In Vitro Fertilization/intracytoplasmic Sperm Injection-embryo Transfer Research Articles

Effects of ovarian response prediction index and follicle-oocyte index on pregnancy outcomes: a retrospective cohort study of 12,218 fresh transfer cycles

Objective: To investigate the potential relationships among the ovarian response prediction index (ORPI), follicle-oocyte index (FOI), and clinical pregnancy rate (CPR) in women undergoing their first in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) fresh cycle transfer. Methods: In this retrospective cohort study, we included 12,218 women who underwent their first IVF/ICSI-ET cycle between December 2014 and January 2021. The primary and secondary outcomes of our study were CPR and cumulative live birth rate (CLBR), respectively. The data were divided into three groups according to the ORPI and FOI tertiles. Multivariate logistic regression analyses, stratification analyses, interaction, restricted cubic splines, and receiver operating characteristic (ROC) curves were constructed to identify the relationships among ORPI, FOI, and CPR. Results: A statistically significant increase in CPR was detected from the lowest to the highest tertile group (ORPI: 48.12%, 54.07%, and 53.47%, P <0.001; FOI:49.99%, 52.95%, and 52.71%, P=0.012). A higher CLBR was observed in the high group (ORPI: 38.63%, 44.62%, and 44.19%, P <0.001; FOI: 41.02%, 43.78%, and 42.59%, P=0.039). Multivariate logistic regression analysis revealed no statistically significant differences between ORPI, FOI, and neither CPR [odds ratio (OR) (95% confidence interval (CI), 0.99 (0.97-1.00) vs. (1.02 (0.84-1.24)] nor CLBR [OR (95% CI), 0.99 (0.97-1.01) vs. 0.99 (0.81-1.20)]. No significant association was found among FOI, ORPI, and CPR, even in the subgroups. Restricted cubic spline analyses indicated the existence of a nonlinear relationship across the entire range of FOI and ORPI. The ORPI and FOI variables had poor predictive ability (AUC< 0.60) for CPR. Conclusions: Both ORPI and FOI are not reliable predictors of clinical pregnancy or live birth outcomes in fresh embryo transfers. Clinicians and researchers should avoid using FOI and ORPI to assess pregnancy outcomes after fresh embryo transfer because of their limited relevance and predictive value.

Impact of the number of previous embryo implantation failures on IVF/ICSI-ET pregnancy outcomes in patients younger than 40 years: a retrospective cohort study.

The objective of this study was to examine the influence of repeated embryo implantation failures on pregnancy outcomes among patients under 40 years of age undergoing in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). A retrospective analysis was conducted on the clinical data of 13,172 patients who underwent 16,975 IVF/ICSI-ET treatment cycles at Henan Reproductive Hospital between January 1, 2015, and December 31, 2018. Patients were categorized into four groups based on the number of previous embryo implantation failure cycles: Group A=no implantation failure, Group B= 1 implantation failure, Group C=2 implantation failures, Group D=≥3 implantation failures. Baseline characteristics and pregnancy outcomes were compared among the four groups. The impact of the number of previous embryo implantation failures on pregnancy outcomes among IVF/ICSI-ET patients was investigated using univariate and multiple regression analyses. Univariate logistic regression analysis demonstrated that factors such as the number of previous embryo implantation failures, female age, basal follicle count, endometrial thickness, total number of oocytes retrieved, type of cycle, number of high-quality embryos transferred, and stage of embryo development significantly affected implantation rate, clinical pregnancy rate, early spontaneous abortion rate, and live birth rate (all P < 0.05). The duration of infertility and anti-Mullerian hormone (AMH) levels were also found to influence implantation rate, clinical pregnancy rate, and live birth rate (all P < 0.05). Upon conducting multivariate logistic regression analysis and adjusting for confounding factors such as age, AMH levels, basal follicle count, endometrial thickness, total number of oocytes obtained, cycle type, number of high-quality embryos transferred, ovarian stimulation protocol, and stage of embryo development, it was revealed that, compared to Group A, Groups B, C, and D exhibited significantly lower implantation and live birth rates, as well as a significantly higher risk of early spontaneous abortion (all P < 0.05). The number of previous embryo implantation failures is an independent factor affecting implantation rate, clinical pregnancy rate, spontaneous abortion rate and live birth rate of patients underwent IVF/ICSI-ET. With the increase of the number of previous embryo implantation failures, the implantation rate, clinical pregnancy rate and live birth rate of patients underwent IVF/ICSI-ET decreased significantly, and the rate of early spontaneous abortion gradually increased.

Effect of chromosomal polymorphisms on the outcome of in vitro fertilization and embryo transfer.

The incidence of chromosomal polymorphisms (CP) is increased in infertile couples, but its impact on reproduction is uncertain, especially undergoing assisted reproductive technology treatment. The purpose of the present study was to investigate the effect of CP on the outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatment METHODS: A total of 1331 infertile couples undergoing IVF/ICSI treatment were involved in this retrospective case-control study. The participants were divided into 4 groups according to CP variations: (i) normal chromosomes (NC) group; (ii) CP group; (iii) both chromosomal polymorphisms (BCP) group; and (iv) double chromosomal polymorphisms (DCP) group. The CP group was further divided into five subgroups: qh+, D/G, inv(9), Yqh+ and Yqh-. The outcomes of IVF/ICSI-ET treatment were compared among the groups. There were no differences observed between the eight groups in terms of number of oocytes retrieved, MII rate, fertilization rate, cleaved embryo rate, and quality embryo rate for both females and males (p > 0.05). In both male and female, some of the CP subgroups experienced more oocyte retrieval operations and more embryo transfer operations to achieve pregnancy than the NC groups (p < 0.05). The rates of live births were significantly lower in some of the CP subgroups compared to the NC group (p < 0.05). In conclusion, the pregnancy outcomes of ET were affected by CP. It was speculated that this may be associated with the effect of chromosome polymorphism on embryo quality, although this could not be observed or determined by morphological evaluation.

