Endometrium immunomodulation by intrauterine insemination administration of treated peripheral blood mononuclear cell prior frozen/thawed embryos in patients with repeated implantation failure

Zygote ◽  
2019 ◽  
Vol 27 (4) ◽  
pp. 214-218 ◽  
Author(s):  
Fattaneh Farifteh Nobijari ◽  
Seyedeh Soheila Arefi ◽  
Ashraf Moini ◽  
Robabeh Taheripanah ◽  
Elham Fazeli ◽  
...  

SummaryIn assisted reproductive technology (ART) programmes, approximately 10% of infertile patients have at least two or three repeated implantation failures (RIFs) after an in vitro fertilization (IVF) protocol. Successful implantation mainly depends on local immune tolerance mechanisms involving a spectrum of cytokines, interleukins and growth factors. The latter have played pivotal roles in the recruitment of immune cells (and notably T-lymphocyte cells). In total, 250 couples participating in frozen–thawed embryo transfer programme were incorporated in a randomized clinical trial (peripheral blood mononuclear cells (PBMC) subgroup: n=122; control subgroup: n=128). In the PBMC group, a blood sample was collected 5 days before the scheduled frozen–thawed embryo transfer; PBMCs were isolated using Ficoll separation and then cultured for 72 h. Two days prior to embryo transfer, 0.4 ml of cultured PBMCs were transferred into the patient’s uterus. Although the clinical pregnancy rate was higher in the PBMC group (34.4%) than in the control group (23.4%), this difference was not statistically significant (P=0.05 in a chi-squared test). Nevertheless, when we limited the analysis to patients with ≥3 RIFs (n=138), there was a significant difference in the clinical pregnancy rate between the PBMC group (38.6%) and the control group (19.7%; P=0.01). Our results imply that PBMC transfer can be part of effective fertility treatment for patients with RIF.

2020 ◽  
Author(s):  
Yuan Liu ◽  
Yixia Yang ◽  
Xinting Zhou ◽  
Yanmei Hu ◽  
Yu Wu

Abstract Background: Previous studies have demonstrated that newborns from fresh embryo transfer are with higher risk of small for gestation (SGA) rate than those from frozen-thawed embryo transfer (FET). It is suggested that supraphysiologic serum estradiol in controlled ovarian stimulation (COS)is one of reasons. Out study aims to investigate whether exogenous estradiol delivered regimens have an impact on live birth rate and singleton birthweight in hormone replacement (HRT)-FET cycles.Methods:This retrospective study involved patients undergoing their first FET with HRT endometrium preparation followed by two cleavage-staged embryos transfer, comparing orally and vaginal estradiol tablets (OVE) group versus oral estradiol tablets (OE) group from January 2015 to December 2018 at our center. A total of 792 patients fulfilled the criteria, including 282 live birth singletons. Live birth was the primary outcome. Secondary outcome included clinical pregnancy rate, singleton birthweight, large for gestational age (LGA) rate, SGA rate, preterm delivery rate. Results:Patients in OVE group achieved higher serum estradiol level with more days of estradiol treatment. No difference in live birth (Adjusted OR 1.327; 95%CI 0.982, 1.794, p=0.066) and clinical pregnancy rate (Adjusted OR 1.278; 95%CI 0.937, 1.743, p=0.121) was found between OVE and OE groups. Estradiol route did not affect birth weight (β=-30.962, SE=68.723, p=0.653), the odds of LGA (Adjusted OR 1.165; 95%CI 0.545, 2.490, p=0.694), the odds of SGA (Adjusted OR 0.569; 95%CI 0.096, 3.369, p=0.535) or the preterm delivery rate (Adjusted OR 0.969; 95%CI 0.292, 3.214, p=0.959).Conclusion:Estrogen orally and vaginally together did not have an impact on clinical outcomes and singleton birthweight compared to estrogen orally taken, but was accompanied with relative higher serum E2 level and potential maternal undesirable risks.


2021 ◽  
Author(s):  
xiaoyue Shen ◽  
Min Ding ◽  
Yuan Yan ◽  
Shanshan Wang ◽  
jianjun Zhou ◽  
...  

