Publications by authors named "Guimin Hao"

23 Publications

  • Page 1 of 1

Effect of orlistat on live birth rate in overweight or obese women undergoing IVF-ET: A randomized clinical trial.

J Clin Endocrinol Metab 2021 May 15. Epub 2021 May 15.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University; The Key Laboratory of Reproductive Endocrinology of Ministry of Education; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China.

Context: Obesity management prior to infertility treatment remains a challenge. To date, results from randomized clinical trials involving weight loss by lifestyle interventions have shown no evidence of improved live birth rate.

Objective: To determine whether pharmacologic weight-loss intervention before in vitro fertilization and embryo transfer (IVF-ET) can improve live birth rate among overweight or obese women.

Design, Setting, And Participants: We conducted a randomized, double-blinded, placebo-controlled trial across 19 reproductive medical centers in China, from July 2017 to January 2019. A total of 877 infertile women scheduled for IVF who had a body mass index of 25kg/m 2 or greater were randomly assigned.

Interventions: The participants were randomized to receive orlistat (n=439) or placebo (n=438) treatment for 4-12 weeks.

Main Outcomes And Measures: Live birth rate after fresh embryo transfer.

Results: The live birth rate was not significantly different between the two groups (112 of 439 [25.5%] with orlistat and 112 of 438 [25.6%] with placebo; P=.984). No significant differences existed between the groups as to the rates of conception, clinical pregnancy, and pregnancy loss. A statistically significant increase in singleton birthweight was observed after orlistat treatment (3487.50g versus 3285.17g in the placebo group; P=.039). The mean change in body weight during the intervention was -2.49kg in the orlistat group, as compared to -1.22kg in the placebo group, with a significant difference (P=.005).

Conclusions: Orlistat treatment, prior to IVF-ET, did not improve live birth rate among overweight or obese women, although it was beneficial for weight reduction.
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http://dx.doi.org/10.1210/clinem/dgab340DOI Listing
May 2021

Effects of multicycle gonadotropin-releasing hormone antagonist protocols on oxidative stress of follicular fluid and ovarian granulosa cells.

Hum Cell 2021 May 8. Epub 2021 May 8.

Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

The effect of repeated multicycle gonadotropin-releasing hormone antagonist (GnRH-ant) protocols on oxidative stress (OS) in follicular fluid (FF) and ovarian granulosa cells (GCs) remains unclear. This study investigated the effects of repeated multicycle GnRH-ant protocols on OS markers of FF and ovarian GCs. A total of 145 patients were enrolled and divided into four groups: 1 cycle group (n = 42), 2 cycles group (n = 37), 3 cycles group (n = 45), and 4-5 cycles group (n = 21). The FF and ovarian GCs of the patients were collected on the day of last oocyte retrieval and the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were tested by ELISA. The results showed that the serum estradiol levels on hCG injection day in the 3 and 4-5 cycles were significantly (P < 0.05) lower than in the 1 and 2 cycles. The number of retrieved oocytes (12.1 ± 3.3 in cycle 1, 11.7 ± 3.1 in cycle 2, 10.4 ± 2.4 in cycle 3, and 9.4 ± 2.4 in cycles 4-5), embryos with two pronuclei (7.6 ± 3.0 in cycle 1, 7.0 ± 2.5 in cycle 2, 6.2 ± 2.6 in cycle 3, and 5.5 ± 2.1 in cycles 4-5), and the rates of high-quality embryos (52.2% in cycle 1, 47.9% in cycle 2, 38.6% in cycle 3, and 36.5% in cycles 4-5), implantation (35.4% in cycle 1, 32.4% in cycle 2, 23.8% in cycle 3, and 22.9% in cycles 4-5) and clinical pregnancy (50.0% in cycle 1, 43.2% in cycle 2, 33.3% in cycle 3, and 23.8% in cycles 4-5) in cycles 3 and 4-5 were significantly (P < 0.05) lower than those in cycles 1 and 2. Compared with 1 and 2 cycles, the 8-OHdG and SOD were significantly increased in the 3-5 cycles, while the CAT and GSH-Px levels were significantly decreased. Together, this study reveals repeated COS with the use of GnRH-ant protocols results in OS and changes the follicle microenvironment of FF and GCs, possibly leading to poor IVF outcomes in patients with 3-5 cycles of COS.
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http://dx.doi.org/10.1007/s13577-021-00545-9DOI Listing
May 2021

Association between exposure to ambient air pollutants and the outcomes of in vitro fertilization treatment: A multicenter retrospective study.

Environ Int 2021 Aug 2;153:106544. Epub 2021 Apr 2.

Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, No. 39 Huaxiang Road, Tiexi District, Shenyang, Liaoning 110022, PR China; Key Laboratory of Reproductive Dysfunction Disease and Fertility Remodeling of Liaoning Province, PR China. Electronic address:

Background: Exposure to ambient air pollution has been reported to be inversely correlated with human reproductive health. However, the results of previous studies exploring the association between air pollution and in vitro fertilization (IVF) outcomes are conflicting, and further research is needed to clarify this association.

Objectives: This study aimed to investigate the associations between exposure to air pollutants and IVF outcomes.

