Aggregates Of Smooth Endoplasmic Reticulum Research Articles

#72 : Embryo Quality and Pregnancy Outcome from Oocytes with Smooth Endoplasmic Reticulum (SER) Aggregates

Background and Aims: Calcium stored and released by the Smooth Endoplasmic Reticulum - SER which has an important role in oocyte maturation, fertilization, and embryo development. The presence of SER aggregate result in the disturbance of calcium stores and its occillation which in turn affect fertilization, embryo develompent, and increasing risk of abnormal cromoseme outcome. Alpha-ESHRE Consensus (2011), strongly recomended to not perform insemination on any oocytes with SER. In the other hand, some previous studies show that healthy babies had been born from oocytes presenting this dymorphism. The aim of this study was to evaluate embryo quality and pregnancy outcome patients derived from oocytes with SER. Method: This study was a crosssectional analysis from 2017-2019 of 223 MII oocytes with SER from 82 women underwent Intra cytoplasmic sperm injection - ICSI. Prior to ICSI, each oocyte was evaluated for the presence of SER Aggregates. The embryological outcome measures were the fertilization rate, embryo quality day 3 and day 5, and pregnancy rates. Results: This study result shown that from 223 oocytes with SER, 89.5% oocytes can be fertilized. Day 3 embryo 66.6% ± 0.000 qualified as good embryo, but only 29.1% ± 0.000 on day 5 embryo. The Pregnancy rate was 30.0%, with 2 miscarriages. It is important to give a well information to the patients on the risk of birth malformations as well as whether a decreased chance of pregnancy exists. Conclusion: Oocyte with SER still has the ability to develop and has the potential to support pregnancy.

P-285 Analysis, including morphokinetic data, of IVF/ICSI cycles with oocytes containing aggregates of smooth endoplasmic reticulum (SER)

Abstract Study question Is there a difference in ART outcomes and morphokinetic parameters for SER+ and SER- cycles and oocytes? Summary answer Fertilisation and blastulation rates are lower in the SER+ group but no difference was seen in pregnancy or live birth rates. What is known already The SER is an organelle found in eukaryotic cells, including oocytes. SERs synthesize lipids and steroids, and store and metabolise calcium ions, needed for fertilization and early embryonic development. SERs can aggregate in the oocyte, forming an intracytoplasmic dimorphism, thought to interfere with reproductive outcomes. It is suggested that SER aggregates in an oocyte may negatively effect embryo development and implantation. Oocytes without SERs, but which arise from the same oocyte cohort as SER+ oocytes may also affect outcomes. Evidence around the safety and use of these SER+ and SER- oocytes is conflicting, with widespread variations in clinical practice. Study design, size, duration A retrospective review was conducted of all IVF/ICSI[MW1] cycles between January 2019 and December 2020 at Merrion Fertility Clinic, Dublin. Cycles containing SER+ oocytes were identified, and their outcomes were compared with those of a matched control group of SER- cycles. Within the SER+ group, results were compared for SER+ and SER- oocytes within the same cohort. Participants/materials, setting, methods Once participants had been identified, a chart review was undertaken noting demographics, IVF protocol used, duration of stimulation, ART and neonatal outcomes and morphokinetic parameters in the embryoscope. Statistical analysis was performed using PRISM. Main results and the role of chance There were 77 SER+ cycles with a total of 135 SER+ oocytes and 645 SER- oocytes, accounting for 8% of total cycles for the study period. These were matched to 64 control cycles with 528 SER- oocytes. 12 embryo transfers occured using blastocysts derived from SER+ oocytes. SER+ cycles had a higher mean oocyte number than controls (9.3 vs 7.3) and 92% of oocytes were mature compared to 88% of the control group. Fertilisation rates were significantly lower in the study group (60% SER+cycle; 68% in SER-cycle), related to the SER+ oocytes in that cohort. Good/top quality blastocyst rates differed (SER+ cycle 28%, SER- cycle 36%) but pregnancy(SER+ cycle 53%, SER- cycle 51%) and livebirth (SER+31%, SER- 32% ) rates were similar, even when blastocysts derived from SER+ oocytes were transferred. 5 morphokinetic variables were studied – time to 2-cell (t2), 3 cell (t3) 4 cell (t4), 5 cell (t5) and time to blastulation (tB). T5 appears to be shorter in embryos derived from SER+ oocytes than in controls, with the other parameters being comparable. In terms of neonatal outcomes there were no congenital malformations reported in the SER+ groups and one case of upper limb amelia in the control group. Limitations, reasons for caution This study is limited by its retrospective nature. We only have embryoscope data on 46 out of 77 patients with SERs, limiting numbers. Embryos transferred which derived from SER+ve oocytes were limited by the clinic policy to only transfer these embryos if no other embryos available. PGT was not performed. Wider implications of the findings This preliminary study shows that, while SER+ cycles have lower fertilisation rates than SER- cycles, pregnancy rates and live birth rates are comparable. Neonatal outcomes are reassuring. Initial analysis of morphokinetic data shows little effect. Larger numbers and further analysis are needed to fully understand the importance of these aggregates. Trial registration number n/a

Characterization of ovarian tissue oocytes from transgender men reveals poor calcium release and embryo development, which might be overcome by spindle transfer.

