Reproductive Biology and Endocrinology最新文献

Müllerian anomalies are congenital conditions characterized by the incomplete development of the female reproductive tract. Women affected by Müllerian anomalies often display additional malformations of the renal, skeletal, and cardiovascular system, and are at a higher risk for infertility and adverse pregnancy outcomes. Several Müllerian anomalies have been reported in association with endometriosis, but it is unclear if all classes or anatomical variations are associated with the disease. Most importantly, both Müllerian anomalies and endometriosis can manifest with a wide degree of variability, adding further complexity to their poorly defined relationship. Retrograde menstruation occurring in obstructive Müllerian anomalies is a well-accepted mechanism for the development of endometriosis. However, endometriosis can occur following surgical correction of the anomaly or in the absence of obstruction. This suggests that other mechanisms may be involved, although the specific pathogenesis remains elusive. This review provides a comprehensive summary of the current state of clinical research on endometriosis in Müllerian anomalies. This review also highlights research and knowledge gaps, informing the development of future experimental designs to address current limitations including heterogeneity of phenotypes, variable comorbidities, and lack of genetic information.

Background: Contrast-induced nephropathy (CIN) defined as an acute kidney injury following the administration of iodinated contrast medium (CM). Hysterosalpingography (HSG) is a radiologic procedure used to investigate the shape and structure of the uterine cavity and the patency of the fallopian tubes in the evaluation of infertility. To date, there have been no reports evaluating the development of CIN after HSG procedure. Therefore, we investigated whether CIN development occurs in infertile women who underwent HSG and its relationship with clinical and laboratory changes in women who underwent HSG.

Methods: This study was undertaken in 65 women who had infertility evaluation, uterine anomalies and/or tubal blockages. CIN was defined as a 25% relative increase, or a 0.5 mg/dL (44 µmol/L) absolute increase, in serum baseline creatinine (SCr) within 72 h of contrast exposure in the absence of alternative conditions. Hysterosalpingography (HSG) was performed using 5-20 ml of contrast medium. All patients performed routine laboratory tests including assessment of serum creatinine and urea and estimated glomerular filtration rates before and 2-3 day after HSG. Statistical analysis was performed with MedCalc Statistical Software Program v22.023 (Ostend, Belgium) program.

Results: The mean ages of participants were 29.5 years and mean BMI were 26.2 kg/m2. The rate of CIN was 12.3% and the severe nephropathy was 1.5% in our study population. The baseline SCr level was 0.59 ± 0.06 mg/dL in women with CIN and 0.67 ± 0.11 mg/dL in women without CIN. The baseline SCr level was significantly lower in CIN group that non-CIN group (p = 0.0309). The SCr level significantly higher in CIN group than non-CIN group 48-72 h after HSG (p = 0.0005). In the multivariate logistic regression analysis, the baseline SCr was found an independent risk factor for the prediction of CIN in women who underwent HSG.

Conclusion: The HSG procedure is generally a safe method, but the iodine-containing contrast material used in HSG may be associated with temporary adverse effects on kidney function.

Research question: To determine whether the use of oral dydrogesterone (DYD) in luteal phase support (LPS) during an artificial cycle provides equivalent clinical and ongoing pregnancy, delivery and miscarriage rates as micronized vaginal progesterone (MVP) in oocyte donation recipients.

Design: This was a retrospective observational study of prospectively collected data from the assisted reproductive technology (ART) Department of Lille University Hospital from July 2018 to July 2022. All recipients underwent endometrial preparation by an artificial cycle. Luteal phase support (LPS) was provided by weekly intramuscular progesterone (IM) (500 mg/2 ml) and either DYD (40 mg/day) or MVP (800 mg/day) for 12 weeks if the pregnancy test was positive. The primary endpoint was the clinical pregnancy rate.

Results: Our study analysed 372 oocyte donation cycles with embryo transfer: 162 embryo transfers with DYD + IM progesterone and 210 embryo transfers with MVP + IM progesterone. After adjustment for confounding factors, our two groups were comparable in terms of clinical pregnancy rates, with 36.7% in the MVP group versus 30.3% in the DYD group (p = 0.55); ongoing pregnancy rates (29,1% versus 25.3%, p = 0.95); miscarriage rates (7.6% versus 4.9%, p = 0.35); and live birth rates (26.7% versus 25.3%, p = 0.86).