Methods: We conducted a multicenter retrospective cohort study involving 20,835 patients from four cities in Northern China, contributing to 11,787 fresh embryo transfer cycles, 9050 freeze-all cycles, and 17,676 frozen-thawed embryo transfer (FET) cycles during 2014-2018. We calculated the daily average concentrations of six criteria air pollutants (PM, PM, O, NO, CO, and SO) during different exposure windows in IVF treatment timeline using data from the air monitoring station nearest to the residential site as approximate individual exposure. Generalized estimation equation models were used to assess the association between air pollution exposure and IVF outcomes.

Results: Exposure to O, NO, and CO during most exposure windows in fresh embryo transfer cycles were correlated with lower possibilities of biochemical pregnancy, clinical pregnancy, and live birth. An inverse association of exposure to O and SO with pregnancy outcomes was observed in FET cycles. In addition, we found a significant association of exposure to air pollutants with a higher risk of ectopic pregnancy and lower oocyte yield.

Conclusions: Our study provided large-scale human evidence of the association between air pollution and adverse human reproductive outcomes in the population opting for IVF. Thus, exposure to air pollutants in the population opting for IVF should be limited to improve treatment outcomes.
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http://dx.doi.org/10.1016/j.envint.2021.106544DOI Listing
August 2021

Sperm mtDNA copy number, telomere length, and seminal spermatogenic cells in relation to ambient air pollution: Results of a cross-sectional study in Jing-Jin-Ji region of China.

J Hazard Mater 2021 03 23;406:124308. Epub 2020 Oct 23.

Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang 050017, PR China; Hebei Key Laboratory of Environment and Human Health, Shijiazhuang 050017, PR China. Electronic address:

Evidences on the association of air pollutants and semen quality were limited and mechanism-based biomarkers were sparse. We enrolled 423 men at a fertility clinic in Shijiazhuang, China to evaluate associations between air pollutants and semen quality parameters including the conventional ones, sperm mitochondrial DNA copy number (mtDNAcn), sperm telomere length (STL) and seminal spermatogenic cells. PM, PM, CO, SO, NO and O exposure during lag0-90, lag0-9, lag10-14 and lag70-90 days were evaluated with ordinary Kringing model. The exposure-response correlations were analyzed with multiple linear regression models. CO, PM and PM were adversely associated with conventional semen parameters including sperm count, motility and morphology. Besides, CO was positively associated with seminal primary spermatocyte (lag70-90, 0.49; 0.14, 0.85) and mtDNAcn (lag0-90, 0.37; 0.12, 0.62, lag10-14, 0.31; 0.12, 0.49), negatively associated with STL (lag0-9, -0.30; -0.57, -0.03). PM was positively associated with mtDNAcn (0.50; 0.24, 0.75 and 0.38; 0.02, 0.75 for lag0-90 and lag70-90) while negatively associated with STL (lag70-90, -0.49; -0.96, -0.01). PM and NO were positively associated with mtDNAcn. Our findings indicate CO and PM might impair semen quality testicularly and post-testicularly while seminal spermatogenic cell, STL and mtDNAcn change indicate necessity for more attention on these mechanisms.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124308DOI Listing
March 2021

Maternal and Neonatal Complications After Natural vs. Hormone Replacement Therapy Cycle Regimen for Frozen Single Blastocyst Transfer.

Front Med (Lausanne) 2020 28;7:338. Epub 2020 Aug 28.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.

To evaluate the maternal and neonatal complications after frozen-thawed blastocyst transfer cycles utilizing different endometrial preparation regimens. This is a retrospective cohort study and a secondary analysis of a multicenter, randomized, controlled trial comparing live birth rate after fresh vs. frozen single blastocyst transfer (Frefro-blastocyst). Reproductive medicine centers. A total of 800 women with regular menstrual cycles undergoing their first cycle of fertilization after frozen-thawed single blastocyst transfer. Endometrium preparation was performed with a natural cycle regimen or hormone replacement therapy (HRT) cycle regimen, at the discretion of local investigators. All pregnancies were followed up until delivery. Maternal and neonatal complications. 513 infertile patients who underwent natural cycles regimen and 287 who underwent HRT cycles regimen were analyzed. The incidences of maternal and neonatal complications were comparable between the natural cycle and HRT cycle regimen. Regarding the risk of gestational diabetes, gestational hypertension, pre-eclampsia, preterm delivery, small for gestational age and large for gestational age, the HRT cycle was still not a significant risk factor after adjusting for potential confounders. The natural cycle regimen yielded an insignificant higher total live birth rate [59.45 vs. 50.17%, = 0.001, adjusted odds ratio (AOR) 1.366, 95% confidence interval (CI) 0.975-1.913], clinical pregnancy rate (68.23 vs. 58.89%, = 0.008, AOR 1.406, 95% CI 0.992-1.991) and ongoing pregnancy rate (62.18 vs. 52.61%, = 0.008, AOR 1.387, 95% CI 0.988-1.948) than did the HRT cycle regimen. However, compared to natural cycles, HRT cycles were associated with a significantly higher risk of biochemical miscarriage (6.86 vs. 18.18%, < 0.001, AOR 0.328, 95% CI, 0.176-0.611). The incidence of maternal and neonatal complications in natural cycle and HRT cycle regimens after frozen single blastocyst transfer were comparable. Frozen-thawed single blastocyst transfer in a natural cycle was associated with lower biomedical miscarriage than the use of the HRT cycle. Frefro-blastocyst was registered at Chinese Clinical Trial Registry, ChiCTR-IOR-14005405.
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http://dx.doi.org/10.3389/fmed.2020.00338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483478PMC
August 2020

Association between Body Mass Index and Reproductive Outcome in Women with Polycystic Ovary Syndrome Receiving IVF/ICSI-ET.

