Intrauterine Infusion and Hysteroscopic Injection of Autologous Platelet-Rich Plasma for Patients with a Persistent Thin Endometrium: A Prospective Case-Control Study.

Objectives: To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods: This prospective case-control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results: After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions: Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM.

Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles.

BACKGROUND: Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes in cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, the effectiveness of iDAScore in cycles with PGT-A has not been thoroughly investigated. Therefore, this study aims to assess the association between artificial intelligence (AI)-based iDAScore (version 1.0) and pregnancy outcomes in single-embryo transfer (SET) cycles with PGT-A. METHODS: This retrospective study was approved by the Institutional Review Board of Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET cycles (n = 482) following PGT-A at a single reproductive center between January 2017 and June 2021. The blastocyst morphology and morphokinetics of all embryos were evaluated using a time-lapse system. The blastocysts were ranked based on the scores generated by iDAScore, which were defined as AI scores, or by KIDScore D5 (version 3.2) following the manufacturer's protocols. A single blastocyst without aneuploidy was transferred after examining the embryonic ploidy status using a next-generation sequencing-based PGT-A platform. Logistic regression analysis with generalized estimating equations was conducted to assess whether AI scores are associated with the probability of live birth (LB) while considering confounding factors. RESULTS: Logistic regression analysis revealed that AI score was significantly associated with LB probability (adjusted odds ratio [OR] = 2.037, 95% confidence interval [CI]: 1.632-2.542) when pulsatility index (PI) level and types of chromosomal abnormalities were controlled. Blastocysts were divided into quartiles in accordance with their AI score (group 1: 3.0-7.8; group 2: 7.9-8.6; group 3: 8.7-8.9; and group 4: 9.0-9.5). Group 1 had a lower LB rate (34.6% vs. 59.8-72.3%) and a higher rate of pregnancy loss (26% vs. 4.7-8.9%) compared with the other groups (p < 0.05). The receiver operating characteristic curve analysis verified that the iDAScore had a significant but limited ability to predict LB (area under the curve [AUC] = 0.64); this ability was significantly weaker than that of the combination of iDAScore, type of chromosomal abnormalities, and PI level (AUC = 0.67). In the comparison of the LB groups with the non-LB groups, the AI scores were significantly lower in the non-LB groups, both for euploid (median: 8.6 vs. 8.8) and mosaic (median: 8.0 vs. 8.6) SETs. CONCLUSIONS: Although its predictive ability can be further enhanced, the AI score was significantly associated with LB probability in SET cycles. Euploid or mosaic blastocysts with low AI scores (≤ 7.8) were associated with a lower LB rate, indicating the potential of this annotation-free AI system as a decision-support tool for deselecting embryos with poor pregnancy outcomes following PGT-A.

Factors Affecting the Potential Efficacy of Intrauterine Platelet-Rich Plasma Infusion on Thin Endometrium in Women with Recurrent Implantation Failure.

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of <7 mm. These women underwent programmed hormone therapy for frozen embryo transfer (FET) and received two autologous intrauterine PRP infusions. Following intrauterine PRP-lysate (PL) infusions, the mean increase in EMT was 1.9 ± 1.2 mm, with EMT reaching 7 mm in 86% of the cases (66/77; average EMT, 8.3 mm). We identified an exceedingly thin EMT as a risk factor impacting the therapeutic efficacy in increasing EMT (p = 0.04, OR: 3.16; 95% CI: 1.03-9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12-3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion.

Increased incidence of live births in implanted day 5 versus day 6 blastocysts following single embryo transfers with PGT-A.

Elective single-embryo transfers of euploid or low-level mosaic blastocysts were analyzed in this retrospective study to determine the correlations of live birth (LB) probability with embryonic developmental features of implanted day 5 (D5, n = 245) or day 6 (D6, n = 73) blastocysts using time-lapse (TL) monitoring. According to the logistic regression analyses (adjusted odds ratio [OR] = 0.341, 95% confidence interval [CI] = 0.169-0.685, P < 0.05), the LB probability was negatively associated with the D6 group. The LB rate of the D5 group was higher than the D6 group (88.2% vs. 75.3%; P < 0.05). Compared with the D5 blastocysts, the D6 blastocysts exhibited comparable dysmorphisms except for the multinucleation at the 4-cell stage (10.9% vs. 2.9%, P < 0.05). Moreover, D6 blastocysts had considerably slower developmental kinetics and poorer blastocyst morphologies. Further analysis confirmed that the LB rate was not associated with developmental kinetics or dysmorphisms but rather with blastocyst morphology (inner cell mass [ICM] grade ≤ C vs. ICM grade A, adjusted OR = 0.155, 95% CI = 0.04-0.596, P < 0.05; trophectoderm [TE] grade ≤ C vs. TE grade A, adjusted OR = 0.157, 95% CI = 0.032-0.760, P < 0.05). In conclusion, D6 implanted blastocysts have a considerably lower LB rate than D5 implanted blastocysts. As determined by TL monitoring, the diminished blastocyst morphology can be one of the primary reasons underlying the decreased likelihood of LB.

