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Preview: Human Reproduction - Advance Access

Human Reproduction Advance Access





Published: Tue, 20 Feb 2018 00:00:00 GMT

Last Build Date: Tue, 20 Feb 2018 04:48:38 GMT

 



Effect of exposure to second-hand smoke from husbands on biochemical hyperandrogenism, metabolic syndrome and conception rates in women with polycystic ovary syndrome undergoing ovulation induction

Tue, 20 Feb 2018 00:00:00 GMT

ABSTRACT
STUDY QUESTION
Does second-hand smoke (SHS) exposure from husbands have adverse effects on sex hormones, metabolic profiles, clinical phenotypes and fertility outcomes in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction?
SUMMARY ANSWER
SHS exposure is associated with worsened biochemical hyperandrogenism, higher incidence of metabolic syndrome and reduced conception rates in women with PCOS.
WHAT IS KNOWN ALREADY
Smoking in women impairs fecundity at some stages of the reproductive process including folliculogenesis, embryo transport, endometrial angiogenesis and uterine blood flow. Yet little is known about the hazard of SHS exposure in women with PCOS.
STUDY DESIGN, SIZE, DURATION
This study was a secondary analysis of the Polycystic Ovary Syndrome Acupuncture and Clomiphene Trial (PCOSAct), a large randomized controlled trial conducted at 27 hospitals from 2012 to 2015 in mainland China.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Out of 1000 women with PCOS, SHS exposure status were available in 500 women, of whom 271 women were non-exposed and 229 exposed to cigarette smoke (170 women ≤10 cigarettes per day as low-SHS exposed and 59 women >10 cigarettes per day as high-SHS exposed). We compared circulating sex steroids, glucose and lipid metabolism, metabolic syndrome and phenotypes, fertility and obstetric outcomes between non-exposed and exposed women.
MAIN RESULTS AND THE ROLE OF CHANCE
Women exposed to SHS, compared to non-exposed women, had a higher serum total testosterone (1.7 vs 1.5 nmol/L, P = 0.01), free androgen index (5.7 vs 4.0, P = 0.001) and lower sex hormone binding globulin (30.1 vs 35.6 nmol/L, P = 0.03). Metabolic syndrome, but not other phenotypes, was more frequent in exposed women as compared to non-exposed women (21.8 vs 13.3%, adjusted odds ratio (OR)=1.66; 95% CI, 1.02–2.71, P = 0.04). Ovulation rates between exposed and non-exposed groups were not significantly different (76.9 vs 82.9%, adjusted OR=0.72; 95% CI, 0.45–1.15, P = 0.17). Conception rates were significant lower in the exposed group (26.6 vs 36.9%; adjusted OR=0.61; 95% CI, 0.41–0.91; P = 0.01), while clinical pregnancy and live birth rates showed a similar trend that was not statistically significant. Gestational age, birth weight and other obstetric outcomes were not affected by SHS exposure.
LIMITATIONS, REASONS FOR CAUTION
Data on SHS exposure were missing in 50% of the women. We did not assay serum nicotine or cotinine levels to quantify the SHS exposure status.
WIDER IMPLICATIONS OF THE FINDINGS
These data suggest that smoking partners of infertile women with PCOS who seek treatment should be advised to quit smoking.
STUDY FUNDING/COMPETING INTEREST(S)
Funding was provided by the National Public Welfare Projects for Chinese Medicine (201107005 and 200807002) and the National Clinical Trial Base in Chinese Medicine Special Projects (JDZX2012036 and 2015B009). There are no conflicts of interest.
TRIAL REGISTRATION NUMBER
ClinicalTrial.gov number: NCT01573858 and chictr.org.cn number: ChiCTR-TRC-12002081.



