O-229 Impact of letrozole co-treatment during ovarian stimulation with gonadotropins for in vitro fertilisation (IVF): a multicentre, randomised, double-blinded placebo-controlled trial

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
N. Søderhamn Bülow ◽  
S O Skouby ◽  
A K Warzecha ◽  
H Udengaard ◽  
C. Yding Andersen ◽  
...  
Keyword(s):  
Placebo Group ◽  
Ovarian Stimulation ◽  
Controlled Trial ◽  
Risk Difference ◽  
Follicular Phase ◽  
Serum Estradiol ◽  
Ongoing Pregnancy ◽  
Double Blinded ◽  
Late Follicular Phase ◽  
Estradiol Levels

Abstract Study question Does reducing estradiol levels with letrozole co-treatment during ovarian stimulation with gonadotropins for IVF impact endocrinological and reproductive outcome markers in expected normal responders? Summary answer Letrozole co-treatment maintained follicular phase physiological serum estradiol levels, increased gonadotropin and androgen levels, and increased progesterone in the luteal phase. What is known already Ovarian stimulation for IVF causes supraphysiologic estradiol levels, which exert pituitary suppression reducing gonadotropin stimulation of the corpus luteum. Furthermore, stimulation may increase progesterone in the late follicular phase, reported to impair clinical outcomes, through a putative effect on endometrial maturation and embryo-endometrial asynchrony. Co-treatment with the highly selective aromatase inhibitor letrozole during ovarian stimulation has been shown to reduce estradiol levels and FSH consumption in poor responders, but conflicting data in relation to oocyte yield and implantation rates. The impact of letrozole co-treatment on hormonal changes and reproductive outcome after co-treatment in normal responders remains to be clarified. Study design, size, duration A multicentre double-blinded randomised placebo-controlled trial conducted in 4 fertility clinics at university hospitals in Denmark from August 2016 to November 2018. 159 women were randomised and 129 completed the study; 67 women in the letrozole group and 62 women in the placebo group. The study was conducted in accordance with the Helsinki Declaration and the ICH-Good-Clinical-Practice. Data collection and reporting followed the guidelines of CONSORT to achieve transparent reporting of trials. Participants/materials, setting, methods Women with expected normal ovarian reserve received an antagonist IVF protocol with fixed-dose FSH and fresh single embryo transfer. Co-treatment consisted of once-daily 5 mg letrozole or placebo from the start of stimulation until the day of triggering final oocyte maturation with human chorionic gonadotropin. Serum was collected on 7 visits from stimulation start to 8 days after oocyte retrieval. Clinical pregnancy was determined with a viable foetus by vaginal ultrasound at gestational week 7. Main results and the role of chance The proportion of patients with progesterone >1.5 ng/ml in the late follicular phase was similar in the letrozole versus placebo group with 6% versus 0%, respectively (OR 0, 95 % CI [0;1.6], P =.12). Mid-luteal progesterone levels >30 ng/ml were observed in 59% versus 31%, respectively, of subjects in the letrozole and placebo group (OR 3.3, 95% CI [1.4;7.1], P =.005). Letrozole treatment decreased estradiol levels by 69% (95 % CI [60%;75%], P <.0001) and increased luteinizing hormone (LH), testosterone, and androstenedione levels significantly in both the follicular and luteal phase. Follicle-stimulating hormone (FSH) concentration was elevated in the letrozole group at stimulation day 5 and at trigger day, and overall FSH consumption was diminished. The ongoing pregnancy rate did not differ between the letrozole and placebo group (31% versus 39% (risk-difference of 8%, 95% CI [-25%;11%], P =.55). Letrozole had no significant additional side effects apart from those frequently seen during ovarian stimulation, though a trend towards less nausea and vomiting was observed in the letrozole co-treated group versus the placebo group (28% versus 44% (risk-difference of 16%, 95% CI [-2%;33%], P =.11). Limitations, reasons for caution The diurnal variation of progesterone has been confirmed since this study was completed, hence the timing of the blood samples was not standardized . However, bias is unlikely due to the randomized design. The study was not powered to show an effect on ongoing pregnancy rates. Wider implications of the findings Letrozole co-treatment during ovarian stimulation with gonadotropins maintained serum estradiol at physiological levels, increased follicular phase levels of gonadotropins and androgens, and luteal progesterone levels. These data indicate that letrozole co-treatment may ameliorate the detrimental impacts of gonadotropin stimulation during IVF in normal responders. Trial registration number NCT02939898 and NCT02946684

