Fresh Embryo Transfer Research Articles

“Try until the last?”—the relevance of fresh embryo transfer outcomes for subsequent same-cohort vitrified–warmed cycles

PurposeTaking into consideration earlier attempts at assisted reproduction and previous pregnancies allows a more differentiated approach when counseling couples regarding their chances in assisted reproductive treatments. The aim of this study was to investigate whether the outcome of fresh embryo transfers affects subsequent same-cohort vitrified–warmed cycles.MethodsThis retrospective cohort study analyzes the outcome of all fresh and frozen embryo transfers (n = 8118) between January 1, 2011, and December 31, 2022. All women who received fresh or frozen embryo transfers at Kepler University Hospital Linz were included. The use of donor eggs, previously cryopreserved oocytes, and freeze-all cycles were excluded from the analysis.ResultsPositive serum βhCG after a fresh cycle has a significant impact on the chances of positive βhCG in a subsequent vitrified–warmed cycle (36.3% [33.2%, 39.5%]; P = 0.002). Negative βhCG after a fresh cycle does not predict the outcome of the following same-cohort embryo transfer (33.1% [30.7%, 35.7%], P = 0.726). Pregnancy rates of the first, second, third, and fourth same-cohort vitrified–warmed embryo transfer remain continuously high, with 32.8%, 30.8%, 28.9%, and 27.1%, respectively.ConclusionsPositive serum βhCG after a fresh embryo transfer has a positive predictive value for the outcome of a subsequent vitrified–warmed embryo transfer. Couples with a negative fresh cycle should not be discouraged from continuing fertility treatment using same-cohort frozen embryos.Trial registrationThis study was prospectively registered at the German Clinical Trials Register on September 5, 2023 (DRKS00032552).

First-trimester uterine artery pulsatility index and preeclampsia risk in pregnancies after artificial frozen embryo transfer: analysis of over 27,000 pregnancies

Accumulating evidence indicates that pregnancies after Artificial Cycle Frozen Embryo Transfer are associated with an increased risk of preeclampsia. Uterine Artery Doppler, along with maternal factors and serum biomarkers, is a crucial biomarker for first-trimester preeclampsia screening, aiding in identifying "high-risk" patients. Guidelines strongly recommend administering aspirin (150mg/day) in these women, owing to robust evidence demonstrating a 62% reduction in the incidence of preeclampsia. Although previous studies suggested lower Uterine Artery Pulsatility Index after Frozen Embryo Transfer, no previous studies explored the impact of the type of endometrial preparation in Uterine Artery Doppler or its influence on estimating 1st-trimester preeclampsia risk. The study aims to evaluate the possible impact of endometrial preparation for frozen embryo transfer on the Uterine Artery Pulsatility Index during the first-trimester preeclampsia screening. This is a retrospective single-center study including 27289 singleton pregnancies (naturally conceived or after assisted reproductive treatment) who underwent the 1st-trimester ultrasound screening at our University Hospital between January 2010 and May 2023. Overall, 27289 pregnancies were included: 23410 naturally conceived and 3879 following assisted reproductive technologies including 391 after ovulation induction and intrauterine insemination, 888 in-vitro fertilization and fresh embryo transfer, and 2600 natural or artificial frozen embryo transfer cycles. An Analysis of covariance (ANCOVA) was conducted to assess if there is an association between the UtAPI value and the mood of conception, adjusting for confounding factors (age, weight, smoking, and oocyte donation). Overall, pregnancies after artificial frozen embryo transfer demonstrated significantly lower 1st-trimester Uterine Artery Pulsatility Index as compared with all other modes of conception in a multivariable regression analysis adjusted for age, weight, smoking, and oocyte donation. The percent difference was 22.6 [CI95%: 20,6; 24,5] compared to naturally conceived pregnancy, 24.5 [CI95%:20,7; 28,1] to Ovulation Induction or intrauterine insemination, 24.8 [CI95%: [22,9; 27,6] to fresh Embryo Transfer and 21.7 [CI95%: [17,6; 25,5] compared to Natural Cycle Frozen Embryo Transfer. When calculating the risk for initiating preventive aspirin administration, the number of patients with increased risk (>1/100) who initiated prophylactic aspirin was significantly lower in the artificial cycle frozen embryo transfer group (7.8% vs 16.0% in natural cycle p<0.001 vs. 11.0% in Fresh embryo transfer p=0.01 vs. 10.5% in ovulation induction or intrauterine insemination p=0.14 vs. 9,3% in naturally conceived pregnancy p=0.03). Surprisingly although significantly fewer patients were considered at high risk for preeclampsia in the Artificial Cycle Frozen Embryo Transfer group, analysis of the actual incidence of preeclampsia demonstrated three times higher preeclampsia incidence in Artificial Cycle group 5.3% (122/2284) as compared with naturally conceived 1.4 % (321/23410), Ovulation Induction and intrauterine insemination 1.3 % (5/391) or Natural Cycle pregnancies 1.6 % (5/316) and more than two times higher when compared to fresh Embryo Transfer pregnancies 2.3 % (20/888), p<0.001. Pregnancies following frozen embryo transfer in artificial cycle are associated with significantly lower Uterine Artery Pulsatility Index during 1st-trimester preeclampsia screening. This results in a significantly lower number of patients being classified as high-risk for developing preeclampsia, despite accumulating evidence that artificial cycles are linked to an increased risk of preeclampsia. Therefore, the first-trimester preeclampsia risk algorithm should be adjusted to accurately assess risk for those undergoing Artificial Cycle Frozen Embryo Transfer, to prevent the under-treatment of patients who are at very high risk of developing preeclampsia and may benefit from prophylactic aspirin.

