Time-lapse imaging of morula compaction for selecting high-quality blastocysts: a retrospective cohort study.

PURPOSE: Before blastocyst development, embryos undergo morphological and metabolic changes crucial for their subsequent growth. This study aimed to investigate the relationship between morula compaction and blastocyst formation and the subsequent chromosomal status of the embryos. METHODS: This retrospective cohort study evaluated embryo development (n = 371) using time-lapse imaging; 94 blastocysts underwent preimplantation genetic testing for aneuploidy (PGT-A). RESULTS: The embryos were classified as fully (Group 1, n = 194) or partially (Group 2, n = 177) compacted. Group 1 had significantly higher proportions of good- and average-quality blastocysts than Group 2 (21.6% vs. 3.4%, p = 0.001; 47.9% vs. 26.6%, p = 0.001, respectively). The time from the morula stage to the beginning and completion of compaction and blastocyst formation was significantly shorter in Group 1 than in Group 2 (78.6 vs. 82.4 h, p = 0.001; 87.0 vs. 92.2 h, p = 0.001; 100.2 vs. 103.7 h, p = 0.017, respectively). Group 1 embryos had larger surface areas than Group 2 embryos at various time points following blastocyst formation. Group 1 blastocysts had significantly higher average expansion rates than Group 2 blastocysts (653.6 vs. 499.2 µm2/h, p = 0.001). PGT-A revealed a higher proportion of euploid embryos in Group 1 than in Group 2 (47.2% vs. 36.6%, p = 0.303). CONCLUSION: Time-lapse microscopy uncovered a positive relationship between compaction and blastocyst quality and its association with embryo ploidy. Hence, compaction evaluation should be prioritized before blastocyst selection for transfer or cryopreservation.

Clinical Usability of Embryo Development Using a Combined Qualitative and Quantitative Approach in a Single Vitrified-Warmed Blastocyst Transfer: Assessment of Pre-Vitrified Blastocyst Diameter and Post-Warmed Blastocyst Re-Expansion Speed.

Improving the safety and efficacy of assisted reproductive technology programs has been a continuous challenge. Traditionally, morphological grading has been used for embryo selection. However, only a few studies have assessed the morphokinetic variables and morphological dynamics of blastocysts. In the present study, we aimed to perform a quantitative analysis of blastocyst diameter and re-expansion speed. This in-depth morphokinetic evaluation can correlate with currently observed pregnancy outcomes. In total, 658 single vitrified-warmed blastocyst transfer cycles were performed between October 2017 and December 2021, which were divided into four groups according to the pre-vitrified blastocyst diameter. After warming, the groups were subdivided according to the blastocyst re-expansion speed. These quantitative measurements were performed using a time-lapse system. Both diameter and speed are essential in determining the blastocyst quality, while age, day of freezing, and blastocyst quality are crucial from a clinical perspective. The application of both quantitative (diameter and speed) and qualitative (blastocyst quality scores) parameters can help evaluate the clinical usability of blastocysts. This method can prove useful for embryologists in counseling their patients and determining pregnancy patient-oriented strategies.

Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study.

This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact StatementWhat is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient.What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran.What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.

Does Post-Warming Extended Culture Duration Affect the Clinical and Obstetric Outcomes of Patients of Advanced Maternal Age? A Single-Center Study.

BACKGROUND: The single vitrified-warmed blastocyst transfer (SVBT) cycle has been increasingly utilized for assisted reproductive technology. Women of advanced maternal age (AMA) comprise a significant portion of patients who have undergone 'freeze-all' cycles. This study investigated the association between the post-warming extended culture duration and pregnancy outcomes in patients of AMA. METHODS: This retrospective cohort study analyzed the outcomes of 697 SVBT cycles between January 2016 and December 2017. The cycles were divided into 3 groups based on the age of the female partners: group I: < 35 years (n = 407), group II: 35-37 years (n = 176); and group III, 38-40 years (n = 114). Data are shown as the mean ± standard error of the mean. Data were analyzed using one-way ANOVA followed by Duncan's multiple range test. Statistical significance was set at P < 0.001. RESULTS: The blastocyst rate, clinical pregnancy rate, and live birth rate (LBR) was significantly lower in the AMA groups. However, there were no significant differences in LBR in the transfer between the AMA and younger groups according to blastocyst morphology and post-warming extended culture duration. CONCLUSION: Post-warming extended culture of blastocysts is not harmful to patients of AMA. It could be a useful parameter in clinical counseling and decision making for fertility treatments.

Correlation between Morphologic Grading and Euploidy Rates of Blastocysts, and Clinical Outcomes in In Vitro Fertilization Preimplantation Genetic Screening.