TSH levels after fresh embryo transfer are associated with reproductive outcomes in euthyroid women undergoing the first IVF/ICSI cycles

To investigate whether there is a relationship between TSH levels on the 14th day post embryo transfer (D14 TSH levels) and the reproductive outcomes in euthyroid women who are free from levothyroxine (LT4) treatment and undergo the first in vitro fertilization /intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET) cycles with the homogeneous ovarian stimulation protocols. This was a prospective study including a total of 599 euthyroid women undergoing the first IVF/ICSI ET cycles. Serum samples were collected and frozen on the 14th day post embryo transfer. TSH levels were measured after the confirmation of clinical pregnancy. The patients were divided into three groups (low-normal ≤ 2.5 mIU/L; high-normal 2.5–4.2 mIU/L; and high > 4.2 mIU/L) based on D14 TSH levels. Reproductive outcomes were compared among the three groups. Binary logistic regression analyses and generalized additive mixed models with smoothing splines were used to investigate the relationship between TSH levels and reproductive outcomes. D14 TSH levels were significantly elevated compared to basal TSH levels, and the degree of TSH elevation was significantly higher in pregnant women compared to that in non-pregnant women. The clinical pregnancy and live birth rates increased significantly in the high-normal D14 TSH groups, and doubled in the high D14 TSH groups compared to the low TSH groups. When adjusted by age, basal TSH, AMH, E2, endometrial thickness, type and causes of infertility, and transferred embryos, the dose-dependent relationships between D14 TSH and clinical pregnancy and live birth were observed. Obstetric outcomes in singleton or twins live birth among the different D14 TSH groups were similar. Elevated D14 TSH levels were associated with better clinical pregnancy and live birth rates, and were not associated with worse obstetric outcomes. The mechanisms to explain the phenomenon remained to be studied.

Effect of hyperandrogenism on pregnancy outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer

Objective: To explore the effects of hyperandrogenism (HA) on pregnancy outcomes in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Methods: A retrospective study was conducted on infertile women with PCOS undergoing IVF/ICSI-ET from January 2017 to June 2021 in our center. Patients were divided into HA group and NON-HA group according to the levels of testosterone. Propensity score matching (PSM) was used to balance the influence of female age and IVF/ICSI-ET for patients with gonadotropin-releasing hormone (GnRH)antagonist protocol and GnRH agonist protocol, separately. After the PSM procedure, 191 cases in HA group and 382 cases in NON-HA group, were included. Hormone levels and pregnancy outcomes were compared in the two groups. Results: The female age was comparable in two groups [HA: (29.6±3.7) vs NON-HA: (29.5±3.6), P=0.665]. The basal luteinizing hormone [(10.82±6.73) vs (7.76±5.30) IU/L], testosterone [(3.27±0.97) vs (1.60±0.59) nmol/L], free androgen index (7.13 vs 2.77), anti-mullerian hormone [(11.37±5.74) vs (9.67±4.67) ng/ml], fasting glucose [(5.18±0.49) vs (5.06±0.42) mmol/L], 1h glucose [(9.34±2.42) vs (7.99±2.21) nmol/L], 2 h glucose [(7.66±2.17) vs (6.64±1.84) nmol/L], 2 h insulin [(129.81±145.49) vs (97.51±86.92) mU/L], total cholesterol [(5.35±0.89) vs (4.92±0.92) mmol/L], triglycerides [(1.55±1.28) vs (1.33±0.77) mmol/L], and low density lipoprotein cholesterol levels [(3.38±0.66) vs (3.14±0.71) mmol/L] were significantly higher in HA group, compared with NON-HA group (P<0.05). The initiated gonadotropin dose was higher in HA group than that in NON-HA group [(126.96±33.65) vs (137.60±38.12) U, P=0.001], but moderate-severe ovarian hyperstimulation syndrome (OHSS) rate was similar in two groups (P>0.05). The rates of implantation, clinical pregnancy, miscarriage, and live birth were comparable between the two groups (P>0.05). Also, in the subgroups, the rates of implantation, clinical pregnancy, live birth, and miscarriage were similar in HA group and NON-HA group. Conclusions: The risks of hormonal abnormality and glucose-lipid metabolic disorder were higher in PCOS women with HA, whereas satisfactory pregnancy outcomes could be achieved under proper ovarian stimulation undergoing IVF/ICSI-ET.

Prevalence of Human Papillomavirus Infection in the Female Partner of Infertile Couples Undergoing IVF/ICSI-ET and Subsequent Reproductive Outcomes.

