2 Minute Medicine Rewind September 23, 2024

Preconception and Early-Pregnancy Body Mass Index in Women and Men, Time to Pregnancy, and Risk of Miscarriage

1. Preconception BMI outside of the normal category in women and men was associated with lower fecundability and subfertility.

2. Overweight and obesity in women before or during early pregnancy were associated with increased odds of miscarriage.

Evidence Rating Level: 1 (Excellent)

Obesity in women has been linked with reduced fertility and increased risk of miscarriage; however, emerging evidence suggests that body mass index (BMI) among men may also be linked with these outcomes. The separate and combined associations of BMI in men and women with fertility and miscarriage are unclear. This study thus evaluated the association between BMI (preconception and early-pregnancy) in women and men with time to pregnancy and risk of miscarriage. This population-based prospective cohort study included couples > 18 years of age living in Rotterdam, who were in pre-conception or pregnancy between August 9, 2017, and July 1, 2021. Couples were allowed to participate more than once for different preconception or pregnancy episodes. Time-to-pregnancy analyses included 3033 episodes among women (median age: 31.6 years [IQR, 29.2-34.5]; median BMI: 23.5 kg/m2 [IQR, 21.2-26.5]) and 2288 episodes among men (median age: 33.4 years [IQR, 30.5-36.8]; median BMI, 24.9 kg/m2 [IQR, 23.0- 27.4]). Miscarriage analyses included 2770 pregnancy episodes among women (median age: 31.5 years [IQR, 28.9-34.3]; median BMI kg/m2: 23.5 [IQR, 21.3-26.7]) and 2189 pregnancy episodes among men (median age: 33.5 years [IQR, 30.4-36.8]; median BMI: 25.0 kg/m2 [IQR, 23.0-27.5]). Higher BMI in women and men was associated with decreased fecundability (fecundability ratio [FR]: women, 0.98 [95% CI, 0.97- 0.99]; men, 0.99 [95% CI, 0.98-1.00]) and greater odds of subfertility (odds ratio [OR]: women, 1.04 [95% CI, 1.02-1.05]; men, 1.03 [95% CI, 1.00-1.06]). Compared to normal weight, increased odds of subfertility was associated with underweight (odds ratio [OR], 1.88 [95% CI, 1.22-2.88]), overweight (OR, 1.35 [95% CI, 1.11-1.63]), and obesity (OR, 1.67 [95% CI, 1.30-2.13]) in women, and obesity in men (OR, 1.69 [95% CI, 1.24-2.31]). Furthermore, the combination of overweight and obesity in both partners was associated with subfertility (OR, 1.41 [95% CI, 1.06-1.87]) compared with normal weight in both partners. Finally, compared with normal weight in women, overweight (OR, 1.49 [95% CI, 1.12-1.98]) and obesity (OR, 1.44 [95% CI, 1.00-2.08]) were associated with increased odds of miscarriage. Overall, this study suggests that BMI outside of the normal category in women and men is a risk factor for decreased fertility, subfertility, and increases odds of miscarriage. These findings indicate that strategies for improving fertility and reducing miscarriage risk may involve optimizing BMI in women and men in preconception care settings. 

Sleep Disturbance and Subsequent Suicidal Behaviors in Preadolescence

1. Parent-reported preadolescent sleep disturbances were associated with risk for suicidal ideation and suicide attempts up to 2 years later.

2. Severe sleep disturbance, particularly nightmares and excessive daytime somnolence, increased the risk for suicidal behaviors.

Evidence Rating Level: 2 (Good)

