Background:In controlled ovarian stimulation (COS) cycles, premature progesterone elevation (PPE) on the HCG trigger day is associated with adverse pregnancy outcomes after in vitro fertilization-embryo transfer (IVF-ET). The aim of this study was to analyze the influencing factors of PPE with the early-follicular phase long-acting GnRH-a long protocol (EFLL) and to explore a dynamic risk-assessment nomogram for PPE to inform risk stratification and early clinical adjustment. Methods:This was a single-center, retrospective cohort study. Patients who underwent their first IVF cycle at our center from January 2019 to December 2019 were included. All patients were treated with the EFLL protocol. Patients were randomly assigned to the training or validation cohort for nomogram development and testing at a ratio of 8:2. After excluding collinear variables, the remaining candidate predictors were screened by the LASSO regression model, and the nomogram was constructed by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curves and calibration curves with bootstrap were used to evaluate the performance of the nomogram. DCA was used to analyze the clinical efficacy of the model. Results:A total of 5193 cycles were included-4154 cycles in the training cohort and 1039 cycles in the validation cohort. The incidence of PPE in the training cohort was 20.51%. Multivariate logistic regression showed that BMI, basal FSH, basal progesterone (bP), AMH, AFC, total duration of Gn, total dosage of exogenous HMG, FSH and P on the 6th day of Gn were found to be independent influencing factors of PPE, and a nomogram model was constructed accordingly. The areas under the ROC curves of the training cohort and the validation cohort were 0.683 (95% CI = 0.663-0.702) and 0.622 (95% CI = 0.583-0.662), respectively. The calibration curve showed that the predicted risk of the model was in good agreement with the actual results in both cohorts. Decision curve analysis (DCA) demonstrated the clinical value of this nomogram. Conclusions:Our nomogram for estimating PPE demonstrates modest discriminative ability and may serve as a preliminary risk stratification tool in COS cycles. It may assist clinicians in identifying patients at higher risk of PPE, thereby informing clinical judgment.
It has been debated whether endometriosis (EMS) adversely affects oocyte quality, potentially leading to a higher incidence of genetically unbalanced embryos or other egg factors that affect the developmental potential. In this study, we explored the effects of endometriosis on risk of chromosomally aberrant in miscarried products of conception (POC) after assisted reproductive treatment (ART), including fresh and frozen cycles. Miscarried POCs were collected from EMS patients (N = 102) and non-EMS patients (N = 441). Single nucleotide polymorphism (SNP) array analysis was conducted on all collected samples. Propensity score matching (PSM, ratio of 1:4) based on maternal age was applied in data analysis. Logistic regression analysis was performed to identify risk factors for chromosomal aberration-induced miscarriage between the two cohorts. A total of 228 (41.99% of 543) conceptuses were identified as having chromosomal aberrations. The results showed that women with EMS had a significantly lower antral follicle count (AFC) (10 ± 5 vs. 14 ± 7, P < 0.01) compared to the control group. Additionally, the EMS group had a relatively lower anti-Mullerian hormone (AMH), higher basal follicle stimulating hormone (FSH) and fewer oocytes, (P > 0.05). There was no significant difference in the chromosomal aberration rate of POCs between EMS and non-EMS groups (35.29% vs. 43.54%; odds ratio (OR) = 1.03, 95% confidence intervals (CIs) 0.79-1.35). This is the first study to show that EMS maybe associated with decreased ovarian reserve, but not related to chromosomal abnormalities in POCs. These results suggest that chromosomal abnormalities may not be the only cause of miscarriage in EMS patients.
The relationship between blastocyst morphological quality and the risk of congenital malformations in assisted reproductive technology (ART) remains poorly understood, limiting clinical decision-making for embryo selection. We conducted a retrospective cohort study of 3986 frozen embryo transfer cycles (January 2014–June 2023) to evaluate whether blastocyst morphological quality influences the risk of congenital malformations. Blastocysts were classified according to Gardner’s grading system, and 1:2 propensity score matching was applied to control for maternal age, BMI, infertility characteristics, and other potential confounders. After matching, 1743 singleton births were analyzed (1162 good-quality vs. 581 poor-quality blastocysts). Baseline characteristics were well balanced between groups. The risk of congenital malformations was similar between good- and poor-quality groups (aOR 1.14, 95% CI 0.54–2.41, P = 0.7310; 1.72% vs. 2.07%), with no significant between-group differences in any ICD-10 organ-specific categories (all P > 0.10). Secondary outcomes showed no significant differences: preterm birth (aOR 0.80, 95% CI 0.57–1.12, P = 0.1976), low birth weight (aOR 1.26, 95% CI 0.72–2.19, P = 0.4172), other neonatal outcomes, and obstetric complications (aOR 0.89, 95% CI 0.64–1.22, P = 0.4629). These findings indicate that blastocyst morphological quality does not influence the risk of congenital malformations, supporting the use of morphologically poor blastocysts when high-quality alternatives are unavailable, which may reduce unnecessary discarding of embryos, alleviate patient anxiety, and improve treatment accessibility.
