Vitrification preservation of good-quality blastocysts for more than 5 years reduces implantation and live birth rates.

STUDY QUESTION: Does vitrification cryopreservation of embryos for more than 5 years affect the pregnancy outcomes after frozen embryo transfer (FET)? SUMMARY ANSWER: Vitrification cryopreservation of good-quality blastocysts for more than 5 years is associated with a decrease in the implantation rate (IR) and live birth rate (LBR). WHAT IS KNOWN ALREADY: Previous studies have predominantly focused on embryos cryopreserved for relatively short durations (less than 5 years), yet the impact of extended cryopreservation duration on pregnancy outcomes remains a controversial issue. There is a relative scarcity of data regarding the efficacy and safety of storing embryos for 5 years or longer. STUDY DESIGN, SIZE, DURATION: This retrospective study involved 36 665 eligible vitrified-thawed embryo transfer cycles from 1 January 2016 to 31 December 2022, at a single fertility center in China. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were divided into three groups according to embryo storage time: Group 1 consisted of 31 565 cycles, with storage time of 0-2 years; Group 2 consisted of 4458 cycles, with a storage time of 2-5 years; and Group 3 included 642 cycles, with storage time exceeding 5 years. The main outcome measures were IR and LBR. Secondary outcome variables included rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage, as well as neonatal outcomes. Reproductive outcomes were analyzed as binary variables. Multivariate logistic regression analysis was used to explore the effect of preservation time on pregnancy outcomes after correcting for confounding factors. In addition, we also assessed neonatal outcomes, such as large for gestational age (LGA) and small for gestational age (SGA). MAIN RESULTS AND THE ROLE OF CHANCE: IRs in the three groups (0-2, 2-5, and >5 years) were 37.37%, 39.03%, and 35.78%, respectively (P = 0.017), and LBRs in the three groups were 37.29%, 39.09%, and 34.91%, respectively (P = 0.028). After adjustment for potential confounding factors, compared with the 0-2 years storage group, prolonged embryo vitrification preservation time (2-5 years or >5 years) did not affect secondary outcomes such as rates of biochemical pregnancy, multiple pregnancy, ectopic pregnancy, and miscarriage (P > 0.05). But cryopreservation of embryos for more than 5 years reduced the IR (adjusted odds ratio (aOR) 0.82, 95% CI 0.69-0.97, P = 0.020) and LBR (aOR 0.76, 95% CI 0.64-0.91, P = 0.002). Multivariate stratified analysis also showed that prolonging the cryopreservation time of blastocysts (>5 years) reduced the IR (aOR 0.78, 95% CI 0.62-0.98, P = 0.033) and LBR (aOR 0.68, 95% CI 0.53-0.87, P = 0.002). However, no effect on cleavage embryos was observed (P > 0.05). We further conducted stratified analyses based on the number and quality of frozen blastocysts transferred, and the results showed that the FET results after transfers of good-quality blastocysts in the >5 years storage group were negatively affected. However, the storage time of non-good-quality blastocysts was not significantly associated with pregnancy outcomes. Regarding the neonatal outcomes (of singletons), embryo vitrification preservation time had no effect on preterm birth rates, fetal birth weight, or neonatal sex ratios. However, as the storage time increased, rates of SGA (5.60%, 4.10%, and 1.18%) decreased, while rates of LGA (5.22%, 6.75%, and 9.47%) increased (P < 0.05). After adjusting for confounding factors, the increase in LGA and the decrease in SGA were significantly correlated with the duration of storage time. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study using data from a single fertility center, even though the data had been adjusted, our findings still need to be validated in further studies. WIDER IMPLICATIONS OF THE FINDINGS: With the full implementation of the two-child policy in China, there may be more patients whose embryos have been frozen for a longer time in the future. Patients should be aware that the IR and LBR of blastocysts are negatively affected when the cryopreservation time is longer than 5 years. Couples may therefore consider shortening the time until FET treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Nature Science Foundation of China (No. 82101672), Science and Technology Projects in Guangzhou (No. 2024A03J0180), General Guidance Program for Western Medicine of Guangzhou Municipal Health Commission (No. 20231A011096), and the Medical Key Discipline of Guangzhou (2021-2023). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Development of a Novel Non-invasive Metabolomics Assay to Predict Implantation Potential of Human Embryos.

