Oocyte Retrieval Cycles Research Articles

Effect of progesterone concentration on hCG trigger day on clinical outcomes after high-quality single blastocyst transfer in GnRH antagonist cycles.

To investigate whether progesterone levels on the human chorionic gonadotropin (hCG) trigger day are associated with clinical outcomes in fresh cycles and the first frozen-thawed cycles (the freeze-all strategy) following the transfer of a high-quality single blastocyst. This single-center retrospective analysis was conducted on patients undergoing in vitro fertilization with the gonadotropin-releasing hormone (GnRH) antagonist protocol from January 2017 to December 2023. The study included the first and second oocyte retrieval cycles with progesterone levels ≤2 ng/ml on hCG trigger day. Clinical pregnancy rates and early miscarriage rates were compared among groups using curve fitting, threshold effect analysis, and multivariable regression. When progesterone levels were between 1 and 2 ng/ml, the pregnancy rate in fresh cycles was only 51% of that in cycles with progesterone levels ≤1 ng/ml (95% CI: 0.33, 0.79, p = 0.0028). And the pregnancy rate decreased by 25% (95% CI: 0.51, 1.09) for frozen cycles, although there was no statistically significant (p = 0.1273). When cycle types were used as a binary variable in multivariate regression analysis, it was found that the clinical pregnancy rate in frozen cycles was 1.84 times higher than in fresh cycles (OR = 1.84, 95% CI: 1.38-2.47). For progesterone levels between 1 and 2 ng/ml, the clinical pregnancy rate in frozen cycles was 2.90 times that of fresh cycles (OR = 2.90, 95% CI: 1.59, 5.29, p = 0.0015). Progesterone levels on hCG day had no impact on the clinical pregnancy rate in thaw cycles, nor did they affect miscarriage rates in fresh or thaw cycles (p > 0.05). When progesterone levels on hCG trigger day were between 1 and 2 ng/ml, the clinical pregnancy rate for frozen-thawed cycles of high-quality single blastocyst transfer using an GnRH antagonist protocol significantly surpasses that of fresh cycles, thus elective frozen embryo transfer after the freeze-all strategy is recommended.

Women may not benefit from repeated frozen embryo transfers: a retrospective analysis of the cumulative live birth rate of 43972 women.

Which specific groups of women would not benefit from repeated frozen embryo transfers (FETs)? Women over 45 years of age should stop treatment after three FET attempts due to the absence of further benefits, while women aged 40-45 years and those with a diminished ovarian reserve and other causes of infertility have a lower chance of improving their cumulative live birth rate (CLBR) within five FET cycles and experience fewer advantages from repeated transfers. In real-life scenarios of ART, women who fail to achieve a live birth often choose to undergo repeated FETs via the freeze-all strategy. This retrospective study included 43972 women who underwent 86496 oocyte retrieval cycles and 82022 FET cycles between January 2010 and March 2023 under the freeze-all strategy. We categorized the population based on the female's age at the first oocyte pick-up (OPU) cycle (Groups 1-6: <30, 30-34, 35-39, 40-42, 43-44, and ≥45 years of age), number of retrieved oocytes at the first OPU cycle (Groups 1-5: 1-5, 6-10, 11-15, 16-20, and >20 oocytes), and causes of infertility (Groups 1-9: tubal factor, male factor, polycystic ovary syndrome, diminished ovarian reserve, endometriosis, other uterine factors, combined factors, unexplained infertility, and other infertility) to analyse their CLBRs within different FET cycles via Kaplan-Meier analysis (optimistic method) and the competing risk method (conservative method). We utilized multivariate Cox and Fine-Gray models to examine the associations between the CLBR and age, the number of retrieved oocytes, and nine causes of infertility. The CLBR decreased with increasing female age over five FET cycles (Groups 1-6: optimistic method: 96.4%, 94.2%, 86.0%, 50.2%, 23.1%, and 10.1%; conservative method: 87.1%, 82.0%, 67.8%, 33.9%, 13.8%, and 3.5%, respectively). Moreover, there was an increasing trend in the number of retrieved oocytes (Groups 1-5: optimistic method: 82.5%, 91.7%, 93.6%, 94.1%, and 96.2%; conservative method: 58.6%, 76.7%, 84.8%, 88.0%, and 92.5%, respectively). Furthermore, the CLBR varied across different causes of infertility (Groups 1-9: optimistic method: 91.7%, 93.1%, 96.6%, 79.2%, 89.9%, 76.1%, 90.0%, 92.9%, and 35.4%; conservative method: 77.3%, 79.4%, 88.9%, 46.7%, 72.7%, 62.1%, 74.4%, 78.8%, and 20.1%, respectively). Calculating the actual CLBR for each person is difficult because some patients have remaining embryos that have not been transferred; additionally, the current statistical methodology uses both optimistic and conservative methods to calculate the CLBR, and in real life, the CLBR falls between the optimistic and conservative curves. Our study is the first to identify specific subgroups of women who fail to benefit from repeated FETs and who require rational discontinuation of treatment following unsuccessful transfer. This study was financially supported by grants from the National Natural Science Foundation of China (grant numbers: 82271732 to Y.K., 82071603 to L.W., 82001502 to Y.L., and 82201888 to X.S.). The authors declare that they have no conflicts of interest in the present study. N/A.

