Reproductive Sciences最新文献

Purpose: To elucidate if morning or evening start of exogenous progesterone (P4) five days before blastocyst embryo transfer (ET) impacts ongoing pregnancy rates (OPR) in artificial cycles.

Methods: Single-centre retrospective cohort study of 6493 artificial cycles for an ET (oestrogens and luteal phase support [LPS] with micronized vaginal progesterone [MVP] 400 mg/12 h), conducted at an infertility clinic, December 2018-July 2022. LPS was given from five days before ET. Until March 2021, LPS was started in the evening of day 0 of P4 exposure ("evening start"); since April 2021, LPS was started in the morning of day 0 ("morning start").

Results: Morning start of LPS (n = 2482 cycles); evening start (n = 3983 cycles). Morning or evening start did not exert any impact in OPR (46.9% vs. 46.3%, p = 0.682), as well as after adjusting for any potential confounders (aOR (95%CI): 1.00 (0.89-1.13); p = 0.996). Regarding serum P4 levels, no differences were found between morning (13.4 ± 5.8 ng/ml) and evening start of LPS (13.2 ± 6.4 ng/ml; p = 0.181). However, suboptimal serum P4 levels on the ET day (< 8.8 ng/ml) were registered in 16.6% (n = 411) vs. 19.8% (n = 788) of cycles with a morning and evening start, respectively (p = 0.001).

Conclusions: A 12-h difference in exogenous P4 initiation does not exert an impact on pregnancy outcomes in artificial cycles with MVP, as far as it is started five days before ET. Results from this study offer a great advantage in patient management, by being able to start LPS either in the morning or in the evening five days before blastocyst transfer.

Fetal growth restriction (FGR) affects between 5-10% of all live births. Placental insufficiency is a leading cause of FGR, resulting in reduced nutrient and oxygen delivery to the fetus. Currently, there are no effective in utero treatment options for FGR, or placental insufficiency. We have developed a gene therapy to deliver, via a non-viral nanoparticle, human insulin-like 1 growth factor (hIGF1) to the placenta as a potential treatment for placenta insufficiency and FGR. Using a guinea pig maternal nutrient restriction (MNR) model of FGR, we aimed to understand the transcriptional changes within the placenta associated with placental insufficiency that occur prior to/at initiation of FGR, and the impact of short-term hIGF1 nanoparticle treatment. Using RNAsequencing, we analyzed protein coding genes of three experimental groups: Control and MNR dams receiving a sham treatment, and MNR dams receiving hIGF1 nanoparticle treatment. Pathway enrichment analysis comparing differentially expressed genelists in sham-treated MNR placentas to sham-treated Control revealed upregulation of pathways associated with degradation and repair of genetic information and downregulation of pathways associated with transmembrane transport. When compared to sham-treated MNR placentas, MNR + hIGF1 placentas demonstrated changes to genelists associated with transmembrane transporter activity including ion, vitamin and solute carrier transport. Overall, this study identifies the key signaling and metabolic changes occurring in the placenta contributing to placental insufficiency prior to/at initiation of FGR, and increases our understanding of the pathways that our nanoparticle-mediated gene therapy intervention regulates.

Alterations in the microbiome composition have been identified in common gynecologic pathologies such as endometriosis carving a new frontier in diagnosis and treatment. We aimed to examine the existing literature on perturbations in the reproductive tract microbiome of individuals with adenomyosis informing future therapeutic targets. To examine the association between the reproductive tract microbiome composition among individuals with adenomyosis when compared to controls that can lead to new research evaluating novel mechanisms of action and treatment modalities. A systematic literature search identified studies that compared differences in microbiome composition using culture-independent microbiome analysis between individuals with adenomyosis when compared to controls. Five observational cross-sectional studies characterizing the lower and upper reproductive tract in humans were included. The diagnostic criteria of adenomyosis included surgical and imaging-based criteria. All studies used a 16S rRNA sequencing method. All individuals were recruited from either China or Thailand. An association between adenomyosis and alterations in the microbiome composition included relative deficiencies in Lactobacillus and relative enrichment of anaerobic and gram-negative bacteria when compared to control participants. Comparative studies suggest that there are significant perturbations in the microbiota composition of individuals with adenomyosis when compared with controls. Limiting conclusions include relative small sample sizes, a homogeneous population, and scant clinical phenotypic data. This systematic review identified significant alterations in the bacterial composition of adenomyosis cases that can be leveraged to design mechanistic studies and future innovative approaches to diagnose and manage this pathology. Trial registration: PROSPERO (CRD42023494563). Registered December 28, 2023.

