Fertility history and intentions of married women, China.

Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.

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.

Preconceptional thyroid stimulating hormone level and fecundity: a community-based cohort study of time to pregnancy.

OBJECTIVE: To investigate the association between preconception thyroid stimulating hormone (TSH) level and time to pregnancy within a community-based population. DESIGN: A community-based cohort study. SETTING: Two free preconception check-up centers. PATIENT(S): Women who enrolled in the National Free Preconception Check-up Projects from January 1, 2018 to December 31, 2018 in Tianhe and Zengcheng districts of Guangzhou city. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Time to pregnancy. RESULT(S): A total of 1,478 women were eligible for the analysis; of these, 1,401 had a preconception TSH level within the range of 0.50 and 5.59 mIU/L (2.5th-97.5th percentiles) were taken as target study population. Among them, 968 (69.1%) couples achieved pregnancy within the first 6 months and 1,082 (77.2%) within 12 months. Dichotomized by the recommended cut-off value of 2.5 mIU/L, the percentage of women conceived in the high TSH level category (2.50-5.59 mIU/L) was comparable to that of the low category (0.50-2.49 mIU/L) (79.0% vs. 78.1%), with a crude fecundity odd ratio of 0.99 (95% confidence interval at 0.87-1.13). No statistically significant difference was observed after the adjustment in all models. Continuous TSH level was further examined, and the nonlinear association between TSH level and fecundity odds ratios was of no statistical significance. CONCLUSION(S): Preconception TSH level was not associated with fecundity in a healthy community-based population. Women attempting pregnancy with a TSH level ≥ 2.5 mIU/L can be reassured that they are unlikely to have an increased time to pregnancy.

Age-specific random day serum antimüllerian hormone reference values for women of reproductive age in the general population: a large Chinese nationwide population-based survey.

BACKGROUND: Antimüllerian hormone, the most reliable biomarker of ovarian reserve, is widely used in various clinical situations. Antimüllerian hormone levels consistently decrease with age. However, there is no standard, age-specific reference values for antimüllerian hormone in women of reproductive age, which limits its application. OBJECTIVE: This study aimed to establish age-specific antimüllerian hormone percentile reference values for women of reproductive age. STUDY DESIGN: A nationwide, population-based cross-sectional survey was conducted between May 2019 and April 2021 in 15 provinces and municipalities in mainland China. A total of 10,053 eligible women aged 20 to 49 years were selected using a multistage stratified sampling procedure. Women who were pregnant, had undergone ovarian surgery, took hormone drugs in the past 3 months, or had an antimüllerian hormone outlier value were excluded from establishing antimüllerian hormone percentile reference values. Serum antimüllerian hormone concentrations were measured using ultrasensitive, 2-site enzyme-linked immunosorbent assays (Ansh Lab, Webster, TX) in the Reproductive Endocrinology Laboratory of Peking University Third Hospital. Generalized additive models for location scale and shape with the Box-Cox t original distribution were used to estimate the fitted antimüllerian hormone percentile reference values. RESULTS: A total of 9112 eligible women aged 21 to 49 years were included in the fitting model. The fitted 50th (2.5th-97.5th) percentiles of antimüllerian hormone values for women aged 21, 25, 30, 35, 40, 45, and 49 years were 4.83 (0.79-18.41), 4.47 (0.72-16.58), 3.67 (0.50-13.82), 2.59 (0.24-10.35), 1.35 (0.05-6.68), 0.33 (<0.01 to 3.40), and 0.04 (<0.01 to 1.77) ng/mL, respectively. The population-based decline rate of antimüllerian hormone accelerated with increasing age, especially age >35 years. The magnitude of the decline of the 25th antimüllerian hormone percentile curve was greater than that of the 75th percentile curve. CONCLUSION: This study established age-specific antimüllerian hormone percentile reference values for women of reproductive age based on a large representative sample of the general population and described antimüllerian hormone changes. These findings may facilitate antimüllerian hormone application in clinical practices.

Changes in the prevalence of polycystic ovary syndrome in China over the past decade.

