Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of ...multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer.
This multicentre, non-blinded, randomised controlled trial was undertaken in 21 academic fertility centres in China. 1650 women with regular menstrual cycles undergoing their first cycle of in-vitro fertilisation were enrolled from Aug 1, 2016, to June 3, 2017. Eligible women were randomly assigned to either fresh or frozen single blastocyst transfer. The randomisation sequence was computer generated, with block sizes of two, four, or six, stratified by study site. For those assigned to frozen blastocyst transfer, all blastocysts were cryopreserved and a delayed frozen-thawed single blastocyst transfer was done. The primary outcome was singleton livebirth rate. Analysis was by intention to treat. This trial is registered at the Chinese Clinical Trial Registry, number ChiCTR-IOR-14005405.
825 women were assigned to each group and included in analyses. Frozen single blastocyst transfer resulted in higher rates of singleton livebirth than did fresh single blastocyst transfer (416 50% vs 329 40%; relative risk RR 1·26, 95% CI 1·14–1·41, p<0·0001). The risks of moderate or severe ovarian hyperstimulation syndrome (four of 825 0·5% in frozen single blastocyst transfer vs nine of 825 1·1% in fresh single blastocyst transfer; p=0·16), pregnancy loss (134 of 583 23·0% vs 124 of 481 25·8%; p=0·29), other obstetric complications, and neonatal morbidity were similar between the two groups. Frozen single blastocyst transfer was associated with a higher risk of pre-eclampsia (16 of 512 3·1% vs four of 401 1·0%; RR 3·13, 95% CI 1·06–9·30, p=0·029).
Frozen single blastocyst transfer resulted in a higher singleton livebirth rate than did fresh single blastocyst transfer in ovulatory women with good prognosis. The increased risk of pre-eclampsia after frozen blastocyst transfer warrants further studies.
The National Key Research and Development Program of China.
OBJECTIVEIn China, there is a unique type of second marriage (SM) family where the woman is remarried, and the man is experiencing his first marriage. Additionally, the woman is older than the man. ...Therefore, these families experience many challenges: psychological, emotional, and societal pressure. Such family is a typical sample for studying sociocultural and psychological stress influencing on outcome of assisted reproductive technology (ART). This study aimed to investigate the impact of social psychological stress on the live birth outcomes AR.METHODSIn this retrospective cohort, second marriage (SM) families who visited the Second Hospital of Hebei Medical University reproductive center between January 2012 to December 2022 were screened, and 561s marriage families (the SM group) with 5600 first marriage (FM) families (the FM group) were included undergoing their first ART cycles. The primary outcome of this study was the live birth rate (LBR).RESULTSThe live birth rate (LBR) of SM group (30.7%) is lower than that of the FM group (43.6%) (p < 0.01). After adjustment by logistic regression, the second marriage group (OR = 1.269, 95%CI 1.031-1.562, p = 0.025) were independent factors associated with the outcome of live birth. After propensity score matching (PSM), the live birth rate of SM group (28.7%) is lower than the FM group (35.9%) (0 = 0.011).CONCLUSIONThe SM family experience higher levels of social and psychological pressure, which lead to lower level of LBR than FM family.
Objective. To examine the association between body mass index (BMI) and the outcome of in vitro fertilization or intracytoplasmic sperm injection embryo transfer- (IVF/ICSI-ET) assisted reproduction ...in women with polycystic ovary syndrome (PCOS) receiving the ultra-long agonist protocol. Methods. We retrospectively identified all women receiving IVF/ICSI-ET for the first time using the ultra-long protocol between January 2013 and January 2018 at our hospital. Only women at ≤35 years of age receiving the first cycle were analyzed. Results. A total of 1782 women were included in the analysis: 42 were underweight, 742 were overweight, 198 were obese, and 800 were normal weight. Gonadotropin dosage and duration were comparable between underweight and normal weight groups but were significantly higher/longer in overweight and obese groups (P<0.008). The number of oocytes retrieved was significantly lower in overweight and obese groups than in the normal weight group (P<0.008). The number of transferable embryos was significantly higher in normal weight group than overweight and obese groups (P<0.008). Embryo implantation rate, clinical pregnancy rate, full-term birth rate, and live birth rate did not differ among the 4 groups. The cycle cancellation rate was lower in the overweight and obese group than normal weight group (P<0.008). The miscarriage rate was higher in the obese group than the normal weight group (P<0.008). In multivariate logistic regression analysis, abnormal BMI was an independent risk for miscarriage (OR: 1.069, 95% CI 1.020, 1.122; P=0.006). Conclusion. Overweight and obesity are associated with poor outcomes in PCOS patients receiving ultra-long protocol. Measures to reduce body weight should be encouraged in overweight and obese PCOS women at ≤35 years of age prior to assisted reproductive technology (ART).
Polycystic ovary syndrome (PCOS) is one of the most common endocrine metabolic disorders characterized by hyperandrogenism, polycystic ovaries and ovulatory dysfunction. Several studies have reported ...that the aberrant expression of miRNAs contributes a lot to disordered folliculogenesis in PCOS, though the role and underlying mechanism of microRNA-200b (miR-200b) and microRNA-200c (miR-200c) in the development of PCOS remain unclear.