The influence of trophectoderm biopsy for preimplantation genetic testing in the serum level of first trimester biomarkers: PAPP-a, βhCG and PIGF

Research questionDoes trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A) affect maternal serum first trimester pregnancy biomarkers (PAPP- A, free β-hCG, PlGF)? DesignRetrospective cohort study, including all singleton pregnancies (n=9794) following either spontaneous conceived (SC) (n=8005) in vitro fertilization and fresh embryo transfers (IVF) (n=478) or frozen embryo transfer of non PGT-A (FET)(n=963) or PGT-A tested embryos (FET+PGT-A) (n=348). In all women with a viable pregnancy at 8-13.6 weeks of pregnancy, we measured serum levels of free β-hCG and PAPP-A . PlGF was measured in 3784 patients. These biomarkers were converted to a multiple of the expected normal median (MoM) for a pregnancy of the same gestational day. We calculated the medians for the multiple of the median and compared them. ResultsFree β-hCG did not differ according to the mode of conception. PAPP-A concentrations were significantly lower in in vitro fertilization and fresh embryo transfers (-0,1 Log10 MoM raw PAPP-A) when comparing to FET+PGT-A (-0,04 Log 10 MoM raw PAPP-A) and SC (-0,0187 Log 10 MoM raw PAPP-A) (p<0,05). PlGF levels were significantly lower in the FET+PGTA group (p<0.05). The difference in means adjusted by CRL was 4.6 pg/ml 95%CI [2.7-6.6] for SC, 3.5 pg/ml 95%CI [0.34-6.6] for IVF and 2.2 pg/ml 95%CI [0.06-4.4] for FET. ConclusionThis study demonstrates that trophectoderm biopsy for PGT-A has a significant impact on first trimester maternal serum PAPP-A and PIGF. This needs to be further validated since it may mislead the estimation of the first trimester risk of aneuploidies and preeclampsia.

Progestin-primed ovarian stimulation

The use of progestins for the prevention of premature ovulation during ovarian stimulation is called progestin-primed ovarian stimulation (PPOS). Response to ovarian stimulation with PPOS and gonadotropin-releasing hormone (GnRH) analogs seem to be similar with the clinically insignificant differences being explained by endocrine characteristics as expected. PPOS has the advantage of oral administration and lower medication cost than GnRH analogs, but the mandatory cancellation of an otherwise possible fresh embryo transfer can render PPOS less cost-effective if a fresh transfer would have been possible. Oocytes collected in PPOS cycles have similar developmental potential, including blastocyst euploidy rates. Frozen embryo transfer outcomes of PPOS and GnRH analog cycles seem similar both in terms of ongoing pregnancy/live birth rates and obstetric and perinatal outcomes. While some studies reported lower cumulative live birth rates with PPOS, they suffer from methodological issues, including arbitrary definitions of cumulative live birth rates. PPOS has been used in all patient types with consistent results and seems a patient-friendly and cost-effective choice when a fresh embryo transfer is not intended.

