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Cureus Jun 2024The existing literature lacks consensus on the effectiveness of utilizing polymorphisms to enhance outcomes in in vitro fertilization (IVF), particularly regarding...
Follicle-Stimulating Hormone Receptor (FSHR) Ser680Asn Genotype Does Not Affect the Follicular Fluid Hormonal Profile in Stimulated Cycles Using Different Gonadotropin Preparations for Ovulation Induction: A Pilot Study.
BACKGROUND
The existing literature lacks consensus on the effectiveness of utilizing polymorphisms to enhance outcomes in in vitro fertilization (IVF), particularly regarding ovulation induction protocols, oocyte and embryo quality, and pregnancy rates. Therefore, the present pilot study aims to assess whether the composition of different gonadotropin preparations affects the ovarian stimulation protocol concerning follicle-stimulating hormone receptor () Ser680Asn genotypes (Ser/Ser, Ser/Asn, and Asn/Asn), in terms of ovulation induction parameters, including oocyte maturation rate, embryo quality, and pregnancy rate.
METHODOLOGY
A total of 94 IVF patients underwent treatment using a GnRH antagonist protocol with four distinct gonadotropin preparations: HMG, HMG/hCG, rFSH, and rFSH/hCG. Follicular fluid (FF) samples were pooled for each patient for analysis.
RESULTS
No statistical differences in the FF hormonal profile (progesterone, testosterone, androstenedione, estradiol, FSH, hCG) among the genotypes were reported either separately for each protocol or in combination for the four different preparations of gonadotropins. The maturation rate of MII oocytes and embryo quality did not differ among women carrying either Ser/Ser, Ser/Asn, or Asn/Asn genotype (p-value=0.475, and p-value=1.000, respectively). Moreover, no statistically significant correlation was revealed among Ser/Ser, Ser/Asn, and Asn/Asn carriers and pregnancy rate (p = 0.588).
CONCLUSIONS
FF hormonal analysis of women undergoing IVF using different ovulation induction protocols and carrying either Ser/Ser, Ser/Asn, or Asn/Asn genotype revealed no significant correlations, in terms of maturation rate of MII oocytes, embryo quality, and pregnancy rate, indicating that the Ser680Asn genotype does not constitute a biomarker for a positive pregnancy outcome. Therefore, the existence of a different mechanism for the expression of Ser680Asn genotypes in the FF hormonal profile related to stimulated cycles is implied.
PubMed: 38863774
DOI: 10.7759/cureus.62116 -
International Journal of Endocrinology 2024During in vitro fertilization-embryo transfer (IVF-ET) treatment, the reproductive endocrine regulatory mechanisms hold pivotal importance. Specifically, the serum...
OBJECTIVE
During in vitro fertilization-embryo transfer (IVF-ET) treatment, the reproductive endocrine regulatory mechanisms hold pivotal importance. Specifically, the serum estradiol ( ) level during ovulation emerges as a critical factor influencing pregnancy outcomes. This retrospective study aimed to comprehensively compare two common clinical regimens based on the grouping of serum levels and the number of oocytes retrieved on the trigger day. Our objective was to evaluate the pregnancy outcomes in IVF-ET patients across different ovarian response groups, exploring the efficacy of the dual-trigger and single-trigger regimens to provide valuable insights for optimizing clinical strategies in the context of IVF-ET.
METHODS
A retrospective analysis was conducted on the clinical data of 2778 infertile patients who underwent ART (IVF/ICSI). Subsequently, a detailed statistical analysis was performed on 1032 patients following an antagonist regimen. Participants were categorized into single-trigger and dual-trigger groups based on real-world trigger protocols, considering different ovarian responses. Comprehensive statistical assessments were conducted on baseline characteristics, ovulation induction, and pregnancy outcomes.
RESULTS
Baseline characteristics and cycle parameters among the three patient groups (high ovarian response, normal response, and poor response) exhibited no significant differences between the dual-trigger and single-trigger regimen groups. Despite the dual-trigger regimen utilizing a significantly lower HCG dose, no notable discrepancies were observed in laboratory results and pregnancy outcomes (embryo transfer rate, pregnancy rate, and live birth rate) for normal and high responders. Remarkably, levels were higher in the dual-trigger group compared to the single-trigger group. In high and normal responders, the dual-trigger regimen demonstrated increased oocyte counts and oocyte acquisition rates, coupled with decreased transfer cancellation rates attributed to ovarian hyperstimulation syndrome (OHSS). Intriguingly, patients with a poor ovarian response experienced no graft cancellations due to OHSS prevention in either group.