Sleep disturbances are a risk factor for suicidal behaviors. In fact emerging evidence suggests a link between sleep disturbance and suicide risk among adolescents; however, research in this field is limited. Additionally, longitudinal studies of suicide risk at the population level and research on preadolescent suicidal behaviors are scarce. This study thus investigated the association between sleep disturbances in preadolescent children with longitudinal risk for suicidal ideation and suicide attempts 2-years later. This longitudinal-cohort study used data from Adolescent Brain Cognitive Development Study, which included children aged 9 or 10 years at baseline and their parents or caregivers who recruited at 21 sites across the US. Baseline recruitment was from June 2016 to October 2018 and 2-year follow-up from June 2018 to January 2021. The Sleep Disturbance Scale for Children 26-item parent-reported inventory was administered at baseline. At the 2-year follow-up, the computerized Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-COMP) was used to assess parent- and youth-reported suicidal behaviors and outcomes (none; passive, active nonspecific, and active specific suicidal ideation; and suicide attempt). Sleep disturbance was further grouped by symptom severity (minimal, moderate, elevated, high, and severe). In total, 8807 youths (mean [SD] age, 9.9 [0.6] years; 4507 males [51.2%]) out of the 10,136 who reported no baseline suicidal ideation or behavior completed the K-SADS-COMP assessment at the 2-year follow-up and were analyzed. At follow-up, 8044 participants (91.3%) had no suicidal behavior, 317 (3.6%) had passive suicidal ideation, 258 (2.9%) had active nonspecific suicidal ideation, 130 (1.5%) had active specific suicidal ideation, and 58 (0.7%) had a first-time suicide attempt. The risk of suicidal behavior at follow-up was increased 1.4 times for youth with high (odds ratio [OR], 1.39; 95% CI, 1.00-1.94; p = 0.05) and 2.7 times for those with severe ([OR], 2.68; 95% CI, 1.44-4.98; p = 0.002) sleep disturbances at baseline. Analyses on sleep subscale and suicidal behavior found that for the most severe level of sleep disturbance, Disorders of Excessive Somnolence (DOES) was associated with a 2.1-fold increased odds (OR, 2.09; 95% CI, 1.01-4.32; p = .05) of reporting suicidal behavior 2 years later compared that in the minimal sleep disturbance level. Compared with youth who reported with no nightmares at baseline, odds of reporting suicidal behavior at follow-up increased 1.7-fold in those who reported sometimes having nightmares (OR, 1.74; 95% CI, 1.07-2.85; p = 0.03) and increased 5-fold in those who reported having daily nightmares (OR, 5.46; 95% CI, 1.42-21.04; p = 0.01). Overall, this study found that greater severity of preadolescent sleep disturbance was associated with increased risk for suicidal behavors 2 years later. These findings indicate that sleep may be an important target for intervention in youth suicide prevention.

Efficacy of Shugan Hewei formula combined with rabeprazole in refractory gastroesophageal reflux disease: randomized, double-blind, placebo-controlled trial

1. Patients randomized to receive a combination of Shugan Hewei formula and rabeprazole were observed to have superior effect to rabeprazole alone in the treatment of refractory gastroesophageal reflux disease.

Evidence Rating: 1 (Excellent)

Refractory GERD (rGERD) refers to GERD that does not respond effectively to standard treatments such as proton pump inhibitors (PPIs). Traditional Chinese medicine (TCM) has been widely used to treat GERD in China. Research has shown the combination of TCM and traditional Western medicine to be effective for reducing GERD symptoms, suggesting that this combination may potentially be effective for treating rGERD. This study thus examined the efficacy of combining Chinese herbal medication Shugan Hewei formula (SHF) with rabeprazole in patients with rGERD. This randomized, double-blind, placebo-controlled trial included 264 adults aged 18-70 years with rGERD from three different hospitals in China. Participants were randomly assigned 1:1 to the treatment group receiving SHF granules (20 mg) combined with rabeprazole (10 mg) and the control group receiving placebo SHF granules (20 mg) combined with rabeprazole (20 mg). Both groups underwent 8 weeks of treatment with 2-week follow-ups. Due to loss to follow-up or other factors, 120 participants were analyzed in the treatment group (mean age ±SD = 53.83 ± 12.35 years, male N (%) = 68 (56.7%)) and 122 in the control group (mean age ±SD = 51.68 ± 11.95 years, male N (%) = 66(54.1%)). Compared to the control group, the treatment group had higher total clinical symptom efficacy, lower total symptom scores, and reduced rGERD major symptom scores, including heartburn, retrosternal pain, regurgitation and belching, and acid regurgitation (p < 0.05). For both groups after 8 weeks, there was a decrease in number of patients with esophagitis grade A (treatment: 40.34% to 17.23%; control: 40.25% to 15.35%) and grade B (treatment: 11.76% to 3.78%.; control: 11.20 to 2.49%), suggesting similar efficacy for the treatment and control groups in improving the degree of esophageal inflammation. Results of the SF-36 scale showed that the treatment group had better improvements in role limitation due to physical health, vitality, general health, somato-physical health, and psychiatric mental health (p < 0.05). Safety assessment found no significant differences before and after treatment in the incidence of liver and kidney function abnormalities. Adverse events were reported in 9 cases at Yueyang Hospital (3 in treatment group, 5 in control group). Overall, this study revealed that combining SHF with rabeprazole was more efficacious in managing rGERD than rabeprazole alone, indicating its potential as a combined Chinese and Western medicine for treating patients with rGERD.

