Reproductive Sciences最新文献

Vitrification has revolutionized embryo cryopreservation, but represents a significant workload in the IVF lab. We evaluated here an ultrafast blastocyst warming procedure in order to improve workflow while maintaining clinical outcome. We first evaluated the expression of main markers of lineage specification in a subset of blastocysts donated to research warmed with ultrafast protocol. We then performed a prospective pseudo-randomized pilot study comparing blastocyst survival, reexpansion and live birth rates between standard (3 steps, 15 min), and ultrafast warming protocol (1 step, 2 min). Finally, survival, reexpansion and live birth rates (LBR) obtained with ultrafast warming protocol were prospectively collected during 3 months and compared with previous indicators. Immunofluorescence experiments showed that staining and spatial organization of cell fate markers were conserved with ultrafast protocol. Survival, reexpansion and LBR were strictly comparable between standard (n = 47 cycles) and ultrafast (n = 39 cycles) groups in the pilot study (100 vs 100%, 80 vs 76% and 29.8 vs 30.7% in standard and simplified groups respectively). Survival, expansion and LBR obtained with the ultrafast warming protocol over the next 3-month period (321 cycles, 336 embryos) were comparable with those obtained with the standard protocol throughout the 6 months (547 FBT cycles, 578 embryos) preceding shifting protocol (97.6 and 29.6% vs 97.8 and 28.3% respectively, p > 0.05 for both). In conclusion, using an ultrafast blastocyst warming procedure results in similar embryology and clinical outcomes compared with standard protocol, but significantly shortens the technical procedure, ultimately improving the overall lab's workflow.

In an attempt to stimulate further theory and research on only children, we introduce two conceptual distinctions: Only children as independent variables vs. only children as dependent variables; and only children by choice vs. only children by circumstances. What little scientific research exists on only children to date focuses almost exclusively on only children as independent variables and fails to make a distinction between only children by choice and only children by circumstances. A focus on only children by choice as dependent variables explores the question of why some women choose to have only one child. As an empirical illustration, analyses of prospectively longitudinal data with a nationally representative sample in the United Kingdom (National Child Development Study) show that women who experience pregnancy complications are significantly less likely to have another child and significantly more likely to have only one child. Our results suggest that increased chances of pregnancy complications that American women now experience alone can explain about 10% of the increase in the number of only children in the United States in the last half century. If certain genes incline women to have pregnancy complications, it is possible that only children by circumstances are genetically more similar to children with siblings than to only children by choice.

Matrix metallopeptidase 9 (MMP9) is a secreted zinc-dependent peptidase known for extracellular remodeling. MMP9 is elevated in tissues from women experiencing preterm labor, and previous research has shown that the addition of combined matrix metallopeptidases 2 and 9 (MMP2/9) enhances uterine contractions. We hypothesized that adding MMP9 alone would enhance myometrial contractions and that specific MMP9 inhibition would suppress uterine contractions. In myometrial tissue from women undergoing term Caesarean sections, we observed an increased contractile response as measured by area under the curve over time in tissues treated with MMP9 compared to vehicle-treated controls (p = 0.0003). This effect was primarily due to increased contraction frequency in MMP9-treated tissues compared to controls (p < 0.0001). Specific inhibition of MMP9 with the highly selective MMP9 inhibitor 1 (AG-L-66085) reduced contractile responses in myometrial tissues from pregnant women. We observed a reduction in the oxytocin-induced contractile response as measured by area under the curve over time (p < 0.0001) and contraction amplitude (p < 0.0068) in AG-L-66085-treated tissues compared to vehicle-treated controls. To determine the effects of MMP9 inhibition in the absence of exogenous oxytocin, we tested the effects of AG-L-66085 on spontaneous contractions. The area under the curve (p = 0.0415) and amplitude (p = 0.0354) of spontaneous contractions were reduced in response to 1 μM AG-L-66085, and the inhibitory effects increased as the AG-L-66085 concentration increased. Together, these data support the hypothesis that elevated MMP9 promotes myometrial contractions and labor, while its inhibition promotes relaxation.

