Diminished Ovarian Reserve Group Research Articles

BCORL1, POF1B, and USP9X copy number variation in women withidiopathic diminished ovarian reserve.

To analyze the copy number variation (CNV) in the X-linked genes BCORL1, POF1B, and USP9X in idiopathic diminished ovarian reserve (DOR). This case-control study included 47 women, 26 with DOR and 21 in the control group. Age, weight, height, BMI, and FSH level were evaluated, as well as antral follicle count (AFC), oocyte retrieval after controlled ovarian stimulation, and metaphase II (MII) oocytes. The CNVs of BCORL1, USP9X, and POF1B genes were measured by quantitative real time PCR (qPCR) using two reference genes, the HPRT1 (X-linked) and MFN2 (autosomal). Protein-protein interaction network and functional enrichment analysis were performed using the STRING database. The mean age was 36.52 ± 4.75 in DOR women and 35.38 ± 4.14 in control. Anthropometric measures did not differ between the DOR and control groups. DOR women presented higher FSH (p = 0.0025) and lower AFC (p < .0001), oocyte retrieval after COS (p = 0.0004), and MII oocytes (p < .0001) when compared to the control group. BCORL1 and POF1B did not differ in copy number between DOR and control. However, DOR women had more copies of USP9X than the control group (p = 0.028). The increase in the number of copies of the USP9X gene may lead to overexpression in idiopathic DOR and contribute to altered folliculogenesis and oocyte retrieval.

P-673 Tubulointerstitial nephritis antigen-like 1 (TINAGL1) expression is lower in the follicular fluid of patients with diminished ovarian reserve (DOR): A novel biomarker

Abstract Study question Are TINAGL1 levels in follicular fluid associated with ovarian reserve in patients undergoing ovarian stimulation for in-vitro fertilization (IVF)? Summary answer TINAGL1 concentration was lower in the follicular fluid (FF) of patients with DOR vs patients without infertility or polycystic ovarian syndrome (PCOS). What is known already TINAGL1 is an extracellular matrix protein involved in cell adhesion, proliferation, migration, and differentiation. TINAGL1 has previously been shown to be expressed in the mouse ovary and to be a serum biomarker that varies throughout the mouse estrous cycle, peaking in the estrous phase. Furthermore, TINAGL1 knockout mice have been shown to be infertile. TINAGL1 expression in the human ovary has not been previously evaluated. Study design, size, duration Between 2019 and 2023, a prospective study of 136 patients undergoing ovarian stimulation and oocyte retrieval (OR) was conducted at a single academic fertility center to assess TINAGL1 levels in luteinized FF and granulosa cells. Study groups were determined by infertility diagnosis: DOR n = 24, polycystic ovary syndrome (PCOS) n = 27, and control n = 85 (undergoing fertility preservation or had a partner with male factor only). Participants/materials, setting, methods TINAGL1 protein levels were quantified in the FF of patients that underwent OR via commercial enzyme-linked immunosorbent assay (ELISA). Granulosa cells were recovered from FF after OR, underwent lysis, RNA extraction, cDNA amplification and TINAGL1 mRNA expression was quantified via quantitative real-time polymerase chain reaction (qPCR). Demographics and infertility diagnoses were collected from the medical record. TINAGL1 levels were compared between the three groups. Statistical analysis was performed with parametric and non-parametric tests as appropriate. Main results and the role of chance Patients with DOR were younger when compared to the control and the PCOS group [Mean(SD) 32.7 (3.8) vs 34.45(3.9) vs 37.7 (3.0) years, p &amp;lt; 0.001] and had lower AMH levels [1.19 (0.8) vs 3.96 (3.03) vs 8.67 (4.56) ng/ml, p &amp;lt; 0.001]. TINAGL1 protein concentration in FF was measured by ELISA. Mean (SD) TINAGL1 levels were highest in PCOS, and lowest in the DOR group. Mean TINAGL1 levels were higher in the FF of the PCOS group when compared to the control group [4.73(7.15) vs 4.45 (4.57) ng/ml, p = 0.83] but this difference did not reach statistical significance. However, mean TINAGL1 FF levels were significantly lower in the DOR group when compared to the control group [2.54 (1.6) vs 4.48 (4.57) ng/ml, p = 0.04]. TINAGL1 was also found to be expressed in the granulosa cells with qPCR. TINAGL1 expression was upregulated by (+89%) in the PCOS group vs the control group (p = 0.0095). Importantly, there was a trend for decreased (-52%) TINAGL1 expression in DOR when compared to the control group (p = 0.67). The latter result should be interpreted with caution since only a subset of samples had sufficient granulosa cells for RNA extraction (DOR=4, control=18, PCOS=5). Limitations, reasons for caution This is a single institution study with a small number of patients in the DOR group (n = 24). Wider implications of the findings This is the first study to show that TINAGL1 is expressed in human granulosa cells. Decreased TINAGL1 may be a biomarker associated with DOR. Future studies should assess serum TINAGL1 levels at baseline and during ovarian stimulation and its contribution to the pathophysiology of DOR. Trial registration number Not applicable

