Increasing Dose Group Research Articles

Does increasing estrogen dose during frozen embryo transfer affect pregnancy rate?

To assess the effect of increasing estrogen doses during hormone therapy frozen embryo transfer (HT-FET) cycles on endometrial thickness and success rates compared to patients who received fixed estrogen dose. A retrospective study from a university-based fertility clinic during the years 2008-2021. We compared two groups: the fixed-dose group (i.e., received 6mg estradiol dose daily until embryo transfer) and the increased-dose group (i.e., the initial estradiol dose was 6mg daily, and was increased during the cycle). clinical pregnancy rate. The study included 5452 cycles of HT-FET: 4774 cycles in the fixed-dose group and 678 cycles in the increased-dose group. Ultrasound scan on days 2-3 of the cycle showed endometrial thickness slightly different between the two groups (4.2mm in the fixed-dose and 4.0mm in the increased-dose group, P = 0.003). The total estrogen dose was higher, and the treatment duration was longer in the increased than the fixed-dose group (122mg vs. 66mg and 17days vs. 11days, respectively; P < 0.001). The last ultrasound scan done before the addition of progesterone showed that the endometrial thickness was significantly thicker in the fixed than the increased-dose group (9.5mm vs. 8.3mm; P < 0.001). The clinical pregnancy rates were 35.8% in the increased-group vs. 34.1% in the fixed-dose group; P = 0.401. The increased-dose group had thinner endometrium despite the higher doses of estrogen and longer treatment duration than the fixed-dose group. However, the pregnancy rates were similar between the two groups.

Effects of Increasing Metformin Dose vs Adding/Switching to Dipeptidyl Peptidase-4 Inhibitors on Glycemic Control in Patients with Type 2 Diabetes

IntroductionMetformin has dose-dependent hypoglycemic effects on patients with type 2 diabetes (T2D). In Japan, metformin has been prescribed at lower doses than in Western countries. We analyzed the effect of increasing the metformin dose on glycemic control and compared it to a combination therapy with dipeptidyl peptidase-4 inhibitors (DPP-4i) and a replacement therapy with DPP-4i.MethodsThis is a cohort study using a Japanese claims database. Patients with T2D who had been initially treated with low-dose metformin (≥ 500 mg/day and < 1000 mg/day) and then given a prescription change by increasing metformin to a higher dose (≥ 1000 mg/day) (increased-dose), adding DPP-4i (drug-added), or switching to DPP-4i (drug-switched) were included in this study. The primary outcome was the change in HbA1c levels at 12 months from the baseline period.ResultsAmong 2,726,437 patients with T2D, 494 were included. Of these patients, 226, 240, and 28 patients were classified as increased-dose, drug-added, and drug-switched groups, respectively. The HbA1c levels at 12 months from the index significantly decreased compared to that during the baseline period. The change was the highest in the drug-added group (− 1.06%), followed by the increased-dose (− 0.91%) and the drug-switched groups (− 0.37%). Among the subset of patients who did not receive any antidiabetic drugs other than metformin or DPP-4i, the highest change in HbA1c levels was observed in the increased-dose group (− 0.84%), followed by the drug-added (− 0.67%) and the drug-switched (− 0.42%) groups. The order of decrease from baseline remained the same for all the study groups after the propensity score weighting adjustment.ConclusionThe effect on glycemic control when increasing the metformin dose was studied in patients who had been receiving low-dose metformin. Increasing metformin dosage shows effectiveness and could be one of the next treatment options in patients who were prescribed low-dose metformin as the first-line treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01017-x.

Effect of transdermal estrogen dose regimen for endometrial preparation of frozen-thawed embryo transfer on reproductive and obstetric outcomes.

PurposePrevious studies have reported different methods of estrogen administration during endometrial preparation for frozen‐thawed embryo transfer (FET). This study aimed to investigate a beneficial regimen of transdermal estrogen administration for FET.MethodsWe investigated the reproductive and obstetric outcomes of FET by comparing the increasing dose (ID) group that mimics changes in serum estradiol during the menstrual cycle and the constant dose (CD) group. Transdermal patches were used for estrogen administration in both groups. In our hospital, we targeted 315 cycles of the ID group in which FET was performed in 2017 and 324 cycles of the CD group in which FET was performed in 2018. In all cases, single embryo transfer was performed.ResultsAll were singleton pregnancies. There was no difference in clinical pregnancy rate (28.9% vs 28.2%, P =.837) and live birth rate (17.3% vs 21.4%, P =.201) between the ID and CD groups. Spontaneous abortion rate was significantly lower in the CD group than in the ID group (37.2% vs 23.0%, P =.041). There was no difference in obstetrical outcomes.ConclusionsIt was considered that the simple CD regimen may be more beneficial than the complicated ID regimen.

