Luteal phase support with oral progesterone improves live birth rate in intrauterine insemination cycles using letrozole.

RESEARCH QUESTION: Does luteal phase support (LPS) with oral progesterone improve the live birth rate (LBR) in patients undergoing intrauterine insemination (IUI) cycles with letrozole? DESIGN: This retrospective cohort study included 1199 IUI cycles with letrozole between January 2017 and December 2021. A nearest neighbour random matching approach was employed to pair the LPS group and the control group in a 1:2 ratio. Eight variables were chosen for matching in the propensity score matching (PSM) model: age; body mass index; duration of infertility; cause(s) of infertility; antral follicle count; basal concentration of FSH; rank of IUI attempts; and leading follicle size. LBR was selected as the primary outcome. RESULTS: In total, 427 LPS cycles were matched with 772 non-LPS (control) cycles after PSM. The LBR was significantly higher in the LPS group compared with the control group (19.7% versus 14.5%; P = 0.0255). The clinical pregnancy rate (23.2% versus 17.6%; P = 0.0245) and ongoing pregnancy rate (20.6% versus 15.8%; P = 0.0437) were also significantly higher in the LPS group. The biochemical pregnancy rate, ectopic pregnancy rate and miscarriage rate were similar in the two groups (P > 0.05). The intergroup comparison revealed no significant variances in terms of gestational age, mode of delivery, ectopic pregnancy rate or abortion rate. Furthermore, there were no significant differences in birth weight or birth length between the two groups. CONCLUSIONS: Luteal support with oral progesterone significantly improved the LBR in IUI cycles with letrozole, but did not affect neonatal outcomes.

Linking African herbivore community enamel isotopes and environments: challenges, opportunities, and paleoecological implications.

Paleoenvironmental reconstructions of fossil sites based on isotopic analyses of enamel typically rely on data from multiple herbivore taxa, with the assumption that this dietary spectrum represents the community's isotopic range and provides insights into local or regional vegetation patterns. However, it remains unclear how representative the sampled taxa are of the broader herbivore community and how well these data correspond to specific ecosystems. Verifying these underlying assumptions is essential to refining the utility of enamel isotopic values for paleoenvironmental reconstructions. This study explores potential links between modern herbivore community carbon isotopic enamel spectra, biome types, and climate in sub-Saharan Africa. This region is one of the most comprehensively isotopically sampled areas globally and is of particular relevance to hominin evolution. Our extensive data compilation reveals that published enamel isotopic data from sub-Saharan Africa typically sample only a small percentage of the taxa documented at most localities and that some biome types (e.g., subtropical savannas) are dramatically overrepresented relative to others (e.g., forests) in these modern data sets. Multiple statistical analyses, including linear models and cluster analyses, revealed weak relationships of associated mammalian herbivore enamel isotopic values, biome type, and climate parameters. These results confound any simple assumptions about how community isotopic profiles map onto specific environments, highlighting the need for more precise strategic approaches in extending isotopic frameworks into the past for paleoecological reconstructions. Developing more refined modern analogs will ultimately allow us to more accurately characterize the isotopic spectra of paleo-communities and link isotopic dietary signatures to specific ecosystems.

Letrozole co-treatment in an antagonist protocol for overweight women undergoing IVF treatment: a retrospective study.

BACKGROUND: Overweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment. METHODS: This retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People's Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome. RESULTS: Letrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P < 0.05). The quantity and quality of embryos were comparable between the two groups (P > 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17-3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05). CONCLUSION: Letrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment.

The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

GM-CSF improves endometrial receptivity in a thin endometrium rat model by upregulating HOXA10.