Therapeutic Effects of Hab Shabyar on Open-Angle Glaucoma: A Double-Blinded, Randomized, Placebo-Controlled Trial

2019 ◽  
Vol 8 ◽  
pp. 1218
Author(s):  
Ebrahim Khalil BaniHabib ◽  
Ali Mostafai ◽  
Seyyed Mohammad Bagher Fazljou ◽  
Ghadir Mohammdi
Keyword(s):  
Placebo Group ◽  
Intraocular Pressure ◽  
Open Angle Glaucoma ◽  
Controlled Trial ◽  
Intervention Group ◽  
Therapeutic Effects ◽  
Open Angle ◽  
The Mean ◽  
The Right ◽  
Double Blinded

Background: Open-angle glaucoma (OAG) is one of the leading causes of blindness worldwide. This study evaluates the therapeutic effects of hab shabyar in patients with open-angle glaucoma. Materials and Methods: In this clinical randomized controlled trial, 50 patients with OAG were randomized into two groups. The intervention group was received a drop of timolol plus 500 mg of hab shabyar every 12 hours. The placebo group was received a drop of timolol every 12 hours plus 500 mg of wheat germ as a placebo. The intraocular pressure in patients with OAG was measured in each group and compared at before the intervention (t1), one month (t2), and two months (t3) after the intervention. Results: The mean decrease in intraocular pressure for the right eye at three times in the intervention group was statistically significant, but the mean decrease in the placebo group was not significant. Similar results were obtained for the left eye at t1 when compared to t3. The patients in the intervention group expressed more satisfaction than the patients in the placebo group (P≤0.001). Conclusion: Our study demonstrated that consumption of timolol plus hab shabyar instead of consuming of timolol alone was probably more effective for reducing intraocular pressure in patients with OAG.[GMJ.2019;In press:e1218]

P–613 Adjuvant letrozole in ovarian stimulation for in vitro fertilization does not reduce uterine peristalsis frequency prior to fresh embryo transfer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Dreye. Holt ◽  
A K Warzecha ◽  
N S Bülow ◽  
S O Skouby ◽  
A L M Englund ◽  
...  
Keyword(s):  
Placebo Group ◽  
In Vitro Fertilization ◽  
Adjuvant Treatment ◽  
Serum Estradiol ◽  
Fresh Embryo Transfer ◽  
Vitro Fertilization ◽  
Physiological Serum ◽  
Estradiol Levels ◽  
Uterine Peristalsis