We investigated the prevalence of human papillomavirus (HPV) infection in the female partner of infertile couples and the reproductive outcomes after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). We conducted a retrospective analysis on 8117 women from infertile couples who underwent IVF/ICSI treatment and evaluated the prevalence of HPV infection in these women. The prevalence of HPV infection in the female partner of infertile couples was 9.2% (747/8117). These HPV-infected female patients undergoing ART were divided into high-risk HPV (hrHPV) (n = 130) and low-risk HPV (lrHPV) groups (n = 94), and non-infected women patients formed the negative group (n = 126). Of the 747 cases infected with HPV, 529 showed hrHPV infection (70.82%; primarily genotypes 16, 52, 53, 58, and 59); 175 exhibited lrHPV infection (23.43%; primarily genotypes 6, 43, 44, 55, 61, and 81); and 43 cases were co-infected with hrHPV and lrHPV (5.76%). Except for the Day-3 high-quality embryo rate, there were no differences in ovum maturation, fertilization, implantation, clinical pregnancy, live birth, or miscarriage rates between women infected with HPV and non-infected women (p > 0.05); however, we noted an increased miscarriage rate after logistic regression analyses (OR, 0.16; 95% CI, 0.03−0.84; p = 0.041). For single-male-factor-induced infertility in couples (smHPV), although we likewise observed no differences in ovum maturation, fertilization, or implantation rates (p > 0.05) between the smHPV group and the negative group, we discerned diminutions in the Day-3 high-quality embryo rate (46.01% vs. 70.04%, p = 0.013), clinical pregnancy rate (46.67% vs. 57.94%, p = 0.003), and live birth rate (33.33% vs. 46.83%, p = 0.027) as well as an augmented miscarriage rate (11.11% vs. 4.76%, p = 0.003), respectively. Logistic regression analyses indicated that smHPV was a risk factor for decreased clinical pregnancy rate (OR, 4.17; 95% CI, 2.31−7.53; p < 0.001) and live birth rate (OR, 1.83; 95% CI, 0.81−2.14; p = 0.045) and elevated miscarriage rate (OR, 6.83; 95% CI, 2.22−21.00; p = 0.001). HPV infection in women was associated with increased miscarriage rate, and single-male-factor infertility influenced reproductive outcomes in couples undergoing IVF/ICSI treatment. Both were potentially due to HPV infection in the couple.

Chromosomal polymorphisms have no negative effect on reproductive outcomes after IVF/ICSI-ET/FET

The present study aimed to explore whether chromosomal polymorphisms (CPs) have negative effects on reproductive outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET)/frozen-thawing embryo transfer (FET)? We conducted a retrospective study consisting of 21,867 assisted reproductive technology treatment cycles, among which, fresh embryo transfer cycles accounted for 10,400, and the rest were FET cycles. According to karyotype of CPs, the former was grouped as: group 1 (male carrier, n = 425), group 2 (female carrier, n = 262), and group 3 (couple without CPs, n = 9713). Accordingly, FET cycles were divided into 3 groups: group 4 (male carrier, n = 298), group 5 (female carrier, n = 311), and group 6 (couple without CPs, n = 10,858). The embryo implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and early miscarriage rate (EMR) were compared among the groups. In fresh embryo transfer cycles after IVF/ICSI, there were no significant differences in the infertility duration, BMI, basal FSH, no. of oocyte, no. of 2PN, endometrial thickness on trigger day, serum E2, P, and LH level on trigger day (P > 0.05). The female age, no. of 2PN embryo cleavage, top-quality embryo, and no. of embryo transferred were significantly different among groups (P < 0.05). The IR was 38.8%, 36.2%, and 34.0% in groups 1, 2, and 3, respectively. The CPR was 55.1%, 52.3%, and 49.7%, respectively. The LBR was 36.9%, 37.4%, and 36.4%, respectively. The CPR and LBR showed no significant differences among groups. The IR was lower and the EMR was higher in group 3 than those of groups 1 and 2. Binary logistic regression analysis indicated that female age, no. of embryo transferred, EMT, LH, and P on the trigger day were independently factors associated with CPR. Besides, no. of embryo transferred, and EMT on trigger day were associated with LBR, while the CPs was not related with CPR and LBR after IVF/ICSI-ET. In FET cycles, the infertility duration was similar (P > 0.05), but the female age, BMI, no. of embryo transferred were significantly different among groups (P > 0.05). The IR was 24.3%, 23.6% and 22.3% in group 4, 5, and 6, receptivity. The CPR was 31.8%, 30.9%, and 30.0%, the LBR was 23.8%,26.3%, and 23.8%, while the EMR was 12.6%, 13.1%, 14.4%, respectively. The IR, CPR, EMR, and LBR showed no significant differences among groups (P > 0.05). Binary logistic regression analysis indicated that female age, infertility duration, and no. of embryo transferred were independently factors affecting CPR and LBR after FET. The CPs were not associated with CPR and LBR after FET. The results suggested that uniparental carrying of CPs have no effects on the reproductive outcomes after IVF/ICSI-ET/FET. However, it is not clear whether both parents carrying CPs would affect pregnancy outcome.

Endometrial thickness is associated with low birthweight in frozen embryo transfer cycles: A retrospective cohort study of 8,235 singleton newborns.

