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Human Reproduction (Oxford, England) Jun 2024Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin...
A modified flexible GnRH antagonist protocol using antagonist early cessation and a gonadotropin step-down approach improves live birth rates in fresh cycles: a randomized controlled trial.
STUDY QUESTION
Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response?
SUMMARY ANSWER
The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle.
WHAT IS KNOWN ALREADY
Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon.
STUDY DESIGN, SIZE, DURATION
An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation.
MAIN RESULTS AND THE ROLE OF CHANCE
Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05).
LIMITATIONS, REASONS FOR CAUTION
A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings.
WIDER IMPLICATIONS OF THE FINDINGS
The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders.
STUDY FUNDING/COMPETING INTEREST(S)
This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453.
TRIAL REGISTRATION DATE
21 November 2021.
DATE OF FIRST PATIENT’S ENROLLMENT
23 November 2021.
PubMed: 38942602
DOI: 10.1093/humrep/deae145 -
Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.Human Reproduction (Oxford, England) Jun 2024What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course...
STUDY QUESTION
What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?
SUMMARY ANSWER
In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.
WHAT IS KNOWN ALREADY
Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.
STUDY DESIGN, SIZE, DURATION
The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.
WIDER IMPLICATIONS OF THE FINDINGS
Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.
STUDY FUNDING/COMPETING INTEREST(S)
The research received no specific funding, and the authors declare no competing interests.
TRIAL REGISTRATION NUMBER
clinicaltrial.gov NCT05557201.
PubMed: 38942601
DOI: 10.1093/humrep/deae146 -
BMJ Paediatrics Open Jun 2024Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic...
BACKGROUND
Limited evidence exists regarding children receiving home healthcare devices (HHDs). This study aimed to describe the range and type of HHD use by children with chronic medical conditions in Japan and explore factors leading to increased use of these devices.
METHODS
This retrospective cohort study was conducted using data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Children receiving HHD aged ≤18 years between April 2011 and March 2019 were included. Children newly administered HHD between 2011 and 2013 were followed up for 5 years, and logistic regression analysis was performed to assess the relationship between increased HHD use and each selected risk factor (comorbidity or types of HHD). The models were adjusted for age category at home device introduction, sex and region.
RESULTS
Overall, 52 375 children receiving HHD were identified. The number (proportion) of children receiving HHD increased during the study period (11 556 [0.05%] in 2010 and 25 593 [0.13%] in 2018). The most commonly administered HHD was oxygen (51.0% in 2018). Among the 12 205 children receiving HHD followed up for 5 years, 70.4% and 68.3% who used oxygen or continuous positive airway pressure, respectively, were released from the devices, while only 25.8% who used mechanical ventilation were released from the device. The following diagnosis/comorbidities were associated with increased HHD use: other neurological diseases (OR): 2.85, 95% CI): 2.54-3.19), cerebral palsy (OR: 2.16, 95% CI: 1.87 to 2.49), congenital malformations of the nervous system (OR: 1.70, 95% CI: 1.34 to 2.13) and low birth weight (OR: 1.68, 95% CI: 1.41 to 2.00).
CONCLUSIONS
This study provides nationwide population-based empirical data to clarify the detailed information regarding children receiving HHD in Japan. This information could assist healthcare professionals in improving the quality of life of these children and their families and help health policymakers consider measures.
Topics: Humans; Japan; Retrospective Studies; Female; Male; Child; Home Care Services; Child, Preschool; Infant; Adolescent; Chronic Disease; Infant, Newborn
PubMed: 38942589
DOI: 10.1136/bmjpo-2024-002685 -
BMJ Paediatrics Open Jun 2024To determine the prevalence and associated factors of scabies among the children living in the Madrasahs (Islamic religious educational institution) of Bangladesh was...
INTRODUCTION
To determine the prevalence and associated factors of scabies among the children living in the Madrasahs (Islamic religious educational institution) of Bangladesh was the objective of the study.
