scholarly journals Impacts of Cyclosporin A on clinical pregnancy outcomes of patients with a history of unexplained transfer failure: a retrospective cohort study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Danni Qu ◽  
Xiangming Tian ◽  
Ling Ding ◽  
Yuan Li ◽  
Wenhui Zhou

Abstract Background A rapid development in assisted reproductive technology (ART) has led to a surge in its popularity among target couples. However, elucidation on the molecular mechanism and effective solutions for a common problem posed by ART, namely transfer failure, is still lacking. The new therapeutic potential of cyclosporin A (CsA), a typical immunosuppressant widely used in the treatment of rejection after organ transplantation, in recurrent pregnancy loss (RPL) patients may inspire some novel transfer failure therapies in the future. To further explore the clinical effects of CsA, this study investigated whether its application can improve clinical pregnancy outcomes in patients with a history of unexplained transfer failure in frozen-thawed embryo transfer (FET) cycles. Methods Data from a retrospective cohort investigation (178 frozen-thawed embryo transfer cycles in 178 patients) were analysed using binary logistic regression to explore the relationship between CsA treatment and clinical pregnancy outcomes; the odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated as a measure of relevancy. Implantation rate was the main outcome measure. Results There was no difference in the fine adjusted OR (95 % CI) of the implantation rate [1.251 (0.739–2.120)], clinical pregnancy rate [1.634 (0.772–3.458)], chemical pregnancy rate [1.402 (0.285–6.909)], take-home baby rate [0.872 (0.423–1.798)], multiple births rate [0.840 (0.197–3.590)], preterm birth [1.668 (0.377–7.373)], abnormal birth weight [1.834 (0.533–6.307)] or sex ratio [0.956 (0.339–2.698)] between the CsA-treated group and control group. No birth defects were observed in the present study. Conclusions Although CsA does not affect infant characteristics, it has no beneficial effects on the clinical pregnancy outcomes in patients with a history of unexplained transfer failure in FET cycles.

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<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<0.01; 64.10% versus 42.38%, P<0.01).Conclusion(s)Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.


2020 ◽  
Author(s):  
Wei Xiong ◽  
Ruiyi Tang ◽  
Peng Wu ◽  
Zhengyi Sun ◽  
jingran zhen ◽  
...  

Abstract Background: GnRH-agonist is used to treat adenomyosis, but its efficacy in adenomyosis patients with uterine enlargement undergoing frozen embryo transfer (FET) is unclear. Methods:The retrospective cohort study comprised 112 adenomyosis patients with uterine enlargement undergoing the first FET circle. A long-term GnRH-a pretreatment was administered to 112 patients with uterine enlargement. These patients were divided into two groups according to the therapeutic effect: patients with a normal-size uterus after GnRH-a treatment (GN group) and patients with an enlarged uterus after GnRH-a treatment (GL group). Results:Not all patients can shrink their uterus to a satisfactory level. After receiving GnRH-a pretreatment, the uterus returned to normal size in 77% of patients (GN group), and 23% of patients had a persistently enlarged uterus (GL group). The pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate were significantly higher in the GN group than in the GL group. Controlling for the confounding factors, normal uterus size (odds ratio [OR] 4.50; P=0.03) and low body mass index (OR 3.13; P=0.03) affected the odds of achieving live birth. The cut-off value selected on the ROC curve of uterus volume after GnRH-a treatment for detecting live birth was 144.7Conclusions:GnRH-a pretreatment was associated with the regression of adenomyosis lesions and improved clinical pregnancy outcomes in the adenomyosis patients with uterine enlargement whose lesion are GnRH-a susceptible on FET cycles. However, about a quarter of patients may not be less responsive to GnRH-a and have poorer pregnancy outcomes, especially in overweight women.


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):  
Li Li ◽  
Dan-Dan Gao ◽  
Yi Zhang ◽  
Jing-Yan Song ◽  
Zhen-Gao Sun

Abstract Objective The principal purpose of this study was to compare reproductive outcomes for stimulated cycles (STC) and hormone replacement cycles (HRC) for endometrial preparation before frozen-thawed embryo transfer (FET) in young women with polycystic ovary syndrome (PCOS). Methods We conducted a retrospective study of 1434 FET cycles from January, 2017 to March, 2020 in our reproductive center, in which stimulated and hormone replacement cycles were used for endometrial preparation. Pregnancy outcomes of couples undergoing routine STC-FET or HRC-FET were analyzed before and after propensity score matching (PSM). Results Data on 1234 HRC protocols (86% of the total) and 200 STC protocols (14%) were collected. After PSM, 199 patients were included in both groups, respectively. There was no significant difference in positive pregnancy rate (52.7% vs. 54.8%, p = 0.763), clinical pregnancy rate (51.8% vs. 52.8%, p = 0.841), live birth rate (45.2% vs. 43.7%, p = 0.762), pregnancy loss rate (9.7% vs. 16.2%, p = 0.164) and ectopic pregnancy rate (1.5% vs. 0.5%, p = 0.615) between STC protocols and HRC protocols. Conclusion STC for endometrial preparation had similar pregnancy outcomes compared with HRC protocols by excluding heterogeneous factors after PSM. Evidence is available which shows that for young women with PCOS who were undergoing in-vitro fertilization, HRC could be a reasonable choice for patients who are unwilling to accept injections. Additionally, STC may offer more flexibility for young PCOS patients and reproductive centres.


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.


2020 ◽  
Author(s):  
Yuan Liu ◽  
Yixia Yang ◽  
Jian Sun ◽  
Xinting Zhou ◽  
Yanmei Hu ◽  
...  

Abstract Background: Previous studies have demonstrated that newborns from fresh embryo transfer have 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. Our study aims to investigate whether exogenous estradiol delivered regimens have an impact on live birth rate and neonatal outcomes in hormone replacement (HRT)-FET cycles. Methods: This was a retrospective study involving patients undergoing their first FET with HRT endometrium preparation followed by the transfer of two cleavage-staged embryos, comparing estradiol administered orally and vaginally (OVE group) versus estradiol administered orally (OE group) from January 2015 to December 2018 at our center. A total of 792 patients fulfilled the criteria, including 228 live birth singletons. The live birth rate was the primary outcome measure. Secondary outcome measures 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 singletons 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 (Adjusted OR 0.969; 95%CI 0.292, 3.214, p = 0.959). Conclusion: Estrogen taken orally and vaginally together did not change live birth rate and singleton neonatal outcomes compared to estrogen taken orally, but was accompanied with relative higher serum E2 level and potential maternal undesirable risks.


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


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