Intracytoplasmic Sperm Injection Treatment Cycles Research Articles

P-745 effectiveness and safety of consecutive single embryo transfer compared to double embryo transfer: results from UK HFEA registry

Abstract Study question How does two-consecutive single embryo transfer (2xSET) affect reproductive outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) compared to double embryo transfer (DET)? Summary answer 2xSET may provide greater or comparable live birth rates with lower multiple birth, preterm birth, and pregnancy loss or neonatal death rates compared to DET. What is known already Elective single embryo transfer (SET) in IVF/ICSI is widely encouraged over DET to minimise the risk of multiple birth and associated morbidities. Despite this, UK multiple birth rates following IVF remain higher than spontaneous conception, with 5% of IVF pregnancies resulting in multiple birth compared to 0.4%-1.2% multiple gestation rates following spontaneous conception. Owing to advancements in cryopreservation techniques, live birth and ongoing pregnancy rates are now comparable between fresh and frozen embryo transfer. Consequently, 2xSET has been suggested as an alternate technique to achieve comparable live birth rates with fewer multiple gestation pregnancies compared to DET. Study design, size, duration This retrospective cohort study was conducted using Human Fertilisation and Embryology Authority (HFEA) register data, which encompasses national data from all IVF clinics in the UK. Within this analysis, all women who underwent their first oocyte collection and IVF or ICSI treatment cycle with subsequent SET, DET or 2xSET between 2010 and 2019 using either blastocyst or cleavage stage embryos were included (N = 125,149). Participants/materials, setting, methods This national retrospective cohort study utilised UK HFEA register data from 2010-2019, including all women who underwent their first oocyte collection and subsequent embryo transfer (N = 125,149). The rate of live birth, multiple birth, preterm birth, and pregnancy loss or neonatal death was compared between SET, DET, and 2xSET IVF/ICSI pregnancies using either blastocyst or cleavage stage embryos, and was stratified by maternal age. Data analysis was conducted in RStudio v4.2, alpha equals 0.05. Main results and the role of chance 2xSET pregnancies following blastocyst-stage transfer achieved a greater live birth occurrence rate of 0.47 (0.13) (median (interquartile range)) than SET, 0.41 (0.13), and DET, 0.38 (0.13) (P < 0.05). When using SET as a reference standard, 2xSET achieved a lower multiple birth rate, odds ratio (OR) of 6.87 (95%CI 6.14-7.68), than DET, OR 28.20 (95%CI 25.20-31.57), and lower preterm birth rate; OR 1.11 (95%CI 1.06-1.15) in 2xSET, and OR 2.80 (95%CI 2.67-2.94) in DET. Pregnancy loss or neonatal death rate was also lower in 2xSET, OR 1.14 (95%CI 1.08-1.21), compared to DET, OR 2.11 (95%CI 1.98-2.24). Conversely, in cleavage-stage embryo transfer pregnancies, no significant difference in live birth occurrence rate was observed, achieving rates of 0.27 (0.21) for SET, 0.26 (0.13) for DET, and 0.29 (0.18) for 2xSET. 2xSET was less likely to result in multiple birth than DET, OR 0.14 (95%CI 0.11-0.19). Moreover, when using SET as a reference standard, 2xSET was less likely to result in preterm birth than DET, OR 1.02 (95%CI 0.87-1.23) and 2.48 (95%CI 2.17-2.82) respectively, as well as pregnancy loss or neonatal death, OR 1.07 (95%CI 0.85-1.35) and 2.03 (95%CI 1.70-2.42) respectively. Limitations, reasons for caution Certain confounders are not recorded within HFEA registry data, including patient body mass index (BMI), evaluation of embryo quality, and endometrial thickness at embryo transfer. Consequently, while our analysis identifies broad trends in embryo transfer success and morbidity, results may differ within certain patient populations. Wider implications of the findings 2xSET may provide greater or comparable live birth rates with lower multiple birth and morbidity than DET. Promotion of 2xSET where appropriate for maternal age and embryo quality should be implemented to enhance reproductive outcomes and reduce the risk of morbidity in IVF/ICSI pregnancies. Trial registration number Not Applicable

The Association of ICSI Outcomes with Semen and Blood Bisphenol A Concentrations of the Male Partner.

This study investigated the association of blood and semen Bisphenol A (BPA) levels of the male partner on the reproductive outcome in intracytoplasmic sperm injection (ICSI) treatment cycles. For this prospective study (ClinicalTrials.gov identifier: NCT02703584), blood and semen samples of the male partner of the 75 women who had ICSI were analyzed. The study group consisted of men who had ICSI for male factor infertility other than azoospermia, while men with normal spermiogram whose partners underwent ICSI due to tubal factor infertility were taken as the study group. Habitual consumption of drinking water from plastic carboys/bottles (PBW) at home was also questioned in both groups as it was considered as chronic BPA exposure. The association of ICSI outcome with blood BPA (bBPA) and semen BPA (sBPA) levels was analyzed in both groups. No significant correlation was found between sperm parameters and bBPA levels in both groups. A negative correlation was found between sBPA levels and total sperm count and progressive sperm motility in men who consumed PBW. Embryo development arrest was found to be significantly higher in patients who have high sBPA levels. Although sBPA levels were not different in PBW consumers, bBPA levels were found to be significantly lower in those who consumed tap water (TW) than those who used PBW. Elevated bBPA were associated with a significant decrease in clinical pregnancy rate. Considering the widespread human exposure to BPA, the effect of BPA on the male reproductive system needs to be further examined.