Conclusion: Oral dydrogesterone seems to be a good alternative to vaginal micronized progesterone for LPS treatment during an artificial cycle, especially in combination with a weekly injection of intramuscular progesterone in the course of oocyte donation.

Background & objective: To analyze whether there is an association between pre-pregnancy lipid parameters and gestational diabetes mellitus (GDM) in women undergoing assisted reproductive technologies (ART), a group especially at risk for GDM, and if so, which parameter is associated the strongest.

Methods: Data was collected at the Reproductive and Genetic Hospital CITIC-Xiangya in Changsha, China from January 2017 to December 2018. The measured lipid parameters include LDL (low-density lipoprotein), HDL (high-density lipoprotein), TC (total cholesterol), and TG (triglycerides).

Results: 119 (15.5%) of the 767 patients developed GDM. On average, women who developed GDM were older, had a higher BMI, LDL, TC, and TG, and lower HDL. After adjusting for confounders, LDL and HDL showed a significant association with GDM (p < 0.05), but TC and TG did not. Binary LDL/HDL and TC/HDL ratios showed the strongest association with GDM incidence (OR 1.957 [95%CI 1.258-3.044] and 1.942 [1.243-3.034] respectively). Subgroup analysis showed that an elevated LDL/HDL ratio also increased GDM risk in subgroups with a typically lower prevalence of GDM, such as young women with a low BMI and low blood pressure. Both lipid ratios (LDL/HDL and TC/HD) show strong interactions with baseline age, fasting plasma glucose, and LH.

Conclusions: In this cohort of Chinese women undergoing ART, pre-pregnancy LDL/HDL and TC/HDL were associated with GDM the strongest from the lipid parameters and could be useful to estimate GDM risk even before ART treatments and pregnancy.

Clinical trial number: NCT03503006 registered on the 21st of March 2018 (on clinicaltrials.gov). https://clinicaltrials.gov/study/NCT03503006?locStr=Changsha,%20Hunan,%20China&country=China&state=Hunan&city=Changsha&cond=ivf&rank=2 .

Background: Ovarian failure (OF) is a multifactorial, complex disease presented by up to 1% of women under 40 years of age. Despite 90% of patients being diagnosed with idiopathic OF, the underlying molecular mechanisms remain unknown, making it difficult to personalize treatments for these patients in the clinical setting. Studying the presence and/or accumulation of SNVs at the gene/pathway levels will help describe novel genes and characterize disrupted biological pathways linked with ovarian failure.

Methods: Ad-hoc case-control SNV screening conducted from 2020 to 2023 of 150 VCF files WES data included Spanish IVF patients with (n = 118) and without (n = 32) OF (< 40 years of age; mean BMI 22.78) along with GnomAD (n = 38,947) and IGSR (n = 1,271; 258 European female VCF) data for pseudo-control female populations. SNVs were prioritized according to their predicted deleteriousness, frequency in genomic databases, and proportional differences across populations. A burden test was performed to reveal genes with a higher presence of SNVs in the OF cohort in comparison to control and pseudo-control groups. Systematic in-silico analyses were performed to assess the potential disruptions caused by the mutated genes in relevant biological pathways. Finally, genes with orthologues in Drosophila melanogaster were considered to experimentally validate the potential impediments to ovarian function and reproductive potential.

Results: Eighteen genes had a higher presence of SNVs in the OF population (FDR < 0.05). AK2, CDC27, CFTR, CTBP2, KMT2C, and MTCH2 were associated with OF for the first time and their silenced/knockout forms reduced fertility in Drosophila. We also predicted the disruption of 29 sub-pathways across four signalling pathways (FDR < 0.05). These sub-pathways included the metaphase to anaphase transition during oocyte meiosis, inflammatory processes related to necroptosis, DNA repair mismatch systems and the MAPK signalling cascade.

Conclusions: This study sheds light on the underlying molecular mechanisms of OF, providing novel associations for six genes and OF-related infertility, setting a foundation for further biomarker development, and improving precision medicine in infertility.

