Good Quality Blastocysts Research Articles

Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations.

To compare cumulative live birth rate (LBR) between progestin-primed ovarian stimulation (PPOS) and GnRH antagonist protocols of preimplantation genetic testing (PGT) cycles in different populations. This was a retrospective cohort study. A total of 865 patients were enrolled and separate analyses were performed for three populations: 498 patients with predicted normal ovarian response (NOR), 285 patients with PCOS, and 82 patients with predicted poor ovarian response (POR). The primary outcome was cumulative LBR for one oocyte retrieval cycle. The results of response to ovarian stimulation were also investigated, including numbers of oocytes retrieved, MII oocytes, 2PN, blastocysts, good-quality blastocysts, and usable blastocysts after biopsy, as well as rates of oocyte yield, blastocyst formation, good-quality blastocysts, and moderate or severe OHSS. Univariable and multivariable logistic regression analyses were used to identify potential confounders that may be independently associated with cumulative live birth. In NOR, the cumulative LBR of PPOS protocol was significantly lower than that of GnRH antagonists (28.4% vs. 40.7%; P=0.004). In multivariable analysis, the PPOS protocol was negatively associated with cumulative LBR (adjusted OR=0.556; 95% CI, 0.377-0.822) compared to GnRH antagonists after adjusting for potential confounders. The number and ratio of good-quality blastocysts were significantly reduced in PPOS protocol compared to GnRH antagonists (2.82 ± 2.83 vs. 3.20 ± 2.79; P=0.032 and 63.9% vs. 68.5%; P=0.021), while numbers of oocytes, MII oocytes and 2PN did not show any significant difference between GnRH antagonist and PPOS protocols. PCOS patients had similar outcomes as NOR. The cumulative LBR of PPOS group appeared to be lower than that of GnRH antagonists (37.4% vs. 46.1%; P=0.151), but not significantly. Meanwhile, the proportion of good-quality blastocysts in PPOS protocol was also lower compared to GnRH antagonists (63.5% vs. 68.9%; P=0.014). In patients with POR, the cumulative LBR of PPOS protocol was comparable to that of GnRH antagonists (19.2% vs. 16.7%; P=0.772). There was no statistical difference in the number and rate of good-quality blastocysts between the two protocols in POR, while the proportion of good-quality blastocysts appeared to be higher in PPOS group compared to GnRH antagonists (66.7% vs. 56.3%; P=0.182). In addition, the number of usable blastocysts after biopsy was comparable between the two protocols in three populations. The cumulative LBR of PPOS protocol in PGT cycles is lower than that of GnRH antagonists in NOR. In patients with PCOS, the cumulative LBR of PPOS protocol appears to be lower than that of GnRH antagonists, albeit lacking statistical difference, whereas in patients with diminished ovarian reserve, the two protocols were comparable. Our findings suggest the need for caution when choosing PPOS protocol to achieve live births, especially for normal and high ovarian responders.

Effects of high-altitude hypoxia on embryonic developmental potential in women undergoing IVF/ICSI procedures.

In this study we examined the effects of long-term adaptation to hypoxia on embryonic developmental potential of oocytes collected from women who underwent IVF/ICSI procedures. We selected young infertile women who lived in a low-altitude normoxic environment (n = 80, altitude < 500m) or high-altitude hypoxic environment (n = 100, altitude > 2500m) for a lengthy period of time and who planned to undergo IVF/ICSI procedures. We then determined the baseline reproductive hormone levels, gonadotropin (Gn) dose and Gn treatment duration during controlled ovarian hyperstimulation (COH), number of oocytes retrieved, number of mature oocytes, oocyte maturation rate, fertilization rate, normal fertilization rate, day (D3) embryo-formation rate, blastocyst formation rate, good-quality formation rate, D5 blastocyst formation rate, and D6 blastocyst formation rate between the two groups. Compared with the low-altitude normoxic group, the various reproductive hormone markers of women in the high-altitude hypoxia group were lower, with LH and T levels significantly reduced (P < 0.05) at 72.29 and 72.44% of the normoxic group, respectively (normoxic group vs. hypoxic group, 5.24 ± 1.61 vs. 3.79 ± 1.21; 0.61 ± 0.18 vs. 0.42 ± 0.15; P < 0.05). During ovarian hyperstimulation, a greater Gn dose and longer Gn treatment duration were required for the hypoxic group to complete COH (normoxic group vs. hypoxic group, 2152.08IU ± 52.76 vs. 2622.09IU ± 123.28; 9.96days ± 1.27 vs. 11.54days ± 1.34, respectively; P < 0.05). The fertilization, cleavage, and D3 embryo-formation rates tended to be higher in the normoxic group than in the hypoxic group (P > 0.05); while the normal fertilization rate tended to lower than in the hypoxic group (P > 0.05). When we conducted an analysis of blastocyst formation rates at different timepoints, we ascertained that the blastocyst formation rate, usable blastocyst rate, and good-quality blastocyst rate of the hypoxic group were all lower than in the normoxic group, with the difference in usable blastocyst rate the most highly significant (normoxic group vs. hypoxic group, 75.31 ± 5.53 vs. 56.04 ± 6.10%, respectively; P < 0.05). In addition, the D5 and D6 blastocyst-formation rates in the normoxic group were slightly higher than in the hypoxic group, revealing that not only were fewer blastocysts formed in the hypoxic group but that there was also a delay in blastocyst formation. In young women undergoing IVF/ICSI treatment, long-term hypoxic adaptation required augmented Gn dose and Gn treatment duration during COH, and blastocyst developmental potential was also attenuated.