Clinical and neonatal outcomes of using a modified micro cryotube for cryopreservation of small numbers of spermatozoa for TESA-ICSI cycles

Cryopreservation of a small number of human spermatozoa is still a major challenge for embryologists. The aim of this study was to evaluate the clinical pregnancy and neonatal outcomes of intracytoplasmic sperm injection (ICSI) using a modified micro cryotube as freezing carrier for freezing small numbers of human spermatozoa collected by testicular sperm aspiration (TESA). We conducted a retrospective study to analyses the ICSI outcomes of using frozen-thawed few testicular spermatozoa in males with obstructive azoospermia (OA) from June 2017 to June 2021. Of 155 ICSI treatment cycles, 79 cycles were allocated to frozen sperm group and a modified micro cryotube was used for freezing testicular sperm, 76 cycles were allocated as fresh sperm group. No significant differences were observed in fertilization rate, good quality embryo rate, and blastocyst rate between the frozen sperm group and fresh sperm group (P > 0.05). Similarly, in the fresh embryo transfer cycles plus the first frozen-thawed embryo transfer cycles, the total clinical pregnancy rate (54.43% vs 57.89%), implantation rate (46.08% vs 49.47%), miscarriage rate (13.95% vs 13.64%) and live birth rate (45.57% vs 48.68%) were not statistically different between the frozen and fresh sperm groups (P > 0.05). In addition, there was no statistical differences in the mean gestational age (38.33weeks ± 1.74 vs 37.89weeks ± 1.87), preterm delivery rate (5.56% vs 10.81%), mean birth weight at delivery (3026.50 g ± 577.64 vs 2977.56 g ± 528.93), and low birth weight (12.50% vs 19.51%) between the two groups (P > 0.05 in all cases). Modified micro cryotube for cryopreservation of rare testicula rretrieved spermatozoa did not negatively affect the pregnancy and neonatal outcomes in TESA-ICSI cycles. The presented method may be a useful alternative for cryopreservation of small numbers of human spermatozoa in clinical setting.

P-206 An evaluation of the incidence of total failed fertilization (TFF) following conventional IVF (cIVF) and the outcome of subsequent intracytoplasmic sperm injection (ICSI) cycles

Abstract Study question What is the incidence of TFF following conventional IVF (cIVF) and the chance of live birth in subsequent ICSI treatment cycles after TFF? Summary answer The incidence of TFF might be higher than previously reported and establishment of in-house benchmarks are recommended. Treatment continuation results in acceptable live birth rates. What is known already TFF following a cIVF is a devastating outcome for patients and physicians. The fear of this unfortunate event is assumable one of the main drivers for overutilizing ICSI. The incidence of TFF after cIVF should be less than 5 % of stimulated cycles based on ESHREs recommended performance indicators. Data on TFF of an unselected population is indeed however only available from an era when ICSI was not in use and showed a higher rate. We investigated the incidence of TFF and evaluated the chance of live birth following of such event at the first cycle. Study design, size, duration A single center, retrospective chart review for the time period of 2010-2021 was done to identify all cycles where cIVF did not result in at least one oocyte with ≥ 2 pronuclei. Also, patients who had more than 2 oocytes retrieved in their first cycle and continued their treatment using ICSI as a fertilization method in their upcoming cycles were selected. Participants/materials, setting, methods A total of 5772 initiated IVF cycles were identified in the electronic database for the examined time period. Criterion for cIVF was normozoospermia and applied as fertilization method in 1001 (17.3%) cycles. All the cases where TFF was noted following cIVF were retrieved and the number of oocytes, the rank of the cycle, female age and the result of upcoming cycles if any were recorded. Data was analyzed using Chi-Square test, p < 0.05 was considered significant. Main results and the role of chance A total of 125 TFF cycles were identified out of the 1001 cIVF cycles (12.49% failed fertilization rate per cIVF). A significantly higher frequency of TFF was seen in cycles where less than 3 oocytes were retrieved compared to those with more than two oocytes (38/99 [38.38%] vs. 87/902 [9.65%], p < 0.001). No statistical difference was detected between the risk of TFF occurring at the first, second or the third rank cIVF cycle (87/664 [13.10%], 30/224 [13.39%], 5/75 [6.67%] respectively; p > 0.05). The differences remained non-significant when only cycles with more than 2 oocytes were analyzed (67/608 [11.02%], 16/199 [8.04%], 4/68 [5.88%] respectively; p > 0.05). Also, different age groups showed similar incidence of TFF (16/157 [10.19%], 41/362 [11.33%], 54/381 [14.17%] and 14/101 [13.86%] in < 30, 31-35, 36-40 and >40 years of age respectively; p > 0.05). A total number of 56 patients were identified who continued their treatment using ICSI as fertilization method in their upcoming cycles. These patients completed 101 cycles resulting in 3 TFF cases (3%) and a fertilization rate of 75.1% (524/698) which was significantly higher to our baseline ICSI fertilization rate (70.9% [25231/35568]; p < 0.05). Nineteen of these 56 patients (33.9%) ended up giving at least one live birth following treatment continuation. Limitations, reasons for caution Selection criteria, e.g. patient characteristics and treatment type such as PGT-A, for choice of fertilization method are probably a source of variation in TFF incidence between centers. It is recommended that laboratories establish their own benchmark values based on their own data for the incidence of TFF. Wider implications of the findings Previous studies identified serum luteinizing hormone and progesterone levels at trigger and the number of oocytes as critical predictors for TFF. The similar chance of TFF after previous successful fertilization suggests more involvement of female factors in TFF. Acceptable live birth rates can be achieved following treatment continuation. Trial registration number not applicable

