ICD-9 code for PCOS diagnosis and women without PCOS served as controls (n = 39780), matched 1:10 by age., Result(s): The mean follow-up was 6.28 ± 4.20 and 6.95 ± 4.33 years in women with PCOS and controls, respectively. The crude incidence rate of diabetes was 14.25/1000 person-years in women with PCOS compared with 3.45 in controls. The crude hazard ratio of diabetes in women with PCOS was 4.23 (95 % CI: 3.73-4.80, p < 0.001). Further stratified by age group, the risk of developing diabetes decreased with increasing age but it remained significantly higher in women with PCOS across all age groups. It also suggested that the incidence rate of diabetes in women with PCOS aged 20-29 is highly comparable to that in healthy women aged ≥ 40. More than half of the incident diabetes captured during the follow-up in women with PCOS cohort were young-onset diabetes., Conclusion: Women diagnosed with PCOS at a younger age have the highest relative risk of developing diabetes, suggesting frequent glycemic status screening is required to detect diabetes at an early stage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Sperm chemotaxis is required for guiding sperm toward the egg. However, the molecular identity of physiological chemoattractant and its involvement in infertility remain elusive. Here, we identify DEFB19/119 (mouse/human orthologs) as a physiological sperm chemoattractant. The epithelia of the female reproductive tract and the cumulus-oocyte complex secrete DEFB19/119 that elicits calcium mobilization via the CatSper channel and induces sperm chemotaxis in capacitated sperm. Manipulating the level of DEFB19 in mice determines the number of sperm arriving at the fertilization site. Importantly, we identify exon mutations in the DEFB119 gene in idiopathic infertile women with low level of DEFB119 in the follicular fluid. The level of DEFB119 correlates with the chemotactic potency of follicular fluid and predicts the infertile outcome with positive correlation. This study reveals the pivotal role of DEFB19/119 in sperm chemotaxis and demonstrates its potential application in the diagnosis of idiopathic infertility., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control., Methods: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness., Results: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01)., Conclusion: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF19, FGF21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to compare the levels of FGF19, FGF21 and lipocalin-2 between subjects with or without PCOS, and to investigate the relationship between proteins and diabetes progression. In this nested case-control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed-up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF19 (P < 0.001) and FGF21 (P = 0.022), but had lower lipocalin-2 (P < 0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P = 0.026, odds ratio (OR) (95% CI): 7.4 (1.3-43.6)), and the positive relationship between FGF21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P = 0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P = 0.026, OR (95% CI)): 2.5 (1.1-5.6)); however, this became attenuated after adjusting for waist and fasting glucose (P = 0.081). In conclusion, there is differential expression of FGF19, FGF21, and lipocalin-2 in PCOS. The serum level of FGF19, and FGF21 is associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.

Ronald Ma and co-authors discuss Emma Norrman and colleagues' accompanying research study on the health of children born with assisted reproductive technology., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RCWM is member of the editorial board of PLOS Medicine. RCWM has received research grants for clinical trials from AstraZeneca, Bayer, MSD, Novo Nordisk, Sanofi, Tricida Inc. and honoraria for consultancy or lectures from AstraZeneca, and Boehringer Ingelheim, all used to support diabetes research at the Chinese University of Hong Kong.

Hepatitis B virus (HBV) can be found in ovarian tissues. This study compared HBV DNA levels in follicular fluid collected during oocyte retrieval with paired serum samples in HBV carriers after ovarian stimulation during IVF treatment for infertility. Sixty-four HBV carrier women referred to the Assisted Reproductive Units of two Hong Kong hospitals were recruited. At oocyte retrieval, the follicular fluid aspirated from the first follicle was collected for study. In 22 women, the first follicular fluid sample from both ovaries was similarly collected and studied. These women were also tested for liver function test and HBeAg. In 28 (43.8%) women, HBV DNA was detected in follicular fluid and the level correlated with serum levels (Spearman's correlation P < .001). There was concordant detection of HBV DNA in both ovaries, and the levels were significantly correlated (Spearman's correlation P = .029). In 40% of women with FF HBV DNA, the follicular fluid:serum ratio was >1.0, suggesting stimulation of HBV replication. These women also had significantly different liver function test results. Increased HBV replication exists in 40% of women with HBV DNA detected in follicular undergoing ovarian stimulation during IVF treatment., (© 2019 John Wiley & Sons Ltd.)

Background: Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up., Methods and Findings: One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias., Conclusions: High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: RCWM acknowledges receiving research support (outside of this work) from AstraZeneca, Bayer, and Pfizer and honoraria or consultancy fees from AstraZeneca and Boehringer Ingelheim, all of which have been donated to the Chinese University of Hong Kong to support diabetes research. CKPL, JCNC and RCWM are co-founders of GemVCare, a diabetes genetic testing laboratory, which was established through support from the Technology Start-up Support Scheme for Universities (TSSSU) from the Hong Kong Government Innovation and Technology Commission (ITC). RCWM is a member of the International Federation of Gynecology and Obstetrics (FIGO) Pregnancy and Non-communicable Diseases Committee and a member of the Executive Board of the Asian Association for the Study of Diabetes (AASD) and Worldwide Diabetes (WWD). RCWM is a member of the editorial board of PLOS Medicine.

