Oocyte Retrieval Cycles Research Articles

Cumulative live birth rate and neonatal outcomes after early rescue ICSI: a propensity score matching analysis

Abstract STUDY QUESTION Is early rescue ICSI (E-RICSI) an effective and safe technique compared to conventional ICSI? SUMMARY ANSWER Despite the higher multi-pronucleus (PN) rate compared to conventional ICSI, E-RICSI did not add extra risks to clinical and neonatal outcomes. WHAT IS KNOWN ALREADY Based on the finding that the second polar body was released in 80% of fertilized oocytes by 4 h after exposure to spermatozoa and in ∼90% of fertilized oocytes by 6 h, E-RICSI brings forward the timing of rescue ICSI to 6 h after initial insemination, and effectively prevents oocyte aging and embryo-uterus asynchrony. However, some researchers still voice concerns about the efficacy and safety of E-RICSI, and comparative studies are limited. STUDY DESIGN, SIZE, DURATION A retrospective cohort study was conducted on patients who underwent conventional ICSI or E-RICSI treatment between January 2015 and December 2020 at a university-affiliated hospital. Using 1:1 propensity score matching, 1496 cases entered each group. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 1496 couples undergoing conventional ICSI oocyte retrieval cycles and 1496 undergoing E-RICSI oocyte retrieval cycles were enrolled in this study, and basic clinical characteristics, embryologic data, clinical outcomes and neonatal data were compared between groups. The embryos in the E-RICSI group were divided into two subgroups: those fertilized by iIVF (IVF subgroup) and those fertilized by E-RICSI (E-RICSI subgroup); the embryologic data, clinical outcomes, and neonatal data for these subgroups were also compared with the conventional ICSI group. Logistic regression was used for statistical analysis with potential confounder adjustment. MAIN RESULTS AND THE ROLE OF CHANCE The 2PN rate, blastocyst formation rate, and viable blastocyst formation rate of the E-RICSI group were significantly lower compared to the conventional ICSI group (2PN rate: P < 0.001; blastocyst formation rate: P < 0.001; viable blastocyst formation rate: P = 0.004), and the multi-PN rate in the E-RICSI group was significantly higher than the conventional ICSI group (P < 0.001). However, the number of 2PN embryos, normal cleavage embryo rate, Day 3 high-quality cleavage embryo rate, and high-quality blastocyst rate were similar between groups. When considering the IVF embryos and E-RCSI embryos in the E-RICSI group independently, the 2PN rate of the conventional ICSI group was significantly lower than E-RICSI subgroup but higher than the IVF subgroup, whereas the blastocyst formation rate and viable blastocyst formation rate were higher than E-RICSI embryos but comparable to IVF embryos. As for the clinical and neonatal outcomes, the implantation rate of the E-RICSI subgroup was significantly lower than the IVF subgroup but comparable to the conventional ICSI group, while the low birthweight (LBW) rate was significantly lower compared with the conventional ICSI group but similar with the IVF subgroup. No other differences were observed among the three groups for cumulative clinical pregnancy rate, cumulative live birth rate, and the pregnancy outcomes per transfer including clinical pregnancy, ectopic pregnancy, miscarriage, and live birth, either in fresh or frozen embryo transfer cycles. Furthermore, neonatal outcomes, including cesarean section, sex ratio, LBW, preterm birth, and macrosomia, were similar among groups. LIMITATIONS, REASONS FOR CAUTION This study is limited by the retrospective design, limited sample size, and short follow-up period. However, our study underlies the need for large-scale, multi-center randomized controlled trials with long-term follow-up. WIDER IMPLICATIONS OF THE FINDINGS Short-term insemination (3 h) combined with E-RICSI may be a safe and effective method to prevent the occurrence of total fertilization failure, and patients with normal or borderline sperm could be encouraged to try IVF first. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by grants from the National Key & Development Program of China (No. 2021YFC2700603) and the National Natural Science Foundation of China (No. 81801443). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Maternal body mass index is not associated with assisted reproductive technology outcomes

The effects of body mass index (BMI) on assisted reproductive technology (ART) outcomes such as ovarian dysfunction, poor ovum quality, and endometrial dysfunction have been studied; however, many aspects remain controversial. Therefore, we retrospectively investigated the relationship between BMI and ART outcomes. For 14,605 oocyte retrieval cycles at our hospital between January 2016 and December 2020, BMI was divided into five groups (< 18.5, 18.5–20.0, 20.0–22.5, 22.5–25.0, ≥ 25 kg/m2) and measured before oocyte retrieval. The normal fertilization and high-grade blastocyst rates were compared. In addition, in the 7,122 frozen-thawed embryo transfers (FET) with highest-grade embryos, the clinical pregnancy, miscarriage, and live birth rates were investigated in the five BMI groups. Multiple regression analysis on normal fertilization and high-grade blastocyst rates revealed no statistically significant differences. Furthermore, after propensity score matching on FET, there was no significant difference in clinical pregnancy, miscarriage, and live birth rates in the BMI groups. BMI is a risk factor for complications during pregnancy; however, it does not affect ART outcomes. Therefore, we believe weight guidance should be provided to women with obesity at the start of infertility treatment, but treatment should not be delayed.

Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study.

To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E2 was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients.