The Influence of Vaginal Dysbiosis on Intracytoplasmic Sperm Injection Outcome.

In women of reproductive age, vaginal infection is a gynaecological condition with various health consequences. Bacterial vaginosis, vulvovaginal candidiasis, and aerobic vaginitis are the most prevalent types of infection. Although reproductive tract infections are known to impact human fertility, no consensus guidelines on microbial control in infertile couples undergoing in vitro fertilization therapy are currently available. This study aimed to determine the effect of asymptomatic vaginal infections on the outcome of intracytoplasmic sperm injection in infertile Iraqi couples. Forty-six asymptomatic infertile Iraqi women were evaluated for genital tract infections by taking a vaginal sample on ovum pick-up for microbiological culture during their intracytoplasmic sperm injection treatment cycle. Based on the acquired results, a multi-microbial community colonized the participant's female lower reproductive tract, and only 13 women achieved pregnancy compared to 33 who did not. Candida albicans was found in 43.5% of the cases, 39.1% Streptococcus agalactiae, 19.6% Enterobacter species, 13.0% Lactobacillus, 8.7% Escherichia coli, 8.7% Staphylococcus aureus, 4.3% Klebsiella, and 2.2% Neisseria gonorrhoeae. However, no statistically significant effect was observed on the pregnancy rate except for Enterobacter spp. and Lactobacilli. In conclusion, the majority of patients had a genital tract infection; Enterobacter spp. had a substantial negative influence on the pregnancy rate, and lactobacilli were highly related to positive outcomes in participating females.

Assisted Oocyte Activation following Intracytoplasmic Sperm Injection: A Sensible Option for Infertile Couples with Severe Teratozoospermia.

The intracytoplasmic sperm injection (ICSI) has significantly improved male factor infertility treatment; however, complete fertilization failure still occurs in 1-5% of ICSI treatment cycles mainly due to oocyte activation failure. It is estimated that around 40-70% of oocyte activation failure is associated with sperm factors after ICSI. Assisted oocyte activation (AOA) as an effective approach to avoid total fertilization failure (TFF) has been proposed following ICSI. In the literature, several procedures have been described to overcome failed oocyte activation. These include mechanical, electrical, or chemical stimuli initiating artificial Ca2+ rises in the cytoplasm of oocytes. AOA in couples with previous failed fertilization and those with globozoospermia has resulted in varying degrees of success. The aim of this review is to examine the available literature on AOA in teratozoospermic men undergoing ICSI-AOA and determine whether the ICSI-AOA should be considered as an adjunct fertility procedure for these patients.

The serum oestradiol/progesterone ratio on the day of OPU + 7, but not the day of OPU + 5, affects the rates of live birth in fresh blastocyst embryo transfer cycles