Прогнозирование эффективности эмбриологического этапа вспомогательных репродуктивных технологий по микробному составу эякулята

Obtaining enough good and excellent quality embryos is one of the key factors for achieving pregnancy using assisted reproductive technologies. This work was aimed at developing a mathematical model for predicting good and excellent quality embryos based on semen microbiota assessment in normozoospermia. The study included 127 men whose semen was used for in vitro fertilization (IVF). Patients were divided into 2 groups depending on the proportion of good-quality blastocyst developed on the 5th day of culturing (good-quality blastocyst development rate, GBDR). The 1st group included 57 patients with GBDR ≥ 40%, the 2nd group included 70 patients with GBDR &lt; 40%. All patients’ semen was assessed at the day of fertilization. Semen parameters were evaluated in accordance with the WHO standards and semen microbiota composition was determined by means of real-time PCR. Discriminant analysis was used for development of the prognostic model. We developed a method for predicting efficiency of the embryological IVF stage in normozoospermia: EGO-Pro-N prognostic index (Embryos of GOod and Excellent quality Prognosis in Normozoospermia). If the EGO-Pro-N value is greater than 0.212, the probability of receiving GBDR ≥ 40% is low. Conversely, if the EGO-Pro-N value is less than or equal to 0.212, the probability is high. Sensitivity and specificity of the method were 71.9% and 70.0% respectively, accuracy was 70.9%. The developed model allows us to predict good and excellent quality embryos based on comprehensive semen microbiota assessment in normozoospermia before IVF.

A new insight into the impact of systemic lupus erythematosus on oocyte and embryo development as well as female fertility.

Systemic lupus erythematosus (SLE) is often associated with adverse reproductive outcomes. But it's currently unclear regarding the role of SLE in oocyte and embryonic development. Also, it's controversial whether SLE has an adverse effect on fertility. There is a lack of comprehensive understanding and assessment of fertility in patients with SLE. This study was aim to investigate oocyte and embryonic development as well as ovarian reserve, and clinical outcomes in SLE patients during in vitro fertilization (IVF) treatment. By combining data on embryonic and gamete development in SLE patients, we hope to provide new insights into a comprehensive assessment of fertility in SLE patients. In this study, we collected data from 34 SLE patients who were previously diagnosed and in remission for a total of 44 IVF cycles and matched 102 infertile women with a total of 148 IVF cycles by Propensity Score Matching (PSM) of 1:3 ratio. We then evaluated baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical outcomes between the two groups. After PSM matching, baseline characteristics including age, infertility types, and duration, as well as infertility causes overall coincided between the two groups. Anti-müllerian hormone (AMH) was significantly lower in the SLE group vs comparison (1.9 vs. 3.3 ng/mL, P=0.001). The SLE group performed a significant reduction in available embryo rate (76.6% vs. 86.0%, P=0.001), good-quality blastocyst formation rate (35.1% vs. 47.0%, P=0.003), and blastocyst formation rate (51.0% vs. 67.7%, P=0.001) compared to the comparison. As for clinical outcomes, the implantation rate in the SLE group was notably lower (37.9% vs. 54.9%, P=0.022). The CLBR following every embryo-transfer procedure was distinctly lower (41.2% vs 64.7%, P=0.016) in the SLE group vs comparison. Also, the conservative and optimal CLBRs following every complete cycle procedure were significantly reduced in the SLE group vs the comparison (P=0.001, both). Patients with SLE present worse outcomes in oocyte and embryonic development, thus yielding compromised female fertility and clinical pregnancy. Individualized fertility assessment and early fertility guidance are necessary for these special groups.

Advanced Paternal Age Affects the Sperm DNA Fragmentation Index and May Lead to Lower Good-quality Blastocysts.