Background: Polycystic ovary syndrome (PCOS) has become a major international public health concern. However, because of controversy about the diagnostic criteria and patient selection, estimates of its absolute prevalence and change with time vary greatly. Methods: We conducted two consecutive nationwide epidemiological surveys of the prevalence of PCOS in representative samples of reproductive-aged women in China in 2010 and 2020. Face-to-face interviews were performed by trained interviewers in each survey. All participants completed a questionnaire and underwent a physical examination, blood sampling, and transvaginal pelvic ultrasound. We assessed hyperandrogenism (H), chronic anovulation (O), and polycystic ovaries (P) to classify the presence of PCOS using the Rotterdam criteria. The prevalence of PCOS among reproductive-aged women was estimated after consideration of differential probabilities of selection and population distribution. We conducted a logistic regression analysis by using the probability of PCOS as a function of the survey year to acquire the trend information across the years. Findings: 28,739 respondents completed the survey, including 15,924 in the previously published 2010 survey and 12,815 in the new 2020 survey. In 2020, 826 participants could be diagnosed as having PCOS, with a weighted prevalence of 7.8% (95%CI: 7.0%, 9.0%) among women aged 20-49 years, leading to an estimate of 24.0 million women of reproductive age affected by this condition in China as a whole. The estimated prevalence in 2020 was higher than that of a decade ago despite identical research methods suggesting a two-thirds increase over the study period. Women with PCOS in 2020 also appeared to have a more severe phenotype overall than those of a decade ago, possibly reflecting a significantly higher prevalence of obesity, hyperandrogenism, and infertility. Interpretation: The prevalence of PCOS in Chinese women has increased significantly over the past 10 years. PCOS is a significant public health problem in women of reproductive age in China and national policy and guidelines should be re-examined in the light of the current data. Funding: National Key R&D Program of China and the National Natural Science Foundation of China.

Spontaneous cephalic version and risk factors for persistent breech presentation: a longitudinal retrospective cohort study.

AIMS: To address the rate of spontaneous version in breech presentation until term and explore the risk factors for persistent breech presentation diagnosed by the second-trimester ultrasound examination. METHODS: This is a retrospective cohort study of pregnant women with a singleton pregnancy who had their ultrasound examination conducted at the time of 22-26 weeks of gestation in the Guangzhou Women and Children's Medical Center. Cox regressions were applied to determine the strength of association between selected risk factors and persistent breech presentation. RESULTS: Among 25,313 pregnant women eligible for analysis, the prevalence of breech presentation was 36.8% (9,306/25,313) at 22-26 weeks of gestation, 4.2% (376/8,876) of which would remain in the breech presentation at the onset of labor (adjusted odds ratio [aOR], 0.39, 95% confidence interval [CI], 0.17-0.88). Multiparity (aOR, 0.39, 95% CI, 0.30-0.52) and longer gestational weeks at delivery (aOR, 0.50, 95% CI, 0.44-0.56) were associated with a lower risk of persistent breech presentation (PBP). Female fetus, lateral or fundal placenta, and known uterine malformation was each associated with an increased odd of 1.4 (aOR, 95% CI, 1.11-1.70), 2.4 (aOR, 95% CI,1.50-3.73), 3.1 (aOR, 95% CI, 1.71-5.53) and 8.7 (aOR, 95% CI, 3.84-19.84) times in the persistent breech presentation, respectively. CONCLUSION: The prevalence of the breech presentation was 36.8% between 22 and 26 weeks of gestation, and approximately 4% would have been in the persistent breech presentation until the onset of labor. Higher educational attainment, multiparity and longer gestational weeks at delivery were significantly decreasing the risk of persistent breech presentation. While the pregnant women with age >40 years, female fetus, lateral or fundal placenta and known uterine malformation were associated increased risk of persistent breech presentation.

Association between serum progesterone concentration in early pregnancy and duration of pregnancy: a cohort study.

Objective: To examine the association between progesterone concentration in early pregnancy and duration of pregnancy and risk of preterm delivery.Methods: Women enrolled in the Born in Guangzhou Cohort Study from 2013-2014, with a singleton pregnancy, who had serum progesterone measured at least one time between 4 and 10 weeks of gestation were included. The association between progesterone concentration both continuous and as categorical variable (quartile) and the risk of preterm delivery was assessed with Cox proportional hazards regression. Differences of length of gestation in four progesterone concentration quartiles were assessed using the Log-rank test.Results: We studied 1860 mother-newborn pairs. The mean overall progesterone concentration was 65.7 ± 21.3 nmol/L, with mean progesterone concentrations in the four quartiles of 42.4 ± 6.2 nmol/L (n = 463), 56.2 ± 3.3 nmol/L (n = 462), 68.9 ± 4.5 nmol/L (n = 470), and 95.1 ± 15.3 nmol/L (n = 465). There was no significantly difference in duration of gestation in four progesterone concentration groups (p=.511). There was no relation between progesterone level and preterm delivery (adjusted hazard ratio (HR) per 10 nmol/l progesterone level 1.00 (95% confidence interval (CI) 0.90, 1.11)). After adjusting for potential confounders, the HR of any preterm delivery for quartiles 1, 2 and 3 versus the highest quartile of progesterone level (> 77.3 nmol/L) was 1.04 (95% CI 0.52, 2.07), 1.17 (95% CI 0.60, 2.28), and 1.46 (95% CI 0.76, 2.78), respectively. When analysis was done for spontaneous preterm delivery only, also no association with first trimester progesterone was found.Conclusion: Lower first trimester serum progesterone concentration is not associated with reduction of length of gestation or increased risk of preterm delivery.

