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RESEARCH QUESTION: Does the co-transfer of a good-quality embryo and a poor-quality embryo influence pregnancy outcomes in comparison to the transfer of a single good-quality embryo in vitrified-warmed blastocyst transfer cycles? DESIGN: This retrospective cohort study involved a total of 11,738 women who underwent IVF/intracytoplasmic sperm injection cycles and vitrified-warmed blastocyst transfer at a tertiary-care academic medical from January 2015 to June 2022. The study population was categorized into two groups: single-blastocyst transfer (SBT; participants who underwent single good-quality embryo transfer, n = 9338) versus double-blastocyst transfer (DBT; participants who underwent transfers with a poor and a good-quality embryo, n = 2400). RESULTS: The live birth rate (LBR) was significantly higher in the DBT group in comparison with the SBT group (65.6% versus 56.3%, P < 0.001). Multivariable logistic regression analysis showed that DBT was an independent predictor for LBR with a strong potential impact (adjusted odds ratio 1.55, 95% confidence interval 1.41-1.71; P < 0.001). However, the multiple birth rate was significantly higher in the good-quality embryo and poor-quality embryo group compared with patients undergoing a single good-quality embryo transfer (41.4% versus 1.8%; P < 0.001). CONCLUSIONS: In vitrified-warmed blastocyst transfer cycles, LBR was higher following DBT with one good-quality and one poor-quality embryo compared with SBT. However, this was at the expense of a marked increase in the likelihood of multiple gestations. Physicians should still balance the benefits and risks of double-embryo transfer.

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Introduction: The delayed-start gonadotropin-releasing hormone antagonist protocol seems effective for patients who are poor ovarian responders, but there are insufficient data on whether it is also effective for patients with poor-quality embryos and low rates of good blastocyst formation. Specifically, the effectiveness of delayed-start gonadotropin-releasing hormone antagonists with progesterone has not been adequately investigated. Therefore, we compared the efficacy of the original delayed-start gonadotropin-releasing hormone antagonist protocol using medroxyprogesterone acetate (MPA) and high-dose gonadotropin in patients with poor ovarian response. Methods: Overall, 156 patients with recurrent assisted reproductive technology failure who underwent the original protocol were included. They received cetrorelix acetate (3 mg) and MPA (10 mg) on cycle day 3, and high-dose gonadotropin was initiated on day 11. When the leading follicle reached 14 mm, ganirelix acetate (0.25 mg) was administered until the trigger day. The number of oocytes retrieved, metaphase II (MII) oocytes, two pronuclear (2PN) zygotes, and good blastocysts and live birth rates were compared between the previous (Cycle A) and original (Cycle B) cycles in three groups (Group A, all patients; Group B, poor responders; and Group C, patients with poor-quality embryos). Results: In Group A (n=156), the number of MII oocytes (3.6 ± 3.3 versus 4.5 ± 3.6), 2PN zygotes (2.8 ± 2.9 versus 3.8 ± 3.1), good blastocysts (0.5 ± 0.9 versus 1.2 ± 1.6), and live birth rates (0.6 versus 24.4) significantly increased in Cycle B. Similar results were obtained in Group B (n=83; 2PN zygotes [1.7 ± 1.7 versus 2.3 ± 1.8], good blastocysts [0.4 ± 0.7 versus 0.9 ± 1.3], live birth rates [0 versus 18.1]) and Group C (n=73; MII oocytes [5.1 ± 3.8 versus 6.6 ± 4.0], 2PN zygotes [4.0 ± 3.4 versus 5.4 ± 3.4], good blastocysts [0.7 ± 1.1 versus 1.6 ± 1.9], and live birth rates [1.4 versus 31.5]). Conclusion: This original protocol increased the number of MII oocytes retrieved, 2PN zygotes, good blastocysts, and live birth rates in both poor responders and in patients with poor-quality embryos.

