Smooth Endoplasmic Reticulum Clusters Research Articles

Should we really discard oocytes with Smooth Endoplasmic Reticulum Clusters (SERC+)?

Background and Aim: Several studies have reported an increased number of unhealthy newborns from SERC + oocytes, consequently, some groups do not recommend their use for in vitro fertilization treatments. However, there are some studies reporting that IVF treatments using SERC + oocytes have given rise to healthy newborns, hence supporting their use. The aim of this study is to determine whether the potential of SERC+ oocytes is compromised for in vitro fertilization.

Metaphase II (MII) human oocytes with smooth endoplasmic reticulum clusters do not affect blastocyst euploid rate

ObjectiveTo investigate whether the rate of euploidy and pregnancy outcomes are affected by smooth endoplasmic reticulum clusters (SERc) and other metaphase II human oocyte dysmorphisms. Materials and methodsRetrospective analysis of the morphologies of metaphase II (MII) human oocytes, which had developed into 590 biopsied blastocysts derived from 109 patients that received preimplantation genetic testing for aneuploidies (PGT-A) cycles between March 2013 and December 2017. The euploid rate of blastocysts that originated from morphologically abnormal or normal oocytes were analyzed. The chromosome status of the blastocysts was determined and analyzed by array comparative genomic hybridization (aCGH) or next generation sequencing (NGS) following trophectoderm biopsy. ResultsAccording to the odds ratios obtained for each oocyte morphotype, no statistically significant relationship was found between oocyte dysmorphisms and euploid rate. Specifically, although SERc-positive oocytes had a higher rate of arrest at two pronuclei, or 2 PN (26.7% vs. 19.4%, p > 0.05), the blastocyst formation rate was not affected as compared with SERc-negative oocytes (40.0% vs. 38.6%, p > 0.05). Among nine euploid embryos derived from oocytes with SERc, three single euploid embryo transfers were performed, of which one resulted in blighted ovum, and two resulted in the births of two healthy, singleton term babies. ConclusionThe results presented here suggest that oocyte dysmorphisms do not affect the euploidy rate of the blastocyst. The occurrence of SERc in the oocyte does not seem to impair the developing blastocyst nor does it interfere with good embryo formation rate and euploid rate. Thus, the embryos derived from SERc-positive oocytes could still be considered for embryo transfer if there are no other embryos available.

Smooth Endoplasmic Reticulum Clusters in Oocytes From Patients Who Received Intracytoplasmic Sperm Injections Negatively Affect Blastocyst Quality and Speed of Blastocyst Development.

Findings regarding the relationship between smooth endoplasmic reticulum clusters (SERCs) in oocytes and blastocyst development have been conflicting. In this study, the effects of SERCs on blastocyst quality and the speed of blastocyst development were evaluated. Patients who received intracytoplasmic sperm injections (ICSI) at our reproductive center from 2016 to 2020 were retrospectively analyzed. SERC (+) oocytes (n = 217) and SERC (–) oocytes (n = 822), as well as SERC (+) cycles (n = 146) and SERC (–) cycles (n = 1,951) were compared. There was no significant difference in embryological, clinical, and neonatal outcomes between the SERC (+) and SERC (–) cycles. The fertilization rate (73.9%), good quality blastocyst rate (26.7%) and the speed of blastocyst development (44.4%) were significantly lower (P < 0.05) in SERC (+) oocytes than in unaffected counterparts (86.2%, 44.1% and 63.4%, respectively). Furthermore, the proportion of blastocysts with trophectoderm (TE) grade C was significantly higher in the SERC (+) oocyte group than in the SERC (–) oocyte group (73.3 vs. 55.9%, P < 0.05). After adjusting for age, years of infertility, endometriosis, stimulation protocols (GnRHa), and male infertility, multiple logistic regression analysis revealed that the presence of SERCs in the oocytes significantly affected the speed of blastocyst development (odds ratio, 2.812; 95% CI, 1.257–6.292; P = 0.012). These findings suggest that the presence of SERCs in oocytes may negatively affect blastocyst quality and the speed of blastocyst development.