Effect of Preimplantation Genetic Testing for Aneuploidies on Live Birth Outcomes and the Influencing Factors in Women of Advanced Maternal Age

To investigate effect of preimplantation genetic testing for aneuploidies (PGT-A) on the reproductive outcomes of women of advanced maternal age (AMA) (≥38 years), and to analyze factors influencing the live birth rate in AMA women who have received PGT-A. A retrospective cohort study was conducted. AMA women undergoing PGT-A were enrolled in the PGT-A group. All of them underwent their first oocyte retrieval cycle between January 2019 and June 2023. AMA women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and their first oocyte retrieval cycle over the same period of time were enrolled in the control group (the non-PGT-A group) via propensity score matching. The PGT-A group and the non-PGT-A group each included 193 cycles, which were followed up until January 2024. Follow-up concerning live births was completed for all oocyte retrieval cycles conducted between January 2019 and October 2022. The reproductive outcomes were compared between the two groups. The primary outcome indicator was cumulative live birth rate (CLBR) per oocyte retrieval, while the secondary outcome indicators were cumulative clinical pregnancy rate (CCPR) per oocyte retrieval and spontaneous abortion rate. For the 145 cycles in the PGT-A group with completed live birth follow-up, binary logistic regression analysis and receiver operator characteristic (ROC) curves were used to analyze the influencing factors of live birth rates. A total of 145 cycles in the PGT-A group and 161 cycles in the non-PGT-A group completed follow-up for live births. The CLBR per oocyte retrieval of the PGT-A group was 25.52% (37/145), while that of the non-PGT-A group was 28.50% (46/161), with no significant difference being observed between the two groups (P<0.05). Of the 193 oocyte retrieval cycles in each group, 53 cycles in the PGT-A group and 72 cycles in the non-PGT-A group resulted in clinical pregnancies, with the difference in the CCPR per oocyte retrieval being statistically significant (27.46% vs. 37.31%, P<0.05). Concerning clinical pregnancies, the spontaneous abortion rate of the PGT-A group was lower than that of the non-PGT-A group, with the difference being statistically significant (7.55% vs. 25.00%, P<0.05). In AMA women who had undergone PGT-A for reproductive assistance, maternal age (odds ratio [OR]=0.786, 95% confidence interval [CI]: 0.635-0.973) and the antral follicle count (AFC) (OR=1.110, 95% CI: 1.013-1.216) were correlated with the outcome of live births outcome. The probability of live births decreased with increasing maternal age and decreasing AFC. When the female age was ≥42 years or when AFC≤8, the expected live birth outcome of PGT-A assisted pregnancy was poor. PGT-A does not affect the CLBR per oocyte retrieval in AMA women, but it can effectively reduce the risks of implantation failure and spontaneous abortion due to fetal aneuploidies. For PGT-A-assisted pregnancy in AMA women, maternal age and AFC are important factors affecting the live birth outcomes.

Association of HOMA-IR with unexpected poor ovarian response in non-obese women in poseidon 1: a retrospective cohort study

BackgroundInsulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR) in non-obese subjects with sufficient ovarian parameters (classified as POSEIDON group 1). This research aims to explore the association between the homeostasis model assessment of insulin resistance (HOMA-IR) and uPOR in non-obese women with normal biomarkers of ovarian reserve.MethodsThe retrospective cohort study was conducted at a fertility center. The main inclusion criteria were age < 35 years, body mass index (BMI) < 28 kg/m2, normal ovarian reserve (anti-Mullerian hormone ≥ 1.2 ng/ml, antral follicle count ≥ 5). Women undergoing the first oocyte retrieval cycle were included consecutively between 2018 until 2023. Patients who have ≤ 9 oocytes retrieved were defined as uPOR. The multivariable logistic model and subgroup analysis were conducted after adjusting confounders.ResultsA total of 6977 cycles were included. The adjusted odds ratio was 1.25 (95% confidence interval [CI], 1.12–1.39) for the increment of Ln HOMA-IR which was taken as a continuous variable. Meanwhile, as a sensitivity analysis, elevated tertile of HOMA-IR exhibited an increase in risk of uPOR for the third tertile (≥ 2.75) when compared with the first tertile (< 1.75) with OR of 1.33 (95%CI, 1.15–1.54). In the subgroup analysis, the positive association remained consistent.ConclusionElevated HOMA-IR values is significantly associated with increased risk of uPOR in non-obese women classified as POSEIDON group 1. Our study provided evidence for the adverse influence of IR on the ovarian response during IVF and shed light on the importance of IR measurement at the time of pre-stimulation among non-obese women.

