High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

PURPOSE: There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). METHODS: We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2 ng/mL or 3-day area under the curve > 4.5 ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. RESULTS: Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol ≥ 4000 pg/mL had a greater likelihood of GBO compared to cycles < 1000 pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000 pg/mL versus 1000-1999 pg/mL and 1000-1999 pg/mL versus 2000-2999 pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999 pg/mL versus 3000-3999 pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999 pg/mL versus ≥ 4000 pg/mL, aRR 0.96, 95% CI 0.9-1.04). CONCLUSION: In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999 pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study.

Background: Gender differences existed in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear. Method: Based on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation. Results: E2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046). Conclusion: Findings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD.

The combination of dydrogesterone and micronized vaginal progesterone can render serum progesterone level measurements on the day of embryo transfer and rescue attempts unnecessary in an HRT FET cycle.

PURPOSE: To evaluate the role of serum progesterone (P4) on the day of embryo transfer (ET) when dydrogesterone (DYD) and micronized vaginal progesterone (MVP) are combined as luteal phase support (LPS) in a hormone replacement therapy (HRT) frozen ET (FET) cycles. METHODS: Retrospective study, including single euploid HRT FET cycles with DYD and MVP as LPS and P4 measurement on ET day. Initially, patients with P4 levels < 10 ng/ml increased MVP to 400 mg/day; this "rescue" was abandoned later. RESULTS: 560 cycles of 507 couples were included. In 275 women, serum P4 level was < 10 ng/ml on the ET day. Among those with low P4 levels, MVP dose remained unchanged in 65 women (11.6%) and was increased in 210 women (37.5%). Women with P4 levels ≥ 10 ng/ml continued LPS without modification. Overall pregnancy rates in these groups were 61.5% (40/65), 54.8% (115/210), and 48.4% (138/285), respectively (p = n.s.). Association of serum P4 levels with ongoing pregnancy rates was analyzed in women without any additional MVP regardless of serum P4 levels (n = 350); multivariable analysis (adjusted for age, BMI, embryo quality (EQ)) did not show a significant association of serum P4 levels with OPR (OR 0.96, 95% CI 0.90-1.02; p = 0.185). Using inverse probability treatment weights, regression analysis in the weighted sample showed no significant association between P4 treatment groups and OP. Compared to fair EQ, the transfer of good EQ increased (OR 1.61, 95% CI 1.22-2.15; p = 0.001) and the transfer of a poor EQ decreased the odds of OP (OR 0.73, 95% CI 0.55-0.97; p = 0.029). CONCLUSION: In HRT FET cycle, using LPS with 300 mg/day MVP and 30 mg/day DYD, it appears that serum P4 measurement and increase of MVP in patients with P4 < 10 ng/ml are not necessary.

Reproducible stability of verbal and spatial functions along the menstrual cycle.

Recent studies have reported brain changes in response to ovarian hormonal fluctuations along the menstrual cycle. However, it remains unclear, whether these brain changes are of an adaptive nature or whether they are linked to changes in behavior along the menstrual cycle, particularly with respect to cognitive performance. To address this knowledge gap, we report results from 3 well-powered behavioral studies with different task designs, leveraging the advantages of each design type. In all three studies we assessed whether verbal or spatial performance (i) differed between cycle phases, (ii) were related to estradiol and / or progesterone levels and (iii) were moderated by individual hormone sensitivity as estimated by premenstrual symptoms. Overall, results of all three studies point towards a null effect of menstrual cycle phase and - to a lesser extent - ovarian hormones on verbal and spatial performance and provided no evidence for a moderation of this effect by individual hormone sensitivity. We conclude that there is substantial consistency in verbal and spatial performance across the menstrual cycle, and that future studies of intra-individual variation are needed.

Progesterone levels during ovarian stimulation in segmented ART cycles inversely correlate with normalized birthweight of neonates conceived through subsequent frozen-thawed embryo transfer.