Alkali and alkaline earth elements in follicular fluid and the likelihood of diminished ovarian reserve in reproductive-aged women: a case‒control study

BackgroundImbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR).MethodsA nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions.ResultsThe DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67–4.43)], Li [OR: 1.89 (1.06–3.42)], and Cs [OR: 1.97 (1.10–3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect.ConclusionThis study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline.Trial registrationRetrospectively registered.

Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study

ObjectiveThis study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years.MethodsA retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW).ResultsThe DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05).ConclusionDOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

The Relationship Between Serum Growth Differentiation Factor-15 (GDF-15) Levels and Clinical Outcomes in Infertile Women Receiving In-vitro Fertilization Treatment

Objective: It has been reported in many studies that Growth Differentiation Factor-15 (GDF-15) has an important role in physiological or pathological processes. As there is no study in the current scientific literature examining the status of GDF-15 in infertility and its treatment outcomes, we aimed to investigate this.&#x0D; Material and methods: According to their ovarian reserve characteristics, 88 infertile women were divided into three groups: normal ovarian reserve (NOR), diminished ovarian reserve (DOR), and polycystic ovary syndrome (PCOS). Estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), and GDF-15 levels were measured in their serum. The antagonist protocol patients' total oocyte, meiosis II (MII) oocytes, embryo count, and clinical pregnancy rates were documented.&#x0D; Results: In terms of serum GDF-15 concentrations, there was no statistically significant difference among the mean values of the three study groups. The mean FSH level at baseline was substantially higher in the DOR group compared to the PCOS group. The median serum AMH levels of all three groups were found to be statistically different. The antagonist protocol patients' total oocytes, meiosis II (MII) oocytes, embryo count, and clinical pregnancy rates were documented.&#x0D; Conclusion: In the present study, a significant and strong correlation between serum GDF-15 level and consequent embryo number was detected. Thereby, serum GDF-15 level may be considered to be a biomarker for predicting IVF clinical outcomes.

Mitochondrial Morphology and Function Abnormality in Ovarian Granulosa Cells of Patients with Diminished Ovarian Reserve.

In this study, we examined the changes in the mitochondrial structure and function in cumulus granulosa cells of patients with diminished ovarian reserve (DOR) to explore the causes and mechanisms of decreased mitochondrial quality. The mitochondrial ultrastructure was observed by transmission electron microscope, and the function was determined by detecting the ATP content, reactive oxygen species (ROS) levels, the number of mitochondria, and the mitochondrial membrane potential. The expression of ATP synthases in relation to mitochondrial function was analyzed. Additionally, protein immunoblotting was used to compare the expression levels of mitochondrial kinetic protein, the related channel protein in the two groups. Patients with DOR had abnormal granulosa cell morphology, increased mitochondrial abnormalities, decreased mitochondrial function, and disturbed mitochondrial dynamics. Additionally, the silent information regulator 1 (SIRT1)/phospho-AMP-activated protein kinase (P-AMPK)-peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) pathway expression was decreased, which was speculated to be associated with the decreased mitochondrial mass in the DOR group. The mitochondrial mass was decreased in granulosa cells of patients in the DORgroup. The mitochondrial dysfunction observed in granulosa cells of patients in the DOR group may be associated with dysregulation of the SIRT1/P-AMPK-PGC-1α-mitochondrial transcription factor A (TFAM) pathway.