Decreased pregnancy rate per embryo transfer in women undergoing assisted reproductive technology after abdominal trachelectomy: A retrospective study

ObjectiveAbdominal trachelectomy (AT) is a fertility-preservation surgery for patients with early-stage cervical cancer. Few studies have reported the outcomes of assisted reproductive technology (ART) in patients after AT. The aim of this study was to evaluate the outcomes of ART after AT. Study DesignIn this retrospective study, we compared the ART outcomes of 13 patients who underwent AT at another hospital prior to undergoing ART at our clinic (T group) and 52 control patients (non-T group) who did not undergo AT prior to ART, selected on the basis of age, time of treatment onset, and serum anti-Müllerian hormone concentrations, matched 1:4, respectively. ResultsCumulative live birth rates were 62% (8/13) and 65% (34/52) in the T and non-T groups, respectively (p = 0.795). The total number of oocyte retrieval cycles was 34 in the T group and 95 in the non-T group. In all oocyte retrieval cycles, no significant differences were noted in the number of oocyte retrievals, rate of fertilization, and presence of good-quality blastocysts (Gardner classification ≥ BB). The total number of embryo transfer (ET) cycles was 55 in the T group and 109 in the non-T group. The pregnancy and live birth rates per ET were lower in the T group than those in the non-T group (pregnancy rate, 20% vs. 39%, p = 0.017; live birth rate, 15% vs. 30%, p = 0.028; respectively). Endometrial thickness before ET was lower in the T group vs. the non-T group: median (range): 7.4 (3.5–14.3) mm vs. 9.0 (5.5–14.9) mm, respectively; p < 0.0001. Multivariate logistic regression models showed that age at oocyte retrieval (adjusted odds ratio [OR], 0.76; 95% confidence interval [CI], 0.66–0.87), use of good-quality blastocysts (adjusted OR, 3.23; 95% CI, 1.20–8.67), and history of AT (adjusted OR, 0.28; 95% CI, 0.11–0.72) were associated with the pregnancy rate per ET. ConclusionThe pregnancy rate per ET was lower in patients with vs. without a history of AT. Clinicians should be aware of the longer time to pregnancy in patients who undergo ART after AT.

The number of prior pregnancy losses does not impact euploidy rates in young patients with idiopathic recurrent pregnancy loss.

Our study aimed to determine the possible factors that might impact the probability of obtaining a euploid blastocyst following intracytoplasmic sperm injection (ICSI) and preimplantation genetic testing for aneuploidy (PGT-A) procedures in idiopathic recurrent pregnancy loss (RPL) patients. This single-center retrospective cohort analysis included 180 oocyte retrieval cycles of 166 women under 35years old and those diagnosed with idiopathic RPL according to American Society of Reproductive Medicine (ASRM) guidelines. Trophectoderm biopsy and next-generation sequencing (NGS) were the techniques used. Patients were stratified by the number of previous losses (Group A: 2, Group B: 3, and Group C: > 3). Baseline and embryological characteristics showed no statistically significant differences. The euploidy rate per analyzed blastocyst was comparable within the groups (63.3%, 58.2%, and 58.5%; p = 0.477). Logistic regression analyses confirmed that only the trophectoderm scores of A and B increased the probability of obtaining a euploid embryo [OR: 1.82, 95% CI (1.120-2.956), p: 0.016]. It is concluded that there was no correlation between the number of previous losses and the chance of finding at least one euploid embryo in ICSI cycles of women younger than 35years.

The effects of high risk of ovarian hyperstimulation syndrome and duration of embryo cryopreservation on perinatal outcomes of single live births in the first frozen embryo transfer cycle after whole embryo cryopreservation

Objective: To investigate the effects of high risk of ovarian hyperstimulation syndrome (OHSS) and duration of embryo cryopreservation on perinatal outcomes of the first frozen-thawed cycle after whole embryo cryopreservation. Methods: The clinical data of 1 804 patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation and achieved singleton live births in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to June 2021 were retrospectively analyzed. According to whether there was high risk of OHSS in the oocyte retrieval cycle, the patients were divided into high-risk group (n=790) and non-high-risk group (n=1 014). The baseline data and perinatal outcomes were compared between the two groups. Multivariate linear regression was applied to analyze the relative factors affecting neonatal weight. And the high-risk group was divided into three subgroups according to different cryopreservation time: the embryos of 96 cycles with a cryopreservation time less than 60 days were defined as group A; the embryos of 587 cycles with a cryopreservation time around 60 to 120 days were defined as group B; the embryos of 107 cycles with a cryopreservation time more than 120 days were defined as group C. The perinatal outcomes were compared among the three groups. The measurement data in this study were represented by［M（Q1，Q3）］. Results: The female age in the high-risk group was 30.0 (27.0, 32.0) years old, which was lower than that in the non-high-risk group 31.0 (29.0, 34.0) (P<0.001). The male age in high-risk group was 30.0 (28.0, 33.0), lower than that in non-high-risk group 32.0 (29.0, 35.0) (P<0.001). The birth weight of high-risk group [3 500.0 (3 200.0,3 800.0) g] was higher than that of control group [3 400.0 (3 150.0,3 800.0) g](P=0.045). Multivariate linear regression analysis showed that female BMI was correlated with neonatal weight, β (95%CI) was 15.37(8.33, 22.41) (P<0.001), and the high risk of OHSS was not correlated with neonatal weight, β (95%CI) was 19.40 (-38.07, 76.87) (P=0.508). There was significant difference in the incidence of low birth weight and very low birth weight among groups A, B and C (all P values<0.05), and the incidence of low birth weight and very low birth weight in group C was higher than that in group B (all P values<0.017). Conclusions: The risk of adverse perinatal outcomes in high-risk OHSS patients who underwent the first frozen-thawed cycle after whole embryo cryopreservation was not increased. However, prolonged cryopreservation of embryos may lead to increased risk of low birth weight and very low birth weight.