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This study was to evaluate whether Intracytoplasmic sperm injection (ICSI) can improve the quality of embryo in patients with poor-quality embryos in the previous In-vitro fertilization (IVF) cycle, which was cancelled before transfer. This was a retrospective cohort study of 178 IVF and 158 ICSI cycles for patients with poor-quality embryos in the previous IVF cycle in the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University from March 2016 to June 2022. The 2 PN rate, oocyte utilization rate , high-quality embryo rate and clinical pregnancy rate were compared between the two groups. Furthermore, the implantation rate, miscarriage rate and cycle cancelation rate were measured and compared. ICSI resulted in a comparable 2 PN rate, oocyte utilization rate and cycle cancelation rate with IVF. The high-quality embryo rate of ICSI group was significantly higher than that of IVF group (5.56% vs. 2.60%, P < 0.05). Eventually, a total of 239 patients performed embryo transfer. ICSI resulted in a significantly higher clinical pregnancy rate (55.56% vs. 40.98%, P < 0.05) compared with IVF, however, there were no notable differences in miscarriage rate and implantation rate. The present study suggested that ICSI significantly improved the high-quality embryo rate and clinical pregnancy of the patients with poor-quality embryos in the previous IVF cycle. Prospective randomized controlled trials are needed to further verify.

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BACKGROUND: Embryos with higher morphologic quality grading may have a greater potential to achieve clinical pregnancy that leads to a live birth regardless of the type of cleavage-stage embryos or blastocysts. Few studies have investigated the impacts of embryo grading on the long-term health of the offspring. OBJECTIVE: This pilot study aimed to examine the associations between embryo morphologic quality and the physical, metabolic, and cognitive development of singletons conceived by in vitro fertilization and intracytoplasmic sperm injection at preschool age. STUDY DESIGN: This matched cohort study included singletons born to infertile couples who underwent fresh cleavage-stage embryo transfer cycles with good- or poor-quality embryos from 2014 to 2016 at the reproductive center of the Women's Hospital, School of Medicine, Zhejiang University. A total of 144 children, aged 4 to 6 years, participated in the follow-up assessment from 2020 to 2021, and the response rate of poor-quality embryo offspring was 39%. Singletons in the good-quality embryo group were matched with singletons in the poor-quality embryo group at a 2:1 ratio according to the fertilization method and the children's age (±1 year). We measured the offspring's height, weight, body mass index, blood pressure, thyroid hormone levels, and metabolic indicators. Neurodevelopmental assessments were performed using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition, and the Adaptive Behavior Assessment System, Second Edition. We also collected data from the medical records. A linear regression model was used to analyze the association between embryo morphologic quality and offspring health outcomes. RESULTS: A total of 48 singletons conceived with poor-quality embryo transfer and 96 matched singletons conceived with good-quality embryo transfer were included in the final analysis. Age, sex, height, weight, body mass index, blood pressure, thyroid function, and metabolic indicators were comparable between the 2 groups. After adjustment for potential risk factors by linear regression model 1 and model 2, poor-quality embryo offspring exhibited a tendency toward higher free thyroxine levels than offspring of good-quality embryo transfers (beta, 0.22; 95% confidence interval, 0.09-0.90; beta, 0.22; 95% confidence interval, 0.09-0.91, respectively), but this difference was not clinically significant. Regarding neurodevelopmental assessments, there was no difference in the full-scale intelligence quotient based on the Wechsler Preschool and Primary Scale of Intelligence (109.96±12.42 vs 109.60±14.46; P=.88) or the general adaptive index based on the Adaptive Behavior Assessment System (108.26±11.70 vs 108.08±13.44; P=.94) between the 2 groups. The subindices of the 2 tests were also comparable. These findings remained after linear regression analysis. CONCLUSION: At 4 to 6 years of age, singletons born from poor-quality embryo transfers have comparable metabolic and cognitive development as those born from good-quality embryo transfers using fresh cleavage-stage embryos. The results of this pilot study indicate that poor-quality embryos that can survive implantation and end in live birth are likely to have a developmental potential comparable to that of good-quality embryos.

