Day Of Embryo Transfer Research Articles

Comparative analysis of superovulated versus uterine-embryo synchronized recipients for embryo transfer in cynomolgus monkeys (Macaca fascicularis).

Assisted reproductive technologies (ARTs), such as intracytoplasmic sperm injection and embryo transfer, are essential for generating genetically edited monkeys. Despite their importance, ARTs face challenges in recipient selection in terms of time and the number of animals required. The potential of superovulated monkeys, commonly used as oocyte donors, to serve as surrogate mothers, remains underexplored. The study aimed to compare the efficacy of superovulated and uterine-embryo synchronized recipients of embryo transfer in cynomolgus monkeys (Macaca fascicularis). This study involved 23 cynomolgus monkeys divided into two groups-12 superovulated recipients and 11 synchronized recipients. The evaluation criteria included measuring endometrial thickness on the day of embryo transfer and calculating pregnancy and implantation rates to compare outcomes between groups. The study found no statistically significant differences in endometrial thickness (superovulated: 4.48 ± 1.36 mm, synchronized: 5.15 ± 1.58 mm), pregnancy rates (superovulated: 30.8%, synchronized: 41.7%), and implantation rates (superovulated: 14.3%, synchronized: 21.9%) between the groups (p > 0.05). The observations indicate that superovulated recipients are as effective as synchronized recipients for embryo transfer in cynomolgus monkeys. This suggests that superovulated recipients can serve as viable options, offering an efficient and practical approach to facilitate the generation of gene-edited models in this species.

A randomized clinical trial of transdermal (gel) versus oral estrogen for endometrial preparation in frozen embryo transfer cycle.

The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

Serum progesterone measurement on the day of fresh embryo transfer and its correlation with pregnancy success rates: A prospective analysis

Studies regarding serum Progesterone (P4) concentration and Clinical Pregnancy Rates (CPR) in fresh Embryo Transfer (ET) after Controlled Ovarian Stimulation Cycles (COS) remain inconclusive. To find a P4 cutoff point on fresh ET day associated with higher CPR, and to identify predictive factors of CPR and P4, the authors conducted a prospective cohort of 106 patients who underwent COS at a public IVF center. The luteal phase was supported with vaginal micronized progesterone (200 mg, 8/8h), beginning on oocyte retrieval day. The primary outcome was CPR beyond the 8th week of pregnancy. A ROC curve was constructed to identify the best cutoff point correlated with higher CPR. Multivariate analysis evaluated predictive variables of CPR and P4 concentration. P4 levels showed no significant differences between pregnant and non-pregnant patients (67.12 ± 31.1 ng/mL vs. 64.17 ± 61.76, p = 0.7465). The cutoff point correlated with higher CPR was P4 ≥ 28.9 ng/mL (AUC 0.5654). Women's age (OR = 0.878; 95 % CI 0.774–0.995) and top-quality embryo transfer (OR = 2.89; 95 % CI 1.148–7.316) were associated with CPR. Women's age ≥ 40 years (OR = 0.0956; 95 % CI 0.0156–0.5851), poor response to COS (OR = 0.0964; 95 % CI 0.0155–0.5966), and follicles ≥ 10 mm (OR = 1.465; 95 % CI 1.013–2.117) were associated with the cutoff point. As the ROC curve was unsatisfactory, P4 ≥ 28.9 ng/mL should not be used to infer gestational success. In fresh ET, P4 concentration may merely reflect a woman's age and individual response to COS rather than being a reliable CPR predictor.