Pure Smooth Endoplasmic Reticulum (SER) Inclusions in Granulocytes of MYH9-Related Disorder Patients

MYH9-related disorders are a group of disorders (May-Hegglin anomaly, Fechtner syndrome, Sebastian syndrome) characterized by macrothrombocytopenia and ribosome inclusions in granulocytes. They are caused by mutations in the MYH9 gene and, depending on the location of the mutation, are associated with extrahematological pathologies (sensorineural hearing loss, progressive nephropathy, presenile cataracts) of variable intensity.The inclusions are formed by single and clustered ribosomes and are partially surrounded by segments of rough endoplasmic reticulum (RER). Typical inclusions in May-Hegglin anomaly are spindle-shaped, well-defined, and contain longitudinal filaments. Those found in Sebastian and Fechter syndromes are round or oval, have no filaments and, sometimes, show cross-striated arrangement of the ribosome aggregates.When reviewing the electron micrographs of the granulocyte inclusions of 10 patients with MYH9-related disorders previously published (Pujol-Moix et al. Haematologica 2004;89:330-337) we observed a special type of inclusion not described in the article. This inclusion has the typical appearance of smooth endoplasmic reticulum (SER) clusters, that is, a meshwork of branching tubules of SER without limiting membranes and no other structures such as ribosomes or RER. In 3 of the patients reviewed, in addition to the typical inclusions of MYH9-related disorder, some granulocytes with SER clusters were observed. These clusters were rounded or oval in shape and, when present, were 1 or 2 per cell (Fig. 1).The patients who presented granulocyte SER clusters are those identified as B4, C6 and D8 in the Haematologica article and are briefly described in Table 1. The patients presenting with SER clusters showed different characteristics such as age, bleeding, platelet counts, and proportion of giant platelets. Therefore, we cannot relate the presence of SER clusters to any clinical or biological characteristic of patients. It should be noticed that we did not find SER clusters in any patient with May-Hegglin anomaly. However, the small number of cases studied does not allow any conclusions to be drawn.SER clusters have been described in different types of cells such as hepatocytes or kidney tubular epitelial cells (Ghadially FN. Ultrastructural Pathology of the Cell and Matrix. Butterwords. London, 1988, pp 422-427). Normal granulocytes (neutrophils, eosinophils, and basophils) besides their own specific granules, also contain other general subcellular structures, including dispersed SER membranes. However, SER membranes forming clusters in these cells have not been previously described. In addition, SER clusters do not seem to correspond to evolved forms of typical MYH9 inclusions, for example by degranulation of the RER, based on the observations that typical inclusions show abundant ribosomes but few RER segments, no appreciable ribosomes are observed in the SER clusters, and the morphology of the tubules forming the SER and RER is different.We suggest that SER clusters could be considered a new type of inclusion in MYH9-related disorders. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

P–570 Embryos originating from oocytes with smooth endoplasmic reticulum clusters have a lower euploidy rate via PGT-A testing using next-generation sequencing

Abstract Study question Does the presence of smooth endoplasmic reticulum clusters (sERCs) in oocytes affect the human embryo ploidy? Summary answer The euploidy rate of embryos originating from sERCs + oocytes is lower What is known already While an expert panel strongly recommended that sERCs+ oocytes should not be inseminated, some normal healthy babies derived from sERCs+ oocytes have been reported. In previous studies have shown that declined fertilization rate and lower proportions of good quality embryos are found in oocytes showing sERCs. The updating findings of the molecular status of sERC+ oocytes elucidated the sERCs+ oocytes may have impaired chromosomal segregation ability. However, no study reveals the relation between sERCs and embryo ploidy. Study design, size, duration A retrospective study enrolled 129 preimplantation genetic testing (PGT) cycles from January 2017 to March 2020 at Chang Gung Memorial Hospital, Lonkou. Participants/materials, setting, methods ICSI fertilization rate, Day5 usable blastocyst rate (D5UBR), total usable blastocyst rate (TUBR), euploidy rate, mosaic rate, and aneuploidy rate are investigated between embryo originating from sERCs+ and sERCs- oocytes. Main results and the role of chance Although higher TBUR in blastocyst derived from sERCs+ oocytes than sERCs- group (73.7% vs. 62.5%) but accompanied lower euploidy rate (7% vs. 29%) and higher aneuploid rate (79% vs. 54%). Limitations, reasons for caution Limited sample size, need a large-scale study to confirm the conclusion. The live-birth rate per embryo transfer cycle was not included for analysis. As we did not perform polar body analysis, we cannot state for sure that embryonic aneuploidy was related to the oocyte. Wider implications of the findings: This study demonstrates that embryos originating from sERCs+ oocytes have a lower euploidy rate. Trial registration number CMRPG3H0751