Several studies show reductions in some seminal parameters in aged men and describe them as a consequence of many age-dependent changes in male organisms. This study aims to evaluate the impact of age on seminal parameters, particularly the DNA fragmentation index (DFI), and outcomes after in vitro fertilization (IVF) cycles. This is a retrospective study that includes 367 patients who underwent sperm chromatin structure assay testing between 2016 and 2021. The participants were split into three groups according to age: < 35years (younger group, n = 63), 35-45years (intermediate group, n = 227), and ≥ 45years (older group, n = 77). The mean DFI (%) was compared. Among all patients, 255 received IVF cycles after DFI evaluation. For these patients, the sperm concentration, motility, and volume, as well as the fertilization rate, mean oocyte age, and good-quality blastocyst formation rate, were analyzed. One-way ANOVA was applied. The older group showed a significantly higher sperm than did the younger group (28.6% vs. 20.8% p = 0.0135). Despite not presenting a significant difference, the DFI level tends to be inversely related to good-quality blastocyst formation since the oocyte age was similar between the groups (32.0 v.s 33.6 vs. 32.3years, respectively, p = 0.1183). Among aged men, the sperm DFI level is increased but other seminal parameters are not modified. Considering that men with a high sperm DFI can present some degree of infertility due to high sperm chromatin damage, male age should also be considered a limiting factor of IVF.

Does embryo quality at transfer affect obstetric outcomes and placental findings?

Do obstetric outcomes and placental findings in pregnancies conceived with IVF vary according to embryo quality? Pregnancies following the transfer of lower-quality embryos were associated with a higher rate of low-lying placentas and several adverse placental lesions. A few studies have shown reduced pregnancy and live births rates with poor-quality embryo transfer, yet with comparable obstetric outcomes. None of these studies included placental analysis. A retrospective cohort study of 641 deliveries of IVF attained pregnancies between 2009 and 2017 was carried out. Live singleton births after IVF with a single blastocyst transfer at a university-affiliated tertiary hospital were included. Excluded were cycles of oocyte recipients and IVM. We compared pregnancies following the transfer of a poor-quality blastocyst (poor-quality group) or a good-quality blastocyst (controls, good-quality group). During the study period, all placentas from complicated and uncomplicated pregnancies were sent to pathology. Primary outcomes were placental findings, including anatomic, inflammatory, vascular malperfusion, and villous maturation lesions, categorized according to the Amsterdam Placental Workshop Group Consensus. Secondary outcomes included obstetric and perinatal outcomes, adjusted for diminished ovarian reserve, fresh versus frozen transfer, and neonatal gender (as indicated by univariable analysis). A total of 132 deliveries in the poor-quality group were compared to 509 controls. A diagnosis of diminished ovarian reserve was more common in the poor-quality group than in the control group (14.3% versus 5.5%, respectively, P < 0.001) and more pregnancies in the poor-quality group were following frozen embryo transfer. After adjustment for confounders, poor-quality embryos were associated with a higher rate of low-lying placentas [adjusted odds ratio (aOR) 2.35, 95% CI 1.02-5.41, P = 0.04] and placentas with a higher rate of villitis of unknown etiology (aOR 2.97, 95% CI 1.17-6.66, P = 0.02), distal villous hypoplasia (aOR 3.78, 95% CI 1.20-11.38, P = 0.02), intervillous thrombosis (aOR 2.41, 95% CI 1.39-4.16, P = 0.001), multiple maternal malperfusion lesions (aOR 1.59, 95% CI 1.06-2.37, P = 0.02), and parenchymal calcifications (aOR 2.19, 95% CI 1.07-4.46, P = 0.03). The study is limited by its retrospective design and the utilization of two grading systems during the study period. In addition, the sample size was limited to detect differences in outcomes of rarer occurrences. The placental lesions demonstrated in our study imply an altered immunological response to the implantation of poor-quality embryos. Yet, these findings were not associated with additional adverse obstetric outcomes and merit reaffirmation in a larger cohort. Overall, the clinical findings of our study are reassuring to clinicians and patients for whom the transfer of a poor-quality embryo is necessary. No external funding was obtained for this study. The authors declare no conflict of interest. N/A.

Smooth endoplasmic reticulum cluster presence does not affect embryo ploidy.

