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1.
Artigo em Inglês | MEDLINE | ID: mdl-32232828

RESUMO

We read with great interest the article by Sauvegrain et al. entitled "Understanding high rates of stillbirth and neonatal death in a disadvantaged, high-migrant district in France: a perinatal audit".1 This well-designed study confirmed again that maternal overweight/obesity increases perinatal mortality. We would like to address some points that merit further attention. The intrauterine environment can affect the long-term health of the offspring has been widely accepted. Maternal high pre-pregnancy body mass index (BMI) increases the risks of fetal exposure to higher maternal triglyceride levels during the first trimester.

2.
Arch Gynecol Obstet ; 301(3): 721-727, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32114673

RESUMO

PURPOSE: To investigate whether there are left-right asymmetries in tubal endometriosis and the factors affecting this predisposition. METHODS: Women who underwent salpingectomy for gynecological diseases and were diagnosed with tubal endometriosis between January 2002 and July 2019 were included in the study. The frequencies of left and right tubal endometriosis were compared with the expected 50% using a binominal test. The demographic characteristics and presence of ovarian endometrioid cysts, adenomyosis, and hydrosalpinx were also analyzed. RESULTS: During the study period of more than 17 years, 305 women were diagnosed with tubal endometriosis. The distribution of tubal endometriosis in the left or right fallopian tubes was analyzed. Tubal endometriosis was found in the left fallopian tube in 168 (55.08%) women, in the right fallopian tube in 93 (30.49%), and bilaterally in 44 (14.43%). Left unilateral tubal endometriosis was found most frequently (64.37%, 168/261), and its incidence was significantly higher than 50% (P < 0.001, binominal test). Furthermore, the frequency of left ovarian endometrioid cysts (58.82%) was higher than that of right ovarian endometrioid cysts (41.18%) (P < 0.001, binominal test). CONCLUSION: Our study confirms that tubal endometriosis is a left-side asymmetric disease, and this predisposition is highly consistent with ovarian endometrioid cysts, which supports the transplantation theory of the origin of endometriosis.

3.
Eur J Obstet Gynecol Reprod Biol ; 248: 156-163, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32217429

RESUMO

OBJECTIVES: To evaluate the preventive effects of low-dose aspirin on the incidence of preeclampsia and pregnancy outcomes of women at high-risk for preeclampsia. STUDY DESIGN: This prospective randomized clinical trial was conducted at the Obstetrics Department of The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, China. It analyzed data from 1105 high-risk women who were divided into the control group (placebo group) and the aspirin group (including three subgroups: 25 mg, 50 mg and 75 mg). The aspirin group in this study was instructed to take aspirin daily before bedtime beginning in the 12th week of pregnancy. MAIN OUTCOME MEASURES: The primary outcome is the occurrence of preeclampsia. The secondary outcomes included maternal and neonatal outcomes (such as premature delivery, FGR etc.), maternal serum biomarkers (including d-dimers, platelet aggregation rates, etc.) and uterine arterial blood flow resistance. The onset of preeclampsia and pregnancy outcomes were recorded after all participants delivered. RESULTS: Low-dose aspirin significantly reduced the incidence of preeclampsia and early-onset preeclampsia. Aspirin also showed significant dose dependence in preeclampsia prevention. The results of Mantel-Haenszel trend test showed that there was a linear relationship between the dosage and the incidence of preeclampsia and early preeclampsia (P < 0.05). Pearson's results showed that the incidence of preeclampsia and early preeclampsia was negatively correlated with aspirin dosage. There was also a linear relationship between the dosage and the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section (P < 0.05). There was no evidence to suggest differences in the incidence of fetal distress, miscarriage and placental abruption among the four groups. The blood resistance S/D value of uterine artery in early pregnancy was the only independent factor affecting the efficacy of aspirin (OR = 1.405; 95 %CI,1.058-1.867; P = 0.019). CONCLUSION: Low-dose aspirin can prevent preeclampsia and early-preeclampsia. Its efficacy is dose-dependent. It can reduce the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section. The prophylactic effect of aspirin on preeclampsia seemed to be greater in patients with higher blood resistance S/D value of uterine artery during early pregnancy.