Abstract Background To evaluate the frozen-thawed embryo transfer (FET) outcomes of repeated cryopreservation by vitrification of blastocysts derived from vitrified-warmed day3 embryos in patients who experienced implantation failure previously. Methods We retrospect the files of patients who underwent single frozen-thawed blastocyst transfer cycles in our reproductive medical center from January 2013 to December 2019. 127 patients transfer of vitrified-warmed blastocysts derived from vitrified-warmed day3 embryos were defined as twice-cryopreserved group. 1567 patients who transfer blastocysts that had experienced once vitrified-warmed were used as once-cryopreserved group. None of them was pregnant at the previous FET. The outcomes were compared between two groups after a 1:1 propensity score matching (PSM). Results The clinical pregnancy rate was 52.76%, live birth rate was 43.31% in twice-cryopreserved group. After PSM,108 pairs of patients were generated for comparison. The clinical pregnancy rate, live birth rate or miscarriage rate was not significantly different between two groups. Logistic regression analysis indicated that double vitrification-warming procedures did not affect FET outcomes in terms of clinical pregnancy rate (OR 0.83, 95%CI 0.47-1.42), live birth rate (OR 0.93, 95%CI 0.54-1.59), miscarriage rate (OR 0.72 95%CI 0.28-1.85). Furthermore, the pregnancy complications rate, gestational age or neonatal abnormalities rate between two groups was also comparable, while twice vitrification-warming procedures might increase the macrosomia rate (19.6% vs. 6.3%, P = 0.05). Conclusion Transfer of double vitrified-warmed embryo at cleavage stage and subsequent blastocyst stage did not affect live birth rate and neonatal abnormalities rate, but there was a tendency to increase macrosomia rate, which needs further investigation.


2021 ◽  
Author(s):  
Bin xu ◽  
Jing Zhao ◽  
Zhaojuan Hou ◽  
Nenghui Liu ◽  
Yanping Li

Abstract Background: It is controversial whether gonadotropin-releasing hormone agonist (GnRHa) pretreatment can benefit the pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles. In most of studies, GnRHa was administered during the mid-luteal phase for pretreatment. Few studies focus on FET cycles with GnRHa administered in early follicle phase.Methods: The retrospective cohort study was conducted in a university-affiliated IVF center. 630 patients in the GnRHa FET group and 1141 patients in the hormone replacement treatment (HRT) FET without GnRHa group from October 2017 to March 2019 were included. The menstruation cycle of these patients was irregular. Results: There were no differences observed between the two groups in patient’s characteristics. However, the GnRHa FET group showed a higher percentage of endometrium with triple line pattern (94.8% vs 89.6%, p<0.001) on the day of progesterone administration, and an increased implantation rate (34.7% vs 30%, p<0.01), biochemical pregnancy rate (60.6% vs 54.3%, p = 0.009), and clinical pregnancy rate (49.8% vs 43.3%, p = 0.008), as compared to that in the HRT FET cycles with similar endometrial thickness, ectopic pregnancy rate, and early miscarriage rate. Binary logistic regression analysis showed the GnRHa FET group to be associated with an increased chance of clinical pregnancy rate compared with HRT FET without GnRHa group (P=0.014, odds ratio [OR] 1.30, 95% confidence interval [CI] 1.06-1.61).Conclusions: Pretreatment with a long-acting GnRHa in early follicular phase can improve the clinical outcome of the FET cycles. However, further randomized control trials (RCTs) will be needed to verify these results.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P K Sim ◽  
P Nadkarni