O-209 The impact of sperm DNA fragmentation on pregnancy outcomes depends on oocyte dimorphisms

Abstract Study question Does the impact of sperm DNA fragmentation (SDF) on Intracytoplasmic sperm injection (ICSI) outcomes depend on the presence of oocyte dimorphisms? Summary answer There is a significant influence of oocyte quality on the impact of SDF on pregnancy outcomes. What is known already Sperm DNA fragmentation has been associated with ICSI outcomes. DNA damage is commonly encountered in human spermatozoa and it has been widely accepted that the oocyte assumes responsibility for the repair and remodelling of both the maternal and paternal genomes during the oocyte-embryo transition. Indeed, spermatozoa with DNA damage can fertilise oocytes and still lead to embryo development due to the oocyte DNA repair capacity. Considering the vital role played by the oocyte in the developmental process, it could be hypostatised that the oocyte quality, translated as oocyte morphology, would influence the machinery responsible for sperm DNA repair after fertilization. Study design, size, duration This cohort study included 3,035 oocytes from 525 patients undergoing ICSI cycles in a university-affiliated IVF-center, between June/2016 and July/2019. Oocytes were split into groups according to the SDF index of the sample used for ICSI: low-fragmentation (&amp;lt;30% SDF, n = 2,277) and high-fragmentation (≥30% SDF, n = 758). Oocytes were evaluated before sperm injection and the dimorphisms were recorded. The influence of SDF index on ICSI outcomes, depending on the presence of oocytes dimorphisms was evaluated. Participants/materials, setting, methods Data was evaluated using generalized linear models (GZLM) followed by Bonferroni post hoc. The results are expressed as mean ± standard error for continuous variables or percentages for dichotomous variables, and p-values. The sample size calculation suggested that a sample of at least 504 subjects had 95% power to detect a 20% effect with a significance level of 5% (α). The study was performed in a private university–affiliated in vitro fertilization (IVF) center. Main results and the role of chance The association of both factors: the presence of oocyte dimorphisms (dark cytoplasm, vacuoles in the ooplasm, and resistant membrane) and high SDF index resulted in the lowest fertilization rate among groups, while oocytes free of these dimorphisms injected with samples with &amp;lt;30% SDF had the highest fertilization rate (p = 0.05, p &amp;lt; 0.01 and p &amp;lt; 0.01 for dark cytoplasm, vacuoles in the ooplasm and resistant membrane respectively). The impact of SDF index on high quality embryos rate on cleavage stage was also influence by the presence smooth endoplasmic reticulum clusters and resistant membrane oocytes (p = 0.013 and p = 0.018). As for the clinical outcomes, the impact of SDF index on the implantation rate was influenced by the presence of vacuoles in the ooplasm (p &amp;lt; 0.01), smooth endoplasmic reticulum clusters (p &amp;lt; 0.01), large perivitelline space (p &amp;lt; 0.01), resistant membrane (p &amp;lt; 0.01), and non-resistant membrane (p &amp;lt; 0.01), while the influence of SDF index on the pregnancy rate was influenced by the presence large perivitelline space (p &amp;lt; 0.01), resistant membrane (p = 0.018) and non-resistant membrane (p &amp;lt; 0.01). The effect of SDF on the miscarriage rate was also increased in the presence of large perivitelline space (p = 0.045), non-resistant membrane (0.037) and centrally located cytoplasmic granular area (p = 0.025). Limitations, reasons for caution The retrospective nature is a limitation. It could be argued that using samples with high SDF index does not necessarily mean that a sperm cell with a fragmented DNA was injected, however, the higher the SDF index, the higher the chance of selecting one with fragmented DNA. Wider implications of the findings The findings presented here highlight the crucial role of male and female factors when facing assisted reproduction. The association of low oocyte quality and high SDF index may lead to impaired results. As the oocyte defect cannot be modified, in vivo upgrading of spermatozoa before the treatment should be encouraged. Trial registration number Not applicable