P-762 Exploring the Efficacy and Beneficial Population of Preimplantation Genetic Testing for Aneuploidy Start from Oocyte Retrieval Cycle: A Real-World Study

Abstract Study question Does preimplantation genetic testing for aneuploidy (PGT-A) increase chance of live birth among women undergoing IVF? What kind of women are most likely to benefit? Summary answer PGT-A is effective in people with specific indications, including maternal aged ≥38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions. What is known already As an embryo-selection technique, PGT-A is extensively used in in-vitro fertilization (IVF), but its efficacy and potential beneficial population is unclear. Study design, size, duration This was a retrospective cohort study. We analyzed data from women who underwent assisted reproduction treatment in the Reproductive and Genetic Hospital of CITIC-Xiangya. We included all first oocyte retrieval cycles from January 1, 2016, to November 31, 2019, and related fresh- and thawed-embryo transfer cycles up to November 31, 2020. Participants/materials, setting, methods The study cohort included 60,580 women. We used 1:3 propensity score matching to balance baseline data between women with PGT-A and without PGT-A. Stratified analyses according to age, body mass index, ovarian reserve/response, and potential indications were predesigned to explore benefits in sub-populations. The main outcome was cumulative live birth rate (CLBR) and the other observed outcomes including live birth rate (LBR), pregnancy loss, clinical pregnancy, pregnancy complications, newborn birth weight and neonatal malformation. Main results and the role of chance A total of 4,195 (95.1%) PGT-A users’ first oocyte retrieval cycles were matched to 10,140 non-users’ oocyte retrieval cycles. We found that women utilizing PGT-A had significantly lower CLBRs (27.5% vs. 31.1%; odds ratio (OR)=0.84, 95% confidence interval (CI), 0.78–0.91; P&amp;lt;.001) following the first oocyte retrieval cycle than did women not utilizing it. However, first transfers among women utilizing PGT-A had significantly higher pregnancy (63.9% vs. 46.9%; OR = 2.01, 95% CI, 1.81–2.23; P&amp;lt;.001) and live birth rates (LBR; 52.6% vs. 34.2%, OR = 2.13, 95% CI, 1.92–2.36; P&amp;lt;.001), as well as lower early miscarriage (12.8% vs. 20.2%; OR = 0.58, 95% CI, 0.48–0.70; P&amp;lt;.001), preterm birth (8.6% vs 17.3%; P&amp;lt;.001), and low birth weight rates (4.9% vs. 19.3%; P&amp;lt;.001). Moreover, subgroup analyses showed patients with maternal aged ≥38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions benefit from PGT-A, exhibiting significantly increasing LBRs following first transfer, without reducing CLBRs. Limitations, reasons for caution The retrospective design introduces inevitable bias. And the data originated from a single IVF center, thus, extrapolation of our findings may be limited, multi-center large data studies are needed to further confirm these findings. Wider implications of the findings Although PGT-A use does not increase and may decrease CLBR per oocyte retrieval cycle, it is effective in people with specific indications. Careful selection of suitable populations and proper clinical management for mosaic embryo transfer are important for effective PGT-A implementation. Trial registration number NA

P-110 Effects of embryo culture under atmospheric oxygen concentration on cumulative live birth rate and birth weight

Abstract Study question The purpose of this study is to compare cumulative live birth rate and perinatal outcomes of embryos cultured in 20% oxygen and 5% oxygen. Summary answer Atmospheric oxygen concentration not only affects the quality of embryos, but also affects the cumulative live birth rate and birth weight after embryo transfer. What is known already Whether 5% oxygen culture can effectively improve the outcome of embryonic pregnancy is still controversial. There is a lack of scientific data support from a large sample, especially regarding the cumulative live birth outcome as the primary outcome. Study design, size, duration This retrospective study included patients who received in vitro fertilization (IVF) treatment with their own first oocyte retrieval cycles from 1 January 2016 through 31 November 2019, with transfer dates limited to 31 November 2020. Our final analytic cohort included 31,566 women. Participants/materials, setting, methods Embryos were cultured at 5% or 20% oxygen concentration until the third day for transplantation or freezing. If prolonged culture was required, embryos of both groups were transferred to the incubator with 5% oxygen concentration to the blastocyst stage until transplantation or freezing. Other laboratory and clinical procedures were consistent between the two groups. Main results and the role of chance The rate of high-quality embryos in the 5% oxygen group was significantly higher than that in the 20% oxygen group （0.51 ± 0.33 vs 0.49 ± 0.33; β = −0.03; 95%CI, −0.03–−0.02; P &amp;lt; 0.001), while the rate of slow-developing embryos was significantly lower （0.52 ± 0.31 vs 0.56 ± 0.31; β = 0.04; 95%CI, 0.03–0.05; P &amp;lt; 0.001). The cumulative live birth rate was significantly higher in the 5% oxygen group than in the 20% oxygen group (62.4% vs 58.6%; adjusted OR = 0.85; 95%CI, 0.81-0.90). The birth weight and Z score （birthweight corrected for gestational age at birth, gender and parity were significantly lower in the 5% oxygen group than in the 20% oxygen group (birth weight: 3.28 ± 0.48 vs 3.30 ± 0.50, adjusted OR = 0.022, 95%CI, 0.004-0.04; Z score: 0.22 ± 1.01 vs 0.26 ± 1.04, adjusted OR = 0.037, 95%CI, 0.001–0.074). No matter what age group, the cumulative live birth rate, pregnancy rate and good birth outcome of the 5% oxygen concentration group were higher than those of the 20% group, while the proportion of no transferable embryos was lower than those of the 20% group. Limitations, reasons for caution Limitations include that oocytes were cultured at 20% oxygen concentration on the fertilization day (D0), and randomly distributed to incubators with different oxygen concentrations until day 1. Because it was a retrospective study, the grouping was not randomized. Wider implications of the findings We counted the largest sample data at present, took the cumulative live birth rate as the main outcome indicator, and tracked the perinatal outcome, using reliable data to prove that atmospheric oxygen concentration has serious and long-term irreversible effects on embryonic development. Trial registration number not applicable