Recent research has proven that peripheral (PS) and central sensitization (CS), mental health, and myofascial dysfunction all play a role, alongside nociception, in the genesis and in the perpetuation of endometriosis' symptoms. However, such components of pain are still largely ignored in clinical practice, although not considering such contributors may entail serious consequences on women's health, including the choice of unnecessary surgery and leaving the real causes of pain untreated. At the present time, we are facing a paradox by which 25-40% of women who undergo laparoscopic surgery for pelvic pain do not have an obvious diagnosis, while the percentage of women with endometriosis who have signs of CS, of depressive or anxiety disorders, or who have an increased pelvic muscle tone ammounts to 41-55%, 15-88% and 28-73%, respectively. Moving from the widely-accepted stepwise approach suggested for endometriosis management, which consists in the initial prescription of low-dose combined oral contraceptives (COCs) or of a progestin monotherapy, followed by GnRH analogues and, ultimately, by surgery, when COCs and progestins have proven ineffective or are not tolerated or contraindicated, we propose an integration of such model which takes into account the identification and the simultaneous treatment of all pain contributors. Our objective is to encourage physicians' awareness of the need of a multidisciplinary, multimodal approach to endometriosis-related pain, and ultimately to promote a reduction in the number of unnecessary surgeries.

Adenomyomectomy, a therapeutic option for women with adenomyosis who wish to preserve their fertility, has been reported to pose a risk of developing placenta accreta spectrum (PAS) and uterine rupture in future pregnancies. However, the specific clinical factors contributing to these occurrences remain elusive. This study aimed to explore the association between hysteroscopic findings after adenomyomectomy and the incidence of PAS in subsequent pregnancies. We conducted a retrospective analysis of 10 patients (11 pregnancies) who had undergone hysteroscopy following adenomyomectomy and had later delivered at our hospital. In 6/10 patients, postoperative hysteroscopy revealed endometrial defects. However, subsequent evaluations confirmed endometrial restoration within 7-21 months, with five patients achieving pregnancy afterward. The only other patient conceived naturally without waiting for endometrial restoration, resulting in uterine rupture from the site of the placenta percreta. The incidence of clinically diagnosed PAS during cesarean section was 100% (1/1) in pregnancies with preconceptional endometrial defects, 20% (1/5) in those with endometrial restoration, and 0% (0/5) in pregnancies without endometrial defects. Similarly, the incidence of pathologically diagnosed PAS was 100% (1/1), 60% (3/5), and 20% (1/5) in these groups, respectively. Thus, endometrial defects were frequently detected after adenomyomectomy and recovered over time, whereas one patient without endometrial restoration developed uterine rupture complicated by PAS. This study demonstrates that while the presence of an endometrial defect identified by postoperative hysteroscopy may be a risk factor for the occurrence of PAS in subsequent pregnancies, allowing sufficient recovery time for the endometrium may help reduce the risk of uterine rupture.

Late-term pregnancy is commonly seen in obstetrics and is linked to adverse outcomes. Corrected fetal adrenal gland volume (cAGV) is an ultrasound marker that was used to predict preterm labor. The objective was to determine whether cAGV, in conjunction with other maternal risk factors, could predict late-term pregnancy among low-risk pregnant women in order to improve obstetric care. A prospective study recruited 177 low-risk primigravida women. Ultrasound-based cAGV was calculated for all participants at 37 weeks. Participants were followed until the day of delivery; accordingly, they were divided into two groups: Control group (137/177) delivered at term (37 + 0/7-40 + 6/7) weeks and late-term group (40/177) who delivered at (41 + 0/7-41 + 6/7) weeks. Maternal age, body mass index (BMI), and gestational age were collected for all participants alongside ultrasound data such as fetal biometry, gender, and estimated fetal weight. The participants' mean age was (27.32 ± 5.17) years. The cAGV was significantly lower among pregnant women who passed their due dates and was inversely correlated to the gestational age (r = - 0.6, P < 0.001). The cAGV exhibited a high probability of predicting late-term pregnancy (OR = 3.47; 95% CI = 1.37 to 8.79; P = 0.009). In contrast, maternal age, maternal BMI, and the presence of a male fetus did not demonstrate any significance as predictors. The cAGV cut-off value (≤ 277mm3/kg) predicted late-term pregnancy (P < 0.001) at a 77.5% sensitivity and 91.2% specificity. The cAGV can predict late-term pregnancy with good sensitivity and specificity. It is proposed as a promising tool for clinical use as non-invasive ultrasound obtained at no extra cost during routine 2-dimensional ultrasound examinations. More studies are warranted to explore further applications in improving feto-maternal outcomes among late-term pregnnat.