4.
Gynecol Endocrinol ; : 1-5, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32208782

RESUMO

We design this study to detect levels of Elabela (ELA) and Apelin (APLN) in women with and without gestational diabetes mellitus (GDM) in the second and third trimesters, and to identify whether there is any association between ELA, APLN, and metabolic parameters. Seventy-nine GDM and 80 control subjects in the second trimester and 87 GDM and 88 healthy subjects in the third trimester were included. In the second trimester, lower ELA levels [(14.1 versus 16.9) ng/ml, p = .025] and higher APLN levels [(1021.8 versus 923.5) pg/ml, p = .046] were observed in GDM patients compared to controls. ELA levels were positively correlated with fasting plasma glucose (FPG) (r = 0.423, p < .001) in the control group, and APLN levels were negatively correlated with triglycerides (TG) (r = -0.251, p = .025) in the control group and total cholesterol (TC) (r = -0.227, p = .044) in the GDM group. ELA appeared to be related to glucose metabolism and APLN is involved in lipid metabolism during pregnancy. The expression of ELA is significantly downregulated from the second trimester to the third trimester.

5.
Biochem Biophys Res Commun ; 524(4): 791-797, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32019676

RESUMO

Increased granulosa cell (GC) proliferation may contribute to abnormal folliculogenesis in patients with polycystic ovary syndrome (PCOS), which affects approximately 10% reproductive aged women. However, the mechanisms underlying increased GC proliferation in PCOS remain incompletely understood. In this study, we identified miR-3940-5p as a hub miRNA in GC from PCOS using weighted gene co-expression network analysis (WGCNA), and real-time polymerase chain reaction (RT-PCR) analysis confirmed that miR-3940-5p was significantly increased in GC from PCOS. Enrichment analysis of predicted target genes of miR-3940-5p indicated potential roles of miR-3940-5p in follicular development and cell proliferation regulation. Consistently, functional study confirmed that miR-3940-5p overexpression promoted granulosa cell proliferation. Integrated analysis of mRNA expression profiling data and predicted target genes of miR-3940-5p identified potassium voltage-gated channel subfamily A member 5 (KCNA5) as a potential target of miR-3940-5p, and was validated by luciferase reporter assay. Finally, functional analysis suggested that miR-3940-5p promoted GC proliferation in a KCNA5 dependent manner. In conclusion, miR-3940-5p was a hub miRNA upregulated in GC from PCOS, and promoted GC proliferation by targeting KCNA5.

6.
Hypertension ; 75(3): 772-780, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32008433

RESUMO

The recommendations for the diagnosis of stage 1 hypertension were recently revised by the American Heart Association primarily based on its impact on cardiovascular disease risks. Whether the newly diagnosed stage 1 hypertension impacts pregnancy complications remain poorly defined. We designed a retrospective cohort study to investigate the associations of stage 1 hypertension detected in early gestation (<20 weeks) with risks of adverse pregnancy outcomes stratified by prepregnancy body mass index. A total of 47 874 women with singleton live births and blood pressure (BP) <140/90 mm Hg were included, with 5781 identified as stage 1a (systolic BP, 130-134 mm Hg; diastolic BP, 80-84 mm Hg; or both) and 3267 as stage 1b hypertension (systolic BP, 135-139 mm Hg; diastolic BP, 85-90 mm Hg; or both). Slightly higher, yet significant, rates and risks of gestational diabetes mellitus, preterm delivery, and low birth weight (<2500 g) were observed in both groups compared with normotensive controls. Importantly, women with stage 1a and stage 1b hypertension had significantly increased incidences of hypertensive disorders in pregnancy compared with normotensive women (adjusted odds ratio, 2.34 [95% CI, 2.16-2.53]; 3.05 [2.78-3.34], respectively). After stratifying by body mass index, stage 1a and 1b hypertension were associated with increased hypertensive disorders in pregnancy risks in both normal weight (body mass index, 18.5-24.9; adjusted odds ratio, 2.44 [2.23-2.67]; 3.26 [2.93-3.63]) and the overweight/obese (body mass index, ≥25; adjusted odds ratio, 1.90 [1.56-2.31]; 2.36 [1.92-2.90]). Current findings suggested significantly increased adverse pregnancy outcomes associated with stage 1 hypertension based on the revised American Heart Association guidelines, especially in women with prepregnancy normal weight.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32081430

RESUMO

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro, but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment.