Publisher Correction: Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by androgen excess, ovulatory dysfunction and polycystic ovaries1, and is often accompanied by insulin resistance2. The mechanism of ovulatory dysfunction and insulin resistance in PCOS remains elusive, thus limiting the development of therapeutics. Improved metabolic health is associated with a relatively high microbiota gene content and increased microbial diversity3,4. This study aimed to investigate the impact of the gut microbiota and its metabolites on the regulation of PCOS-associated ovarian dysfunction and insulin resistance. Here, we report that Bacteroides vulgatus was markedly elevated in the gut microbiota of individuals with PCOS, accompanied by reduced glycodeoxycholic acid and tauroursodeoxycholic acid levels. Transplantation of fecal microbiota from women with PCOS or B. vulgatus-colonized recipient mice resulted in increased disruption of ovarian functions, insulin resistance, altered bile acid metabolism, reduced interleukin-22 secretion and infertility. Mechanistically, glycodeoxycholic acid induced intestinal group 3 innate lymphoid cell IL-22 secretion through GATA binding protein 3, and IL-22 in turn improved the PCOS phenotype. This finding is consistent with the reduced levels of IL-22 in individuals with PCOS. This study suggests that modifying the gut microbiota, altering bile acid metabolism and/or increasing IL-22 levels may be of value for the treatment of PCOS.

Effect of a two-stage intervention package on the cesarean section rate in Guangzhou, China: A before-and-after study.

BACKGROUND: The cesarean section (CS) rate has risen globally during the last two decades. Effective and feasible strategies are needed to reduce it. The aim of this study was to assess the CS rate change after a two-stage intervention package that was designed to reduce the overall CS rate in Guangzhou, China. METHODS AND FINDINGS: This intervention package was implemented by the Health Commission of Guangzhou Municipality in 2 stages (October 2010-September 2014 and October 2014-December 2016) and included programs for population health education, skills training for healthcare professionals, equipment and technical support for local healthcare facilities, and capacity building for the maternal near-miss care system. A retrospective repeated cross-sectional study was conducted to evaluate influences of the intervention on CS rates. A pre-intervention period from January 2008 to September 2010 served as the baseline. The primary outcome was the CS rate, and the secondary outcomes included maternal mortality ratio (MMR) and perinatal mortality rate (PMR), all obtained from the Guangzhou Perinatal Health Care and Delivery Surveillance System (GPHCDSS). The Cochran-Armitage test was used to examine the trends of the overall CS rate, MMR, and PMR across different stages. Segmented linear regression analysis was used to assess the change of the CS rate over the intervention period. A total of 1,921,932 records of births and 108 monthly CS rates from 2008 to 2016 were analyzed. The monthly CS rate declined across the intervention stages (Z = 75.067, p < 0.001), with an average rate of 42.4% at baseline, 39.8% at Stage 1, and 35.0% at Stage 2. The CS rate declined substantially among nulliparous women who delivered term singletons, with an accelerating decreasing trend observed across Stage 1 and Stage 2 (the difference in slopes: -0.09 [95% CI -0.16 to -0.02] between Stage 1 and baseline, p = 0.014; -0.11 [95% CI -0.20 to -0.02] between Stage 1 and Stage 2, p = 0.017). The CS rate in the remaining population increased during baseline and Stage 1 and subsequently decreased during Stage 2. The sensitivity analysis suggested no immediate impact of the universal two-child policy on the trend of the CS rate. The MMR (Z = -4.368, p < 0.001) and PMR (Z = -13.142, p < 0.001) declined by stage over the intervention period. One of the main limitations of the study is the lack of a parallel control group. Moreover, the influence of temporal changes in the study population on the CS rate was unknown. Given the observational nature of the present study, causality cannot be confirmed. CONCLUSIONS: Apparent decline in the overall CS rate was observed in Guangzhou, China, after the implementation of a two-stage intervention package. The decline was most evident among nulliparous women who delivered term singletons. Despite some limitations for causal inference, Guangzhou's experience in controlling the CS rate by implementing composite interventions with public health education and perinatal healthcare service improvement could have implications for other similar areas with high rates of CS.