The Impact of Discharged Loop Diuretic Dose to Home Dose on Hospital Readmissions in Patients with Acute Decompensated Heart Failure: A Retrospective Cohort Study.

Acute decompensated heart failure (ADHF) is associated with a high rate of hospital readmission. The aim of this study is to examine the effect of the discharge diuretic dose compared with the home diuretic dose on hospital readmission in patients with ADHF. A single center retrospective cohort study included patients with a confirmed diagnosis of ADHF with an ejection fraction of less than 40%. The sample was divided in two groups. The first group received a total daily discharge diuretic dose that was greater than the home dose; the second group received a daily discharge diuretic that was equal to or less than the home dose. The primary outcome was all-cause 30-day readmission rate. The secondary outcomes were all-cause 60-day and 90-day readmission rates. A total of 206 patients met inclusion criteria; 117 patients received a higher loop diuretic dose at discharge, while 89 were discharged with a loop diuretic that was equal to or less than the home dose. Patients in the increased-dose group had an all-cause 30-day readmission rate of 20.5% compared with 37.1% of patients with equal or reduced-dose group; P = .007. Additionally, there were lower readmission rates in 60 and 90 days between the increased and equal or reduced groups (33.3% versus 52.8%, P < .017, and 41.0% versus 62.9%, P < .003, respectively. Among patients admitted to hospital with ADHF and reduced ejection fraction, a discharge loop diuretic dose higher than the home dose was associated with decreased all-cause 30-day, 60-day, and 90-day readmission rates.

Randomized Clinical Trial Comparing the Pharmacokinetics of Standard- and Increased-Dosage Lopinavir-Ritonavir Coformulation Tablets in HIV-Positive Pregnant Women

A lopinavir-ritonavir (LPV/r)-based regimen is recommended during pregnancy to reduce the risk of HIV mother-to-child transmission, but the appropriate dose is controversial. We compared the pharmacokinetics of standard and increased LPV/r doses during pregnancy. This randomized, open-label prospective study enrolled 60 pregnant women between gestational weeks 14 and 30. The participants received either the standard dose (400/100 mg twice a day [BID]) or increased dose (600/150 mg BID) of LPV/r tablets during pregnancy and the standard dose for 6 weeks after childbirth. Pharmacokinetics analysis was performed using a high-performance liquid chromatography-tandem mass spectrometry method. Adherent participants who received the standard dose presented minimum LPV concentrations of 4.4, 4.3, and 6.1 μg/ml in the second and third trimesters and postpartum, respectively. The increased-dose group exhibited values of 7.9, 6.9, and 9.2 μg/ml at the same three time points. Although LPV exposure was significantly higher in the increased-dose group, the standard dose produced therapeutic levels of LPV against wild-type virus in all adherent participants, except one patient in the third trimester; 50%, 37.5%, and 25%, and 0%, 15%, and 0% of the participants in the standard- and increased-dose groups failed to achieve therapeutic levels against resistant viruses during the second and third trimesters and after childbirth, respectively. After 12 weeks of treatment and after childbirth, all adherent participants achieved undetectable HIV viral loads, and their babies (49/54) were uninfected. No serious drug-related adverse events were observed. We conclude that the standard dose is appropriate for use during pregnancy and that an increased dose may be necessary for women harboring resistant HIV. (This study has been registered at ClinicalTrials.gov under registration no. NCT00605098.).

Correlation of selective serotonin re-uptake inhibitor use with weight gain and metabolic parameters

Objective: Psychotropic drugs during the treatment period of psychiatric disorders can cause changes in metabolic parameters such as weight, lipid profile, fasting glucose level, and resting metabolic rate. The aim of this study is to investigate the correlation of selective serotonin re-uptake inhibitor (SSRI) use with weight gain and metabolic parameters. Methods: In this study, the resting metabolic rates (RMR) of 14 male patients intended to use selective serotonin re uptake inhibitor at least three months, were measured baseline, first and third month after SSRI use. Body weight, percentage body fat, body mass index and waist/hip ratio were measured before treatment, at the end of the first and second weeks and the first, second and third months. Laboratory tests including total cholesterol, LDL, HDL, VLDL, triglycerides and fasting blood glucose were performed before treatment and at the end of the third month. The correlation of body weight changes with RMR changes was also analyzed. Results: RMR did not differ in the beginning, first month and third month. No statistically significant difference was found in RMR between the beginning and the third month. RMR significantly decreased in the increased-dose group while it wasn’t changed in the constant-dose group. No correlation was found between RMR changes and body weight changes. The mean body weight decreased significantly between the beginning and the first week and the first month. Even though the mean body weight of all patients was higher in the third month than the beginning, no statistically significant difference was found. The total cholesterol levels, body lipid ratio, and waist/hip ratio increased significantly between initiation of treatment and the third month. Conclusion: As a result, we suggest that SSRI’s use did not cause body weight increase due to reduction in RMR. The waist/hip ratio, total cholesterol levels were increased in the third month. Further studies which look more closely to fat metabolism in patients under SSRI’s treatment are necessary.