The presence of vacuoles in blastocysts is negatively associated with euploidy and live birth rates.

OBJECTIVE: To investigate whether the presence of vacuoles in biopsied blastocysts is associated with the likelihood of aneuploidy and clinical outcomes. DESIGN: Retrospective observational study. SETTING: A single reproductive center. INTERVENTION(S): None. PATIENT(S): This study retrospectively analyzed data obtained through preimplantation genetic testing for aneuploidy performed on 3351 blastocysts from 826 patients at a single reproductive center between August 2018 and July 2020. Ultimately, 167 single euploid blastocyst transfers were performed in these patients. Vacuoles existing in the trophectoderm or inner cell mass were observed using blastocyst biopsy. After the biopsy, all blastocysts were vitrified, and embryo transfer was performed in a subsequent treatment cycle. MAIN OUTCOME MEASURE(S): The associations between vacuoles and euploidy or live birth rates were assessed using logistic regression models and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULT(S): Of the 3351 blastocysts from 826 patients, 903 (26.9%) were discovered to have vacuoles. The vacuole-positive group had a significantly lower percentage of euploid blastocysts after TE biopsy than the vacuole-negative group (28.8% vs. 35.5%). Embryos with vacuoles were significantly more likely to be poor quality (30.6% vs. 18.2%). Logistic regression analyses revealed that euploid blastocysts were positively associated with the absence of vacuoles, maternal age, and good embryo quality (vacuole-negative group: adjusted OR 1.291; 95% CI: 1.089-1.530; age <38 years: adjusted OR 1.989; 95% CI: 1.692-2.337; good embryo quality: adjusted OR 1.703; 95% CI: 1.405-2.064). The implantation and live birth rates were significantly lower for the transferred single euploid blastocysts with vacuoles than those without (35.5% vs. 56.6%; 29.0% vs. 52.2%, respectively). The live birth rate was positively associated with the absence of vacuoles (adjusted OR 2.792; 95% CI: 1.180-6.608). CONCLUSION(S): The formation of vacuoles in blastocysts is associated with lower rates of euploidy and live birth. Blastocysts without vacuoles should thus be prioritized for embryo transfer in vitro fertilization cycles.

Biphasic oxygen tension promotes the formation of transferable blastocysts in patients without euploid embryos in previous monophasic oxygen cycles.

This study evaluated whether the concentration of biphasic O2 (5-2%) promotes the formation of qualified blastocysts (QBs) and euploid blastocysts and the probability of cycles with transferable blastocysts. The paired experimental design included a total 90 patients (180 cycles) without euploid blastocysts in previous monophasic O2 (5%) cycles were enrolled for an additional cycle of biphasic O2 (5-2%). In the biphasic O2 (5-2%) group, the QB rate (35.8%, 225/628) was significantly higher than that in the monophasic O2 (5%) group (23.5%, 137/582; p < 0.001). In addition, the euploid blastocyst number (0.5 ± 0.8) and the percentage of cycles with transferable blastocysts were significantly higher in the biphasic O2 (5-2%) group (57.8%, 52/90) than those in the monophasic O2 (5%) group (0 and 35.6%, 32/90, respectively; p < 0.01). Multivariable regression analysis also indicated that the QB rate and the probability of cycles with transferable blastocysts correlated with O2 tension (OR 1.535, 95% CI 1.325-1.777, and OR 3.191, 95% CI 1.638-5.679, respectively; p < 0.001). Biphasic O2 culture can be used as an alternative strategy to increase the euploid QBs and the probability of cycles with transferable blastocysts in patients with a poor prognosis.