METHODS
This cross-sectional study was conducted in eight selected Madrasahs from May to October 2023 among male and female children aged between 3 and 18 years. Children were screened for scabies according to criteria developed by the International Alliance for the Control of Scabies.
RESULTS
It was found that overall prevalence of scabies among the children living in Madrasahs was almost 34% (mild 73.5%, moderate 24.9% and severe 1.6%). Prevalence of scabies among male was higher than female (39.4% vs 28.4%). Male gender (aOR 2.09, 95% CI 1.27 to 3.47, p=0.004) and age (aOR 0.95, 95% CI 0.91 to 0.99, p=0.017) were two significant predictors of scabies among children. Besides, living in Madrasahs having more boarders (aOR 1.37, 95% CI 1.06 to 1.69, p=0.025), shared bedding, clothes or toilet stuffs with other children (aOR 1.46, 95% CI 1.03 to 2.09, p=0.036) and history of pruritus in the close entourage (aOR 4.19, 95% CI 3.07 to 5.73, p<0.001) were associated with a higher chance of being infected by scabies.
CONCLUSION
Almost one-third of the children living in the Islamic boarding schools in Bangladesh are suffering from scabies, more prevalence in male and younger children. Accommodation of higher number of boarders, sharing personal staffs and pruritus in close contacts increase the risk of scabies in these children.
Topics: Humans; Scabies; Male; Bangladesh; Female; Cross-Sectional Studies; Child; Prevalence; Adolescent; Risk Factors; Child, Preschool; Islam; Schools
PubMed: 38942588
DOI: 10.1136/bmjpo-2023-002421 -
Progress in Molecular Biology and... 2024Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include... (Review)
Review
Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) etc. The occurrence of these diseases increases with age and is one of the challenging problems among elderly people. Though, several scientific research has demonstrated the key pathologies associated with NDDs still the underlying mechanisms and molecular details are not well understood and need to be explored and this poses a lack of effective treatments for NDDs. Several lines of evidence have shown that NDDs have a high prevalence and affect more than a billion individuals globally but still, researchers need to work forward in identifying the best therapeutic target for NDDs. Thus, several researchers are working in the directions to find potential therapeutic targets to alter the disease pathology and treat the diseases. Several steps have been taken to identify the early detection of the disease and drug repurposing for effective treatment of NDDs. Moreover, it is logical that current medications are being evaluated for their efficacy in treating such disorders; therefore, drug repurposing would be an efficient, safe, and cost-effective way in finding out better medication. In the current manuscript we discussed the utilization of drugs that have been repurposed for the treatment of AD, PD, HD, MS, and ALS.
Topics: Humans; Drug Repositioning; Neurodegenerative Diseases; Animals
PubMed: 38942541
DOI: 10.1016/bs.pmbts.2024.03.035 -
Journal of Physical Activity & Health Jun 2024The clear public messaging from international health authorities is that individuals should "sit less and move more." While it is acknowledged that this guidance needs...
The clear public messaging from international health authorities is that individuals should "sit less and move more." While it is acknowledged that this guidance needs to be tailored to the age of people and also to their health, and abilities, the guidance is not tailored to their current level of physical behaviors. This opinion piece aims to highlight that although people with excessive sitting and insufficient moderate-to-vigorous physical activity should sit more and move less, for other people their health would be promoted by sitting more and moving less. Thus, physical behaviors are not always "poison" or "medicine," but rather the health impact of changes in physical behaviors depends on people's initial levels. Policy, research, and practice implications of this realization are presented. Only tailoring messaging to age and health status could be far from optimal for people with very different current levels of physical behaviors. Policy, research, and practice will be enhanced when the potential for physical behaviors to be either health hindering or health promoting is adequately considered.
PubMed: 38942416
DOI: 10.1123/jpah.2024-0324 -
Urology Jun 2024To determine whether early vs. delayed autotransplantation are associated with adverse outcomes in patients undergoing renal autotransplantation.
OBJECTIVE
To determine whether early vs. delayed autotransplantation are associated with adverse outcomes in patients undergoing renal autotransplantation.