Can a set of metabolites present in embryo culture media correlate with embryo implantation? Case-control study in two phases: discovery phase (101 samples) and validation phase (169 samples), collected between 2018 and 2022, with a total of 218 participants. Culture media samples with known implantation outcomes were collected after blastocyst embryo transfer (including both PGT and non-PGT cycles) and were analyzed using chromatography followed by mass spectrometry. The spectra were processed and analyzed using statistical and machine learning techniques to identify biomarkers associated with embryo implantation, and to develop a predictive model. In the discovery phase, 148 embryo implantation biomarkers were identified using high resolution equipment, and 47 of them were characterized. Our results indicate a significant enrichment of tryptophan metabolism, arginine and proline metabolism, and lysine degradation biochemical pathways. After transferring the method to a lower resolution equipment, a model able to assign a Metabolite Pregnancy Index (MPI) to each embryo culture media was developed, taking the concentration of 36 biomarkers as input. Applying this model to 20% of the validation samples (N=34) used as the test set, an accuracy of 85.29% was achieved, with a PPV (Positive Predictive Value) of 88% and a NPV (Negative Predictive Value) of 77.78%. Additionally, informative results were obtained for all the analyzed samples. Metabolite concentration in the media after in vitro culture shows correlation with embryo implantation potential. Furthermore, the mathematical combination of biomarker concentrations using Artificial Intelligence techniques can be used to predict embryo implantation outcome with an accuracy of around 85%.

Unlocking the Potential of Assisted Hatching in Assisted Reproductive Technology: A Narrative Review.

The present study is set in the broad field of assisted reproductive technologies (ARTs) and examines various procedures under assisted hatching (AH). It also reviews their effects on implantation success rates. The primary emphasis is on explaining who has benefited and how many have benefited from these interventions. The most important factor determining the success rate of ART is implantation. To increase these rates, we use AH in our clinics to enhance each embryo's chances at life and substantially improve overall results. This comprehensive review includes various approaches, such as chemical-based measures (such as applying Tyrode's solution) and mechanical techniques (such as zona drilling and partial zona dissection). The individual techniques are carefully scrutinized, considering their mechanical detailing, methods of applying therapeutic effects, and the appropriateness of matching present social circumstances. The review begins by analyzing the basic nature of AH as a medium for embryo implantation and then focuses on how this detailed view reveals the advantages and drawbacks of various methods. Moreover, the articles discuss improvements in AH technology and many of the most modern technological developments that can help fine-tune ART issues. A major problem with these methodologies is that they involve serious risks and legal complications. However, a broad assessment of these topics allows us to understand their impact on fertility treatments. This review is written as a guidebook for physicians and researchers working in reproductive medicine. It compiles all current knowledge, providing literature to build on successes that will make breakthroughs possible in ART. Indeed, this is a valuable reference for guiding us in navigating complex AH procedures. It advances ARTs step by step toward perfection.

Platelet-Rich Plasma (PRP) for Endometrial Treatment Efficacy and Safety in Assisted Reproductive Technology: A Comprehensive Review.

Platelet-rich plasma (PRP) is among the new ground-breaking methods called for endometrial disorders detected in assisted reproductive technology (ART). This research work takes account of both a systematic literature review and an exploration of the molecular connections. The report aims to present the capabilities and benefits of the PRP in ART and the nonconformance and dangers involved in its use in ART. However, all these stages of ART need conducive endometrium, live micro embryo, and coordinated interaction between the blastocyst and the uterus. Despite all ART has achieved, implantation failure still exists as a problem having one quarter being attributed to the absence of the endometrial receptivity level. The review points to a corresponding increase in the role of autologous PRP in promoting cell proliferation, neo-angiogenesis, and anti-inflammatory effects to facilitate effective endometrial receptivity. The outcome of prior trials with the PRP approach proved to be positive for women with adenomyosis, thin endometrial lining, recurring implantation failure, chronic endometritis, and Asherman's syndrome. Challenges still exist in the proper placement of PRP for all women with infertility problems as well as how it works for individuals with blood disorders and infections. This study will look into the safest number of doses, the time of acting, and the possible future health hazards that both mother and child may face.

Chinese medicine Jianpi Antai formula improves pregnancy outcomes of in vitro fertilization-embryo transfer in infertile women. / å¥è„¾å®‰èƒŽæ–¹å¯æ”¹å–„ä¸å­•æ‚£è€ ä½“å¤–å—ç²¾-èƒšèƒŽç§»æ¤çš„å¦Šå¨ ç»“å±€.

OBJECTIVES: To evaluate the efficacy and safety of Chinese medicine Jianpi Antai formula in infertile women undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: A total of 300 infertile women who underwent 2 frozen embryo transfer procedures at the Reproductive Medicine Center, Sir Run Run Shaw Hospital were included in the study. The participants were randomly divided into study group and control group. The study group received routine medication plus the Jianpi Antai formula during the period of embryo transfer, while the control group received routine medication only. The general condition, embryo implantation rate, clinical pregnancy rate, live birth rate, and the blood routine and liver and kidney function were evaluated and compared between two groups. RESULTS: There were 277 cases who completed the study, including 134 in the study group and 143 in the control group. The embryo implantation rate (68.7% vs. 55.9%), the clinical pregnancy rate (56.7% vs. 44.8%) and the live birth rate (50.7% vs. 37.8%) in the study group were all higher than those in the control group (all P<0.05). Subgroup analysis revealed that in patients of advanced age (≥35 years) and those with decreased ovarian reserve function (anti-Müllerian hormone <1.68 ng/mL), the embryo implantation rate, clinical pregnancy rate, and live birth rate in the study group were all higher than those in the control group (all P<0.05). During the follow-up period, there were no abnormalities in the basic vital signs of both groups, and no adverse events were reported. CONCLUSIONS: Jianpi Antai formula can safely improve the embryo implantation rate in infertile women undergoing IVF-ET, reduce the embryo miscarriage rate, increase the live birth rate as well as improve the clinical outcomes.

