scholarly journals Frozen Embryo Transfer in Mildly Stimulated Cycle With Letrozole Compared to Natural Cycle in Ovulatory Women: A Large Retrospective Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Danjun Li ◽  
Shuzin Khor ◽  
Jialyu Huang ◽  
Qiuju Chen ◽  
Qifeng Lyu ◽  
...  

ObjectiveTo evaluate the clinical effect of mild stimulation with letrozole on pregnancy outcomes in ovulatory women undergoing frozen embryo transfer (FET) compared to natural cycle.DesignRetrospective observational study.SettingTertiary care academic medical center.PopulationA total of 6,874 infertile women with regular menstrual cycles (21-35 days) met the criteria for this study in the period from 2013 to 2020.MethodsAll patients who were prepared for and underwent FET were divided into two groups: a modified natural cycle (NC) group (n=3,958) and a letrozole cycle group (n=2,916).Main Outcome MeasuresThe primary outcome of the study was clinical pregnancy rate. Secondary outcome measures were endometrial thickness, rates of implantation, positive HCG test, live birth, early miscarriage and ectopic pregnancy.ResultsThe clinical pregnancy rate was not statistically different between the modified NC-FET group and the letrozole-FFT group before (crude OR 0.99, 95% CI 0.90-1.09, P=0.902>0.05) and after propensity score matching (PSM) (crude OR 1.01, 95% CI 0.91-1.12, P=0.870>0.05). After multivariable logistic regression analysis, the clinical pregnancy rate remained insignificant before (adjusted OR 1.00, 95% CI 0.91-1.10, P=0.979>0.05) and after matching (adjusted OR 1.00, 95% CI 0.89-1.11, P=0.936>0.05), respectively. Similarly, in the crude and adjusted analysis, the positive HCG test, implantation, live birth and early miscarriage rates were also comparable in the letrozole-FFT group and modified NC-FET group before and after matching. Furthermore, the endometrial thickness of letrozole-FFT group was similar to that of modified NC-FET group with adjusted analysis.ConclusionOur observation suggests that mild stimulation with letrozole could produce similar pregnancy outcomes in ovulatory patients who undergo FET when compared with a natural cycle.

Author(s):  
Zhiqin Bu ◽  
Xinhong Yang ◽  
Lin Song ◽  
Beijia Kang ◽  
Yingpu Sun

Abstract Background The aim of this study was to explore the impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst. Methods This observational cohort study included a total of 3091 patients undergoing their first frozen-thawed embryo transfer (FET) cycles between April 2015 to March 2019. Endometrial thickness was measured by trans-vaginal ultrasound twice for each patient: on day of progesterone administration, and on day of embryo transfer. The change of endometrial thickness was recorded. Results Regardless of endometrial preparation protocol (estrogen-progesterone/natural cycle), female age, body mass index (BMI), and infertility diagnosis were comparable between patients with an increasing endometrium on day of embryo transfer and those without. However, clinical pregnancy rate increases with increasing ratio of endometrial thickness. Compared with patients with Non-increase endometrium, those with an increasing endometrium on day of embryo transfer resulted in significantly higher clinical pregnancy rate (56.21% vs 47.13%, P = 0.00 in estrogen-progesterone cycle; 55.15% vs 49.55%, P = 0.00 in natural cycle). Conclusions In most patients, endometrial thickness on day of embryo transfer (after progesterone administration) increased or kept being stable compared with that on day of progesterone administration. An increased endometrium after progesterone administration was associated with better pregnancy outcome.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Bayram ◽  
N D Munck ◽  
A Abdala ◽  
I Elkhatib ◽  
A El-Damen ◽  
...  

