Live birth rate per fresh embryo transfer and cumulative live birth rate in patients with PCOS under the POSEIDON classification: a retrospective study.

Background: Ovarian stimulation (OS) for in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in women with PCOS often results in multiple follicular development, yet some individuals experience poor or suboptimal responses. Limited data exist regarding the impact of poor/suboptimal ovarian response on pregnancy outcomes in women with PCOS. Objectives: The aim of this study was to evaluate whether the live birth rate (LBR) per fresh embryo transfer and cumulative live birth rate (CLBR) per aspiration cycle differ in women with PCOS defined by the Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. Methods: A retrospective study involving 2,377 women with PCOS who underwent their first IVF/ICSI cycle at Sun Yat-sen Memorial Hospital from January 2011 to December 2020 was used. Patients were categorized into four groups based on age, antral follicle count, and the number of oocytes retrieved, according to the POSEIDON criteria. The LBR and CLBR were compared among these groups. Logistic regression analysis was performed to assess whether the POSEIDON criteria served as independent risk factors and identify factors associated with POSEIDON. Results: For patients <35 years old, there was no significant difference in the clinical pregnancy rate between POSEIDON and non-POSEIDON patients, whereas POSEIDON patients exhibited lower rates of implantation and live birth. POSEIDON Group 1a displayed lower rates of implantation, clinical pregnancy, and live birth. However, no significant differences were observed in the rates of clinical pregnancy and live birth between POSEIDON Group 1b and non-POSEIDON groups. For patients ≥35 years old, there were no significant differences in the rates of implantation, clinical pregnancy, and live birth between POSEIDON and non-POSEIDON patients. CLBRs were significantly lower in POSEIDON Groups 1 and 2, compared with the non-POSEIDON groups. The levels of body mass index (BMI), follicle-stimulating hormone (FSH), and antral follicle count (AFC) were associated with POSEIDON hypo-response. POSEIDON was found to be associated with lower CLBR, but not LBR per fresh embryo transfer. Conclusions: In patients with PCOS, an unexpected suboptimal response can achieve a fair LBR per fresh embryo transfer. However, CLBR per aspirated cycle in POSEIDON patients was lower than that of normal responders. BMI, basal FSH level, and AFC were independent factors associated with POSEIDON. Our study provides data for decision-making in women with PCOS after an unexpected poor/suboptimal response to OS.

Regulatory effects of Zishen Yutai Pill on endometrial epithelial response in vitro in immunology microenvironment.

Objective: Zishen Yutai Pill (ZYP) is a frequently used traditional Chinese medicine (TCM) preparation in women's health. However, the effects of ZYP on endometrial epithelial response have not been fully explored. Herein, uterine natural killer cell (uNK) secretion medium was used to mimic the uterine microenvironment. Thereafter, an endometrial epithelial cell line (Ishikawa cells) was treated with ZYP-containing serum to elucidate the effects of ZYP on endometrial receptivity.Methods: uNK cells were isolated from decidual tissues of pregnant women undergoing pregnancy termination surgery, and thereafter, uNK secretion medium was collected. ZYP-containing serum was collected from rats after intragastrical administration of ZYP. Ishikawa cells were divided into three groups, one treated with blank control (control group), one treated with uNK secretion medium (uNK group), and one treated with both uNK secretion medium and ZYP-containing serum (ZYP + uNK group). Total RNAs were extracted. Gene expression profiles of Ishikawa in different groups were determined through microarray analysis. mRNA expressions of selected genes were determined through quantitative real-time polymerase chain reaction (qRT-PCR). Expression of intercellular cell adhesion molecule-1 (ICAM-1) was determined using Western blotting (WB). Results: Compared with the uNK group, the gene expressions of ZYP group with a total of 1117 genes were significantly altered, among which 510 genes were upregulated and 607 genes were downregulated. Compared with uNK group, expressions of CSF1, CSF2, SPP1, and ICAM1 were upregulated (P < 0.05). Up-regulation of ICAM-1 expression after treatment of ZYP was further confirmed by WB analysis. Conclusion: In brief, in the presence of uNK cell medium, ZYP could improve the expressions of ICAM1, CSF1, CSF2, TNF, SPP1, etc. However, further exploration should be carried out in in vivo experiments for the validation of the mechanisms of ZYP on endometrial epithelial response.