PURPOSE: To evaluate the association between serum progesterone (P) at the day of ovulation trigger and neonatal birthweight in singletons born after frozen-thawed embryo transfer in segmented ART cycles. METHODS: A retrospective multicenter cohort study involving data from patients who achieved uncomplicated pregnancy and term delivery of ART-conceived singleton babies following a segmented GnRH antagonist cycle. The main outcome was birthweight's z-score of the neonate. Univariate and multivariate linear logistic regression analyses were made to investigate the relation of z-score with variables inherent to the patient and to the ovarian stimulation. The variable P per oocyte was created by dividing the value of progesterone at ovulation trigger by the number of oocytes retrieved at oocyte retrieval. RESULTS: A total of 368 patients were included in the analysis. At univariate linear regression, the birthweight z-score of the neonate appeared to be inversely related to both P levels at the ovulation trigger (- 0.101, p = 0.015) and P levels per oocyte at trigger (- 1.417, p = 0.001), while it was directly related to the height of the mother (0.026, p = 0.002) and to the number of previous live births (0.291, p = 0.016). In multivariate analysis, both serum P (- 0.1; p = 0.015) and P per oocyte (- 1.347, p = 0.002) maintained the significant inverse association with birthweight z-score after adjusting for height and parity. CONCLUSIONS: Serum progesterone level on the day of ovulation trigger inversely correlates with normalized birthweight of neonates in segmented GnRH antagonist ART cycles.

Effect of serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte ratio on pregnancy and neonatal outcomes in women undergoing ICSI cycle.

BACKGROUND: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. METHODS: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. RESULTS: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. CONCLUSIONS: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle.

The diagnostic value of transvaginal color Doppler ultrasonography plus serum ß-HCG dynamic monitoring in intrauterine residue after medical abortion.

To probe the diagnostic value of transvaginal color Doppler ultrasonography plus serum ß-human chorionic gonadotropin (ß-HCG) dynamic monitoring in intrauterine residue after medical abortion.In total, 200 pregnant women undergoing medical abortion in our institution from January 2017 to December 2019 were picked, and assigned to either group A (n = 75, with residue) or group B (n = 125, without residue). We detected serum ß-HCG, progesterone (P), follicle stimulating estrogen (FSH) levels and ultrasonic indicators endometrial thickness (ET), peak systolic velocity (PSV), resistance index (RI) values, dissected correlation of indicators using logistic linear regression analysis, and prospected the diagnostic value of relevant indicators in intrauterine residue after medical abortion utilizingreceiver operating characteristic curve.At 7 days after abortion (T3), total vaginal bleeding and visual analogue scalescore in group A were saliently higher in contrast to group B ( P < .05). At 72 hours after abortion (T2) and T3, serum ß-HCG, P and FSH levels declined strikingly in both groups, but group B held plainly higher decrease rate than group A ( P HC.05). At T3, ET and PSV levels in both groups considerably waned, whereas RI levels notedly waxed, and group B owned markedly higher decrease/increase than group A ( P wa.05). At T3, serum ß-HCG in group A possessed positive association with serum P, FSH, intrauterine ET, PSV levels separately ( P HC.05), whereas negative link with RI levels ( P , .05). The specificity and sensitivity of ß-HCG, P, FSH, ß-HCG/ET, ß-HCG/PSV and ß-HCG/RI in the diagnosis of intrauterine residue after medical abortion were high ( P < .05).Serum ß-HCG dynamic monitoring plus transvaginal color Doppler ultrasonography is of great value in diagnosing intrauterine residue after medical abortion. Serum ß-HCG, P, FSH levels can be combined with the results of intrauterine ET, PSV, RI values, so as to boost the diagnostic accuracy of the intrauterine residue after medical abortion.

Characterizing Factors Influencing Baseline Plasma Biomarkers for Sport-Related Concussion in Adolescents.