METHODS
Patients who underwent renal autotransplantation from June 2012 to September 2022 were divided into two groups based on timing of autotransplant in relation to initial intervention or diagnosis (early cohort: ≤1-year; delayed cohort: >1-year). Primary outcomes were perioperative complications, aborted surgery, renal function (glomerular filtration rate [GFR]), and postoperative complications at most recent follow-up.
RESULTS
Autotransplantation patients (N=72) were predominantly female (68%) and White (54%), with a median age of 49 years. 90% of patients had undergone previous interventions, including stenting (40%) and nephrostomy tubes (49%), primarily for obstruction (64%). Early vs. delayed cohorts had median preoperative disease durations of 143 (IQR 83-222) vs. 673 days (IQR 529-1,703, p<0.001), with similar median follow-up times (879 vs. 818 days, p=0.8). Groups were similar in demographics and comorbidities. There were no significant differences in rates of aborted surgery (15% vs. 4.2%, p=0.3), perioperative complications (15% vs. 17%, p>0.9), long-term complications (49% vs. 48%, p>0.9), or changes in GFR (median change +3 vs. +4, p=0.7). Outcomes were comparable across preoperative disease durations ranging from 6 to 24 months. These findings were confirmed following adjustments for sex, body mass index, American Society of Anesthesiologists classification, race, preoperative creatinine levels, laterality, gastroesophageal reflux disease, diabetes, hypertension, nephrolithiasis, hyperlipidemia, history of colon surgery, urologic surgery, abdominal surgery, and prior interventions in separate logistic models.
CONCLUSIONS
Disease duration before autotransplantation does not influence outcomes, offering reassurance for clinical decision-making in complex cases.
PubMed: 38942394
DOI: 10.1016/j.urology.2024.06.050 -
Annals of Vascular Surgery Jun 2024In the endovascular aneurysm repair (EVAR) era, open surgical repair (OSR) is performed for ruptured abdominal aorta aneurysm (RAAA) in patients with complex aneurysm...
OBJECTIVES
In the endovascular aneurysm repair (EVAR) era, open surgical repair (OSR) is performed for ruptured abdominal aorta aneurysm (RAAA) in patients with complex aneurysm neck and technical difficulties. Understanding the risk factors of OSR is essential for the clinical selection of the ideal surgical procedure. We aimed to re-evaluate the outcomes of OSR and treatment options for RAAA.
METHODS
Patients who underwent OSR for RAAA between January 2010 and December 2022 were enrolled in this single-center, retrospective observational study. Preoperative status, operative findings, and postoperative course were retrospectively reviewed. The Cox proportional hazards model was used to evaluate the association between age and early postoperative mortality.
RESULTS
Among 142 patients, 43 (30.3%) and 99 (69.7%) were aged ≥80 and <80 years, respectively. Postoperative mortality within 30 days occurred in 24 (16.9%) patients (11/43 [25.6%] and 13/99 [13.1%] patients aged ≥80 and <80 years, respectively; hazard ratio [HR]=1.95; P=0.069). In a multivariable analysis, increased postoperative mortality within 30 days was associated with age ≥80 years (adjusted HR, aHR=2.36; P=0.049), the presence of pre- or intraoperative cardiopulmonary arrest (aHR=12.0; P<0.001), and postoperative gastrointestinal disorder (aHR=4.42; P=0.003).
CONCLUSIONS
EVAR may be preferable in older people; however, its use in cases of pre- or intraoperative cardiopulmonary arrest or perioperative gastrointestinal disorders remains controversial, and a careful discussion on the surgical indications is needed in such cases.
PubMed: 38942379
DOI: 10.1016/j.avsg.2024.04.016 -
Annals of Vascular Surgery Jun 2024After autogenous arteriovenous (AV) access creation for end-stage renal disease, a majority of patients will continue on hemodialysis (HD), a minority will receive...
