The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Antioxidants and Fertility in Women with Ovarian Ageing: a Systematic Review and Meta-Analysis.

Ovarian ageing is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios, but their effects on fertility in women with ovarian ageing are still unclear. To address this, a meta-analysis was performed to evaluate the effectiveness and safety of antioxidants on fertility in women suffering from ovarian ageing. A total of 20 randomized clinical trials (RCTs) with 2617 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryos rates but also reduced the dose of gonadotropin, contributing to higher clinical pregnancy rates. According to the subgroup analysis, with regard to different dose settings, better effects were more pronounced with lower doses; in terms of antioxidant types, Coenzyme Q10 (CoQ10) tended to be more effective than melatonin, myo-inositol and vitamins, since when compared with placebo or no treatment, CoQ10 showed more advantages, while small improvements were observed in other drugs. In addition, based on subgroup analysis of CoQ10, the optimal treatment regimen of CoQ10 for improving pregnancy rate was 30 mg/d for three months before the controlled ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from CoQ10 treatment, especially those younger than 35 years old. Our study suggests that antioxidant is an effective and safe complementary therapy for women with ovarian ageing. Appropriate antioxidant treatment should be offered from a low dose according to patients' age and ovarian reserve. This study was registered at PROSPERO (CRD42022359529).

The impact of clinical and laboratory parameters on clinical pregnancy and live birth rates in fresh cycles: a retrospective study of 9608 high-quality cleavage-stage embryos.

BACKGROUND: Evidence from the Istanbul consensus workshop suggests correlations between morphological parameters and embryo developments. 8-cell embryos are the best blastomere stage on day 3. No good quality evidence exists to support high-quality embryonic selection following blastulation and clinical outcomes. This study aimed to investigate the factors that affect blastocyst formation, blastocyst quality, and clinical outcomes of high-quality cleavage-stage embryos in fresh cycles. METHODS: This study was a retrospective analysis of 9608 high-quality cleavage-stage embryos from 2987 couples between January 2017 to June 2021, namely 1520 embryos categorized as "812" (8-cell, grade 2, mild fragmentation), 2961 as "821" (8-cell, grade 2, mild asymmetry), 896 as "711" (7-cell, grade 1), and 517 as "911" (9-cell, grade 1) compared with 3714 embryos categorized as "811" (8-cell, grade 1). The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Blastulation rate (BR), available late blastocyst rate (ABR) and high-quality late blastocyst rate (HBR) were secondary outcome measures. RESULTS: BR, ABR, and HBR had significant differences among the five groups (P < 0.001), while CPR and LBR were also significantly different in cleavage-stage fresh transfer (P < 0.01). The multivariable multilevel logistic regression analysis revealed a significant association between cell number, cell size, blastocyst development and clinical outcomes. For 7 to 9-cell highest-quality embryo, mild fragmentation and more blastomeres were more conducive to blastocyst formation and clinical outcomes. While cleavage-stage embryos developed into blastocysts, the negative impact of their initial morphology on clinical outcomes would be erased. CONCLUSIONS: Our study firstly evaluated blastocyst development and clinical outcomes of high-quality cleavage-stage embryos in fresh cycles, with rankings of 811, 812, 911, 821, and 711. We found the initial morphological characteristics of the high-quality cleavage-stage embryos did not adversely impact clinical outcomes, even as they progressed to the blastocyst stage.

Comparison of the Effects of Single Sperm Cryopreservation and Conventional Cryopreservation on Embryo Culture and Pregnancy in Patients Undergoing Micro-TESE / 中山大学学报(医学科学版)

ObjectiveTo compare the effects of single sperm cryopreservation and conventional cryopreservation on embryo culture and pregnancy in patients undergoing microdissection testicular sperm extraction （micro-TESE）. MethodsA retrospective analysis was done on the patients who underwent micro-TESE at the Reproductive Medicine Center in the Sixth Affiliated Hospital of Sun Yat-Sen University between January 2018 and December 2021. The single sperm cryopreservation group included 39 patients undergoing single sperm cryopreservation and 307 MII oocytes. The conventional cryopreservation group included 39 patients undergoing conventional cryopreservation and 410 MII oocytes. Propensity score matching （PSM） was performed to balance the selection bias. The fertility rate， embryo culture and pregnancy of these two groups were compared. ResultsThere was no statistical difference in age， body mass index （BMI）， years of infertility， basal FSH， basal LH， basal E2， AMH， AFC， number of oocytes retrieved and number of transferred embryos between the two groups （P>0.05）. No significant difference was found in fertilization rate （65.8% vs. 60.49%）， available embryo rate （67.82% vs. 58.87%） and high-quality embryo rate （70.80% vs. 75.34%）. The single sperm cryopreservation group had significantly lower clinical pregnancy rate than conventional cryopreservation group （45.45% vs. 70.0%， P=0.049）. ConclusionIf the patients undergoing micro-TESE have very few sperms， single sperm cryopreservation could be an effective choice to increase the utilization of each sperm and ensure the subsequent sperm retrieval after thawing， but the clinical pregnancy rate is decreased. Due to the limited number of cases， we need a large additional number of cases to observe and analyze.