BackgroundIn an in vitro fertilization (IVF) cycle, the embryo ends its wandering time and begins the process of implantation into the uterine cavity on the seventh day after oocyte pick-up (OPU + 7), which is closer than OPU + 5 to the time of nidation. Therefore, measuring the oestradiol (E2)/progesterone (P) ratio on OPU + 7 may be helpful for predicting pregnancy outcomes.MethodsThis is a retrospective cohort study of 2,257 women undergoing a follicular-phase depot gonadotropin-releasing hormone agonist (GnRH-a) protocol for in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh blastocyst embryo transfer cycles at a university-affiliated fertility center between January 2016 and April 2021. First, 2,257 women were split into two groups based on clinical pregnancy for analyzing the levels of E2 and P and the E2/P ratio on the day of OPU + 2, OPU + 5 and OPU + 7. And then 2,257 cycles were stratified into three groups based on E2/P ratio tertiles on OPU + 7: the low group (1.3–15.7 pg/ng), middle group (15.7–28.8 pg/ng), and high group (28.8–487.2 pg/ng). The threshold effect of the E2/P ratio on OPU + 7 on live birth was investigated using a two-piecewise linear regression model and a smoothing function curve.ResultsThe level of P in the clinical pregnancy group were lower than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (201.9 ± 71.6 ng/ml vs 213.1 ± 77.6 ng/ml, 89.5 ± 88.5 ng/ml vs 99.5 ± 94.9 ng/ml, P < 0.05). The E2/P ratio in the clinical pregnancy group were higher than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (8.4 ± 6.5 pg/ng vs 8.0 ± 6.8 pg/ng, 32.3 ± 38.5 pg/ng vs 25.2 ± 31.0 pg/ng, P < 0.01). The E2/P ratio on OPU + 7 was positively associated with positive hCG (adjusted OR = 1.01; 95% CI, 1.01–1.02; P < 0.0001), clinical pregnancy (adjusted OR = 1.01; 95% CI, 1.00–1.01; P = 0.0067) and live birth (adjusted OR = 1.01; 95% CI, 1.00–1.01; P < 0.001), and a nonlinear correlation was observed between the E2/P ratio and LBR on OPU + 7.ConclusionsA higher E2/P ratio is associated with a higher LBR, but the E2/P ratio should be maintained within a suitable range.

Effects of microvibration stimulation on developmental potential of discarded germinal vesicle oocytes of human.

This research aims to study the effects of continuous microvibration stimulation on the parthenogenetic development of human germinal vesicle oocytes. Ninety-five discarded germinal vesicle oocytes from intracytoplasmic sperm injection treatment (ICSI) cycles performed at Amcare Women's & Children's Hospital between January and December 2021 were used for conventional static culture as well as 10Hz microvibration culture. We investigated the differences between the two groups in terms of oocyte maturation rate, parthenogenetic activation rate, and parthenogenetic blastocyst formation rate. The static culture and 10Hz microvibration culture of 95 oocytes showed that the parthenogenetic blastocyst formation rate in the microvibration culture group was significantly higher than those in the traditional static culture group. A continuous microvibration stimulation can significantly improve the parthenogenetic developmental potential of human immature oocytes.

P–038 Clinical outcomes of 77 testicular sperm extraction treatment cycles in non-mosaic Klinefelter syndrome patients

Abstract Study question What are the clinical results of patients with azoospermia and nonmosaic Klinefelter syndrome, using fresh and cryopreserved sperm? Summary answer The results showed a recovery rate of testicular sperm in the order of 40% and a life newborn rate of 52% when using fresh sperm What is known already In Klinefelter syndrome (KS), the rates of successful testicular sperm retrieval were shown to be similar either using conventional TESE or micro-TESE (Corona et al., 2017), which highlights that the variability observed between studies is due to differences in patient characteristics. There are a few works with a large number of KS patients elucidating the clinical outcomes using fresh and cryopreserved testicular sperm. However, these studies revealed contradictory outcomes, either revealing better (Greco et al., 2013; Vicdan et al., 2016) or worst (Madureira et al., 2014) results with cryopreserved testicular sperm, or finding no differences (Chen et al, 2019). Study design, size, duration This study includes all patients up to 2019 presenting azoospermia due to non-mosaic Klinefelter syndrome (n = 76) that went for infertility consultations in a private fertility clinic. Patients were evaluated by the same Urologist. The genetic analysis of the patients was performed at an academic institution. At examination patients did not refer other complaints besides infertility, and referred to have not received any hormone replacement therapy in the past. Participants/materials, setting, methods The 76 azoospermic patients with non-mosaic Klinefelter syndrome (KS) were treated by testicular sperm extraction (TESE) followed by intracytoplasmic sperm injection (ICSI), using fresh and cryopreserved testicular sperm. Most patients used fresh testicular sperm, where others preferred to postpone ICSI treatment cycles and used cryopreserved testicular sperm. Aneuploidy screening in children was performed by prenatal diagnosis and MLPA (Multiplex ligation-dependent probe amplification). Full embryological, clinical and newborn outcomes are provided. Main results and the role of chance Of the 76 patients with non-mosaic Klinefelter syndrome, one repeated the testicular sperm extraction (TESE) procedure. Testicular sperm were recovered in 31/77 (40.3%) of the cases. Comparisons between the 31 cases with successful sperm recover (group–1) and the 46 cases without a successful TESE (group–2) revealed no significant differences regarding age, time of infertility, testicular volume, serum levels of FSH, LH and testosterone, total number of testicular fragments analyzed, and time of search in samples. The mean male age was 34 years. In most of the cases, the testicular volume was reduced (96.1%), the levels of FSH (98.3%) and LH (94.1%) were increased, and the levels of testosterone were normal (77.6%). There were 25 intracytoplasmic sperm injection (ICSI) treatment cycles using fresh testicular sperm and 22 ICSI treatment cycles using frozen testicular sperm. The rates of fertilization (63.5% fresh sperm vs 41.6% frozen sperm), implantation (37% fresh sperm vs 13.2% frozen sperm), clinical pregnancy (60.9% fresh sperm vs 19% frozen sperm), live birth delivery (52.2% fresh sperm vs 19% frozen sperm) and newborn (65.2% fresh sperm vs 23.8% frozen sperm) were higher in the group using fresh testicular sperm. Chromosome analysis of the 21 newborn was normal. Limitations, reasons for caution Although presenting a high number of cases with azoospermic non-mosaic Klinefelter syndrome treated with testicular sperm extraction and intracytoplasmic sperm injection, future studies are needed with a higher number of cycles using frozen testicular sperm, in order to confirm or rebut that the freezing methodology affects negatively the clinical outcomes. Wider implications of the findings: Data adds further information regarding testicular sperm retrieval rates and use of fresh or frozen testicular sperm in Klinefelter syndrome (KS) patients. High newborn rates were obtained only with fresh testicular sperm. Results also reassure KS patients about the safety relative to any abnormal chromosomal transmission to the born children. Trial registration number Not applicable