CONCLUSION
For patients with high and normal ovarian responses, the utilization of a dual-trigger regimen on the trigger day effectively mitigates the risk of OHSS. Our large sample study supports the substitutability of the dual-trigger regimen over the single-trigger regimen without compromising pregnancy outcomes. However, this conclusion is not applicable to patients with poor ovarian responses. The results of this study highlight the necessity of adopting a customized and individualized treatment approach that should be based on the patient's ovarian response. Additionally, recognizing the pivotal role of the endocrine environment in influencing pregnancy outcomes and the occurrence of OHSS, further exploration of the effects of different triggering regimens on endocrine parameters is warranted. Such investigations will contribute to enhancing the reproductive outcomes of IVF-ET technology.
PubMed: 38855192
DOI: 10.1155/2024/2507026 -
The Journal of Poultry Science 2024Broodiness in egg-laying hens (EHs) leads to ovarian atrophy, resulting in reduced egg-laying performance. However, the ovarian regulatory mechanisms in broody hens...
Broodiness in egg-laying hens (EHs) leads to ovarian atrophy, resulting in reduced egg-laying performance. However, the ovarian regulatory mechanisms in broody hens (BCs) remain elusive. Therefore, ovaries were removed from 300-day-old BCs and EHs for RNA sequencing. Ovarian morphology and histological characteristics of the BC and EH groups were compared and analyzed. The EH group had significantly more hierarchical follicles (HFs) and small yellow follicles (SYFs) than that of the BC group. Although several secondary follicles (SFs) and primary follicles were observed in the ovaries of the EH group, only a few SFs were observed in the ovaries of the BC group. Subsequently, RNA-sequencing analysis was conducted to determine the ovarian expression profiles of the two groups. Transcriptome sequencing identified 259 differentially expressed genes (DEGs) between the BC and EH groups. Of the 259 DEGs, 136 were upregulated and 123 were downregulated. The DEGs were mapped to 22 gene ontology terms and 4 Kyoto Encyclopedia of Genes and Genomes pathways for ovarian tissue. The analysis showed that matrix metalloproteinases 11/13 (MMP11/MMP13) were enriched in the extracellular matrix. The extracellular matrix mediated by MMP13 is affected by follicle-stimulating hormone, prolactin, and estrogen, which are critical signaling pathways that may affect ovarian follicle development to regulate the large yellow follicle reserve process and the ovulation cycle of broody Chahua chickens. These findings indicate that understanding differences in gene expression between the ovarian tissues of BCs and EHs could serve as a valuable reference point for enhancing egg-laying performance in Chahua chickens.
PubMed: 38854637
DOI: 10.2141/jpsa.2024018 -
Journal of Dairy Science Jun 2024Our overarching objective was to characterize associations between genomic merit for fertility and the reproductive function of lactating dairy cows in a prospective...
Reproductive physiological outcomes of dairy cows with different genomic merit for fertility: biomarkers, uterine health, endocrine status, estrus features, and response to ovarian synchronization.