Can spindle transfer (ST) overcome inferior embryonic development of in vitro matured ovarian tissue oocytes (OTO-IVM) originating from testosterone-treated transgender men?ST shows some potential to overcome the embryo developmental arrest observed in OTO-IVM oocytes from transgender men.OTO-IVM is being applied as a complementary approach to increase the number of oocytes/embryos available for fertility preservation during ovarian tissue cryopreservation in cancer patients. OTO-IVM has also been proposed for transgender men, although the potential of their oocytes remains poorly investigated. Currently, only one study has examined the ability of OTO-IVM oocytes originating from transgender men to support embryo development, and that study has shown that they exhibit poor potential.Both ovaries from 18 transgender men undergoing oophorectomy were collected for the purposes of this study, from November 2020 to September 2022. The patients did not wish to cryopreserve their tissue for fertility preservation and donated their ovaries for research. All patients were having testosterone treatment at the time of oophorectomy and some of them were also having menses inhibition treatment.Sibling ovaries were collected in either cold or warm medium, to identify the most optimal collection temperature. Cumulus oocyte complexes (COCs) from each condition were isolated from the ovarian tissue and matured in vitro for 48 h. The quality of OTO-IVM oocytes was assessed by calcium pattern releasing ability, embryo developmental competence following ICSI, and staining for mitochondrial membrane potential. In vitro matured metaphase I (MI) oocytes, germinal vesicle (GV) oocytes, and in vivo matured oocytes with aggregates of smooth endoplasmic reticulum (SERa) were donated from ovarian stimulated women undergoing infertility treatment and these served as Control oocytes for the study groups. ST was applied to overcome poor oocyte quality. Specifically, enucleated mature Control oocytes served as cytoplasmic recipients of the OTO-IVM spindles from the transgender men. Embryos derived from the different groups were scored and analysed by shallow whole genome sequencing for copy number variations (CNVs).In total, 331 COCs were collected in the cold condition (OTO-Cold) and 282 were collected in the warm condition (OTO-Warm) from transgender men. The maturation rate was close to 54% for OTO-Cold and 57% for OTO-Warm oocytes. Control oocytes showed a calcium releasing ability of 2.30 AU (n = 39), significantly higher than OTO-Cold (1.47 AU, P = 0.046) oocytes (n = 33) and OTO-Warm (1.03 AU, P = 0.036) oocytes (n = 31); both values of calcium release were similar between the two collection temperatures. Mitochondrial membrane potential did not reveal major differences between Control, OTO-Warm, and OTO-Cold oocytes (P = 0.417). Following ICSI, 59/70 (84.2%) of Control oocytes were fertilized, which was significantly higher compared to 19/47 (40.4%) of OTO-Cold (P < 0.01) and 24/48 (50%) of OTO-Warm oocytes (P < 0.01). In total, 15/59 (25.4%) blastocysts were formed on Day 5 in the Control group, significantly higher than 0/19 (0%) from the OTO-Cold (P = 0.014) and 1/24 (4.1%) in OTO-Warm oocytes (P = 0.026). Application of ST rescued the poor embryo development, by increasing the Day 5 blastocyst rate from 0% (0/19) to 20.6% (6/29) (P = 0.034), similar to that in the ICSI-Control group (25.4%, 15/59). A normal genetic profile was observed in 72.7% (8/11) of OTO-Cold, 72.7% (8/11) of OTO-Warm and 64.7% (11/17) of Control Day 3-Day 5 embryos. After ST was applied for OTO-IVM oocytes, 41.1% (7/17) of the embryos displayed normal genetic patterns, compared to 57.1% (4/7) among ST-Control Day 3-Day 5 embryos.N/A.Due to the limited access to human oocytes and ovarian tissue, our results should be interpreted with some caution, as only a limited number of human oocytes and embryos could be investigated.The results of this study, clearly indicate that OTO-IVM oocytes originating from transgender patients are of inferior quality, which questions their use for fertility preservation. The poor quality is likely to be related to cytoplasmic factors, supported by the increased blastocyst numbers following application of ST. Future research on OTO-IVM from transgender men should focus on the cytoplasmic content of oocytes or supplementation of media with factors that promote cytoplasmic maturation. A more detailed study on the effect of the length of testosterone treatment is also currently missing for more concrete guidelines and guidance on the fertility options of transgender men. Furthermore, our study suggests a potentially beneficial role of experimental ST in overcoming poor embryo development related to cytoplasmic quality.A.C. is a holder of FWO grants (1S80220N and 1S80222N). A.B. is a holder of an FWO grant (1298722N). B.H. and A.V.S. have been awarded with a special BOF (Bijzonder Onderzoeksfonds), GOA (Geconcerteerde onderzoeksacties) and 2018000504 (GOA030-18 BOF) funding. B.H. has additional grants from FWO-Vlaanderen (Flemish Fund for Scientific Research, G051516N and G1507816N) and Ghent University Special Research Fund (Bijzonder Onderzoeksfonds, BOF funding (BOF/STA/202109/005)), and has been receiving unrestricted educational funding from Ferring Pharmaceuticals (Aalst, Belgium). The authors declare that they have no conflict of interest.N/A.