Diminished ovarian reserve is associated with metabolic disturbances and hyperhomocysteinemia in women with infertility

Background To distinguish the metabolic profile between women with diminished ovarian reserve (DOR) and those with normal ovarian reserve (NOR). Methods In this retrospective study, we enrolled 524 women under the age of 40 who were experiencing infertility: 261 in the DOR group and 263 in the NOR group. Physical characteristics and metabolic parameters were compared between these two groups. Results Women with DOR exhibited a higher propensity for elevated parameters including body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), as well as heightened serum levels of homocysteine (Hcy), triglycerides (TG), low-density lipoprotein (LDL), and triglyceride-glucose (TyG) index, while concurrently experiencing reduced serum levels of high-density lipoprotein (HDL) (P < 0.05). Furthermore, the incidence rates of TG ≥ 1.7 mmol/L, hyperhomocysteinemia (HHcy), BMI ≥ 25 kg/m2, SBP/DBP ≥ 130/85 mmHg, and metabolic syndrome (MS) were significantly elevated within the DOR group as compared to the NOR group (P < 0.05). Conclusion The prevalence of metabolic disturbances and HHcy were notably elevated in women with infertility and DOR compared to those with NOR.

Oxidative stress and inflammatory markers in ovarian follicular fluid of women with diminished ovarian reserve during in vitro fertilization

BackgroundFollicular microenvironment has been proposed as an important factor for oocyte grown and maturation. We sought to evaluate the oxidative stress and inflammatory levels in follicular fluid (FF) and association with embryo quality in patients with diminished ovarian reserve (DOR).MethodsThe current research included 46 DOR cases and 56 normal ovarian reserve (NOR) cases. Twelve representative oxidative stress markers and eight representative inflammatory factors were measured in the FF.ResultsOxidative stress markers total GSH (T-GSH) was decreased in the FF from women with DOR compared with that in NOR group (P = 0.041). More modest differences were observed for reduced GSH (rGSH) and rGSH/GSSG. Women with DOR compared to controls had higher level of TNF-α (P = 0.000) and lower level of IL-18 (P = 0.013). Correlation analysis revealed that GSSG was negatively correlated with normal fertilization rate in NOR group (r = -0.358, P = 0.008), and reduced GSH was negatively correlated with normal fertilization rate in DOR group (r = -0.299, P = 0.049). Moreover, as the regression analysis data showed, the GSSG level was significantly associated with embryo quality indicator.ConclusionsThe FF in DOR patients was accompanied by increased oxidative stress and inflammatory levels. Follicular development of women with DOR might be influenced by unusual IL-18 and TNF-α levels in FF. And oxidative stress marker GSSG in NOR group was a negative predictor for embryo quality.

Determination of tryptophan and its indole metabolites in follicular fluid of women with diminished ovarian reserve

Tryptophan (TRP) and its indole metabolites exhibit numerous biological effects, especially their antioxidant properties. This study used untargeted metabolomics in conjunction with targeted metabolomics to investigate the differential expression of tryptophan and its indole metabolites in follicular fluid (FF) of diminished ovarian reserve (DOR) and normal ovarian reserve (NOR) populations. This study included patients with DOR (n = 50) and females with NOR (n = 35) who received in vitro fertilization and embryo transfer. Untargeted metabolomics suggests that diminished ovarian reserve affects the metabolic profile of FF, TRP and indole metabolites were significantly down-regulated in the DOR group. Targeted metabolomics quantification revealed that the levels of TRP, IPA and IAA in the FF of the DOR group were significantly lower than those of the NOR group (P < 0.01). The concentration of TRP in FF is positively correlated with the available embryo rate in NOR females. These results provide data support to explore the pathogenesis of DOR and to look for new biomarkers and ovarian protectors. Additionally, alterations in TRP and its indole metabolites in FF may indirectly reflect the interaction between intestinal flora and the follicular microenvironment.

