P–347 A comparative RCT of Intrauterine-GCSF versus Subcutaneous-GCSF in Thin Endometrium in IVF-ICSI Cycles

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P C Jindal ◽  
M Singh

Abstract Study question Does GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to GCSF by the subcutaneous route, in IVF-ICSI Cycles? Summary answer Yes, GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to subcutaneous-GCSF, in ART Cycles? What is known already GCSF, is a member of the colony stimulating factor family of cytokines and growth factors. GCSF receptors are expressed in high concentration on dominant follicle, particularly at preovulatory stage.The endometrium also shows an increased expression of these receptors. GCSF concentration rises in the follicular fluid at the same time. Serum levels of GCSF are found to be in direct correlation with levels of GCSF in follicular fluid. Serum levels increase progressively from the day the embryo-transfer to the day of implantation. GCSF has been found to be beneficial in patients with thin endometrium and recurrent implantation failure. Study design, size, duration This was a RCT conducted between 2018–2019. 30 patients with thin endometrium were enrolled in each group. In either group, GCSF was given if endometrium was less than 7mm on day 14, maximum of two doses were administered. Patients undergoing frozen embryo transfer were recruited in the study, after meeting the inclusion and exclusion criteria. Primary outcome measured was increase in endometrium thickness and the secondary outcome was the clinical pregnancy rate and abortion-rate. Participants/materials, setting, methods 60 patients with thin endometrium were randomly divided into two groups. Group A: Inj. GCSF (300 mcg/1 ml) subcutaneously on Day 14 onwards alternate days for two doses. Group B: Inj. GCSF (300 mcg/1 ml) instilled slowly into the uterine cavity using an intrauterine insemination (IUI) catheter under USG guidance. Endometrial thickness was assessed after 48 h. If endometrial thickness was found to be < 7 mm, a second infusion of GCSF was carried out. Main results and the role of chance In the subcutaneous group (group-A) the mean endometrial thickness before GCSF injection was 5.8 ± 0.6 mm and, after injection it increased to 6.9 ± 0.4 mm. Similarly, in the intrauterine group (group-B) the mean endometrial thickness before GCSF was 5.9 ± 0.7 which increased to a mean of 7.9 ± 0.5 after GCSF instillation. The difference between endometrial thickness before and after intrauterine infusion of GCSF was more than that in the subcutaneous group. In group-A, 08 patients conceived out of 30 patients ( clinical pregnancy rate 26.6%) and in group B 11 conceived out of 30 patients in whom GCSF was instilled intrauterine (pregnancy rate 36.6%). Thus, there was a difference in the clinical pregnancy rate in the two groups, the intrauterine group yielding a higher clinical pregnancy rate, but it was not statistically significant. Because of the thin endometrium, we found an abortion rate of 25% (2/8) in the subcutaneous-GCSF group, and an abortion rate of 18% (2/11) in the intrauterine GCSF group. Limitations, reasons for caution There are few potential limitations because of the small sample size. Confounders such as obesity, smoking and alcohol intake, presence of adenomyosis and endometriosis, were not taken into consideration. Though prevalence of obesity is usually low in Indian women. Habits of smoking and alcohol are exceedingly uncommon in Indian women. Wider implications of the findings: Use of GCSF plays an important role in management of patients of thin endometrium undergoing embryo transfer. It is an easily available and economical preparation in developing countries and the intrauterine instillation of GCSF can be easily practiced in an ART unit with good results in resistant thin endometrium patients. Trial registration number Not applicable

2021 ◽  
pp. 68-75
Author(s):  
A.O. Polumiskova ◽  
S.I. Tevkin ◽  
T.M. Jussubaliyeva ◽  
M.S. Shishimorova