To explore the association between endometrial thickness (EMT) and adverse neonatal outcomes in frozen in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. This retrospective study involved a total of 8,235 women under the age of 35 years who underwent IVF/ICSI cycles and received frozen embryo transfer (FET) at a tertiary-care academic medical from January 2015 to December 2019, resulting in a live singleton newborn. Patients were categorized into three groups depending on EMT: ≤7.5 mm, 7.5-12 mm and >12 mm. The primary outcome was low birthweight (LBW). The secondary outcomes were preterm birth (PTB), small-for-gestational age (SGA), large-for-gestational age (LGA) and high birthweight (HBW). Compared with EMT >7.5-12 mm group, the risk of being born LBW was statistically significantly increased in the EMT ≤7.5 mm group (adjusted odds ratio [aOR] 2.179; 95% confidence interval [CI], 1.305-3.640; P=.003), while dramatically decreased in the EMT >12 mm group (aOR 0.584; 95% CI, 0.403-0.844; P=.004). Moreover, newborn gender and pregnancy complications were all independent predictors for LBW. Furthermore, a significant decrease in birthweight was found in the EMT ≤7.5 mm group as compared with EMT >7.5-12 mm group and EMT >12 mm group (3,239 ± 612 vs. 3,357 ± 512 and 3,374 ± 479 g, respectively), and similar result was found in term of gestational age (38.41 ± 2.19 vs. 39.01 ± 1.68 and 39.09 ± 1.5 weeks, respectively). After frozen IVF/ICSI-ET, EMT ≤7.5 mm is independently associated with increased risk of LBW among women with singleton newborns. Therefore, we suggest that women with EMT ≤7.5 mm after achieving pregnancy by IVF/ICSI-ET treatment should warrant more attention to reduce the risk of delivering a LBW newborn.

Role of N-acetylcysteine treatment in women with advanced age undergoing IVF/ICSI cycles: A prospective study.

ObjectiveThe main objective of this study was to explore the efficacy of a new antioxidant N-acetylcysteine (NAC) supplementation in reproductive outcomes of advanced age women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET), and the effect on the expression of L-glutathione (GSH) in follicular fluid (FF) and mitochondrial DNA (mtDNA) copy number of granulosa cells.MethodsThe present prospective randomized controlled study was conducted in 200 patients with advanced age women undergoing GnRH antagonist protocol. The treatment group (group A) consisted of 100 women who received N-acetylcysteine treatment from the menstrual phase of the previous cycle for about 45 days using the GnRH antagonist protocol. The control group (group B) consisted of 100 women who received the same protocol without N-acetylcysteine. Total gonadotrophin dosage the number of oocyte received, high-quality blastocysts, and pregnancy outcomes were compared between two groups. Pregnancy outcomes included biochemical pregnancy rate, clinical pregnancy rate, embryo implantation rate, ectopic pregnancy rate, multiple pregnancy rate, and ongoing pregnancy rate. Follicular fluid (FF) was collected after oocytes were gathered. The GSH content in the FF was tested with enzyme linked immunosorbent assay (ELISA). The mtDNA copy number of the granulosa cells was measured using real-time PCR techniques.ResultsTotal doses of Gn in the NAC treatment group were less than those in the control group (2385.50 ± 879.19 vs. 2527.63 ± 1170.33, P = 0.047). Compared with the control, the number of high-quality blastocysts in NAC treatment increased significantly (1.82 ± 2.12 vs. 1.43 ± 1.58, p = 0.014). Clinical pregnancy rates did not differ in both groups (all P > 0.05). At the same time, the GSH content in the FF differed significantly between the two groups (1.88 ± 1.23 vs. 1.07 ± 0.70, p = 0.001). There was no significant difference in the mtDNA copy number between the two groups (P = 0.157).ConclusionA combination of NAC and Gn treatment is capable of improving the ovarian response to superovulation drugs in assisted reproductive technologies (ARTs) and also in aged populations. The addition of NAC during IVF can improve the quality of blastocysts in advanced age female subjects. However, more clinical trials are required to be designed to confirm this conclusion in future.Ethics and disseminationThe experiment solicited approval from the Institutional ethics committee of the Affiliated Reproductive Hospital of Shandong University. All the participants provided written informed consent. This survey was conducted as per the Declaration of Helsinki and relevant amendments.Trial registration numberwww.chictr.org.cn, identifier ChiCTR2100048297.

Homeostatic Model Assessment for Insulin Resistance Is Associated With Late Miscarriage in Non-Dyslipidemic Women Undergoing Fresh IVF/ICSI Embryo Transfer.