Endometriosis induces gut microbiota alterations in mice

Thu, 15 Feb 2018 00:00:00 GMT

Abstract
STUDY QUESTION
What happens to the gut microbiota during development of murine endometriosis?
SUMMARY ANSWER
Mice with the persistence of endometrial lesions for 42 days develop a distinct composition of gut microbiota.
WHAT IS KNOWN ALREADY
Disorders in the immune system play fundamental roles in changing the intestinal microbiota. No study has used high-throughput DNA sequencing to show how endometriosis changes the gut microbiota, although endometriosis is accompanied by abnormal cytokine expression and immune cell dysfunction.
STUDY DESIGN, SIZE, DURATION
This study includes a prospective and randomized experiment on an animal endometriosis model induced via the intraperitoneal injection of endometrial tissues.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The mice were divided into endometriosis and mock groups and were sacrificed at four different time points for model confirmation and fecal sample collection. To detect gut microbiota, 16S ribosomal-RNA gene sequencing was performed. Alpha diversity was used to analyze the complexity and species diversity of the samples through six indices. Beta diversity analysis was utilized to evaluate the differences in species complexity. Principal coordinate analysis and unweighted pair-group method with arithmetic means clustering were performed to determine the clustering features. The microbial features differentiating the fecal microbiota were characterized by linear discriminant analysis effect size method.
MAIN RESULTS AND THE ROLE OF CHANCE
The endometriosis and mock mice shared similar diversity and richness of gut microbiota. However, different compositions of gut microbiota were detected 42 days after the modeling. Among the discriminative concrete features, the Firmicutes/Bacteroidetes ratio was elevated in mice with endometriosis, indicating that endometriosis may induce dysbiosis. Bifidobacterium, which is known as a commonly used probiotic, was also increased in mice with endometriosis.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
More control groups should be further studied to clarify the specificity of the dysbiosis induced by endometriosis. This study was performed only on mice. Thus, additional data acquired from patients with endometriosis are needed in future research. We only detected the changes of gut microbiota at 42 days after the modeling, while the long-term effect of endometriosis on gut microbiota remains poorly understood. Moreover, we only revealed a single effect of endometriosis on gut microbiota.
WIDER IMPLICATIONS OF THE FINDINGS
This study provided the first comprehensive data on the association of endometriosis and gut microbiota from high-throughput sequencing technology. The gut microbiota changed with the development of endometriosis in a murine model. The communication between the host and the gut microbiota is bidirectional, and further studies should be performed to clarify their relationship.
STUDY FUNDING/COMPETING INTEREST(S)
This research was supported by Grant (81571417) from the National Science Foundation of China and Grant (2015GSF118092) from the Technology Development Plan of Shandong Province. The authors report no conflict of interest.



Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis

Thu, 15 Feb 2018 00:00:00 GMT

AbstractSTUDY QUESTIONWhat is the role of SFRP2 in endometriosis?SUMMARY ANSWERSFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis, regulating endometriosis lesion growth and indicating endometriosis lesion borders together with CTNNB1 (also known as beta catenin).WHAT IS KNOWN ALREADYEndometriosis is a common, chronic disease that affects women of reproductive age, causing pain and infertility, and has significant economic impact on national health systems. Despite extensive research, the pathogenesis of endometriosis is poorly understood, and targeted medical treatments are lacking. WNT signaling is dysregulated in various human diseases, but its role in extraovarian endometriosis has not been fully elucidated.STUDY DESIGN, SIZE, DURATIONWe evaluated the significance of WNT signaling, and especially secreted frizzled-related protein 2 (SFRP2), in extraovarian endometriosis, including peritoneal and deep lesions. The study design was based on a cohort of clinical samples collected by laparoscopy or curettage and questionnaire data from healthy controls and endometriosis patients.PARTICIPANTS/MATERIALS, SETTING, METHODSGlobal gene expression analysis in human endometrium (n = 104) and endometriosis (n = 177) specimens from 47 healthy controls and 103 endometriosis patients was followed by bioinformatics and supportive qPCR analyses. Immunohistochemistry, Western blotting, primary cell culture and siRNA knockdown approaches were used to validate the findings.MAIN RESULTS AND THE ROLE OF CHANCEAmong the 220 WNT signaling and CTNNB1 target genes analysed, 184 genes showed differential expression in extraovarian endometriosis (P < 0.05) compared with endometrium tissue, including SFRP2 and CTNNB1. Menstrual cycle-dependent regulation of WNT genes observed in the endometrium was lost in endometriosis lesions, as shown by hierarchical clustering. Immunohistochemical analysis indicated that SFRP2 and CTNNB1 are novel endometriosis lesion border markers, complementing immunostaining for the known marker CD10 (also known as MME). SFRP2 and CTNNB1 localized similarly in both the epithelium and stroma of extraovarian endometriosis tissue, and interestingly, both also indicated an additional distant lesion border, suggesting that WNT signaling is altered in the endometriosis stroma beyond the primary border indicated by the known marker CD10. SFRP2 expression was positively associated with pain symptoms experienced by patients (P < 0.05), and functional loss of SFRP2 in extraovarian endometriosis primary cell cultures resulted in decreased cell proliferation (P < 0.05) associated with reduced CTNNB1 protein expression (P = 0.05).LIMITATIONS REASONS FOR CAUTIONSFRP2 and CTNNB1 improved extraovarian endometriosis lesion border detection in a relatively small cohort (n = 20), although larger studies with different endometriosis subtypes in variable cycle phases and under hormonal medication are required.WIDER IMPLICATIONS OF THE FINDINGSThe highly expressed SFRP2 and CTNNB1 improve endometriosis lesion border detection, which can have clinical implications for better visualization of endometriosis lesions over CD10. Furthermore, SFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis and positively regulates endometriosis lesion growth, suggesting that the WNT pathway may be an important therapeutic target for endometriosis.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by the Academy of Finland and by Tekes: Finnish Funding Agency for Innovation. The authors have no conflict of interest to declare.[...]