IVF laboratory management through workflow-based RFID tag witnessing and real-time information entry

BackgroundDual-person inspection in IVF laboratories cannot fully avoid mix-ups or embryo transfer errors, and data transcription or entry is time-consuming and redundant, often leading to delays in completing medical records.MethodsThis study introduced a workflow-based RFID tag witnessing and real-time information entry platform for addressing these challenges. To assess its potential in reducing mix-ups, we conducted a simulation experiment in semen preparation to analyze its error correction rate. Additionally, we evaluated its impact on work efficiency, specifically in operation and data entry. Furthermore, we compared the cycle costs between paper labels and RFID tags. Finally, we retrospectively analyzed clinical outcomes of 20,424 oocyte retrieval cycles and 15,785 frozen embryo transfer cycles, which were divided into paper label and RFID tag groups.ResultsThe study revealed that comparing to paper labels, RFID tag witnessing corrected 100% of tag errors, didn’t affect gamete/embryo operations, and notably shorten the time of entering data, but the cycle cost of RFID tags was significantly higher. However, no significant differences were observed in fertilization, embryo quality, blastocyst rates, clinical pregnancy, and live birth rates between two groups.ConclusionsRFID tag witnessing doesn’t negatively impact gamete/embryo operation, embryo quality and pregnancy outcomes, but it potentially reduces the risk of mix-ups or errors. Despite highly increased cost, integrating RFID tag witnessing with real-time information entry can remarkably decrease the data entry time, substantially improving the work efficiency. This workflow-based management platform also enhances operational safety, ensures medical informational integrity, and boosts embryologist’s confidence.

Impact of Luteinizing Hormone on IVF/ICSI Assisted Reproduction on the Initiation Day of Gonadotropin-releasing Hormone Antagonist Protocol.

The aim of the study was to explore the optimal timing of gonadotropin initiation and the reasonable interval of luteinizing hormone (LH) levels in the gonadotropin-releasing hormone antagonist (GnRH-A) protocol. A retrospective cohort study was conducted to analyze the data concerning the oocyte retrieval cycles from 1,361 cases with the GnRH-A protocol implemented. The ovarian responses (including AMH, AFC) in these patients were divided into the poor ovarian response group (an antral follicle count [AFC] ≤ 6, n = 394), the normal ovarian response group (an AFC > 6 and < 15, n = 570), and the high ovarian response group (an AFC ≥ 15, n = 397), according to the AFC. The patients were sub-grouped according to LH levels on the protocol initiation day, and the clinical outcomes (including dose of Gn initiation, Gn administration days, GnRH-ant administration days, P levels on the HCG day, E2 levels on the HCG day, LH levels on the HCG day, number of embryos transferred, total fertilization rate, embryo implantation rate(%), proportion of 2PN, proportion of good-quality embryos, endometrial thickness on the hCG injection day(mm), moderate to severe OHSS, AFC on the initiation day, proportion of type A endometrium on the hCG injection day, clinical pregnancy rate, biochemical pregnancy rate, early abortion rate, ectopic pregnancy rate) were compared. On the GnRH-A protocol initiation day, among all patients with different ovarian responses, the body mass index (BMI) in those with an LH ≥ 5 IU/L was lower. The differences in pregnancy outcomes between the LH < 5 IU/L group and the LH ≥ 5 IU/L group were not statistically significant across the different ovarian response groups, but the LH < 5 IU/L group had a higher proportion of good-quality embryos (80.3±24.9 vs. 74.8±26.9, P =0.035) than the LH≥5IU/Lgroup in those with poor ovarian response. The total fertilization rate (82.2±18.1 vs 85.4±15.1, P =0.021) and proportion of two pronuclei (2PN) (69.0±20.9 vs 72.7±19.9, P =0.035) were higher in the LH ≥ 5 IU/L group than the LH<5 IU/L group for those with normal ovarian responses. The embryo implantation rate (41.4±41.3 vs 52.6±43.4, P =0.012) was higher in the LH ≥ 5 IU/L group than in the LH<5 IU/L group in those with high ovarian response. The results of the multivariate logistic analysis showed that the age of the female partner, number of embryos transferred, proportion of good-quality embryos, endometrial thickness on the hCG injection day, and moderate- to-severe ovarian hyperstimulation syndrome (OHSS) were independent factors correlated with the outcome of live births (P < 0.05). The LH levels on the gonadotropins (Gn) initiation day in the GnRH-A protocol will not affect pregnancy outcomes.