ObjectiveTo evaluate the associations between homeostatic model assessment for insulin resistance (HOMA-IR) and pregnancy outcomes in non-dyslipidemic infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET).Materials and MethodsThis is a retrospective study involving 3,615 non-dyslipidemic infertile women who attend to the Reproductive Medicine Center of Xiangya Hospital, Central South University (CSU) between January 2014 and October 2021. Eligible participants were divided into three groups according to the quartiles of HOMA-IR: Group 1 (HOMA-IR <1.46), Group 2 (1.46 to <2.71) and Group 3 (HOMA-IR ≥2.71). Baseline data, clinical characteristics during the assisted reproductive technology (ART) procedure, pregnancy, and neonatal outcomes were compared among the three groups. Subgroup analysis based on presence or absence of the polycystic ovary syndrome (PCOS) status was also performed to analyze the effects of HOMA-IR among non-PCOS populations.ResultsThe late miscarriage rate and percentage of macrosomia increased with the HOMA-IR group (for late miscarriage rate: 2.23% vs. 3.04% vs. 7.35%, P<0.001; for macrosomia: 0.21% vs. 1.70% vs. 3.23%, P=0.002). Increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.50, 95% CI 1.64-7.47, P=0.001; adjusted OR 3.56, 95% CI 1.56-8.15, P=0.003). In the subgroup analysis, there were 3,165 participants in the non-PCOS group and 450 were assigned to the PCOS group. Late miscarriage rate increased with the HOMA-IR group among non-PCOS populations (2.20% vs. 3.03% vs. 7.67%, P<0.001). Late miscarriage rate of PCOS women were comparable among the three HOMA-IR groups (2.50% vs. 3.06% vs. 5.71%, P=0.634). Among non-PCOS women, increased HOMA-IR (HOMA-IR≥2.71) was positively associated with late miscarriage (crude OR 3.71, 95% CI 1.66-8.30, P=0.001; adjusted OR 3.82, 95% CI 1.59-9.17, P=0.003).ConclusionsLate miscarriage rate and prevalence of macrosomia increased with the HOMA-IR index. Preconception HOMA-IR is an independent risk factor for late miscarriage in normolipidemic women undergoing IVF/ICSI-ET. Controlling insulin resistance before ART might prevent the occurrence of late miscarriage and macrosomia.

Pregnancy and Perinatal Outcomes of Patients With Prior Cesarean Section After a Single Embryo Transfer in IVF/ICSI: A Retrospective Cohort Study.

ObjectiveTo study the influence of the previous cesarean section on the pregnancy outcomes and perinatal outcomes in single embryo transfer (SET) cycles in an in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) setting compared to those with previous vaginal delivery (VD). In addition, the association between fertility outcomes and different cesarean scar defect (CSD) sizes was studied.MethodThis was a retrospective cohort study conducted in the Reproductive Center of the First Affiliated Hospital of Nanjing Medical University. A total of 4,879 patients with previous delivery history undergoing SET were included between January 2015 and April 2019. Patients were divided into the VD group and cesarean delivery (CD) group according to different modes of previous delivery. The primary outcome was live birth rate. The pregnancy outcomes of CD were analyzed as a subgroup and the relationship between pregnancy outcomes as well as the different sizes of CSD were explored by logistic regression analysis.ResultsThere were no significant differences in live birth rate, clinical pregnancy rate, and miscarriage rate between the CD group and VD group. The incidence rates of pregnancy complications such as pregnancy hypertension, gestational diabetes mellitus, placenta abnormalities, premature rupture of membrane, and postpartum hemorrhage were similar in the two groups. Live birth rate was significantly lower in the CSD group (23.77% vs 37.01%, aOR: 0.609, 95% CI: 0.476-0.778) comparing to patients without CSD. There were also significant differences in clinical pregnancy rate (37.52% vs 47.64%, aOR: 0.779, 95%CI: 0.623-0.973) and miscarriage rate (34.55% vs 20.59%, aOR: 1.407, 95%CI:1.03-1.923). Large size CSD significantly decreased live birth rate (13.33% vs 26.29%, aOR: 0.422, 95%CI: 0.197-0.902) and clinical pregnancy rate (25.33% vs 40.09%, aOR: 0.503, 95%CI: 0.272-0.930) compared with small size CSD.ConclusionFor women with previous cesarean sections, the pregnancy outcomes were similar to those with previous VD without increased perinatal complications following SET. The presence of CSD was associated with a marked reduction in live birth rate, especially in patients with large size CSD.

Progestin-Primed Ovarian Stimulation Protocol for Patients With Endometrioma.

ObjectiveTo evaluate the pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) protocol for patients with endometrioma underwent in vitro fertilization/intra-cytoplasmic sperm injection embryo transfer (IVF/ICSI-ET).DesignObservational retrospective cohort study.SettingUniversity affiliated reproductive center.Study Participants605 infertile patients with endometrioma underwent IVF/ICSI-ET from January 2016 to March 2021 were included in this study.MethodsMultivariable logistic regression analyses were conducted to determine the independent effect of controlled ovarian stimulation (COS) protocols on reproductive outcomes of first embryo transfer (ET) cycles. The live birth was primary outcome, the implantation rate, biochemical pregnancy, clinical pregnancy and ongoing pregnancy were secondary outcomes.ResultsCompared to PPOS protocol, the probability of implantation showed no significant difference with ultra-long gonadotrophin-releasing hormone agonist (GnRHa) protocol and gonadotrophin-releasing hormone antagonist (GnRHant) protocol (OR 1.7, 95% CI 0.9-3.1, OR 1.2, 95% CI 0.7-2.1, respectively). The PPOS protocol was correlated with a significantly lower biochemical pregnancy and clinical pregnancy than ultra-long GnRHa protocol in the multivariable logistic regression analysis (OR 2.3, 95% CI 1.1-4.9, OR 2.4, 95% CI 1.1-5.3, respectively). However, there was no significant difference in terms of biochemical pregnancy, clinical pregnancy and ongoing pregnancy between PPOS and GnRHant protocol (OR 1.4, 95% CI 0.7-2.7, OR 1.3, 95% CI 0.7-2.4, OR 1.1, 95% CI 0.6-2.3, respectively). In addition, compared to PPOS protocol, ultra-long GnRHa protocol and GnRHant protocol demonstrated no statistical difference in ongoing pregnancy (OR 2.0, 95% CI 0.9-4.5, OR 2.1, 95% CI 0.6-2.3, respectively). Notably, the ultra-long GnRHa protocol was associated with a significant higher probability of live birth than PPOS protocol both in crude analysis and multivariable logistic regression analysis (OR 2.6, 95% CI 1.3-5.1, OR 2.5, 95% CI 1.1-5.7, respectively). Nevertheless, no statistical difference was found in live birth between PPOS and GnRHant protocol either in crude analysis and multivariable logistic regression analysis (OR1.2, 95% CI 0.6-2.3, OR 1.2, 95% CI 0.6-2.5, respectively).ConclusionsBased on the reproductive outcomes of the first ET cycles in patients with endometrioma, PPOS protocol may associated with inferior reproductive outcomes in terms of biochemical pregnancy, clinical pregnancy and live birth than ultra-long GnRHa protocol. However, there was no significant difference in implantation rate, clinical pregnancy, ongoing pregnancy and live birth between PPOS and GnRHant protocol.

