Day Of Human Chorionic Gonadotropin Research Articles

Effect of follicle size on pregnancy outcomes in patients undergoing first letrozole-intrauterine insemination.

Letrozole has been proven to be an effective method for inducing ovulation. However, littleattentionhasbeenpaidto whether the lead follicle size will affect the success rate of intrauterine insemination (IUI) with ovulation induction with alone letrozole. Therefore, we hope to investigate the effect of dominant follicle size on pregnancy outcomes on human chorionic gonadotropin (hCG) day of the first letrozole-IUI. A retrospective cohort study design was employed. We included patients with anovulation or unexplained infertility undergoing first IUI treatment with letrozole for ovarian stimulation. According to the dominantfolliclesize measured on the day of hCG trigger, patients were divided into six groups (≤ 18mm, 18.1-19.0mm, 19.1-20.0mm, 20.1-21.0mm, 21.1-22.0mm, > 22mm). Logistic models were used for estimating the odds ratios (ORs) with their 95% confidence interval (CIs) for achieving aclinicalpregnancyor alivebirth. A restricted cubic spline was drawn to explore the nonlinear relationship between follicle size and IUI outcomes. A total of 763 patients underwent first letrozole-IUI cycles in our study. Fisherexact test showed significant differences among the six follicle-size groups in the rates of pregnancy, clinical pregnancy and live birth (P < 0.05 in each group). After adjusting the potential confounding factors, compared with the follicles ≤ 18mm in diameter group, 19.1-20.0mm, 20.1-21.0mm groups were 2.3 or 2.56 times more likely to get live birth [adjusted OR = 2.34, 95%CI (1.25-4.39); adjusted OR = 2.56, 95% CI (1.30-5.06)]. A restricted cubic spline showed an invertedU-shaped relationship between the size of dominant follicles and pregnancy rate, clinical pregnancy rate, and live birth rate, and the optimal follicle size range on the day of hCG trigger was 19.1-21.0mm. When the E2 level on the day of hCG trigger was low than 200pg/mL, the clinical pregnancy rates of 19.1-20.0mm, 20.1-21.0mm groups were still the highest. The optimal dominant follicle size was between 19.1 and 21.0mm in hCG-triggered letrozole-IUI cycles. Either too large or too small follicles may lead to a decrease in pregnancy rate. Using follicle size as a predicator of pregnancy outcomes is more meaningful when estrogen on the day of hCG trigger is less than 200pg/ml.

Association between Myometrial Thickness and Assisted Reproductive Technologies Outcomes: A Prospective Cohort Study.

Myometrial thickness has been expected to be a prognosticator for lower uterine segment function. An abnormal function of the uterine muscle layer can cause common and important reproductive problems. This study aimed to evaluate the relationship between baseline myometrial thickness and assisted reproductive technologies (ART) outcomes. In this prospective cohort study, 453 infertile women undergoing ART cycles without any obvious uterine pathology, participated in this prospective cohort study from February 2013 to May 2015. In order to measure the myometrial thickness in the anterior and posterior of the uterine, trans-vaginal ultrasounds were conducted on days 2-4 of the cycle (menstrual phase) preceding ovarian stimulation and the day of human chorionic gonadotropin (hCG) injection. We defined three groups based on the baseline myometrial thickness in the anterior and posterior, including (A) <25 mm, (B) 25-29.9 mm and (C) ≥30 mm. Ovarian stimulation, oocyte retrieval and luteal phase support were performed in accordance with the standard long protocol. Two weeks after embryo transfer, the patients underwent a pregnancy test by checking their serum β-hCG levels. The primary outcome measure was clinical pregnancy rate. Secondary outcome measures were, implantation rate, abortion rate and live birth rate. The clinical pregnancy (P=0.013) and implantation (P=0.003) rates were significantly lower in group A than in two other groups. Although the live birth rate was lower in group A than two other groups, this decrease was not statistically significant (P=0.058). The findings may be a way for clinicians to draw focus on providing therapeutic strategies and a specific supportive care for women with a baseline myometrial thickness <25 mm in order to improve the reproductive outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI).