O-064 Can artificial removal of the zona pellucida with severe fragmentation improve culture and pregnancy outcomes?

Abstract Study question Can artificial removal of the zona pellucida (ZP-free) in patients whose embryos had severe fragmentation improve culture and pregnancy outcomes? Summary answer In patients with severe fragmentation, blastulation and live birth rate were improved by ZP-free procedure, and 14 live babieshave been obtained so far. What is known already In 2020, Yumoto et al. first reported that ZP-free procedure at the pronuclear stage decreased the rate of fragmentation and improved blastulation of 3 pronuclei embryos. 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 transfer of blastocyst derived from 2 pronuclei embryos (2PN) after ZP-free procedure resulted in normal pregnancy and live births in two patients who had had poor-quality embryos only before ZP-free procedure. We also presented culture outcomes improved by ZP-free procedure at the 2023 ESHRE meeting. Study design, size, duration This study included 571 embryos derived from 2PN on 118 cycles in 61 couples obtained between July 2021 and November 2023, whose previous oocyte retrieval cycle had shown massive cytoplasmic fragmentation at the first cleavage confirmed by a time-laps incubator (TLI) in two institutes. Mean age of women was 40.0±3.8 years. Culture and pregnancy outcomes after blastocyst transfer were compared with 1272 embryos derived from 2PN in the past 247 cycles without ZP-free procedure (ZP-intact). Participants/materials, setting, methods All participants provided written informed consent, and IRB approval was obtained. Embryos were placed in 0.125M sucrose-containing HEPES for cytoplasm shrinking at the pronuclear stage. The ZP was partially removed in non-adhesive areas with a laser system. Ooplasms were completely separated from ZP by blowing the medium to adhesion point like a jet car wash. The ZP-free embryos were cultured in TLI up to 7 days, followed by blastocyst cryopreservation for future embryo transfer cycles. 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 outcomes of ZP-free cycle and previous ZP-intact cycle. For day 3 embryos, good, fair and poor grade were 15.6%, 55.3% and 29.1% in ZP-free embryos compared with 3.7%, 42.5%, and 53.8% in ZP-intact embryos, respectively (p &amp;lt; 0.001). As to the blastocysts, blastocysts development and good-quality blastocysts (G3BB or more on day 5 by the Gardner’s classification) rates were 36.9% and 19.4% in ZP-free embryos compared with 23.1% and 6.0% in ZP-intact embryos, respectively (p &amp;lt; 0.001). Clinical pregnancy rates for ZP-free and ZP-intact blastocyst transfer were 36.1% (22/61) and 15.0% (17/113), miscarriage rates were 18.2% (4/22) and 82.4% (14/17), and ongoing pregnancy rates were 29.5% (18/61) and 2.7% (3/113), respectively, with statistical significance after ZPF procedure (P &amp;lt; 0.01). Fourteen live babies have given birth by single blastocyst transfer with ZP-free procedure so far. Limitations, reasons for caution This study was retrospective study without any control group and was conducted at only two fertility centers. It is necessary to conduct sibling oocytes study or extensive randomized controlled trial to create criteria for patients who are benefit from ZP-free procedure. Moreover, safety of ZP-free culture should be evaluated. Wider implications of the findings ZP-free procedure in patients with severe fragmentated embryos at the pronuclear stage, reduced fragmentation and improved blastocyst development and clinical outcomes. We suggest that ZP-free embryos could be proposed as a new treatment option for patients who have had poor quality embryos with severe fragmentation. Trial registration number Not applicable

O-186 A novel micro-insemination method, assisted sperm fusion insemination, increases the embryo utilization rate compared to conventional intracytoplasmic sperm injection