#48 : Blastocyst Versus Day-3 Embryo Transfers After In Vitro Maturation with Pre-Maturation Step (CAPA-IVM) in PCOS Patients

Background and Aims: IVM combined with a pre-maturation step known as capacitation IVM (CAPA-IVM) improves the competence of in-vitro matured oocytes. According to our previous study, the current clinical practice of transferring day-3 embryos resulted in a live birth rate of 35.2% after the first frozen embryo transfer (FET) following CAPA-IVM. Advances in embryo culture systems have allowed us to extend the duration of embryo culture to blastocyst. There is a lack of data on blastocyst transfer following CAPA-IVM. The aim of this study is to compare the effectiveness of blastocyst versus day-3 embryo transfer after CAPA-IVM in PCOS patients. Methods: A retrospective cohort study was conducted at two infertility centers in Vietnam from 1 January 2018 to 28 February 2022. The study compared two groups of PCOSwomen who had frozen embryo transferred (FET) with CAPA-IVM. Group 1 had blastocyst transfer and Group 2 had day-3 embryo transfer. The couples made the final decision on the stage of embryos transferred. The inclusion criteria were women aged between 18-40 years and had freeze-all their embryos. The primary outcome was the live birth rate after the first FET. Results: Out of 275 eligible women for the study, 87 of themhad blastocyst transfer, and 188 had day-3 embryo transfer. The mean number of embryos transferred for blastocyst transfer and day-3 embryo transfer were 1.27 and 1.93, p &lt; 0.001, respectively. Live birth rate after the first transfer was comparable between blastocyst and day-3 embryo transfers (34.5% vs. 37.8%, p=0.696, respectively). The blastocyst transfer group had a significantly lower multiple pregnancy rate as compared to day-3 embryo transfer group (4.6% vs. 18.0%; p=0.005, respectively). Conclusions: Blastocyst transfer had comparable live birth rate but lower multiple pregnancy rate to day-3 embryo transfer after the first FET following CAPA-IVM in PCOS women.

Age and treatment on the day of embryo transfer in recipient mares affect likelihood of pregnancy.

This retrospective evaluation of data from a large commercial embryo transfer facility aimed to determine the extent to which age and treatment on the day of embryo transfer in recipient mares influence the likelihood of pregnancy. Embryo recovery was carried out on days 8-10 post-ovulation using transcervical uterine flushing. Recipient mares grouped according to their age were treated once on the day of embryo transfer (Day 3-8 post ovulation) and were assigned randomly to 1 of 3 groups: Mares in Group A (n=101) received antispasmodic, antimicrobial, and anti-inflammatory drugs. Mares in Group B (n=100) received gentamicin and flunixin meglumine. Group C (control) (n=103) did not receive any treatment. Detomidine (0.008 mg/kg bwt i.v.) was administered to all recipients before transfer of the embryo. The influence of treatment and recipient´s age was calculated using binary logistic regression. Day 16 post-transfer pregnancy rates were highest in Group A (74/101, 73.3a%), when compared to Group B (60/100, 60%), and Group C (57/103, 55.3b%) (a vs b, p<0.05). Pregnancy loss rates at D45 were not different between groups, A (8/74, 10.8%), B (5/60, 8.3%), and C (6/57, 10.5%), respectively (p>0.05). Pregnancy losses were increased in recipient mares 17-22 years (33.3a%) compared to younger recipient mares (2-6 years 7b%, 7-11 years 10%, 12-16 years 8b%) (a:b p<0.05). The regression model showed that the predicted probability for pregnancy after embryo transfer decreased as the age of the recipient mare increased for treated recipients in Group A (p=0.012), there was no effect of treatment and recipient´s age in Group B, and a decreased likelihood of pregnancy in recipients of advanced age (≥12 years of age) in untreated recipients (group C). Likelihood of pregnancy increased following single administration of antispasmodic, antimicrobial, and anti-inflammatory drugs at the time of embryo transfer in recipients 2-12 years of age. Likelihood of pregnancy in recipients decreased in recipients≥12 years of age. These results, obtained under the conditions of a large commercial embryo transfer program, offer an opportunity to improve pregnancy rates in recipient mares≤12 years of age.