Prevalence of polycystic ovary syndrome under NIH criteria among the tenth-grade Chinese schoolgirls in Guangzhou area: a cross-sectional epidemiological survey.

BACKGROUND: Polycystic ovary syndrome (PCOS) is currently considered to have a peri-adolescence onset and continuously influence the reproductive and metabolic health of the patients, while the diagnostic criteria among adolescent population haven't been universally unified till now. This survey seeks to preliminarily evaluate the prevalence of PCOS in the tenth grade schoolgirls in Guangzhou area under NIH criteria and analyze the clinical features of adolescents with PCOS. METHODS: The cross-sectional epidemiological survey was carried out among the tenth grade schoolgirls in Guangzhou area by the method of cluster sampling. The contents of this survey included the questionnaire, physical exams and serum measurements. Until now, totally 1294 girls underwent this survey and 1095 serum samples were restored. 235 non-hirsute (mFG < 6), postmenarcheally 2-year girls were randomly selected as the control group, among which the cut-off value of biochemical hyperandrogenemia was set accordingly. The prevalence of PCOS among this population was preliminarily evaluated according to the NIH criteria. RESULTS: Along with the increase of gynecological age, the menstruations of girls was becoming more regular and the incidence of oligomenorrhea or amenorrhea was declining. Even among those who were less than 2 years after menarche, those whose menstrual cycle were longer than 90 days accounted for lower than 5%. The 95th percentile of mFG score was 6 among the girls who were < 2 years after menarche, and 5 among the girls who were > 2 years after menarche. Among the 235 healthy girls, the 95th percentile values of Testosterone (T), Free androgen index (FAI) and Androstenedione (A2) were 2.28 nmol/mL, 4.37, and 5.20 nmol/mL respectively. Based on the NIH criteria, the prevalence of PCOS in this survey was 3.86%. The prevalence of adolescent PCOS tend to slightly increase with age and gynecological age, but the difference was not statistically significant. The prevalence of PCOS among obese girls was markedly higher than that in lean girls. CONCLUSION: Based on the NIH criteria, the prevalence of PCOS among the tenth grade schoolgirls in Guangzhou area was 3.86%. The diagnosis of hyperandrogenism among adolescents should also be based on both clinical and biochemical parameters.

The Degree of Menstrual Disturbance Is Associated With the Severity of Insulin Resistance in PCOS.

Objective: Insulin resistance (IR) is an important determinant of the phenotype and morbidity of the polycystic ovary syndrome (PCOS). In this study, we aimed to figure out the association between the degree of menstrual disturbance and the severity of IR in women with PCOS. Design: It is a cross-sectional study conducted in an academic tertiary setting. Patients: The patients comprised five hundred twenty-seven women diagnosed with PCOS by the 2003 Rotterdam criteria and 565 controls with regular vaginal bleeding. Interventions: The interventions done for this study are medical history collection, physical examination, and blood sampling. Main outcome measures: The main outcome measures are body mass index (BMI), fasting glucose, fasting insulin, homeostatic model assessment for IR (HOMA-IR), and hormonal parameters. Results: Women with PCOS had a higher level of BMI, HOMA-IR, and HOMA-ß than controls, with a decreased level of sex hormone-binding globulin and QUICK I index. The luteinizing hormone (LH)/follicle-stimulating hormone (FSH), testosterone (T), antral follicle count (AFC), dehydroepiandrosterone sulfate, free androgen index, modified Ferriman-Gallwey score, and the incidence of delayed insulin peak increased with the degree of menstrual disturbance, although there was no significance for the latter four parameters. Women with vaginal bleeding intervals of 45-90 days had a relatively higher level of HOMA-IR and HOMA-ß, although it was adjusted with age and BMI than the other two groups. Similar results were observed in AUCI (area under the curve of insulin) and I/G [the ratio of AUCI and AUCG (area under the curve of glucose)]. Anovulatory women with vaginal bleeding episodes of less than 45 days tended to have higher glucose and insulin levels, area under the curve of glucose (AUCG), area under the curve of insulin (AUCI), HOMA-IR, and HOMA-ß but decreased QUICK I and Matsuda index than those who were ovulatory. Women with vaginal bleeding intervals of longer than 45 days who had hyperandrogenism (HA) showed a higher level of glucose, insulin, HOMA-IR, and HOMA-ß but lower QUICK I and Matsuda Index. Conclusions: In women with PCOS, the severity of IR, the LH/FSH ratio, and androgen level increased with a higher degree of disturbance in menstrual cyclicity (i.e., the vaginal bleeding intervals). Subgroup analysis indicated that the situation of HA may aggravate the disorder of glucose metabolism in women with PCOS. Overall, the interval between episodes of vaginal bleeding may be useful as a ready measure for predicting the severity of IR in PCOS.