Our overarching objective was to characterize associations between genomic merit for fertility and the reproductive function of lactating dairy cows in a prospective cohort study. In this manuscript, we present results of the association between genomic merit for fertility and indicators of metabolic status and inflammation, uterine health, endocrine status, response to synchronization, and estrous behavior in dairy cows. Lactating Holstein cows entering their first (n = 82) or second (n = 37) lactation were enrolled at parturition and fitted with an ear-attached sensor for automated detection of estrus. Ear-notch tissue samples were collected from all cows and submitted for genotyping using a commercial genomic test. Based on genomic predicted transmitting ability values for daughter pregnancy rate (gDPR) cows were classified into a high (Hi-Fert; gDPR > 0.6; n = 36), medium (Med-Fert; gDPR -1.3 to 0.6; n = 45), and low (Lo-Fert; gDPR < -1.3; n = 38) group. At 33 to 39 d in milk (DIM), cohorts of cows were enrolled in the Presynch-Ovsynch protocol for synchronization of estrus and ovulation. Body weights, body condition scores (BCS), and uterine health measurements (i.e., vaginal discharge, uterine cytology) were collected from parturition to 60 DIM and milk yield was collected through 90 DIM. Blood samples were collected weekly through 3 wk of lactation for analysis of β-hydroxybutyrate, nonesterified fatty acids, and haptoglobin plasma concentrations. Body weight, BCS, NEFA, BHB, and Haptoglobin were not associated with fertility groups from 1 to 9 wk after parturition. The proportion of cows classified as having endometritis at 33 to 36 DIM tended to be greater for the Lo-Fert than the Hi-Fert group. The proportion of cows that resumed cyclicity did not differ at any time point evaluated and there were no significant associations between probability or duration and intensity of estrus with fertility group. Cows of superior genetic merit for fertility were more likely to ovulate, have a functional CL, have greater circulating P4, and have larger ovulatory size than cows of inferior fertility potential at key time points during synchronization of estrus and ovulation. Despite observing numerical differences with potential performance consequences for the proportion of cows that responded to synchronization of ovulation and were both cyclic and responded to the Ovsynch portion of the synchronization protocol, we did not observe significant differences between fertility groups. Although not consistent and modest in magnitude, the collective physiological and endocrine differences observed suggested that cows of superior genetic fertility potential might have improved reproductive performance, at least in part, because of modestly improved endocrine status, uterine health, and ability to ovulate.
PubMed: 38851573
DOI: 10.3168/jds.2023-24376 -
Reproductive Biology and Endocrinology... Jun 2024The cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF...
BACKGROUND
The cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF face great psychological pressure and financial burden. A predictive model to estimate CLBR is needed in clinical practice for patient counselling and shaping expectations.
METHODS
This retrospective study included 32,306 complete cycles derived from 29,023 couples undergoing IVF treatment from 2014 to 2020 at a university-affiliated fertility center in China. Three predictive models of CLBR were developed based on three phases of a complete cycle: pre-treatment, post-stimulation, and post-treatment. The non-linear relationship was treated with restricted cubic splines. Subjects from 2014 to 2018 were randomly divided into a training set and a test set at a ratio of 7:3 for model derivation and internal validation, while subjects from 2019 to 2020 were used for temporal validation.
RESULTS
Predictors of pre-treatment model included female age (non-linear relationship), antral follicle count (non-linear relationship), body mass index, number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, tubal factor, male factor, and scarred uterus. Predictors of post-stimulation model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. Predictors of post-treatment model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), cumulative Day-3 embryos live-birth capacity (non-linear relationship), number of previous IVF attempts, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. The C index of the three models were 0.7559, 0.7744, and 0.8270, respectively. All models were well calibrated (p = 0.687, p = 0.468, p = 0.549). In internal validation, the C index of the three models were 0.7422, 0.7722, 0.8234, respectively; and the calibration P values were all greater than 0.05. In temporal validation, the C index were 0.7430, 0.7722, 0.8234 respectively; however, the calibration P values were less than 0.05.
CONCLUSIONS
This study provides three IVF models to predict CLBR according to information from different treatment stage, and these models have been converted into an online calculator ( https://h5.eheren.com/hcyc/pc/index.html#/home ). Internal validation and temporal validation verified the good discrimination of the predictive models. However, temporal validation suggested low accuracy of the predictive models, which might be attributed to time-associated amelioration of IVF practice.
Topics: Humans; Female; Fertilization in Vitro; Adult; China; Retrospective Studies; Pregnancy; Live Birth; Birth Rate; Male; Pregnancy Rate; Ovulation Induction; Embryo Transfer
PubMed: 38849798
DOI: 10.1186/s12958-024-01237-3 -
Scientific Reports Jun 2024Genetic variations in the ovine ovulation rate, which are associated with the FecB mutation, provide useful models by which to explore the mechanisms regulating the...