#200 : The Impact of Serum Progesterone(P4) Level on the Day of Embryo Transfer on Art Outcome

Background and Aims: Physiologically serum progesterone level fluctuates among different stages of pregnancy. The serum level and tissue level of P4 are poorly correlated and also affected by the route of administration, thus creating a challenge for monitoring. Our goal was to determine whether P4 levels on the day of embryo transfer predict pregnancy outcomes in artificial FET cycles. Method: This was a prospective cohort study conducted from Feb 2022 to Dec 2022. Around 337 patients who underwent IVF/ICSI, irrespective of single or double frozen embryo transfer in an HRT cycle, were analyzed. Results: The participant’s mean age was 32.29±4.50 years with a BMI of 24.68±3.82 kg/m2, single embryo transfer vs double embryo transfer was 64(19.0%) vs 273(81.0%) and Serum P4 on day of ET was 28.66±12.51. Pearson’s correlation showed that serum P4 was negatively correlated with BMI (r: -0.131; P = 0.017). The serum P4 grouping was done as per the quartile distribution: Q1: &lt;21.4 ng/ml; Q2: 21.4-27.1 ng/ml; Q3: 27.2-38.1 ng/ml; Q4: [Formula: see text]38.2 ng/ml. Clinical Pregnancy Rate (CPR), 60.7%(Q1); 68.4%(Q2); 64.5%(Q3); 73.8%(Q4); p=0.312) was not significantly different between a female with serum P4 within different quartiles. Miscarriage rates (2.0%, 1.9%, 3.3%, 1.6%; p=0.935) &amp; Ongoing Pregnancy Rates were (48.3%, 56.6%, 44.3%, and 65.2%, respectively, in each quartile. Conclusion: The serum level of Progesterone on the day of embryo transfer while using intramuscular formulation in an artificial cycle had no significant impact on the clinical pregnancy rate.

#129 : The Ratio of Luteal Phase Serum Progesterone and Estradiol Can be Used to Predict Pregnancy in Frozen Embryo Transfer Cycles

Background and Aims: Low serum progesterone (P) levels on day of embryo transfer (ET) and luteal phase have been associated with poorer pregnancy outcome. This study aimed to know if serum estradiol (E2) and P levels during mid and late luteal phase are related with ongoing pregnancy. Method: The serum E2 and P levels from mid luteal phase (5 days after ET) to the day of the [Formula: see text]-hCG check (11 days after ET) in both fresh and frozen embryo transfer (FET) cycles was investigated between January 2019 and December 2021. Eligible patients were reproductive aged women with a normal uterus. Single blastocyst transfer cycles were included. Estradiol valerate (2 mg/bid) was started from day 3 of cycle as hormone replacement and vaginal micronized P (400 mg/bid) was started 5 days before ET in all FET cycles. The 2-degree polynomial fitted data were analysed and logistic linear model and ROC analysis were performed to assess E2 and P4 polynomial coefficients as a predictive test for ongoing pregnancy. Results: A total of 388 patients were included. The overall pregnancy rate was 43.8% and 31.3% for FET and fresh ET, respectively. On day 5 post ET, the serum P levels correlated significantly with ongoing pregnancy and live birth rates, especially in FET cycles. The ROC curve showed that there is a significant day 5 post ET predictive value of serum P4/E2 levels for pregnancy rate, being the AUC (95% CI) = 0.596 (0.539–0.653) for the combination of both fresh and FET cycles; and 0.611 (0.548–0.674) for FET cycles, with best cut-off values of 0.079 and 0.077, respectively. Conclusion: Serum P levels in mid and late luteal phase days are associated with pregnancy outcome both in fresh and frozen ET cycles. Ongoing pregnancies can be predicted using the day 5 post ET serum P4/E2 levels.

GM-CSF improves endometrial receptivity in a thin endometrium rat model by upregulating HOXA10.