Paternal Exposure to Non-essential Heavy Metal Affects Embryo Cleavage and Implantation in Intracytoplasmic Sperm Injection (ICSI) Cycles: Evidence for a Paradoxical Effect.

Although the adverse effects of non-essential heavy metals on semen quality have been demonstrated in experimental animal models and occupational human exposure studies, little is known about the reproductive efficiency of exposed sperm during the process of intracytoplasmic sperm injection (ICSI). Our study aims to evaluate the effect of paternal exposure to non-essential heavy metals on embryo efficiency outcomes (embryo cleavage, fragmentation, implantation, and live birth) in ICSI cycle. Ninety-five heterosexual couples who underwent 95 ICSI cycles and 78 fresh embryo transfers between January 2003 and December 2009 were evaluated. Men whose female partner was undergoing ICSI were asked to provide semen and blood samples. Heavy metal levels (Pb, Cd, As, Hg, Ba, and U) were analyzed using an ion-coupled plasma-mass spectrometry (ICP-MS; Agilent 7500 ce, Agilent Technologies, Germany) equipped with a cell dynamic range (CDR). Paternal exposure to trace heavy metals was found to influence intermediate reproductive endpoints in ICSI cycles. After adjusting for paternal and maternal confounders, paternal blood concentrations of Cd [-0.30(-0.11,-0.02)], As [-0.26(-0.16,-0.11)], and U [-0.22(-0.24,-0.02)] were inversely associated with embryo cell cleavage on day 3. Counterintuitively, paternal blood and semen Pb levels [0.26(0.01,0.22); 0.25(0.03,0.14)] as well as semen U levels [0.27(0.01,0.19)] were positively associated with the proportion of implanted embryos. There were no significant associations observed for clinical pregnancy and live birth rates with any paternal heavy metal concentrations in semen and blood. These findings highlight the importance of paternal health for embryo efficiency outcomes in ICSI treatment cycles and the need for more male partner inclusive counseling in fertility practice. They also underline a paradoxical positive association between some heavy metal pollutants at low exposure levels and reproductive outcomes.

Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; response of women categorized as poor-prognosis to recombinant growth hormone adjuvant therapy (Study 4)

In this fourth study examining the relevance of measuring the IGF profile (IGF-1, IGFBP-3 and the ratio of IGFBP-3/ IGF-1) in women presenting for assisted reproductive technologies (ART), we have examined the influence of recombinant growth hormone (rGH) prescribed as an adjuvant on the profile. Of 1633 ART-naïve women who completed an assessment cycle (AC) workup, and which included an IGF profile, 941 women proceeded to an in-vitro fertilization ± intracytoplasmic sperm injection (IVF±ICSI) treatment cycle during the period January 2011 to December 2019. Among those women, 90 were prescribed rGH because they were classified as likely poor-prognosis cases on the basis of advanced age or evidence of severely reduced ovarian reserve parameters. These women had their IVF±ICSI treatment within 3-months of their AC and consented to a second IGF profile measurement 4-6 weeks during their rGH treatment phase. Of the 90 women prescribed rGH adjuvant, 71 used the adjuvant and 19 deferred the treatment, but still completed the second IGF-profile. The data showed that rGH caused a significant elevation in IGF-1 (p&lt;0.0001) as well as its main binding protein, IGFBP-3 (p&lt;0.001), albeit to a lesser degree. Consequently, the IGF ratio, considered a more reliable marker of IGF-1 activity, was shown to be significantly reduced towards the normal range (p&lt;0.0001). The data of clinical outcomes from these 90 women as well as the entire 941 women entering the IVF±ICSI treatment are presented for comparison, noting these data are not suitable for statistical evaluation as the groupings are disparate and unmatched. Further studies are intended to show the clinical relevance of increasing the IGF-1 levels in the analytical investigation of rGH as an adjuvant in ART.