Objective: To determine the relationship between the presence of detectable HBV DNA in the follicular fluid in HBV carriers with IVF/ICSI treatment outcome., Study Design: A prospective observational study conducted in the Assisted Reproductive Unit, a tertiary referral centre affiliated with the Department of Obstetrics and Gynecology, The Chinese University of Hong Kong; and the Union Reproductive Medicine Centre at Union Hospital, Hong Kong. The primary outcome measure was pregnancy rate. Secondary outcome measures were the prevalence of detectable HBV DNA in the follicular fluid, implantation rate, clinical pregnancy rate, ongoing pregnancy rate and live birth rate., Results: HBV DNA was detected in the follicular fluid of 28 (43.8%) of the 64 women, and the mean level in this group in log 10 copies/mL (±SD) was 4.36 ± 1.85. Women with detectable follicular fluid HBV DNA were younger, lighter, had longer duration of infertility, higher incidence of detectable serum HBV DNA (OR 4.592, 95% C I 2.333-9.038), and significantly wider range in the number of total fertilized, viable embryos, and blastocyst rate, but no difference in cycle characteristics, stimulation and pregnancy outcomes, although the almost doubled ongoing pregnancy/live birth rate per cycle initiated (60.7% versus 38.9%) failed to reach statistical significance due to the small numbers., Conclusion: Our results suggested HBV infection did not appear to be detrimental to the outcome of IVF/ICSI treatment., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Research Question: Does music therapy help in reducing pain and anxiety in women undergoing transvaginal ultrasound-guided oocyte retrieval (TUGOR)?, Design: In this randomized controlled open label study, 209 participants were recruited and randomized into three groups (music group, n = 70; headphone group, n = 70; control group, n = 69). Patients' psychological status was assessed using the visual analogue scale of pain (VAS-P), satisfaction of pain control, state-trait anxiety inventory (STAI), Beck depression inventory (BDI), and general health questionnaire (GHQ). Stress biomarkers, including salivary alpha amylase (sAA) and salivary cortisol (sCort), were measured before and after TUGOR., Results: No significant differences were found in psychological scoring of STAI, BDI, GHQ and the stress biomarkers. Although neither the anxiety scores nor the analgesic requirements differed among the three groups, the visual measure of vaginal pain (median, range) showed music group (20,0-70) was significantly (P = 0.005) lower than headphone group (30,0-90) and control group (30,0-100). The degree of satisfaction with pain control (median, range) in the music group (80,30-100), was significantly (P = 0.001) higher than the headphone group (80,10-100) and control group (70,0-100)., Conclusion: Music is a simple, inexpensive and effective way to reduce pain score and increase satisfaction with pain control during TUGOR procedure, which may justify its routine use., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: Hip fracture is associated with excess mortalities and high rate of hospital re-admission after discharge from the indexed episode. To improve related post-discharge care, we aimed to find out characteristics that were associated with related higher rates of mortality and hospital re-admission., Methods: This was a historical cohort study with following up of 273 patients recruited in a local rehabilitation hospital for 3 years. The outcome of interest was cumulative mortalities and hospital re-admissions in the 1st 3 years after their discharge from the rehabilitation hospital. These outcomes were collected in the hospital data warehouse - the Clinical Data Analysis and Reporting System (CDARS). Eighteen predictors, as proposed by similar studies and our own review, were retrieved from our standard clinical forms as well as from the CDARS. Binary logistic regression was used to test their association with the outcomes and to generate the respective odd ratios., Results: The cumulative overall mortality rates at 0.5-, 1-, 2- and 3- year after hip fracture were 7.2%, 14.0%, 24.6% and 33.4% respectively, while the cumulative "1st ever hospital read-mission" at 0.5-, 1, 2- and 3- years after hip fracture were 29.4%, 41.6%, 59.4% and 71.7% respectively. The most significant predictors i) for mortality at 3- year were: "Being male" (OR 5.33), "Delayed surgery >48 hours" (OR 2.65), "pre-operation albumin level <3.5 g/dl" (OR 2.66), and, ii) for "1st ever hospital readmission" at 0.5-year was "Being Assisted walker or non-walker (after rehabilitation)" (OR 3.83)., Conclusions: Characteristics that define the groups of patients with hip fractures with higher mortality and rate of hospital re-admission were identified. This could help healthcare professionals to focus on target patient groups for closer monitoring and more intensive post-discharge care., Competing Interests: Nil.

Polycystic ovary syndrome is the most common endocrine disorder among women of reproductive age. Although traditionally viewed as a reproductive disorder, there is increasing appreciation that it is associated with significantly increased risk of cardiometabolic disorders. Women with polycystic ovary syndrome may present to clinicians via a variety of different routes and symptoms. Although the impact on reproduction predominates during the reproductive years, the increased cardiometabolic problems are likely to become more important at later stages of the life course. Women with polycystic ovary syndrome have an approximately 2- to 5-fold increased risk of dysglycaemia or type 2 diabetes, and hence regular screening with oral glucose tolerance test is warranted. Although the diagnostic criteria for polycystic ovary syndrome are still evolving and are undergoing revision, the diagnosis is increasingly focused on the presence of hyperandrogenism, with the significance of polycystic ovarian morphology in the absence of associated hyperandrogenism or anovulation remaining uncertain. The management of women with polycystic ovary syndrome should focus on the specific needs of the individual, and may change according to different stages of the life course. In view of the clinical manifestations of the condition, there is recent debate about whether the current name is misleading, and whether the condition should be renamed as metabolic reproductive syndrome.