Legal framework and IVF outcomes: a comparative analysis of fresh and frozen embryo transfers in Switzerland

Research question: To what extent do legislative measures impact standard reproductive outcome parameters? Design: Retrospective cohort study using data from the Swiss national IVF registry analysing the outcomes of 13908 women undergoing ETs resulting from their first lifetime oocyte retrieval before (2014-2016) or after (2020-2022) the revised legislation, allowing extended culture for 12 zygotes. Live birth rates (LBR) and cumulative LBR (cLBR) were compared in fresh and frozen ET strategies in both periods. Adjusted multivariable mixed model analyses were performed to determine odds ratios (OR) and incidence rate ratios (IRR). ResultsBefore the revised legislation, LBR was higher in fresh compared to frozen ET (27.2% vs. 22.7%). After the revised legislation, LBR was lower in fresh ET (29.3% vs. 36.3%) and cLBR was higher in freeze-all strategy (cLBR: 59.0% vs. 39.8%). However, in a multivariable analysis, fresh and frozen ETs did not differ in the odds of live birth (OR = 1.08, 95% CI: 0.95-1.22) and freeze-all were not found to be more effective than fresh strategies (IRR = 1.12, 95% CI 0.98 - 1.27). In a subgroup analysis, fresh blastocyst ET showed higher LBR than cleavage stage ET (OR = 2.01, 95% CI 1.62-2.49). ConclusionThe change in national legislation provided the unique opportunity to evaluate the legal impact on reproductive outcomes: Besides a reduction of multiple deliveries, LBR of frozen ET improved, resulting in a comparable success of fresh and frozen transfer strategies. In addition to technological improvement, the legal framework influences the evolution of clinical practice, thereby contributing to enhanced reproductive outcomes.

Birth weight following frozen versus fresh embryo transfer: A retrospective cohort

Birth weight following frozen versus fresh embryo transfer: A retrospective cohort

Effect of blastomere cell number on ART outcome of fresh single day 3 embryo transfer

PurposeExplore the effect of blastomere cell number on ART outcome of fresh embryo transfer on day 3.MethodsRetrospective analysis of 540 fresh single day 3 embryo transfer cycles at the Reproductive Center of the Third Affiliated Hospital of Guangzhou Medical University from January 1, 2018 to October 31, 2022. Patients were divided into 5–6 cell group (n = 55), 7–9 cell group (n = 457), and ≥ 10 cell group(n = 28) based on the number of blastomeres. Single factor analysis of variance and Pearson's chi square test were used to compare the basic data, cycle information, pregnancy outcome and neonatal outcome. Univariate logistic regression was used to correct for confounding factors and analyze the influencing factors of pregnancy outcome.ResultsThe positive HCG rate were 20%, 43%, 25% for the 5–6-cell, 7–9 cell and ≥ 10 cell groups respectively, with statistically significant differences (P < 0.001). The clinical pregnancy rate was 18%, 42%,21%, respectively (P < 0.001). The live birth rates were 13%, 34%,21% with P-value less than 0.05 which is statistically significant. In order to exclude the influence of confounding factors, multivariable logistic regression analysis was performed, and the outcomes were consistent with previous findings. There were no significant differences found in neonatal outcome between groups (P > 0.05).ConclusionThe results suggested that intermediate cleaving embryos (7–9 cell) still presents the highest clinical potential. Fast and slow cleaving embryos are not conducive to the ART outcome.

LHCGR gene variants are associated with ovarian response and miscarriage risk following fresh and frozen embryo transfer

Background: Currently, infertility is a widespread problem. Despite recent advances in assisted reproductive technologies, success rates still need to be improved. Understanding patients' variability and addressing it with personalized methods may increase the success rates. The aim of the study: The aim of the present study was to analyze the possibility of using variants rs12470652 and rs2293275 of the LHCGR gene to predict ovarian response or pregnancy outcome in assisted reproductive technologies, including the influence of cryopreservation factor. Materials and methods: The present study included 292 infertile women who underwent assisted reproductive technologies. Inclusion criteria were the first or second IVF/ICSI cycle, including women with tubal or/and male factor, anovulation, idiopathic infertility. Exclusion criteria were reduced FSH and/or AMH serum levels. Results: The frequency distribution for rs12470652 and rs2293275 gene variants was AA (94%), AG (6%) and AA (9%), AG (52%), GG (39%) respectively. rs2293275 G allele was found to be associated with low ovarian response. In total, frozen embryo transfer was found to be marginally more efficient, than fresh embryo transfer. In women who became pregnant after fresh embryo transfer, the rs2293275 G allele was statistically significantly found to be a risk factor for miscarriage. Accordingly, frozen embryo transfer hypothesized to be more preferred for rs2293275 G allele carriers to give live birth, than fresh embryo transfer. Meanwhile, fresh embryo transfer might be more effective for rs12470652 G allele carriers to give live birth. Chi-squared test confirmed the results; however, the odds ratio was not applied due to the limited sample size. Further studies and sample increase are required to confirm the results. Conclusion: The present study proposes that LHCGR rs12470652 and rs2293275 genetic variants may improve the prognosis of efficiency of fresh and frozen embryo transfer and might be considered as predictors when planning IVF/ICSI cycles.