Intracytoplasmic Sperm Injection May Not Improve Clinical Outcomes Despite Its Positive Effect on Embryo Results: A Retrospective Analysis of 1130 Half-ICSI Treatments.

Objective: To explore the clinical application value of half-ICSI treatment for infertility in assisted reproductive technology. Method: A retrospective analysis of 1130 half-ICSI treatments was conducted at the Affiliated Reproductive Hospital of Shandong University from January 2011 to December 2015. Patients with low fertilization rates in previous cycles, primary infertility for >5 years with unexplained reason, or secondary infertility for >5 years without fallopian tube factor were involved in this study. The 2PN rate, high-quality embryo rate, oocyte utilization rate, and clinical outcomes were compared between IVF insemination group (IVF group) and ICSI insemination group (ICSI group). The clinical outcome of half-ICSI insemination treatment, grouped according primary and secondary infertility, was also analyzed. Results: Compared with IVF, ICSI resulted in a significantly higher 2PN rate (74.8% vs. 62.9%), high-quality embryo rate (54.6% vs. 51.7%), and oocyte utilization rate (35.9% vs. 32.8%; P<0.05). Among the 884 fresh-embryo transfer cycles, there were no notable differences in clinical pregnancy rate, live birth rate, or neonatal abnormality rate between the IVF and ICSI groups. Among the 792 primary infertility cycles, ICSI resulted in a significantly higher 2PN rate, high-quality embryo rate, and oocyte utilization rate compared with IVF (75.3% vs. 62.4%, 54.3% vs. 50.8%, 36.4% vs. 32.6%, P<0.05). For the 338 secondary infertility cycles, ICSI resulted in a significantly higher 2PN rate (73.6% vs. 63.9%, P<0.05) compared with IVF, but there were no notable differences in other laboratory results. Moreover, the biochemical pregnancy rate of the ICSI group was significantly lower than for IVF in secondary infertility cycles (49.3% vs. 65.6%; P<0.05). A total of 89 cycles (7.9%) with complete IVF fertilization failure showed a low second polar body (2PB) rate (33.6%) after a 5-h short-time fertilization period, including 34 cycles (3.0%) with no 2PB oocytes observed in the IVF group. Conclusion: ICSI insemination improved laboratory results compared with IVF insemination, however, fresh-embryo transfer of ICSI originated embryos did not improve clinical pregnancy and live birth rates. Rescue ICSI has been successfully applied in clinical IVF insemination to avoid fertilization failure. Therefore, as an extra intervention, it is suggested that ICSI be used judiciously.

Abnormal BMI in Male and/or Female Partners Are Deleterious for Embryonic Development and Pregnancy Outcome During ART Process: A Retrospective Study.

Objective: To investigate the effect of BMI in male and/or female partners on embryo development and clinical pregnancy outcome during ART. Methods: Data of 11,130 cycles between January 2018 and December 2020 were retrospectively analyzed. They were divided into Group A, B, C, and D based on couples' BMI values, also were divided into Group I, II, III and IV in IVF cycles and Group i, ii, iii, and iv in ICSI cycles. After grouping, inter-group indicators comparisons and logistic regression analysis were performed. Results: In IVF cycles, CPR in Group I and Group III were higher than Group IV. In Group III, it was higher than Group II. The AR in Group IV was higher, but the LBR was lower than Group I, Group II, and Group III. Logistic regression analysis results suggested that AR in Group IV was higher than that in Group I in IVF cycles, whereas LBR was lower.In ICSI cycles, high-quality embryo rate in Group i and Group ii were both higher than that in Group iii and Group iv. The CPR in Group i was higher than Group ii and Group iv, and in Group iii was higher than Group ii and Group iv. The AR in Group i was lower than Group iii and Group iv, and AR in Group ii was lower than Group iv. LBR, in Group I it was higher than Group ii, Group iii, and Group iv. Logistic regression analysis results suggested CPR in Group ii was significantly lower than that in Group i. AR in Group iii was considerably higher than that in Group i. LBR in Group ii and Group iv were significantly lower than that in Group i. Conclusion: Female higher BMI was not conducive to the formation of high-quality embryos in ICSI cycle. Female and/or male BMI affected AR and LBR more than CPR not only in IVF cycles, but also in ICSI cycles.