8.
Hum Reprod Update ; 26(2): 247-263, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32045470

RESUMO

BACKGROUND: Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. OBJECTIVE AND RATIONALE: The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. SEARCH METHODS: Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). OUTCOMES: Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). WIDER IMPLICATIONS: For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.

9.
Thromb Res ; 187: 63-71, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31958688

RESUMO

INTRODUCTION: Assisted reproductive technology (ART) treatment is a risk factor for pregnancy-related venous thromboembolism (VTE). This study aims to explore the risk factors for elevated fibrin (fibrinogen) degradation products (FDPs), an indicator of hypercoagulability, in late pregnancy among women who underwent ART treatment. MATERIALS AND METHODS: This retrospective case-control study recruited 227 women who spontaneously conceived and 214 women who underwent ART treatment and gave birth. A subgroup analysis of the 214 pregnant women after ART treatment was performed. 156 women with elevated FDP levels and 58 women with normal FDP levels were designated as the case and control groups, respectively. RESULTS: We found that ART treatment was a risk factor for higher FDP. After adjustments were made for confounders in the group of 214 women after ART treatment, fresh embryo transfer (adjusted odds ratio (aOR) = 3.33, 95% confidence interval (CI), 1.57-7.03) and >10 oocytes retrieved (aOR = 2.09, 95% CI, 1.10-3.99) were associated with elevated FDP in late pregnancy. Serum estradiol (E2) levels on human chorionic gonadotropin (hCG) trigger day were higher in the high-FDP group. A positive correlation between E2 on hCG trigger day and FDP was found for both fresh embryo transfer (r = 0.67, p < 0.001) and frozen embryo transfer (FET) (r = 0.53, p < 0.001). CONCLUSIONS: A higher E2 level on hCG trigger day is closely associated with dysfunction of coagulation and fibrinolysis in late pregnancy. When performing the thromboprophylaxis assessment during pregnancy, clinicians should pay more attention to patients who had previous ART treatment and had a high E2 level on hCG trigger day.

10.
Circulation ; 141(1): 67-79, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31779484

RESUMO

BACKGROUND: Mutations in low-density lipoprotein (LDL) receptor (LDLR) are one of the main causes of familial hypercholesterolemia, which induces atherosclerosis and has a high lifetime risk of cardiovascular disease. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is an effective tool for gene editing to correct gene mutations and thus to ameliorate disease. METHODS: The goal of this work was to determine whether in vivo somatic cell gene editing through the CRISPR/Cas9 system delivered by adeno-associated virus (AAV) could treat familial hypercholesterolemia caused by the Ldlr mutant in a mouse model. We generated a nonsense point mutation mouse line, LdlrE208X, based on a relevant familial hypercholesterolemia-related gene mutation. The AAV-CRISPR/Cas9 was designed to correct the point mutation in the Ldlr gene in hepatocytes and was delivered subcutaneously into LdlrE208X mice. RESULTS: We found that homogeneous LdlrE208X mice (n=6) exhibited severe atherosclerotic phenotypes after a high-fat diet regimen and that the Ldlr mutation was corrected in a subset of hepatocytes after AAV-CRISPR/Cas9 treatment, with LDLR protein expression partially restored (n=6). Compared with the control groups (n=6 each group), the AAV-CRISPR/Cas9 with targeted single guide RNA group (n=6) had significant reductions in total cholesterol, total triglycerides, and LDL cholesterol in the serum, whereas the aorta had smaller atherosclerotic plaques and a lower degree of macrophage infiltration. CONCLUSIONS: Our work shows that in vivo AAV-CRISPR/Cas9-mediated Ldlr gene correction can partially rescue LDLR expression and effectively ameliorate atherosclerosis phenotypes in Ldlr mutants, providing a potential therapeutic approach for the treatment of patients with familial hypercholesterolemia.

