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.

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.

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.

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.

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.

Endometrial fluid aspiration immediately prior to embryo transfer does not affect IVF/vitrified-warmed embryo transfer outcomes - a prospective matched cohort study.

RESEARCH QUESTION: Does the endometrial aspiration of ultrasound-invisible fluid immediately preceding embryo transfer affect IVF/vitrified-warmed embryo transfer outcomes? DESIGN: A prospective matched cohort study was conducted in 96 women and 96 control participants to assess the effect on pregnancy outcomes of endometrial aspiration performed immediately before embryo transfer. This study was carried out at a university-affiliated assisted reproductive medical centre between January 2019 and December 2019. Patients were divided into two groups. The EA group had cycles with endometrial aspiration of ultrasound-invisible fluid performed before embryo transfer and the non-EA group featured cycles without endometrial aspiration. The EA group was matched by propensity score with the non-EA group in a 1:1 ratio. The EA group consisted of 99 participants before and 96 participants after propensity score matching. There were 203 and 96 participants in the non-EA group before and after propensity score matching. RESULTS: No significant differences were detected in the baseline characteristics and cycle characteristics of the EA and non-EA groups. No significant between-group differences were found in reproductive outcomes in the overall population. Subgroup analysis of blastocyst transfer cycles showed the implantation rate was significantly higher in the EA group (61 women per group, 57.1% versus 40.8%, relative risk 1.40, 95% confidence interval 1.04-1.88; P = 0.022). Live birth rate, clinical pregnancy rate, ongoing pregnancy rate and multiple pregnancy rate were not different among the groups. CONCLUSIONS: Endometrial aspiration immediately preceding embryo transfer does not affect IVF/vitrified-warmed embryo transfer outcomes. Interestingly, it might improve the vitrified-warmed blastocyst implantation rate. Randomized controlled trials are needed to confirm this result.

Systematic review and meta-analysis for impacts of oral antibiotic treatment on pregnancy outcomes in chronic endometritis patients.

BACKGROUND: Chronic endometritis is a persistent inflammatory condition of the endometrium that negatively affects pregnancy outcomes. The Centers for Disease Control and Prevention guidelines recommend oral antibiotic treatment for chronic endometritis. However, a recent randomized controlled trial concluded that it was unclear whether antibiotic treatment improved pregnancy outcomes. Hence, we performed a systematic review and meta-analysis to validate the impact of oral antibiotic treatments on pregnancy outcomes among patients with chronic endometritis. METHODS: We systematically searched the PubMed, Scopus, Ichushi, CINAHL, and EMBASE databases until May 2021. We compared the pregnancy outcomes in patients with chronic endometritis with and without antibiotic treatment. We then focused on the implantation rate, intrauterine pregnancy rate, and live birth rate to evaluate pregnancy outcomes. RESULTS: Seven studies were included in the meta-analysis. Three hundred seventy-two patients were treated with antibiotics, while 1024 patients were not treated with antibiotics. Various antibiotic regimens were administered during the study period [14-21 days]. Antibiotic treatments for chronic endometritis did not increase the implantation rate (odds ratios [OR] 1.02, 95% confidence interval [CI], 0.78-1.33), intrauterine pregnancy rate (OR 1.08, 95% CI 0.72-1.63), or live birth rate (OR 1.13, 95% CI 0.65-1.97). CONCLUSIONS: Our meta-analysis proved that oral antibiotic treatment did not improve pregnancy outcomes in patients with chronic endometritis. Accordingly, further studies are needed to elucidate the treatment to improve pregnancy outcomes.

Evaluation of the relationship between serum TSH levels and pregnancy outcomes of IVF/ICSI patients in follicular phase long-acting long protocol.