Application of platelet-rich plasma in assisted reproductive technology / 中国输血杂志

Assisted reproductive technology(ART) faces challenges such as low embryo implantation rates due to uterine factors, and infertility caused by ovarian function suppression and abnormal semen. Platelet-rich plasma(PRP), which is rich in various bioactive substances, can play an anti-inflammatory role and promote cell proliferation, vascular regeneration and injury healing, and is now a hot topic in ART. This paper describes the relevant research on PRP in ART for clinical reference, aiming to standardize the application of PRP in ART and provide a new treatment for infertile couples.

Effect of Zishen-Yutai pills on refrozen-thawed embryo transfer in patients with diminished ovarian reserve / 中国组织工程研究

BACKGROUND:Currently,hormone replacement therapy is the main treatment in Western medicine for patients with decreased ovarian function,but these patients are not sensitive to exogenous hormones,leading to unsatisfactory therapeutic effect.Zishen-Yutai pills can nourish the blood and calm the fetus,tonify the kidney and spleen,invigorate qi and strengthen the body.Studies have confirmed that Zishen-Yutai pill is effective in reducing follicle-stimulating hormone index and improving traditional Chinese medicine symptoms in patients with diminished ovarian reserve.However,few studies have been conducted to improve the implantation rate of patients by improving endometrial receptivity. OBJECTIVE:To evaluate the effect of Zishen-Yutai pills on the clinical outcome of patients with diminished ovarian reserve undergoing frozen-thawed embryo transfer again. METHODS:A total of 300 patients with diminished ovarian reserve who underwent frozen-thawed embryo transfer to assist pregnancy after the first failure in the Center of Reproductive Medicine,Changzhou Maternal and Child Health Care Hospital from January 2019 to December 2021 were selected as the study subjects.Subjects were randomly treated with a placebo or Zishen-Yutai pills in a ratio of 1:2,with 100 cases in the treatment group and 200 cases in the control group.However,13 patients fell off due to lack of contact,refusal to take medicine or other reasons.Finally,90 cases in the treatment group and 197 cases in the control group were included in the study.Oral medication was administered 7 days before frozen-thawed embryo transfer transplantation at a dose of 5 g/time,3 times/day.To investigate whether taking Zishen-Yutai pills could improve the clinical outcome of patients with diminished ovarian reserve after frozen-thawed embryo transfer again,the primary outcome measures included clinical pregnancy rate,implantation rate,abortion rate,live birth rate,offspring birth weight and birth defects. RESULTS AND CONCLUSION:Compared with the control group,the clinical pregnancy rate(P<0.05)and implantation rate(P=0.009)were significantly increased after the oral administration of Zishen-Yutai pills.Correlation analysis showed that taking the Zishen-Yutai pill was positively correlated with the number of implanted embryos(r=0.200,P=0.001)and clinical pregnancy(r=0.235,P=0.000).There was no correlation between taking Zishen-Yutai pills and indexes of endometrial thickness and blood flow.It is indicated that Zishen-Yutai pills can improve the clinical pregnancy rate and implantation rate of frozen-thawed embryo transfer recurrence in patients with diminished ovarian reserve.

Clinical efficacy of acupuncture combined with Chinese herbal medication for recurrent implantation failure infertility of kidney deficiency and blood stasis and its effects on serum p38MAPK and JAK/STAT protein expression. / é’ˆè¯ç»“åˆæ²»ç–—è‚¾è™šè¡€ç˜€åž‹åå¤ç§æ¤å¤±è´¥ä¸å­•çš„ä¸´åºŠç–—æ•ˆåŠå¯¹è¡€æ¸ p38MAPK、JAK/STAT蛋白表达的影响.