Vincristine-induced neuropathy in rat: electrophysiological and histological study

Peripheral sensory-motor neuropathy is one of the most frequent side effects of vincristine (VCR) administration, which often limits its usefulness in the treatment of a wide range of neoplastic diseases. The purpose of this work is to study VCR neurotoxicity in experimental animals from clinical, electrophysiological, and histological points of view. Sixty-five rats were used as a control group and 31 rats were divided into two groups and given VCR in two different regimens: the fixed-dose group (0.2 mg/kg) and the increasing-dose group (0.1 mg/kg, by an increment of 0.05 mg/kg/week). VCR was given intraperitoneally once weekly for five consecutive weeks. Electrophysiological examinations of the control and both treated groups were performed and included measurements of nerve conduction velocity and action potential (AP) amplitude of sciatic and tail nerves weekly during the period of treatment and 14 weeks after discontinuation of treatment. Histological sections of sciatic nerves were examined after the appearance of early electrophysiological changes, at the end of the 5th, and 19th weeks of the study (14 weeks after discontinuation of treatment). With the progress of the treatment, an increasing number of rats showing signs of neurological deficits were observed. During the first 5 weeks of this study, electrophysiological testing showed a nonsignificant difference in the conduction velocities of sciatic and tail nerves between the control and the treated groups, whereas a significant decrease in the amplitude of the sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) of the tested nerves was recorded. The reduction in the AP amplitude was associated with histological changes characterized by axonal degeneration with relative demyelination. Fourteen weeks after discontinuation of treatment, a significant increment in the SNAP and CMAP amplitudes of both sciatic and tail nerves was noticed. While the CMAP amplitude of the distal segment of the tail showed nonsignificant increment, lesser number of fibers with axonal and/or myelin lesions were found. The clinical, electrophysiological, and histological results suggest that VCR induces peripheral sensorimotor neuropathy of axonal type more prominent in the fixed- than the increasing-dose group. The discontinuation of VCR permitted the improvement of the electrophysiological and histological changes. The rat can be used as an animal model for studying VCR neurotoxicity. However, further studies on larger number of animals are required to evaluate the type of nerve fiber involvement and the site of damage.

Apoptosis of endometrial cells in the bitch.

The relationship between apoptosis of endometrial cells in the bitch, and the occurrence of degeneration of the endometrial luminal epithelium and regression of the endometrial glandular epithelium was determined. Mature bitches (n = 12) were ovariectomized and treated with hormones to simulate uterine changes that occur during the oestrous cycle. All bitches were treated with oestradiol benzoate (0.6-4.8 microg x kg(-1), i. m., twice per day) for 11-12 days then with progestagen (megestrol acetate, 2 mg x kg(-1), p. o., once per day) for 35-37 days. Bitches were treated daily for a further 3 weeks with megestrol acetate at dose rates of 0.5 mg x kg(-1) (decreased-dose group (n = 3)), 2 mg x kg(-1) (standard-dose group (n = 3)), or 3 (1 wk), 4 (1 wk) and 5 (1 wk) mg x kg(-1) (increased-dose group (n = 3)), or received no treatment (withdrawal-dose group (n = 3)). These bitches were necropsied at the end of the treatment period. A further 10, ovary-intact, bitches were necropsied when in oestrus (n = 1), dioestrus (n = 5), and at 3 weeks (n = 1) and 9 weeks (n = 3) of anoestrus. Degeneration of the luminal epithelium was observed in all bitches except those in oestrus, at 9 weeks of anoestrus and one in dioestrus. Apoptosis was observed in the glandular epithelial cells, stromal cells and endothelial cells of blood capillaries in all bitches except those at oestrous and at 9 weeks of anoestrous. High average apoptotic indices were detected in the basal glandular epithelium of the dioestrous, decreased-dose, standard-dose and increased-dose groups, whereas low apoptotic indices were detected at 3 weeks of anoestrous and in the withdrawal-dose groups. These results indicate that degeneration of cells of the glandular epithelium, but not of the luminal epithelium, was due to apoptosis of these cells.