Abstract Study question Does a novel micro-insemination method, assisted sperm fusion insemination (ASFI), improve fertilization and embryonic development compared to conventional intracytoplasmic sperm injection (C-ICSI)? Summary answer ASFI showed comparable fertilization and blastocyst formation rates to C-ICSI, while achieving significantly higher embryo utilization rates. Furthermore, there were no degenerated oocytes after ASFI. What is known already We have reported that ASFI yielded fertilization and blastocyst rates similar to those obtained with rescue ICSI performed at 6 hours after in vitro fertilization (IVF). In ASFI, fertilization is achieved by pressing a zona pellucida (ZP)-bound sperm onto the oocyte membrane without breaking the oocyte membrane. However, there was a risk of artificial polyspermy because the sperm were pressed against the unfertilized oocytes after IVF. Moreover, it is uncertain whether fertilization occurred with sperm that penetrated into the oocyte via IVF or that were pressed against the oocyte membrane. Clarifying this requires performing ASFI of the oocyte without IVF. Study design, size, duration We prospectively evaluated the effectiveness of ASFI in a sibling oocyte study including 14 subjects from which at least two metaphase II (MII) oocytes and one immature or degenerated oocyte were retrieved. Between December 2022 and October 2023, 119 MII oocytes were obtained in 22 oocyte retrieval cycles and used in the study. Sibling MII oocytes were randomly assigned to a C-ICSI or ASFI group. The present study was approved by the local ethics committee. Participants/materials, setting, methods In the ASFI group, 10,000 motile sperm were incubated with at least one immature or degenerated oocyte for 3 hours in 100 μL of medium per patient. After incubation, the motile sperm bound to the ZP were aspirated directly using an injection pipette. The heads of these ZP-bound sperm were pressed onto the membrane of MII oocytes for 10 seconds using the injection pipette. C-ICSI was conducted using the conventional method. Main results and the role of chance The mean and standard deviation of age of the women and number of MII oocytes per cycle were 39.9 ± 2.2 years and 5.5 ± 1.8, respectively. All sperm collected from the ZP adhered to the MII oocyte membrane after ASFI. Furthermore, time-lapse imaging revealed that all sperm adhering to the MII oocyte membrane were subsequently incorporated into the oocyte. Comparison of the ASFI and C-ICSI groups did not reveal any significant differences in 2 pronuclear embryo rate (ASFI group: 85.4% vs. C-ICSI group: 71.8%), degeneration rate (0% vs. 5.6%), good-quality embryo rate at day 3 (63.4% vs. 52.9%), blastocyst formation rate (67.6% vs. 51.9%), or good-quality blastocyst (Grade 3BB and above by the Gardner criteria) formation rate (29.4% vs. 15.4%). On the contrary, the embryo utilization rate (defined as the total number of embryos transferred and cryopreserved divided by the number of MII oocytes) was significantly higher in the ASFI group compared to the C-ICSI group (47.9% vs. 25.4%, P &amp;lt; 0.05). Limitations, reasons for caution This study was limited by using the ZP for sperm selection. To expand its applicability, a method to identify sperm capable of fusing with an oocyte without using the ZP must be established. Additionally, since our sample size was small, larger studies are required to confirm our findings. Wider implications of the findings ASFI is expected to enhance the survival rate of oocytes and to increase the number of embryos available for implantation, not only compared to rescue ICSI but also C-ICSI. ASFI could aid in understanding fertilization mechanisms by enabling direct observation of oocyte-sperm fusion during the process. Trial registration number UMIN000050184

The role of age and AMH on cumulative live birth rates over multiple frozen-thawed embryo transfer cycles: a study based on low prognosis patients of POSEIDON 3 and 4 groups

BackgroundAmong the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported.MethodsThis retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves.ResultsUnder optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles.ConclusionsThe patients of POSEIDON group 3 may not be considered as traditional “low prognosis” in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.

Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.

For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.

Safety evaluation of single-sperm cryopreservation technique applied in intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.

Neighborhood deprivation in relation to ovarian reserve and outcomes of ovarian stimulation among oocyte donors

ObjectiveTo study the relation of neighborhood deprivation index (NDI) and markers of ovarian reserve and outcomes of controlled ovarian stimulation among young, healthy oocyte donors. DesignRetrospective cohort study Subjects547 oocyte donors who underwent 905 oocyte retrieval cycles (2008-2020) at a private fertility center in Sandy Springs, Georgia, USA. ExposureNDI was calculated using principal component analysis applied to census-level measures of poverty, employment, household composition, and public assistance, which was then standardized and linked to donor information based on donor residence. Main Outcome MeasuresMarkers of ovarian reserve, including antral follicle count (AFC) and anti-Müllerian hormone (AMH) levels, and outcomes of controlled ovarian stimulation including number of total and mature oocytes retrieved and ovarian sensitivity index (OSI) (defined as the number of oocytes retrieved ÷ total gonadotropin dose × 1,000). Multivariable generalized estimating equations with Poisson and normal distribution were used to model the relationship between NDI and outcome measures adjusting for age, BMI, and year of retrieval. ResultsThe mean (standard deviation) age of donors was 25.0 (2.8) years and 29% of the donors were racial/ethnic minorities. There were no associations between donor NDI and ovarian reserve markers. For every interquartile range increase in NDI, there was a reduction of -1.5% (95% CI -5.3, 2.4%) in total oocytes retrieved although the effect estimate was imprecise. Associations of NDI with number of mature oocytes retrieved and OSI were in a similar direction. We observed evidence for effect modification of the NDI and OSI association by donor race. There was a suggestive positive association between NDI and OSI in Black donors but no association in White donors. Conclusion and relevanceIn this cohort of young, healthy, racially diverse oocyte donors, we found little evidence of associations between NDI and markers of ovarian reserve or outcomes of ovarian stimulation.