OBJECTIVES: To observe the effects of acupuncture combined with Chinese herbal medication on pregnancy outcomes in patients with recurrent implantation failure (RIF) infertility of kidney deficiency and blood stasis, and to explore its effects on the protein expression of serum p38MAPK and JAK/STAT. METHODS: Sixty-two patients with RIF infertility of kidney deficiency and blood stasis who were scheduled for artificial cycle frozen-thawed embryo transfer were randomly divided into an observation group (31 cases, 4 cases dropped out) and a control group (31 cases, 3 cases were eliminated). The patients in the control group were treated with conventional artificial cycle frozen-thawed embryo transfer. On the basis of the control group, the patients in the observation group were treated with acupuncture combined with Chinese herbal medication. Acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4) and bilateral Neiguan (PC 6), Zigong (EX-CA 1), Guilai (ST 29), Zusanli (ST 36), Taichong (LR 3), Shenshu (BL 23), Ciliao (BL 32), with each session lasting for 30 minutes, once every other day. Chinese herbal medication was administered to Bushen Huoxue (tonifing the kidney and activating blood circulation) decoction, with one dose per day, starting from the 3rd to 5th day of the menstrual cycle and continuing until 1 day before embryo transfer. Clinical pregnancy rate, embryo implantation rate, live birth rate, and biochemical pregnancy rate were compared between the two groups. TCM symptom score, platelet count (PLT), and plasma D-dimer level were assessed before treatment and 1 day before embryo transfer. Western blot method was used to detect the expression of serum P38MAPK, JAK, and STAT proteins before treatment and 1 day before embryo transfer. RESULTS: In the observation group, the clinical pregnancy rate, embryo implantation rate, and live birth rate were higher (P<0.05), while the biochemical pregnancy rate was lower (P<0.05) than those in the control group. One day before embryo transfer, both groups showed a decrease in TCM symptom scores, PLT, and plasma D-dimer levels compared to those before treatment (P<0.05), and the observation group had lower TCM symptom scores and plasma D-dimer levels than the control group (P<0.05). One day before embryo transfer, the expression levels of serum p38MAPK, JAK, and STAT proteins in both groups were lower than those before treatment (P<0.05), and the observation group had lower serum p38MAPK protein expression than the control group (P<0.05). CONCLUSIONS: Acupuncture combined with Chinese herbal medication can improve the clinical pregnancy rate, embryo implantation rate, live birth rate, and reduce the biochemical pregnancy rate in RIF infertility patients of kidney deficiency and blood stasis. Its mechanism of action may be related to down-regulating plasma D-dimer level and protein expression of serum p38MAPK.

Which transfer day results in the highest live birth rate for PCOS patients undergoing in vitro fertilization?

BACKGROUND: Polycystic ovary syndrome (PCOS) has unusual levels of hormones. The hormone receptors in the endometrium have a hostile effect and make the microenvironment unfavorable for embryo implantation. The use of gonadotropin stimulation during in vitro fertilization (IVF) may have an impact on embryo implantation and live birth rate. According to recent data, the clinical results of day 4 embryo transfer (D4 transfer) were on par with those of day 5 embryo transfer (D5 transfer) in IVF-ET. There are few studies comparing the outcomes of transplants with various etiologies and days. The purpose of this study was to determine which transfer day had the best result for PCOS patients undergoing IVF. METHODS: This retrospective cohort study was conducted in the Xingtai Infertility Specialist Hospital between January 2017 and November 2021. A total of 1,664 fresh ART cycles met inclusion criteria, including 242 PCOS transfers and 1422 tubal factor infertility transfers. CONCLUSIONS: PCOS individuals had the highest live birth rate on D4 transferred. It was not need to culture embryos to blastocysts to optimize embryo transfer for PCOS women. This could be a novel approach to transplantation for PCOS.

Stratified analysis of clinical pregnancy outcomes of sequential embryo transfer in frozen embryo transfer cycles based on different factors: a retrospective study.

OBJECTIVE: To explore the effect of sequential embryo transfer (ET) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycle and the indications of sequential transfer. METHODS: A total of 1440 FET cycles were enrolled in this retrospective study, of which 1080 patients received conventional ET and 360 patients received sequential ET. Further stratified analysis was performed according to the number of previous failed cycles, the number of embryos transferred and the stage of blastocyst (day 5 or 6, denoted D5 or D6) transferred. Comparison of pregnancy rates, implantation rate, miscarriage rate and multiple pregnancy rate among the groups of patients. RESULTS: The clinical pregnancy rate and implantation rate of the sequential ET group were higher than those of the conventional ET group (P < 0.01); however, there was no statistical difference in multiple pregnancy rate and miscarriage rate (P > 0.05). In sequential transfer, the number of transferred embryos (2 or 3) and the stage of transferred blastocysts (D5 or D6) had no effect on clinical pregnancy rate, implantation rate, multiple pregnancy rate and miscarriage rate (P > 0.05). In patients with three or more previous failure cycles, the sequential ET group showed higher clinical pregnancy rate and implantation rate (P > 0.05). CONCLUSIONS: Compared with conventional ET in FET cycle, sequential ET strategy could significantly improve the clinical pregnancy rate and implantation rate. In sequential transfer, patients with three embryos transferred don't have higher pregnancy rate and implantation rate. Besides, sequential transfer is more suitable for patients with repeated implantation failures (RIF), and increase the utilization rate of D6 blastocysts.