Cell-free fetal DNA testing in singleton IVF conceptions

Thu, 15 Feb 2018 00:00:00 GMT

Abstract
STUDY QUESTION
Are fetal fraction, test failure rate and positive predictive value (PPV) of cell-free fetal DNA (cffDNA) testing different in singleton IVF conceptions compared to spontaneous conceptions?
SUMMARY ANSWER
Fetal fraction is significantly lower; test failure rate is higher and PPV of cffDNA testing is lower in singleton pregnancies conceived by IVF than those conceived spontaneously.
WHAT IS ALREADY KNOWN
cffDNA testing, which analyses circulating cffDNA in maternal blood, has very high accuracy for detection of trisomy 21 in the general obstetric population. Focused and conclusive evidence regarding the test characteristics of cffDNA testing in IVF conceived pregnancies is lacking.
STUDY DESIGN, SIZE, DURATION
This was a retrospective cohort study including spontaneously and IVF conceived singleton pregnancies collected consecutively between April 2013 and November 2016. A total of 4633 spontaneously conceived and 992 IVF pregnancies were included.
PARTICIPANTS/MATERIALS, SETTING, METHODS
The study was performed at an obstetric and gynecological ultrasound clinic in Melbourne, Australia. Participants had screening for trisomies 21, 18 and 13, as well as sex chromosome aneuploidies (SCA) performed with cffDNA testing after 10 weeks’ gestation. Multivariate regression analysis was used to determine significant predictors of logarithmically transformed fetal fraction and test failure. Comparison of test characteristics between study groups was performed adopting a significance level of 5%.
MAIN RESULTS AND THE ROLE OF CHANCE
Median fetal fraction was lower (10.3% [interquartile range (IQR), 7.7–13.5] versus 11.9% [IQR, 9.1–15.0]; P = 0.005), test failure rate was higher (5.2 versus 2.2%; P < 0.001) and positive predictive value (PPV) for trisomies 18, 13 and SCA was poorer in IVF pregnancies compared to those spontaneously conceived. Multivariate linear regression analysis demonstrated that IVF conception, increased BMI, earlier gestational age and South and East Asian ethnicities were independent predictors of lower fetal fraction. Multiple logistic regression analysis found IVF conception and increased BMI to be independently associated with test failure. PPV was high for trisomy 21 in IVF conception (100.0%), but was lower for other trisomies when compared with the non-IVF population.
LIMITATIONS REASONS FOR CAUTION
IVF details were unascertainable for 210 cases, as the information was not available through our data collection points. Inability to karyotype some cases at high-risk for SCA, due to patients’ choice, and the occurrence of miscarriages and terminations, resulted in the exclusion of high-risk cases when calculating PPV. Pregnancy outcomes were not available in low-risk pregnancies and negative predictive values could not be calculated.
WIDER IMPLICATIONS OF THE FINDINGS
The limitations revealed by this work should be taken into account during pre-test counseling in pregnant women who conceive by IVF.
STUDY FUNDING/COMPETING INTEREST(S)
No external source of financial support was provided for this research. The authors report no conflicts of interest.