In order to increase the effectiveness of assisted reproductive technologies (ART) programs, it is essential to improve and develop conditions of embryo culture prior its transfer or cryopreservation of expanded blastocysts on the day 5 or 6. The aim of the study was to assess the effect of human blastocysts’ expansion timing on clinical pregnancy rate (CPR), miscarriage rate (MR) and take-home baby rate (THBR) in frozen-thawed cycles during ART programs. The study involved 2275 frozen embryo transfers (FET) of blastocysts expanded on the day 5 (group A) and 170 FET of blastocysts expanded on the day 6 (group B). The pregnancy rates in both groups were 50.8% and 46.5% respectively. There were no statistically significant differences in clinical pregnancy rate 37.4% and 37.0%, miscarriage rate 26.0% and 21.5% in both groups, respectively. THBR, as the main indicator of efficiency in the programs with transfer of post thawed expanded blastocysts on the day 5 (group A) or 6 (group B) were 36.5% and 35.2%, respectively (the difference is insignificant). In conclusion, in cryoprotocols the day of blastocyst expansion (day 5 or 6 of development) does not statistically affect PR, MR and THBR. In FET programs the quality of blastocyst (excellent and good) should be prioritized regardless of the day of cryopreservation.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Racca ◽  
S Santos-Ribeiro ◽  
D Panagiotis ◽  
L Boudry ◽  
S Mackens ◽  
...  

Abstract Study question What is the impact of seven days versus fourteen days’ estrogen (E2) priming on the clinical outcome of frozen-embryo-transfer in artificially prepared endometrium (FET-HRT) cycles? Summary answer No significant difference in clinical/ongoing pregnancy rate was observed when comparing 7 versus 14 days of estrogen priming before starting progesterone (P) supplementation. What is known already One (effective) method for endometrial preparation prior to frozen embryo transfer is hormone replacement therapy (HRT), a sequential regimen with E2 and P, which aims to mimic the endocrine exposure of the endometrium in a physiological cycle. The average duration of E2 supplementation is generally 12–14 days, however, this protocol has been arbitrarily chosen whereas, the optimal duration of E2 implementation remains unknown. Study design, size, duration This is a single-center, randomized, controlled, open-label pilot study. All FET-HRT cycles were performed in a tertiary centre between October 2018 and December 2020. Overall, 150 patients were randomized of whom 132 were included in the analysis after screening failure and drop-out. Participants/materials, setting, methods The included patients were randomized into one of 2 groups; group A (7 days of E2 prior to P supplementation) and group B (14 days of E2 prior to P supplementation). Both groups received blastocyst stage embryos for transfer on the 6th day of vaginal P administration. Pregnancy was assessed by an hCG blood test 12 days after FET and clinical pregnancy was confirmed by transvaginal ultrasound at 7 weeks of gestation. Main results and the role of chance Following the exclusion of drop-outs and screening failures, 132 patients were finally included both in group A (69 patients) or group B (63 patients). Demographic characteristics for both groups were comparable. The positive pregnancy rate was 46.4% and 53.9%, (p 0.462) for group A and group B, respectively. With regard to the clinical pregnancy rate at 7 weeks, no statistically significant difference was observed (36.2% vs 36.5% for group A and group B, respectively, p = 0.499). The secondary outcomes of the study (biochemical pregnancy, miscarriage and live birth rate) were also comparable between the two arms for both PP and ITT analysis. Multivariable logistic regression showed that the HRT scheme is not associated with pregnancy rate, however, the P value on the day of ET is significantly associated with the pregnancy outcome. Limitations, reasons for caution This study was designed as a proof of principle trial with a limited study population and therefore underpowered to determine the superiority of one intervention over another. Instead, the purpose of the present study was to explore trends in outcome differences and to allow us to safely design larger RCTs. Wider implications of the findings: The results of this study give the confidence to perform larger-scale RCTs to confirm whether a FET-HRT can be performed safely in a shorter time frame, thus, reducing the TTP, while maintaining comparable pregnancy and live birth rates. Trial registration number NCT03930706


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Abalı ◽  
F K Boynukalın ◽  
M Gültomruk ◽  
Z Yarkiner ◽  
M Bahçeci

