Serum E2 Research Articles

Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERβ and oxytocin of C57BL/6J female mice.

Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors β immunoreactive neurons (ERβ-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there’s increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERβ-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERβ/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions.

Serum Estradiol and 20 Site-Specific Cancers in Women: Mendelian Randomization Study.

ContextThe causal role of endogenous estradiol in cancers other than breast and endometrial cancer remains unclear.ObjectiveThis Mendelian randomization study assessed the causal associations of endogenous 17β-estradiol (E2), the most potent estrogen, with cancer risk in women.MethodsAs primary genetic instrument, we used a genetic variant in the CYP19A1 gene that is strongly associated with serum E2 levels. Summary statistics genetic data for the association of the E2 variant with breast, endometrial, and ovarian cancer were obtained from large-scale consortia. We additionally estimated the associations of the E2 variant with any and 20 site-specific cancers in 198 825 women of European descent in UK Biobank. Odds ratios (OR) of cancer per 0.01 unit increase in log-transformed serum E2 levels in pmol/L were estimated using the Wald ratio.ResultsGenetic predisposition to higher serum E2 levels was associated with increased risk of estrogen receptor (ER)-positive breast cancer (OR 1.02; 95% CI, 1.01-1.03; P = 2.5 × 10−3), endometrial cancer overall (OR 1.09; 95% CI, 1.06-1.11; P = 7.3 × 10−13), and endometrial cancer of the endometrioid histology subtype (OR 1.10; 95% CI, 1.07-1.13; P = 2.1 × 10−11). There were suggestive associations with breast cancer overall (OR 1.01; 95% CI, 1.00-1.02; P = 0.02), ovarian cancer of the endometrioid subtype (OR 1.05; 95% CI, 1.01-1.10; P = 0.02), and stomach cancer (OR 1.12; 95% CI, 1.00-1.26; P = 0.05), but no significant association with other cancers.ConclusionThis study supports a role of E2 in the development of ER-positive breast cancer and endometrioid endometrial cancer but found no strong association with other cancers in women.

Endogenous hippocampal, not peripheral, estradiol is the key factor affecting the novel object recognition abilities of female rats.

Estradiol (E2) is involved in the regulation of emotional behavior, cognitive function, and neuroplasticity. However, peripheral E2 and central E2 levels do not always fluctuate together. The relationships of peripheral and central E2 with cognitive function are not clear. The aim of this study was to investigate whether peripheral E2, hippocampal E2, or both play a critical role in novel object recognition (NOR), and whether Kalirin-7, an important regulator of spine plasticity, is involved in the modulation of E2 on cognitive behavior. Our results showed that ovariectomy (OVX) significantly reduced serum E2 levels in the 14 weeks following the procedure. However, hippocampal E2 levels did not decrease in the OVX group compared to the sham group until after 14 weeks. Consistent with the changes in hippocampal E2 levels, the investigation ratio in the NOR test and hippocampal Kalirin-7 expression was also not lower in the OVX group than in the sham group until 14 weeks after the procedure. To confirm the relationship between hippocampal E2 levels and NOR ability, we inhibited the production of hippocampal E2 via microinjection of letrozole (LTZ; an aromatase inhibitor) into the hippocampi of rats in the control group and 8-week OVX group. The data indicated that a reduction in E2 levels in the hippocampus significantly impaired NOR ability and simultaneously decreased Kalirin-7 levels in the hippocampus. In conclusion, our study strongly demonstrates that hippocampal E2, but not peripheral E2, plays a critical role in NOR ability and that Kalirin-7 may be involved in this mechanism. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Predictive Values of Serum Progesterone, Human Chorionic Gonadotropin and CA-125 for Pregnancy Outcomes of Threatened Abortion and Subchorionic Hematoma