The reproductive potential of vitrified-warmed euploid embryos declines following repeated uterine transfers

BackgroundRecurrent implantation failure (RIF) represents a vague clinical condition with an unclear diagnostic challenge that lacks solid scientific underpinning. Although euploid embryos have demonstrated consistent implantation capabilities across various age groups, a unanimous agreement regarding the advantages of preimplantation genetic testing for aneuploidy (PGT-A) in managing RIF is absent. The ongoing discussion about whether chromosomal aneuploidy in embryos significantly contributes to recurrent implantation failure remains unsettled. Despite active discussions in recent times, a universally accepted characterization of recurrent implantation failure remains elusive. We aimed in this study to measure the reproductive performance of vitrified-warmed euploid embryos transferred to the uterus in successive cycles.MethodsThis observational cohort study included women (n = 387) with an anatomically normal uterus who underwent oocyte retrieval for PGT-A treatment with at least one biopsied blastocyst, between January 2017 and December 2021 at a university-affiliated public fertility center. The procedures involved in this study included ICSI, blastocyst culture, trophectoderm biopsy and comprehensive 24-chromosome analysis of preimplantation embryos using Next Generation Sequencing (NGS). Women, who failed a vitrified-warmed euploid embryo transfer, had successive blastocyst transfer cycles (FET) for a total of three using remaining cryopreserved euploid blastocysts from the same oocyte retrieval cycle. The primary endpoints were sustained implantation rate (SIR) and live birth rate (LBR) per vitrified-warmed single euploid embryo. The secondary endpoints were mean euploidy rate (m-ER) per cohort of biopsied blastocysts from each patient, as well as pregnancy and miscarriage rates.ResultsThe mean age of the patient population was 33.4 years (95% CI 32.8–33.9). A total of 1,641 embryos derived from the first oocyte retrieval cycle were biopsied and screened. We found no associations between the m-ER and the number of previous failed IVF cycles among different ranges of maternal age at oocyte retrieval (P = 0.45). Pairwise comparisons showed a significant decrease in the sustained implantation rate (44.7% vs. 30%; P = 0.01) and the livebirth rate per single euploid blastocyst (37.1% vs. 25%; P = 0.02) between the 1st and 3rd FET. The cumulative SIR and LBR after up to three successive single embryo transfers were 77.1% and 68.8%, respectively. We found that the live birth rate of the first vitrified-warmed euploid blastocyst transferred decreased significantly with the increasing number of previously failed IVF attempts by categories (45.3% vs. 35.8% vs. 27.6%; P = 0.04). A comparable decrease in sustained implantation rate was also observed but did not reach statistical significance (50% vs. 44.2 vs. 37.9%; P = NS). Using a logistic regression model, we confirmed the presence of a negative association between the number of previous IVF failed attempts and the live birth rate per embryo transfer cycle (OR = 0.76; 95% CI 0.62–0.94; P = 0.01).ConclusionsThese findings are vital for enhancing patient counseling and refining management strategies for individuals facing recurrent implantation failure. By tailoring interventions based on age and ovarian reserve, healthcare professionals can offer more personalized guidance, potentially improving the overall success rates and patient experiences in fertility treatments.Trial registration numberN/A.

Follitropin Alpha versus Follitropin Beta in IVF/ICSI Cycle: A Retrospective Cohort Study.