Endometrial receptivity is a prerequisite for the success of assisted reproduction. Patients with a consistently thin endometrium frequently fail to conceive, owing to low endometrial receptivity, and there are currently very few therapeutic options available. Our previous study demonstrated that intrauterine granulocyte-macrophage colony-stimulating factor (GM-CSF) administration resulted in a significant improvement in clinical pregnancy and implantation rates and was an effective means of increasing endometrial thickness on the day of embryo transfer in patients with thin endometrium. In order to explore the underlying process, an animal model with a thin endometrium was constructed, the homeobox A10 gene (HOXA10) was downregulated, and an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) was employed. Our findings strongly suggest a marked decrease in GM-CSF levels in the thin endometrial rat model, and the suppression of HOXA10 impeded the therapeutic efficacy of GM-CSF in this model. Moreover, we showed that GM-CSF significantly increases endometrial receptivity in the rat model and upregulates HOXA10 via the MAPK/ERK pathway. Our data provide new molecular insights into the mechanisms underlying formation of a thin endometrium and highlight a novel, potential clinical treatment strategy as well as directions for further research.

Oxidative Stress: The Role of Estrogen and Progesterone

The effect of estrogen and progesterone on oxidative status is not yet very clear, improvements and detrimental effects having been reported with the use of menopausal hormone therapy or hormonal contraceptives, respectively. In this study, we evaluated the role played by estrogen and progesterone separately, on the oxidative status of 32 women, 18 to 43 years old, by inducing high levels of estrogen and then adding high levels of progesterone. During a cycle of in vitro fertilization, blood samples were collected prior to gonadotrophin stimulation (low estradiol levels), on the day of oocyte retrieval (high levels of estrogen), and on the day of embryo transfer (high levels of estrogen and progesterone). Total blood levels of oxidants (FORT), antioxidants (FORD), and their ratio FORT/FORD were measured using a colorimetric method based on the Fenton reaction. Seven women measured their early morning body temperature at the same time points. FORT significantly decreased from the low- to the high-estrogen phase (p = 0.023) and increased from the high-estrogen to the high-estrogen–progesterone phase (p = 0.006). FORD showed an opposite but non-significant trend. The FORT/FORD ratio decreased from the low- to the high-estrogen phase (p = 0.0104) and increased from the high-estrogen to the high-estrogen –progesterone phase (p = 0.004). Body temperature (n = 7) decreased in the high-estrogen phase (p = 0.001) and increased from the high-estrogen to the high-estrogen–progesterone phase (p = 0.001). In the seven women, FORT (p = 0.009) and FORT/FORD (p = 0.0056) were linearly related to body temperature values. Our data show opposite effects of estrogen and progesterone on oxidative status. These effects seem to be related to the effect exerted on body temperature regulation.

Retrospective Analysis of Fresh Single Blastocyst Transfer versus Two Cleavage-Stage Fresh Day-3 Embryo Transfer with High-Quality Embryos during Gonadotropin-Releasing Hormone Antagonist Cycles in High Responders

Retrospective Analysis of Fresh Single Blastocyst Transfer versus Two Cleavage-Stage Fresh Day-3 Embryo Transfer with High-Quality Embryos during Gonadotropin-Releasing Hormone Antagonist Cycles in High Responders

Does endometrial compaction before embryo transfer affect pregnancy outcomes? a systematic review and meta-analysis.