Abstract Developing objective measures to diagnose sport-related concussion (SRC) is a top priority, particularly in the pediatric context, given the vulnerability of the developing brain. While advances in SRC blood biomarkers are being made in adult populations, less data are available for adolescents. Clinical validation of blood biomarkers post-SRC will first require investigation in a healthy uninjured state. Further, rapid pubertal changes during adolescence may implicate possible interactions with circulating sex hormones and the menstrual cycle for females. This cross-sectional study aimed to characterize pre-injury plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light (NF-L), ubiquitin C-terminal hydrolase-L1 (UCH-L1), total tau (T-tau), and phosphorylated tau-181 (P-tau-181), considering previous concussion, age, and sex in healthy adolescent sport participants. Possible associations with menstrual cycle phase and circulating sex hormone levels (i.e., progesterone, estradiol, testosterone) were also explored. Pre-injury blood samples were obtained from 149 healthy adolescents (48% female, ages 11-18) participating in a larger Surveillance in High Schools and Community Sports to Reduce Concussions and their Consequences (SHRed Concussions) multi-site longitudinal cohort study. Main outcomes were natural log (ln) transformed plasma GFAP, NF-L, UCH-L1, T-tau, and P-tau-181 concentrations, quantified on the Quanterix Simoa HD-X platform. Mixed-effects multi-variable linear regression was used to assess associations between biomarkers and self-reported previous concussion (yes/no), age (years), sex (male/female), objectively determined menstrual cycle phase (follicular/luteal), plasma progesterone, estradiol, and testosterone. Males had 19.8% lower UCH-L1 (ß = -0.221, 95% confidence interval [CI; -0.396, -0.046]), 18.9% lower GFAP (ß = -0.210, 95% CI [-0.352, -0.068]), and 21.8% higher P-tau-181 (ß = 0.197, 95% CI [0.048, 0.346]) compared with females, adjusting for age and previous concussion. GFAP decreased 9.5% with each 1-year increase in age, adjusting for previous concussion and sex (ß = -0.100, 95% CI [-0.152, -0.049]). No biomarkers were associated with a history of previous concussion. Exploratory investigations found no associations between biomarkers and menstrual cycle phase. Females displayed an age-adjusted negative association between T-tau and progesterone (ß = -0.010, 95% CI [-0.018, -0.002]), whereas males had a negative age-adjusted association between UCH-L1 and testosterone (ß = -0.020, 95% CI [-0.037, -0.002]). As such, age- and sex-specific reference intervals may be warranted for pediatric athlete populations prior to clinical validation of blood biomarkers for SRC. Additionally, hormonal associations highlight the need to consider puberty and development in adolescent studies. Overall, findings suggest these biomarkers are resilient to a history of previous concussion and menstrual cycle phase, supporting continued investigation in adolescent SRC.

Serum progesterone on the day of human chorionic gonadotropin (hCG) trigger as a predictor of in-vitro fertilization (IVF) outcome - a retrospective analysis of seven years.

OBJECTIVE: To investigate the relationship between progesterone (P4) levels on the day of hCG trigger and IVF outcomes. METHODS: This is a retrospective analysis of IVF cycles from January-2013 to December-2019 from a single center. Women (21-39 years) submitted to IVF treatment for various infertility factors were included, while donor oocyte cycles and cancelled cycles were excluded from the study. The primary outcome measure was live birth rate. RESULTS: A total of 2149 cycles were analyzed. Of these, 223 (10.38%) were in the low P4 group (<0.5 ng/ml), 1163 (54.12%) in the normal P4 group (0.5-1.5 ng/ml), and 763 (35.50%) in the high P4 group (>1.5ng/ml). The groups were comparable with respect to age, factor of infertility and baseline AMH. The antagonist protocol was significantly more prescribed to the high P4 group (p<0.001). Live birth rates were 14.4%, 21.6%, and 21% (p<0.001), respectively, in three groups. Univariate analysis found that total cetrotide dose, total number of retrieved and fertilized oocytes, total number of embryos formed, transferred, and vitrified, and P4 on the day of hCG (p<0.001) were statistically significant after adjusting for age and BMI. In multivariate logistic regression after adjusting for age and BMI, only high P4 (aOR:0.60; p<0.001), total cetrotide dose (aOR: 0.82; p<0.001), and total utilizable embryos (aOR:1.11; p=0.029) were statistically significant. CONCLUSIONS: Having an elevated serum progesterone level on the day of hCG trigger was associated with lower pregnancy rates, but this is still not a robust marker to predict live births. More good quality evidence is needed.