Is endometrial receptivity affected in women with endometriosis? Results from a matched pair case-control study of assisted reproductive technology treatments.

RESEARCH QUESTION: Is endometriosis detrimental to embryo implantation? DESIGN: A retrospective matched case-control study of women with a surgical or ultrasound diagnosis of endometriosis at Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano between 2015 and 2021. Women with endometriosis who underwent a 'freeze-all' cycle during an IVF treatment were eligible to be included. They were matched to patients without the disease, who also underwent cryopreserved blastocyst transfer cycles, in a 1:1 ratio by age (±1 year), and number (=) and quality (±1 top versus low) of cryopreserved blastocysts. All women underwent single frozen embryo transfer, and assisted reproductive technology outcomes suggested by the Core Outcome Measure for Infertility Trials initiative were evaluated. The main outcome was the cumulative live birth rate per cycle. RESULTS: One hundred and one women with endometriosis and 101 matched unaffected women were included. Cumulative live birth rate per cycle did not vary between women with and without endometriosis (50% versus 58%, respectively; P = 0.32). On the basis of the Kaplan-Meier analysis, the predicted success rates over four embryos transferred were also similar (74% versus 82%, respectively; P = 0.67). CONCLUSION: In women with moderate or severe endometriosis, these retrospective results seem to indicate no or a limited effect of the disease on endometrial receptivity.

Impact of the number of previous embryo implantation failures on IVF/ICSI-ET pregnancy outcomes in patients younger than 40 years: a retrospective cohort study.

Objective: The objective of this study was to examine the influence of repeated embryo implantation failures on pregnancy outcomes among patients under 40 years of age undergoing in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). Materials and methods: A retrospective analysis was conducted on the clinical data of 13,172 patients who underwent 16,975 IVF/ICSI-ET treatment cycles at Henan Reproductive Hospital between January 1, 2015, and December 31, 2018. Patients were categorized into four groups based on the number of previous embryo implantation failure cycles: Group A=no implantation failure, Group B= 1 implantation failure, Group C=2 implantation failures, Group D=≥3 implantation failures. Baseline characteristics and pregnancy outcomes were compared among the four groups. The impact of the number of previous embryo implantation failures on pregnancy outcomes among IVF/ICSI-ET patients was investigated using univariate and multiple regression analyses. Results: Univariate logistic regression analysis demonstrated that factors such as the number of previous embryo implantation failures, female age, basal follicle count, endometrial thickness, total number of oocytes retrieved, type of cycle, number of high-quality embryos transferred, and stage of embryo development significantly affected implantation rate, clinical pregnancy rate, early spontaneous abortion rate, and live birth rate (all P < 0.05). The duration of infertility and anti-Mullerian hormone (AMH) levels were also found to influence implantation rate, clinical pregnancy rate, and live birth rate (all P < 0.05). Upon conducting multivariate logistic regression analysis and adjusting for confounding factors such as age, AMH levels, basal follicle count, endometrial thickness, total number of oocytes obtained, cycle type, number of high-quality embryos transferred, ovarian stimulation protocol, and stage of embryo development, it was revealed that, compared to Group A, Groups B, C, and D exhibited significantly lower implantation and live birth rates, as well as a significantly higher risk of early spontaneous abortion (all P < 0.05). Conclusions: The number of previous embryo implantation failures is an independent factor affecting implantation rate, clinical pregnancy rate, spontaneous abortion rate and live birth rate of patients underwent IVF/ICSI-ET. With the increase of the number of previous embryo implantation failures, the implantation rate, clinical pregnancy rate and live birth rate of patients underwent IVF/ICSI-ET decreased significantly, and the rate of early spontaneous abortion gradually increased.

Platelet-Rich Plasma Intrauterine Infusion as Assisted Reproduction Technology (ART) to Combat Repeated Implantation Failure (RIF): A Systematic Review and Meta-Analysis.

Background: Repeated implantation failure (RIF) is considered one of the major challenges facing clinician in assisted reproduction technologies (ART) despite the significant advances that have been made in this field. Platelet rich plasma (PRP), also known as autologous conditioned plasma, is a protein concentrate with anti-inflammatory and pro-regenerative characteristics. The use of PRP in women undergoing ART has been studied in the past, with varying degrees of success. The goal of this trial was to see if injecting PRP into the uterus improves pregnancy outcomes in women receiving ART. Methods: PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Clinical Trials were among the databases searched (CENTRAL), from 2015 to 2021. The pooled estimates were calculated using a meta-analysis with a random-effects model. There were 14 studies with a total of 1081 individuals (549 cases and 532 controls). Results: There was no difference in miscarriage rates between women who got PRP and those who received placebo (P≤0.90). Chemical pregnancy (P≤0.00), clinical pregnancy (P ≤0.001), and implantation rate (P≤ 0.001) were all significantly higher in women. Endometrial thickness increased in women who got PRP vs women who received placebo after the intervention (P ≤0.001). Conclusion: PRP may be an alternate therapeutic approach for individuals with thin endometrium and RIF, according to the findings of this comprehensive study. To determine the subgroup that would benefit the most from PRP, more prospective, big, and high-quality randomized controlled trials (RCTs) are needed.