The expression of miR-200b in granulosa cells (GCs) derived from 90 PCOS patients and 70 controls was analyzed by using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Granulosa-like tumor cell line (KGN) was cultured for cell counting kit-8 (CCK-8) assays after over-expression of miR-200b, miR-200c or knockdown phosphatase and tensin homolog (PTEN). TargetScan was used to identify the potential targets of miR-200b and miR-200c, which was further verified by qRT-PCR, western blot and luciferase assays.
Significantly increased expression of miR-200b was observed in PCOS patients compared with the controls. Moreover, over-expression of miR-200b and miR-200c inhibited the proliferation of KGN cells. In addition, our results verified that miR-200b and miR-200c directly targeted PTEN, knockdown of which suppressed KGN cells proliferation.
Our findings demonstrate that miR-200b and miR-200c suppress the proliferation of KGN cells by targeting PTEN, and this might provide new evidence for abnormal proliferation of GCs in PCOS.
This paper aimed to analyze the relationship between baseline prolactin (PRL) levels and live birth rates (LBRs) in patients undergoing embryo transfer who did not have polycystic ovarian syndrome ...(PCOS) using a retrospective design. Patient(s): A total of 20,877 patients who had undergone IVF/intracytoplasmic sperm injection (ICSI) between December 2014 and December 2019. We examined the association between PRL concentrations and LBRs using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was developed. Following adjustment for confounding factors, multivariate regression analysis confirmed a statistically significant correlation between serum PRL and LBR. Particularly, when blood PRL content was less than 14.8 ng/mL, there exists a positive relation between serum PRL and LBRs. In contrast, once PRL concentrations surpassed the inflection point at 14.8 ng/mL, a meaningful relationship could no longer be inferred between serum PRL and LBR. Basal serum PRL levels were segmentally connected with LBRs.
Background Empty follicle syndrome (EFS) is a challenging clinical problem. This study aims to identify the risk factors for EFS, to present pregnancy outcomes in both EFS cycle as well as subsequent ...cycles, and to summarize an effective rescue protocol to improve outcomes. Methods A retrospective analysis between 2016 and 2020 was conducted at our center. Stricter criteria were applied to diagnose EFS. Logistic regression analysis was used to identify the risk factors for EFS. Further analyses were performed within the EFS cycle to present pregnancy outcomes and to find optimal rescue protocols. Long-term follow-up was conducted until live birth was achieved, covering at least two complete oocyte retrieval cycles. Results Among 14,066 patients, 54 (0.38%) were identified as EFS. Patients with polycystic ovary syndrome (PCOS) had a significantly higher risk of developing EFS than non-PCOS ones (aOR = 2.67; 95% CI, 1.47 to 4.83). Within EFS patients, delaying the second oocyte retrieval by 3–6 h significantly improved the rates of obtaining oocyte (97.4% versus 58.3%, P = 0.002), getting embryo available for transfer (92.3% versus 33.3%, P < 0.001), and pregnancy (48.7% versus 8.3%, P = 0.017) compared to other delayed retrieval times. Overall, 31.5% (17/54) and 46.7% (7/15) EFS patients achieved live birth in the EFS cycle and the future cycle, respectively. Conclusions PCOS is an independent risk factor for EFS, indicating that longer exposure time to human chorionic gonadotropin (hCG) may be necessary. Delaying the second oocyte retrieval by 3–6 h is an effective rescue protocol for EFS patients to achieve optimal outcomes. EFS in a single cycle does not necessarily indicate future fertility decline, but repeated EFS may result in poor outcomes.
The purpose of this article is to explore the relationship between the total dose of follicle-stimulating hormone (FSH) applied during controlled ovulation stimulation and the live birth rates (LBRs) ...in non-PCOS population. Many studies have found no difference between the dose of FSH application and pregnancy outcomes such as clinical pregnancy rates after fresh embryo transfer. However, a recent large retrospective analysis found a negative correlation between live birth rates and increasing dose of FSH. It is still controversial about the association between FSH dose and LBRs. In addition, no studies have yet explored the nonlinear relationship between FSH and LBRs. This cohort study included a total of 11,645 patients who had accepted IVF/intracytoplasmic sperm injection (ICSI) at the second hospital of Hebei medical university between December 2014 to December 2019. PCOS was identified by Rotterdam PCOS criteria. We researched the association between FSH total dose and live birth rates (LBRs) using multivariate regression analysis. In addition, a model for nonlinear relationships based on a two-part linear regression was applied. The analysis of threshold effects indicated that LBR increased with every 1000 IU FSH when the concentration of FSH was lower than 1410 IU (OR 1.55, 95% CI 1.05, 2.28); however, a negative association between FSH dose and LBR (OR 0.94, 95% CI 0.89, 0.99) was found when the FSH total dose was higher than 1410 IU. It is worth noting that the relationship between LBR and FSH dose varied among patients of different ages (OR 0.92 vs 1.06, P for interaction < 0.05).