Biomed Res Int 2020 21;2020:6434080. Epub 2020 Aug 21.

Second Hospital of Hebei Medical University, Shijiazhuang, 050000 Hebei, China.

Objective: To examine the association between body mass index (BMI) and the outcome of in vitro fertilization or intracytoplasmic sperm injection embryo transfer- (IVF/ICSI-ET) assisted reproduction in women with polycystic ovary syndrome (PCOS) receiving the ultra-long agonist protocol.

Methods: We retrospectively identified all women receiving IVF/ICSI-ET for the first time using the ultra-long protocol between January 2013 and January 2018 at our hospital. Only women at ≤35 years of age receiving the first cycle were analyzed.

Results: A total of 1782 women were included in the analysis: 42 were underweight, 742 were overweight, 198 were obese, and 800 were normal weight. Gonadotropin dosage and duration were comparable between underweight and normal weight groups but were significantly higher/longer in overweight and obese groups ( < 0.008). The number of oocytes retrieved was significantly lower in overweight and obese groups than in the normal weight group ( < 0.008). The number of transferable embryos was significantly higher in normal weight group than overweight and obese groups ( < 0.008). Embryo implantation rate, clinical pregnancy rate, full-term birth rate, and live birth rate did not differ among the 4 groups. The cycle cancellation rate was lower in the overweight and obese group than normal weight group ( < 0.008). The miscarriage rate was higher in the obese group than the normal weight group ( < 0.008). In multivariate logistic regression analysis, abnormal BMI was an independent risk for miscarriage (OR: 1.069, 95% CI 1.020, 1.122; = 0.006).

Conclusion: Overweight and obesity are associated with poor outcomes in PCOS patients receiving ultra-long protocol. Measures to reduce body weight should be encouraged in overweight and obese PCOS women at ≤35 years of age prior to assisted reproductive technology (ART).
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http://dx.doi.org/10.1155/2020/6434080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463361PMC
April 2021

Ambient air pollution exposed during preantral-antral follicle transition stage was sensitive to associate with clinical pregnancy for women receiving IVF.

Environ Pollut 2020 Oct 25;265(Pt B):114973. Epub 2020 Jun 25.

Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, 050017, PR China; Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, 050017, PR China. Electronic address:

Maternal exposure to air pollution is associated with poor reproductive outcomes in in vitro fertilization (IVF). However, the susceptible time windows are still not been known clearly. In the present study, we linked the air pollution data with the information of 9001 women receiving 10,467 transfer cycles from August 2014 to August 2019 in The Second Hospital of Hebei Medical University, Shijiazhuang City, China. Maternal exposure was presented as individual average daily concentrations of PM, PM, NO, SO, CO, and O which were predicted by spatiotemporal kriging model based on residential addresses. Exposure windows were divided to five periods according to the process of follicular and embryonic development in IVF. Generalized estimating equation model was used to evaluate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for association between clinical pregnancy and interquartile range increased average daily concentrations of pollutants during each exposure period. The increased PM (adjusted OR = 0.95, 95% CI: 0.90, 0.99), PM (adjusted OR = 0.93, 95% CI: 0.89, 0.98), NO (adjusted OR = 0.89, 95% CI: 0.85, 0.94), SO (OR = 0.94, 95% CI: 0.90, 0.98), CO (adjusted OR = 0.93, 95% CI: 0.89, 0.97) whereas decreased O (OR = 1.08, 95% CI: 1.02, 1.14) during the duration from preantral follicles to antral follicles were the strongest association with decreased probability of clinical pregnancy among the five periods. Especially, women aged 20-29 years old were more susceptible in preantral-antral follicle transition stage. Women aged 36-47 years old were more vulnerable during post-oocyte retrieve period. Our results suggested air pollution exposure during preantral-antral follicle transition stage was a note-worthy challenge to conceive among females receiving IVF.
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http://dx.doi.org/10.1016/j.envpol.2020.114973DOI Listing
October 2020

Comparison of the combination of recombinant follicle-stimulating hormone and recombinant luteinizing hormone protocol versus human menopausal gonadotropin protocol in controlled ovarian stimulation: A systematic review and meta-analysis.

J Evid Based Med 2020 Aug 6;13(3):215-226. Epub 2020 Jul 6.

Chinese Evidence-based Medicine Center and CREAT Group, West China Hospital, Sichuan University, Chengdu, PR China.

Objective: To systematically review the efficacy of a combination of recombinant follicle-stimulating hormone (rFSH) and recombinant luteinizing hormone (rLH) protocol versus human menopausal gonadotropin (hMG) protocol in controlled ovarian stimulation (COS).

Methods: PubMed, EMbase, The Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and WanFang Data were searched to collect studies published prior to January 2019 on the efficacy of rFSH combined with rLH versus hMG alone in COS. Two reviewers independently screened the literature, conducted the data extraction, and assessed the risk of bias for all selected studies. Then, Review Manager 5.3 software was used for the meta-analysis.