Risk of Infertility in Males with Obstructive Sleep Apnea: A Nationwide, Population-Based, Nested Case-Control Study.

Obstructive sleep apnea (OSA) yields intermittent hypoxia, hypercapnia, and sleep fragmentation. OSA is associated with chronic medical conditions such as cardiovascular diseases, metabolic syndrome, and neurocognitive dysfunction. However, the risk of infertility in OSA remains unclear due to limited data and lack of long-term population-based studies. The study aims to assess the risk of infertility in obstructive sleep apnea (OSA) by means of a population-based cohort study. The data was utilized from the Taiwan National Health Insurance Research Database (NHIRD) to conduct a population-based cohort study (1997-2013). Compared with the Non-OSA group, the male with OSA and surgery group has the OR (odds ratio) of infertility of 2.70 (95% CI, 1.46-4.98, p = 0.0015), but no significance exists in females with OSA. When the data was stratified according to age and gender, some associations in the specific subgroups were significant. Respectively, males aged 20-35 years old and aged 35-50 years old with a history of OSA and surgery both had a positive association with infertility. (aOR: 3.19; 95% CI, 1.18-8.66, p = 0.0227; aOR: 2.57; 95% CI, 1.18-5.62 p = 0.0176). Male patients with OSA suffer from reduced fertility, but no significant difference was noted in females with OSA. The identification of OSA as a risk factor for male infertility will aid clinicians to optimize long-term medical care. Furthermore, more studies will be encouraged to clarify the effect of OSA on female fertility.

Assessment of Telomere Length and Mitochondrial DNA Copy Number in Granulosa Cells as Predictors of Aneuploidy Rate in Young Patients.

Background: To identify the correlation among female age, cellular aging markers, and aneuploidy rate in in vitro fertilization (IVF) and the preimplantation genetic test for aneuploidy (PGT-A) cycles. Methods: This is a prospective cohort study recruiting 110 infertile women between August 2017 and July 2018. They were divided into young-age (<38 years, n = 60) and advanced-age (≥38 years, n = 50) groups. Peripheral leukocytes were assessed, and the granulosa cells were pooled during oocyte pickup. Mitochondrial DNA (mtDNA) copy number and telomere length (TL) were measured using real-time polymerase chain reaction. PGT-A was performed on the NGS platform. Results: mtDNA copy number and TL were positively correlated in both leukocytes (rho = 0.477, p < 0.001) and granulosa cells (rho = 0.361, p < 0.001), but the two parameters in leukocytes were not correlated with those in granulosa cells. In the young-age group, TL in the granulosa cells was the only factor correlated with the aneuploidy rate (rho = −0.283, p = 0.044), whereas in the advanced-age group, age was the main factor (rho = 0.358, p = 0.018). Conclusions: TL in the granulosa cells was negatively correlated with the aneuploidy rate in the young-age group, supporting the application of PGT-A in younger women.

Disposition of embryos from women who only produced morphologically poor embryos on day three.

BACKGROUND: The presence of only morphologically poor embryos (MPEs) on day3 is common in autologous in vitro fertilization (IVF), particularly among p Tel: 886-7-7317123 Ext. 8916. Fax: 886-7-7322915.atients who have advanced maternal age or are poor responders. However, there are limited data regarding the disposition of embryos from patients who only produced MPEs on day3. The present study was designed to investigate the possible benefits of extended culturing MPEs. Try to detect whether the extended culture (day4 or day5 culture) can improve the live birth rate per cycle? METHODS: This retrospective, observational, single-center, cohort study examined 224 IVF/intracytoplasmic sperm injection (ICSI) cycles between January 2010 and June 2015, in which women only produced MPEs on day3. A total of 544 MPEs were analyzed. The defines a day3 embryo as an MPE if it fails to develop to eight cells, blastomeres of equal size, and less than 20% cytoplasmic fragments. Of the 224 cycles, 89 (39.7%) underwent fresh embryo transfer on day3, and 135 (60.3%) underwent extended culture. Of the 135 extended cultures, 54 cycles (40.0%) experienced day4, or day5 embryo transfer, 16 cycles (11.9%) had all embryos frozen, and 65 cycles (48.1%) had total embryo arrest. RESULTS: Analysis of patient baseline demographic data, cycle characteristics, and cycle outcomes for day3 transfer group and extended culture group indicated that a higher body mass index in the day3 transfer group was the only significant difference (p = 0.006). Both fresh transfer groups had low live birth rates (LBRs) (4.5% vs. 7.4% p = 0.46). After extended culture, 65 cycles (48.1%) were cancelled because the embryos exhibited developmental arrest and 70 cycles (51.9%) grew to day4 or day5. Thirteen frozen embryo transfer (FET) cycles and 22 frozen blastocysts derived from MPEs were thawed. There were more high-quality embryos (p < 0.001), higher implantation rates (IRs) (p = 0.038), and higher LBRs (p = 0.042) for embryos that underwent FET cycles. MPES in extended culture transfer have favorable survival than MPES in day3 transfer. CONCLUSION: The extended culture of MPEs in fresh transfer cycles did not increase the LBR. However, younger females with the extended culture of MPEs followed by FET resulted in significantly higher LBRs and may be a feasible strategy to improve outcomes for patients with poor embryo quality. However, day3 embryo transfer may be a better choice if a fresh transfer is unrestricted and avoid the cycle cancellation. Extended culture may decrease to the transfer of developmental potential arrest embryos to patients.

