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UNASSIGNED: Recurrent miscarriage is one of the most prevalent reproductive diseases. This phenomenon has several reasons, including maternal, hormonal, immunological, and parental genetic factors. Idiopathic recurrent miscarriage (IRM), with no distinctive etiology, involves about half of the recurrent miscarriage cases. Some mutations in mitochondrial DNA can lead to miscarriage. Mitochondrial tRNA (mt-tRNA) mutations cause nearly half of the mitochondrial disorders.
UNASSIGNED: To identify mt- tRNACys&Tyr gene mutations in Iranian women with IRM.
UNASSIGNED: In this case-control study, 100 Iranian women with IRM and 100 women as control without any history of miscarriage were investigated by polymerase chain reaction-single strand conformation polymorphism technique followed by gene sequencing. Bioinformatics analysis were done using human mitochondrial genome database, molecular evolutionary genetics analysis, mammalian mitochondrial-tRNA, etc.
UNASSIGNED: Results showed 4 mt-tRNA mutations including 1 cysteine mt-tRNA mutation (5824C>T) and 3 tyrosine mt-tRNA mutations (5868T>A, 5849C>T, and 5836T>C) in our cases.
UNASSIGNED: Amongst the 4 mutations found, one was novel that is still not reported. Our bioinformatics analysis revealed that these mutations can be pathogenic. They occurred in tRNA-conserved regions and their secondary structure was changed, which can result in mitochondrial dysfunction. Mutations of these genes may help in the assessment of IRM. Further study of all 22 mt-tRNAs possible mutations is recommended to describe their etiologic role in IRM.

UNASSIGNED: The effect of anticoagulant medication in unexplained early recurrent pregnancy loss (RPL) patients is controversial. This clinical trial evaluated the effect of low-molecular-weight heparin (LMWH) on pregnancy outcomes in these patients.
UNASSIGNED: The study was performed as a single-blind randomized clinical trial between 2016 and 2018. Samples were selected from patients who were referred to Avicenna RPL clinic with a history of at least two previously happened early unexplained miscarriages. The eligibility was defined strictly to select unexplained RPL patients homogenously. One hundred and seventy-three patients who got pregnant recently were allocated randomly into two groups LMWH plus low-dose aspirin treatment (Group A = 85) and low-dose aspirin treatment only (Group B = 88)) and were followed up till their pregnancy termination (delivery/abortion). A per-protocol analysis was carried out and all statistical tests were two-sided with a P < 0.05 significance level.
UNASSIGNED: The live birth rates (LBRs) in Groups A and B were 78% and 77.1%, respectively, which did not show any statistically significant difference between the two groups, neither in rates nor in time of abortion. In subgroup analysis for polycystic ovary syndrome (PCOS) patients, the odds ratio for study outcome (intervention/control) was 2.25 (95% confidence interval: 0.65-7.73). There was no major adverse event whereas minor bleeding was observed in 18% of patients in Group A.
UNASSIGNED: LMWH does not improve the LBR in unexplained RPL patients, however, it is recommended to evaluate its effect separately in PCOS patients.

BACKGROUND: Recurrent pregnancy loss (RPL) and infertility are associated with significant psychiatric complications.
The study aimed to investigate the effectiveness of cognitive behavioral therapy (CBT) and sertraline
in the treatment of in depression, anxiety, and infertility stress of depressed infertile women with RPL in comparison
with usual care.
Materials and Methods: A triple-arm randomized controlled trial was carried out on the 60 depressed infertile
women with RPL, a population of Infertility Center of Babol city, Iran, who were randomly assigned into three
groups: pharmacotherapy with sertraline (n=20), psychotherapy with CBT (n=20), and a usual care as control
group (n=20). The participants of psychotherapy received CBT sessions (90 minutes each) over 10 weeks. The
participants in the pharmacotherapy group took 50 mg/day sertraline daily for 22 weeks. Outcomes were assessed
using the Beck Depression Inventory (BDI-II), fertility problem inventory (FPI), and State-Trait Anxiety
Inventory Form Y (STAI-Y) at the beginning of the trial, 10-weeks post-trial, and three months of follow-up.
Using statistical package for the social sciences (SPSS) software, data were analyzed.
Results: CBT considerably reduced the depression symptoms more than sertraline with a moderate effect size
at the post-trial (g=0.11, 95% CI: -0.03 to -0.50). Sertraline showed reduced the scores of state-anxiety more
considerably in comparison with control group by a large effect size of post-trial (g=-1.04, 95% CI: -1.70 to
-0.38). CBT reduced the total scores of FPI more considerably than sertraline, with a large, small size at follow
up-trial [95% CI=-0.03(-0.65, -0.58)]. Both CBT and sertraline were superior to the control group in reducing
depression and infertility stress.
Conclusion: Depression and infertility stress diminished under CBT and sertraline in depressed infertile women with
RPL, with a significant advantage of CBT. Sertraline was superior to CBT in reduction of anxiety (registration number:
IRCT201304045931N3).