Association between duration of progesterone supplementation and clinical outcomes in artificial frozen-thawed embryo transfer cycles.

Objective: The administration of progesterone before transfer in hormone replacement treatment (HRT) is crucial for the clinical outcomes of frozen-thawed embryo transfer (FET), but the optimal duration of progesterone remains controversial. This study aimed to investigate the effect of the duration of progesterone administration on the clinical outcomes of FET cycles. Methods: This prospective cohort study included 353 artificial FET cycles conducted at a reproductive medicine center between April and October 2021. The FET cycles were stratified into four groups based on the duration of progesterone supplementation before the procedure and the embryonic development stage: group P3 (73 patients) received intramuscular progesterone for 3 days and group P4 (87 patients) for 4 days before Day 3 frozen embryo transfer, group P5 (70 patients) for 5 days and group P6 (123 patients) for 6 days before frozen blastocyst transfer. This trial was performed using one or two vitrified embryo(s) when the endometrial thickness reached 7 mm after estrogen supplementation in an artificial cycle. The primary outcome was clinical pregnancy, and secondary outcomes included biochemical pregnancy, implantation, early pregnancy loss, and live births. Results: There were no significant differences in the demographic and clinical characteristics between the groups. No significant difference was observed in the clinical pregnancy rates between groups: 23/73 (31.5%) in group P3 vs 28/87 (32.2%) in group P4 (P = 0.927). Compared to group P5 (41/70, 58.6%), the clinical pregnancy rate was not significantly different in group P6 (77/123, 62.6%, P = 0.753). There was no significant difference in the implantation rates between groups: 33/136 (24.3%) in group P3 vs 34/166 (20.5%) in group P4 (P = 0.431), and 62/133 (46.6%) in group P5 vs 107/231 (46.3%) in group P6 (P = 0.956). The duration of progesterone supplementation (mean: 3.5 ± 0.5 days; range:3-4 days) before Day 3 frozen embryo transfer did not impact clinical pregnancy (odds ratio [OR] 1.048; 95% confidence interval [CI], 0.518-2.119). The duration of progesterone administration (mean: 5.6 ± 0.5 days; range:5-6 days) before frozen blastocyst transfer may not affect clinical pregnancy (OR 1.339; 95% CI, 0.717-2.497). Conclusion: There may be no significant correlation between the duration of progesterone supplementation and pregnancy outcomes in artificial FET cycles, although the clinical pregnancy rate was higher when progesterone supplementation was extended for one day before FET.

Efficacy of Platelet-Rich Plasma in Women with a History of Embryo Transfer Failure: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Assisted reproductive technology (ART) is used to enhance pregnancy in infertile women. In this technique, the eggs are removed from the ovary and fertilized and injected with sperm to make embryos. Unfortunately, embryo implantation failures still occur in many of these women. Platelet-rich plasma (PRP) therapies use a patient's own platelets to promote tissue healing and growth, including endometrium. The growth factors provided by the platelets play a criterial role on the regenerative ability of PRP. In the last years, PRP treatments have been gaining a lot of popularity to treat women with repeated ART failures. In this study, we collected and summarized all information published in the scientific literature to assess the evidence of the PRP effect on pregnancy. We only considered randomized controlled trials (RCT), a type of study designed to be unbiased and considered at the highest level of evidence. Our analysis indicates that PRP therapies might be an effective treatment in cases of poor responsiveness to conventional ART. However, additional studies (well-designed) are necessary to confirm this beneficial effect of PRP.

Day-3 vs. Day-5 fresh embryo transfer.

OBJECTIVE: Embryo transfer on day-5 has been associated with higher success rates, therefore our IVF clinics started to extend embryo culture until blastocyst stage. This study aimed to compare the success rates of day-3 vs. day-5 embryo transfers. METHODS: We had 266 patients included, all having undergone ICSI, with 221 patients having undergone day-3 embryo transfers, and 45 patients having undergone day-5 embryo transfers. Patients with more than five good quality embryos on day-3 were chosen to prolong the culture of embryos into day-5. RESULTS: There were no significant differences in patient characteristics, including baseline LH, FSH, Prolactin and Estradiol hormone levels. In addition, there were also no significant differences in rFSH total dosage and duration of stimulation day. Final estradiol levels, number of follicles, retrieved oocytes, matured oocytes, fertilized oocytes and number of embryos were significantly higher in day-5 compared to day-3 embryo transfer groups. Number of embryos transferred on day-3, were significantly higher compared to day-5. Neither group showed any significant differences in clinical pregnancy, implantation, multiple pregnancy or living birth rates. There were no differences in birth weights and lengths, head circumstances and Apgar Scores between both groups either in singleton or twin group. CONCLUSIONS: Transferring embryos at day-3 may provide the same benefits as day-5 embryo transfers to patients. However, more embryos were required to be transferred to achieve these comparable results.