ObjectiveTo investigate whether TSH levels are associated with the pregnancy outcomes of patients in the follicular phase long-acting long protocol of IVF/ICSI.MethodsThis was a single-central, retrospective study which was conducted in the Reproductive Medicine Center, Renmin Hospital of Wuhan University from February 2019 to April 2021. A total number of 773 patients underwent the follicular phase long-acting long protocol during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment were divided into Group A (0.5 mIU/L ≤ TSH ≤2.5 mIU/L, n = 463) and Group B (2.5 mIU/L < TSH≤ 4.5 mIU/L, n = 310) according to their serum TSH levels. The clinical data and pregnancy outcomes were compared between the two groups. The possible relationship between TSH levels and pregnancy outcomes in people who performed follicular phase long-acting long protocol was investigated.ResultsThe proportion of patients with infertility due to ovulation disorders was significantly greater in Group B than in Group A (p = 0.036). The duration of Gn of Group B was significantly longer than that of Group A (p = 0.001). The Gn dose of Group B was significantly larger than that of Group A (p = 0.002). Besides, the implantation rate and miscarriage rate of embryos transferred on D3 were significantly higher in Group B than that of Group A (p = 0.033, p = 0.026 respectively).ConclusionsThe higher implantation and miscarriage rates of D3 of IVF/ICSI in the follicular phase long-acting long protocol may be related to higher serum TSH levels.

Comparison of ICSI and conventional IVF in non-male factor patients with less than four oocytes.

BACKGROUND: We aimed to analyse our clinical results for a particular subgroup of patients with poor ovarian response (POR) to clarify if lower number of oocytes is a drawback for proceeding to C-IVF. MATERIALS AND METHODS: In this retrospective study, patient files of all couples (#1733) who underwent oocyte retrieval between January 2017 and December 2019 were reviewed and 191 cases diagnosed with non-male factor infertility in which ≤ 3 cumulus-oocyte complexes available for fertilisation were analysed. Exclusion criteria were: woman age > 42, patients with a history of previous ART trial, prenatal genetic testing cycles and couples undergoing total cryopreservation for any indication. Three groups were constructed depending on the method of fertilisation and on semen quality as follows: IVF non-male factor (Group 1, n = 77); ICSI non-male factor (Group 2, n = 65); ICSI male factor-ICSI/MF n = 49 according to WHO reference values. Main outcome parameters were: fertilisation rate, implantation rate and live birth rate. RESULTS: Fertilisation rate per collected COC was significantly higher in group 1 compared to the other two groups (85.68%, 72.58%, 73.33% respectively, p = 0.004). FR per inseminated oocyte also tended to be higher in group 1 but not reaching a statistically significant level. Both techniques yielded similar implantation rates (20.42%, 28.49%, 23.33% respectively, p = 0.407) and live birth rates (26.8%, 30.6%, 31.1%, respectively, p = 0.643). CONCLUSION: In the presence of normal semen parameters, low egg number is not an indication to perform ICSI. The choice of fertilisation method should be based primarily on semen quality, in combination with the patient's previous history regardless of the ovarian reserve.

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.

Positive effect of a new supplementation of vitamin D3 with myo-inositol, folic acid and melatonin on IVF outcomes: a prospective randomized and controlled pilot study.

To assess whether oral supplementation of vitamin D3, myo-inositol, folic acid and melatonin affects IVF outcomes. One hundred and twenty consecutive infertile women attending IVF treatment were 1:1 randomly distributed in two groups. Women in group A (control) were assigned to receive myo-inositol, alpha-lactalbumin and folic acid in the morning, and myo-inositol, folic acid and melatonin in the evening. Women in group B (treated) were assigned to receive analogous treatment, with the addition of cholecalciferol (vitamin D3) in the evening from the early beginning of the luteal phase. 50 patients in group A and 50 in group B underwent blastocyst transfer and were considered in the statistical analysis. Vitamin D3 levels significantly increased after 45 days of treatment: 33.2 ng/ml in group B Vs. 24.3 ng/ml in group A (p < .0001). The implantation rate increased as well: 37.1% in group B Vs. 19.2% in group A (p < .0151). Overall, the results indicate that increased vitamin D3 levels positively correlate with the implantation rate in IVF. Because of the low number of participants, these findings need to be confirmed with larger cohorts of patients.