Efficacy of Dan'e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the "Triple Prevention" Principle.

This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.

The association between systemic immune-inflammation index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study

BackgroundAs a novel prognostic and inflammatory marker, the systemic immune-inflammation index (SII) has come to the foreground in recent years. SII may be used as an indicator reflecting the progressive inflammatory process in patients with polycystic ovary syndrome (PCOS). This study aimed to evaluate the correlation between SII and assisted reproductive outcomes in PCOS patients.ResultsA total of 966 women undergoing in vitro fertilization (IVF) procedure with PCOS were included in the study. The SII was calculated as platelet count (/L) × neutrophil count (/L)/lymphocyte count (/L). Participants were divided into four groups according to SII quartiles calculated at baseline, and the differences of clinical and laboratory outcomes between these four groups were compared. Moreover, a univariate linear regression model was used to evaluate the associations between SII and the outcomes. Patients in the highest SII quartile (Q4) had lower antral follicle count (AFC), estradiol (E2), and progesterone (P) levels on the day of human chorionic gonadotropin (HCG) start compared with the lower three SII quartiles (Q1-Q3). Moreover, our analysis demonstrated that women in the lower SII quartiles had a higher rate of available embryos and blastocyst formation compared with those in the highest SII quartile. Logarithm of SII correlated negatively with available embryo rate, but not with number of available embryos. Additionally, the results of our multivariate logistic regression analyses indicated that the highest SII quartile was negatively associated with biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), live birth rate (LBR), and implantation rate (IR). A non-linear relationship between the SII and number of available embryos, with a negative relationship seen to the right of the inflection point was also found.ConclusionsThe interplay among thrombocytosis, inflammation, and immunity could influence assisted reproductive outcomes in PCOS patients. In this regard, SII may serve as a valuable marker for exploring potential correlations.

#40 : Correlation Between Pre-Trigger Estradiol Levels and the Number of Mature Oocytes in Patients Who Underwent In Vitro Fertilization

Background and Aims: Strong association between pre-trigger estradiol levels on the day of human Chorionic Gonadotropin (hCG) administration and the number of mature oocytes retrieved was widely reported. Consequently, higher estradiol levels measured might give a prediction of the higher number of mature oocytes retrieved on Ovum Pick Up (OPU) procedure. This study was done to investigate the correlation between pre-trigger estradiol levels and number of mature oocytes retrieved in patients who underwent In Vitro Fertilization (IVF) cycles in Indonesian population. Method: A cross sectional study was done at Mbrio IVF Clinic, Mitra Keluarga Hospital Kelapa Gading, Jakarta, Indonesia. Data was collected from the medical records of 77 patients who underwent IVF cycles between September 2021 and March 2023. The level of estradiol on the hCG administration day and the number of mature oocytes retrieved were analysed to find any correlation between both variables using the Spearman Test. Results: There were 77 women who underwent IVF procedures with the age range between 27 and 45-year-old (mean 35,5 ± 4,52). Most of them (83%) had primary infertility and had infertility between 1 to 14 years (mean 5,5 ± 3,48). These subjects came to the clinic mostly due to both male and female factors (49,4%), followed by male factor only (27,3%). E2 on hCG day ranged between 194 to 13.000 pg/ml with the median 2.709 pg/ml, and the mature oocytes retrieved ranged between 0 and 31 with a median of 8 oocytes. A statistically significant correlation (r = 0.827; p&lt;0.01) was found between the estradiol level and mature oocytes retrieved. Conclusion: Pre-trigger Estradiol level can be used as a predictor for the number of mature oocytes retrieved in IVF cycle as these two variables are strongly correlated to each other. A multi-centre study with larger sample size is needed to validate current data.

Effect of Elevated Progesterone Levels on hCG Trigger Day on Clinical Pregnancy Outcome in Short-Acting GnRHa Downregulated Cycles.

Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear. We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis. The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day. In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.