BackgroundEach controlled ovarian hyperstimulation(COH) protocol has its own unique mechanism and hormone pattern. The depot GnRHa protocol has a deeper down-regulation effect and favorable clinical pregnancy rates. The predictive model of the optimal follicle-stimulating hormone (FSH) starting dose in the early follicular phase depot GnRH agonist (EFDGa) protocol has not been reported. Our study was made to explore predictive indicators for determining the optimal FSH starting dose in patients undergoing ovarian stimulation with the EFDGa protocol in assisted reproductive technology (ART), and to develop and validate a nomogram prediction model for the starting dose of FSH.MethodsThis retrospective study included 2733 cycles who underwent fresh cycle transplantation at two large teaching hospitals in China from January to December 2022: center 1 (Reproductive Medicine Center of first affiliated Hospital of Zhengzhou University) provided the data for modelling (n = 938) and internal testing (n = 400), and center 2 (Reproductive Medicine Center of Jiangxi Maternal and Child Health Hospital) provided the data for external testing (n = 1109). Patient demographics, including age, anti-Mullerian hormone (AMH) levels, baseline endocrine profile, and body mass index (BMI), along with information on ovulation stimulation, were collected. Univariate and multivariate linear regression models were used to identify factors influencing the FSH starting dose. A nomogram for the ideal FSH starting dose was developed based on these factors and validated internally and externally. Bland and Altman plots and paired t-tests were conducted to verify the concordance between groups.ResultsMultivariate analysis revealed that patient age, BMI, basal FSH, AMH, and antral follicle count (AFC) were indicators of FSH starting dose. The regression model for predicting FSH starting dose was determined as: Initial FSH dose = 62.957 + 1.780*AGE(years) +4.927*BMI (kg/m²) +1.417*bFSH (IU/ml) - 1.996*AFC - 48.174*AMH (ng/ml). Bland and Altman analysis showed good agreement in the internal validation (bias: 0.583, SD of bias: 33.07IU, 95%LOA: -69.7 to 68.5IU b). Furthermore, validating the model on external cohort (center 2) confirmed that nomogram prediction model is an accurate predictor of FSH starting dose ((bias: -1.437, SD of bias: 38.28IU; 95%LOA: -80.0 to 77.1IU).ConclusionsWe established a model for effectively predicting the ideal FSH starting dose, with the nomogram model providing an intuitive representation of the data. The predictive model demonstrates practical utility, effectively initiating a proper ovarian response and preventing adverse ovarian reactions or the occurrence of ovarian hyperstimulation syndrome. As more IVF cycles are being generated in the future, this model will be valuable in clinicians using basic parameters to assess proper initial dose of FSH.
ObjectiveTo evaluate the impact of endometrial thickness (EMT) variations on clinical outcomes in two distinct ovarian stimulation protocols: the early-follicular long-acting GnRH agonist protocol and the midluteal short-acting GnRH agonist long protocol.MethodsThis retrospective cohort study analyzed 21,290 first-time IVF/ICSI fresh embryo transfer cycles conducted at the Reproductive Center of the First Affiliated Hospital of Zhengzhou University between January 2013 and December 2020. Restricted cubic spline (RCS) analysis was employed to assess the relationship between EMT and clinical pregnancy outcomes.ResultsIn the early-follicular long-acting GnRH agonist protocol group, both clinical pregnancy and live birth rates increased with EMT up to 10.6 mm, beyond which the rates plateaued. Conversely, in the midluteal short-acting GnRH agonist long protocol group, a continuous positive correlation was observed between EMT and both clinical pregnancy and live birth rates. Overall, the early-follicular long-acting protocol demonstrated superior pregnancy outcomes compared to the midluteal short-acting protocol when EMT was less than 15 mm. However, when EMT was ≥15 mm, both protocols yielded comparable clinical pregnancy and live birth rates.ConclusionThe study indicates that in the early-follicular long-acting GnRH agonist protocol, increasing EMT up to 10.6 mm is associated with improved clinical pregnancy and live birth rates, with no further benefits observed beyond this threshold. In contrast, the midluteal short-acting GnRH agonist long protocol exhibits a continuous positive relationship between EMT and pregnancy outcomes. Overall, the early-follicular long-acting protocol offers better clinical outcomes for patients with EMT less than 15 mm, while both protocols perform similarly when EMT is ≥15 mm.