Objective: We aimed to study the predictive values of serum progesterone (P), human chorionic gonadotropin (HCG) and CA-125 for the pregnancy outcomes of threatened abortion complicated with subchorionic hematoma (SCH). Materials and methods: Sixty women with threatened abortion and SCH in 6-1 Oth gestational week, 60 with threatened abortion only and 60 healthy pregnant women were selected as groups A-C respectively. Levels of β-HCG, P, estradiol (E2) and CA-125 in peripheral venous blood were measured by chemiluminescence assay. Serum levels of INF-γ, TNF-α, IL-2, IL-4 and IL-10 were detected by ELISA. Results: Serum β-HCG, P, CA-125 and E2 levels of group A were significantly lower than those in group C (P<0.05). Groups A and B had significantly higher INF-y, TNF-a and IL-2 levels but lower IL-4 and IL-10 ones than those of group C (P<0.05).The hospitalization and vaginal bleeding times of group A were significantly longer than those of groups B and C (P<0.05). The success rate of fetal protection, neonatal body weight and gestational age of groups A and B were significantly lower than those of group C (P<0.05). Serum P, E2 and HCG levels were low in women with threatened abortion and SCH in early pregnancy, but CA-125 level was high, accompanied by increased INF-γ, TNF-α and IL-2 together with decreased IL-4 and IL-10. Conclusion: The onset and progression of SCH may be related to imbalance between T lymphocyte factors towards Th1 direction.

Urinary equol levels are positively associated with urinary estradiol excretion in women

Isoflavones found in soy products are a promising class of nutrients that may have a positive effect on human health. In particular, the phytoestrogen metabolite equol is associated with a reduced risk of developing female hormone-related diseases. However, the effect of equol on estrogen remains unclear. Equol can modify blood and urinary estradiol (E2) levels. The aim of this cross-sectional study was to examine the associations between urinary estrogen levels, equol levels, and equol production status in Japanese women. We analyzed urine samples from 520 women by gas chromatography-mass spectrometry. Urinary E2 and 4-hydroxylated E2 levels were higher in equol producers (EQP) than in non-EQPs (P < 0.0001 and P=0.00112, respectively). After adjusting for age and tobacco use by analysis of covariance, the association remained significant (β = 0.299, P < 0.0001). Analysis of covariance demonstrated that equol levels in urine were also positively associated with urinary E2 (β = 0.597, P < 0.0001). The log equol concentration showed a significant, but moderate, negative association with the serum E2 concentration (β = − 0.0225, P = 0.0462). Our findings suggest that equol may promote urinary E2 excretion and modify blood E2 levels in women.

Dynamic changes in serum steroid hormone during the first trimester of pregnancy between infertile women conceiving with and without hormone replacement therapy

ObjectiveRecent advances in cancer treatment and reproductive medicine have made the post-treatment quality of life an important concern for cancer survivors. We aimed to evaluate the safety of sex hormone (estradiol and progesterone) replacement therapy (HRT) in women who conceived by assisted reproductive technology (ART) with hormone receptor-positive breast cancer. MethodsWe measured serum E2 and P4 levels at 4–10 weeks of gestation in women who conceived naturally or after timed intercourse or intrauterine insemination for infertility without HRT for luteal support (non-HR group; n = 135). We conducted a retrospective comparison of the values from the non-HR group with those of women who conceived by ART with HRT for infertility (HR group; n = 75). ResultsSerum E2 levels were significantly higher in the non-HR group than in the HR group at 5, 6, and 8 weeks of gestation. Similarly, serum P4 levels were significantly higher in the non-HR group than in the HR group at 4, 5, and 6 weeks of gestation. ConclusionsThis study suggests that in cancer reproductive medicine for hormone-dependent breast cancer survivors, HRT administered during the first trimester of a pregnancy after primary disease treatment may not increase the sex hormone levels to levels above those seen in spontaneous pregnancy.

Clinical Efficacy and Safety Study of Mifepristone with Misoprostol Treatment in Patients with Missed Abortion.