Elevated serum progesterone levels on the hCG trigger day have a negative impact on the live birth rate in the first fresh IVF-ET cycle.

To investigate whether there is a relationship between elevated serum progesterone (PROG) on the hCG trigger day and the live birth rate (LBR) in IVF/ICSI cycles, the retrospective analysis was carried out from the patients undergoing the first ART cycles throughout 2016. The PROG levels were measured on the hCG trigger day. The LBR, clinical pregnancy rate (CPR), implantation rate (IR) and other parameter rate values were compared among the three different PROG elevations. A total of 2550 IVF/ICSI cycles fulfilling all the inclusion and exclusion criteria were selected. Finally, three groups [PROG <0.40 ng/mL, 0.40 ≤ PROG < 1.5 ng/mL, PROG ≥ 1.5 ng/mL] were categorised based on the serum PROG levels. LBR, CPR and IR declined as the PROG value increased, while there was no difference in the embryo utilisation rates. Serum PROG levels on the day of hCG administration were negatively associated with the LBR, even in ETs with a good prognosis.Impact StatementWhat is already known on this subject? The clinical effects of PROG are still controversial. Some studies have confirmed that there was not too much association between premature elevation of PROG and live birth, some are still convincing that there is a negative correlation and will result in ART cycles of pregnancy and LBR reduction.What do the results of this study add? Our data substantiated that the high serum PROG level had the lowest LBR, IR and CPR, but the embryo utilisation rate may not have too much to do with the elevated PROG.What are the implications of these findings for clinical practice and/or further research? This study further strengthens the negative impact of elevated PROG levels on pregnancy outcomes, and suggests that frozen thawed embryo transfer appears to be a reasonable and advantageous approach for this subset of patients.

Effect of serum progesterone levels on hCG trigger day on pregnancy outcomes in GnRH antagonist cycles.

Objective: The present study analyzed the effect of hCG trigger day progesterone (P) levels on the live birth rate (LBR) in the gonadotropin-releasing hormone (GnRH) antagonist protocol. Materials and methods: This study was a single-center retrospective study. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles performed from January 2017 to December 2020 were included in the analysis. This study included people with a normal ovarian response to fresh embryo transfer of GnRH antagonist protocols. All cycles were divided into 2 groups by P level on the day of human chorionic gonadotropin (hCG) trigger, P<1.0 ng/ml and P≥1.0 ng/ml. The primary outcome measure was LBR. Result: A total of 867 cycles with P<1.0 ng/ml and 362 cycles with P≥1.0 ng/ml were included in the analysis. The clinical pregnancy rate (CPR) was higher in the P<1.0 ng/ml group than the P≥1.0 ng/ml group (44.9% vs. 37.6%, P=0.02). The early spontaneous abortion rate was comparable between the groups (14.4% vs. 14.7%, P=0.93). For live birth, the rate for the P<1.0 ng/ml group was 35.3%, which was significantly higher than the 29.0% in the P≥1.0 ng/ml group (P=0.03). After binary logistic regression analysis, the P level on the hCG trigger day (adjusted odds ratio=0.74, 95% CI=0.55-0.99, P=0.04) was an independent risk factor for LBR. For the P level on the hCG trigger day, the LBR was lower in the P≥1.0 ng/ml group compared to the P<1.0 ng/ml group. Conclusion: For normal ovarian response patients using the GnRH antagonist protocol, serum P≥1.0 ng/ml on the hCG trigger day resulted in a lower LBR than the P<1.0 ng/ml group. When P≥1.0 ng/ml, whole embryo freezing may be considered.