Consultation and treatment behaviour of infertile couples in China: a population-based study.

RESEARCH QUESTION: The prevalence of infertility in couples actively trying to conceive is 25%. What is the consultation-seeking behaviour, diagnosis and related treatment in infertile couples across China? DESIGN: Large cross-sectional population-based study in 2010-2011, in which 25,270 couples from eight provinces/municipalities in China were approached by a multistage stratified cluster sampling strategy. RESULTS: Among the 2680 couples reporting infertility, 1246 infertile couples consulted a fertility doctor. Age of the couple, man's body mass index and women's educational level were found to be associated with consultation behaviour. After the fertility work-up, diagnoses were tubal infertility (n = 353, 28.3%), unexplained infertility (n = 311, 25.0%), male infertility (n = 234, 18.8%), ovulatory disorder (n = 194, 15.6%) and endometriosis (n = 34, 2.7%), while 8.6% (n = 107) were not classified. Most couples received non-assisted reproductive technology (ART) fertility treatment (n = 906, 89.3%), with a proportion using traditional Chinese medicine (TCM) (n = 298, 29.4%). Intrauterine insemination (n = 62, 6.1%) and IVF/intracytoplasmic sperm injection (n = 57, 5.6%) were less frequent. Medical treatment and outcomes among five subtypes of infertility were also reported: about 30% of couples with unexplained infertility (n = 94, 30.3%) or male infertility (n = 67, 29.0%) used TCM to treat infertility. Apart from patients with endometriosis, of whom 20.6% (n = 7) received ART, patients with other infertility subtypes rarely received ART. For subsequent fertility outcome, 94% of them did not achieve a pregnancy. CONCLUSION: The prevalence of infertility in China is high, but the uptake of treatment is relatively low.

Assisted reproductive technology in Beijing, 2013-2015.

RESEARCH QUESTION: Why are comprehensive and detailed reports of local or national utilization outcomes of assisted reproductive technology (ART) lacking in China? DESIGN: Retrospective collection of data on intrauterine insemination (IUI) and IVF and intracytoplasmic sperm injection (ICSI) in Beijing, including all 12 registered institutions with cycles, started between 1 January 2013 and 31 December 2015. RESULTS: Clinical pregnancy rates (CPR) per aspiration and fresh embryo transfer were 39.1% and 43.2% in 2013, 40.1% and 45.4% in 2014, and 37.8% and 44.5% in 2015; live birth rates (LBR) per aspiration and per fresh embryo transfer were 31.7% and 35.0%, 32.3% and 36.6%, and 30.3% and 35.6%, respectively. In frozen embryo transfer (FET) cycles, the CPR per thawed transfer was 43.4%, 47.2% and 46.2%, respectively, resulting in LBR of 34.3%, 37.4% and 36.5%. The prevalence of multiple pregnancies was 28.0-31.3% for fresh embryo transfer, and 23.5-25.9% for FET. The LBR was 8.8-9.1% after IUI with husband or partner's semen (IUI-H), and 16.7-19.7% after IUI with donor semen (IUI-D). The birth defect rate among live born infants was 1.52%, 0.42% and 0% after IUI-H, 1.05%, 0.39% and 0.66% after IUI-D, 0.71%, 0.56% and 0.46% after fresh embryo transfer, and 0.73%, 0.20% and 0.18% after FET in 2013, 2014 and 2015, respectively. CONCLUSIONS: In Beijing over 3 years, the number of IVF-ICSI cycles has increased and the number of IUI cycles has decreased; IVF-ICSI outcomes are better and safer. Further effort should be made to lower the multiple pregnancy rates. A Chinese nationwide ART registry should be promoted.

Sperm origins and concentration do not impact the clinical outcomes in intracytoplasmic sperm injection cycles.