Background:Endometrial thickness (EMT) has been confirmed to be associated with pregnancy outcomes after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET), but studies on its relationship with neonatal outcomes are still limited. To our knowledge, this study is the first to investigate the relationship between EMT on the day of hCG trigger and the risk of preterm delivery (PTD) in populations undergoing cleavage-stage embryo transfer and blastocyst transfer, respectively. Methods:This study was a retrospective cohort study that included singleton live birth cycles of women who underwent autologous IVF/ICSI-ET at the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. The main study outcome was PTD. The relationship between EMT and PTD was explored using logistic regression in different models. These models were adjusted for baseline characteristics, cycle treatment parameters and maternal pregnancy complications among populations undergoing cleavage-stage embryo and blastocyst transfer. Results:In both the unadjusted model and Model I, which was adjusted for baseline characteristics, compared with that in the EMT 7.5-12 mm group, the risk of PTD was significantly greater in the EMT < 7.5 mm group and significantly lower in the EMT ≥ 12 mm group (P < 0.05). In Model II, which was adjusted for all potential confounding factors, including pregnancy conditions, an EMT ≥ 12 mm retained its independent protective effect against PTD in both populations. In contrast, an EMT < 7.5 mm and PTD (OR 2.19; 95% CI, 0.82-5.88; P = 0.118) did not significantly correlated in the blastocyst transfer population. However, in patients undergoing cleavage-stage embryo transfer, an EMT < 7.5 mm remained an independent risk factor for PTD (OR 2.14; 95% CI, 1.09-4.21; P = 0.027). Conclusions:A thin endometrium on the day of hCG trigger is independently associated with an increased risk of PTD in patients undergoing cleavage-stage embryo transfer but not in those undergoing blastocyst transfer. In contrast, a thick endometrium significantly reduces the risk of PTD in both populations.
Abstract Background The gonadotropin hormone-releasing hormone agonists (GnRH-a) have been widely used for controlled ovarian stimulation in assisted reproductive technology (ART). The early-follicular long-acting GnRH-a long protocol (EFL) and the luteal phase short-acting GnRH-a long protocol (LPS) are commonly used GnRH agonist protocols. We conducted a retrospective analysis to assess and compare the rates of congenital abnormalities and safety profiles in offspring born from the EFL and LPS protocols. Methods We conducted a retrospective cohort study to analyze and compare neonatal data from patients who using EFL or LPS protocols at our center between January 1, 2014, and June 30, 2017. The study ultimately included 1810 neonates from 1401 cycles using the EFL protocol and 2700 neonates from 2129 cycles using the LPS protocol.The main outcome measures are gestational age at delivery, birth weight, and congenital anomaly rate.To assess the influence of various factors on congenital abnormalities, a random-effects logistic regression model was employed. Results The EFL and LPS protocols led to similar congenital anomaly rates (1.64% vs. 2.35%, P = 0.149). No significant differences were found between the two groups regarding birth weight and its categories, newborn gender and congenital anomaly rate. The results of the multivariate logistic regression model indicated no association between congenital anomaly and BMI, duration of infertility, treatment protocol, fertilization method, or embryo transfer stage. Compared with singleton pregnancies, the probability of congenital defects in multiple pregnancies was 2.64 times higher (OR: 2.64, 95% CI: 1.72–4.05, P < 0.0001). Newborns with congenital defects were born with a lower gestational age compared with full-term pregnancies. Conclusion In conclusion, the EFL protocol is considered a safe option for ensuring offspring safety, comparable with the LPS protocol; however, multiple pregnancies represent an independent risk factor for congenital abnormalities. This approach can be widely adopted; however, prioritizing single embryo transfers is strongly recommended to minimize the potential risks associated with multiple pregnancies in offspring.