Congenital heart defects in children born after assisted reproductive technology: a CoNARTaS study.

Children born after assisted reproductive technology (ART) have worse perinatal outcomes compared with spontaneously conceived children. This study investigates whether children conceived after ART have a higher risk of congenital heart defects (CHDs) compared with children born after spontaneous conception (SC). All 7 747 637 liveborn children in Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1987-2015), where 171 735 children were conceived after ART, were included. National ART and medical birth registry data were cross-linked with data from other health and population registries. Outcomes were major CHDs, severe CHDs, 6 hierarchical CHD lesion groups, and 10 selected major CHDs, diagnosed prenatally or up to 1 year of age (Denmark, Finland, and Sweden) and prenatally or at birth (Norway). The association between ART and CHDs was assessed with multivariable logistic regression analysis, with adjustment for available confounders. Major CHDs were detected in 3159 children born after ART (1.84%) and in 86 824 children born after SC [1.15%; adjusted odds ratio (AOR) 1.36; 95% confidence interval (CI) 1.31-1.41]. Risk was highest in multiples, regardless of conception method. Severe CHDs were detected in 594 children born after ART (0.35%) and in 19 375 children born after SC (0.26%; AOR 1.30; 95% CI 1.20-1.42). Risk was similar between ICSI and IVF and between frozen and fresh embryo transfer. Assisted reproductive technology-conceived children have a higher prevalence of major CHDs, being rare, but severe conditions. The absolute risks are, however, modest and partly associated with multiple pregnancies, more prevalent in ART.

Association of ambient temperature and diurnal temperature range with the outcome of in vitro fertilization in women from Hubei, China: A retrospective cohort study

ObjectivesTo examine the relationship between ambient temperature and DTR and pregnancy outcomes in vitro fertilization/intracytoplasmic monosperm injection and embryo transfer (IVF/ICSI-ET) women. MethodsThe study included 5264 women who were treated with IVF/ICSI-ET at two centers in Hubei province from 2017 to 2022. The daily mean, daily maximum, and daily minimum temperatures at the subjects' home addresses were extracted, and DTR values were calculated based on latter two. The associations between ambient temperature and DTR with clinical pregnancy and live birth rates were assessed using multivariate logistic regression models adjusted for covariates. Subgroup analyses were also conducted to explore potential modifiers. ResultHigh/low temperatures as well as a larger DTR had a significant effect on pregnancy outcomes in fresh cycles, but not in FET cycles. Specifically, hot weather exposure to high temperatures was associated with reduced clinical pregnancy rates: Period 4 (embryo transfer to serum HCG testing) (aOR = 0.873, 95%CI: 0.763–0.999). Ambient temperature in cold weather was positively associated with live birth rate: Period 2 (Gn initiation to oocyte retrieval) (aOR = 1.082, 95% CI: 1.01–1.170), Period 3 (oocyte retrieval to embryo transfer) (aOR = 1.111, 95% CI: 1.019–1.212), Period 4 (aOR = 1.134, 95% CI: 1.028–1.252), and Period 7 (85 days prior to oocyte retrieval to serum hCG testing) (aOR = 1.105, 95% CI: 1.007–1.212). For DTR, exposure to larger DTR (Q3) at Period 2, Period 3, and Period 6 (Gn initiation to embryo transfer) reduces clinical pregnancy and live birth rates compared with Q1. Subgroup analyses revealed susceptibility profiles across age groups and residential address populations in different sensitivity windows. ConclusionOur study shows that exposure to hot and cold weather and higher DTR reduces clinical pregnancy rates and live birth rates in women undergoing fresh embryo transfer, but has no significant effect on FET cycles.

Reproductive outcomes in fresh transfer cycles and antagonists with premature luteinizing and/or progesterone surge: a single center retrospective cohort study.

