P–401 Frozen-thawed embryo-transfer adjuvant therapy: one size DOES NOT fit all

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Riviello ◽  
A Riva ◽  
A Bottai ◽  
G Buzzaccarini ◽  
L Marin ◽  
...  

Abstract Study question Does adjuvant therapy after frozen-thawed embryo-transfer (FRET) with CardioAspirin and Prednisone enhance clinical pregnancy rate (CPR) and live birth rate (LBR)? Summary answer Adjuvant therapy enhanced CPR and LBR in study-group. A significant correlation was found confronting blastocyst FRET in study-group versus controls. What is known already Embryo implantation is a rate-limiting step of FRET cycles. It’s a complex process resulting from a balance between inflammation pathways and maternal immune tolerance. Low-dose aspirin unlocks Prostaglandin-F2 synthesis by Cyclooxygenase–1, thus increasing uterine vascular permeability and attachment reaction while reducing vasoconstriction. Pregnancy results from a balance between helper and regulatory T-cells (Treg), the latter protect the embryo from maternal immune attack. Treg cells’ immunosuppressive function is pivotal in pregnancy establishment. Prednisone increases the proportion of Treg cells thus inhibiting inflammation. Many therapy schedules for implantation enhancement are currently used worldwide, although there is no consistent shared evidence. Study design, size, duration Retrospective cohort-control study including 237 subjects who underwent FRET after artificial endometrial-preparation from January 2018 to March 2020. Estrogenic stimulation was either oral or transdermic. The study-group received luteal support (vaginal Progesterone 600 mg/die) and adjuvant therapy (CardioAspirin and Prednisone 25–5 mg); the control-group received luteal support only. Pregnancy test (PT) was scheduled 10–14 days post-transfer (blastocysts or cleavage stage embryos). Second PT and ultrasound were performed 7 days later if the first was positive. Participants/materials, setting, methods Patients referred to Padua University Hospital’s Human Reproduction Pathophysiology Unit. Exclusion criteria: >50/<18 years, fresh embryo-transfer cycles, oocyte-thawing cycles, natural/natural-modified cycles. Male factor was the prevalent fertility issue. Single embryo-transfer was performed in both groups. Mean endometrial thickness was 9 mm trilaminar in both groups. Statistical analysis were carried out using JMP Pro 14 software. Categorical variables were analyzed using Chi-square test or Fisher’s exact test where appropriate. Main results and the role of chance In the study-group, 87 subjects were given luteal support and adjuvant therapy, while in the control-group, 150 subjects received luteal support only. Groups were homogeneous for age, number of embryos transferred, endometrial thickness, endometrial features (trilaminarity) and fertilization tecniques (108 IVF/ 127 ICSI). CPR and LBR were significantly higher in the study-group. CPR was 31.4% in study-group versus 14.8% in controls (p = 0.002), LBR was 27.4% in study-group versus 11.6% in controls (p = 0.002). Since heterogeneity between groups was found regarding the type of embryo transferred (55.3% cleavage-stage versus 44.7% blastocyst, p < 0.01), the groups were split analyzed basing upon the type if embryo transferred. In the cleavage-stage FRET condition no relevant correlation was found between groups. However in blastocyst-FRET group CPR (34.5% study-group versus 18% controls, p = 0.04) and LBR (30.9% study-group versus 12% controls, p = 0.017) were significantly higher in the study-group, thus showing that adjuvant therapy could improve CPR and LBR. Limitations, reasons for caution Limited sample size negatively impacts the study’s power. It would be appropriate to expand the sample to obtain more reliable results. Wider implications of the findings: Although no unanimous consent exists for tout-court adjuvant therapy administration, scientific literature shows that such therapy can help patients with repeated implantation failures or anti-nuclear-antibodies positivity. Assuming that a single-therapy-regimen could perfectly fit all patients is not realistic. We have to move towards patient-tailored adjuvant therapy thinking. Trial registration number Not applicable