The high-altitude hypoxia model demonstrates that insufficiently oxygenated placentas activate compensatory mechanisms to ensure fetal survival, hinging on the transcription factor hypoxia-inducible factor-1. The aim of the present study is to investigate whether and when similar mechanisms are also activated during intrauterine growth restriction (IUGR). A retrospective observational study evaluated a series of umbilical cord blood samples, which provide a realistic representation of the fetal intrauterine status, collected from a cohort of preterm and term neonates, both affected and not affected by IUGR. Results demonstrate that preterm IUGR fetuses receive a lower supply of oxygen and glucose from the placenta, along with a greater provision of lactate and carbon dioxide compared to non-IUGR neonates. Simultaneously, preterm IUGR fetuses increase oxygen extraction and reduce lactate production. These differences between IUGR and non-IUGR placentas and fetuses disappear as the term of pregnancy approaches. In conclusion, this study suggests that hypoperfused placentas in preterm pregnancies with IUGR activate a metabolic reprogramming aimed at favoring glycolytic metabolism to ensure fetal oxygenation, even though the availability of glucose for the fetus is reduced. Consequently, preterm IUGR fetuses activate gluconeogenetic metabolic reprogramming, despite it being energetically expensive. These metabolic adaptations disappear in the last weeks of pregnancy, likely due to physiological placental aging that increases the fetoplacental availability of oxygen. Placental oxygenation appears to be the main driver of metabolic reprogramming; however, further studies are necessary to identify the underlying biological mechanisms modulated by oxygen.

Preeclampsia (PE), an idiopathic hypertensive disorder that arises during pregnancy, poses a serious threat to the health of expectant mothers. Human chorionic trophoblast cells (HTR-8/SVneo) are associated with the development of PE. It has been reported that circ_0008440 expression is abnormally increased in the placental tissues of PE patients. However, the function of circ_0008440 within HTR-8/SVneo cells during PE has yet to be fully elucidated. The study used RT-qPCR and western blot assay to evaluate the expression levels of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 2 (PFKFB2), circ_0008440, and miR-942-5p in PE patients. Cells viability was measured using cell counting kit-8 (CCK-8) assay. Cell cycle assay and 5-ethynyl-2'-deoxyuridine (EDU) assay were used to measure cell proliferation. Cell apoptosis was assessed using flow cytometry assay. Western blot assay was used to detect protein expression. Dual-luciferase reporter assay and RNA pull-down assay were used to assess the interactions among circ_0008440, miR-942-5p, and PFKFB2 in HTR-8/SVneo cells. The study showed that the expression levels of circ_0008440 and PFKFB2 were significantly increased, while the expression of miR-942-5p was significantly decreased in the placental tissues of PE patients. Silencing of circ_0008440 promoted proliferation and tube formation and inhibited apoptosis of HTR-8/SVneo cells. In terms of molecular mechanism, miR-942-5p inhibitor or overexpression of PFKFB2 could partially reverse the effects of circ_0008440 silencing on the biological characteristics of HTR-8/SVneo cells. Collectively, circ_0008440 could act as a sponge of miR-942-5p to regulate the expression of PFKFB2, which further inhibited viability and proliferation of HTR-8/SVneo cells and promoted cell apoptosis.

This study investigates the association between parity and type 2 diabetes mellitus (T2DM) in Japanese women, considering the clinical history of gestational diabetes mellitus (GDM) and menopausal status, which are known risk factors for T2DM. Overall, 30,116 Japanese women (6,588 premenopausal and 23,528 postmenopausal) were included in this cross-sectional study. They were divided into two groups according to menopausal status (premenopausal and postmenopausal women), and the association between parity and T2DM was evaluated using a multiple logistic regression model with possible confounders, including a clinical history of GDM. The association between parity and T2DM was not statistically significant in premenopausal women. In contrast, a linear graded association between parity and T2DM was found in postmenopausal women. Furthermore, the association between parity and T2DM in postmenopausal women was attenuated after adjusting for body weight gain after the age of 20 years. A clinical history of GDM was significantly associated with a high risk for T2DM, regardless of adjustment for body weight gain after the age of 20 years in both premenopausal and postmenopausal women. Parity is associated with an increased risk of T2DM in postmenopausal women but not in premenopausal women. Maintaining appropriate body weight would be beneficial in attenuating the risk of T2DM in postmenopausal women. A clinical history of GDM is a risk factor for T2DM in both pre- and postmenopausal women; therefore, women with a clinical history of GDM require continuous medical care to survey for T2DM.

