P–521 Association between maternal age and euploid blastocyst availability in cycles with less than four two-pronucleate zygotes

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
C Gordon ◽  
E Ginsburg ◽  
C Racowsky ◽  
A Lanes
Keyword(s):  
Embryo Transfer ◽  
Age Groups ◽  
Genetic Diagnosis ◽  
Ovarian Response ◽  
Small Sample ◽  
Poor Responders ◽  
Cleavage Stage ◽  
Fresh Embryo Transfer ◽  
Relative Risks ◽  
The Difference

Abstract Study question For patients with less than four two-pronucleate (2pn) zygotes, is there an age-cutoff above which preimplantation genetic diagnosis for aneuploidy (PGT-A) is futile? Summary answer Women over 40y with less than four 2pn zygotes should consider transfer of a day 3 embryo over culture to blastocyst with PGT-A. What is known already During a typical IVF cycle, there is unavoidable attrition from oocytes retrieved, to embryos obtained, to blastocysts formed such that some patients, particularly those with advanced age or poor ovarian response, may not have blastocysts available to biopsy. While randomized trials have shown improved pregnancy rates with the use of PGT-A in patients of advancing age, these trials primarily included patients with good ovarian reserve and multiple blastocysts available. The optimal age group within poor responders who would benefit most from PGT-A has yet to be determined. Study design, size, duration This was a retrospective cohort study of all fresh autologous IVF or IVF/ICSI cycles in which PGT-A was planned from 1/2012 to 3/2020. Only patients with less than four 2pn zygotes were included. A total of 85 cycles from 75 patients were analyzed. Participants/materials, setting, methods Number of cleavage-stage embryos, blastocysts, biopsy-quality blastocysts and euploid embryos were assessed, after stratification by age. Adjusted relative risks (aRR) and 95% confidence intervals (CI) were calculated adjusting for BMI, AMH, FSH, stimulation protocol, and ICSI. Poisson regression was used for counts. Generalized estimating equations were used to account for patients contributing multiple cycles. Main results and the role of chance There were no differences in number of 2pn zygotes (p = 0.98) or cleavage stage embryos (p = 0.94) across age groups. Patients aged 41–42y had a significantly lower number of blastocysts (1.18 vs. 2.00; aRR 0.59 95%CI: 0.37–0.95) and biopsy-quality blastocysts (0.73 vs. 1.53; aRR 0.50 95% CI: 0.26–0.98) compared to patients <35y.These patients also had fewer euploid embryos available (0.09 vs 0.67), although the difference was not significant in the adjusted model (aRR 0.14 95% CI: 0.01–1.57). None of the patients >42y had euploid blastocysts. When considering the mean and three standard deviations (0.09 [SD 0.3]), 99.7% of patients over 40y have no euploid embryo available for transfer. Limitations, reasons for caution This study was retrospective in nature and limited by small sample sizes when patients were stratified by age. A prospective randomized trial of patients with less than four 2pn zygotes to day 3 fresh embryo transfer vs PGT-A frozen embryo transfer is needed to confirm these findings. Wider implications of the findings: Patients over 40y with less than four 2pn zygotes are at high risk of having no euploid blastocysts. While the literature demonstrates higher live birth rates with the use of PGT-A in women of advancing age, this is inconsequential if there is no embryo available to transfer. Trial registration number Not applicable

scholarly journals Seasonal variability does not impact in vitro fertilization success

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xitong Liu ◽  
Haiyan Bai ◽  
Ben W. Mol ◽  
Wenhao Shi ◽  
Ming Gao ◽  
...  
Keyword(s):  
Seasonal Variation ◽  
Embryo Transfer ◽  
Live Birth ◽  
Seasonal Variability ◽  
Multivariate Logistic Regression Analysis ◽  
Small Sample ◽  
Frozen Embryo Transfer ◽  
Fresh Embryo Transfer ◽  
Significant Difference