The optimal outcome of assisted reproductive technology is a successful live birth after fresh embryo transfer. However, the success pregnancy rate of fresh embryo transfer cycle in antagonist protocol is lower than that observed in other protocols. Despite the use of antagonists (GnRH-ant), the incidence of luteinizing hormone surge and elevated progesterone levels remain at approximately 5%-38%. Progesterone is widely recognized to exert adverse effects on fresh embryo transfer outcomes. This study aimed to investigate the impact of luteinizing hormone surge and progesterone levels on live birth rate following fresh embryo transfer and explore appropriate progesterone thresholds to enhance pregnancy outcomes. This retrospective cohort study included a total of 1,177 antagonist protocol cycles with fresh embryo transfer. The patients were divided into four groups based on the presence of premature LH surge and progesterone level on trigger day>1.5ng/ml. Then, the relationship between the variables and the pregnancy outcome was analyzed and compared in each group. The transient rise of luteinizing hormone did not impact pregnancy outcomes (P=0.345; P=0.3; P=0.787), in contrast to progesterone levels on the day of hCG administration (P=0.047*; P=0.015*; P=0.021*). In cases with luteinizing hormone surge, elevated progesterone levels were correlated with higher antral follicle count (AFC), and as progesterone levels increased, a greater quantity of oocytes and embryos were obtained. However, there was no statistically significant difference in pregnancy outcomes. In cases without luteinizing hormone surge, elevated progesterone levels led to significantly poorer pregnancy outcomes. Furthermore, the curve-fitting and threshold-effect analysis revealed a notable decline in live birth rates when progesterone exceeded or equaled 1.10ng/ml (OR, 0.25; 95% CI, 0.09-0.66; P = 0.005*). The GnRH-ant dosage addition should be carefully selected in flexible antagonist protocols. The presence of elevated progesterone levels may be associated with improved embryo quality when luteinizing hormone surge occurred. In the absence of a luteinizing hormone surge, progesterone levels showed a larger impact on the pregnancy outcome, and fresh embryo transfer should not be performed if the progesterone level on the day of hCG administration is higher than 1.10ng/ml.

Effects of the Zishen Yutai Pill on live births compared with placebo among infertile women with frozen-thawed embryo transfer cycle: A multicentre double-blind randomized controlled trial

BackgroundZishen Yutai Pill exhibited clinical benefit to infertile women undergoing fresh embryo transfer cycles, improving their pregnancy outcomes. However, as the endometrial environment in frozen embryo transfer (FET) is different from fresh cycles, the effects of ZYP on fresh embryo transfer could not be generalized to FET. ObjectiveWe aimed to explore the effects of ZYP on live birth rate in women's FET cycles. MethodsThis multicentre, double-blind, placebo-controlled, randomized study was conducted at 11 reproductive medical centres in China. Women were recruited and randomly assigned to ZYP or placebo intervention (5 g once, 3 times per day) around the time of FET. The live birth rate was set as the primary outcome. Secondary outcomes included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, pregnancy loss rates. Data was analyzed based on the intention-to-treat principle, with per protocol analysis as sensitivity analysis. ResultsBetween December 2017 and April 2019, 934 women were screened, of whom 880 met all eligibility criteria and were allocated to ZYP (n=441) or placebo (n=439). In ITT analysis, the live birth rates were 38.32% (169/441) in ZYP group and 32.57% (143/439) (absolute difference 5.75%, 95%CI [−0.57%, 12.00%], OR 1.29, 95%CI [0.98, 1.70], P=0.08). The intervention of ZYP did not result in significantly differences in all secondary outcomes compared with placebo (all P>0.05). Similar trends were observed in PP analysis. In post hoc analysis, ZYP resulted in higher rates of live birth than placebo among women in specific subgroups, i.e., with miscarriage history (39.23% vs. 26.45%, P=0.01) or advanced maternal age (33.93% vs. 21.85%, P=0.04). ConclusionIn infertile women undergoing FET cycle, intervention with ZYP led to a trend of live birth rate increment compared with placebo, but without statistical significance. However, women with miscarriage history and advanced age could experience possible benefits from ZYP intervention. RegistrationChiCTR-INR-17010809 (http://www.chictr.org.cn).

Cumulative live birth rate of a blastocyst versus cleavage stage embryo transfer policy during in vitro fertilisation in women with a good prognosis: multicentre randomised controlled trial

ObjectivesTo evaluate whether embryo transfers at blastocyst stage improve the cumulative live birth rate after oocyte retrieval, including both fresh and frozen-thawed transfers, and whether the risk of obstetric and...

Does it affect the live birth rates to have a maximum endometrial thickness of 7, 8, or 9 mm in in-vitro fertilization-embryo transfer cycles?