Estimating the causal effect of embryo transfer day on clinical in vitro fertilization outcomes using propensity score matching.

BACKGROUND: For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e., confounding by indication. METHODS: We conducted a retrospective cohort study of 9,090 IVF cycles collected by Lee Women's Hospital in Taichung, Taiwan from 1998 to 2014. We utilized the method of propensity score matching to mimic a randomized controlled trial (RCT) where each patient with Day 5 transfer was matched by another patient with Day 3 transfer with respect to other clinical characteristics. Implantation rate, clinical pregnancy rate, and odds of live birth were compared for women underwent Day 5 transfer and Day 3 transfer to estimate the causal effects. We further investigated the causal effects in subgroups by stratifying age and anti-Mullerian hormone (AMH). RESULTS: Our analyses uncovered an evidence of a significant difference in implantation rate (p=0.04) favoring Day 5 transfer, and showed that Day 3 and Day 5 transfers made no difference in both odds of live birth (p=0.27) and clinical pregnancy rate (p=0.11). With the increase of gestational age, the trend toward non-significance of embryo transfer day in our result appeared to be consistent for subgroups stratified by age and AMH, while all analyses stratified by age and AMH were not statistically significant. CONCLUSIONS: We conclude that for women without strong indications for Day 3 or Day 5 transfer, there is a small significant difference in implantation rate in favor of Day 5 transfer. However, the two protocols have indistinguishable outcomes on odds of live birth and clinical pregnancy rate.

Blastocyst Morphology Based on Uniform Time-Point Assessments is Correlated With Mosaic Levels in Embryos.

Avoiding aneuploid embryo transfers has been shown to improve pregnancy outcomes in patients with implantation failure and pregnancy loss. This retrospective cohort study aims to analyze the correlation of time-lapse (TL)-based variables and numeric blastocyst morphological scores (TLBMSs) with different mosaic levels. In total, 918 biopsied blastocysts with time-lapse assessments at a uniform time-point were subjected to next-generation sequencing-based preimplantation genetic testing for aneuploidy. In consideration of patient- and cycle-related confounding factors, all redefined blastocyst morphology components of low-grade blastocysts, that is, expansion levels (odds ratio [OR] = 0.388, 95% confidence interval [CI] = 0.217-0.695; OR = 0.328, 95% CI = 0.181-0.596; OR = 0.343, 95% CI = 0.179-0.657), inner cell mass grades (OR = 0.563, 95% CI = 0.333-0.962; OR = 0.35, 95% CI = 0.211-0.58; OR = 0.497, 95% CI = 0.274-0.9), and trophectoderm grades (OR = 0.29, 95% CI = 0.178-0.473; OR = 0.242, 95% CI = 0.143-0.411; OR = 0.3, 95% CI = 0.162-0.554), were less correlated with mosaic levels ≤20%, <50%, and ≤80% as compared with those of top-grade blastocysts (p < 0.05). After converting blastocyst morphology grades into scores, high TLBMSs were associated with greater probabilities of mosaic levels ≤20% (OR = 1.326, 95% CI = 1.187-1.481), <50% (OR = 1.425, 95% CI = 1.262-1.608), and ≤80% (OR = 1.351, 95% CI = 1.186-1.539) (p < 0.001). The prediction abilities of TLBMSs were similar for mosaic levels ≤20% (AUC = 0.604, 95% CI = 0.565-0.642), <50% (AUC = 0.634, 95% CI = 0.598-0.671), and ≤80% (AUC = 0.617, 95% CI = 0.576-0.658). In conclusion, detailed evaluation with TL monitoring at the specific time window reveals that redefined blastocyst morphology components and converted numeric TLBMSs are significantly correlated with all of the threshold levels of mosaicism. However, the performance of TLBMSs to differentiate blastocysts with aberrant ploidy risk remains perfectible.