Fucoxanthin Prevents Long-Term Administration l-DOPA-Induced Neurotoxicity through the ERK/JNK-c-Jun System in 6-OHDA-Lesioned Mice and PC12 Cells.

As the most abundant marine carotenoid extracted from seaweeds, fucoxanthin is considered to have neuroprotective activity via its excellent antioxidant properties. Oxidative stress is regarded as an important starting factor for neuronal cell loss and necrosis, is one of the causes of Parkinson's disease (PD), and is considered to be the cause of adverse reactions caused by the current PD commonly used treatment drug levodopa (l-DA). Supplementation with antioxidants early in PD can effectively prevent neurodegeneration and inhibit apoptosis in dopaminergic neurons. At present, the effect of fucoxanthin in improving the adverse effects triggered by long-term l-DA administration in PD patients is unclear. In the present study, we found that fucoxanthin can reduce cytotoxicity and suppress the high concentration of l-DA (200 µM)-mediated cell apoptosis in the 6-OHDA-induced PC12 cells through improving the reduction in mitochondrial membrane potential, suppressing ROS over-expression, and inhibiting active of ERK/JNK-c-Jun system and expression of caspase-3 protein. These results were demonstrated by PD mice with long-term administration of l-DA showing enhanced motor ability after intervention with fucoxanthin. Our data indicate that fucoxanthin may prove useful in the treatment of PD patients with long-term l-DA administration.

Does elevated luteinizing hormone level before trigger mean premature luteinizing hormone surge in advanced-aged women undergoing mild ovarian stimulation?

OBJECTIVE: To explore whether elevated luteinizing hormone (LH) level before trigger means premature LH surge in advanced aged women undergoing mild ovarian stimulation. METHODS: To retrospectively analyze 235 in vitro fertilization/intracytoplasmic sperm injection cycles in women >35 years old with the poor ovarian response (POR) from January 2012 to March 2016. Cycles are named Group 1, Group 2, and Group 3, being treated with gonadotropin-releasing hormone antagonist protocol (76 cycles), mild stimulation protocol using clomiphene citrate (73 cycles), and tamoxifen (86 cycles), respectively. MAIN OUTCOME MEASURE(S): The dynamic change of LH level during stimulation; the proportion of an elevated LH level defined as >10 IU/L on trigger day; the proportion of premature ovulation in each group. RESULTS: Serum LH level increased early in Group 2 and Group 3 and remained significantly higher than that in Group 1 during stimulation. In a sequence of three groups, the proportion of elevated LH levels before the trigger was 11.84, 43.8, and 37.21% (p＜.001) respectively. And the proportion of premature ovulation in patients with elevated LH levels was 11.11, 18.75, and 25% (p = .11) respectively. CONCLUSION: Elevated LH level before trigger does not mean premature LH surge in women more than 35 years old with POR undergoing mild ovarian stimulation with clomiphene or tamoxifen.

Comparison of Cumulative Live Birth Rate Between Aged PCOS Women and Controls in IVF/ICSI Cycles.