Results: There were 2767 patients from 9 studies. The results showed that among patients aged >30 years for IUI, the combination of rFSH and rLH was superior to hMG alone in clinical pregnancy rate per patient (relative risk [RR] = 1.47, 95% confidence interval [CI] 1.02 to 2.12) and endometrial thickness (mean difference [MD] = 0.34, 95% CI 0.04 to 0.64). In patients over 30 years old who received IVF, the results tended to favor the combination of rFSH and rLH in clinical pregnancy rate per patient (RR = 4.48, 95% CI 1.15 to 17.46) and live birth rate per started cycle (RR = 1.69, 95% CI 1.96 to 2.71). In patients less than 30 years old who received IVF, the combination of rFSH and rLH was superior to hMG in the number of retrieved oocytes (MD = 3.70, 95% CI 3.27 to 4.13) and inferior to hMG in number of high-quality embryos (MD = -0.60, 95% CI -0.91 to -0.29).

Conclusion: The combination of rFSH and rLH may have better efficacy than hMG alone in COS. However, considering the limited sample size of the included studies, the current evidence is not definitive.
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http://dx.doi.org/10.1111/jebm.12390DOI Listing
August 2020

Major Factors Affecting the Live Birth Rate After Frozen Embryo Transfer Among Young Women.

Front Med (Lausanne) 2020 24;7:94. Epub 2020 Mar 24.

Center for Reproductive Medicine, Shandong University, Jinan, China.

In recent years, the freeze-all strategy has been widely adopted and applied. However, with the exception of age, the factors that affect the outcomes of frozen embryo transfer are still unclear. Therefore, the identification and mitigation of factors that influence the live birth rate after frozen embryo transfer is a good way to increase the "take-home-baby" rate of frozen embryo transfer. The objective of this study was to identify factors affecting the live birth rate after cleavage-stage frozen embryo transfer in young ovulatory women. This was a secondary analysis from a previously published multicenter randomized controlled trial (ChiCTR-IOR-14005406) that was originally designed to compare the live birth rate and perinatal complications after fresh embryo transfer to those after frozen embryo transfer among ovulatory women. This study was carried out using a portion of the data from the original randomized controlled trial, which included 917 young women who underwent cleavage-stage frozen embryo transfer. The 16 clinical candidate variables potentially affecting the live birth rate after frozen embryo transfer were analyzed. Univariable analysis and multivariable analysis were performed to assess the relationship between predictive factors and outcomes, with the aim of identifying independent predictors of live birth after frozen embryo transfer. In this study, the live birth rate was 53.0% (486/917). Three independent predictors were ultimately identified as the main factors affecting the live birth rate of ovulatory young women. Infertility duration [odds ratio (OR): 0.933, 95% confidence interval (CI): 0.876-0.995, = 0.033], endometrial thickness before frozen embryo transfer (OR: 3.375, 95% CI: 1.556-7.321 = 0.002), and the number of embryos transferred (OR: 2.653, 95% CI:1.226-5,743, = 0.013) were the major factors contributing to the live birth rate after cleavage-stage frozen embryo transfer among young women. The cut-off point for infertility duration was 4.5 years, and the cut-off point for endometrial thickness was 0.89 cm. Infertility duration, endometrial thickness and number of embryos transferred might affect the live birth rate after frozen embryo transfer among young women. This result could help inform clinical decisions and counseling to increase the live birth rate after frozen embryo transfer among young women.
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http://dx.doi.org/10.3389/fmed.2020.00094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105776PMC
March 2020

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase.

J Ovarian Res 2019 Nov 13;12(1):109. Epub 2019 Nov 13.

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder and regarded as the leading cause of anovulatory infertility. PCOS is characterized by reproductive dysfunction and metabolic disorders. Baicalin (BAL) is one of the most potent bioactive flavonoids isolated from the radix of Scutellaria baicalensis. In the present study, we investigated the potential effects of BAL on PCOS in dehydroepiandrosterone-treated rats. We found that BAL notably reduced the serum levels of free testosterone, total testosterone, follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol in PCOS rats. The increase of serum insulin level and HOMA-IR was markedly inhibited by BAL. Moreover, BAL decreased body weights, increased the number of rats with the regular estrous cycle, and ameliorated ovarian histological changes and follicular development in the DHEA-treated PCOS rats. The increase of pro-inflammatory cytokines (TNFα, IL-1β, and IL-18) and decrease of anti-inflammatory cytokine (IL-10) in PCOS rats were suppressed by BAL. BAL induced a significant decrease in the mRNA expression of steroidogenic enzymes, including 3β-HSD, CYP11A1, CYP19A1, StAR, in ovarian tissues in PCOS rats. Furthermore, BAL inhibited the decrease of AMPK protein level and phosphorylation, the decrease of Akt phosphorylation and the increase of 5α-reductase enzyme 1 expression in ovarian tissues in PCOS rats. The effects of BAL were inhibited by an inhibitor of AMPK, dorsomorphin. The upregulation of AMPK contributed to the beneficial effects of BAL. The results highlight the potential role of BAL for the intervention of PCOS.
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http://dx.doi.org/10.1186/s13048-019-0585-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852906PMC
November 2019

Intracytoplasmic sperm injection (ICSI) versus conventional in vitro fertilisation (IVF) in couples with non-severe male infertility (NSMI-ICSI): protocol for a multicentre randomised controlled trial.