This study aimed to develop and validate a predictive model for failure to collect oocytes in the Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Groups 3 and 4 during their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle. A retrospective analysis was conducted on patients in POSEIDON Groups 3 and 4 who underwent their first IVF/ICSI cycle at our center from January 2016 to December 2023. A total of 2,373 patients were randomly assigned to the training or validation cohort at a ratio of 6:4. Univariate analysis, the least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis were used to identify the risk factors. It revealed that the anti-M & uuml;llerian hormone (AMH) concentration, controlled ovarian stimulation (COS) protocols, the number of follicles >= 14 mm on the day of trigger, and the change in estradiol level between the day before trigger and the trigger day (Delta E2) were the independent predictors. A nomogram was constructed accordingly. The areas under the receiver operating characteristic curves (ROC) of the training and the validation cohorts were 0.868 (95% CI: 0.835-0.902) and 0.860 (95% CI: 0.823-0.897), respectively. The calibration curve showed that the predicted risk of the model was in good agreement with the actual results. Decision curve analysis (DCA) demonstrated the clinical value of this nomogram. Our nomogram provides a practical and user-friendly tool for clinical decision-making.
Abstract Background Each controlled ovarian hyperstimulation(COH) protocol has its own unique mechanism and hormone pattern. The depot GnRHa protocol has a deeper down-regulation effect and favourable clinical pregnancy rates, the predictive model of the optimal follicle-stimulating hormone (FSH) starting dose in the early follicular phase depot GnRH agonist (EFDGa) protocol has not been reported. Our study was made to explore predictive indicators for determining the optimal FSH starting dose in patients undergoing ovarian stimulation with the EFDGa protocol in assisted reproductive technology (ART), and to develop and validate a nomogram prediction model for the starting dose of FSH. Methods This retrospective study included 2733 cycles who underwent fresh cycle transplantation at two large teaching hospitals in China from January to December 2022: center 1 (Reproductive Medicine Center of first affiliated Hospital of Zhengzhou University) provided the data for modelling (n = 938) and internal testing (n = 400), and center 2 (Reproductive Medicine Center of Jiangxi Maternal and Child Health Hospital) provided the data for external testing (n = 1109). Patient demographics, including age, anti-Mullerian hormone (AMH) levels, baseline endocrine profile, and body mass index (BMI), along with information on ovulation stimulation, were collected. Univariate and multivariate linear regression models were used to identify factors influencing the FSH starting dose. A nomogram for the ideal FSH starting dose was developed based on these factors and validated internally and externally. Bland and Altman plots and paired t-tests were conducted to verify the concordance and RMSE between groups. Results Univariate analysis revealed that patient age, BMI, baseline FSH, AMH, and antral follicle count (AFC) were indicators of FSH starting dose. The regression model for predicting FSH starting dose was determined as: Initial dose of FSH = 45.984 + 1.728 * AGE (years) + 5.131 * BMI (kg/m²) + 2.455 * bFSH (IU/ml) - 6.697 * AMH (ng/ml) – 3.339 * AFC. Bland and Altman analysis showed good agreement in the internal validation (bias: 0.629, SD of bias: 36.83, 95%LoA: -71.55 - 72.81 IU). Furthermore, validating the model on external cohort confirmed that nomogram prediction model is an accurate predictor of FSH starting dose ((bias: -1.428, SD of bias: 43.21, 95%LoA: -85.11 - 82.15 IU). Conclusions We established a model for effectively predicting the ideal FSH starting dose, with the nomogram model providing an intuitive representation of the data. The predictive model demonstrates practical utility, effectively initiating a proper ovarian response and preventing adverse ovarian reactions or the occurrence of ovarian hyperstimulation syndrome. As more IVF cycles are being generated in the future, this model will be valuable in clinicians using basic parameters to assess proper initial dose of FSH.