The purpose of this study was to compare the efficacy of Follitropin alpha (Gonal-F) and Follitropin beta (Puregon) on cumulative live birth rate (CLBR), defined as the percentage of the number of patients who delivered for the first time in a single ovarian stimulation cycle and the number of patients in all oocyte retrieval cycles. A retrospective cohort study including 2864 infertile patients who underwent ovarian stimulation with Puregon (group A, n=1313) and Gonal-F (group B, n=1551) was conducted between July 2015 and June 2021 at a university-affiliated reproductive medicine center. Reduce potential confounding factors between groups, propensity scores and multivariable logistic regression analyses were estimated to obtain unbiased estimates of outcomes. The primary outcome was the difference in CLBR between the two groups. Each group identified 1160 individuals after propensity score matching (PSM). Baseline characteristics were similar between groups after PSM. The total gonadotrophin (Gn) dose (2400 vs 2325), p=0.038) and cost of Gn usage (5327.9¥ vs 7547.2¥, p<0.001) between the Puregon and Gonal-F groups were statistically significant. Nevertheless, the pregnancy outcomes between the two groups were comparable after fresh embryo transfer and subsequent frozen-thawed embryo transfer. Additionally, there was also no difference observed in the primary outcome of CLBR (52.8% vs 55.7%, p=0.169). Multivariable regression analysis revealed that the type of Gn was not associated with CLBR (p = 0.912). Gonal-F may be a reasonable option for infertile patients who are hesitant to receive more Gn dosage injections. Furthermore, Puregon can eliminate unneeded anxiety and expenses while also administering more flexibility. Taken together, these findings could well be utilized in everyday clinical practice to better inform patients when deciding on an ovarian stimulation strategy.

Risk factors, management, and future fertility of empty follicle syndrome: a retrospective study with real-world data.

Empty follicle syndrome (EFS) is a challenging clinical problem. This study aims to identify the risk factors for EFS, to present pregnancy outcomes in both EFS cycle as well as subsequent cycles, and to summarize an effective rescue protocol to improve outcomes. A retrospective analysis between 2016 and 2020 was conducted at our center. Stricter criteria were applied to diagnose EFS. Logistic regression analysis was used to identify the risk factors for EFS. Further analyses were performed within the EFS cycle to present pregnancy outcomes and to find optimal rescue protocols. Long-term follow-up was conducted until live birth was achieved, covering at least two complete oocyte retrieval cycles. Among 14,066 patients, 54 (0.38%) were identified as EFS. Patients with polycystic ovary syndrome (PCOS) had a significantly higher risk of developing EFS than non-PCOS ones (aOR = 2.67; 95% CI, 1.47 to 4.83). Within EFS patients, delaying the second oocyte retrieval by 3-6 h significantly improved the rates of obtaining oocyte (97.4% versus 58.3%, P = 0.002), getting embryo available for transfer (92.3% versus 33.3%, P < 0.001), and pregnancy (48.7% versus 8.3%, P = 0.017) compared to other delayed retrieval times. Overall, 31.5% (17/54) and 46.7% (7/15) EFS patients achieved live birth in the EFS cycle and the future cycle, respectively. PCOS is an independent risk factor for EFS, indicating that longer exposure time to human chorionic gonadotropin (hCG) may be necessary. Delaying the second oocyte retrieval by 3-6 h is an effective rescue protocol for EFS patients to achieve optimal outcomes. EFS in a single cycle does not necessarily indicate future fertility decline, but repeated EFS may result in poor outcomes.

Impaired embryo development potential associated with thyroid autoimmunity in euthyroid infertile women with diminished ovarian reserve.

The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR). This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%). For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]. TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR.

#276 : Impact of Previous Cesarean Delivery on Pregnancy and Neonatal Outcomes of Subsequent In Vitro Fertilization/Intracytoplasmic Sperm Microinjection and Single Frozen-Thawed Embryo Transfer

Background and Aims: Cesarean delivery (CD) rates continue to rise worldwide. Prior studies have indicated that CD is associated with not only various gynaecological symptoms and obstetric complications but also lower probability of subsequent fertility. However, the recognition about impact of CD on clinical outcomes in subsequent IVF/ICSI-FET is very limited. The purpose was to investigate the effects of previous CD on pregnancy and neonatal outcomes in single frozen-thawed embryo transfer (FET) cycles so that women with a previous cesarean delivery can be given detailed fertility counseling during the ART process. Methods: This is a large retrospective cohort study including a total of 5,750 patients who desired to transfer single vitrified-thawed blastocyst from the same oocyte retrieval cycle as their last live birth between January 2011 and January 2021 in a center for reproductive medicine in Shandong, China, comprising FET cycles of 3,853 previous single CD and 1,897 previous single vaginal delivery (VD). Results: Women with a previous CD had significantly lower rates of biochemical pregnancy (64.52% vs. 71.48% before propensity score matching (PSM), P&lt;0.001; and 65.58% vs. 71.49% after PSM, P&lt;0.001), clinical pregnancy (58.16% vs. 65.79% before PSM, P&lt;0.001; and 59.22% vs. 66.17% after PSM, P&lt;0.001) and live birth (48.17% vs. 55.82% before PSM, P&lt;0.001; and 49.29% vs. 56.10% after PSM, P&lt;0.001) than those with a previous VD. Meanwhile, the CD rate was significantly higher in the CD group (97.85% vs. 18.53% before PSM, P&lt;0.001; and 98.02% vs. 20.51% after PSM, P&lt;0.001). The rates of multiple pregnancy, miscarriage, ectopic pregnancy, multiple live birth, labor complications and preterm and neonatal outcomes were comparable between the two groups. Conclusion: Compared to VD, a previous CD is associated with a significant reduction in the rates of biochemical pregnancy, clinical pregnancy and live birth in patients undergoing subsequent single frozen-thawed blastocyst transfer.