Early Progesterone Change Associated With Pregnancy Outcome After Fresh Embryo Transfer in Assisted Reproduction Technology Cycles With Progesterone Level of >1.5 ng/ml on Human Chorionic Gonadotropin Trigger Day.

Several studies have reported a poor implantation rate for assisted reproduction technology (ART) cycles with elevated progesterone (P4) at the end of the follicular phase. Whether all women with increased P4 on the human chorionic gonadotropin(hCG) trigger day should undergo fresh or frozen embryo transfer (ET) remains to be explored. This study attempted to determine that the P4 level on 2 days before hCG administration and P4 ratio can serve as indicators for fresh ET in normal responders with an elevated P4 level of >1.5 ng/ml on the hCG administration day. This was a retrospective cohort study involving 337 ART cycles with fresh ET for normal responders. Serum P4 levels were measured 2 days prior to hCG day (P4 level I) and on the hCG administration day (P4 level II). The P4 ratio was calculated as follows: P4 ratio = P4 level II / P4 level I. The primary outcome is live birth rate of fresh ET cycles. The ROC curves established that the optimal P4 level I and P4 ratio for pregnancy in ART cycles with high P4 level II were 0.975 ng/ml and 1.62, respectively. Patients with a P4 level I of ≤0.975 ng/ml and P4 ratio of >1.62 were associated with a significantly higher implantation (30.8%, 61/198 vs. 10.3%, 19/184, p < 0.001) and live birth rates (51.6%, 33/64 vs. 15.0%, 9/60, p < 0.001) compared with those with a P4 level I of >0.975 ng/ml and P4 ratio of ≤1.62. A combination of P4 level I and P4 ratio cutoff values of 0.975 ng/ml and 1.62, respectively, had a positive predictive value (PPV) of 82.5% for pregnancy. In conclusion, fresh ET can be an option for women with an early P4 level I under 0.975 ng/ml and a P4 ratio higher than 1.62, especially for those normal responders with an elevated P4 level II >1.5 ng/ml on the hCG administration day. This approach may shorten the time to pregnancy and reduce the cost of ART cycles.

Healthy live births from transfer of low-mosaicism embryos after preimplantation genetic testing for aneuploidy.

PURPOSE: This study evaluated the potential viability of embryos with low mosaicism level (< 50%) by comparing the clinical outcomes of single mosaic versus euploid blastocyst transfer. In addition, the live birth outcomes for various types of mosaicism with respect to abnormalities in chromosome structure and content were analyzed. METHODS: This study included patients who underwent in vitro fertilization with preimplantation genetic testing for aneuploidy (PGT-A). The PGT-A cycles performed through next-generation sequencing with single euploid or mosaic embryo transfers were included. We collected 299 frozen single embryo transfer cycles-216 single euploid and 83 mosaic-between July 2016 and July 2018. This study analyzed clinical outcomes, including fetal karyotyping by using amniocentesis, gestational age at delivery, and live birth weight after single mosaic embryo transfer. RESULTS: The average birth weight of infants in the euploid and mosaic blastocyst transfer groups was 3146.2 and 2997.7 g, respectively. The karyotyping results of prenatal diagnosis in all pregnant women were normal. Our study indicated that mosaic embryos can develop into euploid healthy infants with various levels or types of mosaicism. No significant difference was observed between infants from euploid and mosaic blastocyst transfers. CONCLUSION: If patients have no euploid embryos, mosaic embryos can be transferred as they have potential for implantation and development into euploid healthy infants. This study is invaluable for counseling clinical results after single mosaic embryo transfers.

Clinical Outcomes of Single Mosaic Embryo Transfer: High-Level or Low-Level Mosaic Embryo, Does it Matter?