Background: The decline in women's fertility becomes clinically relevant between 35-40 years old, when there is insufficient ovarian activity, and it becomes more difficult to achieve pregnancy naturally and through artificial reproductive technologies. A competent endometrium is required for establishing and maintaining a pregnancy to term, however, experts in the field underestimate the contribution of endometrial age and its impact on reproductive outcomes remains unclear.

Study design: A systematic search of full-text articles available in PubMed was conducted to retrieve relevant studies published until March 2023. Search terms included: endometrium, uterus, age, aging, pregnancy, and oocyte donation. Terms related to reproductive pathologies were excluded. Eligibility criteria included original, rigorous, and accessible peer-reviewed work, published in English on the effect of age on the uterus and endometrium.

Results: From 11,354 records identified, 142 studies were included for systematic review, and 59 were eligible for meta-analysis of endometrial thickness (n = 7), pregnancy rate (n = 22), implantation rate (n = 10), live birth rate (n = 10) and pregnancy loss rate (n = 11). Studies for the meta-analysis of reproductive outcomes only included transfers of embryos from ovum donation (ovum donors < 36 years old). Age shrinks the uterus; depletes endometrial blood supply through narrow uterine veins and a progressive loss of uterine spiral arteries; disrupts endometrial architecture and cellular composition; alters hormone production, shortening menstrual cycle length and impeding endometrial progression to the secretory stage; and dysregulates key endometrial functions such as adhesion, proliferation, apoptosis, and receptivity, among others. Women over 35-40 years old had significantly thinner endometrium (MD 0.52 mm). Advanced maternal age is associated with lower odds of achieving implantation (27%) and clinical pregnancy (20%), or higher odds of experiencing pregnancy loss (44%).

Conclusion: Due to the effect of age on endometrium reported in this review, managing patients with advanced maternal age may require considering the endometrial factor as a potential tissue to treat with anti-aging strategies. This review provides researchers and clinicians with an updated and in-depth summary of this topic, encouraging the development of new tailored anti-aging and preventive strategies for precision medicine in endometrial factor in infertility.

Trial registration: PROSPERO 2023 (CRD42023416947).

Background: Preeclampsia (PE) is a multifaceted pregnancy syndrome marked by multiple system involvement and a significant contributor to maternal mortality. This condition is characterized by a critical lack of early diagnostic measures and viable therapeutic options, underscoring an urgent need for the identification of reliable markers with both diagnostic and therapeutic potential.

Methods: This study utilized Weighted Gene Co-expression Network Analysis (WGCNA) to explore the role of G protein-coupled receptors (GPCRs) in the pathogenesis of PE.

Results: Our analysis pinpointed CCBP2 (ACKR2) and GPR87 as central PE-associated GPCRs. Experimental validation of these findings revealed that both CCBP2 and GPR87 significantly inhibit the proliferation, migration, and invasion of trophoblast cells-core phenomena underlying the pathology of PE.

Conclusion: Thus, our findings add valuable candidates to the growing list of biomarkers for preeclampsia and offer promising targets for future therapeutic development.

Objective: To study the crosstalk between maternal immune cells and the developing embryo by investigating the immunogenic properties of human blastocyst spent media (SM) on dendritic cells.

Methods: In this prospective multicenter experimental study, human preimplantation embryo spent media were collected after blastocyst formation, grouped based on successful or unsuccessful implantation, and analyzed by protein array or used to stimulate monocyte derived dendritic cells (moDC). The immunomodulatory properties of SM on moDC were investigated by analyzing changes in phenotype, cytokine secretion, indoleamine 2,3-dioxygenase (IDO) activity, and ability to activate T cells.

Results: A plethora of cytokines and growth factors secreted from preimplantation embryos was detected. Exposure to embryo SM altered the phenotype of moDC in a manner dependent on the implantation outcome. Specifically, SM from non-implanted embryos increased the expression of co-stimulatory molecules and activation markers on moDC. Furthermore, SM treated dendritic cells secreted low levels of cytokines and growth factors and were able to stimulate naïve T cells. Activation of IDO was decreased in moDC after stimulation with SM.

Conclusions: Our findings show that human preimplantation embryos secrete an abundance of molecules with the ability to significantly affect and even regulate immune cells in their environment.