AbstractIt is unknown whether seasonal variation influences the outcome of in vitro fertilization (IVF). Previous studies related to seasonal variation of IVF were all small sample size, and the results were conflicting. We performed a retrospective cohort study evaluating the relationship between seasonal variability and live birth rate in the year of 2014–2017. Patients were grouped into four seasons (Winter (December-February), Spring (March-May), Summer (June-August), and Autumn (September-November)) according to the day of oocyte pick-up (OPU). Multivariate logistic regression analysis was performed to evaluate association between seasonal variation and live birth. Models were adjusted for covariates including temperature, sunshine hour, infertility type, infertility duration, infertility factor and BMI. In total 38,476 women were enrolled, of which 25,097 underwent fresh cycles, 13,379 were frozen embryo transfer. Live birth rates of fresh embryo transfer were 50.36%, 53.14%, 51.94% and 51.33% for spring, summer, autumn and winter, respectively. Clinical pregnancy rate between the calendar months varied between 55.1% and 63.4% in fresh embryo transfer (ET) and between 58.8% and 65.1% in frozen embryo transfer (FET) (P-values 0.073 and 0.220). In the unadjusted model and adjust model, seasonal variation was not associated with live birth. In conclusion, there was no significant difference of seasonal variations in the outcome of IVF with fresh embryo transfer and frozen embryo transfer.

P–325 The impact of letrozole on endometrial thickness in IVF cycles

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Ruiter-Ligeti ◽  
S Arab ◽  
W Buckett
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Embryo Transfer ◽  
Endometrial Thickness ◽  
Oocyte Retrieval ◽  
Estradiol Level ◽  
Poor Responders ◽  
Fresh Embryo Transfer ◽  
The Impact

Abstract Study question Does daily administration of letrozole during IVF stimulation affect endometrial thickness ? Summary answer Patients treated with letrozole during fresh IVF cycles had a thinner endometrium on the day of trigger compared to patients who did not receive letrozole. What is known already Letrozole supplementation is commonly used during fertility preservation for breast cancer patients to reduce peak estrogen levels with no adverse effects on embryo outcomes. Studies in poor responders have found that letrozole use resulted in a shorter duration of stimulation and a lower total dose of gonadotropin, with no detrimental effect on IVF outcomes. In normal responders, studies have shown an increase in blastocysts obtained, but have not yet shown an increase in clinical pregnancy rates. There is concern that when a fresh embryo transfer is planned letrozole use may negatively affect endometrial thickness and subsequently diminish pregnancy rates. Study design, size, duration In a retrospective cohort study between January 2009 and June 2019 at a single academic fertility center, we compared the endometrial thickness in 97 cancer patients who underwent IVF-fertility preservation with daily letrozole use to 158 cancer patients who underwent IVF-fertility preservation without letrozole. Participants/materials, setting, methods All women diagnosed with cancer were referred for fertility preservation prior to gonadotoxic treatment exposure and were less than 40 years old at the time of oocyte retrieval. All patients who received letrozole started on day one of stimulation and continued until the day of oocyte retrieval. The primary outcome was endometrial thickness on the day of trigger. The secondary outcomes were number of oocytes retrieved, number of MII retrieved, and maximal estradiol level. Main results and the role of chance During the study period, 336 cancer patients underwent fertility preservation. Eighty-one patients were excluded; 50 because they had an intrauterine device or were on long term oral contraceptives and 31 because endometrial thickness was not documented. Of the remaining 255 patients, 86 had breast cancer, 95 had a hematological cancer and 74 had various other cancers. Ninety-seven cancer patients treated with letrozole were compared to 158 cancer patients who did not receive letrozole. Patients who received letrozole were significantly older (34 vs 28yrs, P < 0.0001). There were no significant differences in baseline characteristics such as BMI, AFC nor in the total duration for stimulation. Endometrial thickness on the day of trigger was significantly less in letrozole treated patients (8 vs 9mm, P < 0.003). There were no significant differences in total number of oocytes retrieved (12.5 vs 11, P = 0.126) nor in the number of mature oocytes (8 vs 8, P = 0.312). Patients in the letrozole group received a higher total gonadotropin dose (2680IU vs 1980IU, P = 0.016). The maximum estradiol level was significantly lower in patients treated with letrozole (1068 vs 3838ml/dl, P = <0.0001). A regression analysis showed that using letrozole during stimulation decreased the endometrial thickness by 0.81mm (CI –1.37 to –0.253, P = 0.005). Limitations, reasons for caution The retrospective nature of this study could have introduced selection and misinformation bias. We report on cancer patients where all oocytes or embryos were vitrified. Without fresh embryo transfer data, it is unclear if a thinner endometrium due to letrozole will effect the implantation or pregnancy rate. Wider implications of the findings: As the use of letrozole expands beyond cancer patients and poor responders, it is important to understand the impact on the endometrium. This study shows that letrozole reduces endometrial thickness. However, the effect on endometrial function remains unknown. Further study is needed before letrozole can be used with fresh transfers. Trial registration number 2020–6370