The benefit of endometrial scratch (ES) prior to embryo transfer is controversial. Systemic analysis has confirmed its potential benefit, especially in women with repeated IVF failures, yet most studies have focused on fresh embryo transfer, and its effect on vitrified-warmed embryo transfer (FET) cycles is yet to be explored. We hereby present our prospective, double-blind, randomized controlled study on the evaluation of the implantation and pregnancy rate after ES prior to natural-cycle FET. A total of 299 patients underwent natural-cycle FET and were randomized to receive ES (n = 115) or endocervical manipulation as control (n = 114) prior to FET cycle, and a total of 196 patients had embryo transfer (93 patients in each group). Our study showed no significant difference in the implantation and pregnancy rate, as well as the clinical and ongoing pregnancy or live birth rates between the two groups. It appears that ES does not have any beneficial effect on an unselected group of women undergoing FET in natural cycles. Further studies on its effect in women with recurrent implantation failure after IVF are warranted., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In this prospective cohort study of 286 women undergoing fresh embryo transfer after IVF, uterine contraction frequency and direction were measured before (-5 min), 5 min after (+5 min) and 60 min after (+60 min) embryo transfer. Mean ± SD uterine contraction frequency at -5 min was 1.8 ± 1.1 contractions per min, increasing significantly (P < 0.05) to 2.0 ± 1.1 at +5 min, and returning back to baseline 1.8 ± 1.1 at +60 min. At -5 min, the proportion of women the with retrograde, antegrade, indeterminate direction and absent contractions were 33%, 44%, 17% and 6%; at +5 min, 40%, 42%, 13% and 5%, and at +60 min, 42%, 38%, 14% and 6%. No significant change was observed in the proportion of direction at these three time points. Logistic regression analysis showed live birth rate was significantly reduced in older women (P = 0.035) and in those with higher uterine contraction frequency at +5 min (P = 0.006). Frequency of uterine contraction immediately after embryo transfer (+5 min) seemed to be a significant predictor of IVF outcome and may help to identify women who could benefit from the use of muscle relaxant therapy to improve outcome., (Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Luteinizing hormone (LH) is crucial for the development of follicular growth and oocyte maturation, especially in the management of poor ovarian responders (PORs). This study presents the results of a prospective double-blinded randomized study to compare the effect of mid-follicular phase recombinant LH (rLH) supplementation with urinary human chorionic gonadotrophin (uHCG) supplementation when using a fixed gonadotrophin-releasing hormone (GnRH) antagonist protocol in IVF cycles. A total of 49 women with poor ovarian response (POR) according to the Bologna criteria were recruited. This study showed no statistically significant difference in cycle cancellation rates, numbers of oocytes retrieved per cycle initiated, fertilization rates, the numbers of embryos obtained per cycle initiated, implantation, clinical pregnancy and live birth rates, although the live birth rate per cycle initiated in the uHCG group (29.2%) was 3.6 times that of the rLH group (8.0%). Further studies are required to verify if uHCG supplementation produces better clinical outcomes compared with rLH in women with POR., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Study Question: Does three-dimensional (3D) versus two-dimensional (2D) ultrasound (US) guidance during embryo transfer (ET) increase the ongoing pregnancy rate in women undergoing ART treatment., Summary Answer: There is no significant difference in the ongoing pregnancy rate of women undergoing 3D versus 2D US-guided ET., What Is Known Already: Studies have suggested that 3D US may confer additional benefits compared with 2D US during ET, although this has not been tested within the context of an RCT., Study Design, Size, Duration: This was a single-blind, single centre prospective RCT performed between April 2015 and April 2016. A total of 481 recruited women were randomised into either a 3D or 2D US-guided ET group., Participants/materials, Setting, Method: Women younger than 42 years in whom the endometrial cavity could be adequately visualised by US underwent ET in a university ART unit following a standard treatment protocol. All US examinations were performed by a single operator. In both 3D and 2D US groups, the inner catheter tip was aimed at the centre of the uterine cavity. The primary outcome measure was ongoing pregnancy rate, defined as the presence of at least one foetus with heart pulsation at 8 weeks of gestation., Main Results and the Role of Chance: There was no significant difference in the ongoing pregnancy rate between the 3D and 2D US groups (35.4% versus 37.1%, P = 0.70; rate ratio 0.96, 95% confidence interval 0.75-1.21). There were also no significant differences in terms of positive hCG rate, biochemical pregnancy rate, implantation rate, clinical pregnancy rate, miscarriage rate, ectopic pregnancy rate and multiple pregnancy rate., Limitations, Reasons for Caution: This study recruited unselected women undergoing routine ET and was therefore not sufficiently powered to assess differences in subsets of women., Wider Implications of the Findings: Although 3D US may be a modern method for demonstrating the ET procedure, it should not be currently recommended as a strategy to improve clinical outcomes in women undergoing ART treatment., Study Funding/competing Interests: This study was funded by the Health and Medical Research Fund of Hong Kong. The authors have no conflicts of interest to disclose., Trial Registration Number: ClinicalTrials.gov Identifier: NCT02413697., Trial Registration Date: 4 April 2015., Date of First Patient's Enrolment: 20 April 2015., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Question: Does the air bubble (embryo flash) position and migration as visualized with 3D ultrasound (US) within 60 min of embryo transfer correlate with clinical outcome following fresh ART transfer cycles?, Summary Answer: The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, are associated with clinical pregnancy., What Is Known Already: Studies assessing the relation between the pregnancy rate and the position of the catheter tip and/or the position of the air bubbles following embryo transfer show conflicting results to date., Study Design, Size and Duration: This was a prospective cohort study including 277 infertile women undergoing ART between July 2011 and August 2013., Participants/materials, Setting and Methods: Good prognosis patients undergoing fresh ART cycles within a single tertiary University unit were assessed by 3D US at 1, 5 and 60 min after embryo transfer. The distance of the embryo flash from the fundus was measured at these time points, along with the direction of the embryo flash movement within 60 min of transfer., Main Results and the Role of Chance: Within 60 min of embryo transfer, 76.4% (198/259) of the embryo flashes migrated towards the fundus, 12.4% (32/259) migrated towards the cervix and 11.2% (29/259) remained static. There was no significant association between the embryo position or movement and the pregnancy rate at 1 and 5 min. At 60 min, however, the pregnancy and implantation rates among subjects with embryo flashes located <15 mm from the fundus was significantly higher than those with embryo flashes located >15 mm from the fundus (46.5 and 32.8% versus 25.8 and 18.2%, respectively; P < 0.05). The pregnancy and implantation rates when the embryo flash was seen moving towards the cervix (25.0 and 15.0%) was significantly lower (P < 0.05 and P < 0.01, respectively) compared with those remaining static (55.2 and 37.7%) or moving towards the fundus (45.5 and 32.8%)., Limitations and Reasons for Caution: Although the air bubbles seen at the time of embryo transfer are thought to represent the position of the embryo, they are in fact a surrogate marker of the embryo itself, as this cannot be directly visualized by US., Wider Implications of the Findings: Following embryo transfer the majority, but not all, embryo flashes undergo significant migration towards the fundus. The location of the embryo flash and the direction of its movement at 60 min, but not at 1 or 5 min after transfer, is associated with clinical outcome. These findings may challenge the traditional notion that the exact position of the embryo flash immediately following embryo transfer is related to clinical outcome., Study Funding/competing Interests: The authors have no relevant funding or conflicts of interest to disclose., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Postoperative pain often is the limiting factor in the rehabilitation of patients after hip fracture surgery., Questions/purposes: We compared an approach using scheduled analgesic dosing with as-needed analgesic dosing in patients after hip fracture surgery, to compare these approaches in terms of (1) resting and dynamic pain intensity, (2) postoperative patient mobility, and (3) functional end points., Methods: We conducted a prospective cohort study of 400 patients who underwent surgical treatment of hip fractures at our hospital. The groups were formed sequentially, such that the first 200 patients formed the intervention group (treated with scheduled analgesic intake for the first 3 weeks after surgery), and the next 200 patients were the control group (treated using a protocol of analgesic administration on request). Resting and dynamic pain intensity, mobility, and functional performance were compared between the two analgesic protocols., Results: As expected, analgesic consumption was lower in the control group (tramadol doses, 27 versus 63; paracetamol doses, 29 versus 63). Despite the large difference in the amounts of analgesics consumed, resting and dynamic pain intensity showed improvement in each group and there was no difference between groups in terms of postoperative pain. However, there was a positive correlation between functional outcomes and analgesic consumption in the control group. The intervention group achieved higher functional performance on discharge (elderly mobility scale, 11 versus 8; functional independence measure, 88 versus 79). On discharge, fewer patients in the intervention group were wheelchair ambulators (3 versus 32), meaning more patients in the intervention group were able to walk., Conclusions: The study showed that a scheduled analgesic intake can improve the functional outcomes of patients with geriatric hip fractures after surgery., Level of Evidence: Level II, therapeutic study. See the guidelines for authors for a complete description of levels of evidence.