Abstract Study question Does the outcome of the first euploid frozen-thawed blastocyst embryo transfer affect the subsequent euploid FBT originating from the same cohort of oocytes? Summary answer The clinical pregnancy rate and ongoing pregnancy rate of the subsequent FBT are higher if a clinical pregnancy was attained in the first euploid FBT. What is known already Numerous factors including patient, cycle and embryological characteristics affect the outcome of an IVF treatment cycle. There is no data available whether the outcome of euploid FBT has an impact on the outcome of the subsequent euploid FBT of embryos originating from the same cohort of retrieved oocytes. Study design, size, duration The study enrolled cycles preimplantation genetic test for aneuploidy (PGT-A) performed between January 2016 and July 2019 at the Bahceci Fulya IVF Center. A total of 1051 patients with single euploid FBT were evaluated and resulted live birth (n = 589, live birth rate (LBR): 56%(589/1051)), miscarriage (n = 100, miscarriage rate (MR): 14.5% (100/689)) and no clinical pregnancy (n = 362, 34,4%, (362/1051)). 159 FBT after the first single euploid FBT originating from the same cohort of oocytes were analyzed. Participants/materials, setting, methods Second euploid FBT cycle after first FBT with a clinical pregnancy were compared to frozen-thawed cycles after a without a pregnancy. Logistic regression analysis was utilized to adjust for potential confounders including female age, body mass index, embryo quality, day of embryo frozen, number previous failed attempt, number of previous miscarriage, endometrial thickness, outcome of the first euploid FBT. Main results and the role of chance The pregnancy outcome from the first euploid FBT in the study group was resulted live birth (25.1%, (40/159)), miscarriage (15.7%, (25/159)) and no clinical pregnancy (59.1%, (94/159). The pregnancy outcome of the subsequent euploid embryo transfer from the same oocyte cohort was clinical pregnancy rate (CPR): (67.3%, (107/159) ongoing pregnancy rate (OPR) (52.2% (83/159) and MR (22.4%, (24/107)). The CPR in the subsequent euploid FBT was 80% (52/65) among patients who achieved a clinical pregnancy in the first euploid FBT and 58.5% (55/94) of those who did not (p = 0.0045). The OPR in the subsequent euploid FBT was 64.6% (42/65) among patients who achieved a clinical pregnancy in first euploid FBT and 43.6% (41/94) of those who did not (p = 0.009). On a multivariate regression analysis, clinical pregnancy in the first euploid FBT was a significant independent predictor for a pregnancy in the subsequent FBT transfer (p = 0.003). Limitations, reasons for caution The limitation of the study is in the retrospective nature of the study. As the PGT-A strategy significantly decreases number of transferable embryos, the sample size of the study is limited. Wider implications of the findings: Identifying predictive factors for the success of euploid FBT is important. These can help physicians while counseling patients regarding the outcome of the previous euploid FBT. Trial registration number NA


2015 ◽  
Vol 46 (4) ◽  
pp. 501-505 ◽  
Author(s):  
M. A. Coelho Neto ◽  
W. P. Martins ◽  
M. L. S. Lima ◽  
M. A. P. Barbosa ◽  
C. O. Nastri ◽  
...  

Author(s):  
Amishi Vijay Vora ◽  
Purnima K. Nadkarni ◽  
Jigna Garasia ◽  
Aditi Nadkarni ◽  
Pooja Nadkarni Singh ◽  
...  

Background: For success in IVF treatment, it is essential that the patient has a responsive endometrium together with many other factors. Inspite of numerous treatments available today for growth of endometrium, there is lack of any ideal drug or protocol for increasing endometrial thickness. The study is an attempt to evaluate the role of two drugs for increasing endometrial growth before embryos transfers.Methods: This study is a retrospective cohort study including 50 patients with previously diagnosed as thin endometrium patients who may or may not have failed previous cycles of IVF. Patients were randomly divided into two groups. First group-Group A (n=25) are patients randomly selected to undergo intrauterine PRP instillation for increase in endometrial thickness before embryo transfer. Second group-Group B (n=25) are randomly selected from a retrospective cohort of thin endometrium to take injection GCSF  as intrauterine infusion (total dose 300mcg) on day of trigger or day 11 of cycle followed by 60 units subcutaneously after embryo transfer. The difference in endometrial thickness during transfer and the pregnancy outcomes were compared.Results: Injection GCSF was found to be more effective than intrauterine PRP in improving endometrial thickness in patients with thin endometrium with a p-value of <0.0001.  It was found that the chemical and clinical pregnancy rates were comparable as the p values were 0.77 and 0.37 respectively and hence statistically not significant. Although patients given injection GCSF had a slightly higher clinical pregnancy rate (44%) as compared to patients given intrauterine PRP which was 28%. All other variables were comparable.Conclusions: In the study it was proven that injection GCSF, is more effective for the treatment of thin endometrium patients as compared to intrauterine PRP infusion. Though the clinical and chemical pregnancy rates were comparable, a higher percentage of women were clinically pregnant in the group given injection GCSF.  Intrauterine PRP can also be a good alternative for thin endometrium.  More studies and RCTS are needed for comparison to prove the effectiveness of these drugs for treatment of thin endometrium.