BMJ Open 2019 09 30;9(9):e030366. Epub 2019 Sep 30.

Centre for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China

Introduction: Intracytoplasmic sperm injection (ICSI), originally introduced as add-on to in vitro fertilisation (IVF) for couples with severe male infertility, is in current clinical practice also used in couples with mild male or even unexplained infertility. However, ICSI has involved unresolved concerns regarding the selection and damage to gametes and the health conditions of the offspring, and it is also labour intensive and therefore more expensive than conventional IVF. High-quality well-powered randomised clinical trials (RCTs) comparing ICSI and IVF are lacking.

Methods And Analysis: We propose a multicentre, open-label RCT in 10 reproductive medical centres across China. We will study couples with non-severe male infertility (defined as a semen concentrate 5-15×10/mL or sperm with a progressive motility 10%-32%) scheduled for their first or second ICSI or IVF cycle, as low fertility rate after fertilisation are more frequent in this population, which could lead to controversy about ICSI or conventional IVF for fertilisation. On the day of oocyte retrieval, eligible participants are after informed consent be randomised to undergo either ICSI or conventional IVF in a 1:1 treatment ratio. Other standard assisted reproductive treatments are similar and parallel between two groups. Our primary outcome is ongoing pregnancy leading to live birth after the first cycle with embryo transfer. To demonstrate or refute a difference of 7% between ICSI and conventional IVF, we need to include 2346 women (1173 in each intervention arm). In addition, we will follow-up neonatal outcomes after delivery to identify the influence of ICSI on offspring.

Ethics And Dissemination: Ethical approval was obtained from Peking University Third Hospital medical science research ethics committee. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals.

Trial Registration Number: ClinicalTrials.gov registry (NCT03298633).
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http://dx.doi.org/10.1136/bmjopen-2019-030366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773417PMC
September 2019

MicroRNA-200b and microRNA-200c are up-regulated in PCOS granulosa cell and inhibit KGN cell proliferation via targeting PTEN.

Reprod Biol Endocrinol 2019 Aug 17;17(1):68. Epub 2019 Aug 17.

Center for Reproductive Medicine, Shandong University; The Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, China; Shandong Provincial Clinical Medicine Research Center for reproductive health, Jinan, 250021, China.

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have reported that the aberrant expression of miRNAs contributes a lot to disordered folliculogenesis in PCOS, though the role and underlying mechanism of microRNA-200b (miR-200b) and microRNA-200c (miR-200c) in the development of PCOS remain unclear.

Methods: The expression of miR-200b in granulosa cells (GCs) derived from 90 PCOS patients and 70 controls was analyzed by using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Granulosa-like tumor cell line (KGN) was cultured for cell counting kit-8 (CCK-8) assays after over-expression of miR-200b, miR-200c or knockdown phosphatase and tensin homolog (PTEN). TargetScan was used to identify the potential targets of miR-200b and miR-200c, which was further verified by qRT-PCR, western blot and luciferase assays.

Results: Significantly increased expression of miR-200b was observed in PCOS patients compared with the controls. Moreover, over-expression of miR-200b and miR-200c inhibited the proliferation of KGN cells. In addition, our results verified that miR-200b and miR-200c directly targeted PTEN, knockdown of which suppressed KGN cells proliferation.

Conclusion: Our findings demonstrate that miR-200b and miR-200c suppress the proliferation of KGN cells by targeting PTEN, and this might provide new evidence for abnormal proliferation of GCs in PCOS.
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http://dx.doi.org/10.1186/s12958-019-0505-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698342PMC
August 2019

Vaginal progesterone gel is non-inferior to intramuscular progesterone in efficacy with acceptable tolerability for luteal phase support: A prospective, randomized, multicenter study in China.

Eur J Obstet Gynecol Reprod Biol 2019 Jun 15;237:100-105. Epub 2019 Apr 15.

Chengdu Women's & Children's Central Hospital, No. 1617, Riyue Avenue, Qingyang District, Chengdu, Sichuan Province, PR China. Electronic address:

Objectives: Research suggests the efficacy of progesterone for luteal phase support in assisted reproduction cycles using gonadotropin-releasing hormone analogues. Our study objective was to compare the efficacy of two available preparations of progesterone, vaginal gel and intramuscular injection, for luteal phase support in assisted reproduction cycles.

Study Design: This study included data gathered from 18 reproductive centers in China. Subjects were randomly allocated to receive progesterone gel or intramuscular progesterone (IMP). The progesterone gel group received micronized progesterone in gel (8%, 90 mg) once daily; the IMP group received IMP (progesterone oil) once daily. The ongoing pregnancy rate was calculated (number of women with a viable pregnancy at 12 weeks divided by the number of women who had undergone an oocyte pickup cycle).

Results: A total of 1313 patients were enrolled in the study, 1248 of whom began treatment. The intention-to-treat set included 527 and 531 patients in the gel and IMP groups, respectively. The ongoing pregnancy rate in the progesterone gel group was non-inferior to that in the IMP group (48.4% [95% confidence interval (CI): 44.0, 52.8] vs. 46.3% [95% CI: 42.0, 50.7]); the between-group rate difference was 2.1% (-4.0, 8.1). There was no difference between the gel group and IMP group on most secondary endpoints, including implantation rate, biochemical pregnancy rate, clinical pregnancy rate, multiple pregnancy rate, early abortion rate, and vaginal bleeding rate, but there was a between-group difference in luteal phase bleeding rate. The safety analysis showed no difference in the incidence of total adverse events.