Progestin-primed ovarian stimulation protocol with or without letrozole for patients with normal ovarian reserve: a retrospective cohort study.

To compare the characteristics and efficacy of progestin-primed ovarian stimulation (PPOS) protocol plus letrozole versus PPOS protocol alone for patients with normal ovarian function who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) assisted pregnancy treatment. From 1 October 2017 to 1 October 2019, 576 patients who underwent IVF/ICSI cycles received PPOS protocol with or without letrozole in the Center of Reproductive Medicine, Renmin Hospital of Shiyan City were included in this retrospective cohort study. The PPOS group included 249 patients who received PPOS protocol alone, and the combined treatment group included 327 patients who received PPOS protocol plus letrozole. The general data and laboratory indicators were detected and used as baseline data. In addition, evaluation of related indicators was performed, including days of gonadotropin (Gn) duration, total amount of dose of Gn and medroxyprogesterone acetate (MPA), hormone levels on the trigger day, number of oocytes retrieved and mature eggs, fertilization rate, cleavage rate, blastocyst formation rate, high-quality embryo rate, methods of endometrial preparation, stage of embryo transfer, endometrial thickness, the number of embryo transfer, biochemical pregnancy rate, clinical pregnancy rate, implantation rate, abortion rate, ectopic pregnancy rate and live birth rate. The risk factors affecting clinical pregnancy rate were detected by binary Logistic regression analysis. In this study, we found that baseline level of Anti-Müllerian hormone (AMH) was significantly higher in combined group compared with PPOS group (p<0.05). The days of Gn duration in combined group were significantly longer than that in PPOS group (p<0.05), and the total amount of dose of Gn and MPA in combined group was significantly less than that in PPOS group (p<0.05). The levels of luteinizing hormone (LH) and progesterone in combined group were significantly higher than that in PPOS group on the trigger day (p<0.05). The number of oocytes retrieved and mature eggs in combined group was significantly more than that in PPOS group (p<0.05). Meanwhile, the fertilization rate, cleavage rate and blastocyst formation rate in combined group were significantly higher than that in PPOS group (p<0.05). There was no significant difference in the characteristics of endometrial preparation and embryo transfer, as well as the pregnancy outcomes. The results of logistic regression analysis showed that stage (p<0.001) (OR=0.281, 95% CI: 0.187, 0.422) and number (p<0.001) (OR=0.333, 95% CI: 0.196, 0.567) of embryos transfer were risk factors for clinical pregnancy rate. Compared with PPOS protocol alone, letrozole combined with PPOS can achieve similar embryo and pregnancy outcomes while reducing the amount of Gn and MPA, which has a higher cost performance and is worth promoting. Stage and number of embryos transfer are risk factors for clinical pregnancy rate.

Caesarean section defects may affect pregnancy outcomes after in vitro fertilization-embryo transfer: a retrospective study

BackgroundCaesarean section rates are rising worldwide. One adverse effect of caesarean section reported in some studies is an increased risk of subfertility. Only a few studies have assessed the relationship between the previous mode of delivery and in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) reproductive outcomes. In this study, we primarily investigated the impact of a history of caesarean section with or without defects on IVF/ICSI-ET outcomes compared to a vaginal delivery history.MethodsThis retrospective study included 834 women who had a IVF or ICSI treatment at our centre between 2015 and 2019 with a delivery history. In total, 401 women with a previous vaginal delivery (VD) were assigned to the VD group, and 433 women with a history of delivery by caesarean section were included, among whom 359 had a caesarean scar (CS) without a defect and were assigned to the CS group and 74 had a caesarean section defect (CSD) and were assigned to the CSD group. Baseline characteristics of the three groups were compared and analysed. Binary logistic regression analyses were performed to explore the association between clinical outcomes and different delivery modes.ResultsThere were no significant differences in the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, mean implantation rate or abnormal pregnancy rate between the CS and VD groups However, the live birth rate and mean implantation rate in the CSD group were significantly lower than those in the VD group (21.6 vs 36.4%, adjusted OR 0.50 [0.27–0.9]; 0.25 ± 0.39 vs 0.35 ± 0.41, adjusted OR 0.90 [0.81–0.99]). Among women aged ≤ 35 years, the subgroup analyses showed that the live birth rate, biochemical pregnancy rate, clinical pregnancy rate, and mean implantation rate in the CSD group were all significantly lower than those in the VD group (21.4 vs 45.8%, adjusted OR 0.35[0.15 ~ 0.85]; 38.1 vs 59.8%, adjusted OR 0.52[0.24–0.82]; 31.0 vs 55.6%, adjusted OR 0.43[0.19–0.92]; 0.27 ± 0.43 vs 0.43 ± 0.43, adjusted OR 0.85[0.43 ± 0.43]). For women older than 35 years, there was no statistically significant difference in any pregnancy outcome among the three groups.ConclusionsThis study suggested that the existence of a CS without a defect does not decrease the live birth rate after IVF or ICSI compared with a previous VD. However, the presence of a CSD in women, especially young women (age ≤ 35 years), significantly impaired the chances of subsequent pregnancy.