Letrozole Supplementation and the Increased Risk of Elevated Progesterone Levels on Trigger Day.

Although using letrozole (LE) during in vitro fertilisation and intracytoplasmic sperm injection (IVF/ICSI) has many advantages, it remains unclear whether LE induces an increase in progestogen during the late follicular phase. The objective of this study was to investigate whether progesterone levels increased under antagonist protocols supplemented with LE on the trigger day using a retrospective cohort study. The study included 1,133 women who underwent IVF/ICSI cycles from January 2018 to June 2020. After propensity score matching (PSM) for baseline characteristics, 266 patients with gonadotropin-releasing hormone-antagonist (GnRH-ant) were matched to 266 patients with letrozole + GnRH-ant (LE GnRH-ant) (PSM 1 cohort), and 283 patients with gonadotropin-releasing hormone-agonist (GnRH-a) were matched to 283 patients with LE GnRH-ant (PSM 2 cohort). In the PSM 1 cohort, patients in the LE GnRH-a group presented higher progesterone levels (1.22 ± 0.95 ng/mL vs 0.86 ± 0.60 ng/mL, P < 0.001), with a higher proportion of patients with progesterone level > 1.5 ng/mL (24.81% vs 7.52%, P < 0.001). In PSM 2 cohort, patients in the LE GnRH-a group presented higher progesterone levels on trigger day (1.23 ± 0.91 ng/mL vs 0.98 ± 0.61 ng/mL, P < 0.001), with a higher proportion of patients with progesterone level > 1.5 ng/mL (25.45% vs 12.70%, P < 0.001). In the PSM 1 cohort, progesterone levels on the trigger day increased by 0.05 ng/mL, with an increase in every retrieved oocyte in the LE GnRH-ant group (ß 0.05 ng/mL [95% CI 0.04, 0.06], P < 0.001), whereas an increase of 0.02 ng/mL was observed in the GnRH-ant group (ß 0.02 ng/mL [95% CI 0.01, 0.03], P < 0.001), with P for interaction being 0.0018. In the PSM 2 cohort, progesterone levels on the trigger day increased by 0.05 ng/mL with an increase in every retrieved oocyte in the LE GnRH-ant group (ß 0.05 ng/mL [95% CI 0.04, 0.06], P < 0.001), whereas an increase of 0.02 ng/mL was observed in the GnRH-a group (ß 0.02 ng/mL [95% CI 0.01, 0.03], P < 0.001), with P for interaction being 0.0002. LE supplementation on the antagonist protocols may increase progesterone levels in the late follicular stage.

Serum vascular endothelial growth factor as a marker for tubal pregnancy.

OBJECTIVE: The objective of this study was to evaluate whether a single measurement of vascular endothelial growth factor could distinguish between intrauterine pregnancy and ectopic pregnancy and to correlate the levels of vascular endothelial growth factor with serum levels of progesterone andß-human chorionic gonadotropin in each subgroup. METHODS: Ninety patients with a positive human chorionic gonadotropin test and either abdominal pain or vaginal bleeding were selected; pregnancies were singletons, spontaneously conceived, 42-56 days of gestational age. All patients had a transvaginal ultrasound examination and were divided into three subgroups: abnormal intrauterine pregnancy, tubal pregnancy, and normal intrauterine pregnancy. Tubal pregnancies were surgically treated and histologically confirmed. Blood samples were collected for the determination of ß-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor and their concentrations were compared in each subgroup. Receiver operating characteristic curve was calculated by comparing the subgroup of tubal pregnancy to the other groups. A Fisher discriminant function analysis was performed. The level of significance was 5%. RESULTS: One-way analysis of variance revealed a significant correlation between the different subgroups and ß-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor serum levels (p<0.001). Vascular endothelial growth factor concentration was significantly higher for patients with tubal pregnancy than for other subgroups (p<0.05). ß-Human chorionic gonadotropin and progesterone levels were higher in the subgroup with normal intrauterine pregnancies compared with the subgroups with tubal and abnormal intrauterine pregnancies (p<0.05). Serum vascular endothelial growth factor level >188.7 ng/mL predicted tubal pregnancy with 96.7% sensitivity, 95.0% specificity, 90.6% positive predictive value, and 98.3% negative predictive value. CONCLUSIONS: Serum vascular endothelial growth factor could be a marker in discriminating intrauterine pregnancy from tubal pregnancy; its levels are increased in women with ectopic pregnancy compared with women with normal and abnormal intrauterine pregnancies.