Abstract Study question Between spontaneous ovulation (SPO) and induced ovulation (INO) comparing clinical pregnancy rate and ongoing pregnancy rate for frozen-thawed embryo transfer (FET) cycle, which is better? Summary answer Both spontaneous ovulation and induced ovulation protocols showed no significant difference in clinical pregnancy rates and ongoing pregnancy rates. What is known already Recent practice worldwide is moving towards elective freezing of all embryos and subsequent frozen-thawed transfer, both for a perceived higher pregnancy rate as well as the significant reduction of ovarian hyperstimulation. The timing of FET can be determined by either detecting the spontaneous Luteinizing Hormone surge (SPO group) or by the administration of hCG (INO group). There is still an ongoing debate to determine which is the best protocol for frozen-thawed embryo transfer in the non-hormone replacement therapy (non-HRT) cycle. Study design, size, duration This retrospective study included 500 FET cycles for patients who had regular menses between June 2017 and June 2020. The FET cycles were grouped by type as follows: SPO (n = 281) and INO (n = 219). The primary outcome was the clinical pregnancy rate and the secondary outcome was ongoing pregnancy rate. Ongoing pregnancy is defined as a viable intrauterine pregnancy at 12 weeks of gestation confirmed on an ultrasound scan. Participants/materials, setting, methods This study was conducted in a single IVF centre. Vitrification was used as the cryopreservation method. To standardize outcome measures, only patients having single blastocyst transfer and aged under 38 years old were included. The average age of the patient was 32.9. Gamete donation, embryo donation, pre-implantation testing and assisted hatching cycles were also excluded from the analysis. Categorical data were analysed using Chi-square test SPSS version 25. Main results and the role of chance Clinical pregnancy rate for SPO group was 54.8% (154/281) versus 52.9% (116/219) in INO group. Even though clinical pregnancy rate was higher in SPO group as compared to INO group, it did not reach significance level (ꭓ2 = 0.17, p = 0.68). As all patients had single blastocyst transferred, the implantation rate was the same as clinical pregnancy rate. Ongoing pregnancy rate was also found higher in SPO group as compared to INO group (135/281, 48.0% and 97/219, 44.3% respectively) but again failed to reach significance level (ꭓ2 = 0.70, p = 0.40). Limitations, reasons for caution The retrospective nature of the study and therefore, the analysis was not adjusted for confounding factors such as blastocyst grading, etiology of infertility, and ethnicity of patients. Wider implications of the findings: In natural cycle, both spontaneous ovulation and induced ovulation protocols had the same pregnancy outcomes for frozen-thawed embryo transfer. However, induced ovulation can facilitate in scheduling FET timing to avoid weekends and public holidays, if necessary. 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).


2019 ◽  
Vol 47 (7) ◽  
pp. 2873-2880 ◽  
Author(s):  
Zhihui Xu ◽  
Wenming Chen ◽  
Chune Chen ◽  
Yikang Xiao ◽  
Xia Chen

Objective To investigate the effect of human chorionic gonadotropin (hCG) intrauterine injection before frozen–thawed embryo transfer (FET) in women with endometriosis. Methods This retrospective cohort study included 45 women with endometriosis who underwent hCG intrauterine injection before FET; each woman was matched with three patients with endometriosis who did not receive hCG intrauterine injection (controls). Data on pregnancy and prenatal outcomes were extracted from medical records and compared. Results Patients in the hCG intrauterine injection group had significantly higher rates of pregnancy and clinical pregnancy (64.4% and 57.8%, respectively) than controls (47.4% and 39.3%, respectively). Neonatal birth weight for both singletons and twins was significantly higher in the hCG group (3486 ± 458 g and 2710 ± 437 g, respectively) than in the control group (3195 ± 401 g and 2419 ± 370 g, respectively). Conclusion Pregnancy rate, clinical pregnancy rate, and birth weight were improved in women with endometriosis who underwent intrauterine hCG injection compared with those who did not receive hCG before FET.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jian-Chun Li ◽  
Yan-Hong Wang ◽  
li-Ying Peng ◽  
Yun Zhou ◽  
Shi-Bin Chao

BackgroundIn recent years frozen-thawed embryo transfer (FET) has played an increasingly important role in ART, but there is limited consensus on the most effective method of endometrial preparation (EP) for FET. Inspired by significantly higher implantation rate and clinical pregnancy rate of the depot GnRH-a protocol, we proposed a novel EP protocol named down-regulation ovulation-induction (DROI) aimed to improve pregnancy outcomes of FET.MethodsThis was a single-center, randomized controlled pilot trial. A total of 307 patients with freeze-all strategy scheduled for first FET were enrolled in the study. A total 261 embryos were transferred in DROI-FET group including 156 patients and 266 embryos were transferred in mNC-FET group including 151 patients. Reproductive outcomes were compared between the two groups.ResultsThe basic characteristics of patients, and the average number, quality and stage of embryos transferred were comparable between the two groups. Our primary outcome, implantation rate(IR) in DROI-FET group, was significantly higher than that of the mNC-FET group (54.41% versus 35.71%, P&lt;0.01). The clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in DROI-FET group was also higher than that in mNC-FET group (69.87% versus 50.33%, P&lt;0.01; 64.10% versus 42.38%, P&lt;0.01).Conclusion(s)Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.


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