There is no clear evidence of clinical significance of endometrial compaction, which can be measured by a reduction in endometrial thickness (EMT) during the follicular-luteal transition before the day of embryo transfer. In this study, we aim to determine whether endometrial compaction has an effect on in vitro fertilization (IVF) success. We searched PubMed, Cochrane, Embase, and Web of Science electronic databases for studies published in English up to March 2023. Heterogeneity between studies was assessed using the I2 statistic. The random effects model and fixed effects model was used to pool the risk ratio (RR) with a corresponding 95% confidence interval (CI). A subgroup analysis was performed based on different methods of ultrasonic measurement and different endometrial compaction rates (ECR). Stata 17.0 software was used for meta-analysis. Pregnancy outcomes, which included clinical pregnancy rate, ongoing pregnancy rate, live birth rate, and spontaneous abortion rate, were evaluated. In this study, 18 cohort studies were included, involving 16,164 embryo transfer cycles. Pooled results indicated that there was no significant difference between the endometrial compaction group and the non-compaction group in terms of clinical pregnancy rate (RR [95% CI]=0.98 [0.90,1.08]; I2=69.76%), ongoing pregnancy rate (RR [95% CI]=1.18 [0.95,1.47]; I2=78.77%), live birth rate (RR [95% CI]= 0.97 [0.92,1.02]; I2=0.00%) or spontaneous abortion rate (RR [95% CI]= 1.07[0.97,1.26]; I2=0.00%). According to the subgroup analysis of ultrasonic measurement methods, in the transvaginal ultrasound (TVUS) combined with abdominal ultrasonography (AUS) cycles of the endometrial compaction group, the rate of ongoing pregnancy (RR [95% CI] = 1.69 [1.26, 2.26]; I2=29.27%) and live birth (RR [95% CI] = 1.27 [1.00,1.61]; I2=62.28%) was significantly higher than that of the non-compaction group. Additionally, subgroup analysis based on ECR revealed a significantly higher rate of ongoing pregnancy when ECR ≥ 15% (RR [95% CI] = 1.99 [1.61, 2.47]; I2=0.00%). Endometrial compaction has no adverse effect on clinical pregnancy rate, ongoing pregnancy rate, live birth rate, or spontaneous abortion rate. A possible explanation for the contradictory findings of previous studies lies in the method by which the EMT is measured. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023430511, identifier CRD42023430511.

Impact of endometrial compaction on reproductive outcomes after cryotransfer of euploid embryos in a modified natural cycle: protocol for a prospective cohort study.

Embryo implantation is a complex and poorly understood process. Most studies to date have focused on the analysis of the endometrium at the end of the estrogenic phase, while the available data on its importance after secretory transformation are limited and inconsistent. Current evidence does not allow for a conclusive interpretation of the changes observed in the pre-implantation endometrium, whether in the natural or replacement cycle, and their relevance in the development of a pregnancy or the implications for clinical practice. Multicenter prospective observational cohort study. Based on our sample size calculation, the study group will consist of 206 women (exposed or "compaction" group: 103 women with a decrease of ≥ 5% in endometrial thickness between the estrogenic phase and the day of embryo transfer; non-exposed "non-compaction" group: 103 women with similar or greater endometrial thickness between these time points). The main objective of this study is to compare the ongoing pregnancy rates in natural cycles for euploid embryo transfer in patients who present endometrial compaction at the time of transfer versus those who with a stable or greater endometrial thickness with respect to the estrogenic phase. The estimated duration of the study is 30 months. Inclusion criteria are: 18 to 50 years of age, with primary or secondary infertility, subjected to endometrial preparation in a modified natural cycle for transfer of a genetically euploid blastocyst, from their own oocyte or oocyte donation, with a normal uterine cavity. Exclusion criteria are: uterine or endometrial disease (e.g., multiple myomatosis, severe adenomyosis, Asherman syndrome, refractory endometrium), conditions that prevent correct ultrasound assessment (tilted uterus), or a history of recurrent implantation failure or repeated miscarriages. The findings from this study will provide valuable insights into the potential influence of the "endometrial compaction" phenomenon on reproductive outcomes during natural cycle endometrial preparation. By examining this aspect, we aim to contribute to a better understanding of the factors that may impact successful outcomes in fertility treatments.

Establishment of a prediction model for the impact of endometrial thickness on the day of embryo transfer on ectopic pregnancy in frozen-thawed embryo transfer cycle.