Confidence intervals for the difference between two relative risks

2020 ◽  
Vol 29 (10) ◽  
pp. 3048-3058
Author(s):  
Joshua N Sampson ◽  
Mitchell H Gail
Keyword(s):  
Human Papillomavirus ◽  
Confidence Interval ◽  
Small Sample ◽  
Control Treatment ◽  
Human Papillomavirus Vaccine ◽  
Relative Risks ◽  
Vaccine Trials ◽  
The Difference ◽  
Small Sample Sizes ◽  
Papillomavirus Vaccine

We provide methods to estimate the confidence interval for the difference between two relative risks. Letting p0, p1, and p2 be the probabilities of an event in three groups (i.e. control, treatment 1, treatment 2), our methods estimate a confidence interval for r =  p1/ p0 −  p2/ p0. We highlight that our methods can handle small sample sizes, covariates, and study populations from multiple strata. We specifically developed these methods for vaccine trials to estimate the difference between two vaccine efficacies, where VE1 = 1 −  p1/ p0, VE2 = 1 −  p2/ p0 and r = VE2 − VE1. We showcase our methods by using interim data from one of these trials to suggest that one dose of the human papillomavirus vaccine may be as efficacious as two doses of the vaccine.

scholarly journals Associations of post-warming embryo or blastocyst development with clinical pregnancy in vitrified embryo or blastocyst transfer cycles

2020 ◽  
Vol 47 (2) ◽  
pp. 140-146
Author(s):  
Yeon Hee Hong ◽  
Jang Mi Lee ◽  
Seul Ki Kim ◽  
Hye Won Youm ◽  
Byung Chul Jee
Keyword(s):  
Embryo Transfer ◽  
Area Under The Curve ◽  
Clinical Pregnancy ◽  
Blastocyst Transfer ◽  
Cleavage Stage ◽  
Blastocyst Development ◽  
Embryo Score ◽  
Cleavage Stage Embryo ◽  
Stage Embryo ◽  
The Difference

Objective: To investigate whether the degree of post-warming embryo or blastocyst development is associated with clinical pregnancy in vitrified embryo or blastocyst transfer cycles.Methods: Ninety-six vitrified cleavage-stage embryos and 58 vitrified blastocyst transfer cycles were selected. All transfer cycles were performed from February 2011 to March 2019, and all vitrified embryos or blastocysts were warmed from 4 PM to 6 PM and then transferred the next morning from 9 AM to 10 AM. The scores of the cleavage-stage embryos and blastocysts were assessed at warming and at transfer using the modified Steer method and the Gardner method, respectively. The mean embryo or blastocyst score, score of the single top-quality embryo or blastocyst, and the difference in the score between warming and transfer were compared between nonpregnant and pregnant women.Results: In the cleavage-stage embryo transfer cycles, both the top-quality embryo score at transfer and the difference in the score between warming and transfer were significantly associated with clinical pregnancy. A top-quality embryo score at transfer of ≥60.0 (area under the curve [AUC], 0.673; 95% confidence interval [CI], 0.531–0.815) and a difference in the score between warming and transfer of ≥23.0 (AUC, 0.675; 95% CI, 0.514–0.835) were significant predictors of clinical pregnancy. In blastocyst transfer cycles, the top-quality blastocyst score at transfer was the only significant factor associated with clinical pregnancy. A top-quality blastocyst score at transfer of ≥38.3 was a significant predictor of clinical pregnancy (AUC, 0.666; 95% CI, 0.525–0.807).Conclusion: The top-quality embryo score at transfer and the degree of post-warming embryo development were associated with clinical pregnancy in vitrified cleavage-stage embryo transfer cycles. In vitrified blastocyst transfer cycles, the top-quality blastocyst score at transfer was the only significant factor affecting clinical pregnancy.