The Impact of Growth Hormone Co-Treatment Duration on Outcomes in IVF/ICSI Cycles Among Poor Ovarian Responders.

The efficiency of in vitro fertilization is improved by growth hormone (GH) during ovarian stimulation. Additionally, patients with diabetes experience impaired insulin resistance and compromised glucose tolerance, which further exacerbate their condition. Due to these side effects, in this study, the duration of GH treatment was compared in IVF/ICSI cycles among poor ovarian responders. In this study, POSEIDON criteria were used to choose patients. Subcutaneous administration of gonadotropin-releasing hormone (GnRH) antagonist was done beginning on the sixth day of the cycle and continuing through the day of human chorionic gonadotropin (hCG) injection. In one group, GH was administered 4 units/day from the 2nd day of the cycle until hCG injection, and in another group, the first dose was administered on the 6th day of the cycle. Following the administration of hCG, which lasted from 24 to 36 hr, oocytes were retrieved with the support of B-mode sonography. In our analysis, no significant differences were observed between the two groups in terms of the number of retrieved oocytes, metaphase II oocytes, and quality of grade A and B embryos. The results show that the treatment or conditions did not have a significant impact on the outcomes among the studied groups. Our findings indicate that a shorter duration of GH administration can yield similar outcomes compared to a longer duration in IVF/ICSI cycles involving poor ovarian responders. This result holds the potential for a more cost-effective and patient-friendly approach in managing assisted reproductive technology procedures. It may lead to reduced side effects and improved adherence to medication regimens in patients.

Pregnancy outcome in long- versus short-acting gonadotropin-releasing hormone agonist cycles in participants with normal ovarian reserve: An RCT.

There is no agreement on which of the 2 gonadotropin-releasing hormone (GnRH) agonist protocols are the most efficient, neither there is any consensus on which one yields a better clinical pregnancy percentage. The present study aims to compare the effectiveness of reduced dosages of long- and short-acting GnRH agonists on pregnancy outcomes. In this randomized controlled clinical trial, 400 women were randomly assigned to 2 groups (n = 200/group): the reduced dosage of long-acting GnRH agonist group (group 1, 1.25 mg Decapeptyl) and the short-acting GnRH agonist group (group 2, 0.5 mg/day Buserelin Acetate). The study was conducted at Mehr Medical Institute, Rasht, Iran between July 2019 and July 2020. Biochemical and clinical pregnancy were compared between groups. No significant differences were observed in the endometrial lining, the total number of retrieved and metaphase-II oocytes, progesterone, and serum estradiol levels on human chorionic gonadotropin day, fertilization rate, and top-quality embryos between the groups. The duration of induction (10.8 1.7 vs. 10 2.1, p 0.001) and the total dosage of gonadotropins (2939.4 945.9 vs. 2441 1247.1, p 0.001) were significantly greater in group 2 than in group 1. No significant differences were observed between the 2 groups in terms of implantation rate, chemical pregnancy rate, and clinical pregnancy rate. A higher percentage of ovarian hyperstimulation syndrome was observed in group 2 (p = 0.005). Due to a lower percentage of ovarian hyperstimulation syndrome in group 1 and similar assisted reproductive technology outcomes in both groups, the long protocol was found to be superior to the short protocol.

Novel predictors for livebirth delivery rate in patients with idiopathic non-obstructive azoospermia based on the clinical prediction model.