OBJECTIVES
After autogenous arteriovenous (AV) access creation for end-stage renal disease, a majority of patients will continue on hemodialysis (HD), a minority will receive definitive treatment with kidney transplantation, and a subset of patients will convert to peritoneal dialysis (PD). Our goal was to identify patient factors associated with early transition from HD to either kidney transplantation or PD.
METHODS
This is a case-control study of all patients with first-time AV access creation in the Vascular Quality Initiative (2011-2022) who had long-term follow-up. Patients who remained on HD after AV access creation were the control group while patients who received early kidney transplant or who converted to PD were the two case groups. Relationship among demographics, comorbidities, neighborhood social disadvantage, and functional status as they relate to renal replacement therapy modality was assessed.
RESULTS
There were 19,782 patients included; the average age was 62±15 years and 57% were male. During the follow-up period of a median 306 (71-403) days, 1.3% underwent a kidney transplantation and 2.3% underwent conversion to PD. On univariable analysis, rates of kidney transplantation or conversion to PD varied with race (P<.001), insurance status (P<.001), Area Deprivation Index (ADI) quintile (P<.001), and several medical comorbidities. On multivariable analysis, impaired ambulation, current smoking, Medicaid or Medicare insurance, Black race, heart failure, body mass index, and older age were associated with decreased transplantation rates. Conversion to PD was associated with ADI Q5, Q4, and Q3. Decreased conversion to PD was associated with impaired ambulation, Hispanic ethnicity, Black race, former smoking, medication-controlled diabetes, and older age.
CONCLUSION
Decreased kidney transplantation was associated with Black race and non-commercial health insurance but not ADI quintile, suggesting disparities exist beyond community-level access to care. Early kidney transplantation conveyed a 3-year survival benefit compared to HD and PD, which had similar survival. Further work is required to increase access to kidney transplantation and PD.
PubMed: 38942372
DOI: 10.1016/j.avsg.2024.06.002 -
Annals of Vascular Surgery Jun 2024Abdominal aortic aneurysm (AAA) screening has been offered to 65-year-old men living in Oslo, Norway, since May 2011. A significant number of AAA-related deaths occurred...
INTRODUCTION
Abdominal aortic aneurysm (AAA) screening has been offered to 65-year-old men living in Oslo, Norway, since May 2011. A significant number of AAA-related deaths occurred in individuals who are not eligible for screening. The primary aim of this study was to describe the group of patients admitted to Oslo University Hospital with a ruptured AAA after the implementation of the local AAA screening project. The following parameters were investigated: AAA detection prior to rupture, surveillance status, eligibility for screening and comorbidities. We also sought to compare outcomes (repair rates and 30-day mortality) between patients with and without an AAA detected prior to rupture.
METHODS
This cohort study included patients admitted acutely to Oslo University Hospital due to a symptomatic or ruptured AAA in the period January 2011 to December 2022. Data on demographics, prior AAA detection, surveillance status, treatment and mortality were collected retrospectively through electronic medical records.
RESULTS
We identified 200 patients with a symptomatic or ruptured AAA, among which 79 (40%) had an AAA detected prior to rupture - one (1%) through screening and 78 (39%) incidentally. Up to 30% of the incidentally detected AAAs were not under any surveillance. Six patients were found eligible for screening: one had attended, three were non-attenders and two had not been invited. Patients with an incidentally detected AAA prior to rupture had a more advanced age and a significantly higher degree of comorbidities than patients without a previously detected AAA, and the repair rates in these groups were 56% and 84% respectively (p < 0.001). Adjusted for comorbidities and risk factors, the odds ratio for repair among patients with incidentally detected AAA was 0.56 (p = 0.292). The 30-day mortality was not significantly different between the two groups (p = 0.097).
CONCLUSION
Most patients with a ruptured AAA were not eligible for screening, but 39% of the patients had an incidentally detected AAA prior to rupture. Standardized reporting and follow-up of incidentally detected AAAs is thus identified as an additional measure to organized screening in the effort to reduce AAA-related mortality.
PubMed: 38942371
DOI: 10.1016/j.avsg.2024.04.017