Currently, medication abortion is widely used in clinical practice in China. The aim of this study was to investigate the effect of mifepristone with misoprostol treatment on the efficacy of patients with missed abortion (MA) and the safety of this drug regimen. 95 patients with MA treated in our hospital from February 2019 to April 2021 were collected as the subjects of this study, and the patients were divided into the control and the research groups according to different treatment modalities. Among them, 46 cases in the control group were treated by diethylstilbestrol combined with oxytocin and 49 cases in the research group were treated by mifepristone combined with misoprostol, and both groups underwent curettage after medication. The rates of complete abortion, time of embryo expulsion, time of operation, intraoperative bleeding, time of postoperative vaginal bleeding, amount of vaginal bleeding, rate of one-time curettage, the levels of serum estradiol (E2), progesterone (P), β-chorionic gonadotropin (β-hCG), and interleukin-18 (IL-18), and the incidence of adverse effects in the two groups were examined and compared. Alanine transaminase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (Scr) were used as indicators to evaluate the safety of the drug. The results showed that the rates of complete abortion and one-time curettage were significantly higher in the study group than in the control group, while the time of embryo expulsion, operation time, intraoperative bleeding, postoperative vaginal bleeding time, and vaginal bleeding were significantly lower than in the control group. The serum E2, P, and β-hCG levels before curettage in both groups were significantly higher, and IL-18 levels were significantly lower than those at the time of admission, with E2, P, and β-hCG levels increasing more and IL-18 levels decreasing more in the research group. After drug treatment, no abnormal changes in liver and kidney functions were observed in both groups, and the incidence of adverse reactions was at a similar and lower level in both groups. This shows that mifepristone with misoprostol is a safer and more effective drug regimen for the treatment of MA, which can regulate the levels of serum sex hormones and inflammatory factors in the body, promote the shedding of placental tissue, and create conditions for improving the rate of curettage.

High Maternal Serum Estradiol in First Trimester of Multiple Pregnancy Contributes to Small for Gestational Age via DNMT1-Mediated CDKN1C Upregulation

High maternal serum estradiol (E2) levels in the first trimester of pregnancy are associated with a high incidence of low birth weight (LBW) and small for gestational age (SGA). This study aimed to investigate the effect of first-trimester high maternal serum E2 levels on fetal growth and the underlying mechanisms in multiple pregnancies. Maternal serum E2 levels of women at 8 weeks of gestation were measured. The expression levels of imprinted genes and DNMT1 were determined by RT-qPCR, and KvDMR1 methylation in embryo tissue, placenta, and newborn cord blood samples was examined by bisulfite sequencing PCR. The effect of E2 on CDKN1C expression was investigated in HTR8 cells. The incidence of SGA was significantly higher in multiple pregnancies reduced to singleton than that in primary singleton pregnancies (11.4% vs. 2.9%) (P < 0.01) and multiple pregnancies reduced to twins than primary twins (38.5% vs. 27.3%) (P < 0.01). The maternal serum E2 level at 8 weeks of gestation increased with the number of fetuses and was negatively correlated with offspring birth weight. CDKN1C and DNMT1 expression was significantly upregulated in embryo tissue, placenta, and cord blood from multiple pregnancies. Furthermore, there was a positive correlation between CDKN1C mRNA expression and KvDMR1 methylation levels. In HTR8 cells, DNMT1 mediated the estrogen-induced upregulation of CDKN1C, which might contribute to SGA. To minimize the risks of LBW and SGA, our findings suggest that abnormally high maternal serum E2 levels should be avoided during the first trimester of multiple pregnancies from assisted reproductive technology (ART).

Clinical Observation on the Improvement of Serum Sex Hormone and Ovarian Function in Premature Ovarian Failure Patients with Deficiency-Cold Syndrome by Combining Wenjing Decoction with Tiaobu Chongren Acupuncture and Moxibustion.

Objective To explore the effect of Wenjing Decoction and Tiaobu Chongren acupuncture and moxibustion therapy on serum sex hormones and ovarian function recovery in premature ovarian failure (POF) patients with deficiency-cold syndrome. Methods From February 2018 to October 2019, 119 POI patients with deficiency-cold syndrome who met the selection criteria were randomly divided into the control group (n = 59) and the observation group (n = 60). The control group was treated with hormone replacement therapy, and the observation group was treated with Wenjing Decoction and Tiaobu Chongren acupuncture and moxibustion therapy on the basis of the control group. Both groups were treated continuously for 3 months. After treatment, the clinical efficacy of the two groups was compared, the Chinese medicine syndrome score, serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH) and bilateral antral follicle count (AFC), mean ovarian volume, and endometrial thickness of the two groups before and after treatment were compared. Result The effective rate of the observation group (93.10%) was higher than that of the control group (77.59%) (P < 0.05). After treatment, the index scores of traditional Chinese medicine syndromes in two groups were lower than before (P < 0.05), and the observation group was lower than the control group (P < 0.05). The serum E2 and AMH levels in the two groups increased, while FSH and LH levels decreased compared with before treatment, and the observation group improved significantly compared with the control group (P < 0.05). The bilateral AFC, mean ovarian volume, and endometrial thickness of the two groups increased compared with before treatment, and the observation group was higher than the control group (P < 0.05). Conclusion On the basis of hormone replacement therapy, the combination of Wenjing Decoction and Tiaobu Chongren acupuncture and moxibustion therapy is effective in treating POF patients with deficiency-cold syndrome, which can effectively regulate their serum sex hormone levels and promote the recovery of ovarian function.