Real value of the oocytes with smooth endoplasmic reticulum aggregates in in vitro fertilization/intracytoplasmic sperm injection cycle: a retrospective cohort study

Objective: The management of oocytes affected by smooth endoplasmic reticulum aggregates (SERa) remains debatable. To understand how to manage SERa+ oocytes and cycles, we performed a retrospective cohort study and analyzed the impact of SERa+ cycles and oocytes on clinical and neonatal outcomes. Methods: We included 4856 cycles (149 SERa+ and 4707 SERa−) from 4201 women (age: 21–42 years) who received in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatments at the Center of Reproductive Medicine, First Affiliated Hospital of Army Military University, from 2016 to 2019. SERa+ cycles had at least one SERa oocyte in the oocyte cohort. All 1722 oocytes in the SERa+ cycle were divided into SERa+ (405) and SERa− (1317) oocytes. Results: The rates of two pronuclei (2PN) and high-quality embryos were lower in SERa+ cycles than in SERa− cycles, regardless of IVF or ICSI (P &lt;0.05). As the proportion of SERa+ oocytes increased in the SERa+ cycles, the rate of high-quality embryos declined gradually (P &lt;0.05). Furthermore, the rate of 2PN in SERa+ oocytes was significantly lower than that in SERa− oocytes (P &lt;0.05). Regardless of whether IVF or ICSI insemination was performed, no significant differences in terms of clinical pregnancy rate and spontaneous abortion rate were observed between SERa+ and SERa− cycles or between SERa+ and SERa− oocytes (P &gt;0.05). Conclusion: Normal fertilization with SERa+ cycles and oocytes was substantially reduced, regardless of the insemination method. Embryos originating from SERa+ oocytes can be transferred when there are no other options, but fully informed consent and strict follow-up of fetal development are mandatory.

The impact of oocytes containing smooth endoplasmic reticulum aggregates on assisted reproductive outcomes: a cohort study

BackgroundThe impact of smooth endoplasmic reticulum aggregates (SERa) on assisted reproductive technology (ART) outcomes was still controversial. Our objective is to investigate the impact of the presence of SERa on intracytoplasmic sperm injection (ICSI) outcomes.MethodsThis was a retrospective cohort study. A total of 1,090 fresh ICSI cycles from 944 patients between January 2016 and June 2020 were included. Outcomes from clinical, embryological and neonatal aspects were compared between SERa + and SERa- cycles as well as between SERa + and SERa- oocytes.ResultsThe total gonadotropin (Gn) dose, number of oocytes retrieved, serum estradiol concentration and number of the available embryo were significantly higher in SERa + cycles than in SERa- cycles (P < 0.05). Comparable two pronuclei (2PN) fertilization rate and poly-pronucleus zygote rate were shown in SERa + and SERa- cycles (P > 0.05), but which were higher in SERa + oocytes than in SERa- oocytes (P < 0.05). No statistical difference in blastocyst formation rate was found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). Good-quality embryo rate was statistically higher in SERa- cycles than in SERa + cycles (P < 0.05), but the difference was comparable between SERa + and SERa- oocytes (P > 0.05). No statistical difference in clinical pregnancy rate, spontaneous abortion rate, live birth rate and premature delivery rate were found in SERa + and SERa- cycles as well as in SERa + and SERa- oocytes (P > 0.05). The implantation rate was comparable in SERa + and SERa- cycles (P > 0.05), but it is higher in the group of only SERa- embryo transfer when compared with the group of mixed SERa + and SERa- embryo transfer (P < 0.05). 159 newborns in SERa + cycles and 140 newborns in SERa- cycles were followed up. Comparable newborn malformation rate was observed between SERa + and SERa- cycles and oocytes (P > 0.05). Logistic regression analysis revealed number of oocytes and total dose of Gn were risk factors for SERa occurrence (aOR = 1.05 and 1.55, P < 0.001).ConclusionOocyte's SERa is correlated with a number of oocytes retrieved and higher Gn dose, but it does not affect pregnancy outcomes and increase newborn malformation rate.

Oocytes With Smooth Endoplasmic Reticulum Aggregates May Not Impact Blastocyst Euploidy Rate.