Abstract Study question Which factors affect the clinical pregnancy rate (CPR) after single euploid frozen embryo transfers (FET), when the blastocyst is transferred in the upper uterine cavity area? Summary answer Blastocyst quality, embryo transfer difficulty and endometrial thickness affect the CPR in FET. What is known already There is a limited understanding of the factors affecting success rates after FET. The most important factors influencing implantation rates are patient characteristics, type of endometrial preparation, embryo quality and transfer difficulty. It has been shown that the position of the euploid blastocyst, measured as distance from the fundus (DFF) of the uterine cavity (mm), affects the implantation potential. Although the ideal location within the uterine cavity is still being debated in very heterogeneous patient populations, most studies have found that the highest pregnancy rates are obtained when the embryo is placed in the upper area of the uterine cavity. Study design, size, duration This single center retrospective cohort study included a total of 603 single euploid FET cycles, in the upper half of the uterine cavity, between January 2019 and November 2020 in ART Fertility Clinic Abu Dhabi, UAE. Participants/materials, setting, methods Trophectoderm biopsy samples were subjected to Next Generation Sequencing to screen the ploidy state. Vitrification and warming were performed using the Cryotop method (Kitazato, Biopharma). The full length of the uterine cavity and the longitudinal distance between the fundal endometrial surface and the air bubble after transfer were measured. Main results and the role of chance The patients were on average 33.9 (19–46) years old. The FET was performed in a natural cycle (NC) (n = 278) or hormone replacement therapy (HRT) (n = 325). Of the 603 transfers which had been performed in the upper half of the uterus, 412 (68.3%) resulted in a pregnancy and 311 (51.5%) in a clinical pregnancy. After bivariate analysis, the clinical pregnancy rate was significantly higher for high quality blastocysts (grade 1–2 versus 3–4) (p < 0.001), after easy embryo transfers (p = 0.001) and for higher endometrial thickness (p = 0.027). After performing a multivariate logistic regression analysis to consider the effect of all explanatory variables (age, Anti Müllerian hormone, body mass index, endometrial thickness, quality of the blastocyst, difficulty of the transfer [requirement of additional instrumentation], presence of mucus or blood on the transfer catheter, day 5 or day 6 biopsy, FET endometrial preparation), the clinical pregnancy was affected by the endometrial thickness: OR 1.20 [1.05–1.37], p = 0.007; transfer difficulty: OR 0.44 [0.25–0.79], p = 0.006; blastocyst quality 3: OR 0.38 [0.18–0.79], p = 0.01 and blastocyst quality 4: OR 0.15 [0.06–0.37], p < 0.0001. Age did not affect the clinical pregnancy after transferring a single euploid blastocyst: OR 1.03 [1.00–1.06], p = 0.052. Limitations, reasons for caution The limitation of this study was its retrospective nature and the small sample size. Other parameters may be important in live birth outcomes. Wider implications of the findings: Optimization of clinical pregnancy outcomes after FET depends on multiple factors. Even after transfer of euploid blastocysts in the upper uterine cavity, the endometrial thickness, transfer difficulty and blastocyst quality will still affect the clinical pregnancy outcomes. Trial registration number NA


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Y Dong ◽  
Y Jia ◽  
Y Sha ◽  
L Diao ◽  
S Cai ◽  
...  

Abstract Study question To evaluate whether the pregnancy outcomes could be improved in implantation failure patients by endometrial receptivity array, endometrial immune profiling, or a combination of both. Summary answer There was no statistical difference between different endometrial receptivity evaluation and treatment in improving the clinical pregnancy rate. What is known already Both endometrial receptivity array and endometrial immune profiling were promised to improve the endometrial receptivity and subsequent clinical pregnancy. However, less is known about the efficiency between each other and whether the combination could further enhance their clinical value. Study design, size, duration Between November 2019 and September 2020, 143 women with a history of at least two or more consecutive implantation failure in IVF/ICSI treatment in Chengdu Xinan Gynecology Hospital were included. They were divided into three groups: ‘ERA + Immune Profiling’ (n = 70), ‘Immune Profiling’ (n = 41), and ‘ERA’ (n = 32). Participants/materials, setting, methods Inclusion criteria were age ≤ 38, with normal uterus and uterine cavity. All patients were suggested to evaluate endometrial receptivity by ERA test (Igenomix, Valencia, Spain) and endometrial immune profiling based on immunohistochemistry simultaneously, who would be free to choose each or both evaluation approaches. Personal Embryo Transfer and/or personal medical care were adopted according to evaluation results. Clinical pregnancy was confirmed by gestational sacs observed under ultrasonography. Main results and the role of chance The overall prevalence of displaced window of implantation (WOI) is 84.3%, and nearly 74.8% (83/111) patients were diagnosed as endometrial immune dysregulation. Clinical Pregnancy rate and embryonic implantation rate decreased in the ‘Immune Test’ groups, but without a statistical difference (P = 0.311, and 0.158, respectively). Multivariable logistic regression analysis showed that different endometrial receptivity evaluation and treatment was not associated the clinical pregnancy rate, suggesting the performance of different endometrial receptivity evaluation and treatment is similar in improving the clinical pregnancy rate. Neither the immune profiling (CD56, P = 0.591; FOXP3, P = 0.195; CD68, P = 0.820; CD163, P = 0.926; CD1a, P = 0.561; CD57, P = 0.221; CD8, P = 0.427; CD138 CE, P = 0.372) nor histologic endometrial dating defined by Noyes criteria (P = 0.374) were associated with ERA phases. Limitations, reasons for caution Although the selection of evaluation approaches was based on patients’ willingness, the variances of baseline characteristics and immune profiling existed in different groups. The immunological treatment efficacy based on immune profiling was not evaluated before embryo transfer. Wider implications of the findings: To our knowledge, this is the first study comparing the pregnancy outcomes after two typical endometrial receptivity evaluation approaches. The findings highlight the unsubstitutability for each assessment, indicating that both asynchronous and pathological WOI contribute to implantation failure. Trial registration number X2019004