The present study aimed to assess whether women with polycystic ovarian syndrome (PCOS) ≥35 years age undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles experienced a higher cumulative live birth rate (CLBR) over a two-year period compared with age- and body mass index (BMI)-matched patients with tubal factor infertility. Through propensity score matching (PSM) approach, the authors retrospectively analyzed the IVF/ICSI outcomes of 263 PCOS patients (35-46 years of age [mean, 37 years]) and 526 age- and BMI-matched tubal factor controls two years after oocyte retrieval. Multivariate regression analysis was performed to explore factors influencing cumulative live birth. Women with PCOS exhibited better ovarian reserve and response, and higher CLBR in two years compared with age- and BMI-matched controls (CLBR: 55.51% in PCOS vs. 38.02% in control, p<0.001). Multivariate logistic regression analysis revealed that the number of transferable embryos and antral follicle counts were both significant independent factors predicting cumulative live birth after adjusting for female age, female body mass index, percentage of transferred blastocysts, number of embryos transferred per embryo-transfer cycle, diagnosis of PCOS and freeze-all cycles (p<0.001, p=0.045). Women with PCOS ≥ 35 years of age demonstrated a higher CLBR over two years compared with age- and BMI-matched controls. This could be explained by favorable oocyte reserve and more available embryos compared with controls, which overcome the compromised oocyte quality in aged PCOS patients.

The Cutoff Value of Low Sex Hormone-Binding Globulin and Its Predictive Role in Impaired Glucose Metabolism Among Chinese Women with Polycystic Ovarian Syndrome.

Background: Low levels of sex hormone-binding globulin (SHBG) is a potential predictor of type 2 diabetes mellitus (T2DM), and when combined with insulin resistance (IR), lead to impaired glucose metabolism. Few studies involve women with polycystic ovarian syndrome (PCOS). Studies on cutoff values of SHBG among Asian women were scanty. Methods: The cutoff level of SHBG was computed using the 25th percentile method. Parameters were compared between the lower and higher SHBG subgroup. Area under the curve (AUC) for sensitivity and specificity of SHBG in predicting IR and impaired glucose metabolism was calculated. Results: This study included 733 patients with PCOS 20-45 years of age and 469 age-matched controls. The 25th percentile of SHBG in the control group was 51.90 nM. There were negative correlations between SHBG and age (r = -0.085, P < 0.05), body mass index (BMI) (r = -0.461, P < 0.01), waist-to-hip ratio (WHR) (r = -0.349, P < 0.01), fasting plasma glucose (r = -0.242, P < 0.01), Glucose-1h (r = -0.303, P < 0.01), Glucose-2h (r = -0.336, P < 0.01), fasting insulin (r = -0.324, P < 0.01), Insulin-1h (r = -0.238, P < 0.01), Insulin-2h (r = -0.307, P < 0.01), and homeostasis model 2 assessment of insulin resistance (HOMA2-IR) (r = -0.329, P < 0.01). Age, BMI, WHR, glucose and insulin levels (both pre- and postload), HOMA2-IR, free testosterone, and dehydroepiandrosterone sulfate were all higher in the lower than the higher SHBG subgroup. The AUC of SHBG for predicting IR was 0.706 [95% confidence interval (CI) 0.665-0.745, P < 0.001], impaired fasting glucose was 0.674 (95% CI 0.513-0.838, P < 0.001), impaired glucose tolerance was 0.637 (95% CI 0.586-0.690, P < 0.001), and T2DM was 0.674 (95% CI 0.556-0.780, P < 0.001). Conclusions: A 51.90 nM should be identified as the cutoff value of SHBG. Women with PCOS with lower SHBG values have a higher risk of developing impaired glucose metabolism. Low SHBG should be a predictive biomarker of impaired glucose metabolism in women with PCOS in southern China.

LNK promotes granulosa cell apoptosis in PCOS via negatively regulating insulin-stimulated AKT-FOXO3 pathway.