Circulating miRNAs (C-miRNAs) occuring in a cell-free form within body fluids and other extracellular environments have garnered attention in recent times. They offer deeper insight into various physiological and pathological processes which include reproductive health. This review delves into their diagnostic potential across a spectrum of reproductive disorders, including conditions affecting ovarian function, male infertility and post pregnancy issues. Through analysis of C-miRNA profiles in bodily fluids, researchers uncover crucial markers indicative of reproductive challenges. Dysregulated C-miRNAs emerge as important players in the progression of several reproductive disorders which is the main focus of this review. Advancements in technology, facilitate precise detection and quantification of C-miRNAs, paving the way for innovative diagnostic approaches. Challenges in studying C-miRNAs, such as their low abundance and variability in expression levels, underscore the need for standardized protocols and rigorous validation methods. Despite these challenges, ongoing research endeavors aim to unravel the complex regulatory roles of C-miRNAs in reproductive biology, with potential implications for clinical practice and therapeutic interventions.

Evidence of endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) have been increasingly reported in varicocele (VCL)-affected testes. However, the mechanisms by which oxidative stress (OS) and ER stress contribute to male infertility in VCL remain unclear. In this study, male Sprague-Dawley rats were divided into a control group, which underwent sham surgery, and a VCL group, in which VCL was surgically induced. Eight weeks postoperatively, the VCL group exhibited significant testicular damage and sperm abnormalities. Western blot analysis revealed upregulation of ER stress-related proteins and downstream apoptotic markers in the VCL group. For further investigation, we developed an in vitro oxidative stress model using GC-2 cells treated with 400 µM hydrogen peroxide (H₂O₂) for 12 h. Cells were also treated with either an ER stress inducer or inhibitor. We found that treatment with H₂O₂ and the ER stress inducer significantly reduced GC-2 cell viability and increased reactive oxygen species (ROS) production, ER stress, and apoptosis. Conversely, treatment with the ER stress inhibitor 4-phenylbutyric acid (4-PBA) alleviated these effects. Our findings suggest a strong association between VCL-induced redox imbalance and ER stress-related injury driven by the UPR in this rat model. Furthermore, 4-PBA effectively reduced germ cell damage induced by ROS-mediated ER stress, offering potential therapeutic insights for treating VCL-related infertility.

There is limited clinical research investigating the optimal transplantation strategy in early oocyte retrieval cycles. We aimed to assess whether the maturation of oocytes from early oocyte retrieval influenced pregnancy outcomes, and to find the optimal embryo transfer strategy (fresh or frozen-thawed embryo transfers) for patients who had early oocyte retrieval and underwent in vitro maturation (IVM). A retrospective cohort study was conducted in a university-based reproductive medical center. A total of 234 women who underwent single embryo transfer after early oocyte retrieval were included. The primary outcome was live birth rate. The live birth rate (12.5% vs. 27.5%, p = 0.005, adjusted p = 0.010) was significantly lower in IVM cycles compared with no IVM cycles. There was a significant decrease in live birth (3.6% vs. 19.0%, p = 0.008, adjusted p = 0.011) and a markedly elevated early pregnancy loss rate (62.5% vs. 11.1%, p = 0.014, adjusted p = 0.012) for IVM fresh cycles compared with no IVM fresh cycles. However, these findings were not repeated in subgroup analysis when frozen-thaw embryos were transferred. These results indicate that patients who underwent early oocyte retrieval and then IVM-intracytoplasmic sperm injection should be recommended the embryo cryopreservation strategy. Resynchronization of the embryo and the endometrium in frozen-thaw embryo transfer cycles may optimize live birth and decrease early pregnancy loss in IVM-intracytoplasmic sperm injection cycles after early oocyte retrieval.