Objective: The purpose of this study was to investigate the effect of body mass index (BMI) before treatment on the cumulative live birth rate (CLBR) over multiple complete in vitro fertilization (IVF) cycles in patients with polycystic ovary syndrome (PCOS). Materials and methods: This study is a single-center retrospective cohort study. It included 5016 patients with PCOS who started their first IVF cycle in our hospital between 2009 and 2018. Kaplan-Meier and log-rank tests were used for the comparison of CLBR across BMI groups. Univariate, multivariate models and stratification analysis were used to evaluate possible influencing factors of CLBR. Smoothing curve fitting was applied to present the correlation between BMI and CLBR. A one-line linear regression model was compared with a twopiecewise linear model using a log-likelihood ratio test. Results: During the 8-year follow-up, 3604 women (71.85%) obtained at least one live birth. The study population was grouped according to BMI, with BMI ranging from [14.53-23.00) kg/m2 in the normal weight group, [23.00-27.50) kg/m2 in the overweight group, and [27.50-37.80] kg/m2 in the obese group, respectively. The CLBR of the obese group and the overweight group were significantly lower than the normal weight group. In the multivariate regression model, HR for CLBR was 0.86 [95%CI: 0.78-0.95] for the obese group, and 0.93 [0.86-1.00] for the overweight group, compared with the normal weight group as control. The curve fitting after adjustment for confounding factors and log-likelihood ratio test showed a one-line linear negative correlation between BMI and CLBR. Conclusion: We concluded that the BMI of PCOS patients had a negative one-line linear correlation with CLBR over multiple complete cycles.
The mechanisms underlying poor ovarian response (POR) in assisted reproductive technology remain unclear, there is no consensus on the management of poor responders, the POSEIDON stratification classifies infertility patients into "expected" or "unexpected" groups to provide a more nuanced picture of POR, but few researchers have discussed the independent predictive factors (smoothed plots and the threshold effect) for live birth in POR patients classified by the new criteria. We conducted a retrospective cohort study using clinical data from 6,580 POR patients classified by the POSEIDON criteria in the First Affiliated Hospital of Zhengzhou University, and explored the live birth based on the results before and after the threshold inflection point of each independent influencing factor. Among 6,580 poor ovarian reserve patients classified by the POSEIDON criteria, 1,549 (23.54%) had live births, and 5,031 (76.46%) did not have live births. Multivariate logistic regression analysis showed that female age (OR 0.901; 95% CI 0.887~0.916; P < 0.001), body mass index (OR 0.963; 95% CI 0.951~0.982; P < 0.001), antral follicle counting (OR 1.049; 95% CI 1.009~1.042; P < 0.001) and controlled ovarian hyperstimulation protocol were independent factors predicting live birth in patients with POR. The threshold effect analysis found that the inflection point of female age was 34 years old, and when age was > 34 years old, the probability of live birth in POR patients dropped sharply (OR 0.7; 95% CI 0.7~0.8; P < 0.001). The inflection point of BMI was 23.4 kg/m2, and BMI had a negative correlation with live birth (OR 0.963; 95% CI 0.951~0.982; P < 0.001). The threshold inflection point of AFC was 8n. Female age, BMI, AFC and COH protocol were independent predictive factors associated with live birth in POR patients classified by the POSEIDON criteria. The smooth curve fit and threshold effect analyses provide clinical management strategies for these patients. In addition, the early-follicular-phase long-acting GnRH-agonist long protocol seems to have a higher live birth rates than other protocols. It is worth highlighting that BMI should be considered as well in the POSEIDON criteria.
目的 探讨不同降调节方案对子宫内膜异位症(EM S)患者的妊娠结局及新生儿结局的影响.方法 回顾性分析2009年1月至2019年12月在我院生殖中心行长/短效促性腺激素释放激素激动剂(GnRH-a)降调节方案促排卵后首次鲜胚移植或冻融胚胎移植(FET)的1805例EMS患者的临床资料,按降调节方案不同分为长效组(n=1499)和短效组(n=306),再根据移植周期的不同分为A组(长效方案所获胚胎新鲜移植周期,n=1394)、B组(长效方案所获胚胎FET周期,n=105)、C组(短效方案所获胚胎新鲜移植周期,n=274)、D组(短效方案所获胚胎FET周期,n=32).比较A、B、C、D组间的临床妊娠率、活产率和单胎活产儿的出生体重、孕周、大于胎龄儿(LGA)发生率、小于胎龄儿(SGA)发生率和巨大儿发生率等临床结局.分析降调节方案和移植周期对上述结局变量的影响.结果 长效组内,A组的活产率、新生儿的出生体重显著低于B组(P<0.05),孕周显著短于B组(P<0.05).短效组内,C组的活产率、LGA发生率显著低于D组(P<0.05).新鲜移植周期相比,A组的临床妊娠率、活产率显著高于C组(P<0.05),巨大儿发生率显著低于C组(P<0.05).FET周期相比,B组的LGA发生率显著低于D组(P<0.05).多因素Logistic回归分析显示:与短效组相比,长效组临床妊娠率高、活产率高、LGA发生率低、巨大儿发生率低(a P<0.05);与FET周期相比,新鲜周期的LGA发生率和巨大儿发生率均显著降低(a P<0.05),而临床妊娠率和活产率无显著差异(aP>0.05).结论 长效GnRH-a降调节方案有利于EMS患者在新鲜移植周期中获得较高的活产率和较低的巨大儿发生率.