Male factor infertility accounts for approximately 50% of all infertility evaluations. A common cause of severe oligozoospermia and azoospermia is Y chromosome microdeletions (YCMs). Men with these genetic microdeletions must typically undergo assisted reproductive technology (ART) procedures to obtain paternity. In this review, we performed a thorough and extensive search of the literature to summarize the effects of YCMs on in vitro fertilization (IVF) outcomes, health abnormalities in offspring and recurrent pregnancy loss (RPL). The PubMed database was searched using specific search terms and papers were identified using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Sperm retrieval amongst men with complete AZFa and/or AZFb deletions is extremely rare and thus data on ARTs is largely unavailable. In AZFc-deleted men undergoing assisted reproduction, the collective fertilization rate (FR) is 59.8%, the clinical pregnancy rate is 28.6% and the live birth rate is 23.4%. When successful, the YCM is always transmitted to the male offspring and the deletion size either remains unchanged or widens. YCMs generally result in decreased fertilization, clinical pregnancy and live birth rates compared to men with intact Y chromosomes during ART interventions. There is a minimal or absent association of YCMs with abnormalities in the offspring or RPL.

OBJECTIVE: To compare the use of the luteinizing hormone (LH) surge versus the last menstrual period (LMP) for the accuracy of pregnancy dating in fertile women with a diagnosis of recurrent early pregnancy loss (REPL).
METHODS: This was an observational cohort study using prospectively collected data at 2 academic REPL programs between 2005 and 2018. Women with a history of REPL and at least 1 subsequent live birth after the evaluation were included. All patients conceived by intercourse timed to the LH surge. Transvaginal ultrasound was examinations were performed 2 weeks after missed menses. The gestational age (GA) was calculated by the LH surge (GALH ), LMP (GALMP ), and first crown-rump length (CRL) that measured 5 mm or greater (GACRL ). A secondary analysis compared GA based on the first measurable CRL of less than 5 mm versus GA based on the first CRL of 5 mm or greater. The GALH and GALMP were compared to determine which measure showed greater concordance with the CRL. The mean absolute difference in days between the GACRL versus GALH and GACRL versus GALMP was determined.
RESULTS: A total of 115 women with 118 subsequent pregnancies resulting in live birth were included, with a mean age at delivery of 35.5 years and a mean of 3.6 prior pregnancy losses. The GALH showed a stronger correlation with the CRL (0.77) than the GALMP (0.63; P = .002). The GALH was more similar to the GACRL than the GALMP , with a mean absolute difference of 2.0 versus 3.1 days (P < .0001).
CONCLUSIONS: When known, the LH surge appears to be more accurate than the LMP and should be used preferentially for dating of early pregnancy.

At present, the etiology and pathogenesis of recurrent early pregnancy loss (REPL) are not completely clear. Therefore, identifying the underlying diagnostic and prognostic biomarkers of REPL can provide new ideas for the diagnosis and treatment of REPL. The chip data of REPL (GSE63901) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to construct a co-expression module for studying the relationship between gene modules and clinical features. In addition, functional analysis of hub genes in modules of interest was performed. A total of 23 co-expression modules were identified, two of which were most significantly associated with three clinical features. The MEbrown module was positively correlated with cyclin E level and the out-of-phase trait while the MEred module was positively correlated with the effect of progesterone. We identified 17 hub genes in the MEred module. The functional enrichment analysis indicated that such hub genes were mainly involved in pathways related to cellular defense response and natural killer (NK) cell-mediated cytotoxicity. In the MEbrown module, we identified 19 hub genes, which were mainly enriched in cell adhesion molecule production, regulation of cellular response to growth factor stimulus, epithelial cell proliferation, and transforming growth factor-β (TGF-β) signaling pathway. In addition, the hub genes were validated by using other datasets and three true hub genes were finally obtained, namely DOCK2 for the MEred module, and TRMT44 and ERVMER34-1 for the MEbrown module. In conclusion, our results screened potential biomarkers that might contribute to the diagnosis and treatment of REPL.