In the present study, we evaluated the impact of sperm origins and concentration on the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles. A total of 1201 ICSI cycles were retrospectively analyzed for male azoospermia or oligozoospermia between January 2015 and December 2015 in the Peking University Third Hospital. Patients were divided into three groups (Group 1 vs Group 2/3; surgically extracted sperm vs ejaculated sperms): Group 1 included 343 ICSI cycles and Group 2 analyzed 388 cycles on semen with sperm concentration <5 × 106 ml-1 (severe oligozoospermia group). Group 3 included 470 cycles with sperm concentration between 5 × 106 ml-1 and 15 × 106 ml-1 (mild oligozoospermia group). Fertilization rates, clinical pregnancy rates, and live birth rates were analyzed and compared among groups of different semen origins and concentrations on the oocyte retrieval day. Group 2 showed a lower fertilization rate than Group 3 (62.9% ± 21.6% vs 66.8% ± 22.1%,P< 0.05). There were no statistically significant differences in clinical pregnancy rate per transfer (51.3%, 46.7%, and 50.0%, respectively), live birth rate per transfer (44.4%, 40.9%, and 41.4%, respectively), accumulative live birth rate (58.3%, 51.0%, and 52.1%, respectively), twin birth rate (18.4%, 10.6%, and 12.6%, respectively), and birth defects rate (0, 0.3%, and 0.2%, respectively) among three groups. The results of this study indicated that sperm origins and concentration do not impact the clinical outcomes in ICSI cycles.

Effect of Levothyroxine on Miscarriage Among Women With Normal Thyroid Function and Thyroid Autoimmunity Undergoing In Vitro Fertilization and Embryo Transfer: A Randomized Clinical Trial.

Importance: Presence of thyroid autoantibodies in women with normal thyroid function is associated with increased risk of miscarriage. Whether levothyroxine treatment improves pregnancy outcomes among women undergoing in vitro fertilization and embryo transfer (IVF-ET) is unknown. Objective: To determine the effect of levothyroxine on miscarriage among women undergoing IVF-ET who had normal thyroid function and tested positive for thyroid autoantibodies. Design, Setting, and Participants: An open-label, randomized clinical trial involving 600 women who tested positive for the antithyroperoxidase antibody and were being treated for infertility at Peking University Third Hospital from September 2012 to March 2017. Interventions: The intervention group (n = 300) received either a 25-µg/d or 50-µg/d dose of levothyroxine at study initiation that was titrated according to the level of thyroid-stimulating hormone during pregnancy. The women in the control group (n = 300) did not receive levothyroxine. All participants received the same IVF-ET and follow-up protocols. Main Outcomes and Measures: The primary outcome was the miscarriage rate (pregnancy loss before 28 weeks of gestation, which was calculated among women who became pregnant). The secondary outcomes were clinical intrauterine pregnancy rate (fetal cardiac activity seen at sonography observation on the 30th day after the embryo transfer), and live-birth rate (at least 1 live birth after 28 weeks of gestation). Results: Among the 600 women (mean [SD] age, 31.6 [3.8] years) randomized in this trial, 567 women (94.5%) underwent IVF-ET and 565 (94.2%) completed the study. Miscarriage rates were 10.3% (11 of 107) in the intervention group and 10.6% (12 of 113) in the control group, with the absolute rate difference (RD) of -0.34% (95% CI, -8.65% to 8.12%) over the 4.5-year study period. Clinical intrauterine pregnancy rates were 35.7% (107 of 300) in the intervention group and 37.7% (113 of 300) in the control group, with an absolute RD of -2.00% (95% CI, -9.65% to 5.69%). Live-birth rates were 31.7% (95 of 300) in the intervention group and 32.3% (97 of 300) in the control group, with an absolute RD of -0.67% (95% CI, -8.09% to 6.77%). Conclusions and Relevance: Among women in China who had intact thyroid function and tested positive for antithyroperoxidase antibodies and were undergoing IVF-ET, treatment with levothyroxine, compared with no levothyroxine treatment, did not reduce miscarriage rates or increase live-birth rates. Trial Registration: Chinese Clinical Trial Registry: ChiCTR-TRC-13004097.

Androgen profile in Chinese women with polycystic ovary syndrome in their reproductive years.