P-363 Ovarian endometriosis deteriorates embryo development in ART cycles: An embryonic time-lapse study

Abstract Study question Does ovarian endometriosis deteriorate embryo quality in terms of morphokinetic parameters determined by time-lapse images? Summary answer Embryos from ovarian endometriosis patients accelerate their early developmental events but decelerate after t5. Completion of late developmental events were significantly delayed in endometriosis group. What is known already Endometriosis may affect the oocyte quality and consequently affect the embryo quality in terms of embryo morphology and implantation ability. Morphokinetic evaluation of embryos provided more developmental details and might be utilised as a tool to distinguish the embryo developmental ability. Only scarce studies with limited case numbers have evaluated the association between endometriosis and developments of embryo in terms morphokinetic observation. Hardly any consensus has ever been drawn. Study design, size, duration The morphokinetic parameters of embryos were compared between patients with or without ovarian endometriosis. A total of 52 ovarian endometriosis cases and 208 controls without endometriosis, receiving their assisted reproductive techniques from April 2020 through June 2022, were included for analysis. Propensity Score Matching with age, BMI and AMH was performed in a ratio of 1:4 in order to eliminate the confounding factors. Participants/materials, setting, methods We analyzed a total of 737 top quality embryos obtained from 348 oocyte retrieval cycles performed at Taipei Fertility Center. 127 embryos were obtained from women affected by ovarian endometriosis and 617 were obtained from unaffected controls. All embryos were cultured in a time-lapse incubator chamber and completed blastulation. Main results and the role of chance Morphokinetic data showed that embryo development is distorted in embryos obtained from women with endometriosis. The timing of early developmental events, including tPNf (22.7 +/- 2.9 hr vs 23.5 +/- 4.1 hr, p = 0.03) and t2 (25.2 +/- 3.1 hr vs 26.1 +/- 4.4 hr, p = 0.03) were significantly shortened in the endometriosis group. However, the timing of late developmental events, including tM (89.7 +/- 9.8 hr vs 86.6 +/- 11.4 hr, p = 0.006) and tB (111.0 +/- 11.0 hr vs 108.3 +/- 12.5 hr, p = 0.03) were significantly prolonged in the endometriosis group. The timing of t5 by morphokinetic observation was found to be equal both in ovarian endometriosis group and control group (50.4 +/- 8.7 hr vs 50.4 +/- 8.4 hr, p = 0.99). The average of KID score of embryos from ovarian endometriosis group was lower than that from normal control, but it did not reached statistical significance (4.07 +/- 2.11 vs 4.49 +/- 2.70, p = 0.27). The initial serum hCG levels in pregnant women from both endometriosis and non-endometriosis participants showed that hCG levels were significantly higher in non-endometriosis cases (628.8 +/- 967.7 mIU/ml vs 1581.5 +/- 1885.1 mIU/ml, p = 0.01). Limitations, reasons for caution This is a retrospective observational study with propensity score matching method to eliminate confounding factors such as age, BMI and AMH. Wider implications of the findings The effects of prolonged morphokinetic parameters on the embryo quality need further study to clarify; however, they may serve as markers in selecting embryos with implantation potential. Trial registration number Not applicable

P-170 A sibling oocyte study using a real-time image analysis system to identify optimal puncture positions in Piezo-ICSI