OVULATION INDUCTION AND SUCCESSFUL LIVE DELIVERY IN A 46.5-YEAR-OLD WOMAN IN OVERT MENOPAUSE BY RESTORING FOLLICULAR SENSITIVITY TO FOLLICLE STIMULATING HORMONE (FSH)

To try to up-regulate FSH receptors on granulosa-theca cells in a woman of very advanced reproductive age in overt menopause whose FSH receptors had been internalized related to elevated serum FSH levels, by inhibiting release of FSH from the pituitary by negative feedback of estrogen. The overall objective was to deliver a live healthy baby. Ethinyl estradiol (EE) 20 micrograms was given to a woman age 46.5 who had amenorrhea for 9 months and who was in overt menopause, as evidenced by failure to have menses following 10mg medroxyprogesterone acetate x 13 days. In addition, the patient had a serum estradiol (E2) of <15 pg/mL, a serum FSH of 117 mIU/mL, and a serum anti-Mullerian level of <0.09 ng/mL. She was treated with EE to lower serum FSH levels rather than E2 because the former does not contribute to the total serum E2 level, and thus allows the treating physician to detect when a follicle has been recruited by rising serum E2 levels. A rising E2 would dictate the addition of pelvic sonography to help determine when a mature dominant follicle was achieved (18mm average diameter with serum E2 ≥200pg/mL). If a mature follicle was achieved, 1mg granulocyte colony stimulating factor (G-CSF) would be given the day before an injection of 10,000 units human chorionic gonadotropin (hCG) to help the oocyte release. At age 42 she had been treated for infertility and was found to have the luteinized unruptured follicle syndrome. She failed to release the oocyte with either hCG or leuprolide acetate but was successful with hCG when G-CSF was added (and delivered a healthy baby despite a day 3 serum FSH of 47 mIU/mL). Progesterone vaginal suppositories 200mg twice daily was supplemented in the luteal phase. After 44 days of EE she was able to attain a mature follicle (E2 273 pg/mL, follicular size 18.8mm average diameter). She released the oocyte, conceived and successfully delivered a full-term healthy baby. A previous case was reported in Human Reproduction in 2000 of a 45-year-old in overt menopause. Successful reversal of menopause was achieved, and she delivered a live baby utilizing this same technique of restoration of FSH sensitivity by using EE without any exogenous FSH stimulation. Precedents are important for patient-physician decisions regarding treatment options. This case shows a live delivery is possible even in a 46.5-year-old menopausal woman using her own oocytes.

PREGNANCY OUTCOMES FOLLOWING A CONVERSION FROM ORAL TO VAGINAL ESTRADIOL DUE TO ENDOMETRIAL HYPOPROLIFERATION: AN ANALYSIS OF FROZEN, EUPLOID SINGLE EMBRYO TRANSFERS

Compared to oral estradiol (E2), vaginal administration of E2 prior to frozen embryo transfer (FET) has been reported to lead to higher serum E2 levels and thicker endometrial linings (1). Therefore, in patients who experience endometrial hypoproliferation with oral E2, converting to vaginal E2 may normalize the endometrial thickness. It is unclear whether this normalization in lining thickness leads to equivalent pregnancy outcomes. This study examines whether pregnancy outcomes are affected when a change to vaginal E2 occurs in patients undergoing FET of a single, euploid embryo.