Objective: To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS)., Design: Randomized controlled double-blind trial., Setting: A tertiary referral center, Hong Kong., Patient(s): Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70)., Intervention(s): Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months., Main Outcome Measure(s): Menstrual status as well as clinical and biochemical hyperandrogenism., Result(s): There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms., Conclusion(s): We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population., Clinical Trial Registration Number: ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry)., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Visceral fat is believed to be important in the pathogenesis of metabolic syndrome and fatty liver. In this study, we examined the relationship between mesenteric fat thickness and other sonographic indices of adiposity and the presence of fatty liver among subjects with polycystic ovary syndrome (PCOS)., Subjects and Methods: A total of 117 Chinese subjects with PCOS were evaluated (mean age, 28.6 ± 6.5 yr; mean body mass index, 24.3 ± 5.3 kg/m(2)). Anthropometric measurements and metabolic risk profile, including a standard oral glucose tolerance test, were assessed in all subjects. All subjects underwent an ultrasound examination for measurement of thickness of mesenteric, preperitoneal, and sc fat as well as evaluation for fatty liver., Results: Forty-six (39.3%) of the subjects had fatty liver. PCOS subjects with fatty liver had higher body mass index, waist circumference, waist-hip ratio, and systolic blood pressure; a more unfavorable lipid profile with higher triglyceride; lower high-density lipoprotein cholesterol; higher fasting glucose and insulin; higher 2-h glucose during oral glucose tolerance test; lower SHBG; and higher alanine aminotransferase. Subjects with fatty liver had increased thickness of preperitoneal, mesenteric, and sc fat, as well as increased carotid intima-media thickness. Abdominal fat thickness showed moderate correlation to alanine aminotransferase as well as fasting insulin. On multivariate logistic regression, fasting insulin and mesenteric fat thickness were identified as independent predictors of fatty liver among subjects with PCOS., Conclusion: Fatty liver is present in a significant proportion of Chinese patients with PCOS. Sonographic measurement of mesenteric fat is an independent determinant of fatty liver among subjects with PCOS and identifies subjects at increased cardiovascular risk.

Objective: To compare the effects of laparoscopic ovarian drilling in treating infertile polycystic ovarian syndrome in patients with and without metabolic syndrome., Design: Retrospective review., Setting: A university-affiliated hospital in Hong Kong., Patients: A total of 89 infertile anovulatory polycystic ovarian syndrome patients, who underwent laparoscopic ovarian drilling with completed metabolic screening and seen over a 5-year period from 2002 to 2007., Main Outcome Measures: The clinical, hormonal, and metabolic characteristics as well as spontaneous ovulation rates, reproductive outcomes, and diabetes risks during pregnancy observed after laparoscopic ovarian drilling., Results: Approximately one fifth (21%) of polycystic ovarian syndrome patients had the metabolic syndrome. There were no differences in spontaneous ovulation rates (68% vs 61%, P=0.76), cumulative pregnancy rates (68% vs 61%, P=0.77), and diabetes risks during pregnancy (64% vs 42%, P=0.13) between patients with and without metabolic syndrome., Conclusion: Laparoscopic ovarian drilling was equally effective in inducing ovulation in polycystic ovarian syndrome patients with metabolic syndrome. Thus, patients with metabolic syndrome should not be precluded from laparoscopic ovarian drilling, which has the additional advantage of enabling full tubo-peritoneal assessment at the same time.

Objective: To examine the prevalence of hepatitis B virus (HBV) infection, the associated causes of subfertility, and the outcomes of the first IVF and embryo transfer treatment cycles in these infertile couples., Design: A retrospective cohort study., Setting: Assisted reproduction technology (ART) unit., Patient(s): Two hundred eighty-seven couples undergoing IVF and embryo transfer cycles., Intervention(s): Analysis of data on patients' characteristics, controlled ovarian hyperstimulation (COH), embryology, and pregnancy (PR) and implantation rates of IVF and embryo transfer cycles according to HBV serostatus of the infertile couples, which was routinely screened., Main Outcome Measure(s): The PRs and the implantation rates., Result(s): Twenty-nine (10.1%) women were HBV seropositive, whereas 32 (11.1%) of their husbands were HBV seropositive. Concerning the causes of infertility, there was a trend toward more tubal blockage (57.1% vs. 42.2%) in the HBV-infected group. Among the 190 women undergoing their first IVF and embryo transfer cycles, both the ongoing PR or live birth rate and implantation rate in HBV group were significantly higher than the controls (53.3% vs. 24.2% per cycle with embryo transfer; and 43.3% vs. 18.4%, respectively)., Conclusion(s): Our results demonstrate for the first time significantly higher PRs and implantation rates of IVF and embryo transfer cycles for couples with at least one partner being HBV seropositive. Further studies to elucidate the underlying mechanisms are warranted., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: This investigation assessed the effect of serum estradiol levels on outcomes of in-vitro fertilization and embryo transfer (IVF) cycles., Materials and Method: This was a retrospective cohort study of 1123 IVF cycles comparing impact of estradiol (E(2)) levels on follicular development, fertilization, embryo quality, implantation, pregnancy rate, miscarriage rate, and selected obstetric complications., Results: We found high serum E(2) levels to be significantly associated with increased number of mature follicles and mature oocytes retrieved (p<0.01, for both). E(2) levels were also associated with more viable and good-quality embryos (p<0.01). There was no significant impact of E(2) on oocyte maturation, fertilization rate, embryo quality, or overall pregnancy rates. Moreover, high E(2) levels were significantly associated with higher implantation rates and reduced incidence of miscarriage (p<0.05, for both)., Conclusion: Within the safety range in clinical practice, our data demonstrate a generally positive effect of high serum E(2) on selected IVF parameters.

Only about 63% of Chinese women with polycystic ovarian syndrome (PCOS) as diagnosed by the 2003 Rotterdam criteria fulfilled the 1990 National Institutes of Health (NIH) diagnostic criteria. Although the NIH criteria are not generally applicable to the Chinese population, women fulfilling the NIH criteria have higher metabolic risk than those who do not and so carry the most clinical significance.

Background: Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidaemia and hypertension which are characteristic features of the metabolic syndrome (MetS)., Methods: A total of 295 premenopausal Chinese women with PCOS diagnosed by the Rotterdam criteria (mean age: 30.2 +/- 6.4 years) and 98 control subjects without PCOS were evaluated for prevalence of MetS and cardiovascular risk factors, including dyslipidaemia and dysglycaemia., Results: Using the 2005 modified Adult Treatment Panel III criteria, MetS (presence of three or more risk factors) was found in 24.9% of PCOS women compared to 3.1% of controls. The prevalence of MetS in PCOS women increased from 16.7% at under 30 years of age to 53.3% at over 40 years. MetS was also more prevalent in overweight and obese (41.3%) than normal-weight PCOS women (0.9%). However, multivariate regression analysis showed that women with PCOS had a 5-fold increase in risk of MetS (odds ratio 4.90; 95% confidence interval: 1.35-17.84) compared with women without PCOS even after controlling for age and BMI, suggesting PCOS alone is an independent risk factor for MetS., Conclusions: There is high prevalence of MetS in Hong Kong Chinese women with PCOS despite their relatively young age. Recognition of these cardiometabolic risk factors requires a high level of awareness in conjunction with early and regular screening.