Recently, reports showed that embryos identified as mosaic after preimplantation genetic testing for aneuploid (PGT-A) could result in live birth with lower pregnancy and higher pregnancy loss rates compared with euploid embryos. However, the effects of mosaicism level on reproductive outcomes remain controversial. This study aimed to examine the level of mosaicism on pregnancy outcomes. Single mosaic embryo transfer was offered to 108 women who only had mosaic embryos. Mosaic embryos were labeled by utilizing next generation sequencing (NGS) based PGT-A for day 5/6 trophectoderm (TE)biopsies. TE biopsies containing < 50% abnormal cells were classified as low-level mosaicism and ≥ 50% as high-level mosaicism. To further confirm the concordance of chromosome constitution between TE and inner cell mass (ICM), 41 remaining embryos designated as mosaic blastocysts donated for research were also analyzed. Comparable live birth rate (LBR) but higher miscarriage rate (MR) was found in the high-level group. (LBR: low vs. high: 44.5% vs. 36%; p = 0.45, MR: low vs. high: 5.1% vs. 30.7%; p = 0.012). Analyses of TE and ICM from the remaining mosaic blastocysts show a poor concordance. This preliminary study demonstrated that high-level mosaic embryos could result in comparable LBR but higher MR.

Failed sperm retrieval from severely oligospermic or non-obstructive azoospermic patients on oocyte retrieval day: Emergent oocyte cryopreservation is a feasible strategy.

PURPOSE: Unexpected sperm retrieval failure on the day of oocyte retrieval is not common but frequently happened in patients with severe oligospermia or non-obstructive azoospermia(NOA). Oocyte cryopreservation is a common strategy after failed collection of sperm when concurrent ovarian stimulation is underwent. However, the use of oocyte vitrification in such male-infertility cases remains unclear. OBJECTIVE: To investigate the outcomes of emergent oocyte cryopreservation after failed sperm retrieval from severe oligospermic or non-obstructive azoospermic (NOA) patients on oocyte retrieval day. METHODS: Design: Retrospective cohort study Setting: Academic fertility center at Lee Women's Hospital, Taiwan, between March 2015 and August 2017. Patients: For 203 couples with NOA(n = 200) or severe oligospermia(n = 3), testicular spermatozoa (n = 67 cycles) or frozen donor sperm (n = 209 cycles) were injected into fresh or frozen-thawed oocytes via 276 intracytoplasmic sperm injection (ICSI) cycles. Main Outcome Measures: Clinical pregnancy and live-birth rates (LBRs). RESULTS: In the 67 cycles involving the use of fresh testicular spermatozoa, no significant differences were observed between fresh and warmed oocytes with respect to the fertilization rates (69.2% vs. 74.1%; p = 0.27), number of Day-3 embryos (8.6±4.4 vs. 6.4±3.4; p = 0.08), number of good-quality Day-3 embryos (4.5±3.9vs. 4.7±3.0; p = 0.45), implantation rates (29.1% vs. 17.8%; p = 0.21), clinical pregnancy rates (36.4% vs. 26.8.0%; p = 0.81), live birth rates (36.4% vs. 14.3%; p = 0.46), or perinatal outcomes. In the 209 cycles involving the use of frozen donor sperm, no significant differences were seen between the two groups, except that the mean birth weights were significantly lower with fresh oocyte pregnancies than with warmed oocytes (2952±196 gm vs 2643±700 gm; p = 0.006). CONCLUSIONS: Emergent oocyte cryopreservation is a feasible strategy to manage unexpected sperm retrieval failure from severe oligospermic or NOA patients on the oocyte retrieval day. There is no detrimental effect on the live birth rate when testicular spermatozoa or frozen donor sperm are injected into the thawed oocytes compared with fresh oocytes.

Embryo morphokinetics is potentially associated with clinical outcomes of single-embryo transfers in preimplantation genetic testing for aneuploidy cycles.