Abstract
Context
Obesity management prior to infertility treatment remains a challenge. To date, results from randomized clinical trials involving weight loss by lifestyle interventions have shown no ...evidence of improved live birth rate.
Objective
This work aimed to determine whether pharmacologic weight-loss intervention before in vitro fertilization and embryo transfer (IVF-ET) can improve live birth rate among overweight or obese women.
Methods
We conducted a randomized, double-blinded, placebo-controlled trial across 19 reproductive medical centers in China, from July 2017 to January 2019. A total of 877 infertile women scheduled for IVF who had a body mass index of 25 or greater were randomly assigned to receive orlistat (n = 439) or placebo (n = 438) treatment for 4 to 12 weeks. The main outcome measurement was the live birth rate after fresh ET.
Results
The live birth rate was not significantly different between the 2 groups (112 of 439 25.5% with orlistat and 112 of 438 25.6% with placebo; P = .984). No significant differences existed between the groups as to the rates of conception, clinical pregnancy, or pregnancy loss. A statistically significant increase in singleton birth weight was observed after orlistat treatment (3487.50 g vs 3285.17 g in the placebo group; P = .039). The mean change in body weight during the intervention was −2.49 kg in the orlistat group, as compared to −1.22 kg in the placebo group, with a significant difference (P = .005).
Conclusion
Orlistat treatment, prior to IVF-ET, did not improve the live birth rate among overweight or obese women, although it was beneficial for weight reduction.
•The first large-scale multicenter retrospective study conducted in Northern China.•Both outcomes of fresh and frozen-thawed embryo transfer cycles in IVF were explored.•Exposure to O3, CO, and NO2 ...are negatively associated with fresh transfer outcomes.•SO2 exposure is inversely correlated with pregnancy outcomes in FET cycles.•Air pollution is associated with higher risk of ectopic pregnancy and lower oocyte yield.
Exposure to ambient air pollution has been reported to be inversely correlated with human reproductive health. However, the results of previous studies exploring the association between air pollution and in vitro fertilization (IVF) outcomes are conflicting, and further research is needed to clarify this association.
This study aimed to investigate the associations between exposure to air pollutants and IVF outcomes.
We conducted a multicenter retrospective cohort study involving 20,835 patients from four cities in Northern China, contributing to 11,787 fresh embryo transfer cycles, 9050 freeze-all cycles, and 17,676 frozen-thawed embryo transfer (FET) cycles during 2014–2018. We calculated the daily average concentrations of six criteria air pollutants (PM2.5, PM10, O3, NO2, CO, and SO2) during different exposure windows in IVF treatment timeline using data from the air monitoring station nearest to the residential site as approximate individual exposure. Generalized estimation equation models were used to assess the association between air pollution exposure and IVF outcomes.
Exposure to O3, NO2, and CO during most exposure windows in fresh embryo transfer cycles were correlated with lower possibilities of biochemical pregnancy, clinical pregnancy, and live birth. An inverse association of exposure to O3 and SO2 with pregnancy outcomes was observed in FET cycles. In addition, we found a significant association of exposure to air pollutants with a higher risk of ectopic pregnancy and lower oocyte yield.
Our study provided large-scale human evidence of the association between air pollution and adverse human reproductive outcomes in the population opting for IVF. Thus, exposure to air pollutants in the population opting for IVF should be limited to improve treatment outcomes.
Background The way of testicular tissue fixation directly affects the correlation and structural integrity between connective tissue and seminiferous tubules, which is essential for the study of male ...reproductive development. This study aimed to find the optimal fixative and fixation time to produce high-quality testicular histopathological sections, and provided a suitable foundation for in-depth study of male reproductive development with digital pathology technology. Methods Testes were removed from both sides of 25 male C57BL/6 mice. Samples were fixed in three different fixatives, 10% neutral buffered formalin (10% NBF), modified Davidson's fluid (mDF), and Bouin's Fluid (BF), for 8, 12, and 24 h, respectively. Hematoxylin and eosin (H&E) staining, periodic acid Schiff-hematoxylin (PAS-h) staining, and immunohistochemistry (IHC) were used to evaluate the testicle morphology, staging of mouse seminiferous tubules, and protein preservation. Aperio ScanScope CS2 panoramic scanning was used to perform quantitative analyses. Results H&E staining showed 10% NBF resulted in an approximately 15-17% reduction in the thickness of seminiferous epithelium. BF and mDF provided excellent results when staining acrosomes with PAS-h. IHC staining of synaptonemal complexes 3 (Sycp3) was superior in mDF compared to BF-fixed samples. Fixation in mDF and BF improved testis tissue morphology compared to 10% NBF. Conclusions Quantitative analysis showed that BF exhibited a very low IHC staining efficiency and revealed that mouse testes fixed for 12 h with mDF, exhibited morphological details, excellent efficiency of PAS-h staining for seminiferous tubule staging, and IHC results. In addition, the morphological damage of testis was prolonged with the duration of fixation time. Keywords: Mouse testis, Fixative, HE staining, IHC staining, PAS staining, Digital pathology
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