To build a prediction model for live birth delivery per intracytoplasmic sperm injection (ICSI) in iNOA patients by obtaining sperm by microdissection testicular sperm extraction (mTESE). A retrospective cohort study of 377 couples with iNOA male partners treated with 519 mTESE-ICSI cycles was conducted from September 2013 to July 2021 at the Reproductive Medical Centre of Peking University Third Hospital. Following exclusions, 377 couples with iNOA male partners treated with 482 mTESE-ICSIs were included. A prediction model for live birth delivery per ICSI cycle was built by multivariable logistic regression and selected by 10-fold cross-validation. Discrimination was evaluated by c-statistics and calibration was evaluated by the calibration slope. The live birth delivery rate per mTESE-ICSI cycle was 39.21% (189/482) in these couples. The model identified that the presence of motile sperm during mTESE, bigger testes, higher endometrial thickness on the day of human chorionic gonadotrophin (hCG) administration (ET-hCG), and higher quality embryos are associated with higher live birth delivery success rates. The results of the model were exported based on 10-fold cross-validation. In addition, the area under the mean ROC curve was 0.71 ± 0.05 after 10-fold cross-validation, indicating that the prediction model had certain prediction precision. A calibration plot with an estimated intercept of -1.653 (95% CI: -13.403 to 10.096) and a slope of 1.043 (95% CI: 0.777 to 1.308) indicated that the model was well-calibrated. Our prediction model will provide valuable information about the chances of live birth delivery in couples with iNOA male partners who have a plan for mTESE-ICSI treatment. Therefore, it can improve and personalize counseling for the medical treatment of these patients.

Elevated estradiol levels on hCG trigger day adversely effects on the clinical pregnancy rates of blastocyst embryo transfer but not cleavage-stage embryo transfer in fresh cycles: a retrospective cohort study.

Elevated estradiol (E2) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E2 at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles. This study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E2 levels when hCG was administered: set 1 (E2 ≤ 2,000 pg/ml), set 2 (E2 = 2,001-3,000 pg/ml), set 3 (E2 = 3,001-4,000 pg/ml), and set 4 (E2 > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses. The multivariate regression model in the cleavage group showed that patients' CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P=0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P=0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E2 levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E2 (adjusted OR = 0.83, 95% CI [0.72-0.96], P=0.012). Elevated E2 levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET.

Factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection in older women.

To analyse the factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in older women, and to establish a risk prediction model. A total of 425 patients receiving IVF/ICSI from March 2018 to March 2020 were divided into pregnancy group (n=194) and non-pregnancy group (n=231). The factors affecting the outcomes of IVF/ICSI were explored by univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed. The two groups had significantly different age, body mass index, dysmenorrhea, parity, times of full-term births, history of cesarean section, basal follicle stimulating hormone, basal antral follicle count (AFC), number of high-quality embryos, and basal estradiol, luteinizing hormone and endometrial thickness on the day of human chorionic gonadotropin (HCG) administration (P<0.05). Age ≥40 years old, dysmenorrhea, history of cesarean section, basal AFC<9, number of high-quality embryos <4, and endometrial thickness on the day of HCG administration <11 mm led to IVF/ICSI failure. The established model exhibited high calibration and discrimination degrees in predicting the outcome of IVF/ICSI. The risk prediction model for the pregnancy outcome of IVF/ICSI in older women helps evaluate the fertility probability and risk, providing references for formulating reasonable assisted reproduction plans.

Guideline No. 315: Prevention of Ovarian Hyperstimulation Syndrome

Summary Statements1.The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I)2.Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III)3.Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2)4.The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I)5.There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III)6.Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2)7.Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2)8.Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations1.The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)2.Gonadotropin dosing should be carefully individualized, taking into account the patient’s age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B)3.Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C)4.Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B)5.A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C)6.Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E)7.Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C)8.Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A)9.Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B)

P-497 High-concentration of E2 post-controlled ovarian hyperstimulation promotes cervical extracellular matrix degradation by up-regulating UBA52