We examined the impacts of the smooth endoplasmic reticulum cluster (sERC) presence on embryonic development and blastocyst ploidy. Patients who underwent oocyte retrieval from January 2019 to November 2021 were included in the study. We classified the oocytes into three groups: normal oocytes in the sERC ( -) cycle, normal oocytes in the sERC ( +) cycle, and sERC ( +) oocytes. Next, the levels of serum estradiol, progesterone, anti-Mullerian hormone, follicle-stimulating hormone, and human menopausal gonadotropin were compared between the groups. Moreover, fertilization, degeneration, and abnormal fertilization rates were compared between groups. To investigate developmental outcomes, the blastocyst and good-quality blastocyst rates after intracytoplasmic sperm injection were compared. The quality of the transferred blastocysts was evaluated at follow-up. Additionally, embryos were submitted for next-generation sequencing analysis to examine the effect of sERC presence on ploidy. The sERC ( +) group had significantly higher serum estradiol, serum progesterone, and serum anti-Mullerian hormone concentrations compared to those in the sERC ( -) group (P < 0.01). The abnormal fertilization rate was higher in the sERC ( +) cycle-sERC ( +) oocyte group (16.1%; 37/230) than in the sERC ( +) cycle-normal oocyte (6.2%; 63/971) and sERC ( -) cycle-normal oocyte groups (7.1%; 174/2467) (P < 0.01). After embryo transfer, nine women gave birth, and no confirmed congenital anomalies were observed. There was no significant difference in ploidy between the sERC ( +) and sERC ( -) groups. The occurrence rates of embryos with euploidy were similar between the sERC ( +) and sERC ( -) groups.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies. Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases. There are currently no effective treatments for patients with unexplained RIF. Since the maternal immune system is intricately involved in mediating endometrial receptivity and embryo implantation, both insufficient and excessive endometrial inflammatory responses during the window of implantation are proposed to lead to implantation failure. Recent strategies to improve conception rates in RIF patients have focused on modulating maternal immune responses at implantation, through either promoting or suppressing inflammation. Unfortunately, there are no validated, readily available diagnostic tests to confirm immune-mediated RIF. As such, immune therapies are often started empirically without robust evidence as to their efficacy. Like other chronic diseases, patient selection for immunomodulatory therapy is crucial, and personalized medicine for RIF patients is emerging. As the literature on the subject is heterogenous and rapidly evolving, we aim to summarize the potential efficacy, mechanisms of actions and side effects of select therapies for the practicing clinician.

Is it necessary for young patients with recurrent implantation failure to undergo preimplantation genetic testing for aneuploidy?

To determine whether preimplantation genetic testing for aneuploidy (PGT-A) can improve the pregnancy outcomes of patients aged under 38 years who have a history of recurrent implantation failure(RIF). Retrospective cohort study. We retrospectively studied the pregnancy outcomes of RIF patients aged under 38 years from January 2017 to December 2021.178 patients were divided into two groups according to whether they underwent PGT-A: the PGT-A group(n=59)and the control group(n=119).In the PGT-A group, we compared the euploidy rate of the different quality and developmental rate blastocysts. In both groups,the patients were the first frozen-thaw single blastocysts transfer after the diagnosis of RIF. Among the pregnancy outcomes, the clinical pregnancy rate was assessed as the primary outcome. The spontaneous abortion rate and ongoing pregnancy rate were the secondry outcomes. The generalized estimation equation was used to adjust for the blastocysts derived from the same patients. Multivariate logistic analysis models were used to compare the pregnancy outcomes between the two groups. In the PGT-A group, 293 blastocysts obtained from59 patients underwent PGT-A. The proportions of euploidy, aneuploidy and mosaic blastocysts were 56.31%, 25.60% and 18.09%, respectively. A comparison of the euploidy rates of different quality blastocysts showed that the rate of good-quality blastocysts was significantly higher than that of poor-quality blastocysts (67.66% vs 46.88%; odds ratio [OR], 2.203; 95%confidence interval[CI], 0.943-3.612; P=0.002). However, no significant difference was observed in the different developmental rates blastocysts. Compared with Day 5 blastocysts, the euploidy rates of Day 6 and Day 7 blastocysts were not significantly different(61.54%vs51.91%; OR,0.945; 95%CI, 0.445-2.010; P=0.884; and 61.54%vs47.37%; OR, 1.106; 95%CI, 0.774-1.578; P=0.581, respectively).As for the pregnancy outcomes, the clinical pregnancy rate was significantly increase after the use of PGT-A compared with the control group(71.19%vs56.30%; OR, 0.538; 95%CI, 0.262-1.104; P=0.039). However, the spontaneous abortion rates and ongoing pregnancy rates were not significantly different between the control and PGT-A groups (21.43% vs 19.40%; aOR,0.727; 95%CI,0.271-1.945; P=0.525; and55.93% vs 45.38%; aOR, 0.649; 95%CI, 0.329-1.283; P = 0.214,respectively). PGT-A improved the clinical pregnancy rate after blastocyst transfer in RIF patients aged under 38 years.