Endometrial receptivity is a prerequisite for the success of assisted reproduction. Patients with a consistently thin endometrium frequently fail to conceive, owing to low endometrial receptivity, and there are currently very few therapeutic options available. Our previous study demonstrated that intrauterine granulocyte-macrophage colony-stimulating factor (GM-CSF) administration resulted in a significant improvement in clinical pregnancy and implantation rates and was an effective means of increasing endometrial thickness on the day of embryo transfer in patients with thin endometrium. In order to explore the underlying process, an animal model with a thin endometrium was constructed, the homeobox A10 gene (HOXA10) was downregulated, and an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) was employed. Our findings strongly suggest a marked decrease in GM-CSF levels in the thin endometrial rat model, and the suppression of HOXA10 impeded the therapeutic efficacy of GM-CSF in this model. Moreover, we showed that GM-CSF significantly increases endometrial receptivity in the rat model and upregulates HOXA10 via the MAPK/ERK pathway. Our data provide new molecular insights into the mechanisms underlying formation of a thin endometrium and highlight a novel, potential clinical treatment strategy as well as directions for further research.

COVID-19 infection after oocyte retrieval did not have detrimental effects on embryo implantation for frozen embryo transfer.

Patients preparing for their renewal fertility treatments with embryos frozen before coronavirus disease 2019 (COVID-19) infection do not need to be concerned about the potential impact of COVID-19 infection on oocyte quality and embryonic development. However, many women are still hesitant to undergo frozen embryo transfer (FET) due to fear of the detrimental effect of COVID-19 infection on endometrial receptivity and embryo implantation. The objective was to explore whether COVID-19 infection after oocyte retrieval is related to an increased risk of adverse pregnancy outcomes in a cohort of Chinese women undergoing FET. A retrospective cohort study was conducted among 300 infertile women undergoing FET with embryos frozen before COVID-19 infection. Women were categorized into noninfection, infection before FET, or infection after FET groups. Multivariable logistic regression was performed to assess the association of COVID-19 infection with clinical pregnancy outcomes, including biochemical pregnancy, clinical pregnancy, and early miscarriage. The implantation rates for patients in the group with infection before FET (29.14%) and the group with infection after FET (30.38%) were not significantly lower than those in the noninfection group (31.03%). The rate of biochemical pregnancy (54.55% vs. 52.27%, p = 0.750; 43.14% vs. 52.27%, p = 0.209) was not significantly different among the three groups. Although the clinical pregnancy rate showed a declining trend from 45.45% in the noninfection group to 38.27% in the group with infection after FET, this result was not statistically significant. The early miscarriage rate was similar in the group with infection before FET and the group with infection after FET compared with that in the noninfection group (3.64% vs. 5.68%, p = 0.496; 6.86% vs. 5.68%, p = 0.739). After adjusting for potential confounders, the biochemical pregnancy rate, clinical pregnancy rate, and early miscarriage rate were not significantly different for patients with infection before or after FET compared with patients without infection. This research indicated that COVID-19 infection after oocyte retrieval with embryos frozen before infection did not cause any detrimental effect on endometrial receptivity for embryo implantation.

Relationships between birth weight discordance and maternal and perinatal risks among twin pregnancies conceived following frozen embryo transfer.