Abstract Study question To explore the effect of high concentration of E2 after controlled ovarian hyperstimulation (COH) on the extracellular matrix of cervical tissue in the second trimester. Summary answer The high concentration of E2 after COH promotes cervical ECM degradation leading to cervical insufficiency of pregnancy in ART by up-regulating UBA52. What is known already Assisted reproductive technology (ART) is a double-edged sword. While effectively solving infertility, ART also associated with many obstetric complications like preterm birth, although, the reason is currently unclear. Cervical insufficiency (CI) caused by degradation of extracellular matrix (ECM) is one of the most important causes of preterm birth. All patients undergoing ART need to receive controlled ovarian hyperstimulation (COH), leading to a sharp rise of the serum level of E2, which has a significant impact on the blood system, liver and kidney, but the effect on the cervix is unclear. Study design, size, duration 1.Retrospectively analyzed the clinical data of our center to compare the incidence of cervical insufficiency between ART singleton pregnancy and natural singleton pregnancy. 2. Establishing a post-COH pregnancy mice model, to analyze how the concentration of E2 affect the cervical ECM. Participants/materials, setting, methods The incidence of CI and the serum level of E2 on the day of human chorionic gonadotropin (HCG) in ART singleton pregnancies and natural singleton pregnancies was compared. The pregnant mice models after COH were established to detect the serum level of E2 and to investigate the structure of the cervical ECM. We detected the overall expression level of collagen and selected the mark gene using RNA-seq. Relevant biological experiments were used for verification 14/5000 Main results and the role of chance The incidence of CI in ART singleton pregnancies was significantly higher than that in natural singleton pregnancies (7.80% vs. 3.54%, p&amp;lt;0.0001) and so was the serum level of E2 in patients with CI during pregnancy than those without (3333 ± 1116.61 pg/ml, n = 40 vs. 2437 ± 1072.2 pg/ml, n = 9, p=0.034). Furthermore, the serum level of E2 was markedly higher in the COH pregnant mice models (175.68 ± 38.72 pg/ml, n = 10 vs. 235.43 ± 67.24 pg/ml, n = 11, p=0.024) and the expression of collagen was reduced significantly, and DEGs related to ECM organization pathway was significantly enriched. Our results indicated that matrix metalloproteinases (MMPs) should not be responsible for the collagen degradation in ECM of cervix. Interestingly, the ubiquitination level of type I collagen increased compared with the control group both in vitro and in vivo experiments. UBA52, a component of the ubiquitin-encoding gene, has been shown to strongly upregulated among these ubiquitination related genes (URGs), and its expression was demonstrated to be E2 concentration dependent. Also, an estrogen response element (ERE) was detected in UBA52 promoter region, and direct binding of ER to ERE was validated, implying that UBA52 might be a key regulator for collagen degradation. Limitations, reasons for caution Firstly, the findings of clinical data were still inevitably subject to retrospective study limitations. Secondly, we found that UBA52 may be the target gene that causes the increased ubiquitination of type I collagen in mouse cervical tissue after COH, but the deeper related mechanism was still unclear. Wider implications of the findings Our research provides evidence that a high concentration of E2 after COH is harmful to cervical function leading to cervical insufficiency, which further underlines the importance of providing special care to women who use ART for pregnancy. Trial registration number not applicable

Elevated follicular cortisone level is a negative predictor of clinical pregnancy in women undergoing fresh embryo transfer

BackgroundAlthough numerous studies have investigated the potential correlation between follicular fluid (FF) steroid concentrations and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes, few have accounted for the effect of controlled ovarian hyperstimulation regimes on FF steroid concentrations. ObjectiveTo comprehensively compare follicular steroid concentrations between women stimulated with gonadotropin-releasing hormone agonist (GnRHa) and antagonist (GnRHant) protocols and to explore the associations between FF steroid concentrations and IVF/ICSI outcomes. MethodsA total of 295 infertile women undergoing IVF/ICSI from January 2018 to May 2020 were enrolled. Eighty-four and 211 women received GnRHa and GnRHant protocols, respectively. Seventeen steroids in FF were quantified by liquid chromatography tandem mass spectrometry (LC–MS/MS), and the correlation of follicular steroids with clinical pregnancy was explored. ResultsFollicular steroid concentrations were similar between the GnRHa and GnRHant groups. Follicular cortisone levels were adversely associated with clinical pregnancy in fresh embryo transfers. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.639 (95% confidence interval = 0.527–0.751, p = 0.025) for predicting non-pregnancy, with an optimal cutoff value of 15.81 ng/mL (sensitivity = 33.3%, specificity = 94.1%). Women with FF cortisone concentrations ≥15.81 ng/mL were fifty times less likely to achieve clinical pregnancy in fresh embryo transfers than those with FF cortisone levels below this threshold (adjusted OR = 0.019, 95% confidence interval = 0.002–0.207, p = 0.001) after adjusting for age, body mass index, baseline serum progesterone levels, serum levels of luteinizing hormone, estradiol and progesterone on human chorionic gonadotropin day, ovarian stimulation protocols, and the number of transferred embryos. ConclusionsThere was no significant difference in intrafollicular steroid levels between GnRHa and GnRHant protocols, and intrafollicular cortisone level ≥15.81 ng/mL was found to be a strong negative predictor of clinical pregnancy in fresh embryo transfers with high specificity.