The KIDScore™ D3 scoring system contributes to the prediction of embryonic development potential: A promising tool for screening high-quality embryos.

Using the KIDScoreTM D3 (KID3) scoring system, day 3 embryos observed by time-lapse imaging (TLI) were scored to explore the predictive value of the KID scoring system on the developmental potential of embryos. The kinetic parameters of 477 normal fertilized embryos from 77 patients who underwent TLI in our hospital from January 2019 to June 2020 were evaluated by KID3, and the embryos were divided into five groups according to the scores for retrospective analysis of blastocyst formation. Additionally, the high-quality blastocyst formation rate, pregnancy rate and early abortion rate were analyzed via KID3 and traditional morphological assessments, and comparisons of differences among different ages were also performed. In the KID3 estimate, the blastocyst or high-quality blastocyst formation rate in the score 5 group was markedly higher than that in the score 1-4 groups. Blastocyst or high-quality blastocyst formation rates in the A group (the results of two evaluation tools indicated they were excellent embryos) and the B group (KID3: excellent embryos, traditional evaluation: not excellent embryos) were evidently increased in comparison with the C or D group (KID3: not excellent embryos, traditional evaluation: excellent embryo or not, respectively). Furthermore, the percentages of score 5 embryos, blastocyst and high-quality blastocyst formation rates for patients ≥ 35 years old were markedly decreased compared with those for patients < 34 years old, while the trends of nondiploid cleavage, multinucleation and asymmetric division were the opposite. Collectively, the KID3 scoring system may be a promising predictive tool for screening embryos with better developmental potential.

Effects of testicular sperm aspiration upon first cycle ICSI-ET for type 2 diabetic male patients.

Male diabetes mellitus (DM) can affect erectile function and sperm quality. In severe cases, DM can lead to retrograde or no ejaculation, so testicular sperm aspiration (TESA) is combined with intracytoplasmic sperm injection (ICSI) to treat subfertility and infertility for DM couples. However, the effect of TESA upon ICSI (TESA-ICSI) for DM patients remains unclear. This research investigated the effect of TESA-ICSI on first cycle ICSI-embryo transfer (ICSI-ET) for type 2 diabetic mellitus (T2DM) patients and the potential mechanisms. The subjects consisted of 1219 male patients with azoospermia or retrograde ejaculation who were treated with TESA-ICSI from 2015.01 to 2019.11. They were classified into two groups, the T2DM group (n = 54) and non-diabetic control group (n = 1165). Sperm selection for injection was performed using motile sperm organelle morphology examination criteria. The number of available embryos and the high-quality embryo rates following a single ET as well as cleavage, fertilization, implantation, clinical pregnancy and the abortion rates were noted. Compared with the non-diabetic group, the available embryo rate (75.20 ± 26.40% vs.78.36 ± 23.25%) and high-quality embryo rate (46.49 ± 30.37% vs. 47.55 ± 28.57%) in the T2DM group were lower and the abortion rate (20.83% vs. 8.88%) was higher, but these differences were not statistically significant. There were no significant differences in clinical pregnancy, implantation, normal fertilization, and cleavage rates between the two groups. The results show that TESA for male T2DM patients does not influence the effect of ICSI. For T2DM patients with severe oligozoospermia, asthenospermia, teratozoospermia, or retrograde ejaculation that do not meet ICSI criteria, TESA-ICSI may perhaps be considered for reproductive assistance. ABBREVIATIONS: DM: diabetes mellitus; TESA: testicular sperm aspiration; ICSI: intracytoplasmic sperm injection; ICSI-ET; ICSI-embryo transfer; LH: luteinizing hormone; mL: milliliter; TES: testosterone; FSH: follicle-stimulating hormone; P: progesterone; HCG: human chorionic gonadotropin.