STUDY QUESTION: Is intertwin birth weight discordance associated with adverse maternal and perinatal outcomes following frozen embryo transfer (FET)? SUMMARY ANSWER: For twins conceived following FET, intertwin birth weight discordance is related to elevated risks of neonatal mortality irrespective of chorionicity, and the risk of hypertensive disorders of pregnancy (HDP) is elevated for the mothers of dichorionic twins affected by such birth weight discordance. WHAT IS KNOWN ALREADY: While the relationships between intertwin birth weight discordance and adverse maternal or fetal outcomes have been studied for naturally conceived twins, similarly comprehensive analyses for twins conceived using ART remain to be performed. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study of all twin births from 2007 to 2021 at Shanghai Ninth People's Hospital in Shanghai, China that were conceived following FET (N = 6265). PARTICIPANTS/MATERIALS, SETTING, METHODS: Intertwin birth weight discordance was defined as a 20% difference in neonatal birth weights. The primary study outcome was the incidence of HDP and neonatal death while secondary outcomes included gestational diabetes, placenta previa, placental abruption, intrahepatic cholestasis of pregnancy, preterm premature rupture of the membranes, Cesarean delivery, gestational age, birth weight, stillbirth, birth defect, neonatal jaundice, necrotizing enterocolitis, and pneumonia incidence. Logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% CIs for maternal and neonatal outcomes. Subgroup analyses were conducted, and Kaplan-Meier survival analysis was used to estimate the survival probability. The sensitivity analysis was performed with a propensity score-based patient-matching model, an inverse probability weighting model, a restricted cubic spline analysis, and logistic regression models using other percentage cutoffs for discordance. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6101 females that gave birth to dichorionic twins during the study interval, birth weight discordance was observed in 797 twin pairs (13.1%). In this cohort, intertwin birth weight discordance was related to an elevated risk of HDP (aOR 1.56; 95% CI 1.21-2.00), and this relationship was confirmed through sensitivity analyses. Hypertensive disease risk rose as the severity of this birth weight discordance increased. Discordant birth weight was also linked to increased odds of neonatal mortality (aOR 2.13; 95% CI 1.03-4.09) and this risk also increased with the severity of discordance. Of the 164 women with monochorionic twins, the discordant group exhibited an elevated risk of neonatal death compared to the concordant group (crude OR 9.00; 95% CI 1.02-79.3). LIMITATIONS, REASONS FOR CAUTION: The limitations of this study are its retrospective nature and the fact that the available data could not specify which twins were affected by adverse outcomes. There is a lack of an established reference birth weight for Chinese twins born at a gestational age of 24-41 weeks. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that twins exhibiting a birth weight discordance are related to an elevated risk of adverse maternal and perinatal outcomes, emphasizing a potential need for higher levels of antenatal surveillance in these at-risk pregnancies. STUDY FUNDING/COMPETING INTEREST(S): Authors declare no conflict of interest. This study was funded by the Clinical Research Program of Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYLJ202118) and the National Natural Science Foundation of China (Grant Nos 82271693 and 82273634). TRIAL REGISTRATION NUMBER: N/A.

Changes in sexual frequency among 51 150 infertile Chinese couples over the past 10 years.

STUDY QUESTION: How did the sexual frequency change and what are the related influencing factors among infertile Chinese couples over the past 10 years? SUMMARY ANSWER: Sexual frequency has declined among infertile Chinese couples over the past decade, with such declines being most pronounced for women between the ages of 18 and 39. WHAT IS KNOWN ALREADY: Many researchers have explored trends in coital frequency and variables associated among healthy individuals in other nations. There have been major changes in all aspects of Chinese life and society over the past decade, including two major fertility policy adjustments. The sexual habits of infertile couples in China remain poorly understood and warrant further investigation. STUDY DESIGN, SIZE, DURATION: A retrospective cohort study of 51 150 infertile couples that visited our facility between January 2011 and December 2020 at a tertiary care academic medical centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome for this study was whether couples had engaged in sexual intercourse ≤4 times/month or >4 times/month. Multivariable logistic regression analyses were performed to detect the association between the variables and sexual frequency. Analyses were further performed to determine whether observed trends remained evident in women from different age subgroups. To assess whether these trends differed before and after the introduction of the universal two-child policy in China (January 2016), we additionally assessed trends in these age subgroups of women relative to the time at which this policy was introduced. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of couples reporting having engaged in sexual intercourse >4 times/month fell over the past decade from 62.7% (2011-2013) to 55.9% (2014-2015) to 52.7% (2016-2020). Declines in sexual frequency were evident for women between the ages of 18 and 39 (P < 0.05), whereas no such changes were evident for women between the ages of 40 and 50. Younger men and women, as well as individuals with a less than junior college education level, reported higher frequencies of sexual intercourse. For women, being remarried and having a more recent diagnosis of infertility were associated with increased coital frequency. This frequency decreased progressively for women as BMI values increased. There was no detected relationship between coital frequency and nationality or history of prior births. LIMITATIONS, REASONS FOR CAUTION: These analyses were dependent on self-reported data, and may thus have been impacted by the over- or under-reporting of sexual frequency as a consequence of social desirability bias. In addition, not all potentially relevant variables were assessed in all analyses, and certain potentially relevant variables such as family income or pornography use were not measured in any analyses. WIDER IMPLICATIONS OF THE FINDINGS: Sexual frequency is closely related to infertility risks. This general downward trend in sexual frequency may warrant concern. At present, these reductions remain an interesting yet unexplained topic worthy of further study. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Key Research and Development Program of China (Grant no. 2018YFC1003000) and the National Natural Science Foundation of China (Grant no. 81771533). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Association of maternal pre-pregnancy body mass index with birth weight and preterm birth among singletons conceived after frozen-thawed embryo transfer.