Abstract Study question Is the newly developed image analysis system capable of visualizing the shape features of the oolemma in real-time, useful for reducing oocyte degeneration during Piezo-ICSI? Summary answer Unintentional membrane rupture (UMR) can be reduced by this real-time image analysis, which lowers the risk of oocyte degeneration following Piezo-ICSI. What is known already UMR in the puncturing process of ICSI often predisposes oocyte degeneration. Identifying the appropriate puncturing positions may decrease the likelihood of UMR and thus degeneration, but this cannot be visualized via a microscope. We have reported that visualization of the shape features of the oolemma using moving image analysis during Piezo-ICSI can locate areas on the oolemma where UMR is likely to occur. It is feasible to assess the incidence of UMR and oocyte degeneration by performing ICSI while selecting appropriate puncturing positions with the aid of the newly developed imaging system. Study design, size, duration Our team have developed an image analysis system called ICSI POSITION DETECTOR (IPD), which can identify areas where rupture is likely to occur and visualize it in real-time using a video monitor. We prospectively evaluated the usefulness of IPD in a sibling oocyte study. From January 2020 to August 2021, a total of 1268 oocytes obtained in 225 oocyte retrieval cycles (average maternal age: 38.3 ± 4.7 years old) was included. Participants/materials, setting, methods The oocytes were randomly assigned to two groups: IPD-using vs. non-IPD-using. In the IPD-using group, Piezo-ICSI was performed at the “appropriate” position with a low chance of UMR indicated by IPD. In the non-IPD-using group, Piezo-ICSI was performed blindly. The rates of UMR, oocyte degeneration, fertilization and embryonic development were compared between the two groups. In addition, in the non-IPD-using group, moving images were recorded during Piezo-ICSI and analyzed retrospectively using IPD. Main results and the role of chance The rates of UMR and degeneration were significantly lower in the IPD-using group compared to the non-IPD-using group (6.0% vs. 11.9%, P &amp;lt; 0.001 and 1.6% vs. 4.6%, P &amp;lt; 0.01, respectively). The rates of fertilization (83.7% vs. 79.7%), blastocyst formation (51.9% vs. 51.0%), and good-quality blastocyst (24.7% vs. 24.3%) were not significantly different. Retrospective analysis of moving images using IPD on the non-IPD-using group showed that in 45.3% of oocytes (286 out of 632) ICSI was performed at a position with a high chance of UMR (inappropriate position). When ICSI was performed at the appropriate positions using IPD, the rates of UMR (6.0% vs. 18.2%, P &amp;lt; 0.001) and degeneration (1.6% vs. 7.3%, P &amp;lt; 0.001) were significantly lower, while the rates of fertilization (83.7% vs. 74.5%, P &amp;lt; 0.01) and blastocyst formation (51.9% vs. 43.0%, P &amp;lt; 0.05) were significantly higher than those when ICSI was performed at an inappropriate position. The rate of good-quality blastocyst (24.7% vs. 19.7%) was also higher, but not statistically significant. These results indicate that IPD can reduce the risk of UMR, thereby lower the degeneration rate. Furthermore, the embryonic development was better when using IPD to identify the appropriate position to perform ICSI, suggesting that UMR seems to be associated with poor ICSI outcome. Limitations, reasons for caution In this study, Piezo-ICSI was performed by only two designated embryologists in a single center. It did not assess clinical outcomes. Further research involving more embryologists is needed. Moreover, it would be feasible to investigate whether the usage of IPD is similarly effective on conventional-ICSI outcome. Wider implications of the findings The application of IPD to perform ICSI at the appropriate position can significantly avoid UMR, and thereby reduce oocyte degeneration and provide better embryonic development. We therefore, consider IPD to be a highly clinically useful tool, which contributes to the production of more embryos that can be used for treatment. Trial registration number not applicable

P-165 Artificial removal of the zona pellucida at the pronuclear stage in patients with poor quality embryos with severe fragmentation

Abstract Study question Is artificial removal of the zona pellucida (ZP) at the pronuclear stage effective in patients with poor quality embryos with severe fragmentation? Summary answer Artificial removal of the ZP at the pronuclear stage significantly improved culture results in patients with poor quality embryos with severe fragmentation. What is known already In 2020, Yumoto et al. first reported that artificial removal of the ZP (ZP-free) at the pronuclear stage decreased the rate of fragmentation and improved the culture outcomes of 3 pronuclei (3PN) embryos reaching to the good blastocysts. Therefore, the ZP may not always be necessary for normal embryonic development after the pronuclear stage. The same group presented at the 37th ESHRE meeting in 2021, that the blastocyst transfer after ZP-free embryo of 2 pronuclei (2PN) resulted in normal pregnancy in two patients with poor-quality embryos resulting in live births. Study design, size, duration This study included 211 of 2PN embryos from 46 cycles for 30 couples obtained between July 2021 and December 2022, whose previous oocyte retrieval cycle showed massive cytoplasmic fragmentation at the first cleavage confirmed by a time-laps incubator (TLI). Average age of women was 38.8years. The embryos with artificial removal of the ZP at the pronuclear stage were cultured in a TLI up to 7 days. All blastocysts were cryopreserved for future embryo transfer cycles. Participants/materials, setting, methods All participants provided written informed consent, and Institutional Review Board approval was obtained. Artificial removal of the ZP at the pronuclear stage was performed by following procedure. 1) Embryos were placed in 0.125M sucrose-containing HEPES for cytoplasm shrinking. 2) The ZP without adhesion was removed with a laser system. 3) Ooplasms were completely separated from ZP by blowing the medium to adhesion point like a jet car wash. 4) ZP-free embryo was obtained. Main results and the role of chance Day 3 embryos were divided into 3 groups using the Veeck’s classification: 8 cell embryos with grade 2 or higher were defined as good, embryos with grade 4 or 5 regardless of the number of cells were defined as poor, and others were defined as fair. We compared the culture results of ZP-free cycle and previous oocyte retrieval cycle (ZP-intact). For day 3 embryos, good, fair and poor grade were 19.4% (41/211), 62.6% (132/211) and 18.0% (38/211) in ZP-free embryos compared with 2.9% (15/561), 37.4% (210/561), and 59.9% (336/561) in the past, respectively (p &amp;lt; 0.001). Good-quality blastocysts were defined as 3BB or more on day 5 by the Gardner’s classification. As to the blastocysts, blastocysts development and good-quality blastocysts rates were 45.0% (95/211) and 27.0% (57/211) in ZP-free embryos compared with 23.0% (112/488) and 6.8% (33/488) in the past, respectively (p &amp;lt; 0.001). Of these, 30 embryo transfers were performed resulting in 11 clinical pregnancies. We had 3 live births without any congenital anomalies and one miscarriage. One was delivered at 33 weeks of gestation with caesarian section, one mother had gestational diabetes. Limitations, reasons for caution This study was retrospective study without any control group and was conducted at only single fertility center. It is necessary to conduct sibling oocytes study to demonstrate the effectiveness of ZP-free culture, and to create criteria who are benefit from ZP-free culture. Moreover, safety of ZP-free culture should be evaluated. Wider implications of the findings ZP-free culture reduced fragments and improved culture outcomes in patients with poor quality embryos with severe fragmentation. ZP-free culture might bring light to the patients who have difficulty obtaining good-quality embryos with severe fragmentation. Trial registration number Not Applicable

Season and temperature do not affect cumulative live birth rate and time to live birth in in vitro fertilization.