BACKGROUND: Polycystic ovary syndrome (PCOS), which is often accompanied by insulin resistance, is closely related to increased apoptosis of ovarian granulosa cells. LNK is an important regulator of the insulin signaling pathway. When insulin binds to the receptor, the PI3K/AKT/FOXO signaling pathway is activated, and FOXO translocates from the nucleus to the cytoplasm, thereby inhibiting the expression of pro-apoptotic genes. METHODS: Granulosa cells were collected from PCOS patients to investigate the relationship between LNK, cell apoptosis and insulin resistance. KGN cells underwent LNK overexpression/silence and insulin stimulation. The AKT/FOXO3 pathway was studied by western blot and immunofluorescence. LNK knockout mice were used to investigate the effect of LNK on the pathogenesis of PCOS. RESULTS: The level of LNK was higher in PCOS group than control group. LNK was positively correlated with granulosa cell apoptosis and insulin resistance, and negatively correlated with oocyte maturation rate. LNK overexpression in KGN cells inhibited insulin-induced AKT/FOXO3 signaling pathway, causing nucleus translocation of FOXO3 and promoting granulosa cell apoptosis. LNK knockout partially restored estrous cycle and improved glucose metabolism in PCOS mice. CONCLUSIONS: LNK was closely related to insulin resistance and apoptosis of granulosa cells via the AKT/FOXO3 pathway. LNK knockout partially restored estrous cycle and improved glucose metabolism in PCOS mice, suggesting LNK might become a potential biological target for the clinical treatment of PCOS.

Citrus Huanglongbing Detection Based on Multi-Modal Feature Fusion Learning.

Citrus Huanglongbing (HLB), also named citrus greening disease, occurs worldwide and is known as a citrus cancer without an effective treatment. The symptoms of HLB are similar to those of nutritional deficiency or other disease. The methods based on single-source information, such as RGB images or hyperspectral data, are not able to achieve great detection performance. In this study, a multi-modal feature fusion network, combining a RGB image network and hyperspectral band extraction network, was proposed to recognize HLB from four categories (HLB, suspected HLB, Zn-deficient, and healthy). Three contributions including a dimension-reduction scheme for hyperspectral data based on a soft attention mechanism, a feature fusion proposal based on a bilinear fusion method, and auxiliary classifiers to extract more useful information are introduced in this manuscript. The multi-modal feature fusion network can effectively classify the above four types of citrus leaves and is better than single-modal classifiers. In experiments, the highest accuracy of multi-modal network recognition was 97.89% when the amount of data was not very abundant (1,325 images of the four aforementioned types and 1,325 pieces of hyperspectral data), while the single-modal network with RGB images only achieved 87.98% recognition and the single-modal network using hyperspectral information only 89%. Results show that the proposed multi-modal network implementing the concept of multi-source information fusion provides a better way to detect citrus HLB and citrus deficiency.

The predictive value of total testosterone alone for clinical hyperandrogenism in polycystic ovary syndrome.

RESEARCH QUESTION: Is the sole measurement of total testosterone sufficient to assess the presence of hyperandrogenism in women with polycystic ovary syndrome (PCOS)? DESIGN: Serum samples from 294 patients with PCOS who met the Rotterdam criteria were used for the analysis of total testosterone by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay (CLIA). The free androgen index (FAI) was calculated as total testosterone (TT)/sex hormone-binding globulin (SHBG) × 100%, and the presence/degree of hirsutism were assessed using the modified and simplified Ferriman-Gallwey (mFG and sFG, respectively) scoring systems. RESULTS: The hirsute subjects presented higher LC-MS/MS-based total testosterone and FAI values than the non-hirsute subjects (all P < 0.001), including those defined based on mFG ≥5 or sFG ≥3. Total testosterone and FAI were both positively correlated with the mFG (rank correlation coefficient [RCC] 0.598 and 0.443, P < 0.001) or sFG (RCC 0.747 and 0.568, P < 0.001) score, and a receiver operating characteristic curve analysis indicated that both parameters could significantly predict the presence of hirsutism determined by the mFG (area under the curve [AUC] 0.797 and 0.725, P < 0.001) or sFG (AUC 0.894 and 0.817, P < 0.001) score. However, similar results were not obtained with the CLIA platform. CONCLUSIONS: In this East Asian population, total testosterone was found to be a strong predictor of the presence and degree of hyperandrogenism (i.e. assessed by the presence and degree of hirsutism), but this finding was obtained only if the total testosterone level was measured by LC-MS/MS and not by CLIA. These findings might have important implications for global epidemiologic, phenotypic and clinical studies of PCOS.

miR-130b regulates gap junctional intercellular communication through connexin 43 in granulosa cells from patients with polycystic ovary syndrome.