Abstract Study question Does adjuvant letrozole in ovarian stimulation (OS) for in vitro fertilization (IVF) decrease the uterine peristalsis frequency (UPF) prior to fresh embryo transfer (ET)? Summary answer Adjuvant letrozole in (OS) for IVF does not reduce the UPF significantly prior to fresh ET. What is known already Throughout the cycle UPF aids spermatozoa transport to the fallopian tube and may affect implantation. At fresh, ET UPF is negatively correlated with implantation- and clinical pregnancy rates and is believed to be modulated by estradiol and progesterone. High levels of estradiol, from multiple follicular development, in OS have been reported to increase UPF, whereas progesterone is considered to be utero-relaxant. The influence of androgens is unclear. Co-treatment with letrozole during gonadotropin OS limits the estradiol rise the supra-physiological estradiol and may therefore reduce UPF prior to fresh ET. Study design, size, duration: This single centre study was nested within a multicentre double blinded RCT investigating the impact of letrozole co-treatment during gonadotropin OS for IVF on late follicular and luteal estradiol, progesterone and testosterone levels. Between 2016 and 2017, 39 women expected normal responders were randomised to co-treatment with letrozole or placebo. Of these, 33 women completed this element of the study. The study was carried out according to the Helsinki Declaration and the ICH-Good-Clinical-Practice. Participants/materials, setting, methods Eligible women were randomised 1:1 to adjuvant treatment with letrozole 5 mg/day or placebo in an antagonist protocol using a fixed dose of recFSH 150 IU/day. Final maturation was triggered with rhCG 6,500 IU and luteal support with vaginal progesterone was administered from the day following oocyte aspiration. Less than one hour prior to fresh ET, six minute duration transvaginal ultrasound recordings of the uterus in sagittal section were performed and blood samples were drawn. Main results and the role of chance A total of 33 women completed the study (letrozole n = 17; placebo n = 16). Age, BMI, and ovarian reserve markers were similar between the groups. On day of ET, serum estradiol levels were significantly suppressed in the letrozole group to mean 867 ± 827 pmol/L compared to 3,110 ± 1,528 pmol/L in the placebo group (P < 0.0001). Mean UPF prior to fresh ET did not differ between the intervention and control group (3.3 ± 0.36 versus 3.5 ± 0.51 per minute respectively, P = 0.108). UPF was assessed and agreed by two observers who were blind to adjuvant treatment. Two patients were excluded due to poor quality of the ultra sound recording. Supra-physiological serum estradiol in the placebo group was negatively correlated with UPF (P = 0.014; R = –0.62), but the more physiological serum estradiol levels in the letrozole group showed no correlation with UPF (P = 0.567; R = 0.15). Serum progesterone levels were similar in both groups and did not show any significant correlation with UPF. Testosterone levels were significantly higher in the letrozole group (P = 0.005) and showed a non-significant trend negatively correlated with UPF in the placebo group (P-value=0.07, R= –0.48). Limitations, reasons for caution The limited sample size risks masking minor effects. Wider implications of the findings: The supra-physiological levels of estradiol were significantly supressed in the intervention group, but UPF prior to fresh ET was similar in both groups. UPF is not strongly correlated to luteal phase sex steroid levels. Any beneficial effect of adjuvant letrozole during OS is not through an impact of UPF. Trial registration number NCT02939898

scholarly journals Ubiquinone Supplementation with 300 mg on Glycemic Control and Antioxidant Status in Athletes: A Randomized, Double-Blinded, Placebo-Controlled Trial

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 823
Author(s):  
Chien-Chang Ho ◽  
Po-Sheng Chang ◽  
Hung-Wun Chen ◽  
Po-Fu Lee ◽  
Yun-Chi Chang ◽  
...  
Keyword(s):  
Placebo Group ◽  
Glycemic Control ◽  
Antioxidant Capacity ◽  
Controlled Trial ◽  
Controlled Study ◽  
Model Assessment ◽  
Glycemic Profile ◽  
Homeostatic Model Assessment ◽  
Total Antioxidant ◽  
Double Blinded

The aim of this study is to investigate the glycemic profile, oxidative stress, and antioxidant capacity in athletes after 12 weeks of ubiquinone supplementation. It was a double-blinded, randomized, parallel, placebo-controlled study. Thirty-one well-trained college athletes were randomly assigned to ubiquinone (300 mg/d, n = 17) or placebo group (n = 14). The glycemic profile [fasting glucose, glycated hemoglobin (HbA1c), homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI)], plasma and erythrocyte malondialdehyde (MDA), total antioxidant capacity (TAC), and ubiquinone status were measured. After supplementation, the plasma ubiquinone concentration was significantly increased (p < 0.05) and the level of erythrocyte MDA was significantly lower in the ubiquinone group than in the placebo group (p < 0.01). There was a significant correlation between white blood cell (WBC) ubiquinone and glycemic parameters [HbA1c, r = −0.46, p < 0.05; HOMA-IR, r = −0.67, p < 0.01; QUICKI, r = 0.67, p < 0.01]. In addition, athletes with higher WBC ubiquinone level (≥0.5 nmol/g) showed higher erythrocyte TAC and QUICKI and lower HOMA-IR. In conclusion, we demonstrated that athletes may show a better antioxidant capacity with higher ubiquinone status after 12 weeks of supplementation, which may further improve glycemic control.

scholarly journals Endothelial Function is improved by Inducing Microbial Polyamine Production in the Gut: A Randomized Placebo-Controlled Trial