11.
J Mol Endocrinol ; 64(1): 43-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786540

RESUMO

Receptive endometrium is a prerequisite for successful embryo implantation, and it follows that poor endometrial receptivity is a leading cause of implantation failure. miRNAs play important roles as epigenetic regulators of endometrial receptivity and embryo implantation through post-transcriptional modifications. However, the mechanisms of action of many miRNAs are poorly understood. In this study, we investigated the role of the miR-183 family, comprising three miRNAs (miR-183-5p, miR-182-5p, and miR-96-5p) in endometrial receptivity and embryo implantation. The miR-183 family shows estrogen-dependent upregulation in endometrial Ishikawa (IK) cells. The miR-183 family also has a positive role in migration and proliferation of IK cells. Furthermore, JAr spheroid attachment experiments show that attachment rates were significantly decreased after treatment of IK cells with inhibitors for miR-183-5p and miR-182-5p and increased after treatment with miR-183-5p-mimic and miR-96-5p-mimic, respectively. The downstream analysis shows that catenin alpha 2 (CTNNA2) is a potential target gene for miR-183-5p, and this was confirmed in luciferase reporter assays. An in vivo mouse pregnancy model shows that inhibition of miR-183-5p significantly decreases embryo implantation rates and increases CTNNA2 expression. Downregulation of CTNNA2 in endometrial cells by miR-183-5p may be significant in mediating estrogenic effects on endometrial receptivity. In conclusion, miR-183-5p and the CTNNA2 gene may be potential biomarkers for endometrial receptivity and may be useful diagnostic and therapeutic targets for successful embryo implantation.

12.
Sci China Life Sci ; 63(1): 18-58, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31813094

RESUMO

Reproductive biology is a uniquely important topic since it is about germ cells, which are central for transmitting genetic information from generation to generation. In this review, we discuss recent advances in mammalian germ cell development, including preimplantation development, fetal germ cell development and postnatal development of oocytes and sperm. We also discuss the etiologies of female and male infertility and describe the emerging technologies for studying reproductive biology such as gene editing and single-cell technologies.

13.
Behav Sleep Med ; : 1-13, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830816

RESUMO

Objective: Poor sleep quality is common during pregnancy. Although a few studies have investigated the associations between maternal sleep quality and fetal birth weight (BW), no evidence has been clearly demonstrated. Our aim was to investigate the effects of sleep quality during pregnancy on the newborn BW z-scores.Participants: 1466 mother-infant pairs were included in the present study based on an ongoing prospective cohort.Methods: Questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and scales for psychosocial status were administered at each trimester. BW z-scores were calculated based on the INTERGROWTH-21st standard. A generalized estimating equation model was applied to evaluate the associations between trimester-specific sleep quality and newborn BW after adjusting for potential confounders. Multivariable logistic regression models were applied to examine the impacts of maternal sleep quality on small-for-gestational-age (SGA) or low birth weight (LBW).Results: We found that maternal PSQI scores in the first and third trimesters were negatively associated with BW z-scores among female newborns (ß = -0.032, 95% CI: -0.063, -0.001, P= .043; ß = -0.031, 95% CI: -0.060, -0.003, P= .033, respectively). However, no relationship was observed between maternal sleep quality and BW in male neonates. Additionally, poor sleep quality in late pregnancy was a risk factor for LBW (OR = 1.501, 95% CI: 1.082-2.082).Conclusions: The BW z-scores of female newborns decreased as maternal sleep quality in the first and third trimesters worsened. This finding suggests that sleep during pregnancy may influence fetal weight in a trimester- and gender-specific manner.

14.
Sci China Life Sci ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31701403

RESUMO

We conducted a retrospective cohort study of 9,552 women experiencing their second delivery between 2014 and 2016 at the International Peace Maternity and Child Health Hospital to investigate the association between the interpregnancy interval (IPI) and adverse perinatal outcomes. With the 12-23-mon IPI as the reference category, logistic regression analyzes were used to examine associations between different IPIs (<12, 12-23, 24-59, 60-119, and ≥120 mon) and perinatal outcomes (gestational diabetes mellitus, premature membrane rupture, gestational hypertension, preterm birth, low birth weight, and macrosomia). Compared with the 12-23-mon IPI category, women with longer IPIs had a higher risk of adverse perinatal outcomes, and those with an IPI ≥120 mon had the highest risk of gestational diabetes mellitus and premature membrane rupture (adjusted odds ratio (OR) 1.76, 95% confidence interval (CI) 1.32-2.35 and adjusted OR 2.03, 95% CI 1.53-2.67, respectively). These results indicate that a longer IPI is associated with a higher risk of adverse perinatal outcomes and an IPI of ≥120 mon appears to be independently associated with a higher risk of gestational diabetes mellitus and premature membrane rupture.