To assess the effect of endometrial thickness (EMT) on live birth rates (LBR) in women with endometrial lining between 7.0-9.9 mm. This retrospective cohort study included women who underwent fresh and frozen embryo transfers between 2008 and 2018, grouped according to their maximum EMT; group 1, 7.0-7.9 mm; group 2, 8.0-8.9 mm; and group 3, 9.0-9.9 mm and underwent blastocyst transfer. The study included 7,091 in-vitro fertilization cycles: 1,385 in group 1, 3,000 in group 2, and 2,706 in group 3. The combined LBR was 22.2%. The mean age of women at oocyte retrieval day was 36.7±4.5 years. There was no difference in female age at oocyte retrieval or in the quality of embryos transferred between the three groups. Group 1 had more diagnoses of diminished ovarian reserve (25.8% vs. 19.5% and 19.1%; p<0.001) and less male factor infertility compared with group 2 and 3, respectively (25.0% vs. 28.8% and 28.5%; P=0.024). LBR was higher with increasing endometrial thickness, group 2 vs. group 1 (22.0% vs. 17.4%; P=0.0004), group 3 vs. group 1 (25.0% vs. 17.2%; p<0.001), and group 3 vs. group 2 (25.0% vs. 22.0%; P=0.008). After controlling for confounding factors, these three groups did not differ in LBR (group 1 vs. group 2, odds ratio [OR], 1.08; 95% confidence interval [CI], 0.83-1.4; P=0.54 and group 1 vs. group 3, OR, 1.16; 95% CI, 0.90-1.51; P=0.24). Live birth rates in women with endometrial thickness between 7.0-9.9 mm were not affected by different cut-offs when blastocyst transfer was performed.

High concentration of estrogen resulted by COH may affect the secretion of pro-angiogenic factors in uNK cells by downregulating the expression of IL-11 in decidual stromal cells.

High serum estrogen concentrations after controlled ovarian hyperstimulation (COH) and fresh embryo transfers are associated with the increased risk of pregnancy complications resulting from aberrant placentation. Uterine natural killer (uNK) cells are important for establishment of pregnancy and normal placentation. It has been found that the proliferation and function of uNK cells are compromised by COH. However, the underlying role of high concentration of estrogen following COH in the abnormalities of uNK cells is poorly understood. Expression of cytokines and immunophenotype study of uNK was performed by flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression; Western blot was performed to quantify protein levels. The secretion level of pro-angiogenic factors in uNK cells is significantly reduced by co-culture with decidual stromal cells (DSCs) induced by high estrogen. It was discovered that COH and supraphysiologic levels of estrogen downregulated IL-11 in decidual tissue of mice. Additionally, we found that the downregulation of IL-11 is a major factor contributing to the downregulation of VEGF and PLGF in uNK cells. Moreover, we found that uNK cells may acquire IL-11Rα sequentially during differentiation and that only a portion of uNK cells are IL-11Rα positive. Lastly, we discovered that IL-11 may regulate VEGF and PLGF secretion in uNK cells via the ERK signaling pathway. These results suggested the downregulation of IL-11 expression in DSCs caused by high estrogen levels affects the secretion of pro-angiogenic factors in uNK cells, which provided an explanation for the pregnancy complications caused by COH.

Enhancing predictive models for egg donation: time to blastocyst hatching and machine learning insights

BackgroundData sciences and artificial intelligence are becoming encouraging tools in assisted reproduction, favored by time-lapse technology incubators. Our objective is to analyze, compare and identify the most predictive machine learning algorithm developed using a known implantation database of embryos transferred in our egg donation program, including morphokinetic and morphological variables, and recognize the most predictive embryo parameters in order to enhance IVF treatments clinical outcomes.MethodsMulticenter retrospective cohort study carried out in 378 egg donor recipients who performed a fresh single embryo transfer during 2021. All treatments were performed by Intracytoplasmic Sperm Injection, using fresh or frozen oocytes. The embryos were cultured in Geri® time-lapse incubators until transfer on day 5. The embryonic morphokinetic events of 378 blastocysts with known implantation and live birth were analyzed. Classical statistical analysis (binary logistic regression) and 10 machine learning algorithms were applied including Multi-Layer Perceptron, Support Vector Machines, k-Nearest Neighbor, Cart and C0.5 Classification Trees, Random Forest (RF), AdaBoost Classification Trees, Stochastic Gradient boost, Bagged CART and eXtrem Gradient Boosting. These algorithms were developed and optimized by maximizing the area under the curve.ResultsThe Random Forest emerged as the most predictive algorithm for implantation (area under the curve, AUC = 0.725, IC 95% [0.6232–0826]). Overall, implantation and miscarriage rates stood at 56.08% and 18.39%, respectively. Overall live birth rate was 41.26%. Significant disparities were observed regarding time to hatching out of the zona pellucida (p = 0.039). The Random Forest algorithm demonstrated good predictive capabilities for live birth (AUC = 0.689, IC 95% [0.5821–0.7921]), but the AdaBoost classification trees proved to be the most predictive model for live birth (AUC = 0.749, IC 95% [0.6522–0.8452]). Other important variables with substantial predictive weight for implantation and live birth were duration of visible pronuclei (DESAPPN-APPN), synchronization of cleavage patterns (T8-T5), duration of compaction (TM-TiCOM), duration of compaction until first sign of cavitation (TiCAV-TM) and time to early compaction (TiCOM).ConclusionsThis study highlights Random Forest and AdaBoost as the most effective machine learning models in our Known Implantation and Live Birth Database from our egg donation program. Notably, time to blastocyst hatching out of the zona pellucida emerged as a highly reliable parameter significantly influencing our implantation machine learning predictive models. Processes involving syngamy, genomic imprinting during embryo cleavage, and embryo compaction are also influential and could be crucial for implantation and live birth outcomes.