This study aims to investigate the factors affecting the ectopic pregnancy (EP) rate in the frozen-thawed embryo transfer (FET) cycle. This study retrospectively analyzed 5606 FET cycles, including 5496 cycles resulting in intrauterine pregnancy and 110 cycles resulting in EP. Smooth curve fitting and piece-wise linear regression were utilized to evaluate a non-linear association between endometrial thickness (EMT) and EP. Multiple logistic regression analysis was used to study the effect of EMT on the embryo transfer (ET) day and other indexes on EP rate after adjusting for confounding factors. A nomographic prediction model was employed to predict EP occurrence. The predictive efficacy of the model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC), utilizing the bootstrap sampling method for internal validation. After accounting for the confounding factors, the segmented linear regression analysis indicated that the EMT inflection point was 9mm; the EP rate significantly decreased by 28% with each additional millimeter of EMT up to 9mm (odds ratio (OR) = 0.72; 95% confidence interval (CI), 0.53-0.99; P = 0.0412) while insignificantly decreased when the EMT was greater than 9mm (OR = 0.91; 95% CI, 0.76-1.08; P = 0.2487). Multivariate logistic regression analysis revealed that after adjusting for confounders, EP risk significantly increased in the number of previous EPs ≥ 1 (OR = 2.29; 95% CI, 1.26-4.16; P = 0.0064) and tubal factor infertility (OR = 3.86; 95% CI, 2.06-7.24; P < 0.0001). Conversely, EP risk was significantly reduced by the increased EMT (OR = 0.84; 95% CI, 0.74-0.96; P = 0.0078) and the blastocyst transfer (OR = 0.45; 95% CI, 0.27-0.76; P = 0.0027). These variables were used as independent variables in a nomogram prediction model, resulting in an AUC of 0.685. The nomination models were internally verified using self-sampling (bootstrap sampling resampling times = 500). This validation yielded an AUC of 0.689, with a sensitivity of 0.6915 and a specificity of 0.5790. The internal validation indicated minimal fluctuations in the AUC, signifying a relatively stable model. Undergoing EMT on the day of ET poses a separate EP risk in the FET cycle; to mitigate the EP incidence, the EMT should exceed 9mm before ET. Furthermore, previous EPs and tubal factor infertility were additional factors independently increasing EP risk. Furthermore, implementing blastocyst transfer demonstrated that EP incidence was significantly reduced. Utilizing a nomogram predicting system enables EP risk evaluation before ET for individual patients, establishing a basis for devising clinical strategies for ET.

Effect of individualized luteal phase support due to serum progesterone levels at embryo transfer day in frozen-thawed cycles

Effect of individualized luteal phase support due to serum progesterone levels at embryo transfer day in frozen-thawed cycles

Compression of Genetic Expression of Progesterone and Prostaglandin E2 Between PCOS and Non-PCOS Women

Several hormones may interact with the implantation process by mobilizing several molecular modulators in a spatiotemporal manner. A total of 31 women were selected intentionally, then divided into (16) with polycystic ovarian syndrome and (15) healthy women with male factor, the blood serum samples were analyzed by real-time quantitativepolymerase chain reaction (RT- qPCR) for measurement of the fold of expression for Progesterone (P4) and Prostaglandin (PGE2) in the day of ova pick up (OPU) and after 14 days of embryo transfer (ET) in pregnant and non-pregnant women for PCOS and Non-PCOS groups. The results showed that there were no statically significant differences encountered between non-PCOS andPCOS groups in the expression of progesterone and prostaglandin genes (P 0.7296) and ( P 0.0530) respectively. Conclusion: 1- P4 and COX-2 expression in women PCOS is less common in healthy women than in menopausal women. 2- COX-2 is one of the indicators to consider in the case of blastocyst adhesion to the uterine wall.3-In both the PCOS and non-PCOS groups, there was a small increase in P4 and PGE2 expression on the day of ova collection and after 14 days after embryo transfer.

No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture.

Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception? There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study. Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions. This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia). From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders. In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer. This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables. Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation. The study was financed by a research grant from Gedeon Richter. There are no conflicts of interest for all authors to declare. N/A.

Initiating luteal phase support with sc progesterone based on low serum progesterone on the transfer day in true natural cycle frozen embryo transfers.