Objective: To identify predictors of rehabilitation outcomes for the development of a case-mix system to rehabilitate patients suffering from hip fractures., Design: Prospective cohort study., Setting: Two hospitals in Hong Kong., Patients: A cohort of hip fracture patients in 2005 (n=303) with a mean age of 82 years was studied. Rehabilitation outcomes were defined as: mortality, length of stay, placement, ambulation status, activity of daily living at the time of discharge and at 6-month follow-up. A comparison between groups and multivariate analysis was conducted to validate the best predictors., Main Outcome Measures: Potential predictors and rehabilitation outcomes., Results: Two predictors, the Abbreviated Mental Test score of lower than 6 (odds ratio=0.19, P<0.05) and the Functional Independence Measures score of lower than 75 (odds ratio=38.0, P<0.05), at the time of admission to the rehabilitation setting were found to be related to outcomes. Our findings provided further support for a case-mix system based on these two factors, as they could correctly assign patients into three groups with different baseline characteristics and outcomes. A review of the possible limitations of the existing service with respect to each case-mix group was also conducted., Conclusion: A case-mix system utilising the cognition and activity of daily living function is recommended. Revisions of respective care plans are advocated with more realistic outcome expectations and specific actions for the respective case-mix groups. An evaluation study on the usefulness of this case-mix classification could then follow.

Objectives: To identify the characteristics of Hong Kong Chinese women with polycystic ovarian syndrome and to compare different diagnostic criteria., Design: Retrospective study., Setting: Gynae-endocrinology Clinics in the Prince of Wales Hospital, Hong Kong., Patients: Ninety Hong Kong Chinese women with polycystic ovarian syndrome who were diagnosed according to the hospital's criteria., Main Outcome Measures: Prevalence of typical features of polycystic ovarian syndrome, including anovulation and hyperandrogenism (with other endocrine causes excluded), polycystic ovarian features on ultrasonography, luteinising hormone predominance, obesity, and insulin resistance., Results: Almost all (98.9%) patients with polycystic ovarian syndrome presented with anovulation, only 48.9% of them had clinical or biochemical evidence of hyperandrogenism. Typical ultrasound appearances of polycystic ovaries were observed in 86.7% of patients. Luteinising hormone predominance and insulin resistance were demonstrated in 67.8% and 40.7% of the cohort, respectively. Eight-six (95.6%) patients should have also been diagnosed with polycystic ovarian syndrome based on the 2003 Rotterdam new criteria. About 60% of patients who screened positive for insulin resistance had normal fasting serum glucose levels. The same proportion who had full screening for insulin resistance by oral glucose tolerance tests and fasting serum glucose to insulin ratios had discordant results of these two tests., Conclusions: The 2003 Rotterdam new diagnostic criteria for polycystic ovarian syndrome are generally applicable to the Hong Kong Chinese population. Early detection of insulin resistance in patients with polycystic ovarian syndrome can be ensured by performing an oral glucose tolerance test combined with measurement of fasting serum glucose to insulin ratio.

Purpose: To evaluate the responses of cultured oviduct mucosal cells to exogenous estradiol treatment in regulating the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors., Methods: The mucosal layer of the ampullary regions of the human oviduct was isolated and cultured with (study groups) or without (control group) the addition of exogenous estradiol in five different concentrations. Semiquantitative reverse-transcriptase-polymerase chain reaction was performed on the oviduct mucosal cells before and after the 6-day culture., Results: There were no significant differences in the mRNA expression of VEGF and its receptors, both KDR and flt-1, between the five study groups and the control group., Conclusions: The mRNA expression of VEGF and its receptors is not altered by exogenous estradiol treatment in cultured oviduct. This helps to explain the mechanism of temporal regulation of VEGF in human oviduct, which reaches the peak level in the peri-ovulatory stage when both the serum estradiol and gonadotropins concentrations are high.

Objective: To report the birth of a healthy baby after transfer of blastocysts derived from frozen eggs and frozen spermatozoa., Design: Case report., Setting: University-based assisted reproduction center., Patient(s): A 37-year-old woman with secondary infertility of 4 years' duration., Intervention(s): Retrieved oocytes were cryopreserved in 1.5 M 1,2-propanediol (PROH) and 0.3 M sucrose by a slow freezing-rapid thawing protocol, semen cryopreservation, and insemination by intracytoplasmic sperm injection (ICSI) at 4 hours after thawing., Main Outcome Measure(s): Fertilization and embryo development to blastocyst stage, pregnancy, and outcome., Result(s): Ten of 14 frozen oocytes survived after thawing. Eight of them were fertilized by performing ICSI and three developed into 7- to 8-cell embryos on day 3. Two of these embryos developed into blastocysts on day 5 and were transferred. This resulted in a successful pregnancy and the delivery of a healthy baby boy., Conclusion(s): This case demonstrates the feasibility of inseminating the frozen-thawed human oocytes after 4 hours of in vitro culture and the zygotes derived from frozen oocytes and frozen spermatozoa can be cultured to blastocysts resulting in the live birth of a healthy baby boy.

Background: This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF., Methods: Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation., Results: There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant., Conclusion: A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.

The mucosal cells were isolated from the ampullary regions of 20 human oviducts and cultured with or without hCG in five different concentrations (1-100 ng/mL). As analyzed by the semiquantitative reverse-transcriptase polymerase chain reaction, hCG treatment significantly increased mRNA expression of vascular endothelial growth factor and its receptor flt-1 in the cultured mucosal cells in a dose-dependent manner but had no effect on the expression of another receptor, KDR.

Objective: To compare the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1) in the implantation and nonimplantation sites of the human oviduct with ectopic gestation., Design: Prospective observational study., Setting: University-based Obstetrics and Gynecology Department., Patient(s): Ten women undergoing laparoscopic salpingectomy for tubal pregnancy., Intervention(s): The mucosal layer was isolated from the implantation and nonimplantation sites of the oviduct tissue with ectopic gestation. Semiquantitative reverse transcriptase-polymerase chain reaction was performed., Main Outcome Measure(s): The differences in the mRNA expression of VEGF and its receptors between the implantation and nonimplantation sites of the oviduct tissue., Result(s): The mRNA expression of VEGF and its receptors, both KDR and flt-1, was significantly higher in the implantation site of the human oviduct with ectopic gestation compared with the nonimplantation site., Conclusion(s): The results suggest that VEGF may be the angiogenic factor responsible for the implantation and placentation of an ectopic pregnancy in the oviduct.