Letrozole co-treatment in an antagonist protocol for overweight women undergoing IVF treatment: a retrospective study

BackgroundOverweight women undergoing IVF treatment have lower success rates. Letrozole, an aromatase inhibitor, has been used as an adjunct for IVF treatment, but its specific effects in overweight women have not been investigated. This study was to explore the effects of letrozole co-treatment in an antagonist protocol for overweight infertile women undergoing IVF treatment.MethodsThis retrospective cohort study included overweight infertile women who underwent IVF/ICSI treatment and fresh embryo transfer (ET), with or without letrozole co-treatment in an antagonist protocol, from 2007 to 2021 at Shanghai Ninth People’s Hospital (Shanghai, China). A total of 704 overweight infertile women were included: 585 women were in the antagonist group, and 119 women were in the letrozole co-treatment group. The primary outcome was the live birth rate after fresh ET. Propensity score-based patient-matching was employed to balance the covariates between the groups. Multivariate logistic regression analysis was also performed to estimate odds ratio (OR) and 95% confidence interval (CI) for association of letrozole co-treatment and the live birth outcome.ResultsLetrozole co-treatment induced significant changes in hormonal profile on the trigger day. The letrozole group exhibited a decrease in the total number of follicles compared to the antagonist group, but a higher proportion of large follicles at oocyte retrieval (P < 0.05). The quantity and quality of embryos were comparable between the two groups (P > 0.05). The letrozole co-treatment group had a significantly higher live birth rate than the control group (38.7% vs. 22.6%, P = 0.026). With multivariate logistic regression analysis, letrozole co-treatment was associated with higher odds of live birth after adjusting for potential confounding factors (adjusted OR = 2.00, 95% CI = 1.17–3.39, P = 0.011). Letrozole presented no significant associations with obstetrical or neonatal complications (P > 0.05).ConclusionLetrozole co-treatment in an antagonist protocol may offer potential benefits for overweight infertile women undergoing IVF treatment. Further research is warranted to validate these findings and explore the broader implications for letrozole co-treatment.

Luteinizing hormone supplementation with human menopausal gonadotropin versus low dose human chorionic gonadotropin during ovarian stimulation does not affect live birth rates after fresh and frozen embryo transfer.

Luteinizing hormone (LH) plays an important role in ovarian follicle maturation. Human menopausal gonadotropin (hMG) or low dose human chorionic gonadotropin (hCG) can provide LH supplementation during in vitro fertilization (IVF) ovarian stimulation, though studies directly comparing their impact on IVF outcomes are limited. The aim of the study was to determine whether LH supplementation with hMG versus low dose hCG during IVF stimulation affects live birth rate. Fresh and frozen embryo transfers (ET) from 2017 to 2021 after standard long or antagonist protocols supplemented with hMG (75-250 IU) or low dose hCG (50-100 IU) during stimulation cycles in our academic center were included. Statistical analysis was performed with T-tests, Mann-Whitney U tests, Chi-square, and multiple linear and logistic regression. Four hundred and sixty eight unique stimulation cycles resulting in 213 fresh and 412 frozen embryo transfers were analyzed. There was a lower mature oocyte yield (10.9 vs. 11.8, p = 0.044) but similar high-quality blastocyst yield (3.6 vs. 3.9, p = 0.11) for hMG vs low dose hCG. Live birth rates per transfer were comparable for fresh (42% vs. 49%, p = 0.24) and frozen (46% vs. 53%, p = 0.45) embryo transfers. Multiple logistic regressions showed no association between supplemental gonadotropin and live birth for both fresh and frozen embryo transfers. Fresh and frozen IVF-ET pregnancy outcomes were comparable after hMG versus low dose hCG supplementation, suggesting flexibility in supplemental LH dosing regimens that may address patient or physician preference or cost concerns.