Conclusions: Progesterone gel showed good efficacy and safety outcomes and therefore provides an alternative method of luteal support in Chinese in vitro fertilization patients.
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http://dx.doi.org/10.1016/j.ejogrb.2019.04.012DOI Listing
June 2019

Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial.

Lancet 2019 03 28;393(10178):1310-1318. Epub 2019 Feb 28.

Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; The Key Laboratory of Reproductive Endocrinology of Ministry of Education, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China; Center for Reproductive Medicine, Ren Ji Hospital, Shanghai, China; School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai, China. Electronic address:

Background: Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer.

Methods: This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405.

Findings: 825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 [50%] vs 329 [40%]; relative risk [RR] 1·26, 95% CI 1·14-1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 [0·5%] in frozen single blastocyst transfer vs nine of 825 [1·1%] in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 [23·0%] vs 124 of 481 [25·8%]; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 [3·1%] vs four of 401 [1·0%]; RR 3·13, 95% CI 1·06-9·30, p=0·029).

Interpretation: Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies.

Funding: The National Key Research and Development Program of China.
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http://dx.doi.org/10.1016/S0140-6736(18)32843-5DOI Listing
March 2019

Efficacy and safety of Ding-Kun-Dan for female infertility patients with predicted poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection: study protocol for a randomized controlled trial.

Trials 2018 Feb 20;19(1):124. Epub 2018 Feb 20.

Reproductive Center, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 88 Chang Ling Street, Xi Qing district, Tianjin, 300112, China.

Background: Women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) who have a predicted poor ovarian response (POR) present a challenge for reproductive medicine specialists. Traditional Chinese medicine (TCM) is commonly used in China for such patients, in the belief that it will improve the ovarian response and ultimately increase pregnancy rates. However, there is a lack of high-quality evidence about the effect of TCM on improving ovarian response in such patients. The purpose of this study is to evaluate ongoing viable pregnancy rate at 12 weeks' gestation and related indicators of ovarian response in fertile women who have a predicted poor ovarian response having immediate versus delayed IVF/ICSI after 3 months of Ding-Kun-Dan (DKD) pre-treatment.

Methods/design: This study is a multicenter, randomized controlled, parallel-group, phase III, superiority clinical trial. Two hundred and seventy-eight eligible female infertility patients with POR will be included in the study and randomly allocated into an immediate treatment group and a DKD group in a 1:1 ratio. Both groups will receive IVF or ICSI as a standard treatment while in the DKD group, a commercially available Chinese medicine, DKD, will be administrated for 3 months before the IVF/ICSI cycle starts. The primary outcome of the study is the ongoing pregnancy rate at 12 weeks' gestation. The secondary outcomes include total gonadotropin dosage, duration of stimulation, estradiol (E) and progesterone (P) levels on human chorionic gonadotropin (hCG) trigger day, cycle cancellation rate, number of oocytes retrieved, high-quality embryo rate, biochemical pregnancy rate, the change of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and E levels and all side effects, safety outcomes, and any adverse events. The protocol was approved by the Ethics Committee of the First Teaching Hospital of Tianjin university of TCM (approval no. TYLL2017[K] 004).

Discussion: IVF/ICSI is increasingly used to treat couples desiring a baby. Many of these women will have poor ovarian function. In China, DKD is commonly used for these patients prior to undergoing IVF/ICSI. There is no effective treatment for poor ovarian response in Western medicine currently. It is important, therefore, to undertake this randomized control trial to determine whether DKD is effective or not.

Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011697 . Registered on 19 June 2017.
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http://dx.doi.org/10.1186/s13063-018-2511-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819272PMC
February 2018

The correlation of anandamide with gonadotrophin and sex steroid hormones during the menstrual cycle.

Iran J Basic Med Sci 2017 Nov;20(11):1268-1274

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.

Objectives: The purpose of this study was to investigate the change in plasma anandamide (AEA) levels throughout the normal menstrual cycle, and to analyze the relationship among AEA, sex steroids and gonadotrophins.

Materials And Methods: The patients were fertile women with normal menstrual cycle, proposed to get fertilization (IVF) treatment due to oviduct obstruction or male infertility. Patients were divided into two groups, cross-sectional (n=79) and longitudinal (n=10). The plasma AEA levels were examined by the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) system. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P) were measured by chemiluminescence.

Results: The AEA levels in the late follicular phase were slightly higher than those in the early follicular phase. Subsequently, the AEA levels peaked at the time of ovulation in both two cohorts. Finally, the lowest AEA levels were measured in the luteal phase. Moreover, there were highly significant positive correlations between the plasma AEA concentration and the serum levels of FSH, LH and E2, whereas the AEA level was not correlated with P during the normal menstrual cycle.

Conclusion: Our observations reveal a dynamic change in the plasma AEA level, which is closely associated with the levels of gonadotrophin and sex steroid hormones, suggesting that the hormones may be involved in the regulation of AEA levels during the menstrual cycle. Our studies help to design new strategies to improve implantation and treatments for reproductive diseases.
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http://dx.doi.org/10.22038/IJBMS.2017.9488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749362PMC
November 2017

The Roles of Anandamide, Fatty Acid Amide Hydrolase, and Leukemia Inhibitory Factor on the Endometrium during the Implantation Window.