Objective: To evaluate the effect of adjuvant low-dose aspirin on utero-ovarian blood flow and ovarian responsiveness in poor responders undergoing IVF., Design: Prospective randomized, double-blind, placebo-controlled study., Setting: University-affiliated teaching hospital., Patient(s): Sixty patients classified as poor responders undergoing IVF., Intervention(s): Supplementation with low-dose aspirin (80 mg daily) or placebo to a long down-regulation protocol., Main Outcome Measure(s): Doppler measurement of intraovarian and uterine pulsatility index was performed before (baseline) and after ovarian stimulation (day of hCG administration). Duration of use and dose of gonadotropins, cycle cancellation rate, number of mature follicles recruited, and oocytes retrieved were also measured., Result(s): High cancellation rates were found in both groups (33.3% vs. 26.7%, placebo vs. treatment). There were no significant differences in total dose of hMG used (66 vs. 57 hMG, 75 IU ampules), median number of mature follicles recruited (3.5 vs. 3.0), or median number of oocytes retrieved (4 vs. 3). No significant differences were found in either intraovarian or uterine artery pulsatility index measured at baseline or on the day of hCG administration., Conclusion(s): Supplementation with low-dose aspirin failed to improve either ovarian and uterine blood flow or ovarian responsiveness in poor responders undergoing IVF.

Objective: To determine whether oviduct mucosal cell culture with exogenous 17beta E(2) supports the continued production of oviductin, a putative embryotrophic protein., Design: Semiquantitative reverse-transcriptase polymerase chain reaction analysis of oviductin mRNA expression after oviduct mucosal cell culture in the presence of 17beta E(2). Three different culture systems were studied to investigate the response to E(2)., Setting: University-based obstetrics and gynecology department., Subjects: Oviduct tissue was obtained from 18 women undergoing laparoscopy for benign gynecologic conditions., Intervention(s): The mucosal layer was isolated from the oviduct tissue and exposed to three different culture systems, which contained various concentrations of 17beta E(2), or vehicle-only control., Main Outcome Measure(s): The relationship between exposure to 17beta E(2) and expression of oviductin messenger (m)RNA by cultured oviduct mucosal cells., Result(s): There was a significant increase in oviductin mRNA expression after the addition of 17beta E(2) to the culture system in which the in vivo cell-to-cell and cell-to-basement-membrane contacts of the oviduct had been maintained., Conclusion(s): Estradiol failed to alter oviductin mRNA expression in oviduct mucosal cells cultured under conditions in which the ciliated mucosal cell phenotype plus the cell-to-cell and cell-to-basement-membrane contacts of the oviduct were lost. However, with a culture system that maintained the cell architecture, E(2) initiated and significantly increased oviductin mRNA expression.

Objective: To examine the localization of vascular endothelial growth factor receptors (VEGF-R) and the changes in VEGF-R messenger ribonucleic acid (mRNA) expression in various regions of the oviduct from fertile women throughout the ovulatory cycle., Design: Prospective observational study., Setting: University-based obstetrics and gynecology department., Patient(s): Twenty-two women who underwent laparoscopic tubal sterilization or hysterectomy for a benign gynecological condition., Intervention(s): The mucosal layer was isolated from the oviduct tissue. Immunohistochemistry and a semiquantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) was performed., Main Outcome Measure(s): Immunohistochemical localization of VEGF-R proteins in oviduct tissue, and the differences of VEGF-R mRNA expression in the various regions of the oviduct and in the various stages of the ovulatory cycle., Result(s): Immunohistochemical study localized VEGF-R, both KDR and flt-1, in the oviduct luminal epithelium, smooth muscle cells as well as blood vessels within the oviduct. Messenger RNA expression of KDR, but not flt-1, was significantly higher in the ampullary and infundibular regions than in the isthmus. Messenger RNA expression of flt-1, but not KDR, varied significantly in the oviduct along the course of an ovulatory cycle, with the highest level in the periovulatory stage., Conclusion(s): These results suggest that the two VEGF receptors may have different roles in the oviduct. Our data support a role for KDR in oviduct angiogenesis whereas flt-1 appears to be important in the temporal regulation of oviductal secretion.

Background: The adverse effects of hydrosalpinx on the outcomes of IVF have been well documented, but the mechanisms of hydrosalpinx fluid formation remain unclear. This study compares the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1) in the hydrosalpinx with that in the healthy oviduct., Methods: Oviduct tissue was collected from 10 infertile women with hydrosalpinx and 10 parous women with healthy oviduct. The mRNA expression of VEGF and its receptors in isolated oviduct epithelial cells were analysed using semi-quantitative reverse-transcriptase PCR., Results: mRNA expression of VEGF and its receptor flt-1 in the hydrosalpinx was significantly higher than that in the healthy oviduct, but no significant difference was demonstrated for the KDR receptor., Conclusions: This study supports the notion that VEGF may play an important role in the hydrosalpinx fluid formation, possibly by promoting vascular and epithelial permeability and therefore serum transudation.

Objective: To determine whether oviduct mucosal cell culture with exogenous hCG or 17-beta estradiol (E(2)) supports the continued production of oviductin, a putative embryotrophic protein., Design: Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of oviductin mRNA expression after oviduct mucosal cell culture in the presence of hCG or 17-beta E(2)., Setting: University-based Obstetrics and Gynecology Department., Subject(s): Ten women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids., Intervention(s): The mucosal layer was isolated from the oviduct tissue, subjected to routine culture conditions with the addition of various concentrations of hCG or 17-beta E(2) or the equivalent vehicle-only control and semiquantitative RT-PCR performed., Main Outcome Measure(s): The relationship between exposure to hCG or 17-beta E(2) and expression of oviductin mRNA by cultured oviduct mucosal cells., Result(s): There was a significant increase in oviductin mRNA expression after the addition of hCG to the culture medium but only in samples that had maintained a baseline level of oviductin expression. Addition of 17-beta E(2) to the culture medium had no significant effect on oviductin mRNA expression., Conclusion(s): Under standard cell culture conditions, baseline human oviductin mRNA expression is increased by the addition of hCG. This effect is likely to be a secondary or synergistic effect as exogenous hCG failed to restore oviductin mRNA expression in samples where expression was lost after culture. E(2) failed to alter oviductin mRNA expression in oviduct mucosal cells cultured under these conditions.