BACKGROUND: The standard morphological evaluation has been widely used for embryo selection, but it has limitations. This study aimed to investigate the correlation between morphologic grading and euploidy rate of in vitro fertilization (IVF) preimplantation genetic screening (PGS) and compare the pregnancy rates in young and old ages. METHODS: This is a retrospective study using the medical records of patients who underwent IVF procedures with PGS between January 2016 and February 2017 in a single center. The embryo grades were categorized into 4 groups: excellent, good, fair, and poor. Basic characteristics, euploidy rates, clinical pregnancy (CP) rates and ongoing pregnancy rates were analyzed. RESULTS: The excellent group had significantly higher rate of euploid embryos than fair group (47.82% vs. 29.33%; P = 0.023) and poor group (47.82% vs. 29.60%; P = 0.005). When the four groups were recategorized into two groups (excellent and good vs. fair and poor), they also showed significant difference in euploidy rates (44.52% vs. 29.53%; P = 0.002). When the patients were divided into two groups by age 35, the CP rates for those under and over 35 years old were 44.74% and 47.83%, respectively, which showed no significant difference. CONCLUSION: The significant differences among the euploidy rates of different morphologic embryo grades demonstrated the positive correlations between the morphologic grading of the embryo and the euploidy rate of PGS. Additionally, there was no significant difference between the younger and older patients' CP rates. These findings emphasize the fact that old age patients might benefit from PGS whatever the indication of PGS is.

Effects and pregnancy outcomes of L-carnitine supplementation in culture media for human embryo development from in vitro fertilization.

AIM: Antioxidants have been studied to be effective in improving embryo qualities from in vitro fertilization. L-carnitine (LC) has been known to reduce reactive oxygen species and enhance adenosine triphosphate production, which contribute to the development of a high-quality embryo. This is the first study to include both mouse and human subjects and aimed to evaluate whether LC supplementation in culture media has any beneficial effect on the development of the embryos, as well as its clinical outcomes. METHODS: Mouse embryos were used as models in the animal studies for cell immunofluorescent staining evaluation. Inner cell mass and trophectoderm (TE) cells were counted and statistically analyzed between LC and control groups. For human studies, medical records of patients with infertility undergoing in vitro fertilization procedures from January to May 2017 were included and the embryos were divided into two groups at the two pronuclear stage. Statistical analysis was performed to compare the embryo status and clinical outcomes of the two groups. RESULTS: In the animal study, the LC group showed significantly higher numbers of cells in the inner cell mass and trophectoderm, indicating better development. In the human studies, there were significantly higher numbers of good-quality embryos on days 2, 3 and 5 in the LC group than in the control. The clinical outcomes, such as implantation, clinical pregnancy and ongoing pregnancy rates, were also higher in the LC group than in the control. CONCLUSION: LC supplementation in culture media improved human embryo quality and eventually achieved better pregnancy outcomes.

Preimplantation genetic diagnosis for couples with a Robertsonian translocation: practical information for genetic counseling.

PURPOSE: To evaluate the proportions of abnormal and normal embryos detected by preimplantation genetic diagnosis (PGD) of infertile couples of whom one was a Robertsonian translocation (RT) carrier, and to provide practical information, including details of reproductive outcomes, to aid in genetic counseling of such couples. METHODS: We retrospectively analyzed all PGD cycles conducted to deal with RT at our center between January 2000 and December 2009. Subject demographic and clinical data were compared with the results of PGD. RESULTS: Employing PGD, we conducted a total of 66 cycles on 34 couples of whom one was an RT carrier, including 24 female and 10 male carriers. Of the 514 blastomeres tested, 161 (31.3%) were normal or balanced. Of the 57 cycles that included embryo transfer, 17 (29.8%) attained positivity for human chorionic gonadotropin (hCG). A total of 17 embryos were implanted and 16 babies, including two sets of twins, were born. The takehome baby rate was 41.2% per couple and the loss rate 6.6%. Receiver operating characteristic curve analysis showed that the proportion of alternate embryos associated with a sensitivity of 70.6% for prediction of clinical pregnancy following PGD was 0.31. Sex of the carrier and type of translocation were not significantly associated with pregnancy outcomes. CONCLUSION: Couples with RT may benefit from PGD; pregnancy success rate is improved and embryo loss reduced. We found that about 30% of embryos were of normal or balanced chromosomal constitution and that the percentage of normal or balanced embryos was predictive of PGD outcome.

Molecular and cytogenetic characterization of two azoospermic patients with X-autosome translocation.

PURPOSE: To report two azoospermic patients with reciprocal X-autosome translocations. METHODS: Cytogenetic analysis utilizing GTG-banding and Yq microdeletions shown by polymerase chain reaction (PCR) with 12 sequence-tagged site (STS) markers for Y chromosome microdeletions. RESULTS: Cytogenetic analysis showed one man with 46,Y,t(X;19)(q22;q13.3) and the other with 46,Y,t(X;8)(p22;q11). Neither had any Yq microdeletions shown. The patient with 46,Y, t(X;8)(p22;q11) showed a slightly lower than normal testosterone level. By NCBI-Blast search, we found four testis-specific genes, t-complex-associated-testis-expressed 1-like (TCTE1L), Ferritin, heavy polypeptide-like 17 (FTHL17), Testis expressed sequence 13A (TEX13A), and Testis expressed sequence 13B (TEX13B) located near breakpoints on X chromosome. FTHL17, TEX13A, and TEX13B are spermatogonially-expressed, germ-cell-specific genes. CONCLUSION: This is the first clinical report of azoospermia with reciprocal X-autosome translocations on Xp22 and q22. These translocations on Xp22 and q22 may be direct genetic risk factors for azoospermia.