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Purpose: This article aims to assess how differences in maternal age distributions between IVF clinics affect the performance of an artificial intelligence model for embryo viability prediction and proposes a method to account for such differences., Methods: Using retrospectively collected data from 4805 fresh and frozen single blastocyst transfers of embryos incubated for 5 to 6 days, the discriminative performance was assessed based on fetal heartbeat outcomes. The data was collected from 4 clinics, and the discrimination was measured in terms of the area under ROC curves (AUC) for each clinic. To account for the different age distributions between clinics, a method for age-standardizing the AUCs was developed in which the clinic-specific AUCs were standardized using weights for each embryo according to the relative frequency of the maternal age in the relevant clinic compared to the age distribution in a common reference population., Results: There was substantial variation in the clinic-specific AUCs with estimates ranging from 0.58 to 0.69 before standardization. The age-standardization of the AUCs reduced the between-clinic variance by 16%. Most notably, three of the clinics had quite similar AUCs after standardization, while the last clinic had a markedly lower AUC both with and without standardization., Conclusion: The method of using age-standardization of the AUCs that is proposed in this article mitigates some of the variability between clinics. This enables a comparison of clinic-specific AUCs where the difference in age distributions is accounted for., (© 2023. The Author(s).)

Medical Assisted Reproduction proved its efficacy to treat the vast majority forms of infertility. One of the key procedures in this treatment is the selection and transfer of the embryo with the highest developmental potential. To assess this potential, clinical embryologists routinely work with static images (morphological assessment) or short video sequences (time-lapse annotation). Recently, Artificial Intelligence models were utilized to support the embryo selection procedure. Even though they have proven their great potential in different in vitro fertilization settings, there is still considerable room for improvement. To support the advancement of algorithms in this research field, we built a dataset consisting of static blastocyst images and additional annotations. As such, Gardner criteria annotations, depicting a morphological blastocyst rating scheme, and collected clinical parameters are provided. The presented dataset is intended to be used to train deep learning models on static morphological images to predict Gardner's criteria and clinical outcomes such as live birth. A benchmark of human expert's performance in annotating Gardner criteria is provided., (© 2023. The Author(s).)

The aim of this study was to assess the ability of three individual blastocyst morphology parameters - expansion and hatching (EH) stage, inner cell mass (ICM) grade and trophectoderm grade - to predict outcome of a cycle with single-blastocyst transfer. The study was a secondary analysis of data prospectively collected in a large multicentre trial. A total of 618 intracytoplasmic sperm injection patients undergoing ovarian stimulation in a gonadotrophin-releasing hormone antagonist cycle with compulsory single-blastocyst transfer on day 5 were included. In the simple logistic regression analysis, all three blastocyst morphology parameters were statistically significantly (P<0.005 for each) associated with positive human chorionic gonadotrophin, clinical and ongoing pregnancy rates and live birth rates, while only the ICM grade was significantly (P=0.033) associated with early pregnancy loss rate. Blastocyst EH stage was the only significant predictor of live birth (P=0.002) in the multiple logistic regression. In conclusion, although all three blastocyst morphology parameters were related to treatment outcome of fresh single-blastocyst cycles, selection of high-quality blastocysts for transfer should consider first the EH stage. Transfer of a blastocyst with ICM grade A may reduce the risk of early pregnancy loss. Choosing the embryo(s) with the best implantation potential is essential for securing each couple the highest chance of achieving pregnancy after assisted reproduction. The selection of embryo(s) for transfer at the blastocyst stage is based on morphology parameters of expansion and hatching stage, inner cell mass grade and trophectoderm grade. The aim of this study was to assess the relative impact of each parameter in predicting the probability of a successful outcome. The study was a secondary analysis of data prospectively collected in a large multicentre trial. A total of 618 patients who underwent single-blastocyst transfer on day 5 were included. Statistical analysis showed that all three blastocyst morphology parameters were significantly associated with positive human chorionic gonadotrophin (βHCG), clinical and ongoing pregnancy rates and live birth rates. Only the inner cell mass grade was significantly associated with early pregnancy loss between the positive βHCG test and confirmation of ongoing pregnancy 10-11weeks after transfer. The expansion and hatching stage was the only significant predictor of live birth in the multiple logistic regression analysis. In conclusion, although all three blastocyst morphology parameters were related to treatment outcome of fresh single-blastocyst cycles, selection of high-quality blastocysts for transfer should consider first the expansion and hatching stage. Transfer of a blastocyst with inner cell mass grade A may reduce the risk of early pregnancy loss., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to compare two methods of cryopreservation for the cleavage-stage human embryo: slow freezing and vitrification., Methods: A total of 466 Day 3 embryos, donated with consent, underwent cryopreservation by either slow freezing in straws or vitrification using the cryoloop. The vitrification procedure did not include dimethyl sulfoxide, but rather employed ethylene glycol and 1,2-propanediol as the cryoprotectants. Survival, embryonic metabolism and subsequent development to the blastocyst were used to determine the efficacy of the two procedures., Results: Significantly, more embryos survived the vitrification procedure (222/234, 94.8%) than slow freezing (206/232, 88.7%; P < 0.05). Consistent with this observation, pyruvate uptake was significantly greater in the vitrification group, reflecting a higher metabolic rate. Development to the blastocyst was also higher following vitrification (134/222, 60.3%) than following freezing (106/206, 49.5%; P < 0.05). In a separate cohort of 73 patients who had their supernumerary embryos cyropreserved with vitrification, the resulting implantation rate and clinical pregnancy rate were 30 and 49%, respectively., Conclusions: Analysis of metabolism revealed that vitrification had less impact on the metabolic rate of the embryo than freezing, which was reflected in higher survival rate and subsequent development in vitro. Excellent pregnancy outcomes followed the warming and transfer of vitrified cleavage-stage embryos. These data provide further evidence that vitrification imparts less trauma to cells and is, therefore, a more effective means of cryopreserving the human embryo than conventional slow freezing. Clinicaltrials.gov identifier: NCT00608010.