ObjectiveTo investigate whether the euploidy rate of blastocysts derived from smooth endoplasmic reticulum aggregates (SERa) positive cycles and oocytes are impacted.DesignRetrospective cohort study.Method(s)A total of 601 preimplantation genetic testing (PGT) cycles with at least one oocyte retrieved in our center between April 2017 and May 2021 were initially included in the study. Women>35 years and PGT cycles with chromosomal structural rearrangements (PGT-SR) were excluded. Embryological and blastocyst ploidy outcomes were compared among SERa+ oocyte, sibling SERa- oocytes and oocytes in SERa- cycles.ResultsNo significant difference was observed among the SERa+ oocyte group, sibling SERa- oocyte group, and SERa- cycle group in the normal fertilization rate (82.1% vs. 77.8% vs. 83.1%, respectively, P=0.061), blastocyst formation rate (71.0% vs. 72.5% vs. 68.4%, respectively, P=0.393), good quality blastocyst formation rate (46.4% vs. 48.3% vs. 42.6%, respectively, P=0.198). No significant difference was observed in the euploidy rate (50.0% vs. 62.5% vs. 63.3%, respectively, P=0.324), mosaic rate (12.5% vs. 9.7% vs. 13.4%, respectively, P=0.506), and aneuploidy rate (37.5% vs. 27.8% vs. 23.2%, respectively, P=0.137) among the three groups.ConclusionOur results suggest that the euploidy rate of blastocysts derived from SERa+ cycles and oocytes may not be impacted.

P-205 Blastocyst derived from oocytes with smooth endoplasmic reticulum aggregates (SERa) has similar clinical and perinatal outcomes with those of oocytes without SER

Abstract Study question This study was to investigate effect of SERa on the fertilization rate, embryonic development after ICSI, and clinical and perinatal outcomes after single blastocyst transfer. Summary answer SERa (+) derived embryo can be selected as embryos for transfer when no available SERa (-) derived embryos. What is known already Based on findings that the risk of congenital abnormalities in the newborn is higher in ovum with SERa in the cytoplasm, the Istanbul consensus workshop at the 2011 meeting of the ESHRE recommended against fertilizing ovum with SERa due to these risks. However, there have been several reports of healthy infants born from embryos derived from SERa, suggesting that, while more long-term follow-up is necessary, healthy births are possible from such embryos. In 2017, the 2011 recommendations were reviewed in the Alpha/ESHRE consensus (Vienna), which said the approach should be determined on a case-by-case basis. Study design, size, duration We retrospectively investigated 23,007 oocytes which was retrieved between January 2016 and March 2020. Of these, 1,038 oocytes (4.5%) with visible SERa comprised SERa (+), while 21,969 oocytes (95.5%) without SERa comprised SERa (-). Participants/materials, setting, methods SERa were observed under the microscopy after denudation. The rate of fertilization, good-quality day-3 embryos, good-quality day-5 blastocysts, and day-5, 6 or 7 blastocysts were evaluated for both groups. We also compared the rate of clinical pregnancy, live birth, miscarriage, and birth defects in single blastocyst transfer between SERa (+) derived 114 blastocysts and SERa (-) derived 6,290 blastocysts from January 2016 and December 2018. Main results and the role of chance The results are shown. 2PN fertilization rate outcomes after ICSI (SERa(-) eggs vs. SERa(+)eggs),81.4%(17,873/21,969) vs.79.4% (823/1,038),and good-quality day3 rate was 61.1%(10,927/17,873)vs.60.9% (501/823) which was not significantly different. Good-quality day5 blastocyst rate was 46.5% (7,876/16,955) vs. 39.8%(304/763), and day 5 blastocyst success rate was 60.8% (10,317/16,955) vs.54.3% (414/763), which were both significantly lower with SERa(+). (P &amp;lt; 0.001) The day 6 blastocyst success rate was 69.9% (11,849/16,955) vs. 65.5% (500/763) (P = 0.01), and the day 7 blastocyst success rate was 70.9% (12,024/16,955) vs. 67.5% (515/763) (P = 0.04), which were all significantly lower with SERa(+).The clinical pregnancy rate was 39.4% (2,481/6,290) vs. 35.1% (40/114), the live birth rate was 27.7% (1,745/6,290) vs. 26.3% (30/114), and the miscarriage rate was 27.5% (683/2,481) vs. 20.0% (8/40) and the congenital abnormality rate was 1.6% (29/1,757) vs. 0% (0/30) for SERa(-) embryos and SERa(+) embryos, respectively, which were not significantly different. Blastocyst derived from oocytes with SERa has similar clinical and perinatal outcomes with those of oocytes without SERa. Significant differences were examined using the chi-squared test, with p &amp;lt; 0.05, indicating a significant difference. Limitations, reasons for caution Embryos derived SERa (+) were transferred when the patient did not want any more oocytes retrievals, no embryos derived SERa (-) were available, and only if the couple desired embryo transfer after the problems associated with SERa (+) embryos were fully explained. Wider implications of the findings To the best of our knowledge, this study is the largest number of live births investigating the outcome of SERa (+) derived embryos. SERa (+) derived embryo can be selected as embryos for transfer when no available SERa (-) derived embryos. Trial registration number Not Applicable

Oocytes With Smooth Endoplasmic Reticulum Aggregates Are Not Associated With Impaired Reproductive Outcomes: A Matched Retrospective Cohort Study.