Transcriptomic profiling of human granulosa cells between women with advanced maternal age with different ovarian reserve

BackgroundAge-related diminished ovarian reserve (DOR) is not absolute. Some advanced maternal age (AMA) still have normal ovarian reserve (NOR) and often show better pregnancy outcomes. Exploring the transcriptomic profile of granulosa cells (GCs) in AMA could lead to new ideas for mitigating age-related diminished ovarian reserve.AimThis study aimed to analyze the transcriptomic profile of GCs in AMA with different ovarian reserve.ResultsIn total, 6273 statistically significant differential expression genes (DEGs) (|log2fc|> 1, q < 0.05) were screened from the two groups, among which 3436 genes were upregulated, and 2837 genes were downregulated in the DOR group. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the potential functions of dysregulated genes in AMA with DOR or NOR were predicted. The GO enrichment analysis revealed that the DEGs were mainly enriched in obsolete oxidation–reduction process, mitochondrion, metal ion binding, ATP binding, etc. The KEGG pathway enrichment analysis revealed that the above-mentioned DEGs were mainly enriched in ferroptosis, regulation of actin cytoskeleton, oxidative phosphorylation, etc. Meanwhile, verification of the mRNA expression levels of DEGs revealed the possible involvement of “ferroptosis” in age-related diminished ovarian reserve.ConclusionsFrom a new clinical perspective, we presented the first data showing the transcriptomic profile in GCs between AMA with different ovarian reserve. At the same time, we identified the role of ferroptosis in the GCs of AMA, providing a new biological basis for studying ovarian aging and improving pregnancy outcomes of AMA.

Increased serine synthesis in cumulus cells of young infertile women with diminished ovarian reserve.

What are the differences in gene expression of cumulus cells (CCs) between young women with diminished ovarian reserve (DOR) and those of similar age with normal ovarian reserve (NOR)? Gene expression and metabolome profiling analysis demonstrate that the de novo serine synthesis pathway (SSP) is increased in the CCs of young women with DOR. The incidence of DOR has risen, tending to present at younger ages. Its mechanisms and aetiologies are still poorly understood. Abnormal metabolism is present in luteinized CCs of patients with DOR. Previous studies have revealed that mitochondrial dysfunction and impaired oxidative phosphorylation in CCs are related to DOR in women of advanced age. The pathogenic mechanisms likely differ between young women with DOR and cases associated with advanced maternal age. Several studies have examined amino acid metabolism in the follicle, with a focus on embryo development, but less information is available about CCs. The physiological significance of de novo serine synthesis in follicles and oocytes remains largely unknown. CC samples were obtained from 107 young infertile women (age <38 years) undergoing ICSI, from July 2017 to June 2019, including 54 patients with DOR and 53 patients with NOR. Oocyte development data were analysed retrospectively. Comprehensive genome-wide transcriptomics of CCs was performed. Differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to categorize the functions of the DEGs and identify significantly enriched pathways. The transcript and protein levels of key enzymes involved in serine synthesis were verified in additional samples using quantitative real-time PCR (qRT-PCR) (n = 10) and capillary western blotting (n = 36). Targeted metabolomics of amino acids in CC extracts was performed by ultrahigh-performance liquid MS (UHPLC-MS/MS). The number of oocytes (2.4 ± 2.2 versus 12.1 ± 5.3) and metaphase II oocytes (2.1 ± 2.0 versus 9.9 ± 4.9) retrieved was significantly decreased in the DOR versus the NOR group, respectively (P < 0.0001). The rates of fertilization (80.7% versus 78.8%), viable embryos (73.7% versus 72.5%), and high-quality embryos (42.8% versus 49.0%) did not differ between the DOR and NOR groups, respectively (P > 0.05). A total of 95 DEGs were found by transcriptome sequencing. GO and KEGG analyses demonstrated that the DEGs were linked to amino acid metabolism and suggested significantly higher activity of the de novo SSP in the CCs of young women with DOR. Further qRT-PCR and capillary western blotting revealed that key enzymes (PHGDH, PSAT1, PSPH, and SHMT2) involved in de novo serine synthesis were upregulated, and UHPLC-MS/MS analysis showed increases in serine and glycine (a downstream product of serine) levels in the CCs of young patients with DOR. Our data clearly demonstrate that the de novo SSP, which diverts 3-phosphoglycerate from glycolysis to serine synthesis, was upregulated in young DOR CCs. N/A. Regarding the reproductive capacity of young patients DOR, the pregnancy outcomes were not analysed. The sample size was limited, and only women undergoing ICSI were examined since this was a prerequisite for the acquisition of CCs, which may cause selection bias. The exact mechanisms by which the SSP in CCs regulates ovarian reserve still require further study. Our research presents new evidence that alterations of the SSP in CCs of young infertile women are associated with DOR. We believe this is a significant contribution to the field, which should be key for understanding the cause and mechanisms of ovarian hypofunction in young women. This work was supported by grants from the Ministry of Science and Technology of China (2018YFC1005001) and National Natural Science Foundation of China (31601197). There were no competing interests. N/A.