2019 ◽  
Author(s):  
Jianyuan Song ◽  
Tingting Liao ◽  
Liu Jiang ◽  
Houming Su ◽  
Licheng Ji ◽  
...  

Abstract Purpose To explore the effect of different concentrations of peak serum estradiol levels on endometrial receptivity quantitatively. Methods In our reproductive medicine center, two best quality of day 3 (D3) embryos were transferred or frozen according to E 2 and progesterone levels on the day of human chorionic gonadotropin (hCG) administration and the number of oocytes retrieved. The remaining embryos were cultured to blastocyst stage and frozen. The patients were then categorized into three groups. The patients with frozen-thawed D3 embryo transfer in artificial cycles without blastocyst frozen served as group 1, those with fresh D3 embryo transfer without blastocyst frozen as group 2, and those with fresh D3 embryo transfer with blastocyst frozen as group 3. Each group was further stratified into 4 sub-groups according to E 2 levels on the day of hCG administration. Clinical pregnancy rate, implantation rate and abortion rate of frozen-thawed and fresh D3 embryo transfer were compared among the three groups in the same stratified E 2 levels. Results For E 2 <7,000 pg/mL, group 1 and group 2 had similar clinical pregnancy rate and implantation rate. But for E 2 ≥7,000 pg/mL, the clinical pregnancy rate in group 1 was significantly higher than in group 2 (p<0.05). For E 2 <7,000 pg/mL, pregnancy rate and implantation rate in group 1 were significantly lower than those in group 3 (P<0.05). But for E 2 ≥7,000 pg/mL, the pregnancy rate in group 1 was significantly higher than in group 3 (P<0.05). There was no significant difference in the abortion rate between group 1 and group 2, or between group 1 and group 3. Conclusions High serum E 2 concentration does not impair implantation and pregnancy rates unless exceeding a certain limit (e.g. 7,000 pg/mL) on the day of hCG administration. Since peak E 2 level was related to OHSS and adverse pregnancy outcomes, further study is needed to set a threshold peak E 2 level for fresh embryo transfer.


Author(s):  
Pramod Gade ◽  
Aher Gautam S ◽  
Vazifdar Sharmeen

Background: This was a prospective observational study conducted over a twelve-month duration in our institute to compare the combined effect of metformin and myoinositol with metformin alone. Method: A total of sixty patients were included in the study, and they were divided into two groups depending on whether they were given the combination or the single drug. Group A (n=30) was given Myoinositol 600 mg+Metformin 500 mg thrice a day, and Group B ( n=30) was given only Myoinositol 600 mg thrice a day. The outcome measure was clinical pregnancy rate and improvement in clinical and hormonal parameters after drug therapy. Results: BMI (p<0.01), modified Ferriman Gallaway score (p>0.05), and the was a significant improvement in the hormonal parameters (LH,FSH) in both the groups and the levels were found to be comparable after a period of 6 months. The clinical pregnancy rate after six cycles of ovulation was significantly higher in Group A as compared to Group B. In Group A, the total clinical pregnancy rate was 43.33%, and in Group B, it was 26.67%, respectively, and the end of 6 months and the difference was statistically significant (p = <0.01) Conclusion: Equal response in reduction of hormonal levels and clinical and laboratory parameters were seen in both groups, while better results in terms of clinical fertility rates were observed in the group that was given a combination of myoinositol with metformin.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Dogra ◽  
N Singh ◽  
S Mathur