15.
J Dev Orig Health Dis ; : 1-11, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679538

RESUMO

Maternal supraphysiological estradiol (E2) environment during pregnancy leads to adverse perinatal outcomes. However, the influence of oocyte exposure to high E2 levels on perinatal outcomes remains unknown. Thus, a retrospective cohort study was conducted to explore the effect of high E2 level induced by controlled ovarian stimulation (COH) on further outcomes after frozen embryo transfer (FET). The study included all FET cycles (n = 10,581) between 2014 and 2017. All cycles were categorized into three groups according to the E2 level on the day of the human Chorionic Gonadotropin trigger. Odds ratios (ORs) and their confidence intervals (CIs) were calculated to evaluate the association between E2 level during COH and pregnancy outcomes and subsequent neonatal outcomes. From our findings, higher E2 level was associated with lower percentage of chemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth as well as increased frequency of early miscarriage. Preterm births were more common among singletons in women with higher E2 level during COH (aOR1 = 1.93, 95% CI: 1.22-3.06; aOR2 = 2.05, 95% CI: 1.33-3.06). Incidence of small for gestational age (SGA) was more common in both singletons (aOR1 = 2.01, 95% CI: 1.30-3.11; aOR2 = 2.51, 95% CI: 1.69-3.74) and multiples (aOR1 = 1.58, 95% CI: 1.03-2.45; aOR2 = 1.99, 95% CI: 1.05-3.84) among women with relatively higher E2 level. No association was found between high E2 level during COH and the percentage of macrosomia or large for gestational age. In summary, oocyte exposure to high E2 level during COH should be brought to our attention, since the pregnancy rate decreasing and the risk of preterm birth and SGA increasing following FET.

16.
BMJ Open ; 9(9): e030366, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31575574

RESUMO

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 5-15×106/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).

17.
J Cell Mol Med ; 23(12): 8381-8391, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31576674

RESUMO

The eutopic endometrium has been suggested to play a crucial role in the pathogenesis of adenomyosis. However, the specific genes in eutopic endometrium responsible for the pathogenesis of adenomyosis still remain to be elucidated. We aim to identify differentially expressed genes (DEGs) and molecular pathways/networks in eutopic endometrium from adenomyosis patients and provide a new insight into disease mechanisms at transcriptome level. RNA sequencing (RNA-Seq) was performed with 12 eutopic endometrium from adenomyosis and control groups. Differentially expressed genes in adenomyosis were validated by quantitative real-time PCR (qPCR) and immunochemistry. Functional annotations of the DEGs were analysed with Ingenuity Pathway Analysis (IPA). Quantitative DNA methylation analysis of CEBPB was performed with MassArray system. A total of 373 differentially expressed genes were identified in the adenomyosis eutopic endometrium compared to matched controls. Bioinformatic analysis predicted that IL-6 signalling and ERK/MAPK signalling were activated in adenomyosis endometrium. We also found that the increased expression and DNA hypomethylation of CEBPB were associated with adenomyosis. Our results revealed key pathways and networks in eutopic endometrium of adenomyosis. The study is the first to propose the association between C/EBPß and adenomyosis and can improve the understanding of the pathogenesis of adenomyosis.