Front Endocrinol (Lausanne) 2017 16;8:268. Epub 2017 Oct 16.

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Background/aims: We investigated the role of the endocannabinoid system (ECS) in the endometrium of unexplained infertility (UI) patients, and effect of anandamide (AEA) on leukemia inhibitory factor (LIF).

Methods: Patients were divided into UI and control groups. Endometrium samples were collected at the midluteal phase. Levels of cannabinoid type 1 (CB1), fatty acid amide hydrolase (FAAH), and LIF were examined. LIF productions were measured after AEA, CB1 antagonist AM251, and CB2 antagonist AM630 stimulation.

Results: Rates of available embryo, successful implantation and pregnancy, and the endometrial thickness of UI group were significantly lower than control, suggesting uterine receptivity was decreased in UI group. FAAH and LIF levels were significantly decreased, whereas endometrial CB1 was slightly increased in UI group. LIF production was promoted by low amount of AEA administration (1-10 μM), while the promotion was reduced by higher concentration of AEA (50 μM). LIF levels were decreased by AM251 or AM630, compared with AEA alone. Expressions of FAAH and LIF were closely associated with uterus receptivity and implantation rate of UI patients. Different concentrations of AEA could stimulate dynamic changes in LIF production.

Conclusion: Our data indicated the important role of the ECS in human fertility, which may promote new strategies for successful implantation and treatments for reproductive diseases.
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http://dx.doi.org/10.3389/fendo.2017.00268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650704PMC
October 2017

Heyan Kuntai capsule versus dehydroepiandrosterone in treating Chinese patients with infertility caused by diminished ovarian reserve: a multicenter, randomized controlled trial.

J Tradit Chin Med 2017 Aug;37(4):530-537

Department of Reproductive Center, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.

Objective: To evaluate the clinical efficacy and safety of Heyan Kuntai capsule (HYKT) in treating women with infertility caused by diminished ovarian reserve (DOR).

Methods: One hundred eight eligible patients from three Chinese hospitals were randomly divided into an HYKT treatment group (n = 55) or a dehydroepiandrosterone (DHEA) treatment group (n = 53). Patients in the HYKT group were treated orally with four 0.5 g HYKT three times a day; patients in the DHEA group were treated with one 25.0 mg DHEA capsule three times a day. All patients were treated for 3 months and followed up over a 3-month period.

Results: Of 108 patients, 12 dropped out: six from the HYKT group, and six from the DHEA group. Eleven patients got pregnant during the treatment. Serum anti-Müllerian hormone levels and antral follicle counts increased significantly in both groups after treatment (P < 0.05) especially in the HYKT group (P < 0.05). Serum follicle stimulating hormone (FSH) levels and FSH/luteinizing hormone ratios decreased (P < 0.05) with no significant difference between the two groups. Estradiol levels in the HYKT group and DHEA-sulfate levels in the DHEA group both increased (P < 0.05). The spontaneous pregnancy rates were 12% and 11% in the HYKT and DHEA groups, respectively (not significant). During the follow-up period, 16 patients in the HYKT group underwent in vitro fertilization-embryo transfer (IVF-ET) and the number of retrieved oocytes was (5.1 c1.8). In DHEA group, 20 patients underwent IVF-ET and the number of retrieved oocyte was (4.2 ± 1.9) (not significant); clinical pregnancy rates were 38% in the HYKT group and 20% in DHEA group (not significant). No significant adverse reactions were observed.

Conclusion: HYKT can improve the ovarian reserve and hormone levels in patients with infertility caused by DOR. Pregnancy rates after HYKT treatment were similar to those of DHEA treatment. HYKT might be an alternative to the treatment of infertility caused by DOR.
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August 2017

Premature Progesterone Rise Positively Correlates with Clinical Pregnancy Rate in In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) Patients with good Ovarian Response.

Horm Metab Res 2017 May 28;49(5):372-379. Epub 2017 Mar 28.

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Infertility affects millions of couples worldwide resulting in distress and depression. In the past several decades, in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) have been developed with high efficiency and success rate. The possible effects of gonadotropin administration on follicular metabolism have been discussed but the outcomes remain controversial. The aim of this study was to identify whether serum progesterone on the day of human chorionic gonadotropin (hCG) administration and the ratio of serum progesterone and the number of oocyte retrieved (P/O) had a predictive role for the outcomes of IVF/ICSI. Eight hundred and twenty-five patients were enrolled between January 2012 and December 2012. A positive correlation between progesterone and IVF/ICSI outcomes were found in patients with good ovarian response using receiver operating characteristic (ROC) curve. We found that when progesterone level was higher than 1.04 ng/ml in good ovarian responses, the implantation rate and clinical pregnancy rate were both reduced compared to the rates in patients exhibiting lower progesterone level (progesterone≤1.04 ng/ml). Moreover, the rise of serum progesterone on the day of hCG was negatively correlated with luteinizing hormone (LH) level. This study used 1.04 ng/ml as a definition of progesterone elevation and an adverse effect of serum progesterone rise was observed on clinical pregnancy rate.
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http://dx.doi.org/10.1055/s-0043-104384DOI Listing
May 2017

Restored Plasma Anandamide and Endometrial Expression of Fatty Acid Amide Hydrolase in Women With Polycystic Ovary Syndrome by the Combination Use of Diane-35 and Metformin.