ObjectiveTo investigate whether the reproductive outcomes of oocytes with smooth endoplasmic reticulum aggregates (SERa) are impaired.MethodsA total of 2893 intracytoplasmic sperm injection (ICSI) cycles were performed between January 2010 and December 2019 in our center. In 43 transfer cycles, transferred embryos were totally derived from SERa+ oocytes. Each of the 43 cycles was matched with a separate control subject from SERa- patient of the same age ( ± 1 year), embryo condition, main causes of infertility, type of protocols used for fresh or frozen embryo transfer cycles. The clinical pregnancy, implantation, ectopic pregnancy and live birth rate were compared between the two groups.Results43 embryo transfer cycles from SERa- patient were matched to the 43 transferred cycles with pure SERa+ oocytes derived embryos. No significant difference was observed in clinical pregnancy rate (55.81% vs. 65.11%, p=0.5081), implantation rate (47.89% vs. 50.70%, p=0.8667) and live birth rate (48.84% vs. 55.81%, p=0.6659) between the SERa+ oocyte group and the matched group. No congenital birth defects were found in the two groups.ConclusionOur results suggest that the implantation, clinical pregnancy, live birth and birth defects rate of embryos derived from oocytes with SERa are not impaired.

Occurrence of smooth endoplasmic reticulum aggregates in metaphase II oocytes: relationship with stimulation protocols and outcome of ICSI and IVF cycles.

Is there any association between the appearance of smooth endoplasmic reticulum aggregates (SERa) in oocytes and ovarian stimulation, embryological, clinical and neonatal outcomes of ICSI and IVF cycles? A suboptimal prolonged ovarian stimulation is detrimental to oocytes by inducing the occurrence of SERa, which reduces the reproductive potential of oocytes. Controlled ovarian stimulation recruits oocytes of different qualities. Based on current evidence, it was agreed that non-homogeneous cytoplasm may represent the normal variability among oocytes rather than a dysmorphism with developmental significance. The only exception is the appearance of SERa within the ooplasm. Owing to the lack of univocal evidence in this literature about the safety of injecting oocytes with SERa and the mechanism responsible for the occurrence of SERa, this topic is still a matter of debate. A retrospective, longitudinal cohort study performed at a tertiary level public infertility center. We included 1662 cycles (180 SERa+ and 1482 SERa-) from 1129 women (age: 20-44 years) who underwent IVF/ICSI treatments in 2012-2019. The SERa+ cycles had at least one SERa+ oocyte in the oocyte cohort. The SERa- cycles had morphologically unaffected oocytes. We collected stimulation data and embryological, clinical, neonatal outcomes of SERa- and SERa+ cycles and oocytes. Overall, 347 out of 12436 metaphase II oocytes (2.8%) were affected by SER. We performed only 12 transfers involving at least one SERa+ embryo. Stimulation length (P = 0.002), serum progesterone (P = 0.004) and follicle size (P = 0.046) at trigger, number of retrieved (P = 0.004) and metaphase II (P = 0.0001) oocytes were significantly higher in SERa+ than SERa- cycles. Fertilization rate was significantly (P < 0.0001) reduced in SERa+ cycles and oocytes compared to SERa- counterparts. Embryos of SERa+ cycles had a lower blastocyst formation rate compared to embryos of SERa- cycles (P = 0.059). Statistical analysis according to a generalized estimating equation model performed at patient level demonstrated that the duration of ovarian stimulation was predictive of SERa+ oocytes appearance. The clinical success of SERa+ cycles was lower than SERa- cycles, although no differences in neonatal birthweights or malformations were recorded in sibling unaffected oocytes of SERa+ cycles. Given that SERa+ oocytes were discarded in our center for years and transfers of embryos originating from affected oocytes were generally avoided, clinical outcomes of SERa+ cycles are largely attributable to the transfer of embryos derived from unaffected oocytes of SERa+ cycles and we did not have data about newborns from affected oocytes, since none of the transfers involving SERa+ embryos resulted in a progressive clinical pregnancy. For the first time, we speculate that the late-follicular phase elevated serum progesterone caused by a suboptimal prolonged ovarian stimulation may be detrimental to the oocytes by inducing the occurrence of SERa, resulting in negative effects on their reproductive potential. This raises the question of whether some stimulation regimens could be worse than others and a change in stimulation protocol would reduce the possibility of producing oocytes with suboptimal maturation. In particular, our data highlight the importance of correct timing of the trigger in order to maximize oocyte collection, not only in terms of numerosity but also their reproductive potential. None. N/A.

Is it time to reconsider how to manage oocytes affected by smooth endoplasmic reticulum aggregates?