MicroRNAs (miRNAs) are small, noncoding RNAs that negatively regulate gene expression post-transcriptionally. We explored whether connexin 43 (Cx43) was differently expressed in luteinized granulosa cells from women with polycystic ovary syndrome (PCOS) compared with luteinized granulosa cells from women with a normal menstrual cycle, and whether certain miRNAs regulate the Cx43 level and gap junctional intercellular communication (GJIC). The miRNA profile was investigated in ovarian cortex tissues from five women with PCOS and five women without PCOS using a miRNA microarray. The levels of miR-130b and Cx43 mRNA were measured using real-time PCR in human luteinized granulosa cells from 20 women with PCOS and 25 women without PCOS. Protein and mRNA expression analysis and luciferase assays were conducted to confirm the substrate of miR-130b. PCOS ovarian cortex showed differential expression of miRNAs compared with non-PCOS ovarian cortex. Furthermore, miR-130b levels were increased in PCOS ovarian cortex and in luteinized granulosa cells compared with those in women with normal menstrual cycles, whereas the level of Cx43 mRNA, the identified target of miR-130b, was decreased in granulosa cells from patients with PCOS. Overexpression of miR-130b in a granulosa cell line resulted in reduced Cx43 protein levels and inhibited GJIC using scrape loading and dye transfer assay. Meanwhile, inhibition of miR-130b increased the Cx43 level. In conclusion, miR-130b was increased in PCOS granulosa cells, where it targets Cx43 to affect GJIC. The results of the present study suggested that miR-130b, via post-transcriptional regulation of Cx43, is involved in the pathophysiology of PCOS, which provides new insight into the pathological mechanism of PCOS.

Does an FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? A randomized, double-blinded, placebo-controlled study.

STUDY QUESTION: Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? SUMMARY ANSWER: An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI. WHAT IS KNOWN ALREADY: Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS). STUDY DESIGN, SIZE, DURATION: This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000-10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS. MAIN RESULTS AND THE ROLE OF CHANCE: There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI -6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively. LIMITATIONS, REASONS FOR CAUTION: This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger. WIDER IMPLICATIONS OF THE FINDINGS: Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246). TRIAL REGISTRATION DATE: 20 May 2012. DATE OF FIRST PATIENT'S ENROLMENT: 10 June 2012.

A Phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in in vitro fertilization (Lotus II): results from the Chinese mainland subpopulation.

Lotus II, a randomized, open-label, multicenter, international study compared the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) gel for luteal support in IVF. A prespecified subgroup analysis was performed on 239 Chinese mainland subjects from the overall study population (n = 1034), who were randomized to oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily from the day of oocyte retrieval until 12 weeks of gestation. The aim was to demonstrate non-inferiority of oral dydrogesterone to MVP gel, assessed by the presence of a fetal heartbeat at 12 weeks of gestation. In the Chinese mainland subpopulation, there was a numerical difference of 9.4% in favor of oral dydrogesterone, with ongoing pregnancy rates at 12 weeks of gestation of 61.4% and 51.9% in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 9.4%; 95% CI: -3.4 to 22.1); in the overall population, these were 38.7% and 35%, respectively (adjusted difference, 3.7%; 95% CI: -2.3 to 9.7). In both the Chinese mainland subpopulation and the overall population, dydrogesterone had similar efficacy and safety to MVP gel. With convenient oral administration, dydrogesterone has potential to transform luteal support treatment.

The synergistic effects of vitamin D and estradiol deficiency on metabolic syndrome in Chinese postmenopausal women.

OBJECTIVE: Recent studies show that vitamin D (VitD) deficiency is associated with metabolic syndrome (MetS). Current evidence suggests that estrogen and VitD have similar physiological functions and potentially interact with bone health. We investigated the association between estradiol (E2) and 25-hydroxyvitamin-D [25(OH)D] with MetS and its components in Chinese postmenopausal women. METHODS: In this cross-sectional study, we examined 616 postmenopausal women (aged 49-86 y) from southern China who were not taking estrogen and VitD/calcium supplements. At the end of data collection, serum E2 and 25(OH)D were measured for each participant. MetS was defined according to the 2006 International Diabetes Federation standard. RESULTS: There was a positive correlation between 25(OH)D and E2. Higher 25(OH)D was associated with a favorable lipid profile, blood pressure, and glucose level. E2 was negatively associated with cholesterol, triglycerides, and blood pressure. The odds ratio for MetS was 2.19 (95% CI, 1.19-4.01, P value for trend=0.009) for deficient compared with sufficient women after multivariable adjustment. This association remained unchanged after further adjusting for E2 levels. After stratified analysis by VitD status, low E2 increased MetS risk in women with VitD deficiency (odds ratio = 3.49, 95% CI, 1.45-8.05 for the lowest vs the highest tertile). CONCLUSIONS: These results suggest a synergistic role of VitD and E2 deficiency in MetS in Chinese postmenopausal women.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