A higher incidence of smooth endoplasmic reticulum clusters with aromatase inhibitors.

PurposeThis study aimed to analyze whether a regimen of aromatase inhibitor (AI) could reduce the occurrence of smooth endoplasmic reticulum clusters (sERCs) in oocytes.Method(s)The AI and the clomiphene citrate (CC) regimens were compared, regarding the sERC (+) rates and the serum estradiol and progesterone levels on the date of hCG administration, and the duration of AI, CC, and hMG administration.Result(s)The occurrence of sERCs in oocytes from patients treated with AI was significantly higher than that in oocytes from those treated with CC. Both the serum estradiol and progesterone levels were found to be significantly higher in sERC (+) than in sERC (‐) cycles. With regard to the CC cycles, no significant differences were detected. The duration of AI and hMG administration was longer for sERC (+) than for sERC (‐) cycles.ConclusionAs AI did not reduce the occurrence of sERCs, the elevation of estradiol may not be the cause of sERC occurrence but a consequence. Considering the higher levels of progesterone and longer duration of hMG in sERC (+) cycles, the negative effects of premature luteinization, which frequently occur with the AI protocol, should be investigated further.

Simulated physiological oocyte maturation has side effects on bovine oocytes and embryos.

Oocyte maturation is a complex process involving nuclear and cytoplasmic modulations, during which oocytes acquire their ability to become fertilized and support embryonic development. The oocyte is apparently "primed" for maturation during its development in the dominant follicle. As bovine oocytes immediately resume meiosis when cultured, it was hypothesized that delaying resumption of meiosis with cyclic nucleotide modulators before in vitro maturation (IVM) would allow the oocytes to acquire improved developmental competence. We tested the Simulated Physiological Oocyte Maturation (SPOM) system that uses forskolin and 3-isobutyl-1-methylxanthine for 2h prior to IVM against two different systems of conventional IVM (Con-IVM). We evaluated the ultrastructure of matured oocytes and blastocysts and also assessed the expression of 96 genes related to embryo quality in the blastocysts. In summary, the SPOM system resulted in lower blastocyst rates than both Con-IVM systems (30 ± 9.1 vs. 35 ± 8.7; 29 ± 2.6 vs. 38 ± 2.8). Mature SPOM oocytes had significantly increased volume and number of vesicles, reduced volume and surface density of large smooth endoplasmic reticulum clusters, and lower number of mitochondria than Con-IVM oocytes. SPOM blastocysts showed only subtle differences with parallel undulations of adjacent trophectoderm plasma membranes and peripherally localized ribosomes in cells of the inner cell mass compared with Con-IVM blastocysts. SPOM blastocysts, however, displayed significant downregulation of genes related to embryonic developmental potential when compared to Con-IVM blastocysts. Our results show that the use of the current version of the SPOM system may have adverse effects on oocytes and blastocysts calling for optimized protocols for improving oocyte competence.

Strontium fails to induce Ca2+ release and activation in human oocytes despite the presence of functional TRPV3 channels.