We correlated Anti-Mullerian hormone (AMH) levels and other parameters for ovarian reserve to the gestational age at the time of pregnancy loss in women with idiopathic recurrent miscarriage. In a retrospective study, 79 patients had suffered a total of 266 miscarriages. When comparing women with an \"unembryonic\" to those with an \"embryonic\" most recent miscarriage, there was no difference in median age (36.3 years, IQR 31.6-40.1 versus 34.2 years, IQR 29.9-38.0; p = 0.303) but in median AMH levels (0.7, IQR 0.2-18, versus median 1.8, IQR 1.3-3.3, respectively, p = 0.044) and in the rate of patients with an AMH ≤ 1 ng/mL (23/37, 62.2%, versus 8/42, 19%; p < 0.001). Thus, AMH might add to the diagnostic process in recurrent miscarriage in the future.

Etiologic factors for recurrent miscarriage (RM) include autoimmune diseases, the most frequently antiphospholipid syndrome and thyroiditis. Some women who suffer from RM might also have an altered immune system. We aimed to evaluate possible associations between anti-thyroid and anti-phospholipid antibodies in women with RM. In a retrospective case series 1 on 156 women with RM, major outcome parameters were antibodies against cardiolipin, β2-glycoprotein I, thyreoperoxidase (TPO-Ab), and thyroglobulin (TG-Ab). Significant (p<0.05) positive correlations were found between TPO-Ab and TG-Ab (r=0.577), TPO-Ab and IgG anti-cardiolipin antibodies (r=0.284), TPO-Ab and IgG anti- β2-glycoprotein I antibodies (r=0.196), and TG-Ab and IgG anti-cardiolipin antibodies (r=0.193), as well as between all types of anti-phospholipid antibodies. Women with both increased TPO-Ab and TG-Ab levels revealed higher (p<0.001) IgG anti-cardiolipin and IgG anti-β2-glycoprotein I antibodies. Anti-thyroid antibodies were linked to anti-phospholipid antibodies and should be in the focus of future research on RM.

OBJECTIVE: Are the genes that gained novel expression in the endometria of Eutherian (placental) mammals more likely to be dysregulated in patients with endometrial-associated recurrent early pregnancy loss (REPL)?
CONCLUSIONS: There was a significant enrichment of genes dysregulated in REPL patients among the Eutherian-specific endometrial genes.
BACKGROUND: Pregnancy loss is the most common complication of human pregnancy. REPL has multiple etiologies, including dysregulation of endometrial function, leading to \'suboptimal\' implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown.
METHODS: Endometrial biopsies were obtained from 32 REPL patients during the mid-luteal phase, and evaluated for glandular development arrest based on elevated nuclear cyclin E levels in gland cells, and for out-of-phase endometrial development based on histology. Gene expression levels were measured using Illumina Human HT-12v4 BeadChip arrays.
METHODS: Differentially expressed genes were identified between patients with (i) out-of-phase (n = 10) versus normal (n = 22) histological dating and (ii) abnormally elevated (n = 9) versus normal (n = 23) cyclin E levels in the nuclei of endometrial glands, using a likelihood ratio test. Enrichment of dysregulated genes in REPL endometria among Eutherian-specific genes was tested by permutation. Gene ontology and pathway enrichment analyses were carried out for the dysregulated genes.
RESULTS: Fifty-eight and eighty-one genes were identified as differentially expressed at P < 0.001 in women with out-of-phase histological dating and abnormally elevated glandular cyclin E levels, respectively. Genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P = 0.002 for histology, P = 0.021 for cyclin E), as well as for genes involved in immune response and signaling pathways with essential roles in implantation and endometrial biology.
CONCLUSIONS: Small sample size limits the statistical power to detect dysregulated genes, and the lack of non-REPL control women does not allow us to test for the contribution of these genes to overall risk of REPL.
CONCLUSIONS: Enrichment of functional gene categories, as well as genes gained expression in the Eutherian endometria, help to identify molecular etiologies that contribute to normal functioning of the endometrium. These pathways are also strong candidates for successful pregnancy outcomes. Using the evolutionary history of mammalian gene expression in the endometrial tissue may be a promising approach to discover genes involved in female reproductive disorders.
BACKGROUND: This work is supported by National Institutes of Health (NIH) grant R01 HD21244 to C.O. Authors declare no competing interests.