Purpose of Review: To give an overview of the current status and future directions of blastocyst transfer and outcome with particular focus on markers of blastocyst quality and their relationship with implantation., Recent Findings: In addition to morphological markers, future embryo grading systems, in general, and blastocyst grading systems, in particular, will be based upon metabolic, genetic and epigenetic markers that will increase their efficiency. Metabolic markers such as soluble human leukocyte antigen-G, analysis of specific gene mutations in the trophectoderm by real-time multiplex polymerase chain reaction and analysis by microarray of differential gene expression will be operational in the near future for accurate blastocyst grading and selection., Summary: Gamete and embryo quality as well as culture conditions affect blastocyst formation and quality. Characteristics of the zygote and the cleavage-stage embryo determine the developmental potential of the embryo up to the blastocyst stage. There appears to be a strong relationship between blastocyst quality and implantation. Accurate grading is important for selection of the most implantation-competent blastocyst. Similar to grading systems used in the cleavage-stage embryo, current blastocyst grading systems are mainly based upon morphological characteristics. Incorporation of metabolic, genetic and epigenetic markers will undoubtedly improve the selection process, making it possible to transfer a single blastocyst yielding high pregnancy rates.

A more detailed blastocyst grading system provides a better selection of blastocysts with the highest implantation potential. Grading systems will help to decrease the number of blastocysts to be transferred without compromising high implantation and pregnancy rates.

This study was undertaken to compare the outcome of day 3, day 5, and frozen-thawed embryo transfer cycles where embryo culture was undertaken using the G1.2-G2.2 versus GIII series sequential media. A total of 400 day 3, 73 day 5 and 126 frozen-thawed embryo transfer cycles were analysed. Treatment cycles were quasi-randomized on the day of oocyte retrieval to embryo culture in G1.2-G2.2 versus GIII series sequential media. Randomization was undertaken according to alternating weekdays. Significantly more embryos were of grade 1 or 2 quality on day 3 in the GIII group (P < 0.05). Likewise, more embryos in the GIII group had eight blastomeres on day 3 (P < 0.05) and were able to hatch spontaneously (P < 0.05). For day 3 embryo transfer cycles, implantation and clinical pregnancy rates were 14.4 and 25.7% versus 37.8 and 50.3% in G1.2-G2.2 and GIII groups respectively (P < 0.05). For day 5 embryo transfer cycles, implantation rates were significantly higher (29 versus 45%; P < 0.05) in the GIII group. There was a trend towards higher pregnancy rates; however, this did not reach statistical significance due to fewer cycles analysed in this group. In-vitro culture in GIII series sequential media yields better quality embryos that implant more efficiently, compared with culture in G1.2-G2.2 media.