Cumulative live birth rate of a blastocyst versus cleavage stage embryo transfer policy during in vitro fertilisation in women with a good prognosis: multicentre randomised controlled trial

1. Blastocyst stage embryo transfers resulted in cumulative live birth rates comparable to that of cleavage stage embryo transfer in women with at least four embryos available during IVF treatment.

2. Blastocyst stage group transfers had a higher live birth rate after fresh embryo transfer, lower cumulative pregnancy loss rate, and lower mean number of embryo transfers needed to result in a live birth; however, the incidence of moderate preterm birth (32 to <37 weeks) in singletons was higher.

Evidence rating: 1 (Excellent)

Standard practice for in vitro fertilisation (IVF) treatment or intracytoplasmic sperm injection (ICSI) has shifted the timing of embryo transfer from the cleavage stage of embryo development to the blastocyte stage. Despite many theoretical advantages of embryo transfer at the blastocyte stage compared to the traditional transfer at the cleavage stage, there is insufficient research on its effectiveness, safety, and clinical value. Additionally, it is unclear whether the blastocyte or cleavage stage embryo transfer is superior in terms of cumulative live birth rate, including live births from both fresh and frozen-thawed embryo transfers. This study thus compared the cumulative live birth rates after IVF or ICSI with blastocyte or cleavage stage embryo transfers, as well as the risk of obstetric and perinatal complications. This multicenter randomized controlled trial included women aged 18-43 years who were scheduled for their first, second, or third IVF or ICSI oocyte retrieval cycle, and had a minimum of four embryos available on day 2 after oocyte retrieval. This trial was conducted between 18 August 2018 and 17 December 2021 at 21 Dutch hospitals and clinics. Participants were randomly assigned 1:1 to the blastocyte stage group or cleavage stage group on day 2 after oocyte retrieval. Fresh embryos were transferred on day 5 after oocyte retrieval in the blastocyte group and on day 3 after oocyte retrieval in the cleavage group. The primary study outcome was cumulative live birth rate of pregnancies arising from fresh or frozen-thawed embryo transfers within a year after randomisation. Out of the 1202 women randomised, 603 were allocated to the blastocyte stage group (mean age (SD) = 33.9 (4.2) years, mean BMI (SD) = 24.2 (4.4) kg/m2) and 599 were allocated to the cleavage stage group (mean age (SD) =  34.1 (4.2) years, mean BMI (SD)= 24.5 (4.5) kg/m2). There was no difference in the cumulative live birth rate between the blastocyst group and cleavage group (58.9% (355 of 603) vs 58.4% (350 of 599); risk ratio 1.01, 95% confidence interval (CI) 0.84 to 1.22). Compared to the cleavage group, the blastocyst group had a higher live birth rate after fresh embryo transfer (37% (223 of 603) vs 29.5% (177 of 599); risk ratio 1.26, 95% CI 1.00 to 1.58), lower cumulative pregnancy loss rate (16.3% vs 24.2%; risk ratio 0.68, 95% CI 0.51 to 0.89), and lower mean number of embryo transfers needed to result in a live birth (1.55 vs 1.82; p < 0.001). However, the blastocyte group had a higher incidence of moderate preterm birth (32 to <37 weeks) in singletons (1.87, 95% CI 1.05 to 3.34). Both groups had similar obstetric and perinatal outcomes of birth weight, gestational age at delivery, and small or large for gestational age. Overall, this study found that blastocyst stage embryo transfer resulted in cumulative live birth rates comparable to that of cleavage stage embryo transfer in women with at least four embryos available during IVF treatment. Study findings also suggest that blastocyst stage transfers may increase live birth rate per fresh transfer, reduce pregnancy loss, and require fewer embryo transfers, although there may be an increase in moderate preterm births. Future studies are needed to validate study findings.