Diminished ovarian reserve may not be associated with a poorer fresh cycle outcome in women < 38 years

BackgroundPrevious studies have discussed the pregnancy outcomes of diminished ovarian reserve (DOR) patients. However, data on embryonic development potential, neonatal outcomes, and maternal complications of DOR patients still remained unknown. This is the first study to investigate the risk of DOR on pregnancy and perinatal outcomes among women < 38 years.MethodsRetrospective cohort study was conducted. Patients (< 38 years of age) undergoing their first oocyte retrieval cycle were included. Patients were divided into DOR group and non-DOR group. Pregnancy outcomes of fresh cycle and cumulative live birth rate and perinatal outcomes after one oocyte retrieved cycle were compared between DOR and non-DOR group.Result(s)From January 2016 to September 2020, there were 8,179 patients involved: 443 patients in the DOR group and 7,736 patients in the non-DOR group. The incidences of live birth and clinical pregnancy did not differ significantly between patients with or without DOR after fresh cycle transfer, but the cumulative live birth rate was significantly lower in DOR group. Among women who had singleton live births, after binary logistic regression, the rates of maternal complications and neonatal outcomes were comparable in the two groups.Conclusion(s)DOR patients (< 38 years of age) showed similar pregnancy outcomes in the first fresh embryo transfer cycle but a lower chance of live birth after a whole oocyte retrieval cycle to non-DOR patients and DOR is not associated with adverse perinatal outcomes.

8-oxoguanine DNA Glycosylase (OGG1) may be a Diagnostic Indicator of Diminished Ovarian Reserve (DOR).

Oxidative/antioxidant imbalance is considered a causal cause of diminished ovarian reserve (DOR). 8-oxyguanine DNA glycosylase (OGG1) has been reported to act as an antioxidant by binding non-catalytically to oxidation-induced DNA damage in the promoter region. This study aimed to evaluate serum OGG1 concentrations in patients with or without DOR and to explore the clinical value of OGG1 as a novel diagnostic indicator for DOR. Sixty-four women with DOR and seventy-eight women with normal ovarian reserve (NOR) from the reproductive medical center of Renmin Hospital of Wuhan University were included. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine serum OGG1 levels in patients on 2-5 days of the menstrual cycle. Data regarding the enrolled patients were also obtained from the database of the hospital, including age, body mass index (BMI), anti-Müllerian hormone (AMH), etc. Results: OGG1 levels were increased in the DOR group (2.08 ± 0.70 vs 1.46 ± 0.47 nmol/L, P < 0.001) and negatively correlated with AMH levels (Spearman r = -0.586, P < 0.001). After adjusting for age and BMI, a negative association between OGG1 and AMH remained (β = -0.619, P < 0.001). ROC curve analysis showed that a cut-off value of 1.765 nmol/L had an appropriate sensitivity (81.30%) and specificity (76.90%) for discriminating individuals with and without DOR, with the area under the curve (95% CI) of 0.870 (0.814 to 0.926), P < 0.001. We determined that serum OGG1 levels might be suggested as a new diagnostic indicator for DOR.