Does a hyperechogenic endometrial mass in the uterus during controlled ovarian stimulation affect assisted reproductive technology cycle outcomes?

ObjectivesHealthy embryos and endometrial receptivity are keys to the success of in-vitro fertilization and embryo transfer (IVF–ET). Abnormal transvaginal ultrasonography (TVU) findings in the endometrium are a concern during assisted reproductive technology (ART) treatments. Observation of a hyperechogenic endometrial mass (HEM) during controlled ovarian stimulation (COS) in an IVF or intracytoplasmic sperm injection (ICSI) cycle is a dilemma. Here we investigated whether an HEM would affect ART cycle outcomes. Study designWe analyzed all data from patients who underwent IVF or ICSI treatment cycles from January 1, 2009 to December 31, 2016 at our institution. Patients diagnosed with an HEM were included. Each woman was matched with two control subjects of similar age (± 1 year), in terms of the number of cycles, type of infertility (primary or secondary), protocol used for COS, but with no HEM identified by TVU. Baseline characteristics, COS response, and pregnancy outcomes after ET were compared. ResultsIn all, 1088 patients were diagnosed with an HEM. Of these, 426 met the inclusion criteria and were matched with 852 controls. Baseline characteristics showed no significant differences between the groups. The peak endometrial thickness was significantly greater in the experimental group than in the control group (1.15 ± 0.18 cm vs. 1.08 ± 0.21 cm, p < 0.001). The live birth rates were 43.7% vs 46.2% in the experimental and control groups, respectively. There were no significant between-group differences in the rates of biochemical or clinical pregnancy or abortions at any stage. ConclusionsNewly diagnosed HEMs < 18 mm in diameter monitored by TVU did not impair the outcomes of ART following COS in this study. If other conditions are suitable, completion of ART cycles should be the appropriate approach in such cases. Key messageNewly diagnosed hyperechogenic endometrial masses measuring <18 mm in diameter monitored by TVU during COS did not adversely affect the outcomes of these IVF/ICSI–ET cycles.

Performing ICSI within 4 hours after denudation optimizes clinical outcomes in ICSI cycles

BackgroundThe study aimed to investigate whether and how general and partial time intervals between processes, from human chorionic gonadotrophin (HCG) trigger to intracytoplasmic sperm injection (ICSI), affected the laboratory and reproductive outcomes in ICSI cycles.MethodsThis was a retrospective data analysis of 3602 women who underwent ICSI treatment cycles using partner or donor sperms, performed at Reproduction Medicine Center of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology (Wuhan, China) between October 2016 and September 2018. The clinical pregnancy rate was the major outcome in the study. The fertilization and available embryo rates were secondary outcomes.ResultsData from 3602 consecutive fresh ICSI cycles was analysed. Multivariate linear regression and logistic regression analysis of factors related to fertilization and clinical pregnancy rates showed that fertilization rate (P = 0.001) and clinical pregnancy rate (P = 0.037) were significantly associated with denudation (DN)-ICSI interval. Long DN-ICSI interval was associated with higher rate of fertilization than short DN-ICSI interval but significantly decreased clinical pregnancy rate when the interval is over 4 h (P < 0.05).ConclusionsDN-ICSI time interval can act as an independent predictor for clinical outcomes in ICSI cycles. The optimal time for ICSI is within 4 h after oocyte denudation for excellent laboratory and reproductive outcomes in ICSI cycles.

Predictors of live birth in women with a history of biochemical pregnancies after assisted reproduction treatment

ObjectivesTo ascertain whether women with a history of biochemical pregnancies (BPs) in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles have decreased chances of live birth (LB); and (2) to build a predictive model for LB in this particular population of infertile women. MethodsIn order to achieve the first objective, data from 1536 women that had a LB using autologous fresh or frozen embryos, or dropped out of further IVF/ICSI treatments after completing one to three unsuccessful treatment cycles were retrospectively analyzed. A subpopulation of 90 women that experienced one or more BPs in our assisted reproduction unit were selected to build a predictive logistic regression model for LB. ResultsLB percentages significantly decreased from a value of 55.3 % in women with no history of previous BPs to 30.9 % and 11.1 % in women that displayed a history of one or more than one BP, respectively. Three out of 35 selected potential predictors were finally included into the model: “number of the last embryo transfer cycle resulting in a BP”, “women’s age”, and “oligo-, astheno-, and/or teratozoospermia”. The value of the c-statistic was 0.819 (asymptotic 95 % CI: 0.724-0.913). The model adequately fitted the data with no significant over or underestimation of predictor effects. Conclusion(1) A history of BPs is negatively associated with later chance of LB in women undergoing a series of IVF/ICSI treatment cycles; and (2) LB probability of women with a history of BPs can be predicted using a model with excellent discriminatory capacity.