2021 ◽  
Vol 7 (5) ◽  
pp. 1842-1852
Author(s):  
Longying Shen ◽  
Chang Liu

Objective: To research the influence of the pelvic floor muscle massage on pregnancy outcome of patients treated with frozen-thawed embryo transfer (FET). Methods: We choose 120 patients who will have the frozen-thawed embryo transfer after it is unfreezed, and they are departed into two groups averagely, 60 of observation group and 60 of control group. Both groups start taking estradiol valerate twice a day on the third day of the menstrual cycle, 3mg one time. 14 days later, all patients need to inject progesterone except taking estradiol valerate. The observation group: Starting the pelvic floor muscle massage from the end of menstruation till the day of injecting progesterone, 15-20 minutes, 50 HZ, the acupoints are huiyin and baliao. The contrast group doesn't have any other therapeutic measures. We will transfer the high-quality embryo on the suitable day. We contrast the basic conditions, the embryo, the endometrial thickness and types of uterine endometrium. To analyze the endometrial blood type, PI, RI, S/D, biochemical pregnancy rate, clinical pregnancy rate and early abortion rate. Results: There are no statistical result in transferring conditions, the endometrial thickness and types of uterine endometrium. After the treatment, we find that: 1. in the observation group, after the treatment of pelvic floor muscle massage ,the endometrial blood of the menstrual 17th day compared with the menstrual 9th day, type I decreases clearly, type If and B increase evidently(p<0.05);2. in the observation group after the treatment of pelvic floor muscle massage, we get that the indexes RI, PI and S/D of the menstrual 17th day compared with the menstrual 9th day , reduced remarkably(p<0.05);3 the observation group of patients after treatment, the menstrual 17th day endometrial blood flow decreased significantly than control group in blood flow I type, type If + B increased significantly,(p < 0.05) ;4. The observation group of patients after treatment, PI, RI and S/D of the menstrual 17th days was lower than control group significantly (P < 0.0S);S. in the observation group of patients after treatment ,the endometrial thickness compared with the control group was no statistically different (p>0.05), but the endometrial thickness of the observation group was higher than the control group;6.the implantation rate and clinical pregnancy rate are higher in the observation group than those in the control group. Conclusion: The pelvic floor muscle massage improves the endometrial thickness and endometrial blood conditions, so as to increase the clinical pregnancy rate of patients with frozen-thawed embryo transfer (FET).


2020 ◽  
Author(s):  
caixia sun ◽  
zhongmin wang

Abstract Objective: To clarify the efficacy of vascular smooth muscle technology in the treatment of thin endometrial infertility, and to provide a theoretical basis for the further diagnosis and treatment of thin endometrial infertility. Methods: In accordance with the inclusion and exclusion criteria, 2015.01-2020.01 selected thin endometrial infertility patients undergoing freeze-thaw embryo transfer at the Female Pelvic Floor Urinary Reconstructive Center in Dalian Municipal Women and Children’s Medical Center were selected according to different treatment methods. For the two groups, pure estrogen therapy was used as the control group, and vascular smooth muscle technology combined with estrogen therapy was used as the study group. All patients' endometrial thickness and pregnancy and delivery were recorded before and after treatment. Results: 1. The endometrial thickness of the study group was significantly larger than that of the control group after treatment, the difference was statistically significant ( P <0.05); 2. 80 patients in the study group, 13 cases of successful pregnancy and delivery, 5 cases of biochemical pregnancy; the endometrial changes of the 50 patients in the control group was not obvious after treatment, none of the endometrial thicknesses reached the embryo transfer standard, and none were transplanted. Conclusion: Vascular smooth muscle technology can effectively increase the thickness of endometrium, with the aim of assisting to improve the pregnancy success rate of thin endometrial infertility through vascular smooth muscle technology.


2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Jiaming Li ◽  
Zhaoyue Wang ◽  
Lan Dai ◽  
Lijuan Cao ◽  
Jian Su ◽  
...  

We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP). Eighty-eight patients were separated into the control (cyclosporine A plus prednisone) and experimental (rapamycin plus prednisone) groups. The CD4+CD25+CD127lowregulatory T (Treg) cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR) was similar in both groups (experimental group versus control group: 58% versus 62%,P=0.70). However, sustained response (SR) was more pronounced in the experimental group than in the control group (68% versus 39%,P<0.05). Both groups showed similar incidence of adverse events (7% versus 11%,P=0.51). As expected, the low pretreatment baseline level of Treg cells was seen in all patients (P<0.001); however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP.