No advantage of single day 6 good-quality blastocyst transfer versus single day 5 poor-quality blastocyst transfer in frozen-thawed cycles stratified by age: a retrospective study

BackgroundBlastocyst developmental speed, morphological grading and patient age are associated with pregnancy outcomes of frozen-thawed cycles. This study aimed to compare the clinical and neonatal outcomes between poor-quality D5 blastocysts and good-quality D6 blastocysts stratified by patient age.MethodsA total of 1,623 cycles were divided into two groups: group A (n = 723) received one D5 poor-quality blastocyst; group B (n = 900) received one D6 good-quality blastocyst. Pregnancy and neonatal outcomes were compared among the four groups stratified by 35 years of age.ResultsWhen patients were in the same age group, there was no significant difference in terms of age, body mass index, infertility duration, infertility type, fertilization method, proportion of endometrial preparation protocols, and endometrial thickness between D5 poor-quality and D6 high-quality blastocysts groups. Live birth rate of D5 poor-quality blastocysts was higher than that of D6 high-quality blastocysts for patients aged < 35 years (35.48% vs. 31.13%, p > 0.05), but there was no statistical difference. The same trend was showed for patients aged ≥ 35 years (29.09% vs. 21.28%, p > 0.05). Moreover, when patients were in the same age category, there was no significant difference in terms of gestational age, birth weight, birth height, and rates of preterm birth, low birth weight, and very low birth weight between groups A and B.ConclusionsThe preferential selection of poor-quality D5 blastocysts for transfer compared to high-quality D6 blastocysts is recommended, especially for advanced age patients. Single good-quality D6 blastocyst transfer can be considered for the acceptable live birth rate.

Double-edged sword: effects of human sperm reactive oxygen species on embryo development in IVF cycles

BackgroundThe exact role of sperm reactive oxygen species (ROS) in early embryo development has yet to be fully identified, and most of existing research did not differentiate female infertility factors, ignoring the importance of oocyte quality in embryo development and the large differences in oocyte quality in women with infertility of different etiologies. And there has been no relevant report on whether different types of sperm ROS have distinct effects on embryo development. This study aimed to study the impact of selected sperm ROS, namely, sperm mitochondrial ROS (mROS) and hydrogen peroxide, on human embryo development after conventional in vitro fertilization (IVF) cycles in patients with normo-ovulatory infertility vs. anovulatory infertility.MethodsThis was a prospective investigation including 393 couples underwent IVF cycles, among whom 90 patients had anovulatory infertility and 303 patients had normo-ovulatory infertility in a public university-affiliated in vitro fertilization center. Sperm mROS and hydrogen peroxide testing were performed by flow cytometry and analyzed for their relationship with embryo development indices on days 1–6 after IVF. Multivariate logistic regression analysis was used to control for female potential confounders. The nonlinear effects of sperm ROS on embryo development were analyzed by the Restricted cubic spline (RCS) method.Results1. Multivariate linear logistic regression analysis showed that high proportion of mROS positive sperm improved the 2PN rate (OR = 1.325, 95% CI: 1.103–1.595), day 3 embryo utilization rate (OR = 1.362, 95% CI: 1.151–1.614) and good-quality day 3 embryo rate (OR = 1.391, 95% CI: 1.089–1.783) in patients with anovulatory infertility. High percentage of sperm mROS and hydrogen peroxide had adverse effects on cleavage-stage embryo and blastocyst development in patients with normo-ovulatory infertility. 2. For patients with polycystic ovarian syndrome (PCOS) anovulatory infertility, there were significant distinct effects on embryo development indices between sperm mROS and hydrogen peroxide, and the increased rate of sperm mROS improved the good-quality day 3 embryo rate (OR = 1.435, 95% CI: 1.045–1.981); however, high percentage of sperm hydrogen peroxide reduced the blastocyst utilization rate (OR = 0.555, 95% CI: 0.353–0.864) and the good-quality blastocyst rate (OR = 0.461, 95% CI: 0.292–0.718). 3. Multivariate RCS analysis revealed that sperm ROS had a nonlinear (such as a parabolic curve) effect on embryo development in patients with anovulatory infertility (P < 0.05), and either greatly increased or greatly decreased affected cleavage-stage embryo and blastocyst development. The effects of sperm ROS in patients with normo-ovulatory infertility were both linear and nonlinear.ConclusionsThese findings indicate that contrary effects of sperm mROS on embryo development depending on whether patients treated with IVF cycles had normal ovulation. Regardless of whether the patients ovulated normally, increased sperm hydrogen peroxide rate damaged blastocyst development. It is necessary to evaluate male sperm ROS levels and the female ovulatory state to determine an individualized intervention plan before starting cycles, as this may be beneficial for infertile couples.