RESEARCH QUESTION: Are the morphokinetics of euploid blastocysts evaluated by a generally applicable algorithm associated with the clinical outcomes of single-embryo transfer (SET)? DESIGN: Time-lapse microscopy was used to compare morphokinetic variables between expanded blastocysts derived from preimplantation genetic testing for aneuploidy cycles using high-resolution next-generation sequencing (hr-NGS). The clinical efficacy of the morphokinetic algorithm KIDScore D5 was evaluated after euploid SET. RESULTS: Compared with euploid blastocysts, low-level mosaic blastocysts presented comparable morphokinetic and morphological features. However, high-level mosaic blastocysts exhibited significant delays in t5 (median 51.9 h post insemination (hpi), P = 0.034) (where t is the time for the embryo to reach the specific stage in hours after ICSI or conventional IVF) and t8 (median 58.6 hpi, P = 0.032) accompanied by a prolonged time period for the third cell cycle (median 14.7 h, P = 0.012). A significantly higher incidence (P = 0.011) of multinucleation indicated a susceptibility of high-level mosaic blastocysts to mitotic errors. Only a delay in the time for the embryo to reach the full blastocyst stage (median 106.0 hpi, P = 0.039) was revealed in aneuploid blastocysts, reflecting the reduced formation of good-quality blastocysts (42.6% versus 65.7%, P < 0.001). Euploid blastocysts with specific morphokinetic characteristics were graded using the KIDScore D5 algorithm. Grade C embryos achieved significantly lower rates of clinical pregnancy, implantation and ongoing pregnancy (25%, 25% and 10%, respectively) compared with the grade A (76.2%, 79.4% and 68.3%, respectively) or grade B (62.5%, 66.7% and 62.5%, respectively) embryos (P = 0.0171 to <0.0001). CONCLUSIONS: Although morphokinetic features appear dissimilar in embryos with different diploid-aneuploid mosaic levels, predicting chromosomal abnormalities using morphokinetics alone is still insufficient. When combined with hr-NGS, use of the generally applicable KIDScore D5 algorithm has the potential to discriminate euploid blastocysts with different developmental competence.

Peripheral CD56+CD16+ NK Cell Populations in the Early Follicular Phase Are Associated With Successful Clinical Outcomes of Intravenous Immunoglobulin Treatment in Women With Repeated Implantation Failure.

The percentage of peripheral CD56+CD16+ NK cells in the early follicular phase on days 2-3 of the menstrual cycle in repeated implantation failure (RIF) patients was used to evaluate the impact of intravenous immunoglobulin (IVIG) on ART cycles. A total 283 patients with RIF consisting of at least 3 ART failures and at least 2 high quality embryo transfers were recruited. A logistic regression analysis for the peripheral immunological profile was completed to predict implantation success and compare the implantation and pregnancy rates between groups with ≤10.6 and >10.6% of CD56+CD16+ NK cells in the early follicular phase. The logistic regression and receiving operating curve analyses showed that patients with ≤ 10.6% of peripheral CD56+CD16+ NK cells in the early follicular phase showed a lower pregnancy rate within the RIF group without IVIG. Patients with peripheral CD56+CD16+ NK cells ≤ 10.6% and without IVIG treatment showed significantly lower implantation and pregnancy rates (12.3 and 30.3%, respectively) when compared with the CD56+CD16+ NK cells >10.6% group (24.9 and 48.0%, respectively, p < 0.05). Furthermore, the patients with CD56+CD16+ NK cells ≤ 10.6% given IVIG starting before ET had significantly higher implantation, pregnancy, and live birth rates (27.5, 57.4, and 45.6%, respectively) when compared with the non-IVIG group (12.3, 30.3, and 22.7%, respectively, p < 0.05). Our results showed that a low percentage of peripheral CD56+CD16+ NK cells (≤10.6%) in the early follicular phase is a potential indicator of reduced pregnancy and implantation success rates in RIF patients, and IVIG treatment will likely benefit this patient subgroup.

Growth hormone supplementation may improve the pregnancy rate and endometrial receptivity among women aged more than 40 years undergoing in vitro fertilization.

BACKGROUND: Growth hormone (GH) supplements have been shown to improve pregnancy and live-birth rates, suggesting that GH has a beneficial effect on oocyte quality. However, the effects of GH on implantation and receptivity remain unknown. This study evaluated the efficacy of GH in women aged more than 40 years participating in assisted reproductive technology (ART) programs. METHODS: Cycles of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in women aged more than 40 years (range, 40-43 years) between January 2009 and March 2014 at a university-based reproductive center were reviewed. Women were divided into two groups, those with and without GH co-stimulation. ART outcomes were evaluated. RESULTS: Supplement of GH significantly lowered cycle cancellation rate by increasing the per cycle rates of harvesting at least one oocyte and transferring at least one embryo (80.2% vs. 69.4%). GH increased the per cycle clinical pregnancy (15.9% vs. 6.8%) and favorable ultrasonic endometrial pattern (60.9% vs. 39.3%) rates. GH also increased the per transfer clinical pregnancy (19.9% vs. 9.9%) and implantation (11.2% vs. 5.2%) rates and the rate of a favorable ultrasonic endometrial pattern (65.1% vs. 45.0%). CONCLUSION: GH supplementation reduces the cycle cancellation rate in women aged more than 40 years, and increases the favorable ultrasonic endometrial pattern, pregnancy, and implantation rates by its beneficial actions on embryo quality and endometrial receptivity.