Efficacy of hepatic arterial infusion chemotherapy in patients with primary liver cancer with portal vein tumor thrombosis: a comparative analysis of different perfusion chemotherapeutic regimens

1. Overall survival and progression-free survival between the oxaliplatin + raltetrexed regimen and the fluorouracil + leucovorin calcium (FOLFOX) were not significantly different in patients with primary liver cancer (PLC) with portal vein thrombosis (PVT).

2. The oxaliplatin + raltetrexed regimen was superior to the FOLFOX regime for type II portal vein tumor thrombosis, single tumor, and multiple tumor subgroups.

Evidence rating: 2 (Good)

Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion of primary liver cancer (PLC). Studies have shown that combining transarterial chemoembolization (TACE), a treatment for PLC and PVTT, with hepatic arterial infusion chemotherapy (HAIC) may improve the survival rate of PLC patients with PVTT. However, the effectiveness of different drug regimes for the TACE and HAIC combination in PLC with PVTT remains controversial. This study thus compared the effectiveness and safety of different drug regimes for HAIC combined with TACE therapy for PLC patients with PVTT, specifically comparing the oxaliplatin + raltetrexed regimen and oxaliplatin + fluorouracil + leucovorin calcium (FOLFOX) regimen. This retrospective study recruited 248 patients with PLC from the Second Affiliated Hospital of Chongqing Medical University between January 2019 to October 2022. Participants were divided into the oxaliplatin + raltitrexed group and FOLFOX groups. The median and overall follow-up time was 6 and 20 months, respectively. After excluding patients with metastatic tumors from other sites or those lost to follow-up, there were 60 patients in the oxaliplatin+ ratitetrexed regimen group (mean age = 54.18 (51.22–57.18) years, male = 55%) and 74 patients in the FOLFOX regimen group (mean age = 51.89 (49.64–54.29) years, male = 65%). Average tumor size was 9.4 cm (range 3.0–18.7 cm). Although the oxaliplatin + raltitrexed group had a higher median overall survival (OS) (10.82 vs 8.67 months), median progression-free survival (PFS) (10.02 vs 7.07), higher objective response rate (ORR) (18.3% vs. 13.5%), and disease control rate (DCR) (70.0% vs. 64.8%), these differences were not significant. Subgroup analysis by PVTT classification revealed patients with type II PVTT in the oxaliplatin + raltitrexed group had a higher OS (12.08 vs 7.26, p = 0.008), and higher PFS (11.68 vs 6.26, p = 0.014) than those in the FOLFOX group. Further subgroup analyses revealed that for patients with type II PVTT involving the right branch, the oxaliplatin + raltitrexed group had a higher OS (13.54 vs 6.89 months, p = 0.015) and higher PFS (13.35 vs 6.27, p = 0.030) compared to the FOLFOX group. Subgroup analyses by tumor number found OS and PFS to be higher after treatment with oxaliplatin + raltitrexed in the subgroups with a single-tumor (OS: 11.25 vs 7.81 months, p = 0.044; PFS: 10.66 vs 5.95, p = 0.041) and multiple tumors (OS: 12.96 vs 9.10, p = 0.046; PFS: 12.54 vs 8.24, p = 0.047) compared to after FOLFOX treatment. Pain adverse effects occurred in 24 (40.0%) patients in the oxaliplatin + raltitrexed group and 42 (56.7%) patients in the FOLFOX group (p=0.034); however, incidences of other adverse reactions were similar between the two groups. Overall, this study found oxaliplatin + raltitrexed regimen to be superior to the FOLFOX regime for PLC patients with type II PVTT, one tumor, and multiple tumor subgroups. Future prospective studies are needed to confirm study findings.

Image: PD

©2024 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.