The influence of day 3 embryo cell number on the clinical pregnancy and live birth rates of day 5 single blastocyst transfer from frozen embryo transfer cycles

BackgroundTo evaluate the influence of day 3 embryo cell number on the clinical pregnancy and live birth rates of day 5 single blastocyst transfer in frozen embryo transfer (FET) cycles.MethodsOur retrospective study included 3761 day 5 single blastocyst FET cycles between January 2015 and December 2019. These FET cycles were divided into three groups according to the day 3 embryo cell number: 939 cycles in the < 8-cell group, 1224 cycles in the 8-cell group and 1598 cycles in the > 8-cell group. The clinical pregnancy and live birth rates were compared among the three groups.ResultsThe clinical pregnancy rate of day 5 single blastocyst transfer in FET cycles increased significantly as the day 3 embryo cell number increased (52.2%, 61.4% and 66.8%, P < 0.001). Similarly, the live birth rate increased significantly as the day 3 embryo cell number increased (42.7%, 49.8% and 54.9%, P < 0.001). The results of the subgroup analysis showed that the clinical pregnancy and live birth rates were not significantly different among the three groups when good-quality blastocysts were transferred. The clinical pregnancy and live birth rates increased significantly as the day 3 embryo cell number increased when fair- and poor-quality blastocysts were transferred.ConclusionThe day 3 embryo cell number needs to be considered when day 5 single blastocyst transfer is performed in FET cycles, especially when fair- and poor-quality blastocysts are used for transfer. The transfer of a day 5 single blastocyst derived from an embryo with faster development on day 3 may shorten the time to achieving a live birth.

Calcium ionophore improves embryonic development and pregnancy outcomes in patients with previous developmental problems in ICSI cycles

BackgroundCalcium (Ca2+) ionophores are now mainly considered as efficient treatments for fertilization failure. Recently, its application for rescuing poor embryo development was proposed but still non-routine. This study aimed to explore whether Ca2+ ionophore improves embryo development and pregnancy outcomes in patients with poor embryo development in previous intracytoplasmic sperm injection (ICSI) cycles.MethodsThis study included 97 patients undergoing assisted oocyte activation (AOA) with Ca2+ ionophore (calcimycin, A23187) treatment. Preimplantation embryonic development and clinical outcomes were compared between ICSI-AOA cycles (AOA group) and previous ICSI cycles of the same patients in which poor embryo developmental potential was present (non-AOA group). Subgroups stratified by maternal age (< 35, 35–40, ≥ 40 years, respectively) were analyzed separately.ResultsA total of 642 MII oocytes were collected in AOA group, and 689 in non-AOA group. Significantly higher day 3 good quality embryo rate (P = 0.034), good quality blastocyst formation rate (P < 0.001), and utilization rate (P < 0.001) were seen in AOA group. Similar results were seen in each subgroup. For pregnancy outcomes, there were significant differences in clinical pregnancy rate (P = 0.039) and live birth rate (P = 0.045) in total group. In subgroup aged < 35 years, biochemical (P = 0.038), clinical (P = 0.041), and ongoing pregnancy rate (P = 0.037) in AOA group were significantly higher than that in non-AOA group. No significant improvement for clinical outcomes for subgroups aged 35–40 and aged ≥40.ConclusionThe study suggests that calcimycin could improve preimplantation development and pregnancy outcomes in patients aged < 35 years with embryo developmental problems in previous ICSI cycles.

Increased ammonium in culture medium may promote cellular apoptosis and negatively affect pluripotency of human blastocysts.

To determine the association between ammonium concentration in culture medium and blastocyst development and to assess the influence of increased ammonium concentration on the expression of Bax, Bcl-2 and Oct4. A total of 254 cleavage-stage embryos were individually cultured in 30μL G2-plus medium on Day 3, and then culture media samples were collected on Day 5 for ammonium concentration determination immediately after evaluating the embryos morphology. Poor-quality blastocysts (combined score of CC) were used for gene expression analysis. The blastocyst formation rate, good-quality blastocyst rate and relative expression levels of Bax, Bcl-2 and Oct4 were analyzed. Based on receiver operating characteristic curve, the cutoff value of ammonium concentration produced by embryos was 16.07μmol/L (AUC = 0.722, 95% CI 0.637-0.807; P = 0.000), so all embryos were assigned to two groups according to the cutoff value: normal group (< 16.07μmol/L) and increased group (≥ 16.07μmol/L). There was a significant difference in blastocyst formation rate (80.5% vs 59.0%, P < 0.01) between normal group and increased group, as well as for good-quality blastocyst rate (21.0% vs 3.4%, P < 0.01). A significantly higher expression level of Bax (P < 0.05) and considerably lower expression level of Oct4 (P < 0.01) were observed in increased group compared to normal group. Our data demonstrated for the first time that increased ammonium concentration in culture medium may promote cellular apoptosis and negatively affect pluripotency of human blastocyst.

Prediction of live birth in vitrified-warmed 1PN-derived blastocyst transfer: Overall quality grade, ICM, TE, and expansion degree.