STUDY QUESTIONAre the transient receptor potential cation channels vanilloid 3 (TRPV3) present and able to mediate strontium (Sr2+) induced artificial activation in human oocytes?SUMMARY ANSWERSr2+ did not induce Ca2+ rises or provoke activation in human oocytes, however, mRNA for the TRPV3 channel was present in metaphase II (MII) human oocytes after IVM and TRPV3 agonists induced Ca2+ rises and oocyte activation, demonstrating the channels were functional.WHAT IS KNOWN ALREADYSelective activation of TRPV3 by agonists induces Ca2+ entry and promotes mouse oocyte activation, and the absence of TRPV3 channels in mouse oocytes prevents Sr2+ mediated artificial activation. Sr2+ is sometimes used to overcome fertilization failure after ICSI in the clinic, but its efficiency is still controversial and the mechanism(s) of how it mediates the Ca2+ flux has not been studied yet in human.STUDY DESIGN, SIZE, DURATIONThe protein distribution (n = 10) and mRNA expression level (n = 19) of the TRPV3 channels was investigated in human MII oocytes after IVM. The Sr2+ (10 mM) and TRPV3 agonists (200 μM 2-aminoethoxydiphenyl borate [2-APB] and 200 μM carvacrol)-induced Ca2+ response was analyzed in human (n = 15, n = 16 and n = 16, respectively) and mouse oocytes (n = 15, n = 19 and n = 26, respectively). The subsequent embryonic developmental potential following the parthenogenetic activation using these three agents was recorded in human (n = 10, n = 9 and n = 9, respectively) and mouse (n = 20 per agent) oocytes, by determining pronucleus, or 2-cell and blastocyst formation rates.PARTICIPANTS/MATERIALS, SETTING, METHODSMII oocytes from B6D2F1 mice (6–10 weeks old) as well as human IVM oocytes and IVO oocytes (from patients aged 25–38 years old) with aggregates of smooth endoplasmic reticulum clusters were used. The expression of TRPV3 channels was determined by immunofluorescence staining with confocal microscopy and RT-PCR, and the temporal evolution of intracellular Ca2+ concentration was measured by time-lapse imaging after exposure to Sr2+ and TRPV3 agonists (2-APB and carvacrol). Artificial activation efficiency was assessed using these agents.MAIN RESULTS AND THE ROLE OF CHANCESr2+ did not promote Ca2+ oscillations or provoke activation in human oocytes. Transcripts of TRPV3 channels were present in IVM MII human oocytes. TRPV3 protein was expressed and distributed throughout the ooplasm of human oocytes, rather than particularly concentrated in plasma membrane as observed in mouse MII oocytes. Both agonists of TRPV3 (2-APB and carvacrol), promoted a single Ca2+ transient and activated a comparable percentage of more than half of the exposed human oocytes (P > 0.05). The agonist 2-APB was also efficient in activating mouse oocytes, however, significantly fewer mouse oocytes responded to carvacrol than 2-APB in both the Ca2+ analysis and activation test (P < 0.001).LIMITATIONS REASONS FOR CAUTIONThe availability of fresh IVO matured oocytes in human was limited. Data from TRPV3 knockout model are not included.WIDER IMPLICATIONS OF THE FINDINGSThe benefit of clinical application using Sr2+ to overcome fertilization failure after ICSI requires further validation.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by FWO-Vlaanderen, China Scholarship Council and Special Research Fund from Ghent University (Bijzonder Onderzoeksfonds, BOF). No competing interests are declared.

A higher incidence of cleavage failure in oocytes containing smooth endoplasmic reticulum clusters.

In human oocytes, sERCs are one of the dysmorphic phenotypes that have been reported. Significantly reduced pregnancy rates and a comparatively higher number of abnormities in live births appear to be associated with the presence of sERCs in oocytes. However, some reports have shown that healthy babies can be born, without any reduced pregnancy rates, from oocytes observed to contain sERCs. Thus, the clinical and scientific significance of oocytes that harbor sERCs remains controversial. The presence of sERCs was evaluated using a time-lapse system while studying the dynamic changes within oocytes and embryos. Logistic regression analysis was carried out to explore the independent variables for meiotic and mitotic cleavage failure.. The incidence of mitotic cleavage failure and the incidence of meiotic cleavage failure during the second polar body extrusion in oocytes with sERCs were found to be significantly higher than that in oocytes without sERCs. Furthermore, ICSI was found to have a greater frequency of meiotic failure than IVF. In cases of cleavage failure, an embryonic cell could become tetraploid and may induce abnormal chromosomal configurations. Some cells exposed to cleavage failure may become trophectoderm cells and form placental abnormalities. Even if they develop into trophectoderm cells, the ICM can be susceptible to further cleavage failure and may in turn cause further aneuploidy. For these reasons, it is important to monitor pregnancies and births derived from oocytes that contained sERCs.