To explore whether season and temperature on oocyte retrieval day affect the cumulative live birth rate and time to live birth. This was a retrospective cohort study. A total of 14420 oocyte retrieval cycles from October 2015 to September 2019. According to the date of oocyte retrieval, the patients were divided into four groups (Spring(n=3634);Summer(n=4414); Autumn(n=3706); Winter(n=2666)). The primary outcome measures were cumulative live birth rate and time to live birth. The secondary outcome measures included the number of oocytes retrieved, number of 2PN, number of available embryos and number of high-quality embryos. The number of oocytes retrieved was similar among the groups. Other outcomes, including the number of 2PN (P=0.02), number of available embryos (p=0.04), and number of high-quality embryos (p<0.01) were different among the groups. The quality of embryos in summer was relatively poor. There were no differences between the four groups in terms of cumulative live birth rate (P=0.17) or time to live birth (P=0.08). After adjusting for confounding factors by binary logistic regression, temperature (P=0.80), season (P=0.47) and duration of sunshine(P=0.46) had no effect on cumulative live births. Only maternal age (P<0.01) and basal FSH (P<0.01) had an effect on cumulative live births. Cox regression analysis suggested no effect of season(P=0.18) and temperature(P=0.89) on time to live birth. Maternal age did have an effect on time to live birth (P<0.01). Although season has an effect on the embryo, there was no evidence that season or temperature affect the cumulative live birth rate or time to live birth. It is not necessary to select a specific season when preparing for IVF.

The effect of carrier characteristics and female age on preimplantation genetic testing results of blastocysts from Robertsonian translocation carriers.

To analyze factors affecting segregation and ploidy results from Robertsonian carriers, and determine chromosomes involved impact chromosome stability during meiosis and mitosis. This retrospective study include 928 oocyte retrieval cycles from 763 couples with Robertsonian translocations undergoing preimplantation genetic testing for structural rearrangements (PGT-SR) using next-generation sequencing (NGS) between December 2012 and June 2020.The segregation patterns of the trivalent of 3423 blastocysts were analyzed according to the carrier's sex and age. A total of 1492 couples who received preimplantation genetic testing for aneuploidy (PGT-A) were included as the control group and matched according to maternal age and testing time stage. A total of 1728 (50.5%) normal/balanced embryos were identified from 3423 embryos diagnosed. The rate of alternate segregation in male Robertsonian translocation carriers was significantly higher than that in female carriers (82.3% vs. 60.0%, P < 0.001). However, the segregation ratio exhibited no difference between young and older carriers. Further, increasing maternal age decreased the proportion of transferable embryo cycle in both female and male carriers. And the ratio of chromosome mosaic from the Robertsonian translocation carrier group was significantly higher than that in the PGT-A control group (1.2% vs. 0.5%, P < 0.01). The meiotic segregation modes were affected by the carrier sex and were independent of the carrier's age. Advanced maternal age decreased the probability of obtaining a normal/balanced embryo. In additional, the Robertsonian translocation chromosome could increase the possibility of chromosome mosaicism during mitosis in blastocysts.

Effect of oral contraceptives pretreatment on cumulative clinical pregnancy of oocyte retrieval cycle in polycystic ovary syndrome women with gonadotropin releasing hormone antagonist protocol

Objective: To investigate the effect of pretreatment with oral contraceptives (OC) on cumulative clinical pregnancy of oocyte retrieval cycle in polycystic ovary syndrome (PCOS) women with gonadotropin releasing hormone (GnRH) antagonist protocol. Methods: A retrospective cohort study was conducted to analyze PCOS women who underwent in vitro fertilization-embryo transfer (IVF-ET)/intracytoplasmic sperm injection (ICSI) treatment with GnRH antagonist in the Reproductive Medical Center of Peking University First Hospital from January 2017 to December 2020. A total of 225 patients were divided into OC pretreatment group (119 patients) and non-pretreatment group (106 patients), according to whether they received OC before GnRH antagonist protocol. The baseline information, IVF, and pregnancy outcomes of the two groups were compared. A multivariate logistic regression model was used to analyze the effect of OC pretreatment on cumulative clinical pregnancy of the oocyte retrieval cycle. Results: The age of 225 patients was (31.1±3.3) years old. The ages of patients in the OC pretreatment group and non-pretreatment group were (31.0±3.3) and (31.2±3.3) years old (P>0.05), respectively. The cumulative clinical pregnancy rate of oocyte retrieval cycle was significantly higher in the OC pretreatment group than that in the non-pretreatment group (79.8%, 95 patients; 67.0%, 71 patients; P=0.029). Age <35 years old (OR=3.199, 95%CI: 1.200-8.531, P=0.020), OC pretreatment (OR=3.129, 95%CI: 1.305-7.506, P=0.011), number of oocytes retrieved (OR=1.102, 95%CI: 1.007-1.206, P=0.035) and number of high-quality embryos (OR=1.536, 95%CI: 1.205-1.957, P=0.001) were related factors for the cumulative clinical pregnancy of oocyte retrieval cycle. Conclusions: OC pretreatment before GnRH antagonist protocol can significantly increase the cumulative clinical pregnancy rate of oocyte retrieval cycle in women with PCOS. Age <35 years old, OC pretreatment, the number of oocytes retrieved, and the number of high-quality embryos were related factors for the cumulative clinical pregnancy of oocyte retrieval cycle.

Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations.

To compare cumulative live birth rate (LBR) between progestin-primed ovarian stimulation (PPOS) and GnRH antagonist protocols of preimplantation genetic testing (PGT) cycles in different populations. This was a retrospective cohort study. A total of 865 patients were enrolled and separate analyses were performed for three populations: 498 patients with predicted normal ovarian response (NOR), 285 patients with PCOS, and 82 patients with predicted poor ovarian response (POR). The primary outcome was cumulative LBR for one oocyte retrieval cycle. The results of response to ovarian stimulation were also investigated, including numbers of oocytes retrieved, MII oocytes, 2PN, blastocysts, good-quality blastocysts, and usable blastocysts after biopsy, as well as rates of oocyte yield, blastocyst formation, good-quality blastocysts, and moderate or severe OHSS. Univariable and multivariable logistic regression analyses were used to identify potential confounders that may be independently associated with cumulative live birth. In NOR, the cumulative LBR of PPOS protocol was significantly lower than that of GnRH antagonists (28.4% vs. 40.7%; P=0.004). In multivariable analysis, the PPOS protocol was negatively associated with cumulative LBR (adjusted OR=0.556; 95% CI, 0.377-0.822) compared to GnRH antagonists after adjusting for potential confounders. The number and ratio of good-quality blastocysts were significantly reduced in PPOS protocol compared to GnRH antagonists (2.82 ± 2.83 vs. 3.20 ± 2.79; P=0.032 and 63.9% vs. 68.5%; P=0.021), while numbers of oocytes, MII oocytes and 2PN did not show any significant difference between GnRH antagonist and PPOS protocols. PCOS patients had similar outcomes as NOR. The cumulative LBR of PPOS group appeared to be lower than that of GnRH antagonists (37.4% vs. 46.1%; P=0.151), but not significantly. Meanwhile, the proportion of good-quality blastocysts in PPOS protocol was also lower compared to GnRH antagonists (63.5% vs. 68.9%; P=0.014). In patients with POR, the cumulative LBR of PPOS protocol was comparable to that of GnRH antagonists (19.2% vs. 16.7%; P=0.772). There was no statistical difference in the number and rate of good-quality blastocysts between the two protocols in POR, while the proportion of good-quality blastocysts appeared to be higher in PPOS group compared to GnRH antagonists (66.7% vs. 56.3%; P=0.182). In addition, the number of usable blastocysts after biopsy was comparable between the two protocols in three populations. The cumulative LBR of PPOS protocol in PGT cycles is lower than that of GnRH antagonists in NOR. In patients with PCOS, the cumulative LBR of PPOS protocol appears to be lower than that of GnRH antagonists, albeit lacking statistical difference, whereas in patients with diminished ovarian reserve, the two protocols were comparable. Our findings suggest the need for caution when choosing PPOS protocol to achieve live births, especially for normal and high ovarian responders.

A Monocentric Randomized Controlled Clinical Trial to Compare Single- and Double-Lumen Needles in Oocyte Retrieval Procedure in Assisted Reproductive Technologies.

The purpose was to determine any difference in outcomes, primarily in terms of number of retrieved oocytes per procedure, between two different needles used for oocytes retrieval procedure in Assisted Reproductive Technologies: the single-lumen needle (SLN) versus the double-lumen needle (DLN) with follicle flushing after aspiration. This randomized controlled trial included oocyte retrieval (OR) cycles for IVF and ICSI performed in 18 to 42-year-old women between March 2019 and January 2021 at a tertiary-care Fertility Center. A total of 200 ORs were randomized, 100 in each group. The mean number of retrieved oocytes was not different between groups (10.2 ± 6.5 for DLNs vs. 10.7 ± 7.0 for SLNs, p = 0.810). No significant differences were observed also in terms of number of retrieved oocytes/punctured follicles (83.0% ± 27.0% vs. 81.0% ± 22.0%, p = 0.916), number of retrieved oocytes/follicles at trigger (78.0% ± 29.0% vs. 78.0% ± 27.0%, p = 0.881), number of mature oocytes (7.6 ± 5.3 vs. 8.0 ± 5.1, p = 0.519), and pregnancy rate (27% vs. 23%, p = 0.514). However, the time required to retrieve each oocyte was longer using the DLN (1.5 ± 1.3 vs. 1.1 ± 0.9 minutes, p = 0.002). The present study confirmed the new perspectives on the sole use of SLNs in terms of saving time, without affecting the number of retrieved oocytes. Trial registration number and date of registration NCT03611907; July 26, 2018.