Women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) might benefit from maintaining serum luteinizing hormone levels: A retrospective analysis.

We aimed to evaluate the effect of serum luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) injection day (LHHCG) on outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) patients. It is a retrospective cohort study involving 620 women who had an IVF cycle in Taizhou Hospital Affiliated to Wenzhou Medical University between 2018-2020. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups. The numbers of follicles (≥ 14 mm) on HCG day, retrieved oocytes, mature oocytes, and two pronuclei (2PN) embryos in women with LHHCG < 2 IU/L were more than those with LHHCG ≥ 2 IU/L. Women with LHHCG < 2 IU/L had lower high-quality embryo rate (42.2% vs. 46.5%, p = 0.002) and implantation rate (40.0% vs. 58.8%, p = 0.044) compared to those with LHHCG ≥ 2 IU/L. When LHHCG < 2 IU/L, there was no significant difference in implantation rates in patients < 35 years compared to those ≥ 35 years. When LHHCG ≥ 2 IU/L, patients < 35 years old had higher implantation rates (71.7% vs. 41.2%, p < 0.001) compared to those ≥ 35 years old. The success rates of IVF fertilization and ICSI fertilization and biochemical and clinical pregnancy rates were not significantly different between groups. Our results demonstrated that women undergoing IVF/ICSI-ET might benefit from maintaining LHHCG levels at ≥ 2 IU/L. In addition, age might associate with LHHCG levels and be a better determining factor of the transfer outcome than serum LHHCG levels for IVF/ICSI-ET.

Application value of tumor necrosis factor inhibitors in in vitro fertilization-embryo transfer in infertile women with polycystic ovary syndrome

BackgroundClinical value of tumor necrosis factor (TNF) inhibitors in in vitro fertilization-embryo transfer (IVF-ET) in infertile women with polycystic ovary syndrome (PCOS) was investigated in this study.MethodsA retrospective analysis was performed on the clinical data of 100 PCOS patients who received IVF-ET for the first time at Hebei Institute of reproductive health science and technology from January 2010 to June 2020. The patients were divided into Inhibitor group and Control group according to whether they were treated with or without TNF inhibitors. Next, the two groups were subject to comparison in terms of the days of gonadotropin (Gn) use, total dosage of Gn, trigger time, hormone level and endometrial condition on the day of human chorionic gonadotropin (HCG) injection, the effects of two different regimens on controlled ovarian hyperstimulation (COH) and pregnancy outcomes.ResultsThere were no significant differences in baseline characteristics between the two groups, including age, duration of infertility, body mass index (BMI), ovarian volume, antral follicle count, and basal hormone levels. Compared with the Control group, the days of Gn use and trigger time of patients in the Inhibitor group were significantly shortened, and the total Gn dosage was notably reduced. In terms of sex hormone levels on the HCG injection, the Inhibitor group displayed much lower serum estradiol levels while higher serum luteinizing hormone and progesterone (P) levels than the Control group. Notably, the high-quality embryo rate was also significantly increased with the use of TNF inhibitors. However, significant differences were not observed in endometrial thickness (on the day of HCG injection), proportion of endometrial A, B and C morphology (on the day of HCG injection), cycle cancellation rate, number of oocytes retrieved, fertilization rate, and cleavage rate between the two groups. Importantly, the clinical pregnancy rate in the Inhibitor group was significantly higher than that in the Control group, but there was no significant difference in the biochemical pregnancy rate, early abortion rate, multiple birth rate, ectopic pregnancy rate and number of live births between the two groups.ConclusionCollectively, after application of TNF-α inhibitor regimen, superior overall treatment effect can be observed in infertile PCOS patients receiving IVF-ET. Therefore, TNF inhibitors have certain application value in IVF-ET in infertile women with PCOS.