Rehmannioside D mitigates disease progression in rats with experimental-induced diminished ovarian reserve via Forkhead Box O1/KLOTHO axis

This study aims to explore the impact of Rehmannioside D (RD) on ovarian functions of rats with diminished ovarian reserve (DOR) and its underlying mechanisms of action. A single injection of cyclophosphamide was performed to establish a DOR rat model, and fourteen days after the injection, the rats were intragastrically administrated with RD for two weeks. Rat estrus cycles were tested using vaginal smears. Ovarian tissues were histologically evaluated, the number of primordial, mature, and atretic follicles was calculated, and the apoptotic rate of granulosa cells. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by ELISA assays. Protein levels of Forkhead Box O1 (FOXO1), KLOTHO, Bcl-2, and Bax were investigated in ovarian tissues of DOR rats. The binding between FOXO1 and KLOTHO was verified by ChIP assay. High-dose administration of RD into DOR rats improved their estrus cycles, increased ovarian index, enhanced the number of primordial and mature follicles, reduced the number of atretic follicle number, and ovarian granulosa cell apoptosis in addition to inhibiting FSH and LH levels and upregulating E2 expression. FOXO1 and KLOTHO were significantly suppressed in DOR rats. FOXO1 knockdown partially suppressed the protective effects of RD on DOR rats, and KLOTHO overexpression could restore RD-induced blockade of DOR development despite knocking down FOXO1. FOXO1 antibody enriched KLOTHO promoter, and the binding between them was reduced in DOR group compared to that in sham group. RD improved ovarian functions in DOR rats and diminished granulosa cell apoptosis via the FOXO1/KLOTHO axis.

Serum and Follicular Fluid Thiol/Disulfide Homeostasis in Diminished Ovarian Reserve Patients Undergoing In Vitro Fertilization/Intracytoplasmic Sperm Injection Treatment.

The etiologies of diminished ovarian reserve (DOR) are still poorly understood, and many factors such as age, autoimmunity, genetics, idiopathicity, iatrogenesis, and oxidative stress (OS) play a role. Oxidative cellular damage increases following reactiveoxygenspecies (ROS)-induced aging. This is the first study to evaluate the serum and follicular fluid (FF) thiol/disulfide homeostasis in patients under 35 years of age with DOR undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). In this study, DOR was defined by the Poseidon criteria, and Poseidon group 3 women were selected as the study group (n = 40). The control group was composed of patients with the diagnosis of mild-moderate male factor infertility (n = 30). The FF and serum native and total thiol levels, the markers of the antioxidant system,were significantly decreased in the DOR group compared with the control group (p = 0.021) (p = 0.037) (p = 0.029) (p = 0.04). On the other hand, we found no significant differences in the oxidant parameters between the groups (p > 0.05). An intrinsic deficiency of antioxidants can play an important role in the etiology of DOR. The dietary addition of antioxidants could be beneficial in DOR patients.

Screening for Adrenocortical and Thyroid Peroxidase Antibodies to Look for Underlying Autoimmune Etiologies in Women under 35 with Idiopathic Dimished Ovarian Reserve