PATIENTS WHO REQUIRE SUPRA-PHYSIOLOGIC ESTROGEN SUPPLEMENTATION TO ACHIEVE ADEQUATE ENDOMETRIAL THICKNESS FOR EUPLOID EMBRYO TRANSFERS ARE AT INCREASED RISK OF PRETERM DELIVERY AND LOWER BIRTH WEIGHT

Supra-physiologic estradiol (E2) levels are associated with decreased live birth rates in frozen embryo transfer cycles, possibly due to an underlying endometrial defect requiring additional supplementation.1 This study aims to determine whether patients with elevated serum E2 levels during single euploid frozen-thawed embryo transfer (FET) are at increased risk for neonatal morbidity including preterm birth and low birth weight.

The discrepancy of aromatase expression in epicardial adipose tissue between CHD and non-CHD patients.

Epicardial adipose tissue (EAT) aromatase converts androstenedione and other adrenal androgens into oestrogens. The locally produced oestradiol (E2) may have cardiovascular protective effects. Little is known about the relationship between EAT aromatase level and coronary heart disease (CHD). Here, we compared EAT aromatase levels in CHD versus non-CHD patients and assessed the relationship between EAT aromatase levels and lesion degree in the coronary arteries. EAT and blood specimens were obtained from patients undergoing thoracotomy prior to cardiopulmonary bypass. Serum E2 levels were obtained from our hospital laboratory. EAT aromatase expression was determined by RT-qPCR and ELISA assays. All patients underwent coronary angiography and the level of coronary lesions was evaluated with the SYNTAX score. Compared with non-CHD patients, CHD patients had lower EAT aromatase mRNA and protein levels. In the CHD patients, EAT aromatase and oestrogen levels negatively correlated with the severity of coronary artery disease. Our data revealed that reduced EAT aromatase levels correlated with coronary atherosclerotic lesions. Reduced EAT aromatase protein levels may aggravate the severity of atherosclerosis. Future studies should investigate the mechanisms regulating aromatase expression in epicardial fat.

Urinary Metal Mixtures and Hormone Levels during the Menopausal Transition: the Study of Women’s Health Across the Nation (SWAN)

BACKGROUND AND AIM: Epidemiologic studies on associations between metal exposures and sex hormones in women have been limited, and results have been mixed. We assessed associations of urinary metals concentrations with longitudinal serum levels of follicle-stimulating hormone (FSH) and estradiol (E2). METHODS: We examined data from 1,355 women aged 45-56 years at baseline (1999-2000), followed through 2017, from the Study of Women’s Health Across the Nation. Baseline urinary concentrations of 15 metals (arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc) were determined. Serum levels of FSH and E2 were measured repeatedly over 17 years of follow-up. Linear mixed effects models were used to evaluate associations between individual metals and hormone levels. The least absolute shrinkage and selection operator (LASSO) penalized linear mixed effects models were used to evaluate associations between metal mixtures and hormone levels. An environmental risk score (ERS) was used to integrate metal mixture effects from LASSO results. RESULTS:After adjustment for confounders, one standard deviation increase in log-transformed baseline urinary metal concentrations were associated with 3.53% (95% CI: 0.42%, 6.73%) higher levels of FSH for cadmium, 5.61% (95% CI: 2.50%, 8.82%) higher levels for lead, and 3.06% (95% CI: -5.87%, -0.17%) lower levels for cobalt. For E2 levels, one standard deviation increase in log-transformed urinary metal concentrations were associated with 2.88% (95% CI: -5.31%, -0.38%) lower levels for mercury, 5.20% (95% CI: -7.56%, -2.78%) lower levels for lead, and 2.44% (95% CI: -4.74%, -0.09%) lower levels for tin. The ERS was associated with higher FSH and lower E2 levels. CONCLUSIONS:Results from this prospective cohort study of midlife women suggested that metals, including lead, cadmium, mercury, cobalt, tin, and metal mixtures were associated with serum FSH and E2 levels, consistent with findings that metal exposures affect reproductive aging. KEYWORDS: metals, mixtures, estradiol, follicle-stimulating hormone, cohort study

Serum estrogen and its soluble receptor levels in Egyptian patients with acute leukemia: case-control study