Background: Numerous studies have reported that transfer of blastocysts derived from monopronuclear (1PN) zygotes achieved live births. However, the potential value of morphology grading for the prediction of 1PN blastocyst viability is unclear, and the blastocyst selection criterion for successful pregnancy has not been set up yet. The aim of this study is to assess the ability of the blastocyst morphology grading system based on three parameters, namely, inner cell mass (ICM), trophectoderm (TE), and expansion degree and to predict outcomes of a cycle with single 1PN blastocyst transfer. Methods: A total of 266 vitrified-warmed 1PN-derived blastocyst transfer cycles for IVF treatment at Shanghai Ninth People's Hospital between 2007 and 2020 were included. The study was performed on single blastocyst transfers. Electronic records of patients were retrospectively analyzed. In the current study, the blastocysts were classified into three groups: "good," 3-6AA, 3-6AB, 3-6BA; "medium," 3-6BB, 3-6AC, 3-6CA; and "poor," 3-6BC, 3-6CB, 3-6CC. The basal characteristics, embryo grading, and clinical outcomes were compared between the three groups. The association of morphology parameters with pregnancies and live births was analyzed. Logistic regression was adopted to set up a prediction model of live births. Results: Transfer of the good-quality blastocysts achieved significant higher pregnancies (biochemical pregnancy: 59%; clinical pregnancy: 56.4%, and live birth 48.7%) than those in the group of the medium (biochemical pregnancy: 59%; clinical pregnancy: 49.6%; live birth: 40.4%) or poor-quality (biochemical pregnancy: 38.4%; clinical pregnancy: 34.9%; live birth: 26.7%) blastocysts (p < 0.05). There was a significant association between ICM and live birth. A prediction model of live births involving ICM, TE, and expansion degree was set up. Conclusion: In 1PN transfer cycles, a higher overall blastocyst quality is shown to correlate most strongly with optimal pregnancy and live birth outcomes. The selection of high-quality blastocysts for transfer should consider the ICM score first. The prediction model of live births based on ICM, TE, and expansion degree may help predict successful pregnancy in 1PN single-blastocyst transfer cycles.

Impact of Spermatozoa Cryopreservation on Clinical Outcomes of Intracytoplasmic Sperm Injection in Patients with Azoospermia: A Retrospective Cross-Sectional Study

Background: This study was undertaken to evaluate the effect of cryopreservation on the clinical outcomes of intracytoplasmic sperm injection (ICSI) cycles using sperm retrieved from testicular sperm extraction (TESE) in patients with azoospermia. Methods: This retrospective analysis included the clinical data of 56 pairs of fresh and frozen sperm injection cycles from 56 couples after TESE from January 2019 to December 2021 at the Reproductive Medicine Center of the First Affiliated Hospital of Sun Yat-sen University, of which 42 pairs were ICSI cycles using fresh and frozen sperm from the same TESE procedure. We compared the embryological and laboratory characteristics and pregnancy outcomes of the subsequent first embryo transfer (ET) cycles between the fresh and frozen groups. Results: There were no significant differences in the fertilization, cleavage, good-quality day 3 embryo, blastocyst formation, and good-quality blastocyst rates between the groups. However, when only paired ICSI cycles of fresh and frozen sperm from the same TESE procedure were analyzed, we observed that the good-quality day 3 embryo rate (44.8% vs 33.2%, p = 0.029) and blastocyst formation rate (57.5% vs 41.3%, p = 0.028) in the fresh group were significantly higher than those in the frozen group. Implantation, clinical pregnancy, early miscarriage, and live birth rates of the first ET cycle were not significantly different in either group. Conclusions: ICSI using fresh testicular sperm after TESE in patients with azoospermia appears to yield better embryological and laboratory outcomes than ICSI using cryopreserved testicular sperm, but the success rate of the subsequent first ET cycles does not seem to be affected.

Low-grade inflammation is negatively associated with live birth in women undergoing IVF

Research questionIs low-grade inflammation, detected by C-reactive protein (CRP), a marker of IVF outcome addressing both blastocyst quality and pregnancy outcome? DesignThis sub-study of a multicentre randomized controlled trial included 440 women undergoing IVF treatment with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Serum CRP was measured on cycle day 2–3 (baseline) and on the day of ovulation triggering. The association between CRP concentrations and reproductive outcomes (number of retrieved oocytes, number of good-quality blastocysts, pregnancy, pregnancy loss and live birth), were analysed, adjusting for relevant confounders. ResultsA negative association was found between higher baseline CRP concentrations and live birth rate (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62–0.96, P = 0.02) and higher CRP concentrations at baseline were associated with pregnancy loss among women who conceived (OR 1.37, 95% CI 1.07–1.76, P = 0.01). When testing for a specific cut-off, CRP concentrations above 2.34 (the highest quartile) were more likely to be associated with pregnancy loss (P = 0.02) and a lower chance of live birth (P = 0.04) compared with the lowest quartile. No associations were found between CRP concentrations and pregnancy outcomes on the day of ovulation triggering, and there were no associations between CRP concentrations and the number of good-quality blastocysts. ConclusionsHigher CRP concentrations at cycle day 2–3, before starting ovarian stimulation, are negatively associated with chance of live birth, possibly because of an increased risk of pregnancy loss. No association was found between the number of good-quality blastocysts and CRP concentration. More studies are needed to investigate the impact of low-grade inflammation.