Background: Autoimmune disorders are more common in premature ovarian insufficiency (POI) than in the general population. The most important association is with autoimmune Addison’s disease. Measurement of adrenocortical antibodies (ACA) and/or 21-hydroxylase antibodies (21-OH) is recommended in every POI patients as they appear to be the marker with the highest diagnostic sensitivity for autoimmune POI. Also thyroid peroxidase autoantibodies (TPO-Ab) should be assayed due to the common association between thyroid disease and POI. The underlying etiologies of diminished ovarian reserve (DOR) in young women can be expected to be similar to the etiology of POI since they represent a continuum in the phenotypic expression of premature ovarian aging. Methods: This pilot case-control study was conducted between January 2019 and April 2020. The study group consisted of patients under the age of 35, who was infertile and diagnosed with idiopathic DOR by ovarian reserve tests during infertility work up. Controls were patients of the same age range who diagnosed with isolated tubal factor or male infertility and had functional ovarian reserve test results during infertility work up. Patients with a history of ovarian surgery, cancer, genetic or autoimmune disease were excluded. Abnormal ovarian reserve tests are defined as antral follicle count &lt;5 and anti-mullerian hormone (AMH) &lt;1.2 ng/dL corresponding to group 3 according to POSEIDON criteria. In total, 35 DOR patients and 35 controls were included in the study. ACA and TPO-Ab screening were performed in serum samples using indirect immunofluorescence method. Demographics and family history of autoimmune diseases were also evaluated. Results: A higher rate of ACA positivity was detected in the DOR group (34.3%) compare to controls (17.1%), although it was not found to be statistically significant (p = 0.101, p &lt; 0.05). The incidence of family history of autoimmune diseases in first degree relatives was positively correlated with ACA positivity (p = 0.006, p &lt; 0.05). In DOR group, autoimmune disease history in the family was significantly higher in ACA (+) patients compared to ACA (–) individuals (p = 0.03, p &lt; 0.05). TPO-Ab positivity rates were similar between 2 groups (17.1% vs 20%, p = 0.759, p &lt; 0.05). Conclusions: Even if there is no specific treatment option yet for autoimmune ovarian damage, screening for ACA or 21-OH antibodies may be considered in young women with idiopathic DOR, especially those with a family history of autoimmune disease, based on knowledge that identification of women with autoimmune POI is clinically important for the identification of subclinical autoimmune Addison’s cases.

Effect of PFOA exposure on diminished ovarian reserve and its metabolism

Owing to its difficulty in degrading and ease of accumulation in the body, perfluorooctanoic acid (PFOA) has a detrimental effect on reproduction. This study aimed to examine the effect of PFOA concentration in follicular fluid during ovulation stimulation on embryo quality and the impact of PFOA exposure on the metabolic components of follicular fluid. This was a single-center prospective study that included 25 patients with diminished ovarian reserve (DOR), 25 with normal ovarian reserve (NOR), and 25 with polycystic ovary syndrome (PCOS). Follicular fluid samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. We demonstrated that the PFOA levels of follicular fluid in the DOR group were higher than those in the NOR group and PCOS group (P < 0.05). PFOA concentration in the PCOS group was negatively correlated with high-quality embryos (P < 0.05). To gain more insight into the impact of PFOA on the metabolic composition of follicular fluid, we classified the DOR group based on the PFOA concentration, for which metabolomic analysis was performed. In the high-concentration PFOA group, there was an increase and a decrease in three and nine metabolites, respectively, compared to that in the low-concentration group. These results suggest that PFOA may alter the metabolic composition of follicular fluid, thus, affecting ovarian reserve function.

Diminished ovarian reserve is a risk factor for preeclampsia and placental malperfusion lesions

To assess obstetric outcomes and placental findings in pregnancies attained by invitro fertilization (IVF) in patients with diminished ovarian reserve (DOR). Retrospective cohort study. University-affiliated tertiary hospital. DOR, defined as an antral follicle count (AFC) of 6 or less (DOR group), compared with patients with no DOR and an antral count above 6 (control group). Live singleton births after IVF between 2009 and2017. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, as categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes. A total of 110 deliveries of patients with DOR were compared with 772 controls. Maternal age was higher in the DOR group than in the control group (36.3 ± 4.4 years vs. 35.3 ± 4.1 years, P=.02). Patients with DOR were more likely to have a diagnosis of endometriosis (P=.02) and less likely to have a diagnosis of male factor (P<.001), ovulation disorder (P<.001), or tubal factor (P=.04), or a transfer of a blastocyte (P=.007). After adjustment for confounders, pregnancies in the DOR group were notable for a significantly higher rate of preeclampsia (8.1% vs. 2.7%, adjusted odds ratio: 3.05, 95% confidence interval: 1.33-6.97). On placental examination, DOR was associated with a higher rate of fetal vasculopathy (P=.01) and multiple fetal vascular malperfusion lesions (P=.03), and a lower rate of circummarginate insertion (P=.01) and intervillous thrombosis (P=.02). DOR, specifically defined as an AFC of 6 or less, is associated with a higher incidence of preeclampsia and multiple placental fetal vascular lesions.