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1188 ◽  
Author(s):  
Mitsuharu Matsumoto ◽  
Yusuke Kitada ◽  
Yuji Naito
Keyword(s):  
Placebo Group ◽  
Endothelial Function ◽  
Controlled Trial ◽  
Reactive Hyperemia ◽  
Intestinal Bacteria ◽  
Bifidobacterium Animalis ◽  
Parallel Group ◽  
Peripheral Arterial ◽  
Double Blinded ◽  
Arterial Tone

Recently, it was demonstrated that spermidine-induced autophagy reduces the risk of cardiovascular disease in mice. Intestinal bacteria are a major source of polyamines, including spermidine. We previously reported that the intake of both Bifidobacterium animalis subsp. lactis (Bifal) and arginine (Arg) increases the production of putrescine, a spermidine precursor, in the gut. Here, we investigated the effects of Bifal and Arg consumption on endothelial function in healthy subjects. Healthy individuals with body mass index (BMI) near the maximum value in the “healthy” range (BMI: 25) (n = 44) were provided normal yogurt containing Bifal and Arg (Bifal + Arg YG) or placebo (normal yogurt) for 12 weeks in this randomized, double-blinded, placebo-controlled, parallel-group comparative study. The reactive hyperemia index (RHI), the primary outcome, was measured using endo-peripheral arterial tone (EndoPAT). The change in RHI from week 0 to 12 in the Bifal + Arg YG group was significantly higher than that in the placebo group, indicating that Bifal + Arg YG intake improved endothelial function. At week 12, the concentrations of fecal putrescine and serum putrescine and spermidine in the Bifal + Arg YG group were significantly higher than those in the placebo group. This study suggests that consuming Bifal + Arg YG prevents or reduces the risk of atherosclerosis.

Physical Therapy for Patellofemoral Pain

2002 ◽  
Vol 30 (6) ◽  
pp. 857-865 ◽  
Author(s):  
Kay Crossley ◽  
Kim Bennell ◽  
Sally Green ◽  
Sallie Cowan ◽  
Jenny McConnell
Keyword(s):  
Placebo Group ◽  
Physical Therapy ◽  
Therapy Group ◽  
Controlled Trial ◽  
Placebo Treatment ◽  
Quadriceps Muscle ◽  
Patellofemoral Pain ◽  
Therapy Regimen ◽  
Average Pain ◽  
Double Blinded

Background Although physical therapy forms the mainstay of nonoperative management for patellofemoral pain, its efficacy has not been established. Hypothesis Significantly more pain relief will be achieved from a 6-week regimen of physical therapy than from placebo treatment. Study Design Multicenter, randomized, double-blinded, placebo-controlled trial. Methods Seventy-one subjects, 40 years of age or younger with patellofemoral pain of 1 month or longer, were randomly allocated to a physical therapy or placebo group. A standardized treatment program consisted of six treatment sessions, once weekly. Physical therapy included quadriceps muscle retraining, patellofemoral joint mobilization, and patellar taping, and daily home exercises. The placebo treatment consisted of sham ultrasound, light application of a nontherapeutic gel, and placebo taping. Results Sixty-seven participants completed the trial. The physical therapy group (N = 33) demonstrated significantly greater reduction in the scores for average pain, worst pain, and disability than did the placebo group (N = 34). Conclusions A six-treatment, 6-week physical therapy regimen is efficacious for alleviation of patellofemoral pain.

Subnormal follicular-phase serum progesterone levels and elevated follicular-phase serum estradiol levels in young women with insulin-dependent diabetes

Steroids ◽  
1990 ◽  
Vol 55 (12) ◽  
pp. 560-564 ◽  
Author(s):  
Barnett Zumoff ◽  
Lorraine Miller ◽  
Leonid Poretsky ◽  
Charles D. Levit ◽  
Ellen H. Miller ◽  
...  
Keyword(s):  
Young Women ◽  
Follicular Phase ◽  
Insulin Dependent Diabetes ◽  
Serum Estradiol ◽  
Serum Progesterone ◽  
Insulin Dependent ◽  
Estradiol Levels

scholarly journals Relationship between inhibin A and B, estradiol and follicle growth dynamics during ovarian stimulation in normo-ovulatory women