This study aimed to determine changes in uterine artery Doppler parameters in unexplained recurrent pregnancy loss (URPL) and to explore serum markers possibly associated with them. This retrospective case-control study included 107 URPL women and 107 control women. The mean pulsatility index (PI), resistive index (RI), and systolic-to-diastolic values for uterine arteries in URPL women were significantly higher than those in the controls (P < 0.05). The cutoff values of PI and RI differentiating the women with URPL from the controls were confirmed by ROC and Youden's index. Given a PI cutoff value of 2.6, the prevalence of URPL was significantly elevated in the high-PI group (74.58%) compared with that in the low-PI group (40.65%, P < 0.0001), with sensitivity and specificity of 63% and 69%, respectively. With an RI cutoff value of 0.86, the prevalence of URPL in the high-RI group (65.28%) was significantly elevated compared with that in the low-RI group (42.25%, P = 0.001), with sensitivity and specificity of 66% and 75%, respectively. The levels of serum D-dimers and anticardiolipin antibody (ACA)-IgM in URPL women were significantly higher than those in the controls. A positive correlation existed between the levels of ACA-IgM and uterine artery RI in URPL women (r = 0.43, P < 0.01). These results indicated that URPL women may be at a relatively high risk of a prothrombotic state, and the increased ACA-IgM deserves attention for its role in the elevated uterine artery Doppler parameters in URPL women.

Preeclampsia (PE) is the most common pregnancy-related complication responsible for maternal mortality and morbidity. PE pathogenesis is characterized by placental dysfunction, impaired invasion of trophoblast, and defective spiral artery remodelling. Even after many years of research on PE, the etiology and pathophysiology of PE is still elusive. Our earlier studies have shown deregulated maternal and placental fatty acid and lipid metabolism to be associated with the pathogenesis of PE. Currently available lipidomics data have shown that glycerophospholipids, sphingolipid and cholesterol metabolism are mainly altered in preeclampsia. Including these five metabolites (SM C28:1, SM C30:1, LPC C19:0, LPE C20:0, propane-1,3-diol) with currently used protein biomarkers like sFlt-1/PlGF will improve PE prediction. Similarly, CE17:1 and CER(d20:1/24:1) alongwith sFlt-1/PlGF makes a better prediction of PE than sFlt-1/PlGF alone A comprehensive map of lipid profiles in early pregnancy may provide an improved understanding of disease pathogenesis and will be useful predictive biomarkers. In this article, we aimed to summarize the significance of lipid metabolism in the preeclampsia pathogenesis and altered lipidome signatures in preeclampsia. We also discuss the future scope of lipidomics in aiding early prediction of PE and future cardiovascular risk in both mother and child.

Early pregnancy loss (EPL) is the most common complication in assisted reproductive technology (ART). However, the precise causes for nearly 50% patients remain unexplained. In the current study, we aimed to discover the differentially expressed profiling of mRNAs and lncRNAs by RNA sequencing (RNA-seq). Human chorionic villi tissues were collected from patients with EPL and natural control (NC) group. RNA sequencing (RNA-seq) of these specimens was performed for transcriptome analysis. As a result, we identified a total of 141 mRNAs and 137 lncRNAs that were significantly differentially expressed between villi tissues from EPL and NC. Functional enrichment analyses indicated enrichment of differentially expressed genes involved in pathways were associated with growth hormone receptor binding, PI3K-Akt signaling pathway, Jak-STAT signaling pathway, transcriptional misregulation in cancer, metabolic pathways and Rap1 signaling pathway. Additionally, the co-expression networks (lncRNA-miRNA-mRNA) was constructed based on the correlation analysis between the differentially expressed RNAs.7 mRNAs and 6 lncRNAs were successfully technically validated with RT-PCR. In conclusion, our results suggest a direction for the further study of EPL-related mRNAs and lncRNAs and may ultimately assist in understanding the pathogenesis of EPL.

DNA damage in spermatozoa is a major cause of male infertility. It is also associated with adverse reproductive outcomes (including reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage). The damage to sperm DNA occurs during the production and maturation of spermatozoa, as well as during their transit through the male reproductive tract. DNA damage repair typically occurs during spermatogenesis, oocytes after fertilization, and early embryonic development stages. The known mechanisms of sperm DNA repair mainly include nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), and double-strand break repair (DSBR). The most severe type of sperm DNA damage is double-strand break, and it will be repaired by DSBR, including homologous recombination (HR), classical non-homologous end joining (cNHEJ), alternative end joining (aEJ), and single-strand annealing (SSA). However, the precise mechanisms of DNA repair in spermatozoa remain incompletely understood. DNA repair-associated proteins are of great value in the repair of sperm DNA. Several repair-related proteins have been identified as playing critical roles in condensing chromatin, regulating transcription, repairing DNA damage, and regulating the cell cycle. It is noteworthy that XRCC4-like factor (XLF) and paralog of XRCC4 and XLF (PAXX) -mediated dimerization promote the processing of populated ends for cNHEJ repair, which suggests that XLF and PAXX have potential value in the mechanism of sperm DNA repair. This review summarizes the classic and potential repair mechanisms of sperm DNA damage, aiming to provide a perspective for further research on DNA damage repair mechanisms.