We retrospectively analyzed clinical data from 45,912 in vitro fertilization/intracytoplasmic sperm injection cycles in our reproductive medical center. We compared the clinical outcomes of three different ovarian hyperstimulation protocols in poor ovarian responders (classified by the POSEIDON criteria) to determine the most effective protocol for each POSEIDON group. In POSEIDON groups 1 and 3, the early-follicular-phase long-acting GnRH-agonist long (EFLL) protocol was associated with higher pregnancy rates per transfer and higher live birth rates than the mid-luteal-phase short-acting GnRH-agonist long (MLSL) and GnRH-antagonist protocols. We also examined the relationship between advanced age and reproductive outcomes, and observed a negative correlation between age and live birth rate for each protocol (EFLL: OR = 0.890, 95% CI: 0.870 - 0.911, P < 0.001; MLSL: OR = 0.907, 95% CI: 0.885 - 0.926, P < 0.001; GnRH-antagonist: OR = 0.891, 95% CI: 0.857 - 0.926, P < 0.001). In terms of clinical outcomes, EFLL was the most effective protocol for young poor ovarian responders. However, there were no differences in the implantation rates, clinical pregnancy rates, or live birth rates among the protocols in older patients. Age is thus the most important determinant of oocyte quality, embryo ploidy, and delivery rate.
BACKGROUND Patients with endometriosis (EMs) are routinely advised to take GnRH-a for 3-6 months to improve the internal reproductive environment, but this may not be necessary. MATERIAL AND METHODS This retrospective study examined the effects of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) with shortened (n=311) or conventional (n=213) long-term pituitary downregulation in EMs patients between January 2013 and July 2017. RESULTS The 2 groups showed no significant differences in gonadotropin (Gn) dose, number of oocytes retrieved, or miscarriage rate. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels on the initiation day and the LH level on human chorionic gonadotropin (hCG) day (1.22±1.39 vs. 0.74±0.55 P=0.0026) were higher in the study group than in the control group. The cumulative live birth rates in the second cycle were 69.13% in the study group (95% confidence interval (CI), 64-74.27%) vs. 68.54% in the control group (95% CI, 62.31-74.78%, P=0.88, respectively). CONCLUSIONS This study showed that the shortened regimen and the ultralong regimen did not produce different pregnancy outcomes after ART, and the single-application, long-term GnRH-a protocol may serve as a cost-effective and safe treatment protocol for EMs patients.
目的:分析行体外受精/卵胞浆内单精子显微注射(IVF/ICSI)的25岁及以下女性的助孕特征及结局.方法:回顾性分析第一周期行IVF/ICSI助孕的12350例患者的临床资料,其中女性年龄20~岁522例,23~岁3030例,26~30岁8798例.比较3个年龄组患者的临床特征、助孕过程及妊娠结局.结果:3组不孕年限、男性因素不孕者占比、促性腺激素(Gn)用量和使用时间、HCG日雌二醇水平、ICSI占比差异均有统计学意义(P<0.05).20~岁组、23~岁组促性腺激素(Gn)用量和使用时间均小于26~30岁组(P<0.05),20~岁组男性因素不孕者占比、HCG日雌二醇水平、ICSI占比大于26~30岁组(P<0.05);23~岁组单个取卵周期活产率低于26~30岁组,全部周期累积活产率高于26~30岁组(P<0.05).精子来源为丈夫射出且受精方式为IVF人群3组间单个取卵周期活产率和全部周期累积活产率差异无统计学意义(P>0.05).结论:IVF/ICSI助孕时,20~岁、23~岁及26~30岁女性生育能力基本相同.