The Effect of Sildenafil Citrate on Poor Endometrium in Patients Undergoing Frozen-Thawed Embryo Transfer following Resection of Intrauterine Adhesions: A Retrospective Study.

BACKGROUND: The recent studies have shown that sildenafil citrate can enhance estrogen-induced proliferation of the endometrium in infertile women. OBJECTIVE: This study was aimed to investigate whether sildenafil citrate could affect pregnancy outcomes in infertile women receiving frozen-thawed embryo transfer (FET) after resection of intrauterine adhesions (IUAs). MATERIALS AND METHODS: A total of 310 subjects who met the inclusion criteria were recruited and divided into the control group (group A) and the sildenafil citrate group (or the SC group, group B). The 2 groups were, respectively, divided into 2 subgroups based on the severity of reformed adhesions: (1) group A1 (with mild IUAs) and group A2 (with moderate to severe IUAs) and (2) group B1 (with mild IUAs) and group B2 (with moderate to severe IUAs). Therapeutic effects of sildenafil citrate on the cases were evaluated after resection of IUAs during FET cycles. Endometrial thickness, endometrial pattern, and pregnancy outcomes were evaluated and compared between the 2 groups. RESULTS: There was no significant difference in the number of embryos transferred between the 2 groups. The endometrial thickness in group B (0.80 [0.68-0.90] cm) was significantly higher than that in group A (0.73 [0.35-0.80] cm). Besides, the biochemical pregnancy rate, clinical pregnancy rate, and live birth rate (LBR) were 71.60, 50.83, and 39.17% in group B, which were significantly higher than those in group A, namely, 57.36, 34.73, and 23.68%, respectively (p < 0.05). The univariate analysis and multivariate logistic regression showed that the LBR in either subgroups of group B after vaginal sildenafil treatment was significantly higher than that in the corresponding control group (p < 0.05). CONCLUSIONS: It was observed that the administration of sildenafil citrate during FET could effectively improve the poor endometrial conditions after FET following the resection of IUAs.

Competence of embryos showing transient developmental arrest during in vitro culture.

PURPOSE: In vitro developing embryos may apparently show no developmental progress during 24 h and resume their development up to the blastocyst stage. The present study was conducted to assess their ability to implant and to give rise to a live birth when replaced at day 5 (fresh or vitrified/warmed) as compared to continuously developing embryos. METHODS: Embryo development follow-up and grade were prospectively recorded in a photo database. The studied period was from April 2011 to July 2017. The studied embryos included transient arrested embryos (TAE) that showed the same developmental stage at two subsequent observations, i.e. between day 2 and day 3 (d2 and d3), between day 3 and day 4 (d3 and d4) and between day 4 and day 5 (d4 and d5). TAE were compared to continuously developing embryos (CDE). Elective day 5 embryo transfers were performed. RESULTS: Woman age was higher in TAE (34.3±3.9) than in CDE (32.9±4.8) (p<0.01). TAE were more frequently (63.1%) observed after ICSI than after conventional IVF (55.9%) (p<0.01). Implantation rate was reduced in TAE as compared to CDE, after both fresh (10.0% vs 23.8% [p<0.01]) and vitrified/warmed (12.9% vs 19.0% [p<0.01]) embryo transfers. Delivery rate was also lower after the transfer of fresh (8.3% vs 19.4% [p<0.01]) and vitrified/warmed (8.5% vs 14.1% [p<0.01]) TAE as compared to CDE. Implantation and delivery rates were not statistically different whether embryo arrested between day 2 and day 3 (d2 and d3), between day 3 and day 4 (d3 and d4) or between day 4 and day 5 (d4 and d5). CONCLUSION: TAE may be considered for transfer at a lower priority than CDE and associated with inferior prognosis than CDE.