Dysmorphic patterns are associated with cytoskeletal alterations in human oocytes.

Are specific morphological anomalies in human mature oocytes, as revealed by transmitted light microscopy, associated with intrinsic damage to the meiotic spindle and actin cytoskeleton? Aggregates of smooth endoplasmic reticulum (SER) and domains of centrally localized granular cytoplasm (GC) reflect intrinsic damage to the oocyte cytoskeleton, namely alterations in spindle size, chromosome misalignment and cortical actin disorganization. In preparation for ICSI, oocytes are often selected for use in treatment by morphological criteria, but the rationale and implications of this practice are controversial. Very little information is available on the relationship between oocyte morphology and intrinsic cellular characteristics, such as the actin cytoskeleton, meiotic spindle and chromosome alignment. A total of 170 metaphase II (MII) oocytes were donated by consenting IVF patients and analysed; 62 were classified as morphologically normal (control), 54 had SER clusters and 54 had centrally localized GC. Supernumerary oocytes were fixed within 3 h from recovery and stained for tubulin, chromatin and actin. Spindles were analysed for 1D and 2D characteristics by high-performance confocal microscopy. Chromosomes were classified as scattered or aligned and the conformation and intensity of cortical actin was evaluated. In comparison with control oocytes, both SER and GC oocytes showed greater spindle length (P = 0.033 and 0.003, respectively) and GC oocytes also showed greater spindle width (P= 0.049) and area (P= 0.036). Control and SER oocytes had statistically comparable rates of chromosome displacement from the metaphase plate, unlike GC oocytes where chromosome displacement occurred at higher rate (P = 0.013). In situations where a complete Z-stack was reconstructed from a polar angle, chromosome disposition was classified as being normal when two sets of concentric arrays were visible. Based on these parameters, the proportions of oocytes with normal chromosomal arrangement or partial/total disarrangement was not statistically different between control and SER oocytes. Conversely, in GC oocytes, chromosome disarrangement was higher (P = 0.002). All control oocytes displayed a continuous meshwork of suboolemmal actin, which appeared as an uninterrupted ring in thin optical sections. In contrast, in SER and GC groups, integrity of suboolemmal actin was observed in only 66.7 and 42.9% of oocytes, respectively (P = 0.0001). N/A. Only two of several known oocyte dysmorphisms were investigated, while oocyte quality was assessed only by cytoskeletal criteria. This study represents a significant step toward a more objective assessment of oocyte morphology, offering information that can assist embryologists to make a more aware and rationally founded decision on whether, and with what possible implications, oocytes with certain dysmorphic characters should be used for treatment or discarded. More generally, it also demonstrates that morphometric parameters of the cytoskeleton and chromosome organization can be used as biomarkers of oocyte quality. This study was funded by Biogenesi Reproductive Medicine Centre (Monza, Italy). All authors declare no conflict of interests.

Developmental potential of oocytes with smooth endoplasmic reticulum clusters and their behaviors observed by time-lapse recording system