Blastocyst quality and perinatal outcomes of frozen-thawed single blastocyst transfer cycles.

ObjectiveTo investigate the effects of blastocyst quality and morphological grade on the perinatal outcomes in patients undergoing frozen-thawed single blastocyst transfer cycles.MethodsThis single-center retrospective cohort study included 2648 singleton neonates resulting from frozen-thawed single blastocyst transfers performed between January 2017 and September 2021. Multivariate logistic regression was performed to evaluate perinatal outcomes for their association with blastocyst quality and morphological parameters.ResultTransfer of a good-quality blastocyst in a frozen-thawed cycle was associated with a lower rate of preterm delivery (PTD, adjusted OR =0.7, 95% CI 0.5-0.9; P=0.020) and a higher likelihood of a male neonate (adjusted OR =1.2, 95%CI 1.0-1.5; P=0.048). Compared with grade C inner cell mass (ICM) blastocyst transfer, grade B ICM (adjusted OR =0.5, 95%CI 0.2-0.9; P=0.027) and grade A ICM (adjusted OR =0.6, 95%CI 0.3-1.5; P=0.290) blastocyst transfers were associated with a lower rate of PTD, which was more evident for grade B ICM. After adjusting for confounders, the likelihood of a male neonate (grade B TE, OR =1.2, 95%CI 1.0-1.5, P=0.037; grade A TE OR =1.9, 95%CI 1.3-28, P=0.002) increased with increasing trophectoderm (TE) quality. Compared with expansion stage 4, the likelihood of a male neonate was 1.5 times greater with transfer of a stage 6 blastocyst (OR =1.5, 95%CI 1.0-2.3; P=0.06), and the risk of small for gestational age (SGA) was greater with transfer of a stage 5 blastocyst (adjusted OR =3.5, 95%CI 1.5-8.0; P=0.004). The overall grading of the blastocyst, expansion stage, ICM grade, and TE grade were not associated with length at birth, birthweight, large for gestational age (LGA), or birth defects (all P>0.05).ConclusionsIn frozen-thawed single blastocyst transfer cycles, transfer of a good-quality blastocyst was associated with a lower rate of PTD and a greater likelihood of a male neonate. Transfer of grade B ICM blastocysts decreased the rate of PTD, and TE quality was positively correlated with the likelihood of a male neonate.

GOOD QUALITY SINGLE BLASTOCYST TRANSFER IMPARTS BETTER PREGNANCY OUTCOMES COMPARED TO TRANSFER OF EITHER TWO GOOD QUALITY OR ONE GOOD AND ONE POOR BLASTOCYST IN FRESH IVF CYCLES

To compare pregnancy outcomes in terms of clinical pregnancy (CPR), Live Birth (LBR) and Missed pregnancy (MPR) rates following transfer of either one good quality blastocyst or two good quality blastocysts or one good and one poor quality blastocyst in fresh transfer cycles.

What to advise to patients with only one good quality blastocyst, PGT-A or not? Outcomes of 2064 cycles

PurposeTo evaluate whether preimplantation genetic testing for aneuploidy (PGT-A) is beneficial for patients who have only one blastocyst available for biopsy or transfer.MethodsThis retrospective study was based on 1126 single blastocyst PGT-A and 938 non-PGT-A cycles, a total of 2064 ART cycles which resulted in a single good quality blastocyst in women between 20 and 45 years old. The PGT-A group had 225 single euploid embryo transfer cycles and the non-PGT-A group had 938 single blastocyst embryo transfer cycles.ResultsIn the generalized linear mixed model (GLMM), female age and PGT-A variables were found to be significant variables on pregnancy outcomes. In the PGT-A cases, regardless of the effect of other variables, the probabilities of clinical pregnancy and live birth were found to be 3.907 and 3.448 fold higher respectively than in the non-PGT-A cases (p < 0.001). In non PGT-A cases, the probability of a total pregnancy loss was found to be 1.943 fold higher (p = 0.013).ConclusionPGT-A in the presence of a single blastocyst significantly increases clinical pregnancy and live birth rates and decreases total pregnancy losses regardless of age. In addition, aneuploid embryo transfer cancelations prevent ineffective and potentially risky transfers.