Objectives: To evaluate the supplementation of leukemia inhibitory factor (LIF) or epidermal growth factor (EGF) in a single culture system (IVF50) and a sequential culture system (IVF50-S2) to determine whether they had any additional benefit on embryo development and implantation., Design: Prospective controlled animal study., Setting: University research laboratory., Subject(s): Two-cell embryos from F1(CBA x C57BL) mice., Intervention(s): Embryos were randomly cultured in different growth factor-treated or untreated in vitro systems., Main Outcome Measure(s): Blastocyst formation and morphology, total cell numbers of day 5 blastocysts, birth rates, and characteristics of the offspring., Result(s): The beneficial effects of LIF or EGF on blastocyst development and morphology were observed only in IVF50 medium but not in sequential IVF50-S2 media. In addition, blastocysts generated from the LIF-supplemented cultures had higher total cell numbers and higher total birth rates after transfer compared to those from IVF50 medium alone. No significant effect on fetal development was observed but pups born after treatment in LIF-supplemented sequential cultures had prolonged gestation and increased birth weights., Conclusion(s): The beneficial effects of LIF and EGF on in vitro blastocyst development are mainly seen under suboptimal culture conditions (simple medium only) and their effects are masked in an improved in vitro system (sequential culture media). Supplementation of culture media with such factors, however, is still an attractive approach in enhancing embryo viability through increased total cell numbers. The beneficial effect of LIF in improving implantation and subsequent increased birth rates should be further explored.

In this study, we examined the localization of vascular endothelial growth factor (VEGF) and the changes in VEGF mRNA expression in various regions of the oviduct in fertile women throughout the ovulatory cycle. Oviduct tissue was collected from 22 women undergoing laparoscopic tubal sterilization or hysterectomy for a benign gynecological condition. Oviduct sections were divided into isthmus, ampullary, and infundibular regions. Serial cross sections were analyzed for the presence of VEGF by specific immunohistochemical staining. The mucosal layer was isolated, and a semiquantitative reverse transcription polymerase chain reaction was performed. Immunohistochemical study revealed VEGF in the oviduct luminal epithelium, smooth muscle cells, and blood vessels within the oviduct. VEGF mRNA expression in oviduct was the highest during the periovulatory stage, and the expression in the ampullary and infundibular regions was higher than that in the isthmus. There was a significant positive correlation between serum FSH and LH concentrations and VEGF mRNA expression. There was no significant correlation between serum estradiol and progesterone concentrations and VEGF mRNA expression. These results suggest that VEGF in human oviduct may play an important role related the early reproductive events, which occur predominantly in the ampulla during the periovulatory phase when serum FSH and LH concentrations are high.

Background: Hydrosalpinx fluid may be toxic to sperm and early embryo growth. Information concerning the effect of hydrosalpinx fluid on embryo development during organogenesis is lacking., Methods: Rat embryos at gestational day 9.5 were cultured for 48 h with 80% rat serum and 20% of either hydrosalpinx fluid (study group) or lactated Ringer's solution (control group). Embryos were scored for growth and development at the end of the culture period., Results: Hydrosalpinx fluid, collected from 10 patients, was tested for embryotoxicity individually. Median total morphological scores were significantly lower in embryos exposed to hydrosalpinx fluid from three of the 10 patients (43.0 versus 47.0, P = 0.01; 36.0 versus 45.0, P < 0.001; 36.0 versus 46.5, P = 0.003). This was accompanied by a significant reduction in median yolk sac diameter (4.0 versus 5.2 mm, P < 0.001 and 4.0 versus 5.0 mm, P < 0.001) and somite number (17.5 versus 22.5, P < 0.001 and 17.0 versus 21.5, P = 0.008) in the latter two patients., Conclusions: Hydrosalpinx fluid in some patients may contain toxin(s) that is potentially teratogenic.

Objective: To examine the accuracy of clinical diagnostic methods in assessing vaginal bleeding in pregnant women before 28 weeks' gestation., Methods: 772 consecutive women who presented with threatened abortion before 28 weeks' gestation were studied. Structured history and physical examination were performed on each woman as initial clinical assessment. This was followed by transvaginal sonography to determine the status of pregnancy. The accuracy of diagnoses at different clinical stages (history, physical examination, and transvaginal sonography) relative to the final diagnosis was compared using the kappa coefficient (kappa)., Results: Clinicians were unable to accurately diagnose or predict the status of the pregnancy from history alone (kappa = 0.33; 95% CI 0.28, 0.38) or after physical examination (kappa = 0.57; 95% CI 0.52, 0.62). Transvaginal sonography led to an accurate diagnosis of pregnancy status (kappa = 0.96; 95% CI 0.95, 0.98) in most cases, except where an ectopic pregnancy existed. Absence of abdominal tenderness (p = 0.04), cervical excitation (p = 0.02), and incorrect identification of retained products of conception on transvaginal sonography (p = 0.01) were features of missed ectopic pregnancy., Conclusions: The clinical assessment of threatened abortion by history and physical examination is unreliable in most cases. The diagnostic accuracy is improved by the addition of transvaginal sonography. Even with the help of transvaginal sonography, a small proportion of ectopic pregnancies will be missed., (Copyright 2003 S. Karger AG, Basel)

Objective: To compare blood mercury concentrations of infertile couples with those of fertile couples in Hong Kong, and to examine the relationship between blood mercury concentrations and seafood consumption., Design: Case-control study., Setting: In vitro fertilisation (IVF) Unit and Antenatal Unit of a university teaching hospital. Sample One hundred fifty-seven infertile couples attending IVF treatment and 26 fertile couples attending antenatal care without known occupational exposure to mercury., Methods: Mercury concentrations in whole blood were measured by cold vapour atomic absorption spectrophotometry. A dietitian recorded the quantity of seafood consumption among infertile couples via a food-frequency questionnaire. Blood mercury concentrations and quantity of seafood consumption were compared between infertile and fertile couples., Main Outcome Measures: Whole blood mercury concentrations, quantity of seafood consumption., Results: Infertile couples had higher blood mercury concentrations than fertile couples. 'Infertile males with abnormal semen' and 'infertile females with unexplained infertility' also had higher blood mercury concentrations than their fertile counterparts. Blood mercury concentrations were positively correlated with quantity of seafood consumption. Infertile subjects with elevated blood mercury concentrations consumed a larger amount of seafood., Conclusion: Higher blood mercury concentration is associated with male and female infertility. Higher seafood consumption is associated with elevated blood mercury concentrations in our infertile population.