We previously reported that oocyte morphology was associated with embryo quality and viability, suggesting that controlled assessment of oocyte morphology is useful to predict human embryo quality.During intracytoplasmic sperm injection (ICSI), we occasionally observe oocytes with smooth endoplasmic reticulum clusters (sERC) (Otsuki et al, 2004), which are thought to disappear after fertilization and be closely associated with poor prognosis in achieving pregnancy. This study aimed to investigate the developmental potential of oocytes with sERC and their behaviors using time-lapse recording system. Research study We collected the data of 6,765 matured oocytes retrieved after controlled ovarian hyper-stimulation from August 2010 to September 2015. During ICSI, three experienced embryologists noticed oocytes containing vacuole-like structures, which were defined as sERC by their disappearance at the zygote stage. These embryos were incubated and imaged by either high-resolution time-lapse cinematography or EmbryoScope®. Developmental velocity, rate of clinical use in embryo transfer or cryopreservation, and achieving pregnancy were compared between oocytes with [sERC(+)] and without sERC [sERC(-)]. Of the 6,765 mature oocytes, 46 (0.7%) showed sERC(+). The developmental velocity of embryos derived from sERC(+) oocytes was significantly higher than that of sERC(-) oocytes, including the time of 2nd polar body (PB) extrusion, pronuclei (PN) formation, and syngamy from the ICSI procedure (in h: 2.5±0.6 vs. 2.9±1.0, 7.6±2.4 vs. 9.9±3.9, and 20.7±2.2 vs. 23.7±4.5, respectively; P<0.05). The sERC all disappeared by 4.3±1.2 h after ICSI in the period from 2nd PB extrusion to PN formation. The rate of clinical use of sERC(+) oocytes was 80.4% (37/46), of which 6 underwent fresh embryo transfer and 31 were cryopreserved. In total, 15 embryos were transferred (6 fresh embryos, 9 frozen/thawed embryos), the pregnancy rate was 40% (6/15), and miscarriage rate was 33.3% (2/6). Moreover, the live birth rate was 50.0% (3/6) and one is still ongoing. Healthy babies were born from oocytes with sERC(+). This study demonstrated that oocytes with sERC could develop into good quality embryos and achieve successful pregnancy resulting in healthy babies. Further follow-up of the children are clearly needed, and mechanisms of the emergence of sERC and its impact on embryonic development are still under investigation. Detailed studies with molecular biological methods are necessary.

Embryological outcomes in cycles with human oocytes containing large tubular smooth endoplasmic reticulum clusters after conventional in vitro fertilization

There have been no studies analyzing the effect of large aggregates of tubular smooth endoplasmic reticulum (aSERT) after conventional in vitro fertilization (cIVF). The aim of this study was to investigate whether aSERT can be identified after cIVF and the association between the embryological outcomes of oocytes in cycles with aSERT. This is a retrospective study examining embryological data from cIVF cycles showing the presence of aSERT in oocytes 5–6 h after cIVF. To evaluate embryo quality, cIVF cycles with at least one aSERT-metaphase II (MII) oocyte observed (cycles with aSERT) were compared to cycles with normal-MII oocytes (control cycles). Among the 4098 MII oocytes observed in 579 cycles, aSERT was detected in 100 MII oocytes in 51 cycles (8.8%). The fertilization rate, the rate of embryo development on day 3 and day 5–6 did not significantly differ between cycles with aSERT and control group. However, aSERT-MII oocytes had lower rates for both blastocysts and good quality blastocysts (p < 0.05). aSERT can be detected in the cytoplasm by removing the cumulus cell 5 h after cIVF. However, aSERT-MII oocytes do not affect other normal-MII oocytes in cycles with aSERT.

Deliveries of babies with normal health derived from oocytes with smooth endoplasmic reticulum clusters

To examine the impact on development of derived embryos from smooth endoplasmic reticulum clusters (SERC) in human metaphase II (MII) oocytes. Retrospective analysis at Kyono ART Clinic. Comparison of embryological development, pregnancy, live birth and fetal malformation between oocytes with SERC (the SERC(+) group) and those without (the SERC(-) group) in 2,158 patients (3,758 cycles) after ICSI. Fertilization and implantation rate were significantly lower in SERC(+) MII oocytes than in SERC(-) MII oocytes. After the transfer of fresh and vitrified embryos derived from SERC(+) oocytes, 14 pregnancies resulted in 14 healthy babies, including 2 from fresh embryo transfer (ET) and 12 from vitrified-warmed ET, with no malformations. The presence of SERC in MII oocytes was associated with significantly lower fertilization rates and implantation rates than seen in SERC(-) MII oocytes within SERC (+) cycles. However, SERC had no impact on post-implantation development as well as neonatal outcome.