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PURPOSE: To explore whether artificial oocyte activation (AOA) can improve embryo developmental potentiality and pregnancy outcomes for patients with a history of embryo developmental problem. METHODS: This was a retrospective study and candidate patients with embryo development problems were collected. A total of 1422 MII eggs from the enrolled 140 patients were randomized divided equally into 2 groups, half for the AOA group (AOA), and the rest of sibling mature eggs for the control group (non-AOA). The patients were further divided into two subgroups: (1) the rate of good-quality day 3 embryos was 0% (group 1, n = 66); (2) the rate of good-quality day 3 embryos ranged from 1 to 30% (group 2, n = 74). RESULTS: In the early embryonic growth, there were no significant differences in the outcomes of AOA and non-AOA groups in terms of normal fertilization rates, cleavage rates, day 3 good-quality embryo rates and available blastocyst rates (72.7% vs. 79.3%, 97.4% vs. 98.0%, 20.1% vs. 19.7%, 6.6% vs. 8.4% in group 1, respectively; 77.7% vs. 81.9%, 98.1% vs. 97.0%, 25.8% vs. 22.1%, 9.6% vs. 9.3% in group 2, respectively). In the late embryonic growth, no significant differences were found in biochemical and clinical pregnancy rates, implantation rates, miscarriage rates, and live-birth rates (50.0% vs. 45.2%, 45.2% vs. 40.5%, 37.3% vs. 31.3%, 10.5% vs. 11.8%, 40.5% vs. 35.7%, respectively) between two groups. In addition, neonatal outcomes were similar in both the groups as well. CONCLUSION: Our study demonstrated that the AOA using ionomycin 1 h after ICSI did not bring benefits to the early or late development of embryos derived from patients with a history of embryo developmental problems.

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Outcomes among women who transferred only Gardner's grade BB or lower quality frozen embryos transferred (FET) are not well known. Our objective is to study whether transferring 2 versus 1 frozen low-quality blastocysts will increase the live birth rate (LBR) and the multiple pregnancy rate (MPR). This is a retrospective cohort study including 1104 FET cycles. Only day 5-6 blastocysts of grade BB or lower quality were included. Clinical pregnancy rate (CPR), MPR, and LBR per cycle were compared between single embryo transfer (SET) (n = 969) and double embryo transfer (DET) (n = 135). CPR and MPR were compared between SET and DET in grade BB, BC, CB, and CC individually. Among SET, BB blastocysts had higher CPR 34% (P = 0.0001) and a sub-significant increase in LBR 19% (P = 0.059) in comparison to other grade SET. Among all BB, MPR was significantly higher when transferring two versus one (5.9 vs. 1.9, P = 0.009). If age at egg collection ≥ 40 years (n = 97), no difference was found in CPR (11.1 vs. 11.7, P = 0.9), MPR (0 vs. 0), and LBR (6.3 vs. 0,P = 0.13) when SET or DET was performed. If age was < 40 years (n = 818), the MPR was significantly higher in DET than SET (6.7 vs. 1.63, P = 0.004). In egg donor cycles (n = 189), there was no difference in CPR, MPR, and LBR between SET and DET. Single embryo transfer should be offered even in women ≥ 40 years of age or transferring lower quality embryos since transferring more did not increase outcomes in this group, and SET is likely the safest path.

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OBJECTIVE: Embryo quality assessment with morphological evaluation remains the first-line method of assessment to select the best embryo for transfer. We aimed to determine if an effect of poor quality embryos on good quality ones exists, whether by a paracrine effect or an adverse endometrial influence, when they are transferred together. MATERIALS AND METHODS: We included 412 couples, who underwent intracytoplasmic sperm injection (ICSI) cycles in a tertiary IVF center. Single embryo transfer with a good quality embryo and double embryo transfers with a good + poor quality embryo were evaluated. Overall pregnancy (PR) and live birth rates (LBR) were our main outcome measures. RESULTS: When PR and LBR are compared, there was no statistical significance between single embryo transfer (SET) and double embryo transfer (DET) groups (51.7 % vs 53.7 %, p = 0.620 and 47 % vs 43.1 %, p = 0.117). When the PR and LBRs were compared between SET from poor cohort and DET group, the outcomes were better in DET group (22.1 % vs 53.7 %, p < 0.001 and 22.1 % vs 43.1 %, p < 0.001). The PR and LBRs of SET from good cohort were significantly better than those of DET (64.4 % vs 53.7 %, p < 0.001 and 57.7 % vs 43.1, p < 0.001). When the PR and LBRs of SET from good cohort and SET from poor cohort were compared, better results were obtained in SET from good cohort. CONCLUSION: The addition of poor quality embryo even is of benefit to the LBR, in the setting of when there is only one good quality blastocyst available for the transfer.