Analysis of the women with the AMH concentrations below the limit of reference range but with the ideal number of retrieved oocytes.

Serum anti-Mullerian hormone (AMH)shows a strong positive correlation to the number of oocytes retrieved but the patients undergoing assisted reproductive technology (ART) with lower AMH concentrations also could retrieve an ideal number of oocytes sometimes. The aim of the current study was to assess the performance of this population. This retrospective study included a total of 44 in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment cycles as test group, in which their AMH levels were below the limit of reference range but more than 7 eggs were retrieved, and 103 control cases enrolled from May 2016 to December 2018 after matched with the same range of age from 24 to 38years old and the same number range of retrieved oocytes from 7 to 18 and chosen randomly according to clinical ovarian stimulation protocols by the ratio of 3:7. Several parameters, which include age, basal endocrine status, number of oocytes, the maturation rate of eggs, 2PN fertilization rate, 3PN rate, total fertilization rate, cleavage rate, 8-cell embryo rate of D3 and the utilization rate of embryo, were compared and evaluated between twogroups by Wilcoxon rank-sum test and t test for two independent samples. Although the same age range from 24 to 38years and the same retrieval eggs from 7 to 18, compared with the control group, the test group showed less number of oocytes collected (9.455 vs 10.767, p = 0.016), younger ages (28.36 vs 32.59, p = 0.000), and higher FSH of basal endocrine status (9.783 vs 7.338, p = 0.021). Between the two groups, there were no significant differences in parameters such as the mature eggs (7.05 vs 7.92, p = 0.079), the mature oocyte rate (74.189% vs 73.916%, p = 0.924), the number of 2PNs (5.36 vs 5.91, p = 0.236), 2PN rate (73.678% vs 75.125%, p = 0.769), the number of 3PNs (0.39 vs 0.50, p = 0.773), 3PN rate (5.104% vs 5.592%, p = 0.697), number of total fertilizations (6.77 vs 7.35, p = 0.241), total fertilization rate (96.461% vs 93.166%, p = 0.332), cleavage rate (82.003% vs 81.382%, p = 0.673), the number of 8-cells on D3 (1.59 vs 1.91, p = 0.227), the rate of 8-cell on D3 (36.259% vs 41.084%, p = 0.551) and the utilization rate of embryo (62.853% vs 61.824%, p = 0.806). These findings indicate that there are no significant differences in the maturation of oocytes and the embryo quality for the women with low AMH level and ideal retrieval eggs but they should undergo IVF treatment and achieve successful pregnancy as soon as possible due to the higher basal FSH, the relatively fewer number of retrieval eggs and the possibility of coming diminished ovarian reserve (DOR) or poor respond (PR) despite their younger ages.

Time-lapse videography reveals different morphokinetic profiles of human embryos displaying direct or reverse cleavage at different stages of development: A retrospective sibling embryo study

Objective: To investigate morphokinetic characteristics of embryos displaying either reverse cleavage or direct cleavage during the first, second or third cleavage cycle.Methods: A total of 167 in vitro fertilization and/or intracytoplasmic sperm injection treatment cycles undertaken by 167 women [aged (35.0±4.6) years] were included for reverse cleavage analysis, and a total of 167 in vitro fertilization and/or intracytoplasmic sperm injection treatment cycles undertaken by 167 women [aged (33.8 ±4.3) years] were included for direct cleavage analysis in this study. Using a sibling-embryo design, morphokinetic profiles (both before and after the onset of abnormal event) of embryos displaying reverse cleavage (n=241) or direct cleavage (n=244) were compared with their unaffected siblings (the controls) in the first, second and third cell cycles (n=32, n=142, n=562; n=195, n=412, n=205, respectively), at different developmental stages up to day 3. Results: Direct cleavage embryos demonstrated significantly delayed cleavage rates prior to the event regardless of developmental stage of the occurrence, while reverse cleavage embryos showed similar cleavage rates to their unaffected siblings. Post event, direct cleavage embryos sped up cleavage rates while reverse cleavage embryos slowed down.Conclusions: Altered morphokinetic profiles are displayed by direct cleavage embryos both before and after their occurrence and reverse cleavage embryos after the occurrence, which could potentially confound morphokinetic comparisons if not separated from their unaffected sibling embryos. Further study is warranted in order to fully understand the biological mechanisms of such events.