Exploring the efficacy and beneficial population of preimplantation genetic testing for aneuploidy start from the oocyte retrieval cycle: a real-world study

BackgroundPreimplantation genetic testing for aneuploidy (PGT-A) is widely used as an embryo selection technique in in vitro fertilization (IVF), but its effectiveness and potential beneficiary populations are unclear.MethodsThis retrospective cohort study included patients who underwent their first oocyte retrieval cycles at CITIC-Xiangya between January 2016 and November 2019, and the associated fresh and thawed embryo transfer cycles up to November 30, 2020. PGT-A (PGT-A group) and intracytoplasmic sperm injection (ICSI)/IVF (non-PGT-A group) cycles were included. The numbers of oocytes and embryos obtained were unrestricted. In total, 60,580 patients were enrolled, and baseline data were matched between groups using 1:3 propensity score matching. Sensitivity analyses, including propensity score stratification and traditional multivariate logistic regression, were performed on the original unmatched cohort to check the robustness of the overall results. Analyses were stratified by age, body mass index, ovarian reserve/responsiveness, and potential indications to explore benefits in subgroups. The primary outcome was cumulative live birth rate (CLBR). The other outcomes included live birth rate (LBR), pregnancy loss rate, clinical pregnancy rate, pregnancy complications, low birth weight rate, and neonatal malformation rate.ResultsIn total, 4195 PGT-A users were matched with 10,140 non-PGT-A users. A significant reduction in CLBR was observed in women using PGT-A (27.5% vs. 31.1%; odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.78–0.91; P < 0.001). However, women using PGT-A had higher first-transfer pregnancy (63.9% vs. 46.9%; OR = 2.01, 95% CI 1.81–2.23; P < 0.001) and LBR (52.6% vs. 34.2%, OR = 2.13, 95% CI 1.92–2.36; P < 0.001) rates and lower rates of early miscarriage (12.8% vs. 20.2%; OR = 0.58, 95% CI 0.48–0.70; P < 0.001), preterm birth (8.6% vs 17.3%; P < 0.001), and low birth weight (4.9% vs. 19.3%; P < 0.001). Moreover, subgroup analyses revealed that women aged ≥ 38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions benefited from PGT-A, with a significant increase in first-transfer LBR without a decrease in CLBR.ConclusionPGT-A does not increase and decrease CLBR per oocyte retrieval cycle; nonetheless, it is effective in infertile populations with specific indications. PGT-A reduces complications associated with multiple gestations.

Oocyte cryopreservation in mosaic Turner syndrome with polycystic ovaries

To report a case of a patient with Turner syndrome (TS) mosaicism and polycystic ovarian syndrome (PCOS), who underwent successful ovarian stimulation, oocyte retrieval, and cryopreservation. Case report. A female patient with mosaic TS (45,X [24%]/46,XX [76%]) and a paternally inherited balanced reciprocal translocation t(2:6) diagnosed with PCOS. Controlled ovarian stimulation, oocyte retrieval, and cryopreservation. Successful oocyte retrieval and cryopreservation. We report an interesting case of a patient with TS mosaicism 45,X [24%]/46,XX [76%] and a paternally inherited t(2:6) balanced reciprocal translocation, who was diagnosed with PCOS on the basis of oligomenorrhea and ultrasound polycystic ovary morphology (antral follicle count of 17 and >20, left and right ovaries, respectively), underwent 2 cycles of ovarian stimulation, oocyte retrieval, and cryopreservation, resulting in 19 cryopreserved oocytes. Our case highlights the importance of early counseling regarding fertility options in patients with mosaic TS and the need for careful monitoring of ovarian reserve during this process, which could be done by measuring the anti-müllerian hormone or antral follicle count. It also underscores the possibility of women with mosaic TS being affected by PCOS.

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 &amp;lt; 0.001; blastocyst formation rate: P &amp;lt; 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 &amp;lt; 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 &amp; 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.