BACKGROUND: To explore the effect of pre-pregnancy body mass index (BMI) on neonatal outcomes among singletons born after frozen embryo transfer (FET). METHODS: This large retrospective cohort study included 18,683 singleton infants born after FET during the period from Jan 1, 2007 to Dec 31, 2019. The main outcomes were large for gestational age (LGA) and preterm birth. Logistic regression models with generalized estimating equations for clustering by patients to estimate odds ratios of LGA and preterm birth. RESULTS: Overweight was positively associated with LGA overall (adjusted OR 1.78 [95%CI 1.60-1.98]), and this association was consistent across age categories. The underweight was inversely associated with LGA among mothers younger than 35 years (adjusted OR 0.49 [95%CI 0.39-0.62] among mothers younger than 30 years; adjusted OR 0.47 [95%CI 0.37-0.60] among mothers aged 30-34 years), but this association was no significant among mothers 35 years or older. Overweight was positively and significantly associated with preterm birth overall (adjusted OR 1.52 [95%CI 1.30-1.77]) and consistently across age categories. The underweight mothers younger than 30 years had a decreased risk of preterm birth (adjusted OR 0.70 [95%CI 0.51-0.97]), but the underweight was no significantly associated with preterm birth among women aged 30 years of older. CONCLUSIONS: The risks of LGA and preterm birth were increased in singletons born to overweight mothers, regardless of the maternal age. Underweight decreased the risk of LGA and preterm birth for younger mothers. These findings are important for providing preconceptional counseling to specifically targeted women at high risk of LGA and preterm birth.

Prevalence and factors associated with overweight or obesity among 2- to 6-year-old children in Hunan, China: a cross-sectional study.

OBJECTIVE: To compare the prevalence of overweight or obesity (ow/ob) with WHO BMI cut-off points, International Obesity Task Force (IOTF) cut-off points and Chinese BMI criteria and examine its potential factors among preschool children in Hunan Province. DESIGN: A cross-sectional survey including anthropometric measurements and questionnaires about children's information, caregivers' socio-demographic characteristics and maternal characteristics. χ2 tests and univariate and multivariate binary logistic regression were performed to evaluate the possible factors of ow/ob. SETTING: Hunan, China, from September to October 2019. PARTICIPANTS: In total, 7664 children 2 to 6 years of age. RESULTS: According to Chinese BMI criteria, about 1 in 7-8 children aged 2-6 years had ow/ob in Hunan, China. The overall estimated prevalence of ow/ob among 2- to 6-year-old children was significantly higher when based on the Chinese BMI criteria compared with the WHO BMI cut-off points and IOTF cut-off points. According to Chinese BMI criteria, ow/ob was associated with residing in urban areas, older age, male sex, eating snacking food more frequently, macrosomia delivery, caesarean birth, heavier maternal prepregnancy weight and pre-delivery weight. CONCLUSION: The prevalence of ow/ob in preschool children in Hunan Province remains high. More ow/ob children could be screened out according to Chinese BMI cut-offs compared with WHO and IOTF BMI criteria. In the future, targeted intervention studies with matched controls will be needed to assess the long-term effects of intervention measures to provide more information for childhood obesity prevention and treatment.