Concerning contemporary in-vitro fertilisation (IVF) practice, the use of frozen embryo transfer (FET) cycles has become more common than fresh transfers. Natural cycle (NC), programmed artificial cycle and mild stimulation cycle are primary endometrium preparation cycles. Monitoring serum progesterone levels in FET cycles are in the scope of current research focus. Low progesterone levels on the day of embryo transfer is presumed to negatively affect pregnancy outcomes, while progesterone supplementation may improve pregnancy rates. The purpose of our trial is to evaluate whether initiating subcutaneous (SC) progesterone supplementation on the day of embryo transfer when serum progesterone levels are below 10 ng/mL in tNC-FET will result in pregnancy rates comparable to those of patients with sufficient serum progesterone. Retrospective single centre study was conducted between August 2022 and April 2023 with 181 tNC-FETs. Patients were separated into groups according to serum progesterone concentrations (≥10 ng/mL and <10 ng/mL) on embryo transfer (ET) day. S.c progesterone (25 mg) was given on the day of ET when serum progesterone was <10 ng/mL, continuing until the 10th gestational week. Blood samples for pregnancy tests were collected 12 days after ET. Outcome parameters were pregnancy rate, clinical pregnancy rate (CPR), miscarriage rate, multiple pregnancy rate, biochemical pregnancy, and ongoing pregnancy rate (OPR). About half (49.7%) had adequate progesterone concentrations (≥10ng/mL) on ET day. There was no significant difference between the groups regarding positive pregnancy test, OPR, multiple pregnancies, and miscarriage rates (57.8% versus 52.7%; 34.4% versus 29.7%, 1.1% versus 2.2%; 7.8% versus 5.5%; respectively, for progesterone concentrations on ET day ≥10 ng/mL and <10 ng/mL). With 55.2% of transfers leading to clinical pregnancy, significant differences emerged in biochemical pregnancy and CPR (3.3% vs 12.1%, P=0.02; 54.4% vs 40.7%, P=0.03, for ≥10 ng/mL and <10 ng/mL progesterone concentrations on ET day). This study indicates that nearly half of the tNC-FETs may need luteal phase support due to low progesterone. However, 25 mc sc progesterone rescued the luteal support and yielded similar OPR as compared to normal progesterone group. Further studies are needed for understanding optimal progesterone levels, supplementation effectiveness, and potential benefits of earlier supplementation in FETs.

Luteal phase support using micronized vaginal progesterone as pessaries or capsules in artificial cycles: is there any difference?

Research questionIs there a difference between the proportion of patients with serum progesterone <8.8 ng/ml on the day of embryo transfer when micronized vaginal progesterone (MVP) for luteal phase support (LPS) is given as pessaries versus capsules? DesignThis retrospective, matched-cohort, single-centre study compared pessaries (Cyclogest) versus capsules (Utrogestan, Progeffik) for LPS in hormone replacement treatment–embryo transfer (HRT-ET) cycles. Patients under 50 years old with a triple-layer endometrial thickness of ≥6.5 mm underwent transfer of one or two blastocysts. Serum progesterone concentrations were measured on the day of transfer; patients with concentrations <8.8 ng/ml received a single ‘rescue’ dose of additional progesterone by subcutaneous injection. ResultsIn total 2665 HRT-ET cycles were analysed; 663 (24.9%) used pessaries for LPS and 2002 (75.1%) used capsules. Mean serum progesterone concentrations with standard deviations on the day of embryo transfer were significantly higher in the group using MVP pessaries compared with those using capsules (14.5 ± 5.1 versus 13.0 ± 4.8 ng/ml; P = 0.000). The percentage of participants with suboptimal serum progesterone concentrations on the day of embryo transfer (<8.8 ng/ml) was significantly lower in the pessary group than the capsule group (10.3%, 95% confidence interval [CI] 7.9–12.6% versus 17.9%, 95% CI 16.2–19.6%; adjusted odds ratio 0.426, 95% CI 0.290–0.625; P = 0.000). No differences in pregnancy outcome were observed between the groups. ConclusionsUsing MVP pessaries rather than capsules for LPS resulted in significantly fewer patients having suboptimal serum progesterone concentrations on the day of embryo transfer. Consequently, almost 50% fewer patients in the pessary group needed rescue treatment.