Genetic variations in the ovine ovulation rate, which are associated with the FecB mutation, provide useful models by which to explore the mechanisms regulating the development of mammalian antral follicles. In order to study the effects of the FecB mutation on cumulus cell differentiation, preovulatory follicles were aspirated and cumulus cells were isolated from three FecB genotypes (homozygous, heterozygous and wild type) of Small Tail Han (STH) sheep superstimulated with FSH. Transcriptome information from tens of thousands of cumulus cells was determined with the 10 × Genomics single-cell RNA-seq technology. Under the superovulation treatment, the observed number of preovulatory follicles in the ovaries of FecB carriers was still significantly higher than that in the wild-type (P < 0.05). The expression patterns of cumulus cells differed between FecB carriers and wild-type ewes. The screened cumulus cells could also be further divided into different cell clusters, and the differentiation states and fates of each group of cumulus cells also remained different, which supports the notion that heterogeneity in gene expression is prevalent in single cells. The oxidative phosphorylation pathway was significantly enriched in differentially expressed genes among the cell differentiation branch nodes of cumulus cells and among the differentially expressed genes of cumulus cells from the three genotypes. Combined with the important role of oxidative phosphorylation in the maturation of COCs, we suggest that the oxidative phosphorylation pathway of cumulus cells plays a crucial role in the differentiation process of cumulus cells and the mutation effect of the FecB gene.
Topics: Animals; Cumulus Cells; Female; Sheep; Single-Cell Analysis; Mutation; Transcriptome; RNA-Seq; Gene Expression Profiling; Ovarian Follicle; Cell Differentiation; Single-Cell Gene Expression Analysis
PubMed: 38849498
DOI: 10.1038/s41598-024-64001-y -
PloS One 2024The causal relationship between sex hormone-binding globulin (SHBG) and infertility has remained unclear. Thus, we used Mendelian randomization (MR) to investigate this...
BACKGROUND
The causal relationship between sex hormone-binding globulin (SHBG) and infertility has remained unclear. Thus, we used Mendelian randomization (MR) to investigate this relationship.
METHODS
Risk factors for SHBG were extracted from European individuals within the UK Biobank using single-nucleotide polymorphism (SNP) data. Summary-level data for infertility outcomes were obtained from the FinnGen dataset. The causal relationship between SHBG and infertility was examined using inverse variance weighted, weighted model, weighted median, and MR-Egger regression analyses. Additionally, Cochran's Q test and Egger intercept tests were used to confirm the heterogeneity and pleiotropy of identified instrumental variables (IVs).
RESULTS
Our findings revealed a significant negative association between sex hormone-binding globulin (SHBG) levels and infertility, particularly with anovulation, a specific form of female infertility. However, SHBG did not exert a causal impact on male infertility or on female infertility of tubal origin.
CONCLUSIONS
SHBG expression offers protection against the development of certain types of female infertility, suggesting it is a potential therapeutic target for infertility.
Topics: Sex Hormone-Binding Globulin; Humans; Mendelian Randomization Analysis; Female; Polymorphism, Single Nucleotide; Male; Infertility, Female; Infertility, Male; Risk Factors; Infertility; Anovulation
PubMed: 38848344
DOI: 10.1371/journal.pone.0304216 -
Frontiers in Microbiology 2024Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut...
INTRODUCTION
Folliculogenesis and oligo/anovulation are common pathophysiological characteristics in polycystic ovary syndrome (PCOS) patients, and it is also accompanied by gut microbiota dysbiosis. It is known that physical activity has beneficial effects on improving metabolism and promoting ovulation and menstrual cycle disorder in PCOS patients, and it can also modulate the gastrointestinal microbiota in human beings. However, the mechanism remains vague. Irisin, a novel myokine, plays a positive role in the mediating effects of physical activity.
METHODS
Mice were randomly divided into the control group, PCOS group and PCOS+irisin group. PCOS model was induced by dehydroepiandrosterone (DHEA) and high-fat diet (HFD). The PCOS+irisin group was given irisin 400μg/kg intraperitoneal injection every other day for 21 days. The serum sex hormones were measured by radioimmunoassay. Hematoxylin and Eosin (H&E) Staining and immunohistochemistry (IHC) were conducted on ovarian tissue. The feces microbiota and metabolomic characteristics were collected by 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS).
RESULTS
In this study, we demonstrated that irisin supplementation alleviated reproductive endocrine disorders of PCOS mice, including estrous cycle disturbance, ovarian polycystic degeneration, and hyperandrogenemia. Irisin also improved the PCOS follicles dysplasia and ovulation disorders, while it had no significant effect on the quality of oocytes. Moreover, irisin could mitigate the decreased bacteria of Odoribacter and the increased bacteria of Eisenbergiella and Dubosiella in PCOS mice model. Moreover, irisin could alleviate the increased fecal metabolites: Methallenestril and PS (22:5(4Z,7Z,10Z,13Z,16Z)/ LTE4).