Did the revised Alpha/ESHRE consensus (Vienna, 2017) bring a real answer on managing oocytes with aggregates of smooth endoplasmic reticulum (SERa)? According to the currently available literature, a case by case approach on the time of injecting/inseminating SERa+ oocytes may be not helpful for embryologists making a decision, so we suggest fertilizing both SERa+ and SERa- oocytes and prioritizing embryos derived from SERa- oocytes. In 2011, the Istanbul consensus recommended not to inject/inseminate SER+ oocytes due to adverse foetal outcomes reported in literature. At the end of 2017, a panel of experts reconsidered this recommendation and advised a case by case approach. Hence, with a lack of clear recommendations, in-vitro fertilization practitioners still have heterogeneous attitudes when managing SERa+ oocytes. In this context of controversy, an updated review could be helpful in (i) forming a common language for managing cases of SERa+ oocytes and (ii) offering the most ethical practice and best care for patients seeking infertility treatment or fertility preservation. This review (with a last literature search on 1 June 2018) evaluated the effect of the SER dysmorphism on embryological and neonatal outcomes. Studies were considered for inclusion if they were prospective or retrospective cohort or case-control studies. Electronic searches of the Pubmed and Embase databases were done using the keyword combination: smooth endoplasmic reticulum, SER, oocyte and zygote. Abstracts and articles written in English and limited to humans were included. The search returned a total of 726 studies among which 21 met the inclusion criteria. The literature does not unanimously support a negative association between SERa and embryogenesis, implantation or assisted reproductive therapy outcomes. The reviewed studies reported 112 neonatal outcomes after transfers where at least one embryo originated from oocyte affected by SERa. They included 101 healthy babies, three live births with malformations, three neonatal deaths, one stillbirth and four medical interruptions of pregnancy. After transfer of embryos exclusively derived from SERa+ oocytes, a total of 48 healthy newborns were reported along with four babies with perinatal complications (including one ventricular septal defect), one stillbirth, one neonatal death and one pregnancy termination for multiple malformations. As with any review, this review was limited by the quality of the included studies especially in terms of possible methodological limitations, the limited sample size and the retrospective aspect of the studies. Among the 21 selected studies, seven were abstracts and two were case reports. Of the remaining 14 studies, only three were prospective. The tools used in identifying SERa+ oocytes may have varied from one study to another and a consequent misclassification cannot be excluded. Considering the poor resolution of light microscopy in detecting SER aggregates, we are not sure that apparently SERa- oocytes do not really exhibit such a dysmorphism if they were analysed under electronic microscopy or a time lapse system. In the light of the existing data and the lack of a real link between fertilizing SERa+ oocytes and the occurrence of embryo aneuploidy/malformations, we think that discarding SERa+ oocytes may be not the most ethical approach even in patients with large cohorts on the day of oocyte retrieval. Avoiding the wastage of oocytes and embryos with respect to medical ethics remains a constant concern in daily IVF practice. Thus, we recommend that all mature oocytes could be fertilized and embryos originating from SERa- oocytes would be preferably transferred, even if they come from a cohort with SERa+ oocytes. The remaining embryos derived from SERa+ oocytes could be considered with a lower priority for transfer after obtaining consent from the couple if a strict follow-up of the pregnancy and the baby is performed. We have no conflict of interest to declare and no funding was received. N/A.

Live Birth Rates in In vitro Fertilization Cycles with Oocytes Containing Smooth Endoplasmic Reticulum Aggregates and Normal Oocytes.

Aims:The aims of this study were to compare the live birth, embryological and pregnancy outcomes after intracytoplasmic sperm injection (ICSI) in patients who have oocytes with smooth endoplasmic reticulum aggregates (SERa+ cycles) and patients with normal oocytes and to compare the pregnancy outcomes based on the observed frequency of SERa.Settings and Design:The current study was a retrospective case record review of patients undergoing ICSI from 2012 to 2016 in a specialty fertility center.Materials and Methods:The patients were divided into two groups based on the presence of SERa: patients with at least one oocyte containing SERa (SERa+ cycles) (n = 112) and patients with normal oocytes (n = 839). The primary outcome measure was live birth rate. The secondary outcome measures were fertilization rate, cleavage rate, blastocyst formation rate, clinical pregnancy rate, miscarriage rate, and anomalies in children born.Results:Women with SERa+ cycles showed similar live birth rates, fertilization rates, cleavage rates, blastocyst formation rates, clinical pregnancy rates, miscarriage rates, and abnormalities in children compared to women with normal oocytes. A gradual reduction in live birth rates was observed when the percentage of oocytes containing SERa increased. The group containing >50% of oocytes with SERa demonstrated no live births.Conclusions:Presence of SERa had no major overall negative impact on key embryological and live birth outcomes. A reduction in the live birth rate with increasing proportion of SERa oocytes was observed, with no live births in the group with >50% or all affected oocytes.