From fertilization to blastocyst: a comparative study of testicular to ejaculated sperm in intracytoplasmic sperm injection (ICSI) treatment cycles

From fertilization to blastocyst: a comparative study of testicular to ejaculated sperm in intracytoplasmic sperm injection (ICSI) treatment cycles

Expression of Target Genes in Cumulus Cells Derived from Human Oocytes with and without Blastocyst Formation

Objective: The transcriptional profile of cumulus cells (CCs) during oocyte maturation provides information for predicting oocyte developmental competence. Our previous study using a mouse model indicated that there were nine different genes related to oocyte development potential expressed in CCs during oocyte maturation. The purpose of this study was to elucidate whether gene expression levels of CCs during oocyte maturation are associated with oocyte developmental competence. Methods: The human CCs collected from each oocyte were divided into two groups after tracking depending on whether or not they developed to the blastocyst stage: (1) the oocytes were developed to blastocyst stage after fertilization (B+) and (2) the oocytes were not developed to blastocyst stage after fertilization (B−). The expression levels of the nine selected genes (ARRB1, ATP2C1, CDH5, CNTNAP1, LGR4, MKLN1, RHOBTB1, SIX2, and SMC2) were examined. CCs were obtained from 29 women who were undergoing intracytoplasmic sperm injection treatment cycles. Quantitative reverse transcriptase-polymerase chain reaction analysis was performed on cumulus masses collected before insemination. Each sample was run three times. Statistically significant differences in mRNA expression of the target genes in independent samples were evaluated by two-tailed Student's t-test, and P Results: There were significant differences in the mRNA expression levels of ARRB1 (P = 0.016), LGR4 (P = 0.025), and SMC2 (P = 0.013) between the groups B+ and B−. Gene expression of ARRB1, LGR4, and SMC2 in CCs is related to blastocyst development. Conclusions: Analysis of expression of ARRB1, LGR4, and SMC2 genes in CCs as biomarkers may provide predictive information on oocyte developmental competence before insemination and fertilization.

Effect of morphokinetics and morphological dynamics of cleavage stage on embryo developmental potential: A time-lapse study

ObjectiveUsing a non-invasive method to select the most competent embryo is essential in in vitro fertilization (IVF). Since the beginning of clinical application of time-lapse technology, several studies have proposed models using the time-lapse imaging system for predicting the IVF outcome. This study used both morphokinetic and morphological dynamic parameters to select embryos with the highest developmental potential. Materials and MethodsA total of 23 intracytoplasmic sperm injection treatment cycles with 138 fertilized oocytes were included in this study. All embryos were cultured to the blastocyst stage, and embryo development was recorded every 10 min by using a time-lapse imaging system. Morphokinetic parameters and eight major abnormal division behaviors were studied to determine their effects on blastocyst formation. The most influential variables were used in hierarchical classification for blastocyst formation prediction. ResultsSeveral parameters were significantly related to the developmental potential. Embryos with the timing of pronuclear fading (tPNF) of >26.4 h post insemination (hpi), the timing of division to two cells (t2) of >29.1 hpi, and the timing of division to four cells (t4) of >41.3 hpi showed the lowest blastocyst formation rate. The abnormal division behaviors of fragmentation >50%, direct cleavage, reverse cleavage, and delayed division or developmental arrest were found to be detrimental to blastocyst formation. On the basis of these results, we propose a hierarchical model classification, in which embryos are classified into groups A-D according to their developmental potential. The blastocyst formation rates of groups A, B, C, and D were 80.0%, 77.8%, 53.7%, and 22.2% (p < 0.001). The good blastocyst rates of groups A, B, C, and D were 60.0%, 44.4%, 14.6%, and 11.1% (p = 0.007). ConclusionWe propose a hierarchical classification system for blastocyst formation prediction, which provides information for embryo selection by using a time-lapse imaging system.

Examining the efficacy of six published time-lapse imaging embryo selection algorithms to predict implantation to demonstrate the need for the development of specific, in-house morphokinetic selection algorithms

To study the efficacy of six embryo-selection algorithms (ESAs) when applied to a large, exclusive set of known implantation embryos. Retrospective, observational analysis. Fertility treatment center. Women undergoing a total of 884 invitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment cycles (977 embryos) between September 2014 and September 2015 with embryos cultured using G-TL (Vitrolife) at 5% O2, 89% N2, 6% CO2, at 37°C in EmbryoScope instruments. None. Efficacy of each ESA to predict implantation defined using specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic curve (AUC), and likelihood ratio (LR), with differences in implantation rates (IR) in the categories outlined by each ESA statistically analyzed (Fisher's exact and Kruskal-Wallis tests). When applied to an exclusive cohort of known implantation embryos, the PPVs of each ESA were 42.57%, 41.52%, 44.28%, 38.91%, 38.29%, and 40.45%. The NPVs were 62.12%, 68.26%, 71.35%, 76.19%, 61.10%, and 64.14%. The sensitivity was 16.70%, 75.33%, 72.94%, 98.67%, 51.19%, and 62.33% and the specificity was 85.83%, 33.33%, 42.33%, 2.67%, 48.17%, and 42.33%, The AUC were 0.584, 0.558, 0.573, 0.612, 0.543, and 0.629. Two of the ESAs resulted in statistically significant differences in the embryo classifications in terms of IR. These results highlight the need for the development of in-house ESAs that are specific to the patient, treatment, and environment. These data suggest that currently available ESAs may not be clinically applicable and lose their diagnostic value when externally applied.