Author(s):  
Gülşen Doğan Durdağ ◽  
Gizem Bektaş ◽  
Esengül Türkyılmaz ◽  
Halime Göktepe ◽  
Meltem Sönmezer ◽  
...  

Objective: In frozen-thawed embryo transfer (FET) cycles, preparing a synchronous endometrium for the embryo is essential. Aim of this study is to provide individualized luteal support in hormonally replaced FET cycles, and to evaluate mid-luteal serum progesterone levels and pregnancy outcomes.Study Design: In this prospective cohort study, 30 patients were included in a university hospital in six month-period. Serum progesterone level on embryo transfer day was monitored, and if it was found to be below the lower limits defined by previous studies (10 ng/mL), additional 100 mg intramuscular micronized progesterone was administered once.Mid-luteal progesterone levels and pregnancy outcomes were recorded.Results: There was no significant difference between mid-luteal progesterone levels of the patients whose transfer day progesterone was above and below 10 ng/mL (p=0.481). Although clinical pregnancy rate tended to be higher in patients whose mid-luteal progesterone was above 10 ng/mL, it was also not statistically significant.Conclusion: This is the first study in which vaginal progesterone treatment was supported by intramuscular progesterone according to serum progesterone values for the purpose of individualized progesterone support. Significant difference was not found in pregnancy outcomes. However, further studies are required to optimize management and improve pregnancy rates in hormonally treated FET cycles.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
E Turkgeldi ◽  
B Shakerian ◽  
S Yildiz ◽  
I Keles ◽  
B Ata

Abstract Study question Does endometrial thickness (EMT) predict live birth (LB) after fresh and frozen-thawed embryo transfer (ET) and is there a lower EMT cut-off for ET? Summary answer Once intracavitary pathology and inadvertent progesterone exposure is excluded, EMT is not predictive for LB. EMT is not linearly associated with probability of LB. What is known already EMT is commonly used as a marker of endometrial receptivity and in turn, assisted reproductive technology treatment success. ET is often cancelled or postponed if EMT is below an arbitrary cut-off. However, the available evidence on the relationship between EMT and LB rates is conflicting and too dubious to hold such strong stance. An overwhelming majority of the studies on the subject are retrospective, they use different arbitrary cut off values ranging between 6 to 9 mm with heterogeneous stimulation and transfer protocols. Study design, size, duration Records of all women who underwent fresh or frozen-thawed ET in Koc University Hospital Assisted Reproduction Unit between October 2016 - August 2019 were retrospectively screened. All women who underwent fresh or frozen-thawed blastocyst transfer during the study period were included. Every woman contributed to the study with only one transfer cycle for each category, i.e., fresh ET and frozen-thawed ET. Participants/materials, setting, methods After ruling out endometrial pathology, EMT was measured on the day of ovulation trigger for fresh ET cycles, and on the day of progesterone commencement for frozen-thawed ET. ET was carried out, regardless of EMT, if there was no suspicion of inadvertent progesterone exposure, i.e., due to follicular phase progesterone elevation in fresh or premature ovulation in frozen ET cycles. Main results and the role of chance 560 ET cycles, 273 fresh and 287 frozen-thawed, were analyzed. EMT varied from 4mm to 18mm. EMT were similar between women who achieved a LB and who did not after fresh ET [10.5 (9.2 – 12.2) mm and 9 (8 – 11) mm, respectively, p = 0.11]. Ovarian stimulation characteristics and proportion of women who received a single embryo were similar (69% vs 68.3%, respectively, p = 0.91). Women who achieved a LB was significantly younger than those who did not [35 (32–38) and 37 (33–41), respectively, p &lt; 0.01]. Women who had a LB and who did not after frozen-thawed ET had similar EMT of 8.4 (7.4 – 9.7) mm and 9 (8 – 10) mm, respectively (p = 0.38). Women who achieved a LB were significantly younger than those who did not [32 (29–35) vs 34 (30–38) years, p = 0.04]. The proportion of women who received a single ET was similar between women who achieved a LB and who did not after a FET [86/95 (90.5%) vs 181/192 (94.3%), respectively, p = 0.26]. Area under curve values of EMT for predicting LB in fresh, frozen-thawed and all ET were 0.56, 0.47 and 0.52, respectively. EMT and LB rate were not linearly correlated in fresh or frozen-thawed ET cycles. Limitations, reasons for caution Although our study is retrospective, no women was denied ET due to EMT in our center. Only patients undergoing ET were included in the analysis, which may introduce bias due to the selection of couples who were competent enough to produce at least one blastocyst fit for transfer. Wider implications of the findings: Since women with thin endometrium had reasonable chance for LB even in the absence of a cut-off for EMT in this unique dataset, delaying or denying ET for any given EMT value alone does not seem justified. Further studies in which ET is carried out regardless of EMT are needed. Trial registration number Not applicable