Improving the clinical outcomes by extended culture of day 3 embryos with low blastomere number to blastocyst stage following frozen-thawed embryo transfer.

PURPOSE: This study aimed to investigate whether the extended culture of day 3 (D3) embryos with low blastomere number to blastocyst following frozen-thawed embryo transfer improved the clinical outcomes. METHODS: This was a retrospective study of clinical data of women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in the Tangdu Hospital. The patients were divided into groups with 4-5, 6, 7-9 and > 9 cells based on the blastomere number of D3 embryos. The clinical outcomes were compared. RESULTS: In fresh transfer cycles, the implantation and clinical pregnancy rates significantly decreased, while the abortion rate significantly increased in the groups with 4-5 and 6 cells compared with those with 7-9 and > 9 cells. In frozen-thawed transfer cycles, the clinical pregnancy and implantation rates for a single blastocyst transfer cycle showed no significant differences in the groups with 4-5 and 6 cells compared with those with 7-9 and > 9 cells. However, the abortion rate was significantly higher in the group with 4-5 cells than in that with 7-9 and > 9 cells. In the double blastocyst transfer cycle, the clinical pregnancy rate showed no significant differences among the groups with 4-5, 6, and 7-9 cells. CONCLUSION: The implantation and clinical pregnancy rates of D3 embryos with 6 cells significantly decreased; these embryos were not considered as high-quality embryos. Extended culture of D3 embryos with ≤ 6 blastomeres to blastocysts, particularly 6-cell embryos, resulted in a similar clinical pregnancy rate as that of blastocysts derived from D3 embryos with ≥ 7 blastomeres.

[Transcutaneous electrical acupoint stimulation improves pregnancy outcomes of in vitro fertilization- embryo transfer : A meta-analysis of randomized controlled trials].

OBJECTIVE: To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on the pregnancy outcomes of in vitro fertilization-embryo transfer (IVF-ET) based on the available clinical evidence. METHODS: We searched PubMed, MEDLINE, EMBASE, Cochrane Library, CNKI, VIP, CBM and Wanfang Database up to February 2021 for published randomized controlled trials (RCT) relevant to TEAS for the improvement of the pregnancy outcomes of IVF-ET. We performed literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria, followed by a meta-analysis with the RevMan 5.3 software. RESULTS: A total of 2 206 cases of IVF-ET from 9 RCTs were included, 1 018 in the TEAS group and 1 188 in the control. The clinical pregnancy rate was significantly higher in the TEAS than in the mock TEAS and non-TEAS control groups (RR = 1.85, 95% CI: 1.42－2.42, P < 0.001; RR = 1.23, 95% CI: 1.10－1.39, P = 0.0004), and so was it before and after oocyte retrieval (RR = 1.50, 95% CI: 1.03－2.17, P = 0.03; RR = 1.47, 95% CI: 1.12－1.92, P = 0.005). The TEAS group also showed dramatically improved embryo implantation rate (RR = 1.49, 95% CI: 1.24－1.79, P < 0.0001) and live birth rate (RR = 1.44, 95% CI: 1.04－1.98, P = 0.03) compared with the control. CONCLUSIONS: As a safe and non-invasive treatment, TEAS can significantly improve the pregnancy outcomes of IVF-ET, with definite effectiveness. /.

Value of transferring embryos derived from monopronucleated (1PN) zygotes at the time of fertilization assessment.