The importance of infertility duration and follicle size according to pregnancy success in women undergoing ovulation induction with gonadotropins and intrauterine insemination

In this study, we aimed to evaluate the effect of infertility duration and dominant follicle size measured on the day of human chorionic gonadotropin (HCG) administration on pregnancy rates in infertile women undergoing ovulation induction (OI) with gonadotropin (GND). A total of 352 patients aged 20 to 41 years who were diagnosed with unexplained infertility or polycystic ovary syndrome (PCOS) were included in this study. Patients with a history of multifollicular development or follicle stimulating hormone (FSH) value more than 12 IU/ml were excluded from the study. The demographic and clinical features of the patients were obtained from the patients’ files and hospital automation system and recorded for each woman. The demographic and clinical features of the patients were recorded. Patients were divided into two groups as live birth (group 1, n = 47) and non-live birth groups (group 2, n = 305). There were no statistically significant differences in regard to age, infertility type, follicle stimulating hormone (FSH) level, oestradiol (E2) level, antral follicle count (AFC), cycle characteristics, GND type, number of follicles, E2 level and endometrial thickness on HCG day, total GND dose, dominant follicle size (p > 0.05). Infertility duration in group 1 was 3.5 ± 2.1; in group 2, 4.7 ± 3.9 years. This difference was statistically significant (p = .014). According to this study, live birth rates after GND + IUIs(intrauterine insemination) were significantly affected by the duration of infertility. But the dominant follicle size and endometrial thickness measured on HCG day in GND and IUI cycles did not have a significant effect on pregnancy rates. IMPACT STATEMENT What is already known on the subject? It is thought that the timing of the ovarian triggering is vital for the success of intrauterine insemmination (IUI) treatment. What do the results of this study add? According to our results live birth rates after GND + IUIs were significantly affected by the duration of infertility. What are the implications of these findings for clinical practice and/or further research? It is determined that the duration of infertility is significant and patients should be encouraged to the treatment as soon as possible.

Effects of trigger-day progesterone in the preimplantation genetic testing cycle on the embryo quality and pregnancy outcomes of the subsequent first frozen-thawed blastocyst transfer.

To assess whether progesterone (P) levels on the trigger day during preimplantation genetic testing (PGT) cycles are associated with embryo quality and pregnancy outcomes in the subsequent first frozen-thawed blastocyst transfer (FET) cycle. In this retrospective analysis, 504 eligible patients who underwent ICSI followed by frozen-thawed embryo transfer (FET) with preimplantation genetic test (PGT) between December 2014 and December 2019 were recruited. All patients adopted the same protocol, namely, the midluteal, short-acting, gonadotropin-releasing hormone agonist long protocol. The cutoff P values were 0.5 and 1.5 ng/ml when serum P was measured on the day of human chorionic gonadotropin (HCG) administration, and cycles were grouped according to P level on the day of HCG administration. Furthermore, the effect of trigger-day progesterone on embryo quality and the subsequent clinical outcome of FET in this PGT population was evaluated. In total, 504 PGT cycles were analyzed. There was no significant difference in the number of euploid blastocysts, top-quality blastocysts, euploidy rate, or miscarriage rate among the three groups (P>0.05). The 2PN fertilization rate (80.32% vs. 80.17% vs. 79.07%) and the top-quality blastocyst rate (8.71% vs. 8.24% vs. 7.94%) showed a downward trend with increasing P, and the between-group comparisons showed no significant differences (P>0.05). The clinical pregnancy rate (41.25% vs. 64.79%; P<0.05) and live birth rate (35.00% vs. 54.93%; P<0.05) in subsequent FET cycles were substantially lower in the high-P group than in the P ≤ 0.5 ng/ml group. After adjustments were made for confounding variables, multivariate logistic regression analysis revealed that the high-P group had a lower clinical pregnancy rate (adjusted OR, 0.317; 95% CI, 0.145-0.692; P=0.004) and live birth rate (adjusted OR, 0.352; 95% CI, 0.160-0.773; P=0.009) than the low-P group in subsequent FET cycles, and the differences were significant. This study demonstrates that in the PGT population, elevated P on the trigger day may diminish the top-quality blastocyst rate (although there is no difference in the euploidy rate). Trigger-day P is an important factor influencing clinical outcomes in subsequent FET cycles.