A retrospective study of 5,982 embryos in 619 blastocyst-stage embryo transfer cycles revealed that detection of multinucleated blastomeres either on day 2 or 3 signifies a poor prognosis for blastocyst formation and that no good-quality blastocyst can be expected from an embryo with more than one multinucleated blastomere. Patients should be counseled regarding a poor prognosis when multiple embryos with multinucleated blastomeres are present.

The purpose of this study was to assess the outcome of blastocyst transfer in relation to the presence or absence of excess blastocysts available for cryopreservation. The study was designed as a retrospective case series in a tertiary care private hospital. The study group consisted of 450 blastocyst stage embryo transfer cycles. In 139 cycles there were excess freezeable blastocysts (group 1), in 78 cycles there were excess but unfreezeable blastocysts (group 2), and in 233 cycles there were no excess blastocysts (group 3). A mean of three blastocysts was replaced in all groups. Treatment cycle characteristics, implantation and pregnancy rates following fresh and cryopreserved blastocyst transfer were assessed in each group. More embryos reached the blastocyst stage in group 1 and more blastocysts were of good quality. In group 1, clinical pregnancy and implantation rates (71 and 41%) were significantly higher compared with groups 2 (56 and 27%) and 3 (43 and 19%). Embryos that were selected for transfer among a cohort of good quality blastocysts yielded the highest implantation and pregnancy rates. Given a clinical pregnancy rate of 71%, an implantation rate per embryo of 41%, and a multiple pregnancy rate of 58%, serious consideration should be given to a single blastocyst transfer in these patients.

Background: Embryo quality may be accurately assessed as early as the pronuclear zygote phase, as shown in recent studies. However, it is not known whether good quality zygotes are destined to become good quality cleavage stage embryos and blastocysts., Methods: In this retrospective study, 86 intracytoplasmic sperm injection-embryo transfer cycles were studied where each available embryo was scored from the zygote until the blastocyst stage. Embryonic normality parameters such as pronuclear pattern, early cleavage, cleavage stage embryo grade, the presence of embryos with > or =8 cells on day 3 and blastocyst quality were recorded. Embryo transfer was undertaken at the blastocyst stage and the outcome was studied according to the pronuclear pattern exhibited by the zygotes., Results: Embryos that showed an ideal pronuclear pattern (0 PN pattern) cleaved earlier and faster and resulted in better quality cleavage stage embryos and blastocysts. The incidence of blastocyst formation was 72% in zygotes showing a 0 PN pattern, compared with 12.7% in zygotes with double pronuclear abnormality. Higher implantation and pregnancy rates were obtained when at least one blastocyst derived from a 0 PN pattern zygote was included in the set of embryos to be transferred., Conclusions: Our results indicate that the pronuclear pattern of the zygote is closely related to blastocyst formation and quality. Blastocysts derived from 0 PN zygotes have a higher potential for implantation.

Objective: To determine the feasibility and success of blastocyst-stage embryo transfers in patients having only fair and poor quality cleavage-stage embryos on day 3., Design: Prospective case study with historic controls., Setting: Tertiary care private hospital IVF center., Patient(s): A total of 158 day 5 embryo transfer cycles in patients with grade 3 and grade 4 cleavage-stage embryos. Control group consisted of 162 day 3 transfer cycles performed with embryos of similar quality., Intervention(s): In vitro culture of embryos up to the blastocyst stage., Main Outcome Measure(s): The percentage of cycles that culminated in the transfer of at least one blastocyst and implantation and pregnancy rate related to the day of transfer., Result(s): In the day 3 transfer group, a mean of 5.2 embryos were replaced per patient. This was significantly more than the mean of 2.4 embryos that could be replaced on day 5 (P <.001). The clinical pregnancy rate per embryo transfer was 27.2% and 33.5% in the two groups, respectively (P >.05). The implantation rate per embryo was significantly higher in the day 5 transfer group (15% vs. 5.9%). The multiple pregnancy and abortion rates were similar between the groups., Conclusion(s): Transfer of fair and poor quality embryos at the blastocyst stage is feasible and is associated with higher implantation rates as compared to transfer of similar quality embryos on day 3.