Clinical outcomes analysis of infertile women with unicornuate uterus in IVF-ET

PurposeTo explore the pregnancy outcomes, and neonatal status, arising from embryo transfer in unicornual uterine infertility patients. MethodsWe analyzed 2499 cycles of clinical data from in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) from 1st May 2016 to 1st May 2018 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University, including 109 women with unicornuate uterus (the observation group) and 2390 women with normally shaped uterus (the control group). ResultsThere were no significant differences in embryo implantation rate, clinical pregnancy rate or miscarriage rate (41.88 % VS 42.36 %, P = 0.904; 48.62 % VS 55.94 %, P = 0.133; 11.01 % VS 8.99 %, P = 0.474) between the two groups. The live birth rate in the observation group was lower than that in the control group (35.78 % VS 45.82 %, P = 0.040). The fetal birth weight of the observation group was lower than that of the control group among single-born live births (3009.12 ± 430.59 g VS 3413.40 ± 492.25 g, P = 0.017), but the differences were not observed in the sex ratio at birth, premature birth rate, low birth weight infant (LBW) rate and macrosomia rate (P > 0.05). The fetal birth weight of the observation group was lower than that of the control group among twins live births (2480.00 ± 190.32 g VS 2606.02 ± 471.59 g), but the difference between the groups did not reach statistical significance (P > 0.05)．Logistic regression analysis showed that age, number of embryos transplanted and uterine morphology were independent influencing factors of live birth. ConclusionCompared with women with normal uterus, the live birth rate of women with unicornuate uterus is low, and the birth weight of newborns with single birth is reduced.

Effectiveness of ultra-long protocol on in vitro fertilization/intracytoplasmic sperm injection-embryo transfer outcome in infertile women with endometriosis: A systematic review and meta-analysis of randomized controlled trials.

To evaluate the effectiveness of ultra-long protocol on reproductive and controlled ovarian hyperstimulation outcome in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in infertile women with endometriosis versus long protocol. We retrieved articles without language restrictions in the Elsevier ScienceDirect, Embase, Medline, PubMed, Web of Science, China National Knowledge Infrastructure, Wan Fang Data Knowledge Service Platform and China Science and Technology Journal Database from inception to August 2020. RCTs including the comparison of reproductive outcome of infertile patients with endometriosis who underwent ultra-long protocol and long protocol were selected. Data extraction was conducted using RevMan 5.3. A total of nine RCTs in compliance with the standard literature were included. This meta-analysis suggested that ultra-long protocol with a 3-month downregulation could increase clinical pregnancy rate of infertile women with endometriosis (RR=1.31, 95% CI:1.11 ~ 1.55, P = 0.002) versus long protocol. However, subgroup analysis found the different protocol provided no significant difference in improving clinical outcomes in patients with different disease stage of endometriosis. The ultra-long protocol could improve the clinical pregnancy rate of infertile women with endometriosis compared with long protocol with a 3-month downregulation. And ultra-long protocol could be effective to increase the ongoing pregnancy rate compared to long-protocol. But, the efficacy of ultra-long protocol is not different between early and advanced stage of endometriosis.

The Association Between Previous TORCH Infections and Pregnancy and Neonatal Outcomes in IVF/ICSI-ET: A Retrospective Cohort Study.

Objective: This study aimed to investigate the associations between previous TORCH infection (cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella) with pregnancy and neonatal outcomes in couples undergoing IVF/ICSI-ET.Materials and Methods: A total of 18,074 couples underwent fresh IVF/ICSI-ET (in vitro fertilization/intracytoplasmic sperm injection–embryo transfer) cycles were included in our analyses. TORCH infection status was determined by serological confirmation of cytomegalovirus, toxoplasmosis, herpes simplex virus, and rubella IgG in the absence of IgM antibodies. Clinical pregnancy, ectopic pregnancy, miscarriage, live birth, preterm birth, congenital malformation, and perinatal death were evaluated in both infection and non-infection group. Multivariate logistic regression was applied to calculate odds ratio.Results: Previous toxoplasmosis infection is associated with a significantly decreased preterm birth rate [P = 0.045, OR = 0.755 (95% CI, 0.571–0.997), Adjusted OR = 0.749 (95%CI, 0.566–0.991)]. No differences in clinical pregnancy, ectopic pregnancy, miscarriage, and perinatal death were observed between the corresponding TORCH infection group [IgM (–) IgG(+)] and the non-infection group [IgM (–) IgG (–)].Conclusions: Previous TORCH infections were not associated with adverse pregnancy and neonatal outcomes in IVF/ICSI-ET overall, and toxoplasmosis infection might be associated with a lower preterm birth rate in patients underwent IVF/ICSI-ET. The necessity of TORCH IgG screening in IVF procedure might need re-evaluation, and further cost-effective analysis might be helpful for the clinical management strategy.