Background: This open label study compared the effectiveness of patient-controlled sedation (PCS), with physician-administered sedation (PAS) during transvaginal ultrasound-guided oocyte retrieval (TUGOR)., Methods: A total of 106 patients was randomized using a computer model to receive either PCS (n = 51) or PAS (n = 55). Intra-operative sedation and co-operation were measured on a 5-point scale while severity of pain, and doctor and patient satisfaction were assessed using a 100 mm visual analogue scale. Number of oocytes retrieved and fertilization, cleavage and clinical pregnancy rates were also recorded., Results: Levels of sedation and co-operation were similar between groups. The pain score was higher in the PCS group during (mean +/- SD, 53 +/- 23 versus 35 +/- 24; P < 0.01) and 2 h after the procedure (29 +/- 27 versus 17 +/- 22; P < 0.05). Doctors were less satisfied with PCS than PAS (62 +/- 25 versus 71 +/- 26; P < 0.05) while patients were highly satisfied with both methods (76 +/- 23 versus 74 +/- 21; not significant). There were no oversedation or peri-operative complications. Fertility outcomes were similar. Patients tended to prefer PCS when given the choice of sedation method., Conclusion: Although PCS provides less analgesia then PAS during TUGOR, it is safe, satisfactory and accepted by patients.

Background: The follicular microenvironment is an important determinant of oocyte development. The aim of this study was to examine whether the myo-inositol (MI) content in human follicular fluid (FF) was associated with better oocyte quality., Methods: A total of 53 patients treated with IVF was recruited to a prospective observational study. FF and serum samples collected were divided into two groups: group A consisted of FF associated with matured and fertilized oocytes, whilst group B was from follicles with immature and unfertilized oocytes., Results: Patient's age, total ampoules of HMG used, days of stimulation, basal levels of FSH, estradiol (E(2)) levels on the day of HCG, and serum MI content were not significantly different between the two groups. FF volume and its MI content were significantly higher in group A compared with group B (P < 0.05). The levels of MI in FF were positively correlated with the amount of E(2) in their corresponding FF samples and also correlated with embryo quality., Conclusions: We propose that higher concentrations of MI and E(2) in human FF appear to play a role in follicular maturity and provide a marker of good quality oocytes.

Study Objective: To determine the frequency of intrauterine adhesions (IUA) after conservative management, medical evacuation, and surgical evacuation for spontaneous abortion., Design: Prospective follow-up study (Canadian Task Force classification II-2)., Setting: Gynecology unit in a teaching hospital., Patients: Eighty-two women who had been treated with conservative management, medical evacuation, or surgical evacuation of retained products of conception after spontaneous abortions in a randomized, controlled trial., Measurements and Main Results: Hysteroscopic diagnosis of IUA 6 months after initial treatment was the primary outcome measure. No cases of IUA were found in patients managed conservatively or by medical evacuation, whereas two cases (7.7%) of filmy IUA were detected in those managed by surgical evacuation. There was no statistical significant difference in the rate of self-reported reduced menstrual flow 6 months after initial treatment by any method., Conclusion: The prevalence of IUA was low after each modality of treatment for spontaneous abortion. Conservative management and medical evacuation are both acceptable alternatives to standard surgical evacuation.

Gonadotropin releasing hormone agonists (GnRHa) are commonly used during in vitro fertilization and embryo transfer (IVF/ET) treatment cycles to downregulate the hypothalamic-pituitary-ovarian axis prior to ovarian stimulation with gonadotropins. It has been suggested that profound downregulation may have an adverse effect on IVF/ET outcome. The aim of this study was to examine the relationship between the degree of downregulation and IVF/ET outcome. A retrospective analysis was performed on 151 IVF/ET cycles conducted over a six month period. Intensity of downregulation was assessed using measurements of serum concentrations of luteinizing hormone (LH) and estradiol (E2) made at the end of a two week downregulation period. There was no correlation between serum concentration of LH (whether used alone or in combination with E2) and IVF/ET pregnancy rates. However, those subjects who were more suppressed according to the E2 concentration (< 148 pmol/l, [median]) required significantly more gonadotropins (3306 IU versus 2863 IU, p < 0.05) and took longer for follicles to reach maturity (10.9 days versus 9.7 days, p < 0.05). They also had a lower pregnancy rate per embryo transfer (10.4% versus 28.6%, p < 0.05) compared with those having a higher basal E2 concentration. We conclude from this study that the basal serum E2 concentration rather than the LH concentration is a more sensitive indicator of the intensity of downregulation by GnRHa and it may be a better predictor of IVF outcome.

Objective: To determine whether oviduct mucosal cell culture supports the continued production of oviductin, a putative embryotrophic protein., Design: Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis of oviductin messenger RNA (mRNA) expression after oviduct mucosal cell culture., Setting: University-based obstetrics and gynecology department., Patient(s): Ten women undergoing laparoscopy for tubal sterilization or hysterectomy for uterine fibroids., Intervention(s): The mucosal layer was isolated from the oviduct tissue and subjected to routine culture conditions; semiquantitative RT-PCR was performed., Main Outcome Measure(s): The relationship between duration of cell culture and expression of oviductin mRNA., Result(s): There was a significant reduction in oviductin mRNA expression after 3 days in culture, with a complete loss after 6 days in 70% of the samples and after 12 days in the remaining 30%. CONLCUSION(S): This is the first study to investigate whether oviductin mRNA continues to be expressed in cultured human oviduct mucosal cells. Our results suggest that oviduct mucosal cells lose their ability to produce oviductin after short-term culture. This method of culture does not appear to be appropriate for a coculture system reliant upon oviductal secretion of oviductin.

This is a prospective study to assess the psychiatric morbidity in Chinese infertile women who underwent treatments with assisted reproductive technology and also the impact of treatment failure. The 30-item General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were employed before and 3 weeks after the assisted reproductive technology treatment. Data from 372 patients who completed the questionnaires and failed the treatment were analyzed. Before treatment, 33% of the participants scored above the GHQ cutoff, and 8% had a BDI score of 20 or above, signifying moderate to severe depression. Following failed treatment, 43% scored above GHQ cutoff, and 8% had BDI scores 20 or above. The posttreatment GHQ and BDI scores were significantly higher than the corresponding scores at baseline (p < 0.001). About 13% of the participants reported self-harm ideas. The severity of depression following a failed treatment was positively associated with the duration of infertility (p < 0.05), but not with the posttreatment BDI scores, age, education, and number of previous treatment episodes. Our results show that one third of the women who sought infertility treatment had an impaired psychological well-being. Following failed treatment, there was a further deterioration in mental health, and about 10% of the participants were moderately to severely depressed. Proper psychological care and counseling should be an integral part of infertility management among the Chinese population., (Copyright 2002 S. Karger AG, Basel)