Effect of different levels of serum progesterone on day of frozen ET on clinical outcome

BackgroundProgesterone (P4) plays a critical role in a natural menstrual cycle. It is an essential hormone to have successful embryo implantation into the endometrium.ObjectiveIn the current study, we compared the clinical outcomes of patients with different levels of P4 on embryo transfer day and aimed to determine the optimum threshold for P4 in the luteal phase.Material and methodsWe performed a prospective cohort study on 100 patients who were referred to the Taleqani Infertility Treatment Institute to undergo frozen embryo transfer (FET). Endometrial preparation was programmed using an estrogen (E2) and progesterone supplement. FET was carried out 3 days after administration of the first dosage of progesterone. We measured serum progesterone levels on embryo transfer day. Clinical pregnancy was the main investigated outcome. We used a parametric receiver operating characteristic curve (ROC) to determine the best-cut points of P4 on embryo transfer day.ResultsOverall, the average endometrial thickness was 7.9 ± 0.2 mm. We observed no association between endometrial thickness and clinical pregnancy (P value = 0.719). The mean number of the transferred embryos in all investigated cycles was 1.5 ± 0.5, and 80.0% of the transferred embryos were high quality (high and medium level). The average progesterone level in cycles with clinical pregnancy was 17.2 ± 3.3 ng/mL. It was only 13.4 ± 9.4 in patients without clinical pregnancy. The observed difference was statistically significant (P value = 0.032). The estimated AUC for the drawn ROC curve was 0.71 indicating a high predictive value.ConclusionThe current study demonstrated that high and low serum progesterone (P4) levels on embryo transfer day were associated with reduced clinical outcomes following blastocyst transfer during IVF/ICSI. However, more studies with large sizes are required in this regard.

A model for predicting low progesterone levels on the day of embryo transfer in hormonally prepared vitrified-warmed embryo transfer cycles: A secondary analysis of a prospective cohort study.

To develop a model that predicts low progesterone (P) levels on the day of embryo transfer (ET) based on patient and cycle characteristics, including serum estradiol (E2 ) concentration after vaginal administration of micronized E2 for endometrial preparation. A prospective cohort of 193 patients scheduled for cryopreserved blastocyst transfer during an artificial endometrial preparation cycle, using micronized E2 vaginally for first 4 days (4 mg/day), followed by oral administration (6 mg/day). Blood sampling for E2 was performed prospectively on day-5 of vaginal administration and analysis was performed retrospectively. On sixth day of P treatment (daily 300 mg of vaginal micronized P tablets), P levels were measured on ET day. Primary outcome measure was serum P levels after vaginal E2 administration. Patients with low P levels on the day of ET (<7.8 ng/mL, 25th percentile) were heavier (p < 0.001) and exhibited lower day 5 serum E2 levels (p < 0.001) compared with patients with adequate P levels. Multivariate linear regression analysis revealed that weight (p = 0.003) and day 5 E2 levels (p < 0.001) were independently associated with the P levels. The sensitivity, specificity, and positive and negative predictive values (%) were 71.4, 55.6, 35.4, and 85.1 for weight ≥ 65 kg; 71.4, 61.8, 38.9, and 86.4 for day 5 E2 ≤ 1615 pg/mL; 59.2, 83.3, 54.7, and 85.7 for the combination of these two variables; and 82.9, 62.5, 54.7, and 87.0 for the sequential inclusion of these variables, respectively. Low day 5 E2 levels following vaginal administration and high weight are independently associated with low P levels on the day of ET. Predictive performance is enhanced when these variables are considered sequentially or in combination.