2005 ◽  
Vol 152 (3) ◽  
pp. 395-401 ◽  
Author(s):  
Femke P Hohmann ◽  
Joop S E Laven ◽  
Frank H de Jong ◽  
Bart C J M Fauser
Keyword(s):  
Ovarian Stimulation ◽  
Follicular Phase ◽  
Inhibin B ◽  
High Dose ◽  
Low Doses ◽  
Serum Concentrations ◽  
Inhibin A ◽  
Phase Group ◽  
The Relationship ◽  
Late Follicular Phase

Objective: To investigate the relationship between serum concentrations of inhibin A, inhibin B and estradiol (E2) and the number of developing follicles during the administration of exogenous follicle-stimulating hormone (FSH) in various regimens in normo-ovulatory volunteers and to evaluate if inhibins act as suitable markers for the number of developing follicles during ovarian stimulation. Design and methods: Serial hormone determinations and assessment of follicle numbers were carried out during unstimulated cycles and during various interventions with exogenous FSH. Subjects were randomized for FSH administration into the following groups: a single high dose (375 IU) during the early follicular phase (group A), 5 consecutive low doses (75 IU/day) starting in the mid follicular phase (group B) or daily low doses (75 IU/day) during the early to late follicular phase (starting on cycle days 3, 5 or 7; groups C, D and E respectively). Results: Extending the FSH window increases the number of small antral follicles and hence inhibin B serum concentrations. If such an intervention results in multi-follicular growth, mid follicular phase inhibin B (P = 0.001) as well as late follicular phase inhibin B and inhibin A levels are significantly (P < 0.05 and P < 0.01 respectively) increased compared with mono-follicular cycles or the natural cycle. Although mid follicular inhibin B levels correlated well with the number of small antral (P < 0.05) and pre-ovulatory (P < 0.001) follicles in the late follicular phase, mid follicular inhibin A and estradiol serum concentrations only correlated with the number of pre-ovulatory follicles (P < 0.001 and P < 0.01 respectively). Conclusions: The present data extend our understanding of the relationship between follicle dynamics, serum inhibins and FSH during ovarian hyperstimulation. However, although mid follicular inhibin B does correlate with the number of developing follicles, it does not facilitate the identification of women at risk for multiple follicle development.

Preoperative Oral Rofecoxib and Postoperative Pain in Patients after Laparoscopic Cholecystectomy: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial

2005 ◽  
Vol 71 (10) ◽  
pp. 827-829 ◽  
Author(s):  
Rob Schuster ◽  
David Stewart ◽  
Lynn Schuster ◽  
Gregory Greaney ◽  
Kenneth Waxman
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Placebo Group ◽  
Postoperative Pain ◽  
Hospital Stay ◽  
Controlled Trial ◽  
Group Versus ◽  
Cox 2 ◽  
Double Blinded ◽  
Cox 2 Inhibitors ◽  
The Impact

Cyclooxygenase-2 (COX-2) inhibitors are a class of drugs that may avoid some of the side effects of narcotics and nonsteroidal anti-inflammatory drugs (NSAIDs). We performed a randomized, double-blinded, placebo-controlled trial giving a single oral dose of the COX-2 inhibitor rofecoxib 25 mg or placebo preoperatively to determine the impact upon postoperative pain, complications, narcotic use, and hospital stay after laparoscopic cholecystectomy. Investigators and patients were blinded. Pain was measured on a 10-point visual analogue scale. Eighty patients were randomized: 40 to the rofecoxib group and 40 to the placebo group. The amount of pain between the two groups postoperatively was equivalent. Pain was recorded at 1 hour, 4.03 ± 1.93 in the rofecoxib group versus 4.38 ± 1.34 in the placebo group ( P = 0.36); at 6 hours, 3.00 ± 1.12 in the rofecoxib group versus 2.78 ± 0.78 in the placebo group ( P = 0.42); and at 24 hours, 1.64 ± 0.67 in the rofecoxib group versus 2.68 ± 1.90 in the placebo group ( P = 0.17). The amount of pain medication received and lengths of hospital stay was not significantly different between the two groups. Our data demonstrate no significant benefit of preoperative oral rofecoxib in patients undergoing laparoscopic cholecystectomy.

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