Background: Polycystic ovary syndrome (PCOS) patients have a better ovarian reserve and age-related improvement in endocrine disturbances than non-PCOS patients. The effects of age on in vitro fertilization (IVF) treatment outcomes associated with cumulative live birth rate (CLBR) remain unclear. Objectives: To study the effect of age on CLBR after the first ovarian stimulation in IVF in PCOS patients. Method: This retrospective cohort study included 3,502 PCOS patients and 18,596 patients with tubal factor infertility, who underwent their first IVF cycles and subsequent frozen embryo transfer (ET) attempts. The primary outcome was CLBR associated with a single stimulation cycle and secondary outcomes included the implantation rate, clinical pregnancy rate, live birth rate (LBR), large for gestational age (LGA) rate, small for gestational age (SGA) rate, and preterm birth (PTB) rate of fresh ET cycles. Results: PCOS patients over 40 years had a higher implantation rate (27.8 vs. 15.7%, P < 0.05), clinical pregnancy rate (51.4 vs. 26.1%, P < 0.05), LBR (42.3 vs. 18.2%, P < 0.05), and CLBR (50.0 vs. 21.5%, P < 0.05) than non-PCOS patients over 40 years. These rates were comparable between PCOS patients aged 35 to 40 years and those aged over 40 years (P = 0.263, 0.385, and 0.112, respectively). The changes in the implantation rate, clinical pregnancy rate, and CLBR by age were slower for PCOS patients than for non-PCOS patients (all P < 0.05). Among PCOS patients less than 35 years, BMI was negatively associated with CLBR [aOR: 0.961 (0.939–0.985); P < 0.05]; however, among PCOS patients over 35 years, instead of BMI (P = 0.353), age [aOR: 0.891 (0.803–0.990); P < 0.05] and the number of oocytes retrieved [aOR: 1.093 (1.002–1.078); P < 0.05] were significantly associated with CLBR. No significant differences in LGA, LGA, or PTB were detected between PCOS and non-PCOS patients over 35 years (all P > 0.05). Conclusions: The declines in treatment outcomes with age are slower for PCOS patients than for non-PCOS patients. For patients over 40 years, PCOS patients have reproductive advantages over non-PCOS patients. In contrast to younger PCOS patients (<35 years), older PCOS patients (≥35 years) may benefit less from taking time to lose weight before IVF treatment, and the immediate initiation of assisted reproductive treatment is essential.
Background: Female overweight/obesity has been reported to be associated with compromised pregnancy outcomes in fresh embryo transfer cycles. It is unclear whether the cumulative live birth rate (CLBR) is adversely affected after all viable embryos are transferred from the first ovarian stimulation cycle. Objectives: To investigate whether the CLBR was compromised in obese women. Method: A total of 9,772 young women underwent their first IVF/ICSI cycles from January 2012 to October 2017. Pregnancy outcomes were compared according to female BMI. Results: Among 1,671 women with polycystic ovary syndrome (PCOS), those with a BMI ≥ 28 kg/m2 had a lower cumulative clinical pregnancy rate (CCPR) and CLBR during the first complete ovarian stimulation cycle. Additionally, the pregnancy loss rate was increased in this group, although the difference was not significant. Among the 8,101 women without PCOS, the CCPR and CLBR of obese patients was also significantly decreased, and this group also showed increased pregnancy loss rates. Moreover, overweight women also had a decreased CLBR. Conclusions: Female obesity adversely affected the CLBR after utilizing the viable embryos from first oocytes retrieval.