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


2016 ◽  
Vol 33 (12) ◽  
pp. 1553-1557 ◽  
Author(s):  
Jigal Haas ◽  
Jim Meriano ◽  
Carl Laskin ◽  
Yaakov Bentov ◽  
Eran Barzilay ◽  
...  

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.


Author(s):  
T R Zaat ◽  
J P de Bruin ◽  
M Goddijn ◽  
M van Baal ◽  
E B Benneheij ◽  
...  

Abstract STUDY QUESTIONS The objective of this trial is to compare the effectiveness and costs of true natural cycle (true NC-) frozen embryo transfer (FET) using urinary LH tests to modified NC-FET using repeated ultrasound monitoring and ovulation trigger to time FET in the natural cycle. Secondary outcomes are the cancellation rates of FET (ovulation before hCG or no dominant follicle, no ovulation by LH urine test, poor embryo survival), pregnancy outcomes (miscarriage rate, clinical pregnancy rates, multiple ongoing pregnancy rates, live birth rates, costs) and neonatal outcomes (including gestational age, birthweight and sex, congenital abnormalities or diseases of babies born). WHAT IS KNOWN ALREADY FET is at the heart of modern IVF. To allow implantation of the thawed embryo, the endometrium must be prepared either by exogenous estrogen and progesterone supplementation (artificial cycle (AC)-FET) or by using the natural cycle to produce endogenous oestradiol before and progesterone after ovulation to time the transfer of the thawed embryo (NC-FET). During a NC-FET, women visit the hospital repeatedly and receive an ovulation trigger to time FET (i.e. modified (m)NC-FET or hospital-based monitoring). From the woman’s point of view, a more natural approach using home-based monitoring of the ovulation with LH urine tests to allow a natural ovulation to time FET may be desired (true NC-FET or home-based monitoring). STUDY DESIGN, SIZE, DURATION This is a multicentre, non-inferiority prospective randomised controlled trial design. Consenting women will undergo one FET cycle using either true NC-FET or mNC-FET based on randomisation. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on our sample size calculation the study group will consist of 1464 women between 18 and 45 years old who are scheduled for FET. Women with anovulatory cycles, women who need ovulation induction and women with a contra indication for pregnancy will be excluded. The primary outcome is ongoing pregnancy. Secondary outcomes are cancellation rates of FET, pregnancy outcomes (including miscarriage rate, clinical pregnancy, multiple pregnancy rate and live birth rate). Costs will be estimated by counting resource use and calculating unit prices. STUDY FUNDING/COMPETING INTEREST(S) The study received a grant from The Dutch Organisation for Health Research and Development (ZonMw 843002807; www.zonmw.nl). ZonMw has no role in the design of the study, collection, analysis, and interpretation of data or writing of the manuscript. Dr. Broekmans reports personal fees from member of the external advisory board for Merck Serono, grants from Research support grant Merck Serono, outside the submitted work;. Dr. Cantineau reports and Unrestricted grant of Ferring B.V. to the Center for Reproductive medicine, no personal fee. Author up-to-date on Hyperthecosis. Congress meetings 2019 with Ferring B.V. and Theramex B.V. Dr. Goddijn reports Department research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the submitted work. Dr. Groenewoud reports personal fees from Titus Health Care, outside the submitted work; Dr. Lambalk reports grants from Ferring, grants from Merck, from Guerbet, outside the submitted work. The other authors have none to declare. TRIAL REGISTRATION NUMBER Dutch Trial Register (Trial NL6414 (NTR6590), https://www.trialregister.nl/). TRIAL REGISTRATION DATE 23 July 2017 DATE OF FIRST PATIENT’S ENROLMENT 10 April 2018


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