Impact of blood levels of progesterone on the day of ovulation onset on clinical, laboratory and reproductive parameters of young patients undergoing assisted reproduction: a cross-sectional study.

OBJECTIVE: To assess whether there is an association between the level of progesterone on the day of administration of human chorionic gonadotropin and clinical and laboratory characteristics, in addition to the results of in vitro fertilization of patients with a good prognosis. METHODS: A cross-sectional study comprising 103 women who underwent intracytoplasmic sperm injection treatment, between November 2009 and May 2015, aged ≤35 years, with no comorbidities, with fresh embryo transfer. Data were collected from patient medical records. RESULTS: There was a weak positive correlation between the level of progesterone on the day of human chorionic gonadotropin and the number of follicles larger than 14mm (ß=0.02, p=0.001), retrieved oocytes (ß=0.01, p=0.01) and oocytes in metaphase II (MII) (ß=0.02, p=0.02); that is, the increase in progesterone level has a slight association with increased values of these variables. Body mass index was inversely correlated with progesterone level on the day of human chorionic gonadotropin (ß=-0.01, p=0.02). No association was found between the level of progesterone on the day of human chorionic gonadotropin and the protocols used for controlled ovarian stimulation, quality of transferred embryos and the pregnancy rate. CONCLUSION: There is an association between the value of progesterone on the day of human chorionic gonadotropin administration with body mass index, number of follicles larger than 14mm, number of retrieved oocytes and oocytes in metaphase II. Unlike embryo quality and pregnancy rate, which do not have a statistically significant relation with this value in the population studied.

Preliminary results of blood growth differentiation factor-9 (GDF-9) measurement in cats: future aspects of GDF-9 on stage of the cycle and spaying history.

Growth differentiation factor-9 (GDF-9), an oocyte-derived member of the TGF-ß superfamily, plays an essential role in regulation of follicular development. This study aimed to determine the cyclic changes in serum GDF-9 concentration, compare its levels before and after ovariohysterectomy (OHE), and investigate its potential as a tool in ovarian remnant syndrome (ORS) diagnosis in cats. GDF-9 measurements were performed on 50 cats referred for routine OHE. The stage of the estrous cycle was determined by vaginal cytology and measurement of serum estradiol and progesterone levels was carried out to detect the cyclic changes in circulating GDF-9. One week after OHE, serum samples were collected again from 30 cats to reveal differences in GDF-9 levels. GDF-9 levels in the follicular phase were significantly higher than those in the interestrus (p⟨0.05). The postoperative analysis could be performed. GDF-9 levels slightly decreased one week after OHE (p=0.053). In conclusion, blood GDF-9 levels change during the estrous cycle, and may decrease with age in cats. However, further studies are needed to reveal the efficiency of GDF-9 in ORS diagnosis.

Correlation of LH level and steroid concentrations in GnRH antagonist protocol: A sub-analysis of Ganirelix phase III study of China.