Abstract Study question Does intralipid supplementation in women with unexplained recurrent implantation failure (RIF) with elevated uterine natural killer cell (uNK) levels improve pregnancy outcomes during IVF? Summary answer Intralipid supplementation appears to improve clinical pregnancy rate in women with unexplained RIF with elevated uNK cell levels. What is known already The increased numbers of uNK cells in peri-implantation endometrium have been reported in women with recurrent miscarriage (RM) and RIF after IVF. However, reports are contradictory when it comes to correlation of increased numbers of uNK cells with pregnancy outcome. Current opinion suggests there is a potential for intralipid therapy in improving reproductive outcome, although data on live birth rate is very limited. No studies have assessed the effect of intralipid on IVF outcomes in RIF women based on elevated uNK cells. Identified studies have all used pNK cell testing as preferred diagnostic tool for analysis of NK cell levels. Study design, size, duration A randomized placebo controlled trial was conducted at Division of Reproductive Medicine at tertiary care institute. Thirty women with RIF and fifty fertile controls with age &lt;35 years having regular menstrual cycles and no hormonal treatment in last 3 months were enrolled in the study from January 2019 to December 2020 for uNK cell testing. Randomization was done using random numbers and sealed envelopes. Only the subjects were masked and allocation concealment was done. Participants/materials, setting, methods Subjects included RIF 20–35 years, normal ovarian reserve, unexplained and tubal factors, normal karyotype and normal uterine cavity. Cut off for uNK cells was derived from fertile controls by immunohistochemical staining of CD56+ cells from midluteal endometrial biopsy sample. Subjects with elevated uNK cell levels were randomized during IVF to group A (Intralipid) or group B ( saline ). The infusion was repeated within one week of positive pregnancy test and then every 2 weeks. Main results and the role of chance The mean age and BMI were comparable between fertile control and study group(29.45±3.3 vs 31.17±3.3 years, 22.97±1.89 vs 23.21±2.2 kg/m2 ;p&gt;0.05). The median uNK cell levels was 7%(used as cut off) in fertile controls and 13.5% in RIF. 18 women (60%, 18/30) with RIF who had elevated uNK cell level (&gt;7%) were randomized. Four women were lost to follow up. The median age, BMI, number of previous failed cycles and duration of infertility were comparable between Group A(n = 7) and Group B(n = 7){30(IQR:27–31) vs 33(IQR:30–34)years, 22.7(IQR:21.08–24.4) vs 22.6(IQR:21.37–24.2)kg/m2, 2(IQR:2–3) vs 2(IQR:2–3), 8(IQR:7–8) vs 8(IQR:7–10)years}. The median FSH, AMH and AFC were 5.86(IQR:5.13–7.67)mIU/l, 2.4(IQR:2.16–6.12)ng/ml, 10(IQR:8–12) in Group A which were comparable with Group B {6.2(IQR:4.78–6.5)mIU/l, 4.8(IQR:2.67–6.25)ng/ml, 12(IQR:12–16) }. All patients underwent antagonist protocol. The clinical pregnancy rate was 57.14%(4/7) in group A which was significantly higher as compared to 28.6%(2/7) in group B(p &lt; 0.05). None of the patients reported any side effects due to intralipid. Limitations, reasons for caution The limitation of present study is its small sample size. However, the study is currently recruiting more RIF patients, and these are the interim results of the same. More RCTs with larger sample size are required to assess the efficacy of intralipid in this specific subset of population. Wider implications of the findings: The present study suggests the beneficial effect of intralipid in women with unexplained RIF with elevated uNK cell levels in increasing the chemical and clinical pregnancy rate. However, ongoing pregnancy rate and live birth rate should be investigated further in this subset of population. Trial registration number CTRI/2019/01/017213


2013 ◽  
Vol 1 (1) ◽  
pp. 38-44
Author(s):  
Mitko Ivanovski ◽  
Slavjanka Popovska

Aim: The aim of the present study was to determine the importance of the depth of embryo replacement into the uterine cavity (upper or lower half endometrial cavity) on the implantation clinical pregnancy rates.Material and Methods: In this prospective observational were included 160 patients underwent controlled ovarian hyperstimulation followed by IVF/ICSI and embryo transfer. On the day of embryo transfer under direct transabdominal ultrasound guidance, the transfer catheter was advanced to a defined distance from the uterine fundus, up to the point estimated for transfer: 10 ± 2.5 mm (Group A) and 15 ± 2.5 mm (Group B).Results: In total, 160 patients, aged 24-42 years were included in the study. Overall clinical pregnancy rate were 41.2%. Analysis of our results demonstrated that pregnancy rate is significantly influenced by transfer distance from the fundus where the  pregnancy rate decreases from 48.7% in group B to 34.5%  in group A (p<0.05). There was not significantly difference in abortion rate between the two groups.Conclusion: In conclusion, our results suggest that depth of embryo replacement inside the uterine cavity may influence the pregnancy rates and should be considered as an important factor to improve the success of IVF cycles.


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