BackgroundAcute leukemias are malignant neoplastic diseases that arise from either lymphoid [ALL] or myeloid [AML] cell lines that are distinguished by the proliferation of BM non-functional immature cells and subsequently released into the bloodstream. ALL is prevalent malignancy in young, while AML in older. Diagnosis is usually routinely performed through peripheral blood count and smear then confirmed by BM aspirate. It is remarkable to notice that leukemia can be manifested at high, low, and even at normal leucocyte count. While treatment results have improved steadily over the last decades in younger and adults, limited changes have been in survival among subjects of age > 60 years. Aim of the work is to measure the serum estrogen [E2] and its soluble receptor [ER] levels in acute leukemia patients and extrapolate its possible clinical significance. This study included 40 [20 females and 20 males] healthy volunteers clinically free from any disease, 40 [20 females and 20 males] AML patients, and 40 [20 females and 20 males] ALL. To all subjects, serum E2 and its soluble ER level were investigated by ELISA.ResultsSerum E2 [pg/ml] level was lower in AML and ALL female and male patients groups than control group. Serum ER [ng/ml] level was lower in AML and ALL female and male patients groups than control group.ConclusionEstimation of serum E2 and its soluble ER level is of edifying diagnostic value. Determination of serum E2 and its soluble ER level in AML and ALL patients is of value in deciding treatment therapeutic target protocol.

Evaluation of the relationship between serum estradiol levels on human chorionic gonadotropin administration day and intracytoplasmic sperm injection outcomes: A retrospective population-based study.

BackgroundThe correlation between high estradiol (E2) levels induced by controlled ovarian hyperstimulation (COH) and pregnancy is controversial.ObjectiveTo assess the effect of serum E2 levels on the day of human chorionic gonadotropin administration on the intracytoplasmic sperm injection (ICSI) outcome.Materials and MethodsThe current study included 551 participants who had undergone ICSI between May 2014 and May 2016. Based on E2 levels, the individuals aged 37 yr (n = 502) and 37-42 yr (n = 49) were categorized into six and three groups, respectively. ICSI outcomes including the number of retrieved oocytes (NRO), number of embryos (NE), pregnancy rate, and abortion rate were analyzed in both groups.ResultsAmong participants aged 37 yr, the NRO and NE were 8.69 3.82 and 5.24 2.32, respectively and they had a significant correlation with the E2 level on human chorionic gonadotropin administration day (p 0.001 for both). Among participants aged 37 yr, NRO and NE were 5.18 3.17 and 3.40 2.23, respectively, and the NRO (p 0.001), NE (p 0.001), pregnancy rate (p 0.001), abortion rate (p = 0.007), and the number of grade A and B embryos (p = 0.003) had a significant association with the E2 level.ConclusionCOH is a costly procedure that may have negative effects on endometrial receptivity. Thus, in order to prevent these effects and also to reduce the costs of COH, we recommend gaining optimum number of oocytes rather than maximum number during the procedure.

Comparative analysis of the hormone production and gene expression profiles in ovine uterus tissue during oestrus cycle synchronized using medroxyprogesterone acetate plus eCG and prostaglandin analogue

The combination of medroxyprogesterone acetate (MPA) and gonadotropin chorionic (eCG) has been widely used to synchronize oestrus cycle in sheep, but their effects on the gene expression in uterine tissue are yet to be elucidated. To evaluate the effect of MPA + eCG or prostaglandin analogue (PA) treatments on the rate of oestrus cycle synchronization, as well as further hormone production and gene expression profiles in uterine tissue, 14 Santa Inês ewes were randomly selected. The MPA + eCG group (n=7) received intravaginal insertion of MPA-impregnated sponges for 14 days and was administered 350 IU eCG on the day of sponge withdrawal. The PA group (n=7) was administered two doses of 100 μg of PA separated by 12 days. The ewes were assessed for the rate of oestrus cycle synchronization and the serum concentrations of progesterone (P4) and estradiol (E2). Additionally, the expression of estrogen receptor (ERα), progesterone receptor (P4R), and immunolocalization of interferon receptor (IFNAR1) in the uterine tissue samples collected 15th day post-mating were examined. The rate of oestrus cycle synchronization was 100% (n=7/7) and 57.14% (n=4/7) in the MPA + eCG and PA groups, respectively. Moreover, the MPA + eCG group exhibited higher serum concentration of P4 than the PA group (p &lt; 0.05). However, the E2 serum concentration did not differ between the two groups (p &gt; 0.05). The relative expression of P4R and ERα mRNA analyzed using real-time PCR and immunodetection of IFNAR1 were similar between the two groups tested (p &gt; 0.05). Conclusively, MPA + eCG treatment improved the rate of oestrus cycle synchronization and endogenous P4 production; however, it did not affect the expression of sex steroid receptors and IFNAR1 in uterine ovine tissue.