Objective To evaluate the effect of different methods on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in patients with polycystic ovary syndrome (PCOS). Methods This retrospective study examined the outcomes of IVF/ICSI with different down-regulated long protocols in PCOS. All first IVF/ICSI treatment cycles between January 2015 and December 2016 in Reproduction and Genetics Hospital of the First Affiliated Hospital of Zhengzhou University were analyzed. Patients were recruited, who were treated with follicular phase long-acting gonadotropin-releasing hormone agonist (GnRH-a) down-regulated long protocol as study group (n=851) and luteal phase short-acting Triptorelin down-regulated long protocol as control group (n=632). The pregnancy outcomes were analyzed. Results The basal line in age, body mass index (BMI), cycle cancellation rate of ovarian hyperstimulation syndrome (OHSS), average number of transplanted embryos were comparable in the two groups. Total dosage and duration of gonadotropin (Gn) used, endometrial thickness and estradiol level on the human chorionic gonadotropin (hCG) trigger day in study group were higher than those in control group, while the number of the oocyte retrieval and transplantable embryos was lower than that in control group, the differences were statistically significant (P<0.01). In study group, the clinical pregnancy rate (76.17%) and the live birth rate [34.43% (95% CI=31.24%-37.62%)] were higher than those in control group [59.26%, P<0.01; 24.68% (95% CI=21.32%-28.05%), P<0.01]. But the total cumulative live birth rate was comparable in the two groups [69.21% (95% CI=66.11%-72.31%) vs. 67.88% (95% CI=64.24%-71.52%), P=0.584 3]. When the results were stratified in BMI, the cumulative live birth rate got better outcome in BMI≥25.00 kg/m2 subgroup without statistically significant (P=0.126 5). Conclusion PCOS patients can get better live birth rate and similiar cumulative live birth rate after follicular phase long-acting GnRH-a down-regulated long protocol. Key words: Polycystic ovary syndrome; Fertilization in vitro; Gonadotropin-releasing hormone agonist; Cumulative live birth rate
BACKGROUND:Endometriosis is the major cause of progressive pelvic pain and subfertility. Up to 50% of reproductive-age women suffer from pelvic pain. Endometriosis is a classic indication for IVF. Compared with women whose inability to procreate is caused by simple tubal infertility, women with endometriosis often have lower pregnancy rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The administration of gonadotrophin-releasing hormone (GnRH) agonists prior to IVF/ICSI can improve the successful pregnancy rate. Whether a briefer treatment interval would be efficacious has not been studied.METHODS/DESIGN:Eligible and consenting women will be randomly assigned to one of two treatments (one cycle of a GnRH agonist or two cycles of a GnRH agonist) prior to IVF/ICSI using a table of random numbers. The primary outcome of this trial is clinical pregnancy rate. Other outcomes include gonadotrophin (Gn) duration, the total dose of follicle-stimulating hormone (FSH) used, number of oocytes retrieved, number of embryos available for transfer, implantation rate, the abortion rate, live birth rate, and incidence of moderate-to-severe ovarian hyperstimulation. The sample size of this trial is estimated to be 421 participants for each of the two arms. Appropriate interim analyses will be conducted by a data monitoring and ethics committee (DMEC), and the final test will be an intention-to-treat analysis.TRIAL REGISTRATION:This trial has been assigned the following registry number: NCT03006406 .
Primordial germ cells (PGCs) derived from human embryonic stem cells (hESCs) represent as a desirable experimental model as well as a potential strategy for treating male infertility. Here, we developed a simple and feasible method for differentiation of PGCs from hESCs by using CHIR99021 (an inhibitor of glycogen synthase kinase 3) and retinoic acid (RA). We firstly found that the deleted in azoospermia-like (DAZL) protein can be detected in 3 d CHIR99021 plus 9 d retinoic acid treated cultures and 12 d CHIR99021 plus retinoic acid co-treated cultures, but not expressed in single CHIR99021 treated cultures, single retinoic acid treated cultures, as well as 3 d retinoic acid plus 9 d CHIR99021 treated cultures. Next, we showed that several PGCs' markers were expressed in the 12 d CHIR99021 and retinoic acid co-treated cultures or 3 d CHIR99021 plus 9 d retinoic acid treated cultures. Moreover, meiosis was initiated in CHIR99021 and retinoic acid co-treated cultures as evidenced by a significant expression of the punctate synaptonemal complex protein 3 (SCP3). Fluorescent in situ hybridization (FISH) analysis indicated that a small percentage of putative 1N populations were formed. Mechanically, we found that β-catenin relocated into nucleus after the treatment of 3 d CHIR99021 suggesting that Wnt signaling pathway was activated. Furthermore, blockade of Wnt signaling pathway by IWR-1 can reverse CHIR99021 and retinoic acid mediated-effects. Taken together, our results indicate that CHIR99021 combined with retinoic acid can effectively differentiate hESCs into PGCs via activating Wnt signaling pathway.