Complex chromosomal aberrations in a fetus originating from oocytes with smooth endoplasmic reticulum (SER) aggregates

ABSTRACTThe presence of smooth endoplasmic reticulum aggregates (SERa) in the ooplasm is considered as the most severe oocyte dysmorphism due to its serious and potentially lethal outcomes in offspring. In the present case report, a couple underwent their first intracytoplasmic sperm injection (ICSI) cycle using a gonadotrophin releasing hormone (GnRH) antagonist protocol, followed by fetal ultrasound scanning and amniocentesis. SERa were observed in all oocytes retrieved. A singleton pregnancy was established. The second trimester fetal ultrasound scan revealed a female fetus with overlapping fingers in both hands, and amniocentesis was performed for the detection of chromosomal abnormalities. Comprehensive genetic analysis with the combined use of array-comparative genomic hybridization (CGH), fluoresence in situ hybridization (FISH) and conventional cytogenetics revealed a complex chromosome rearrangement (CCR) involving three break points on two chromosomes, resulting in a reciprocal translocation with a cryptic 2q31 deletion. A week following amniocentesis, there was rupture of amniotic membranes and a stillborn was delivered. This is the first case in the literature to report a CCR with concomitant 2q31 deletion resulting in a well-defined and clinically recognizable contiguous gene syndrome with an abnormal phenotype in a fetus arising from a cohort of oocytes affected by SERa. It is suggested that fertilization and transfer of oocytes with SERa should be avoided, until further research establishes whether there is a causal relationship between the presence of SERa and chromosomal abnormalities in the resulting fetus.Abbreviations: SER: smooth endoplasmic reticulum; ICSI: intracytoplasmic sperm injection; GnRH: gonadotrophin releasing hormone; CGH: comparative genomic hybridization; FISH: fluoresence in situ hybridization; FSH: follicle stimulating hormone; hCG: human chorionic gonadotrophin; OHSS: ovarian hyperstimulation syndrome; IVF: in vitro fertilization; MII: metaphase II; GV: germinal vesicle; CCR: complex chromosome rearrangement

Presence of aggregates of smooth endoplasmic reticulum in MII oocytes affects oocyte competence: molecular-based evidence.

Does the presence of aggregates of smooth endoplasmic reticulum (SERa) impact the transcriptome of human metaphase II (MII) oocytes?. The presence of SERa alters the molecular status of human metaphase II oocytes. Oocytes presenting SERa are considered dysmorphic. Oocytes with SERa (SERa+) have been associated with reduced embryological outcome and increased risk of congenital anomalies, although some authors have reported that SERa+ oocytes can lead to healthy newborns. The question of whether or not SERa+ oocytes should be discarded is still open for debate, and no experimental information about the effect of the presence of SERa on the oocyte molecular status is available. This study included 28 women, aged <38 years, without any ovarian pathology, and undergoing IVF treatment. Supernumerary MII oocytes with no sign of morphological alterations as well as SERa+ oocytes were donated after written informed consent. A total of 31 oocytes without SERa (SERa-) and 24 SERa+ oocytes were analyzed. Pools of 8-10 oocytes for both group were prepared. Total RNA was extracted from each pool, amplified, labeled and hybridized on oligonucleotide microarrays. Analyses were performed by R software using the limma package. The expression profiles of SERa+ oocytes significantly differed from those of SERa- oocytes in 488 probe sets corresponding to 102 down-regulated and 283 up-regulated unique transcripts. Gene Ontology analysis by DAVID bioinformatics disclosed that genes involved in three main biological processes were significantly down-regulated in SERa+ oocytes respective to SERa- oocytes: (i) cell and mitotic/meiotic nuclear division, spindle assembly, chromosome partition and G2/M transition of mitotic cell cycle; (ii) organization of cytoskeleton and microtubules; and (iii) mitochondrial structure and activity. Among the transcripts up-regulated in SERa+ oocytes, the most significantly (P = 0.002) enriched GO term was 'GoLoco motif', including the RAP1GAP, GPSM3 and GPSM1 genes. Raw microarray data are accessible through GEO Series accession number GSE106222 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE106222). Data validation in a larger cohort of samples would be beneficial, although we applied stringent criteria for gene selection (fold-change >3 or <1/3 and FDR < 0.1). Surveys on clinical outcomes, malformation rates and follow-up of babies born after transfer of embryos from SERa+ oocytes are necessary. We provide information on the molecular status of SERa+ oocytes, highlighting possible associations between presence of SERa, altered oocyte physiology and reduced developmental competence. Our study may offer further information that can assist embryologists to make decisions on whether, and with what possible implications, SERa+ oocytes should be used. We believe that the presence of SERa should be still a 'red flag' in IVF practices and that the decision to inseminate SERa+ oocytes should be discussed on a case-by-case basis. This study was partially supported by Ferring Pharmaceuticals. The authors have no conflicts of interest to declare.

Clinical outcomes after IVF or ICSI using human blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER–MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER–MII.

Реализация программ вспомогательных репродуктивных технологий у пациенток с агрегатами гладкого эндоплазматического ретикулума в цитоплазме ооцитов

Реализация программ вспомогательных репродуктивных технологий у пациенток с агрегатами гладкого эндоплазматического ретикулума в цитоплазме ооцитов

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.

The impact of Alpha/ESHRE consensus regarding oocytes with aggregates of smooth endoplasmic reticulum (SERa) on in vitro fertilization outcome.