This paper is a retrospective analysis of the sole transfer of monopronucleated zygotes (1PN) embryos both in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) to determine the value of transferring embryos formed from 1PN. In fresh cycles, 1PN cleavage-stage embryos (1PN cleavage fresh) were transferred. In frozen-thawed cycles, 1PN blastocyst-stage embryos (1PN blast frozen) were transferred. We used comparison groups: for fresh cycles, 2PN cleavage-stage embryos (2PN cleavage fresh) were transferred; and for frozen-thawed cycles, 2PN blastocyst-stage embryos (2PN blast frozen) were transferred. Comparison groups were matched for cycle and patient characteristics to the 1PN group. Finally, for fresh cycles, live birth rates (LBR) in the 1PN cleavage group were significantly lower than those in 2PN cleavage group, both for IVF [LBR = 7.64% vs. pregnancy rate (PR) = 22.12%, P = 0.003, respectively] and ICSI (LBR = 0% vs. LBR = 20.00%, P < 0.001, respectively). For frozen-thawed IVF cycles, the PR in the 1PN blastocyst group were comparable with those of the 2PN blastocyst group (1PN: LBR = 33.14% vs. 2PN: LBR = 37.24%, P = 0.289, respectively), while in ICSI, the PR in the 1PN blastocyst group were lower than those in the 2PN blastocyst group (LBR = 15.25% vs. LBR = 40.68%, P = 0.002, respectively). So, for IVF, blastocyst culture was capable of selecting normal 1PN embryos for transfer and achieves satisfying outcomes. However, for ICSI, blastocyst culture was not effective enough to eliminate abnormal embryos and 1PN embryo transfer needed to be treated with caution.

Effect of endometrial injury during menstruation on clinical outcomes in frozen-thawed embryo transfer cycles: A randomized control trial.

AIM: To explore the clinical effect of endometrial injury (EI) on the third day of the menstrual cycle before frozen-thawed embryo transfer (frozen-thawed ET) on patients experienced two or more implantation failures. METHODS: A total of 200 patients who suffered at least two failed hormone-replacement therapies and frozen-thawed ET were randomly divided into two groups: EI group and control group (n = 100 in each group). Patients in the EI group received local EI with a Pipelle catheter on the third day of the menstrual cycle before frozen-thawed ET. Primary outcomes were live birth, clinical pregnancy and implantation rates. Secondary outcomes were biochemical, multiple and ectopic pregnancy rates and abortion rates. RESULTS: The rate of live birth in EI group (51.00%) was significantly higher than that of control group (36.00%) (P = 0.032). Clinical pregnancy and implantation rates in EI group were significantly higher comparing to control group (64.00% vs 48.00%, P = 0.023 and 46.74% vs 30.11%, P = 0.001). The rate of multiple pregnancy in EI group (37.50%) was significantly higher than that of control group (18.75%) (P = 0.031). No significant difference in ectopic pregnancy rate and abortion rate was observed between EI group and control group. CONCLUSION: Applying EI to patients experienced two or more implantation failures on the third day of the menstrual cycle before frozen-thawed ET can improve clinical outcomes.

Evaluation of the endometrial receptivity assay and the preimplantation genetic test for aneuploidy in overcoming recurrent implantation failure.

PURPOSE: To evaluate the clinical usefulness of the endometrial receptivity array (ERA) and the preimplantation genetic test for aneuploidy (PGT-A) in patients with severe and moderate recurrent implantation failure (RIF). DESIGN: A retrospective multicenter cohort study was conducted in patients who failed to achieve implantation following transfer of 3 or more or 5 or more embryos in at least three single embryo transfers; patients were classified as moderate or severe RIF, respectively. Patients with previous RIF were compared based on the testing they received: PGT-A, ERA, or PGT-A+ERA versus a control group with no testing. Mean implantation rate and ongoing pregnancy rates per embryo transfer were considered primary outcomes. Multiple logistic regression analysis was performed and adjusted ORs were calculated to control possible bias. RESULTS: Of the 2110 patients belonging to the moderate RIF group, those who underwent transfer of euploid embryos after PGT-A had a higher implantation rate than those who did not. Additionally, the PGT-A group had a significantly higher rate of ongoing pregnancy. The same outcomes measured for the 488 patients in the severe RIF group did not reveal any statistically significant improvements. The use of the ERA test did not appear to significantly improve outcomes in either group. CONCLUSIONS: PGT-A may be beneficial for patients with moderate recurrent implantation failure but not for severe cases. At its current level of development, ERA does not appear to be clinically useful for patients with RIF.