Objective: To determine the relationship between blastocyst quality and the results of embryo transfer at the blastocyst stage., Design: Retrospective case analysis., Setting: Tertiary care private hospital IVF center., Patient(s): A total of 350 blastocyst-stage embryo transfer cycles., Intervention(s): In vitro culture to the blastocyst stage was undertaken in 350 ICSI cycles where four or more cleavage-stage embryos were available on day 3., Main Outcome Measure(s): Relationship between blastocyst quality and implantation and clinical and multiple pregnancy rates., Result(s): Transfer of at least one grade 1 or grade 2 blastocyst or one hatching blastocyst was associated with very high implantation and pregnancy rates. However, transfer of grade 3 blastocysts yielded very low implantation and pregnancy rates., Conclusion(s): There appears to be a strong correlation between blastocyst quality and success of blastocyst transfer.

Progression to the blastocyst stage of embryos derived from testicular round spermatids in men with non-obstructive azoospermia was studied. A total of 56 men were studied in whom partial spermatogenesis failure had occurred where only very few spermatozoa (fewer than the number of oocytes retrieved) were extracted from multiple testicular biopsy specimens. Oocytes remaining after intracytoplasmic injection of testicular spermatozoa (group 1) were injected with round spermatids (ROSI, group 2). Only embryos derived from group 1 were transferred. Remaining embryos were observed under culture for 8 days and their progression to the blastocyst stage was recorded. Of the 546 oocytes injected with testicular spermatozoa, 404 (73.9%) showed evidence of 2-pronuclear (2PN) fertilization. Injection of testicular round spermatids resulted in 2PN fertilization rate of 50% (P < 0.05). Using a four-point grading system, 53% of the good quality embryos (grade 1 or 2) in group 1 reached the blastocyst stage compared with 25% in group 2 (P < 0.05). The rate of progression to the blastocyst stage of grade 3 and grade 4 embryos was 46 and 8.5% in the two groups respectively (P < 0.05). Using a different three-point grading system for the blastocysts, 75.3% of the blastocysts in group 1 were either grade 1 or grade 2 and 24.7% were grade 3. However, in group 2 all blastocysts were grade 3. All embryos observed in group 1 reached the blastocyst stage by day 5 or 6 compared with 25% of the embryos reaching the blastocyst stage by this time in group 2. While 31.2% of the blastocysts in group 1 showed evidence of spontaneous hatching in vitro, none of the blastocysts in group 2 hatched. In conclusion, progression to the blastocyst stage occurred at a much lower and slower rate in embryos derived from testicular round spermatids. Furthermore, all blastocysts resulting from ROSI were of poor quality and none showed spontaneous hatching. These results may explain the dismal outcome associated with ROSI.

Excess embryos from patients undergoing intracytoplasmic sperm injection and embryo transfer for male infertility were cultured to determine the rate and timing of their progression to the blastocyst stage. In 194 embryo transfer cycles, four embryos with the morphologically best grading were transferred and at least two embryos were cultured. The cycles were classified as: group 1: no excess embryos reached blastocyst stage, group 2: >50% of embryos reached blastocyst stage by days 4-5, group 3: <50% of embryos reached the blastocyst stage by days 4-5, group 4: >50% of the embryos reached blastocyst stage by days 6-7, group 5: <50% of the embryos reached blastocyst stage by days 6-7. All groups were similar regarding female age, duration of infertility, and parameters of ovarian stimulation. In group 1, clinical pregnancy and implantation rates were 14 and 11% respectively, and were similar to those of group 4. In group 2, clinical pregnancy and implantation rates were 75 and 33%. Multiple implantations occurred in 81% of group 2 or 3 cycles, compared to none in group 1 cycles. The results suggest that the development potential of the embryo is intrinsic, and that embryos which carry a high potential for development yield a high clinical pregnancy rate and multiple implantations.