[Medication of Compound Amino Acid Capsules for obstructive azoospermia patients undergoing percutaneous epididymal sperm aspiration and intracytoplasmic sperm injection].

OBJECTIVE: To investigate the effects of Compound Amino Acid Capsules (CAAC) for obstructive azoospermia (OA) patients undergoing percutaneous epididymal sperm aspiration (PESA) and ICSI. METHODS: We retrospectively studied 134 cycles of PESA-ICSI in OA males, who were divided into a CAAC group (n = 64) and a control group (n = 70), the former, aged (32.1 ± 5.7) years, treated with CAAC for 3 months before PESA-ICSI while the latter, aged (32.3 ± 4.5) years, left untreated. We compared the rates fertilization, cleavage, high-quality embryos and blastocyst formation between the two groups of patients. RESULTS: Compared with the control, the CAAC group achieved significantly higher rates of high-quality embryos (ï¼»67.4 ± 13.8ï¼½% vs ï¼»74.3 ± 12.6ï¼½%, P < 0.05) and blastocyst formation (ï¼»60.3±14.2ï¼½% vs ï¼»66.8±14.6ï¼½%, P < 0.05), but no statistically significant differences were observed between the two groups in the ages of the males and females, number of oocytes retrieved, or the rates of fertilization and cleavage. CONCLUSIONS: Medication of Compound Amino Acid Capsules can effectively improve the rates of high-quality embryos and blastocyst formation in obstructive azoospermia patients undergoing PESA-ICSI.

Outcomes of intracytoplasmic sperm injection using the zona pellucida-bound sperm or manually selected sperm.

PURPOSE: Zona pellucida (ZP)-bound sperm used for intracytoplasmic sperm injection (ICSI) enhances embryo quality, implantation, and clinical pregnancy rates. This study aimed to assess the pregnancy outcomes and clinical significance of ICSI with ZP-bound sperm. METHOD: A total of 84 infertile couples who underwent cycles of ICSI following failed in vitro fertilization between June 2012 and February 2014 were enrolled and randomized (1:1): in the treatment group, ICSI was performed using ZP-bound sperm; in the control group, ICSI was performed in a standard manner. Rates of fertilization, cleavage, high-quality embryos, and clinical pregnancy were compared between the two groups. RESULTS: There were no significant differences in age, infertile period, gonadotrophin dose, number of metaphase II oocytes, and number of embryo transfers between the two groups (P > 0.05). The clinical pregnancy rate was higher in the treatment group than in the control group, but without statistical significance (60.5 vs. 47.6 %, P > 0.05). No significant differences in the rates of fertilization and cleavage were observed (83.0 vs. 81.6 %, and 96.3 vs. 96.5 %, both P > 0.05), but higher rates of high-quality embryos and useable embryos were observed with ZP-bound sperm compared with controls (66.1 vs. 50.8 % and 76.0 vs. 66.3 %, both P < 0.05). CONCLUSIONS: ICSI using ZP-bound sperm might increase the embryo quality and number of useable embryos, possibly improving the clinical pregnancy outcome of ICSI.

Effects ofCangfu Congxian Decoction on mRNA Expression of IGF-1R in Human Mural Granulosa Cells of PCOS Patients / 中国中医药信息杂志

Objective To explore the effects ofCangfu Congxian Decoction on the mRNA expression of IGF-1R in human mural granulosa cells;To explore the action mechanism for the treatment of polycystic ovary syndrome (PCOS) patients.Methods Totally 48 patients undergoing IVF-ET were randomly divided into treatment group and control group by random number table, 24 cases in each group. Patients in the control group accepted GnRHa/FSH/hCG stimulation, while the treatment group tookCangfu Congxian Decoction orally on the basic treatment of the control group. Serum E2, LH, and P concentration on HCG injection day, number of ovum, high quality embryo rate and clinical pregnancy rate were evaluated. The mRNA expression of IGF-1R on mural granulosa cells in the mature follicle was detected by real-time PCR.Results Compared with the control group, there was no significant difference in serum E2, LH, and P concentration on HCG injection day of treatment group (P>0.05), while the treatment group had higher high quality embryo rate than that of the control group (P0.05). The mRNA expression of IGF-1R on granulosa cells in treatment group was significantly higher than the control group (P<0.01).Conclusion The mechanism ofCangfu Congxian Decoction for treating PCOS is up-regulating the mRNA expression of IGF-1R in mural granulosa cells and increasing high quality embryo rate.