Age is a major prognosticator in extremely low oocyte retrieval cycles.

OBJECTIVE: Clinical prognosis appears to be varied in females with poor ovarian response (POR), and poor responders defined by the Bologna criteria might not be sufficiently homogeneous. The aim of this study was to determine the major predictor of reproductive outcomes in extremely low oocyte retrieval cycles. MATERIALS AND METHODS: A cohort of fresh in vitro fertilization/intracytoplasmic sperm injection cycles (n = 858) was analyzed from January 2001 to September 2014. Females from whom zero, one, two, or three oocytes were retrieved following ovarian stimulation were examined. Univariate analyses were performed to determine the association of pregnancy rate with potential confounding variables. Multiple logistic regression analysis was subsequently performed to identify factors that affected the occurrence of pregnancy. RESULTS: The clinical pregnancy rate was higher in women aged < 40 years, long protocol, and high embryo score in univariate analysis. After adjusting for confounding factors in multivariate analysis, the maternal age [odds ratio (OR) = 0.91], primary or secondary infertility (OR = 1.99), number of matured oocytes retrieved (OR = 0.64), and score of embryos transferred (OR = 1.39) were significantly associated with the clinical pregnancy rate per cycle and per transfer. In the age subgroup analysis, POR females aged < 35 years significantly demonstrated the highest number of matured oocytes, embryo scores, and clinical pregnancy rates compared with POR females aged 35-40 years and ≥ 40 years. CONCLUSION: This study highlights the predictive value of maternal age and embryo quality on the probability of pregnancy in females with extremely low oocyte retrieval cycles. Young females with few eggs collected can still achieve acceptable pregnancy probability as long as they have good-quality embryos. Future randomized control trials for POR using the Bologna criteria should first stratify patients into different age groups.

Reassessing the feasibility of the zygote score for predicting embryo viability in IVF/ICSI using the GnRH antagonist protocol compared to the long protocol.

BACKGROUND: Many factors from the oocyte/sperm or the process of fertilization may affect the zygote formation. The zygote score (Z-score) describes the quality of a human zygote based on its pronuclear morphology, nucleolar precursor bodies, and alignment of polar bodies, and it can be used in the selection process at the zygote stage for embryo transfer or cryopreservation. OBJECTIVE: The aim of this retrospective cohort study was to investigate the relationship between different controlled ovarian stimulation (COS) protocols and the zygote score (Z-score) and to assess the feasibility of the Z-score for predicting embryo survival in the GnRH-antagonist (GnRH-ant) protocol. METHODS: It is a retrospective, single-center cohort study. A total of 3,826 zygotes with normal fertilization were analyzed from 744 in vitro fertilization /intra-cytoplasmic sperm injection (IVF/ICSI) cycles (long protocol n = 392; GnRH-ant n = 352) between Jan 2010 and April 2014 in the IVF unit of Chang-Gung Memorial Hospital Kaohsiung Medical Center. RESULTS: The Z-score distribution differed significantly between these two protocols. The overall Z-score was poorer for zygotes from GnRH-ant cycles (p<0.05). Univariate and multivariate analyses indicated the type of COS protocol is one of the main determinants of Z-score grading. Our study found good-quality day 3 embryo/blastocyst formation and the cumulative embryo survival rate were correlated with the Z-score but not the COS protocol. With the GnRH-ant protocol, the number of Z1 in the transferred cohort embryos was significantly correlated with the clinical pregnancy rate (r = 0.976; p = 0.024) and live birth rate (r = 0.971; p = 0.029). This correlation was not seen with the long protocol. CONCLUSIONS: The Z-score distribution for the GnRH antagonist cycles was poorer than that of the long protocol, but the Z-score system is a valuable parameter for predicting embryo viability in the GnRH-ant protocol, providing a strong correlation with the clinical pregnancy rate and live birth rate.