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14658-e14658
Author(s):  
Xuezhong Yang ◽  
Benjamin Weinberg ◽  
Jimmy J. Hwang ◽  
Christina Sing-Ying Wu ◽  
Madeeha Akram ◽  
...  

e14658 Background: The 5-year survival of PAC with surgery alone is below 10%, and with adjuvant chemotherapy increases to about 20%. The original GITSG adjuvant study demonstrating a survival benefit compared to surgery could be attributed to the use of 2-years of weekly IV bolus 5FU, and not only chemoradiation. In theory, the prolonged exposure to therapy could maintain pressure on dormant cancer cells that may remain in G0 arrest, by attacking them as they infrequently enter G1/S phase. To evaluate this hypothesis, we retrospectively evaluated our pts who were treated with or without maintenance Cape. Methods: Pts in the Georgetown/Lombardi Cancer Center EMR since Oct 2007 were sought for PAC that was resected with curative intent, received standard adjuvant chemotherapy with or without chemoradiation. The study group received maintenance cape for at least 2 months, and the control group was monitored until disease recurrence. Only pts with complete follow-up survival data were analyzed. Results: 20 pts met the criteria as study group, and 58 pts as the control group. In the study group, cape was usually given 1000mg orally twice a day, Monday through Friday following adjuvant therapy, for an indefinite period, up to 2 years. Pts received cape for median duration of 12.5 months (2 to 24 months), and the median follow-up duration was 33 months (16 to 78 months). The median overall survival (OS) for the study group was 48 months. The 2 year OS was 94%, and 5 year OS was 40%. The median recurrence free survival (RFS) was 39 months. The 2 year RFS was 67%, and the 5 year RFS was 25%. Common toxicities were mild hand-and-foot syndrome and fatigue. 4 pts discontinued cape due to toxicities: febrile neutropenia, severe fatigue, weight loss and diarrhea. The control group was of comparable staging, and the median OS was 22 months, 5 year OS rate was 16%, median RFS was 13 months, 2 year RFS was 19%. Conclusions: In this single institute retrospective controlled cohort study, Cape maintenance therapy following adjuvant therapy in resected PAC is associated with a significantly (p<0.05) higher OS and PFS compared to the control group. This approach should be studied in a RCT.


2020 ◽  
Vol 27 (08) ◽  
pp. 1626-1630
Author(s):  
Nathumal Maheshwari ◽  
Nadeem Noor ◽  
Adnan Bashir ◽  
Bilawal Hingorjo ◽  
Arshad Ali ◽  
...  

Objectives: To evaluate the efficacy of oral zinc as adjuvant therapy in acute diarrhea comparing frequency and volume of stool and duration of diarrhea in children. Study Design: Case Control study. Setting: Department of Paediatrics, Shaheed Muhtrama Benazir Bhutto Medical College Layari General Hospital, Karachi. Period: September 2017 to August 2018. Material & Methods: A sample of 200 children, age 5- 15 years, suffering from acute diarrhea was divided into control and cases (study group). Oral zinc therapy (20 mg once daily) was given 14 days and its efficacy was observed in terms of stool frequency, stool volume and duration of diarrhea. Variables were noted at 24 hours and 48 hours and on 7th day of hospitalization. Data was analyzed on SPSS statistical software (version 22.0) at 95% confidence interval (P≤ 0.05). Results: Mean ± SD age in control and study group was noted as 9.1± 5.43 years and 9.5±6.02 years respectively (P=0.053). 89% of children of study group were discharged on 3rd day of hospitalization compared to only 45% from control group.  Zinc treated study group shows significant decrease in frequency of loose stools, stool volume and lesser duration of hospital stay. Conclusion: Oral zinc therapy was effective in decreasing the frequency of loose stools and volume and lesser duration of hospital stay in children.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Cedri. . Durnerin ◽  
M Peigné ◽  
J Labrosse ◽  
M Guerout ◽  
C Vinolas ◽  
...  