ABSTRACT Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Could semiquantitative analysis of real-time ultrasound elastography distinguish more liver parenchyma alterations of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome?

OBJECTIVE: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. SUBJECTS AND METHODS: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. RESULTS: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. CONCLUSION: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Close correlation between hyperandrogenism and insulin resistance in women with polycystic ovary syndrome-Based on liquid chromatography with tandem mass spectrometry measurements.

BACKGROUND: To investigate the correlation between hyperandrogenism (HA) and insulin resistance (IR) in women with polycystic ovary syndrome (PCOS) by measuring serum total testosterone (TT) using a liquid chromatography and tandem mass spectrometry assay (LC-MS/MS). METHODS: This cohort study included 332 patients with PCOS, 63 patients with IR and 276 with controls. TT levels were measured by LC-MS/MS and chemiluminescent immunoassay (CLIA); glucose and insulin levels were determined by an oral glucose tolerance test (OGTT). RESULTS: Compared with CLIA, LC-MS/MS differentiated more cases with high TT levels among the non-PCOS subjects with IR In patients with PCOS, LC-MS/MS-based TT levels or a combination with the mFG score detected a significantly higher incidence of HA in subjects with IR identified by hyperinsulinemia (HIN), HOMA-IR or impaired fasting glucose (IFG) than in those without IR Conversely, the IR rates demonstrated by HIN, HOMA-IR, or IFG were remarkably higher in the LC-MS/MS-defined high TT subgroup than in the normal TT subgroup. However, the CLIA platform could not discern a difference in HA incidence between IR and non-IR subgroups or in IR rate between high and normal TT populations. ROC curves also proved that HIN, HOMA-IR, and IFG were positive contributors to HA as measured by LC-MS/MS CONCLUSIONS: The correlation between HA and IR has always been underestimated, partly owing to the less accurate methods previously used to measure TT. HIN, HOMA-IR, and IFG are likely to contribute to the development of HA from a clinical perspective.

Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial.