Independent value of PMOI on hCG day in predicting pregnancy outcomes in IVF/ICSI cycles.

The aim of this study was to determine whether, on the day of human chorionic gonadotropin (hCG) injection, the progesterone to number of mature oocytes index (PMOI) can be used alone or together with other parameters in a fresh embryo transfer in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle to predict pregnancy outcome. This was a retrospective cohort study of all couples who underwent a clinical pregnancy and received a fresh IVE/ICSI cycle at a single large reproductive medical center between June 2019 and March 2022. The study involved a total of 1239 cycles. To analyze risk factors associated with pregnancy outcomes on the day of HCG injection, univariate and multivariate logistic regression analyses were used. The area under the curve (AUC) was determined, and PMOI and other factors were compared using receiver operating characteristic (ROC) curves. The clinical pregnancy rate was significantly higher in group A (60.76%) than in the other groups (Group B: 52.92% and Group C:47.88%, respectively, p =0.0306). Univariate and multivariate logistic regression revealed that PMOI levels were significantly correlated with the probability of pregnancy outcome, independent of other risk factors. More importantly, PMOI levels independently predict the occurrence of pregnancy outcome, comparable to the model combining age. The optimal serum PMOI cutoff value for pregnancy outcome was 0.063 ug/L. Our results suggest that PMOI levels have an independent predictive value for pregnancy outcome in fresh IVF/ICSI cycles.

Effect modification by developmental stage of embryos on the association between late follicular phase progesterone elevation and live birth in fresh transfers

BackgroundLate follicular phase progesterone elevation (LFPE) during ovarian stimulation is associated with reduced live birth rates (LBRs) after cleavage-stage embryo transfer. However, due to better synchronization with a stimulated endometrium, prior studies shown that LFPE had no effect on transferring embryos at blastocyst stage. The study aim to exam whether the developmental stage of embryos and serum progesterone levels on the day of human chorionic gonadotropin (hCG) administration jointly affect the odds of live birth in fresh fresh IVF/intracytoplasmic sperm injection (ICSI) cycles. MethodsThe single-center retrospective cohort study included a total of 4,471 fresh embryo transfer cycles with 2,342 at cleavage stage versus 2,129 at blastocyst stage. Patients underwent IVF/ICSI with ovarian stimulation in gonadotropin-releasing hormone antagonist protocol. The serum progesterone level was examined both as a continuous variable and as a categorical variable by quartiles. Analysis was performed using the generalized estimating equations framework and multivariate regression models.ResultsLBRs were inversely associated with progesterone as a continuous variable on the day of hCG in both the cleavage-stage (crude OR 0.87, 95%CI 0.73–1.03; adjusted OR 0.80, 95% CI 0.65–0.98) and the blastocyst-stage (crude OR 0.66, 95%CI 0.56–0,78; adjusted OR 0.61, 95%CI 0.50–0.73) groups. The interaction testing was highly significant (P = 0.018) indicating an effect modifying role of stage of embryos transferred on the association of pregesterone values with the LBRs in fresh cycles. A similar pattern for a greater reduction in ORs for live birth in cycles with blastocysts transfer was also observed when progesterone was analyzed by interquartile ranges. The findings remained unchanged in subgroup analysis stratified by types of ovarian response.ConclusionsIn fresh cycles, detrimental effect of late follicular phase progesterone elevation on live birth was more prominent in blastocyst-stage group compared with that in clevaged-stage group.