Large comparative studies of androgen profiles in women with polycystic ovary syndrome (PCOS) and healthy women are scarce, and the application of the free androgen index (FAI) in diagnosing PCOS has lagged behind in China. Androgen profiles of women aged between 19 and 45 years with PCOS (n = 833) were compared with controls (n = 2732). The women with PCOS had an elevated androgen level (total testosterone, androstenedione and free androgen index) through their reproductive years. In the 'healthy' reference population (consisting of 821 controls without PCOS and without disorders affecting androgen concentrations), FAI, total testosterone and androstenedione were weakly but negatively correlated with age. In women with PCOS, androstenedione was negatively correlated with age (r = -0.106; P = 0.002), whereas increased total testosterone and FAI, and decreased SHBG, were observed in the group aged 40-45 years. After adjusting for body mass index (BMI), age was negatively correlated with FAI and androstenedione, and positively correlated with sex hormone-binding globulin (SHBG) (all P < 0.001). Hyperandrogenaemia seemed to worsen in the oldest women with PCOS, which might be explained by the increasing BMI. About 1.9% of the PCOS control population was diagnosed with PCOS using the FAI upper limit of 6.0, determined by the 95th percentile of the 'healthy' reference group. Body weight management should be emphasized for women with PCOS throughout their lives, and assay of SHBG and FAI is highly recommended in China.

Overexpression of Lnk in the Ovaries Is Involved in Insulin Resistance in Women With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) progression involves abnormal insulin signaling. SH2 domain-containing adaptor protein (Lnk) may be an important regulator of the insulin signaling pathway. We investigated whether Lnk was involved in insulin resistance (IR). Thirty-seven women due to receive laparoscopic surgery from June 2011 to February 2012 were included from the gynecologic department of the Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Samples of polycystic and normal ovary tissues were examined by immunohistochemistry. Ovarian cell lines underwent insulin stimulation and Lnk overexpression. Expressed Lnk underwent coimmunoprecipitation tests with green fluorescent protein-labeled insulin receptor and His-tagged insulin receptor substrate 1 (IRS1), and their colocalization in HEK293T cells was examined. Ovarian tissues from PCOS patients with IR exhibited higher expression of Lnk than ovaries from normal control subjects and PCOS patients without IR; mainly in follicular granulosa cells, the follicular fluid and plasma of oocytes in secondary follicles, and atretic follicles. Lnk was coimmunoprecipitated with insulin receptor and IRS1. Lnk and insulin receptor/IRS1 locations overlapped around the nucleus. IR, protein kinase B (Akt), and ERK1/2 activities were inhibited by Lnk overexpression and inhibited further after insulin stimulation, whereas IRS1 serine activity was increased. Insulin receptor (Tyr1150/1151), Akt (Thr308), and ERK1/2 (Thr202/Tyr204) phosphorylation was decreased, whereas IRS1 (Ser307) phosphorylation was increased with Lnk overexpression. In conclusion, Lnk inhibits the phosphatidylinositol 3 kinase-AKT and MAPK-ERK signaling response to insulin. Higher expression of Lnk in PCOS suggests that Lnk probably plays a role in the development of IR.

Defining hyperandrogenaemia according to the free androgen index in Chinese women: a cross-sectional study.

OBJECTIVE(S): To determine the normative cut-off value for the free androgen index (FAI) among reproductive-age women in China. DESIGN: Cross-sectional, population-based study. SETTING: A multistage systematic cluster random sampling among 16 communities from two rural and two city regions. PATIENT(S): A total of 1526 women were randomly selected from a representative sample of 3009 women aged 20-45 years from the general population of southern China. Among these women, 444 subjects without known factors affecting androgen levels were selected as the reference group. INTERVENTION(S): Subjects underwent physical examination, blood tests of hormone and metabolic profiles, and ultrasound evaluations. MEASUREMENT OF THE MAIN OUTCOMES: The FAI was calculated according to the following equation: FAI = 100 × total testosterone (nmol/l)/sex hormone-binding globulin (nmol/l). The normative cut-off value of the FAI was computed based on the 5th-95th percentiles and K-means cluster analysis (K = 2). RESULTS: A reference range of 0·7-6·4 of the FAI was indicated by the 5th and 95th percentiles. K-means cluster analysis identified 6·1 as the cut-off value for the FAI in the total population, which was close to the upper limit determined by the 95th percentile. Hyperandrogenic women present with elevated risk factors for metabolic disorders. The mean FAI values decreased with age among the total population, as evaluated by either K-means clustering or a percentile analysis. The FAI value was negatively correlated with age (r = -0·185, P < 0·0001) and positively correlated with body mass index after adjustment for age (r = 0·250, P < 0·0001). CONCLUSION: A reference range of 0·7-6·4 FAI was indicated by the 5th and 95th percentiles among the reference group, which excluded the subjects with factors known to affect androgen levels; 6·1 was identified by the K-means cluster analysis as the cut-off value of the FAI for the general population. Hyperandrogenic women present with higher risks for metabolic disorders.