P–500 Euploid embryo-transfer reduces advanced maternal age patients’ anxiety in the waiting period before the pregnancy-test

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M Forte ◽  
F Faustini ◽  
R Venturella ◽  
E Rania ◽  
E Alviggi ◽  
...  
Keyword(s):  
Embryo Transfer ◽  
Maternal Age ◽  
Genetic Diagnosis ◽  
Advanced Maternal Age ◽  
Single Embryo Transfer ◽  
Pregnancy Test ◽  
Waiting Period ◽  
Infertile Women ◽  
The Difference ◽  
Euploid Embryo

Abstract Study question Can PGT-A reduce the anxiety generally experienced by infertile women undergoing IVF in the waiting period between embryo transfer and the pregnancy test? Summary answer PGT-A reduces anxiety in infertile women after embryo transfer, probably due to a gain of confidence in their treatment route. What is known already The waiting period, i.e. the time between embryo-transfer and the pregnancy-test, is considered unpredictable and unmanageable, thus figuring amongst the most stressful steps of an IVF treatment. This is mainly imputable to women’s lost sense of control over the outcome. Uncertainty is in fact a source of fear and elevated distress. PGT-A has been shown to improve live birth rate per embryo transfer and reduce miscarriage rate per clinical pregnancy across several trials and observational studies worldwide, especially in advanced maternal age (AMA) women. Here, we investigated if euploid embryo transfer does involve also lower emotional burden over untested one. Study design, size, duration Prospective observational study evaluating the level of anxiety in the waiting period among women undergoing euploid or untested embryo transfer. Data were collected between September 2019 and September 2020 in a public hospital. A total of 48 infertile women were recruited: 25 undergoing euploid single embryo transfer after trophectoderm biopsy and NGS, and 23 undergoing untested single embryo transfer. Participants/materials, setting, methods To measure the level of anxiety, the two groups completed the STAI (State Trait Anxiety Inventory) questionnaire at two time points: before starting the ovarian stimulation (T0), and at day 8 after embryo transfer (T1). The chosen questionnaire has been previously validated to capture the level of patients’ anxiety during the waiting period. Outcomes of T0 were used to control for individual level state of anxiety at T1. Main results and the role of chance The two groups showed similar reproductive history and sociodemographic characteristics except for female age, which was higher in the PGT-A group (37.7±3.2 yr versus 32.3±2.2 yr in the control). This is due to AMA (maternal age >35 yr) being the main indication to PGT-A. Conversely, the duration of infertility was similar in the two groups (3.8±2.2 yr versus 3.7±1.9 in the control). At T0 all patients showed similar levels of anxiety (46.4 points versus 49.9 in the control, 95%CI of the difference: from –9.97 to 3.03 points, p = 0.3). Remarkably, at T1 instead, the women undergoing euploid embryo transfer showed a significantly decreased level of anxiety with respect to the control (39.9 points versus 53.4; 95% CI of the difference: from –18.26 to –8.69, p < 0.01). This difference remained significant also after controlling for the baseline value at T0, and adjusting for potential confounding factors in a multivariate analysis (adjusted p-value<0.01). Limitations, reasons for caution The sample size is small, yet the study resulted powered enough to reveal the considerable advantage of PGT-A toward the primary outcome. We analysed only the waiting period here. Therefore, data will be collected in the future at subsequent gestational stages, such as when prenatal genetic diagnosis is usually conducted. Wider implications of the findings: Women undergoing PGT-A seem reassured by the technique. This is probably due to the gain of confidence and control derived from an increased expectation of success. From this perspective, assessing women’s wellbeing and attitude towards all different clinical procedures should become a critical part of their treatment. Trial registration number None

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