Clin Ther 2017 Apr 11;39(4):751-758. Epub 2017 Mar 11.

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

Purpose: Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment.

Methods: Serum levels of anandamide and 2-arachidonoylglycerol andexpression of cannabinoid receptors and fatty acid amide hydrolase (FAAH) in the endometrium were compared between women with PCOS and infertile women without PCOS, as well as women with PCOS before and after treatment with Diane-35 and metformin. Cannabinoid receptors and FAAH in the endometrium were stained using the immunohistochemical method. Results were analyzed by calculating integrated optical density.

Findings: Plasma anandamide was increased significantly in women with PCOS compared with infertile women without PCOS. Treatment with Diane-35 and metformin reversed this increase in women with PCOS. No significant difference in 2-arachidonoylglycerol was observed between the infertile women with or without PCOS. The women with PCOS had lower endometrial expression of FAAH compared with infertile women without PCOS, whereas no significant difference in endometrial expression of cannabinoid receptors was observed between the women with PCOS and infertile women without PCOS. We found that after treatment with Diane-35 and metformin, FAAH expression tended toward a significant increase compared with women before the treatment.

Implications: Endocannabinoid system may be involved in the progression of PCOS, and serum anandamide could serve as a potential biomarker of clinical diagnosis of PCOS.
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http://dx.doi.org/10.1016/j.clinthera.2017.02.007DOI Listing
April 2017

Decreased expression of fatty acid amide hydrolase in women with polycystic ovary syndrome.

Gynecol Endocrinol 2017 May 28;33(5):368-372. Epub 2017 Jan 28.

a Department of Reproduction , The Second Hospital of Hebei Medical University , Shijiazhuang , China.

This study aimed to investigate the correlation between endocannabinoids and polycystic ovary syndrome (PCOS), and the expression levels of endocannabinoids in different phases of menstruation. The expression of cannabinoid receptors (CB1) and fatty acid amide hydrolase (FAAH) in the endometrium were immunohistochemically stained and compared between women with PCOS and the control group. Integrated optical density (IOD) was assessed to analyze their expression levels. The CB1 and FAAH were expressed in endometrial epithelial cytoplasm. No significant difference in CB1 level was observed between PCOS and non-PCOS women. Additionally, the expression of CB1 did not fluctuate with menstrual cycle. However, the FAAH levels were lower in the PCOS group than the non-PCOS group (p < 0.05). FAAH levels in secretory phases were significantly elevated compared to menstrual and proliferative phases (p < 0.05). Our results demonstrate that the endocannabinoid system may play an important role in menstruation, and dysregulation of the system may result in PCOS.
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http://dx.doi.org/10.1080/09513590.2016.1269742DOI Listing
May 2017

Impact of Body Mass Index on Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection Among Polycystic Ovarian Syndrome Patients.

Cell Physiol Biochem 2016 17;39(5):1723-1734. Epub 2016 Oct 17.

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

Background: The aim of this study is to assess the effect of body mass index (BMI) on outcomes of in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) among polycystic ovarian syndrome (PCOS) and non-PCOS patients.

Methods: This was a retrospective cohort study that was performed in the Second Hospital of Hebei Medical University. Patients who were under 35 years old were included in the study and were divided into four groups based on their BMI. The number of retrieved oocytes, implantation rate, clinical pregnancy rate, miscarriage rate and live births among PCOS and non-PCOS patients were compared between different BMIs.

Results: IVF/ICSI pregnancies in obese PCOS women had a considerably higher risk of miscarriage and low rate of clinical pregnancy than in non-obese PCOS pregnancies. However, in non-PCOS patient, obesity significantly elevated miscarriage rate but did not affect clinical pregnancy rate.

Conclusion: Obesity in PCOS patients led to poor outcomes of IVF/ICSI.
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http://dx.doi.org/10.1159/000447873DOI Listing
February 2017

MicroRNA-224 regulates self-renewal of mouse spermatogonial stem cells via targeting DMRT1.

J Cell Mol Med 2016 08 21;20(8):1503-12. Epub 2016 Apr 21.

Department of Reproduction, The Second Hospital of Hebei Medical University, Shijiazhuang, China.

MicroRNAs (miRs) play a key role in the control of gene expression in a wide array of tissue systems, where their functions include the regulation of self-renewal, cellular differentiation, proliferation and apoptosis. However, the function and mechanisms of individual miRs in regulating spermatogonial stem cell (SSC) homeostasis remain unclear. In the present study, we report for the first time that miR-224 is highly expressed in mouse SSCs. Functional assays using miRNA mimics and inhibitors reveal that miR-224 is essential for differentiation of SSCs. Mechanistically, miR-224 promotes differentiation of SSCs via targeting doublesex and Mab-3-related transcription factor 1 (DMRT1). Moreover, WNT/β-catenin signalling pathway is involved in miR-224-mediated regulation of SSCs self-renewal. We further demonstrate that miR-224 overexpression increases the expression of GFRα1 and PLZF, accompanied by the down-regulation of DMRT1 in mouse testes. Our findings provide novel insights into molecular mechanisms regulating differentiation of SSCs and may have important implications for regulating male reproduction.
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http://dx.doi.org/10.1111/jcmm.12838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956939PMC
August 2016