Diminished ovarian reserve may not be associated with a poorer fresh cycle outcome in women < 38 years

BackgroundPrevious studies have discussed the pregnancy outcomes of diminished ovarian reserve (DOR) patients. However, data on embryonic development potential, neonatal outcomes, and maternal complications of DOR patients still remained unknown. This is the first study to investigate the risk of DOR on pregnancy and perinatal outcomes among women < 38 years.MethodsRetrospective cohort study was conducted. Patients (< 38 years of age) undergoing their first oocyte retrieval cycle were included. Patients were divided into DOR group and non-DOR group. Pregnancy outcomes of fresh cycle and cumulative live birth rate and perinatal outcomes after one oocyte retrieved cycle were compared between DOR and non-DOR group.Result(s)From January 2016 to September 2020, there were 8,179 patients involved: 443 patients in the DOR group and 7,736 patients in the non-DOR group. The incidences of live birth and clinical pregnancy did not differ significantly between patients with or without DOR after fresh cycle transfer, but the cumulative live birth rate was significantly lower in DOR group. Among women who had singleton live births, after binary logistic regression, the rates of maternal complications and neonatal outcomes were comparable in the two groups.Conclusion(s)DOR patients (< 38 years of age) showed similar pregnancy outcomes in the first fresh embryo transfer cycle but a lower chance of live birth after a whole oocyte retrieval cycle to non-DOR patients and DOR is not associated with adverse perinatal outcomes.

Association between HOMA-IR and ovarian sensitivity index in women with PCOS undergoing ART: A retrospective cohort study.

Insulin resistance (IR) may play a central role in the pathophysiology of polycystic ovary syndrome (PCOS). Controlled ovarian stimulation (COS) in PCOS women in the setting of assisted reproductive technology (ART) is always a challenge for clinicians. However, it remains unclear whether IR in women with PCOS correlates with reduced ovarian sensitivity to exogenous gonadotropin (Gn). This study aimed to explore the association between homeostasis model assessment of insulin resistance (HOMA-IR) and ovarian sensitivity index (OSI). In this retrospective cohort study, we explored the association between Ln HOMA-IR and Ln OSI based on smoothing splines generated by generalized additive model (GAM). Then the correlation between HOMA-IR and OSI was further tested with a multivariable linear regression model and subgroup analysis. 1508 women with PCOS aged 20-39 years undergoing their first oocyte retrieval cycle were included consecutively between 2018 until 2022. We observed a negative association between Ln HOMA-IR and Ln OSI by using smoothing splines. In multivariable linear regression analysis, the inverse association between Ln HOMA-IR and Ln OSI was still found in PCOS women after adjustment for potential confounders (β = -0.18, 95% CI -0.25, -0.11). Compared with patients with the lowest tertile of HOMA-IR, those who had the highest tertile of HOMA-IR had lower OSI values (β = -0.25, 95% CI -0.36, -0.15). Our study provided evidence for the inverse correlation between IR and the ovarian sensitivity during COS in PCOS women. Herein, we proposed new insights for individualized manipulation in PCOS patients with IR undergoing ART.

Controlled ovarian stimulation for endometriosis patients with ultra-long GnRH-agonist or GnRH-antagonist protocols: A retrospective study by propensity score matching.

Although in vitro fertilization with embryo transfer is the most effective treatment for infertile patients with endometriosis, ovarian stimulation protocols are controversial. We recruited 639 patients with endometriosis from January 2016 to June 2020; 111 and 528 patients were treated with the gonadotropin-releasing hormone (GnRH) antagonist and ultra-long GnRH agonist protocols, respectively. Potential baseline differences between the regimens were adjusted by propensity score matching. Clinical and laboratory data, including the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLBR), were compared. Ovulation induction required significantly longer use of gonadotropins in the GnRH agonist group. However, the GnRH agonist group had a lower starting dose of gonadotropin (all p < 0.05). Furthermore, significantly lower clinical pregnancy, implantation, and live birth rates were observed in the GnRH antagonist group receiving fresh assisted reproductive technology cycles (all p < 0.05); however, pregnancy outcomes using the subsequent freeze-thaw cycles for the same oocyte retrieval were not significantly different. CCPR and CLBR for the oocyte retrieval cycles of the antagonist and ultra-long agonist protocols were similar. The ultra-long agonist protocol resulted in more favorable implantation of fresh embryos and improved clinical outcomes of the fresh cycle. This novel strategy could be appropriate for endometriosis patients who are temporarily unsuitable for fresh embryo transfer. The GnRH antagonist protocol can be combined with the whole embryo freezing strategy to achieve CCPR and CLBR similar to the ultra-long agonist regimen, thus simultaneously avoiding the long pre-treatment duration of GnRH agonists during the ultra-long agonist protocol.

The Advantage of Growth Hormone Alone as an Adjuvant Therapy in Advanced Age and BMI ≥ 24 kg/m2 with In Vitro Fertilization Failure Due to Poor Embryo Quality.

This study aimed to assess the effects of GH adjuvant therapy on the cumulative live birth rate in patients with poor embryo quality and to determine the characteristics of patients who are more responsive to GH. A retrospective cohort study was carried out in patients who have suffered from previous IVF failure due to poor embryonic development and underwent IVF with or without a 6-week pretreatment with GH in the subsequent cycle from January 2018 to December 2020. Clinical parameters including the cumulative live birth rate between the (-) GH and (+) GH groups were compared. Multivariate analysis was performed to ascertain associations between clinical parameters and cumulative live birth rate. Upon analysis of the clinical data from 236 IVF cycles, 84 patients received GH and 152 did not receive GH. In frozen embryo transfer cycles, compared with the (-) GH group, the implantation rate and live birth rate were significantly higher in the (+) GH group (p < 0.05). After adjusting for possible confounding factors, GH improved cumulative live birth per oocyte retrieval cycle by 1.96 folds (p = 0.032). Furthermore, when patients were subdivided based on age and BMI, a significant increase in the cumulative live birth rate was found in the (+) GH group of patients between 35 and 42 years old and BMI ≥ 24 kg/m2, respectively (p < 0.05). GH may increase the live birth rate in women who experienced IVF failure because of poor embryonic development, particularly in obese patients and women with advanced age.