CONCLUSION
These results suggest that irisin may alleviate the status of PCOS mice model by modulating androgen-induced gut microbiota dysbiosis and fecal metabolites. Hence, our study provided evidence that irisin may be considered as a promising strategy for the treatment of PCOS.
PubMed: 38846566
DOI: 10.3389/fmicb.2024.1373077 -
Frontiers in Endocrinology 2024Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the... (Observational Study)
Observational Study
Vitamin D binding protein correlate with estrogen increase after administration of human chorionic gonadotropin but do not affect ovulation, embryo, or pregnancy outcomes.
BACKGROUND
Vitamin D binding protein (DBP) might increase substantially after ovarian stimulation and hence could be associated with IVF/ICSI outcomes because it determines the fraction of free bioavailable 25(OH) vitamin D. In this study, we aim to determine whether DBP is associated with E2 level after ovarian stimulation and IVF/ICSI outcomes.
DESIGN
analysis of a prospective observational cohort.
SETTING
Single-center study.
PARTICIPANTS
2569 women receiving embryo transfer.
INTERVENTION
None.
MAIN OUTCOME MEASURES
The main outcomes were oocyte and embryo quality as well as pregnancy outcomes.
RESULTS
DBP concentration correlates with E2 on hCG day (=day of inducing ovulation with hCG; correlation coefficient r = 0.118, P<0.001) and E2 x-fold change to baseline level (r = 0.108, P<0.001). DBP is also positively correlated with total 25(OH)D (r = 0.689, R = 0.475, P<0.001) and inversely with free 25(OH)D (r=-0.424, R=0.179, P<0.001), meaning that E2-stimulated DBP synthesis results in a decrease of free 25(OH)D during ovarian stimulation. However, such alteration does not affect IVF/ICSI outcomes when considering confounding factors, such as the number and quality of oocytes nor embryo quality as well as pregnancy outcomes.
CONCLUSION
DBP concentration correlates with the degree of E2 increase after ovarian stimulation. DBP is also positively correlated with total 25(OH)D and inversely with free 25(OH)D, suggesting that the proportion of free 25(OH)D decreases during ovarian stimulation caused by E2-stimulated DBP synthesis. However, such alteration does not affect clinical IVF/ICSI outcomes.
Topics: Humans; Female; Pregnancy; Vitamin D-Binding Protein; Adult; Ovulation Induction; Chorionic Gonadotropin; Pregnancy Outcome; Ovulation; Prospective Studies; Fertilization in Vitro; Estrogens; Embryo Transfer; Pregnancy Rate; Sperm Injections, Intracytoplasmic
PubMed: 38846489
DOI: 10.3389/fendo.2024.1401975 -
Trials Jun 2024Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the...
BACKGROUND
Women with polycystic ovary syndrome (PCOS) are usually selected to undergo an ovulation induction regimen or a programmed regimen for endometrial preparation in the frozen-thawed embryo transfer (FET) during their IVF/ICSI treatment. The programmed regimen permits flexible scheduling of embryo transfer but requires long-term usage of exogenous estrogen and higher dosages of luteal support while the letrozole ovulation regimen needs lower dosages of luteal support only. Recently, multiple studies have shown that the letrozole ovulation regimen can improve pregnancy outcomes of FET in women with PCOS compared with the programmed regimen. However, most of these studies are retrospective, and prospective studies are urgently needed the evidence from the perspective study is insufficient.
METHODS/DESIGN
We are undertaking a multicentre, randomized, controlled clinical trial of an endometrial preparation regimen for FET in women with PCOS. The eligible women are randomly assigned to either the letrozole ovulation regimen or the programmed regimen for endometrial preparation. The primary outcome is the clinical pregnancy rate.
DISCUSSION
The results of this study will provide evidence for whether the letrozole ovulation regimen for endometrial preparation could improve pregnancy outcomes in PCOS women undergoing FET.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR2200062244. Registered on 31 July 2022.
Topics: Humans; Polycystic Ovary Syndrome; Female; Letrozole; Pregnancy; Embryo Transfer; Ovulation Induction; Randomized Controlled Trials as Topic; Multicenter Studies as Topic; Pregnancy Rate; Cryopreservation; Treatment Outcome; Fertility Agents, Female; Ovulation; China; Adult; Infertility, Female
PubMed: 38845035
DOI: 10.1186/s13063-024-08164-z