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BACKGROUND: While single embryo transfer (SET) is widely advocated, double embryo transfer (DET) remains preferable in clinical practice to improve IVF success rate, especially in poor prognosis patients with only poor quality embryos (PQEs) available in addition to one or no good quality embryos (GQEs). Furthermore, previous studies suggest PQE might adversely affect the implantation of a GQE when transferred together. This study aims to evaluate the effect of transferring an additional PQE with a GQE on the outcomes in poor prognosis patients. METHODS: A total of 5037 frozen-thawed blastocyst transfer (FBT) cycles between January 2012 and May 2019 were included. Propensity score matching was applied to control for potential confounders, and we used generalized estimating equations (GEE) models to identify the association between the effect of an additional PQE and the outcomes. RESULTS: Overall, transferring a PQE with GQE (Group GP) achieved significantly higher pregnancy rate (PR), live birth rate (LBR) and multiple pregnancy rate (MPR) than GQE only (group G). The addition of a PQE increased LBR in patients aged 35 and over and in patients who received over 3 cycles of embryo transfer (ET) (48.1% vs 27.2%, OR:2.56, 95% CI: 1.3-5.03 and 46.6% vs 35.4%, OR:1.6, 95% CI: 1.09-2.35), but not in women under 35 and in women who received less than 3 cycles of ET (48.7% vs 43.9%, OR:1.22, 95% CI: 0.93-1.59 and 48.3% vs 41.4%, OR:1.33, 95% CI: 0.96-1.85). Group GP resulted in significantly higher MPR than group G irrespective of age and the number of previous IVF cycles. CONCLUSIONS: An additional PQE does not negatively affect the implantation potential of the co-transferred GQE. Nevertheless, the addition of a PQE contributes to both live birth and multiple birth in poor prognosis patients. Physicians should still balance the benefits and risks of DET.

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PURPOSE: To study if the transfer of morphological grade-CC blastocyst is effective and safe. METHODS: This retrospective study included 2585 frozen-thawed embryo transfer (FET) cycles with grade-BB blastocysts and 102 FET cycles with grade-CC blastocysts during the period from January 2006 to December 2017. Pregnancy and neonatal outcomes of couples in two groups were analyzed before and after propensity score matching. RESULTS: Pregnancy outcomes showed no significant difference in the rates of biochemical pregnancy, ectopic pregnancy, miscarriage, multiple gestation, gestational age (P > 0.05). However, the rates of intrauterine implantation, clinical pregnancy, and live birth were significantly lower in the grade-CC blastocyst transfer group than those in the grade-BB blastocyst transfer group (18.9% vs 46.0%, 21.6% vs 51.3%, 16.7% vs 41.4%, all P < 0.001, respectively) before and after propensity score matching. The assessment of neonatal outcomes showed no statistically significant differences in the birth weight, low birth weight, early-neonatal death, and birth defect, etc., similar results were also observed in the two matched cohorts. CONCLUSION: Morphologically grade-CC blastocysts should be transferred rather than discarded, resulting in acceptable pregnancy and neonatal outcomes, which is beneficial to infertile patients suffering from repeated poor-quality embryos.