Abstract Study question Does systematic dydrogesterone supplementation in artificial cycles (AC) for frozen-thawed embryo transfer (FET) during Covid–19 pandemic modify outcomes compared to prior individualized supplementation adjusted on serum progesterone (P) levels ? Summary answer Systematic dydrogesterone supplementation in AC for FET is associated with similar outcomes compared to prior individualized supplementation in patients with low P levels. What is known already In AC for FET using vaginal P for endometrial preparation, low serum P levels following P administration have been associated with decreased pregnancy and live birth rates. This deleterious effect can be overcome by addition of other routes of P administration. We obtained effective results by adding dydrogesterone to vaginal P and postponing FET by one day in patients with low P levels. However, in order to limit patient monitoring visits and to schedule better FET activity during Covid–19 pandemic, we implemented a systematic dydrogesterone supplementation without luteal P measurement in artificial FET cycles. Study design, size, duration This retrospective study aimed to analyse outcomes of 394 FET after 2 different protocols of artificial endometrial preparation. From September 2019 to Covid–19 lockdown on 15th March 2020, patients had serum P level measured on D1 of vaginal P administration. When P levels were &lt; 11 ng/ml, dydrogesterone supplementation was administered and FET was postponed by one day. From May to December 2020, no P measurement was performed and dydrogesterone supplementation was systematically used. Participants/materials, setting, methods In our university hospital, endometrial preparation was performed using sequential administration of vaginal estradiol until endometrial thickness reached &gt;7 mm, followed by transdermal estradiol combined with 800 mg/day vaginal micronized P started in the evening (D0). Oral dydrogesterone supplementation (30 mg/day) was started concomitantly to vaginal P in all patients during Covid–19 pandemic and only after D1 P measurement followed by one day FET postponement in patients with P levels &lt;11 ng/ml before the lockdown. Main results and the role of chance During the Covid–19 pandemic, 198 FET were performed on D2, D3 or D5 of P administration with dydrogesterone supplementation depending on embryo stage at cryopreservation. Concerning the 196 FET before lockdown, 124 (63%) were performed after dydrogesterone addition from D1 onwards and postponement by one day in patients with serum P levels &lt;11 ng/ml at D1 while 72 were performed in phase following introduction of vaginal P without dydrogesterone supplementation in patients with P &gt; 11 ng/ml. Characteristics of patients in the 2 time periods were similar for age (34.5 + 5 vs 34.1 + 4.8 years), endometrial thickness prior to P introduction (9.9 + 2.1 vs 9.9 + 2.2 mm), number of transferred embryos (1.3 + 0.5 vs 1.4 + 0.5) , embryo transfer stage (D2/D3/blastocyst: 8/16/76% vs 3/18/79%). No significant difference was observed between both time periods [nor between “dydrogesterone addition and postponement by 1 day” and “in phase” FET before lockdown] in terms of positive pregnancy test (39.4% vs 39.3% [44% vs 30.5%]), heartbeat activity at 8 weeks (29.3% vs 28% [29% vs 26.4%]) and ongoing pregnancy rates at 12 weeks (30.7% but truncated at end of October 2020 vs 25.5% [26.6% vs 23.6%]). Limitations, reasons for caution Full results of the Covid–19 period will be further provided concerning ongoing pregnancy rates as well as comparison of live birth rates and obstetrical and neonatal outcomes. Wider implications of the findings: These results suggest that systematic dydrogesterone supplementation is as effective as individualized supplementation according to serum P levels following administration of vaginal P. This strategy enabled us to schedule easier FET and limit patient visits for monitoring while maintaining optimal results for FET in AC during the Covid–19 pandemic. Trial registration number Not applicable


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