Clinical efficacy of acupuncture combined with Chinese herbal medication for recurrent implantation failure infertility of kidney deficiency and blood stasis and its effects on serum p38MAPK and JAK/STAT protein expression / 中国针灸

OBJECTIVES@#To observe the effects of acupuncture combined with Chinese herbal medication on pregnancy outcomes in patients with recurrent implantation failure (RIF) infertility of kidney deficiency and blood stasis, and to explore its effects on the protein expression of serum p38MAPK and JAK/STAT.@*METHODS@#Sixty-two patients with RIF infertility of kidney deficiency and blood stasis who were scheduled for artificial cycle frozen-thawed embryo transfer were randomly divided into an observation group (31 cases, 4 cases dropped out) and a control group (31 cases, 3 cases were eliminated). The patients in the control group were treated with conventional artificial cycle frozen-thawed embryo transfer. On the basis of the control group, the patients in the observation group were treated with acupuncture combined with Chinese herbal medication. Acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4) and bilateral Neiguan (PC 6), Zigong (EX-CA 1), Guilai (ST 29), Zusanli (ST 36), Taichong (LR 3), Shenshu (BL 23), Ciliao (BL 32), with each session lasting for 30 minutes, once every other day. Chinese herbal medication was administered to Bushen Huoxue (tonifing the kidney and activating blood circulation) decoction, with one dose per day, starting from the 3rd to 5th day of the menstrual cycle and continuing until 1 day before embryo transfer. Clinical pregnancy rate, embryo implantation rate, live birth rate, and biochemical pregnancy rate were compared between the two groups. TCM symptom score, platelet count (PLT), and plasma D-dimer level were assessed before treatment and 1 day before embryo transfer. Western blot method was used to detect the expression of serum P38MAPK, JAK, and STAT proteins before treatment and 1 day before embryo transfer.@*RESULTS@#In the observation group, the clinical pregnancy rate, embryo implantation rate, and live birth rate were higher (P<0.05), while the biochemical pregnancy rate was lower (P<0.05) than those in the control group. One day before embryo transfer, both groups showed a decrease in TCM symptom scores, PLT, and plasma D-dimer levels compared to those before treatment (P<0.05), and the observation group had lower TCM symptom scores and plasma D-dimer levels than the control group (P<0.05). One day before embryo transfer, the expression levels of serum p38MAPK, JAK, and STAT proteins in both groups were lower than those before treatment (P<0.05), and the observation group had lower serum p38MAPK protein expression than the control group (P<0.05).@*CONCLUSIONS@#Acupuncture combined with Chinese herbal medication can improve the clinical pregnancy rate, embryo implantation rate, live birth rate, and reduce the biochemical pregnancy rate in RIF infertility patients of kidney deficiency and blood stasis. Its mechanism of action may be related to down-regulating plasma D-dimer level and protein expression of serum p38MAPK.

Elevated serum progesterone levels on the hCG trigger day have a negative impact on the live birth rate in the first fresh IVF-ET cycle.

To investigate whether there is a relationship between elevated serum progesterone (PROG) on the hCG trigger day and the live birth rate (LBR) in IVF/ICSI cycles, the retrospective analysis was carried out from the patients undergoing the first ART cycles throughout 2016. The PROG levels were measured on the hCG trigger day. The LBR, clinical pregnancy rate (CPR), implantation rate (IR) and other parameter rate values were compared among the three different PROG elevations. A total of 2550 IVF/ICSI cycles fulfilling all the inclusion and exclusion criteria were selected. Finally, three groups [PROG <0.40 ng/mL, 0.40 ≤ PROG < 1.5 ng/mL, PROG ≥ 1.5 ng/mL] were categorised based on the serum PROG levels. LBR, CPR and IR declined as the PROG value increased, while there was no difference in the embryo utilisation rates. Serum PROG levels on the day of hCG administration were negatively associated with the LBR, even in ETs with a good prognosis.Impact StatementWhat is already known on this subject? The clinical effects of PROG are still controversial. Some studies have confirmed that there was not too much association between premature elevation of PROG and live birth, some are still convincing that there is a negative correlation and will result in ART cycles of pregnancy and LBR reduction.What do the results of this study add? Our data substantiated that the high serum PROG level had the lowest LBR, IR and CPR, but the embryo utilisation rate may not have too much to do with the elevated PROG.What are the implications of these findings for clinical practice and/or further research? This study further strengthens the negative impact of elevated PROG levels on pregnancy outcomes, and suggests that frozen thawed embryo transfer appears to be a reasonable and advantageous approach for this subset of patients.