BACKGROUND: Based on the data obtained from a phase III, multicenter, open-label, randomized clinical trial that compared the use of GnRH agonist vs. antagonist for LH-suppression in IVF cycles, the present study attempted to determine the effect of LH level on steroid concentrations and IVF outcomes in the GnRH antagonist protocol. METHODS: A total of 109 patients with the GnRH antagonist protocol were stratified into three subgroups according to the stimulation day six LH levels (LH <25%, 25-75%, and >75%), and the effect of LH on steroid biosynthesis and the related IVF outcomes between subgroups was observed. RESULTS: In comparing the three subgroups of GnRH antagonist, no difference in number of oocytes, top quality embryos and ongoing pregnancy was observed. The high LH group on day six was exposed to significantly lower concentrations of rFSH from day six onwards, and had significantly higher estradiol levels on the day of hCG. The progesterone levels did not differ between groups at the start of the stimulation, but patients with the highest LH on day six also had significantly (P < 0.0001) higher progesterone levels on day six (higher estradiol on day six and hCG, lower total rFSH dosage). Due to the significantly lower increase in progesterone in the high LH group between day six and the day of hCG, no difference in progesterone level was observed on the day of hCG. CONCLUSIONS: For steroid biosynthesis, early follicular phase LH levels help pregnenolone metabolize primarily via the ∆5 pathway in the GnRH antagonist stimulation protocol, but not via the ∆4 pathway.

Effect of slightly elevated progesterone on hCG trigger day on clinical pregnancy rate in GnRH-ant IVF/ICSI cycles.

BACKGROUND: It was been agreed that significantly elevated progesterone level on the hCG trigger day have detrimental effect on clinical outcomes in IVF/ICSI cycles. However, few studies explored whether slightly elevated progesterone level also same impact on clinical outcomes. METHODS: We retrospectively studies the effect of slightly elevated progesterone level on outcomes of IVF/ICSI in GnRH-ant cycles. Propensity score matching was used to confounding variables. The women were divided into two groups according to the progesterone level: Group 1: < 1.0 ng/ml; Group 2: 1.0 ng/ml-1.5 ng/ml. Then compare the clinical pregnancy rate (CPR) between the two groups. RESULT: A total of 847 IVF/ICSI cycles were included in the present study. The average CPR per transfer cycle was 51.7%. CPR of group 1 was 55.22%, significantly higher than that of group 2 (40.66%, P = 0.013). Progesterone level on the day of hCG injection was further evaluated at threshold increments of 0.1 ng/ml, and the CPR was decreased dramatically once the progesterone level higher than 1.4 ng/ml. CONCLUSION: The slight elevation progesterone level on the hCG trigger day may have a negative effect on the clinical pregnancy in GnRH-ant cycles. In the case of progesterone > 1.4 ng/ml on the hCG injection day, freeze-all strategy was recommended. The present retrospective study aimed to evaluate the effect of slightly elevated progesterone (1.0 ng/ml ~ 1.5 ng/ml) on outcomes of IVF/ICSI in GnRH-ant cycles. Slightly elevated progesterone level leaded to significant lower clinical pregnancy rate (CPR) that that of group with normal progesterone level (40.66% vs. 55.22%, P = 0.013). The CPR was decreased dramatically once the progesterone level higher than 1.4 ng/ml. So slightly elevated progesterone level on the trigger day may have a negative effect on the clinical pregnancy in GnRH-ant cycles. In the case of progesterone > 1.4 ng/ml on the hCG injection day, freeze-all strategy was recommended.

Changes of Mental State and Serum Prolactin Levels in Patients with Schizophrenia and Depression after Receiving the Combination Therapy of Amisulpride and Chloroprothixol Tablets.