Background: Prior research showed that elevated serum uric acid (SUA) levels in women with polycystic ovary syndrome (PCOS) before in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) treatment can lead to a lower rate of live birth and an increased risk for low birthweight. Nonetheless, it is not known whether elevated SUA results in similar reproductive outcome in women without PCOS. This study aimed to exploring the relationship between pre-pregnancy SUA levels and reproductive outcomes in non-PCOS women undergoing IVF/ICSI treatment.

Methods: This single-center, retrospective study included 13,325 women without PCOS undergoing their first IVF/ICSI fresh embryo transfer cycles from January 2014 to December 2022 at a university-affiliated reproductive medicine center in China. The trends for pregnancy, obstetric and perinatal outcomes across quartiles of SUA levels were assessed. A logistic regression analysis was applied to control for baseline and cycle characteristics. Generalized addition model was used to draw spline smoothing plot.

Results: There was no significant decreasing or increasing trend in the clinical pregnancy rate and live birth rate with the increase in quartiles of SUA levels. For Obstetric and perinatal outcomes following a single live birth, the percentage of hypertensive disorders in pregnancy (1.6-4.1%, P_trend<0.001), gestational diabetes mellitus (5.9-13.9%, P_trend<0.001), premature rupture of membranes (0.6-1.5%, P_trend=0.016), preterm birth (6.3-9.2%, P_trend=0.009), macrosomia (2.3-5.5%, P_trend<0.001), large for gestational age (10.8-14.9%, P_trend=0.002) all increased significantly from the lowest quartile to the highest. Logistic regression results showed that compared with those in quartile 1, the risk of maternal and infant complications mentioned above was still significantly higher in quartile 4 after adjusting for reproductive related factors. When further confounding factors were added, including body mass index (BMI), blood pressure, fasting blood glucose, and blood lipids related indicators, only gestational diabetes mellitus and macrosomia showed a significant increase.

Conclusion: In women without PCOS, SUA levels before IVF/ICSI treatment do not affect the probabilities of clinical pregnancy and live birth. An elevated SUA level is associated with an increased risk for hypertensive disorders in pregnancy, gestational diabetes mellitus, premature rupture of membranes, preterm birth, macrosomia, and large for gestational age. For gestational diabetes mellitus and macrosomia, the association is independent of BMI, blood pressure, blood glucose, and blood lipid.

Background: Erectile dysfunction (ED) has been linked to insulin resistance (IR), with various surrogate indices being used to assess this association. This systematic review and meta-analysis aimed to evaluate the relationship between IR indices and the incidence and severity of ED.

Methods: A comprehensive search across PubMed, Embase, Web of Science, and Scopus was carried out. Required data were extracted and meta-analyzed. The Newcastle-Ottawa Scale (NOS) was employed to evaluate the studies' risk of bias. Sensitivity analyses and meta-regressions were conducted to explore heterogeneity and the impact of confounding variables.

Results: Seventeen studies with a total of 3810 patients with ED and 8252 without ED were included. Meta-analysis revealed that males with ED had significantly higher levels of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) (SMD = 0.59, 95% CI [0.15, 1.03], I² = 82%, P < 0.01), Triglyceride-Glucose Index (TyG) (SMD = 0.53, 95% CI [0.31, 0.75], I² = 69%, P < 0.01), and Visceral Adiposity Index (VAI) (SMD = 0.45, 95% CI [0.25, 0.64], I² = 76%, P < 0.01) compared to those without ED. However, there was no significant correlation between a one-unit increase in HOMA-IR (OR = 0.63, 95% CI [0.03, 13.69], I² = 91%, P = 0.77) or TyG (OR = 0.53, 95% CI [0.02, 11.53], I² = 88%, P = 0.68) and the odds of ED. Additionally, a one-unit increase in VAI was associated with more severe ED (SMD = 0.34, 95% CI [0.03, 0.64], I² = 16%, P = 0.03). The diagnostic accuracy of these indices varied.

Conclusions: The results indicate a significant connection between insulin resistance and erectile dysfunction, as shown by HOMA-IR, TyG, and VAI. Yet, their usefulness in predicting ED is restricted because of significant differences and inconsistencies in diagnostic precision. More research is required to determine the clinical importance of these indices in treating ED.