STUDY QUESTION: Is oral dydrogesterone 30 mg daily non-inferior to 8% micronized vaginal progesterone (MVP) gel 90 mg daily for luteal phase support in IVF? SUMMARY ANSWER: Oral dydrogesterone demonstrated non-inferiority to MVP gel for the presence of fetal heartbeats at 12 weeks of gestation (non-inferiority margin 10%). WHAT IS KNOWN ALREADY: The standard of care for luteal phase support in IVF is the use of MVP; however, it is associated with vaginal irritation, discharge and poor patient compliance. Oral dydrogesterone may replace MVP as the standard of care if it is found to be efficacious with an acceptable safety profile. STUDY DESIGN, SIZE, DURATION: Lotus II was a randomized, open-label, multicenter, Phase III, non-inferiority study conducted at 37 IVF centers in 10 countries worldwide, from August 2015 until May 2017. In total, 1034 premenopausal women (>18 to <42 years of age) undergoing IVF were randomized 1:1 (stratified by country and age group), using an Interactive Web Response System, to receive oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects received either oral dydrogesterone (n = 520) or MVP gel (n = 514) on the day of oocyte retrieval, and luteal phase support continued until 12 weeks of gestation. The primary outcome measure was the presence of fetal heartbeats at 12 weeks of gestation, as determined by transvaginal ultrasound. MAIN RESULTS AND THE ROLE OF CHANCE: Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates in the full analysis sample (FAS) at 12 weeks of gestation of 38.7% (191/494) and 35.0% (171/489) in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 3.7%; 95% CI: -2.3 to 9.7). Live birth rates in the FAS of 34.4% (170/494) and 32.5% (159/489) were obtained for the oral dydrogesterone and MVP gel groups, respectively (adjusted difference 1.9%; 95% CI: -4.0 to 7.8). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP gel. LIMITATIONS, REASONS FOR CAUTION: The analysis of the results was powered to consider the ongoing pregnancy rate, but a primary objective of greater clinical interest may have been the live birth rate. This study was open-label as it was not technically feasible to make a placebo applicator for MVP gel, which may have increased the risk of bias for the subjective endpoints reported in this study. While the use of oral dydrogesterone in fresh-cycle IVF was investigated in this study, further research is needed to investigate its efficacy in programmed frozen-thawed cycles where corpora lutea do not exist. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that oral dydrogesterone is a viable alternative to MVP gel, due to its comparable efficacy and tolerability profiles. Owing to its patient-friendly oral administration route, dydrogesterone may replace MVP as the standard of care for luteal phase support in fresh-cycle IVF. STUDY FUNDING/COMPETING INTERESTS(S): This study was sponsored and supported by Abbott. G.G. has received investigator fees from Abbott during the conduct of the study. Outside of this submitted work, G.G. has received non-financial support from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope and Gedeon Richter, as well as personal fees from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope, VitroLife, NMC Healthcare, ReprodWissen, Biosilu, Gedeon Richter and ZIVA. C.B. is the President of the Belgian Society of Reproductive Medicine (unpaid) and Section Editor of Reproductive BioMedicine Online. C.B. has received grants from Ferring Pharmaceuticals, participated in an MSD sponsored trial, and has received payment from Ferring, MSD, Biomérieux, Abbott and Merck for lectures. G.S. has no conflicts of interest to be declared. A.P. is the General Secretary of the Indian Society of Assisted Reproduction (2017-2018). B.D. is President of Pune Obstetric and Gynecological Society (2017-2018). D.-Z.Y. has no conflicts of interest to be declared. Z.-J.C. has no conflicts of interest to be declared. E.K. is an employee of Abbott Laboratories GmbH, Hannover, Germany and owns shares in Abbott. C.P.-F. is an employee of Abbott GmbH & Co. KG, Wiesbaden, Germany and owns shares in Abbott. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Origio, Besins, Ferring and Mithra (now Allergan); and H.T. has received consultancy fees from Finox-Gedeon Richter, Merck, Ferring, Abbott and ObsEva. TRIAL REGISTRATION NUMBER: NCT02491437 (clinicaltrials.gov). TRIAL REGISTRATION DATE: 08 July 2015. DATE OF FIRST PATIENT'S ENROLLMENT: 17 August 2015.

Should All Women with Polycystic Ovary Syndrome Be Screened for Metabolic Parameters?: A Hospital-Based Observational Study.

This hospital-based observational study aims to estimate differences in metabolic abnormalities between different polycystic ovary syndrome (PCOS) phenotypes and their distribution characteristics. The prevalence of metabolic abnormalities among different PCOS phenotypes, including diabetes mellitus (DM), metabolic syndrome (MS), pre-diabetes mellitus (pre-DM), insulin resistance (IR) and dyslipidemia were compared. A total of 2436 women who were ≥18 years old and who were hospitalized in Sun Yat-Sen University affiliated hospital from 1998 to 2015 in GuangZhou, China, were included in this study. PCOS phenotypes were recorded according to the 2003 Rotterdam criteria, including the polycystic ovary morphology (PCO), hyperandrogenism (HA) and ovulation dysfunction (OD) phenotype (PCO+HA+OD); the ovulation phenotype (PCO+HA); the non-PCO phenotype (HA+OD); and the non-HA phenotype (PCO+OD). Notably, 56% of the patients had the classic phenotype (PCO+HA+OD). Importantly, there was no significant difference in the prevalence of metabolic abnormalities or the distribution characteristics of the metabolic abnormalities among these four PCOS phenotypes. Our study supports the notion that metabolic abnormalities and the distribution characteristics of metabolic abnormalities should not be used to distinguish among the various clinical PCOS phenotypes.