OBJECTIVE: To investigate the changes in mental state and serum prolactin levels in patients with schizophrenia and depression after receiving the combination therapy of amisulpride and chloroprothixol tablets. METHODS: A total of 148 schizophrenic patients with depression were randomly divided into control group (N = 73) and study group (N = 75). The control group was treated with clopidothiol, and the study group was treated with amisulpride. Symptom scores, sleep quality, adverse reactions, therapeutic effects, prolactin, and progesterone levels, HAMD, PANSS, and PSP scores were compared between the two groups. RESULTS: The symptom scores of both groups were significantly reduced, but when compared to the control group, the symptom scores of the research group were significantly reduced more significantly (P < 0.05); serum GDNF levels of both groups were significantly increased, while serum NSE, IL-1, and MBP levels were significantly reduced (P < 0.05). However, the research group altered more substantially (P < 0.05) than the control group; the overall PSQI score of the research group was lower (P < 0.05) than the control group; and the incidence of adverse responses in the control and study groups was 12.3 percent and 4.0 percent. The research group had a lower rate of adverse responses (P < 0.05) than the control group, and the effective treatment of the control and research groups was 82.2 percent and 98.7%, respectively. The research group had a lower rate of adverse reactions (P < 0.05) than the control group, while the control and research groups' successful treatment rates were 82.2 percent and 98.7%, respectively. When compared to the control group, the research group had a greater treatment efficiency (P < 0.05); blood prolactin and progesterone levels were considerably lowered in both groups, but the reductions in the research group were more evident (P < 0.05). Both groups had considerably lower HAMD and PANSS scores, and both had significantly higher PSP scores, although the difference in the research group was more evident (P < 0.05). CONCLUSION: For people with schizophrenia and depression, a combination of amisulpride and chloroprothixol pills has a considerable effect. It can help patients with their clinical symptoms and sleep quality while also lowering their serum prolactin levels, which is favorable to their illness recovery. As a result, the combined treatment of amisulpride and chloroprothixol pills deserves to be promoted and used.

Chronic Estrus Disrupts Uterine Gland Development and Homeostasis.

Female mice homozygous for an engineered Gnrhr E90K mutation have reduced gonadotropin-releasing hormone signaling, leading to infertility. Their ovaries have numerous antral follicles but no corpora lutea, indicating a block to ovulation. These mutants have high levels of circulating estradiol and low progesterone, indicating a state of persistent estrus. This mouse model provided a unique opportunity to examine the lack of cyclic levels of ovarian hormones on uterine gland biology. Although uterine gland development appeared similar to controls during prepubertal development, it was compromised during adolescence in the mutants. By age 20 weeks, uterine gland development was comparable to controls, but pathologies, including cribriform glandular structures, were observed. Induction of ovulations by periodic human chorionic gonadotropin treatment did not rescue postpubertal uterine gland development. Interestingly, progesterone receptor knockout mice, which lack progesterone signaling, also have defects in postpubertal uterine gland development. However, progesterone treatment did not rescue postpubertal uterine gland development. These studies indicate that chronically elevated levels of estradiol with low progesterone and therefore an absence of cyclic ovarian hormone secretion disrupts postpubertal uterine gland development and homeostasis.

The Influence of Intravaginal Gestagens Treatment on the Morphological Features and Endometrial Steroid Hormone Receptors Content during Anestrus Type II in Dairy Cattle.

BACKGROUND: Gestagens are the most widely used therapy in anestrus type II. The aim of this research is to evaluate the effectiveness of the vaginal progesterone inserts therapy in anestrus type II in cows. METHODS: The study was conducted on 33 cows. Progesterone (PR) and estrogen (ER) receptors expression in endometrium was assessed on a molecular level based on mRNA tissue expression. Additionally, blood 17ß-estradiol and progesterone levels were evaluated. RESULTS: A decrease in mRNA expression of A and B PR and ER α was noted in treated and untreated animals. In the treated group, an increase of ERß mRNA expression was observed, while a decreased was found in untreated animals. There was increased PR, ERα and ß expression in endometrial tissue in treated cows, and decreased expression of these factors in untreated cows. In the treated group, recurrence of ovarian cyclicity was noted in 52% of animals and pregnancy was obtained in 34.8% of them, while in the untreated group, recurrence did not occur. In the control group, spontaneous recurrence of ovarian cyclicity was not observed. An increase of PR expression was correlated with increased proliferation of endometrial cells. CONCLUSIONS: It seems likely that the endometrium is well developed and ready for placentation after removing the exogenous source of progesterone and preventing the recurrence of cyclicity of ovaries.