Association of ABO blood groups with ovarian reserve: a retrospective cohort study in Chinese Han women younger than 40 years with infertility

BackgroundOvarian reserve reflects both the quantity and quality of oocytes available for procreation and is affected by many known and unknown factors. ABO blood type is related to several infertility processes, but it is unclear whether and how ABO blood type affects ovarian reserve.ObjectiveThe purpose of the study was to explore the correlation between ABO blood types and ovarian reserve in infertile Chinese Han women under 40 years of age undergoing the in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI)-embryo transfer (IVF/ICSI-ET) treatment.MethodsWomen aged < 40 years who underwent IVF/ICSI-ET at our institution and had a documented ABO blood type were eligible for this study. In this study, patients were divided into two groups according to the diminished ovarian reserve (DOR) group (AMH < 1.1 ng/mL, AFC < 6) and the non-diminished ovarian reserve (non-DOR) group (AMH ≥ 1.1 ng/mL, AFC ≥ 6). The relationship between ovarian reserve and ABO blood group was determined by correlation analysis.ResultsIn this retrospective cohort study, clinical data were collected from 1690 Chinese Han women treated with IVF/ ICSI-ET in hospital records between April 2019 and March 2020 in the affiliated hospital of Southwest Medical University, located in Luzhou, China. The differences in age, duration of infertility, BMI, FSH, FSH / LH, and p (DOR vs non-DOR) for each parameter (DOR vs non-DOR) were statistically significant, and the differences in LH and E2 were not statistically significant. ABO blood groups were most prevalent in the DOR group with O (143, 34.8%) and A (122, 29.7%) and in the non-DOR group with A (428, 33.5%) and O (419, 32.8%). ABO blood groups were most prevalent in the DOR group with O (n = 57, 30.5%) and A (n = 54, 28.9%) and in the non-DOR group with A (n = 335, 34.0%) and O (n = 323, 32.8%) were the most frequent in the non-DOR group.ConclusionsIn this retrospective cohort study, we confirmed the lack of a significant association between ABO blood type and ovarian reserve. Further studies are needed to clarify whether there is any prognostic correlation between ABO blood group and ovarian reserve in women undergoing IVF/ICSI-ET.

Influence of Diminished Ovarian Reserve on Early Embryo Morphokinetics during In Vitro Fertilization: A Time-Lapse Study.

There is great controversy as to whether women with Diminished Ovarian Reserve (DOR) exhibit only a quantitative decrease in ovarian reserve or also impaired oocyte and embryo quality. In this retrospective study, we aimed to evaluate the impact of DOR on embryo morphokinetic parameters with a time-lapse system. 1314 embryos were obtained from 256 couples undergoing IVF or ICSI cycles, with 242 embryos in the DOR group as classified by the Bologna and POSEIDON criteria and 1072 embryos derived from the Normal Ovarian Reserve (NOR) group. For each morphokinetic parameter (t2, t3, t4, t5, t8, tB, ECC2, cc2a, ECC3, s2, s3), a generalized linear mixed model was created to control for female age, BMI, smoking status, method of insemination and correlation between oocytes from a same cohort. No significant association was found between DOR and any of the morphokinetic parameters studied. In a secondary analysis, we evaluated the influence of maternal aging, comparing morphokinetic characteristics between two age groups (<37 and ≥37 years). In the univariate analysis, we found that embryos from older women displayed a slower embryo development (in particular for t3, t4, t5, tB, and ECC2), although without statistical significance in the multivariate analysis. In conclusion, our study did not reveal any substantial impact of ovarian aging on early morphokinetic parameters and suggested potential biases that may be a source of controversy in the literature.