18.
Reproduction ; 158(5): 465-475, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505459

RESUMO

Fertilization failure often occurs during in vitro fertilization (IVF) cycles despite apparently normal sperm and oocytes. Accumulating evidence suggests that mitochondria play crucial roles in the regulation of sperm function and male fertility. 3-Nitrophthalic acid (3-NPA) can induce oxidative stress in mitochondria, and melatonin, as an antioxidant, can improve mitochondrial function by reducing mitochondrial oxidative stress. The role of sperm mitochondrial dysfunction in fertilization failure during IVF is unclear. The present study revealed that spermatozoa with low, or poor, fertilization rates had swollen mitochondria, increased mitochondria-derived ROS, and attenuated mitochondrial respiratory capacity. 3-NPA treatment enhanced mitochondrial dysfunction in sperm. Spermatozoa with poor fertilization rates, and spermatozoa treated with 3-NPA, had reduced penetration ability. The concentration of melatonin was decreased in semen samples with low and poor fertilization rates. Melatonin, not only decreased excessive mitochondria-derived ROS, but also 'rescued' the reduced penetration capacity of spermatozoa treated with 3-NPA. Taken together, the study suggested that mitochondria-derived ROS and mitochondrial respiratory capacity are independent bio-markers for sperm dysfunction, and melatonin may be useful in improving sperm quality and overall male fertility.

19.
Thyroid ; 29(10): 1475-1484, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31347461

RESUMO

Background: Subclinical thyroid disease occurs in approximately 5-8% of all pregnancies and is associated with a higher risk of adverse outcomes such as miscarriage, preterm birth, and suboptimal child neurodevelopment. It is generally assumed that subclinical thyroid disease that persists from early to late pregnancy is associated with a higher risk of adverse outcomes than transient disease. However, it is unknown as to what percentage of women with subclinical disease during early pregnancy have persistent disease in the third trimester. Methods: This study comprised 42,492 mothers for whom early and late pregnancy thyrotropin (TSH), free thyroxine (fT4), triiodothyronine (T3), or TPOAbs were available and who did not receive thyroid treatment before or during pregnancy. We adjusted for potential confounders, including maternal age, parity, anthropometrics, and ß-hCG concentrations. Results: Subclinical hypothyroidism and hypothyroxinemia persisted in 24.8% and 17.7% of cases. Overt hyperthyroidism persisted in 8.4% of cases while subclinical hyperthyroidism persisted in 20.9% of cases. Low T3 persisted in 43.4% of cases while elevated T3 persisted in 15.7% of cases. TPOAb positivity persisted in 84.0% of cases. In women with subclinical hypothyroidism, a TSH below ∼5 mU/L at the time of diagnosis was associated with an up to 50% lower risk of persistency. The fT4 concentration at diagnosis predicted hyperthyroidism persistency and TPOAb positivity predicted persistency of all disease entities. Conclusions: Early pregnancy thyroid disease only persists until the third trimester in 8.4-24.8% of cases when left untreated. The main predictor for persistency is TPOAb positivity, with TPOAb-positive women having a lower risk that subclinical hypothyroidism or hypothyroxinemia persists, but a higher risk that (subclinical) hyperthyroidism persists.

20.
J Clin Endocrinol Metab ; 104(12): 5853-5863, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31216012

RESUMO

CONTEXT: Previous studies suggest that maternal thyroid function affects fetal growth, but the association between combined thyroid hormones from early to late pregnancy and newborn birth weight remains unknown. OBJECTIVE: To explore the association of maternal thyroid function during early and late pregnancy with birth weight. DESIGN: A large prospective cohort study of a Chinese population. SETTING: This study recruited pregnant women who underwent first-trimester prenatal screenings at the International Peace Maternity and Child Health Hospital between January 2013 and December 2016. PARTICIPANTS: This study enrolled 46,186 mothers in whom TSH, free thyroxine (FT4), T3, and thyroid peroxidase antibody concentrations were measured in the first and third trimesters and in whom data on birth weight were available. MAIN OUTCOME MEASURES: Birth weight, small for gestational age, large for gestational age (LGA). RESULTS: A higher TSH or FT4 concentration, or a lower T3 concentration, during the first or third trimester was associated with a lower birth weight. The lowest percentiles of maternal FT4 (FT4 < 2.5th percentile) in both trimesters were associated with a 0.34-SD higher birth weight. The effect estimates were greater in those in the first trimester (0.23 SD) or in the third trimester (0.17 SD). The association of maternal TSH and FT4 with birth weight differed according to fetal sex. CONCLUSIONS: Persistently low FT4 concentrations throughout pregnancy were associated with higher birth weight and an increased risk of LGA. Based on these findings, we recommend monitoring mildly altered concentrations of thyroid hormone throughout pregnancy.

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