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OBJECTIVE: To determine if transferring a lower-quality embryo with a good-quality blastocyst is detrimental, given that evidence suggests that embryos can signal the endometrium and that embryo quality may affect negatively endometrial receptivity. DESIGN: Retrospective cohort study. SETTING: In vitro fertilization center. INTERVENTION(S): Single- versus double-embryo transfer. PATIENT(S): Patients with a double-embryo transfer of a good-quality blastocyst plus a lower-quality blastocyst, early blastocyst, or morula were compared with patients receiving a single good-quality blastocyst. MAIN OUTCOME MEASURE(S): Live birth, multiple gestation. RESULT(S): In this study, 4,640 in vitro fertilization cycles were analyzed. In none of the analyses did transferring a second lower-quality embryo negatively affect birth rate. In the primary analysis, transferring a second lower-quality embryo increased live birth by 10% and the multiple birth rate by 15%. The addition of a fair- or poor-quality blastocyst or early blastocyst markedly increased the twin birth rate by 22%-27% with an 8%-12% increase in live birth. The addition of a morula did not increase live birth but resulted in 12% more multiples. In women younger than 38 years, adding a lower-quality embryo increased the birth rate by 7% but resulted in 18% increase in multiples. In women 38 years or older, adding a lower-quality embryo increased the live birth rate by 9% with a 15% increase in multiples. CONCLUSION(S): Addition of a lower-quality embryo does not have a detrimental effect on a good-quality blastocyst and results in a small increase in live births. However, this is at the expense of a marked increase in the likelihood of multiple gestations.

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PURPOSE: To evaluate the effect of embryo quality on pregnancy outcomes. METHODS: This retrospective analysis included 80 live singleton births, resulting from morphologically good-quality embryo transfers, and 25 live singleton births that resulted from morphologically poor-quality embryo transfers between January, 2008 and December, 2014. Cleavage embryos that were graded as ≥2, according to the Veeck classification system, and blastocysts that were graded as ≥3BB, according to the Gardner classification system, were defined as good quality. The obstetric and neonatal outcomes were compared between the poor- and good-quality embryo transfer groups. RESULTS: The mean maternal age between the groups was similar. The blastocyst transfer rate was higher in the good-quality, than in the poor-quality, embryo transfer group. Other characteristics, including parity, infertility duration, the intracytoplasmic sperm injection rate, frozen-thawed embryo transfer rate, endometrial thickness, and hormone values before the embryo transfer, were similar between the groups. The obstetric and neonatal outcomes of live births between the two groups were not different in terms of preterm delivery, birthweight, small or large size for gestational age, malformation, umbilical artery cord pH of <7.20, hypertensive disorders of pregnancy, gestational diabetes mellitus, chorioamnionitis, placenta previa, and placental abruption. CONCLUSION: The obstetric and neonatal outcomes of live births between the poor- and good-quality embryo transfers were equivalent.

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This study was performed to elucidate the changes in IFNT messenger RNA (mRNA) levels in in vivo-fertilized and parthenogenetic bovine embryos and their interferon-τ (IFNT) secretion amounts during the elongation phase. We assessed the induction capability of maternal recognition of pregnancy by parthenogenetic embryos and attempted cotransfer of in vivo-fertilized and parthenogenetic embryos. The expression level of IFNT mRNA in in vivo-fertilized embryos peaked on Day 18 after estrus, and the highest amount of uterine IFNT was observed on Day 20. Transfer of 10 parthenogenetic embryos produced a detectable amount of uterine IFNT. Transfer of one or three parthenogenetic embryos inhibited luteolysis. An increase in ISG15 mRNA levels in peripheral granulocytes was induced by the transfer of three parthenogenetic embryos. Cotransfer of three parthenogenetic embryos significantly improved the pregnancy rate on Day 40 in code 3 in vivo-fertilized embryos compared with single transfer without parthenogenetic embryos (65% vs. 35%). However, the pregnancy rate on Day 90 (35%) in cotransfer of code 3 in vivo-fertilized embryos did not differ from that upon single transfer (29%), because the cotransfer group had a higher incidence of pregnancy loss than with single transfer (47% vs. 17%) after Day 40. Cotransfer did not affect the pregnancy rate of code 2 in vivo-fertilized embryos. The incidence of pregnancy loss was higher in cotransfer of code 2 in vivo-fertilized embryos than in single transfer (30% vs. 7%). In conclusion, parthenogenetic embryos in the elongation phase secreted IFNT, enabling induction of maternal recognition of pregnancy. The present study revealed that enhancement of the maternal recognition of pregnancy using parthenogenetic embryos promoted the viability of poor-quality embryos until Day 40 of gestation. However, the incidence of pregnancy loss increased after Day 40 in the cotransfer of parthenogenetic embryos. A technique for promoting the full-term survival of poor-quality embryos is needed.

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