Vaginal Progesterone Gel versus Intramuscular Progesterone for Luteal Phase Support in Suboptimal Responders Undergoing Assisted Reproductive Cycles

Background: The purpose of this research is to compare the efficacy of 8% micronized vaginal progesterone gel (VAG) at 180 mg daily versus intramuscular progesterone (IMP) in oil at 100 mg daily for luteal phase support (LPS) after fresh single embryo transfer (SET) in Patient-Oriented Strategies Encompassing Individualized Oocyte Number (POSEIDON) Group 1b patients, and to ascertain whether the type of LPS predicts live birth in these patients. Methods: A total of 2420 assisted reproductive technology (ART) cycles performed in Ondokuz Mayıs University IVF Unit were analysed retrospectively. The data of POSEIDON Group 1b (unexpected suboptimal responders) who underwent antagonist in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles were included. All patients were categorized into groups according to the form of LPS, specifically VAG and IMP. Pregnancy, clinical pregnancy rate (CPR), live birth rate (LBR), spontaneous abortion rate and predictors of live birth (age, infertility duration, body mass index (BMI), type of progesterone used for luteal support, serum day 3 estradiol, serum progesterone on the day of human coryonic gonadotrophin (HCG), total duration of induction, serum estradiol on the day of HCG, the total number of oocytes retrieved, number of mature oocytes obtained, average gonadotropin dose per day, total gonadotropin dose administered and total number of embryos retrieved) were analyzed. Results: There was no statistically significant difference between the micronized VAG and IMP groups in terms of age (31 (23–35) vs. 27 (23–35), p = 0.319). There were no statistically significant differences in pregnancy outcomes between the two groups concerning CPR per transfer (70.6% vs. 75.6%; p = 0.364), ongoing pregnancy per cycle (36.2% vs. 39.5%; p = 0.577), and LBR per cycle (34.4% vs. 36.1%; p = 0.785). The spontaneous abortion rates (36.2% vs. 36.8%; p = 0.921) were similar between VAG and IMP groups. The type of LPS did not emerge as a parameter predicting pregnancy (odds ratio (OR): 0.718, 95% confidence interval (95% CI): 0.652–1.313, p = 0.451), clinical pregnancy (OR: 0.598, 95% CI: 0.592–1.289, p = 0.562) and live birth (OR: 0.802, 95% CI: 0.661–1.202, p = 0.580). The logistic regression analysis aimed at assessing the influence of confounding factors, namely age, BMI, and duration of infertility on pregnancy rate, CPR and LBR, did not reveal statistically significant results (p &gt; 0.05). Conclusions: VAG 180 mg daily provide similar pregnancy outcomes compared to 100 mg daily IMP in POSEIDON Group 1b patients undergoing antagonist fresh IVF/ICSI cycles.

New Insight of Lipiodol Flush on Pregnancy Outcomes in Women with Recurrent Implantation Failure Undergoing IVF/ICSI: a Prospective Study Based on Propensity Score Matching.

Pregnancy outcomes in women with recurrent implantation failure (RIF) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): does treatment with lipiodol flush matter? In this propensity score-matched study, we recruited 966 RIF patients who underwent IVF/ICSI from two tertiary hospitals. These patients were divided into groups based on whether they received lipiodol flush or not. Further stratification was applied to investigate the effect of lipiodol flush on pregnancy outcomes in RIF patients with different cycle type of embryo transferred. Then, patients subjected to lipiodol flush were categorized into three groups based on the duration of the interval: short interval (≤ 3months), moderate interval (3-6months), and long interval (≥ 6months). The groups were well-matched at baseline. The lipiodol flush group exhibited a significantly lower incidence of biochemical pregnancy (46.27% vs. 56.22%, p = 0.046) and live birth (25.87% vs. 37.31%, p = 0.014). Subgroup analysis for fresh embryo transfer cycles revealed no significant differences in pregnancy outcomes. Among RIF patients underwent frozen-thawed embryo transfer cycle, a statistically significant difference in the live birth rate was observed in the lipiodol flush group when compared to the control group (26.40% vs. 37.21%, p = 0.030). Analysis of different lipiodol flush intervals demonstrated a significantly lower live birth rate in the lipiodol flush group. Our results challenge the value of lipiodol use in clinical practice for the treatment of RIF.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900024273. Registered 4 July 2019.