Limits imposed by the experimental design of a large prospective non-inferiority study on PGT-A invalidate many of the conclusions.

The New England Journal of Medicine recently published a large study addressing the efficacy of preimplantation genetic testing for aneuploidy (PGT-A). The 14-centre randomized control non-inferiority trial used cumulative live birth rate (CLBR) as a clinical endpoint to examine the value of PGT-A and concluded that conventional IVF was not inferior to IVF with PGT-A. Unfortunately, the experimental design was highly flawed; and in fact, the data generated in the study do not support the major conclusions presented in the publication. The embryos in each patient's three-embryo pool, which were available for transfer, were selected solely by morphology. The investigators then randomized patients to either the PGT-A group or the control group. It is important to note that PGT-A screening in the study group was done only after the embryos were selected. PGT-A was not really used in a meaningful way, which would have been for the PGT-A results to help in selecting which embryos would be in the three-embryo group. Thus, the outcomes were wholly determined prior to the study intervention. The ultimate delivery rate for each group of three embryos was determined when they were selected by morphology. The randomization, which occurred after embryo selection, would assure equal distribution of those cohorts destined to deliver and those destined to fail to the two study groups, the PGT-A and control groups. Thus, there was no potential for PGT-A to enhance selection and thus no possible way to improve the cumulative outcomes. Since there was no possible way for the control group to be inferior, the experimental design precluded any chance of evaluating the primary endpoint of the study. The primary question of the study was never evaluated. Another serious flaw was that the study was initiated prior to knowing how to interpret the data provided in the PGT-A analytical result. Specifically, the design excluded mosaic embryos from transfer despite the literature demonstrating the significant reproductive potential for these embryos. When accounting for the lost deliveries induced by this non-evidence-based decision, the expected delivery rates in the two groups become virtually identical. That is an important issue because the data from the study actually demonstrate the safety of PGT-A without diminution in outcomes from the impact of trophectoderm biopsy or the discarding of competent embryos which had wrongfully been considered aneuploid. A final serious flaw in the experimental design and interpretation of the data surrounding the issue of the miscarriage rate. The investigators noted that the miscarriage rate was lower in the PGT-A group but stated that its impact was insufficient to alter the CLBR. Of course, by design, the CLBRs were limited to being equivalent. There was no potential for enhanced outcomes in the PGT-A group and thus no possibility that the lower risk of miscarriage in the PGT-A group would raise the CLBR. The benefit of a lower miscarriage rate is real and significant. Its relevance should not be diminished based on the lack of a change in the CLBR since that was never possible in this study. The investigators of the study concluded that the CLBR with conventional ART is equivalent to that with PGT-A, but a simple review of the experiment reassigns their genuine findings to those of a safety study. Significantly, the data in the study demonstrate that the intervention of PGT-A is safe. This study neither supports nor refutes the efficacy of clinical PGT-A.

Comparison of embryo implantation potential between time-lapse incubators and standard incubators: a randomized controlled study.

RESEARCH QUESTION: What are the potential clinical benefits of embryo culture and assessment in a time-lapse incubator compared with a standard incubator using static assessment? DESIGN: This large multicentre, single-blinded, randomized controlled study included 1224 participants randomly assigned (1:1) to the time-lapse or standard incubator group. In all patients one or two embryos were transferred on day 3. The primary outcome was the implantation rate in the first embryo transfer cycle. Secondary outcomes included the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate. RESULTS: Among 1224 participants recruited, 1182 underwent embryo transfer. The number of successfully implanted embryos in the first transfer cycle was significantly higher in the time-lapse incubator group (time-lapse group: 52.35%, standard incubator group: 47.11%, P = 0.014). The implantation rate in the first embryo transfer cycle was still significantly higher in the time-lapse group than the standard incubator group after adjusting for age, body mass index, medical centre and embryo status (relative risk 1.11, 95% confidence interval 1.02-1.20, P = 0.020). However, the cumulative implantation rate, live birth rate in the first embryo transfer cycle and cumulative live birth rate were not statistically different between the groups. CONCLUSIONS: The implantation rate in the first embryo transfer cycle was significantly improved in the time-lapse group, but the effect of the time-lapse system on the cumulative implantation rate or cumulative live birth rate was not significant. The embryo assessment method offered by time-lapse systems rather than an undisturbed environment may play an important role in improving the implantation rate in the first embryo transfer cycle. These results are only applicable to young patients.