The present study aimed to gather information on the impact of Alpha/European Society of Human Reproduction and Embryology (ESHRE) consensus regarding oocytes with aggregates of smooth endoplasmic reticulum (SERa) on in vitro fertilization outcome. In particular, we investigated if patients undergoing intracytoplasmic sperm injection (ICSI) and whose oocytes are discarded due to SERa have a higher chance of embryo transfer cancellation compared to patients without SERa oocytes. This is a nested case-control study drawn from the cohort of women referring for in vitro fertilization with ICSI. Cases were patients showing at least one oocyte with SERa at the time of injection. Controls were subsequent patients showing no SERa oocytes and matched ratio 1:1 for age, clinical indication to in vitro fertilization (IVF), and body mass index. The main outcome was the rate of embryo transfer cancellation. The percentage of women experiencing a transfer cancellation (absence of suitable oocytes or viable embryos) in their ICSI cycle were significantly higher in cases (18%) compared to controls (8%) (p = 0.02); however, adjusted odds ratio for FSH and number of SERa oocytes, of follicles, of retrieved oocytes, and of inseminated oocytes were not statistically significant. We have shown that the exclusion of SERa oocytes from ICSI cycles causes an increased frequency of transfer cancellation. This effect is mostly due to the reduced number of available oocytes after exclusion of SERa oocytes.

Policy of IVF centres towards oocytes affected by Smooth Endoplasmic Reticulum aggregates: a multicentre survey study.

The presence of Smooth Endoplasmic Reticulum aggregates (SERa) has been reported to be associated with adverse outcomes. An Alpha-ESHRE Consensus was published in 2011, strongly recommending to not inseminating affected oocytes. On the other hand, healthy babies have been born from oocytes presenting this dysmorphism. We surveyed several European IVF centres, to assess their attitudes concerning affected oocytes. This survey is based on a computer format and includes questions regarding the fate of affected oocytes. About 14% of centres who answered our survey discard SERa+ oocytes. 43% of centres that do not discard the oocytes, register and follow up neonatal data. About a quarter of centres inform their patients about this dysmorphism. Half of them require an informed consent prior to transferring affected embryos. Twenty-one centres reported having SERa+ births, with one reporting a malformation. 48% of centres declared having been influenced by the Alpha-ESHRE Consensus, in their management policy of SERa+ oocytes. Few centres scrupulously respect the recommendations of the Alpha-ESHRE Consensus and discard affected oocytes. Since it is essential to determine if there truly is an impact of this dysmorphism and whether the guidelines are still valid, transfer of affected embryos should only be done when accompanied with data recording and monitoring of all foetal malformations from IVF. Clarifying the situation will allow IVF centres to correctly inform patients about the risk of birth malformations as well as whether a decreased chance of pregnancy exists.

Can healthy babies originate from oocytes with smooth endoplasmic reticulum aggregates? A systematic mini-review.

Is it time to reconsider whether oocytes affected by smooth endoplasmic reticulum aggregates (SERa) should still be destroyed? At the time of writing, the literature shows that 171 apparently healthy babies have been born from SERa+ cycles amongst which 22 were from SERa+ oocytes. The SER dysmorphism has been associated with negative embryological, clinical and neonatal outcomes, which led to a recommendation in 2011 to avoid inseminating affected oocytes. The data in the literature are nevertheless conflicting and some centres have continued using SERa+ oocytes. A systematic mini-review of the literature to 7 November 2013 was performed with the keywords 'Smooth Endoplasmic Reticulum' and 'oocyte', limited to humans and written in English. Articles (Pubmed) and major abstracts where the effect of the SER dysmorphism was studied as an individual feature on embryological, clinical or neonatal outcomes were included in this review. From a total of 297 publications identified, 13 were selected as being relevant to this review. One hundred eighty-three babies have been reported to be born from SERa+ cycles, 171 were healthy, 8 live births presented malformations, 3 were neonatal deaths, 1 was a stillborn and additionally 4 terminations of pregnancy occurred. Data concerning SERa+ oocytes in the literature are scarce, the studies are small, heterogeneous and results are conflicting. The malformations observed could be due to over-reporting of scattered alarming results. Alternatively, an under-reporting of complications cannot be excluded. Centres that have or that are including transfers of SERa+ embryos in their IVF procedures should publish their clinical and neonatal outcomes as well as the follow-up of children. The birth of healthy babies from SERa+ embryos is encouraging and might lead in the future to a revision of the current consensus on the SER dysmorphism. Further research is needed to understand the origin of this dysmorphism and help avoid its occurrence. Therefore, until we have a better understanding of the situation, transfers of affected embryos should be carried out with caution. We have no conflicts of interest to declare and no funding was received.

Reply: Delivery of normal babies from embryos originating from oocytes showing the presence of smooth endoplasmic reticulum aggregates

Reply: Delivery of normal babies from embryos originating from oocytes showing the presence of smooth endoplasmic reticulum aggregates