Development of babies following use of embryos with smooth endoplasmic reticulum clusters (sERC) in human metaphase II oocytes

Development of babies following use of embryos with smooth endoplasmic reticulum clusters (sERC) in human metaphase II oocytes

Influence of oocyte dysmorphisms on blastocyst formation and quality

To identify the association between oocyte dysmorphisms and blastocyst developmental competence. Case-control study. Private assisted reproduction center. This study included 5,516 embryos, which were obtained from 605 patients undergoing intracytoplasmic sperm injection cycles in which ET was performed on day 5 of embryo development. Intracytoplasmic sperm injection and ET. The morphologic characteristics of the blastocysts, namely the degree of blastocoel expansion and hatching status, the size and compactness of the inner cell mass (ICM), and the cohesiveness and number of trophectoderm cells, were correlated with oocyte dysmorphisms. Of the 5,516 embryos evaluated, 2,920 (52.9%) reached the blastocyst stage. The blastocysts' degree of expansion and hatching status were decreased by the presence of aggregates of smooth endoplasmic reticulum clusters, large perivitelline space, and shape abnormalities. The presence of a large perivitelline space also decreased the ICM and trophectoderm cell quality. Aggregates of smooth endoplasmic reticulum clusters also decreased the ICM quality, pregnancy rate, and the miscarriage rate. The results presented here suggest that the individual identification of oocyte dymorphisms may be a prognostic tool for blastocyst development and quality. However, the results do not diminish the importance of cleavage-stage embryo morphology assessment to predict blastocyst development competence.

Intracytoplasmic Morphological Abnormalities in Human Oocytes

In human oocytes, many types of abnormal phenotypes have been observed both within the cytoplasm and outside of the cytoplasm. The morphological evaluation of oocytes and its impact on embryo quality has been controversial. However, abnormal oocyte phenotypes can be directly influenced by the follicular environment, ovarian function and the effects of ovarian stimulation used in assisted reproductive technology. This review focuses on four critical intracytoplasmic anomalies; fluid-filled vacuoles, smooth endoplasmic reticulum clusters (sERC), refractile bodies / lipofuscin bodies and centrally located cytoplasmic granularity (CLCG). The fine structures, morphological and immunochemical characteristics and the possible mechanism giving rise to each phenotype are discussed.

Impact of smooth endoplasmic reticulum clusters (SER) in oocyte cytoplasm on embryo quality and pregnancy outcome

Impact of smooth endoplasmic reticulum clusters (SER) in oocyte cytoplasm on embryo quality and pregnancy outcome

P-55: Clinical outcome of transferences of human embryos derived from oocytes with smooth endoplasmic reticulum clusters (SERC)

P-55: Clinical outcome of transferences of human embryos derived from oocytes with smooth endoplasmic reticulum clusters (SERC)

The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes.

During ICSI, we occasionally observe pronucleus sized translucent vacuoles. We investigated why these vacuoles occur and determined the effect on pregnancy outcome. Translucent vacuole-positive oocytes and the corresponding cohort were examined by transmission electron microscopy (TEM) and histochemical staining with DiI and ER-Tracker. Stimulation methods, hormonal levels, patients' condition and grade of transferred embryos were compared between vacuole-positive and vacuole-negative cycles. By TEM, we confirmed that the vacuoles were tubular-type smooth endoplasmic reticulum clusters (sERCs). Numerous small sERCs were also observed in the oocytes from the same cohort. Veeck's grades of transferred embryos were higher in sERC-positive cycles and fertilization rate was similar to those of sERC-negative cycles. However, in sERC-positive cycles, significantly lower pregnancy and higher biochemical pregnancy rates were shown. Serum estradiol levels on the day of hCG administration were significantly higher in sERC-positive cycles. The presence of sERCs is associated with lower chances of successful pregnancy, even in sERC-negative oocytes from the same cohort that are transferred along with the sERC-positive oocytes. High estradiol levels could be one of the causes of sERC formation.