Endometrial thickness is associated with incidence of small-for-gestational-age infants in fresh in vitro fertilization–intracytoplasmic sperm injection and embryo transfer cycles

To investigate whether endometrial thickness (EMT) is associated with adverse obstetric and neonatal outcomes in fresh invitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. Retrospective cohort study. University-based reproductive medical center. Women under the age of 42 years who underwent IVF/ICSI treatment and received fresh ET in our unit from January 2017 to December 2018, resulting in a live singleton birth. Controlled ovarian hyperstimulation and IVF/ICSI; fresh ET. Birth weight, gestational age, small for gestational age (SGA), large for gestational age (LGA), placenta previa, placental abruption, hypertensive disorders, and gestational diabetes mellitus. The risk of being born SGA was statistically significantly increased in the EMT ≤7.5 mm group compared with those from the EMT >12 mm group (adjusted odds ratio [aOR] 2.391; 95% confidence interval [CI], 1.155-4.950). Moreover, maternal body mass index, secondary infertility, preterm delivery, and hypertensive disorders were all independent predictors for SGA. The mean birth weights of singletons in women with EMT ≤7.5 mm were lower than in the groups with EMT >7.5-12 mm and EMT >12 mm (3.25 ± 0.56 kg vs. 3.38 ± 0.51 kg and 3.39 ± 0.53 kg, respectively). After fresh IVF/ICSI-ET, the risk of SGA was increased twofold in women with EMT ≤7.5 mm compared with women with EMT >12 mm. We suggest that women with a thin EMT after obtaining a pregnancy by IVF should receive improved prenatal care to reduce the risk of delivering a SGA infant.

Growth hormone supplementation may improve the pregnancy rate and endometrial receptivity among women aged more than 40 years undergoing in vitro fertilization

BackgroundGrowth hormone (GH) supplements have been shown to improve pregnancy and live-birth rates, suggesting that GH has a beneficial effect on oocyte quality. However, the effects of GH on implantation and receptivity remain unknown. This study evaluated the efficacy of GH in women aged more than 40 years participating in assisted reproductive technology (ART) programs. MethodsCycles of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in women aged more than 40 years (range, 40–43 years) between January 2009 and March 2014 at a university-based reproductive center were reviewed. Women were divided into two groups, those with and without GH co-stimulation. ART outcomes were evaluated. ResultsSupplement of GH significantly lowered cycle cancellation rate by increasing the per cycle rates of harvesting at least one oocyte and transferring at least one embryo (80.2% vs. 69.4%). GH increased the per cycle clinical pregnancy (15.9% vs. 6.8%) and favorable ultrasonic endometrial pattern (60.9% vs. 39.3%) rates. GH also increased the per transfer clinical pregnancy (19.9% vs. 9.9%) and implantation (11.2% vs. 5.2%) rates and the rate of a favorable ultrasonic endometrial pattern (65.1% vs. 45.0%). ConclusionGH supplementation reduces the cycle cancellation rate in women aged more than 40 years, and increases the favorable ultrasonic endometrial pattern, pregnancy, and implantation rates by its beneficial actions on embryo quality and endometrial receptivity.

Risk of low birth weight infants in women conceived through in vitro fertilization and fresh embryo transfer

Objective To analyze the risk factors of low birth weight (LBW) in infants who were conceived through fresh embryo transfer after in vitro fertilization. Methods We retrospectively reviewed the medical records of 4 930 live babies born after in vitro fertilization/intra-cytoplasmic sperm injection- embryo transfer (IVF/ICSI-ET) at Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University between January 2011 to December 2016. They were 3 474 singletons and 1 456 pairs of dizygotic twins. According to their birth weight, all singletons were divided into two groups: the LBW singleton group (<2 500 g, n=252) and the control singleton group (≥2 500 g, n=3 222). Two dizygotic twin groups, the LBW dizygotic twin group (<2 500 g, n=1 014) and the control dizygotic twin group (≥2 500 g, n=442), were set up as well. Clinical characteristics of the infants in different groups and risk factors of LBW were analyzed. Independent samples t-test, Mann-Whitney U test, Chi-square test, and logistic regression were used for statistical analysis. Results (1) The rates of LBW were 7.25% (252/3 474) in singletons and 69.64% (1 014/1 456) in dizygotic twins. (2) In singleton pregnancies, the maternal body mass index (BMI) of the LBW group was lower than that of the control group [(20.9±2.8) vs (21.3±2.7) kg/m2, t=2.162, P=0.031], while the rates of preterm delivery and blastocyst transfer were higher [61.7% (153/252) vs 5.7% (182/3 222), 8.7% (22/252) vs 5.1% (163/3 222), χ2=814.232 and 6.234, respectively, all P 10 970 pmol/L) and different gender of twins were independent risk factors for LBW in dizygotic twin pregnancies (adjusted OR=4.51, 1.35 and 1.45, 95%CI: 3.50-5.82, 1.06-1.74 and 1.09-1.93, all P<0.05). Conclusions High maternal serum E2 level after controlled ovarian stimulation (COS) in fresh embryo transfer cycle may be one of the risk factors for LBW in twin pregnancies. Key words: Infant, low birth weight; Fertilization in vitro; Embryo transfer; Estradiol; Ovulation induction; Risk factors