17β-Estradiol alleviates intervertebral disc degeneration by inhibiting NF-κB signal pathway

AimTo investigate the effect of 17β-Estradiol (E2) on intervertebral disc degeneration (IVDD) and the related mechanism. Materials and methodsImmunohistochemistry was used to detect the expression of estrogen receptor β (ERβ) within intervertebral discs of humans and rats. After that, rat IVDD model was established by needle puncture and bilateral ovariectomy. Then, the serum E2 level was detected by enzyme linked immunosorbent assay, and the degree of IVDD was evaluated by X-ray, magnetic resonance imaging, hematoxylin and eosin staining, and Safranin O-Fast Green staining. Finally, we used immunohistochemistry and immunofluorescence staining to determine the effect of E2 on nuclear factor kappa-B (NF-κB) signal pathway both in vivo and in vitro. Key findingsWe identified that IVDD was associated with lower levels of ERβ and ERβ levels were inversely correlated with IVDD. The histological staining and radiological results showed that E2 supplement could alleviate IVDD progression. Additionally, immunohistochemistry staining demonstrated that E2 could inhibit nucleus pulposus cell (NPC) apoptosis, matrix metalloproteinases (MMPs) synthesis, and degradation of extracellular matrix (ECM) by inhibiting the activation of NF-κB signal pathway. Furthermore, immunofluorescence staining showed that the above effects of E2 on the NF-κB signal pathway could be blocked by the estrogen receptor antagonist ICI182780 in vitro. Finally, inhibition of NF-κB signal pathway by BAY11-7082 could reduce MMPs synthesis and ECM degradation of NPCs. SignificanceCollectively, these findings indicated that E2 could effectively ameliorate IVDD by inhibiting NPC apoptosis via inhibition of NF-κB signal pathway.

P–670 Urine estrone–3-glucuronide (E3G) assay: is there any place during ovarian stimulation for IVF cycles?

Study questionCould the urine estrone–3-glucuronide (E3G) assay be used efficiently to monitor a controlled ovarian hyperstimulation (COH) cycle, in comparison to a serum estradiol (E2) assay?Summary answerE3G testing provides an alternative to serum E2 assessment and a new “patient friendly” approach for COH monitoring.What is known alreadyIn many IVF clinics basic monitoring tools for controlled ovarian stimulation during IVF procedure are ultrasound measurements of follicle growth and hormone assessment of serum E2 levels. The monitoring can occur 4–6 times during stimulation, but repeated blood sampling causes patient stress. In contrast, E3G sampling, one of principal metabolites of estradiol in urine, is non-invasive and can be performed by the patients themselves and measured by fluorescent immunoassay. A correlation has been shown between concentrations of E2 present in plasma and concentrations of E3G in different phases of menstruation cycle.Study design, size, durationThis is a pilot, prospective study, in a single IVF clinic. Twenty female participants were recruited November 2020 -January 2021, aged 25–43 years and BMI: 18–28kg/m2. Dynamic change of serum E2 and urine E3G at ovarian stimulation monitoring are being analyzed.Participants/materials, setting, methodsConcurrent urine E3G and serum E2 values were collected from patients who provided between 2 and 4 samples on different days of their COH IVF cycle. Serum E2 values were assessed routinely, while E3G values were measured and validated using a fluorescent immunoassay Mira Fertility Plus® analyzer.Main results and the role of chance: The urine E3G of assay was validated for intra- and inter-assay variability with a coefficient of variation of < 20%. It was also validated for analytical and functional sensitivity and sample stability. Linear regression of serum E2 and E3G values of 56 early morning urine samples who had evaluated between Days 4 and 13 of menstruation cycle provided an R = 0,81. Urine E3G values also correlated to follicle growth. Patient survey results showed that urine sampling was the preferred method of analysis.Limitations, reasons for cautionWe have provided proof of principle that urine E3G measurement can be accurately carried out using fluorescent immunoassay technology during routine COH for IVF cycles. The patients’ study group has to be expanded in order to enable us to find the appropriate place of urine E3G assay in COH protocol.Wider implications of the findings: Urine E3G testing correlates well to serum E2 assessment in COH. Urine E3G assay provides an alternative to serum-based assessment. The ease of urine sampling allows a reduction in patient discomfort during venopuncture, costs, time, and infection risks in epidemics/pandemics, like COViD–19, and offers a patient-friendly approach to ovarian stimulation.Trial registration numberNA

P–593 Self-monitoring of hormones via a urine-based hormonal assay — a topical endeavour into telemedicine in medically-assisted reproduction (MAR)

Study questionHow can cycle monitoring using a urine-based hormonal assay device improve current clinical practice in medically assisted reproduction (MAR)?Summary answerA urine-based hormonal assay has the potential to overcome the inconvenience of blood tests and reduce the frequency of appointments, waiting times and patient burden.What is known alreadyCycle monitoring via ultrasound and serum-based hormonal assays during MAR can provide information on the ovarian response and assist in optimising treatment strategies and reducing complications, such as ovarian hyperstimulation syndrome (OHSS). However, blood tests may cause inconvenience to patients due to repeated venepuncture and the need for frequent clinic appointments. Urine-based assays have been historically used by fertility specialists in clinics, but since got replaced by more practical and automated serum-based assays. Novel technology utilising rapid chromatographic immunoassay to test urinary reproductive hormones in a home setting could provide an alternative to current serum-based testing at clinics.Study design, size, durationA questionnaire was disseminated among 24 fertility specialists (2019–2020) on the use of ultrasound and serum-based hormone monitoring in clinical practice. In addition, the literature on the reliability of urine-based hormonal assays compared to serum-based hormonal assays during MAR was reviewed in order to examine if urine-based hormonal monitoring could be re-introduced in clinical practice using novel state-of-the-art technology.Participants/materials, setting, methodsAll 24 surveyed fertility specialists responded, representing 10 countries from across Europe, Asia and Latin America. Questions assessed the frequency and role of hormonal monitoring, the hormones tested and the drawbacks of blood tests. The PubMed search engine was used to search the Medline database for publications between 1960–2020 with (MeSH-) search terms related to cycle monitoring (e.g. fertility monitoring, controlled ovarian stimulation, ovulation confirmation) and hormonal assays (e.g. estrone–3-glucuronide or E1–3G).Main results and the role of chanceThe survey confirmed that many fertility practitioners (n = 22/24) routinely conducted hormone monitoring during MAR, primarily for guiding dose adjustments (n = 20/24) and indicating risk of OHSS (n = 20/24). The reported drawbacks of blood tests included validity of results from different service providers, long waiting times and discomfort to patients due to travelling to clinics for tests and repeated venepunctures. The hormones routinely checked were E2 (n = 22/22), P4 (n = 18/22) and LH (n = 15/22). The literature review revealed a relatively high correlation (correlation coefficients 0.85–0.95) between serum E2 and urinary E1–3G in gonadotrophin stimulated cycles (Lessing 1987, Catalan 1989, Rapi 1992 and Alper 1994). No studies assessed the correlation between serum P4 and urinary PdG or between serum LH and urinary LH in stimulated cycles. In natural cycles, the correlation coefficients between serum P4 and urinary PdG seemed to be slightly higher than those between serum E2 and urinary E1–3G (0.73–0.94 vs. 0.54–0.88) (Denari 1981, Munro 1991, Roos 2015, Stanczyk 1980). One study reported a moderate correlation coefficient (0.72) between serum and urinary LH in natural cycles (Roos 2015).Limitations, reasons for cautionThere is risk of selection-bias for fertility specialists included in survey, however, the 100% response rate is reassuring. The correlation coefficients between serum- and urine-based hormonal assay and the cost-effectiveness and time-efficiency of urinary assay should be confirmed in further clinical studies using a novel state-of-the-art remote urinary monitoring device.Wider implications of the findings: Remote hormonal monitoring can be part of a novel digital health solution that includes remote ultrasound and tele-counselling to link clinics and patients at home. Especially during the unprecedented times of the COVID–19 pandemic, the prospect of remote monitoring system has the potential to improve patient experience during fertility treatment.Trial registration numberNot applicable