Novel and conventional embryo parameters as input data for artificial neural networks: an artificial intelligence model applied for prediction of the implantation potential.

OBJECTIVE: To describe novel embryo features capable of predicting implantation potential as input data for an artificial neural network (ANN) model. DESIGN: Retrospective cohort study. SETTING: University-affiliated private IVF center. PATIENT(S): This study included 637 patients from the oocyte donation program who underwent single-blastocyst transfer during two consecutive years. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The research was divided into two phases. Phase 1 consisted of the description and analysis of the following embryo features in implanted and nonimplanted embryos: distance and speed of pronuclear migration, blastocyst expanded diameter, inner cell mass area, and trophectoderm cell cycle length. Phase 2 consisted of the development of an ANN algorithm for implantation prediction. Results were obtained for four models fed with different input data. The predictive power was measured with the use of the area under the receiver operating characteristic curve (AUC). RESULT(S): Out of the five novel described parameters, blastocyst expanded diameter and trophectoderm cell cycle length had statistically different values in implanted and nonimplanted embryos. After the ANN models were trained and validated using fivefold cross-validation, they were capable of predicting implantation on testing data with AUCs of 0.64 for ANN1 (conventional morphokinetics), 0.73 for ANN2 (novel morphodynamics), 0.77 for ANN3 (conventional morphokinetics + novel morphodynamics), and 0.68 for ANN4 (discriminatory variables from statistical test). CONCLUSION(S): The novel proposed embryo features affect the implantation potential, and their combination with conventional morphokinetic parameters is effective as input data for a predictive model based on artificial intelligence.

Reduced oxygen tension improves embryo quality but not clinical pregnancy rates: a randomized clinical study into ovum donation cycles.

OBJECTIVE: To investigate the effect of low O2 tension during in vitro culture in terms of ongoing pregnancy rates in ovum donation cycles. DESIGN: Randomized trial. SETTING: Private university-affiliated IVF center, university-based hospital. PATIENT(S): A total of 1,125 cycles of ovum donation. INTERVENTION(S): Embryo culture in an atmosphere of 5.5% CO2, 6% O2, and 88.5% N2 versus a dual-gas system of 5.5% CO2 in air. MAIN OUTCOME MEASURE(S): Ongoing clinical pregnancy rates per intention-to-treat (ITT) patients. RESULT(S): The use of low O2 tension achieved a 41.3% ongoing pregnancy rate per ITT compared with a 40.8% rate obtained for 5% CO2 in air. The mean number of blastomeres and the percentage of top-quality embryos were significantly higher after lower O2 concentration during in vitro culture (7.1 ± 3.6 and 28.6% vs. 7.3 ± 8.4 and 32.1%, respectively). CONCLUSION(S): In the ovum donation cycles undergoing day-3 embryo transfers, the use of low O2 tension did not improve ongoing pregnancy rates per cycle and per transfer. However, it benefited embryo quality, demonstrating the potential negative impact of high O2 tension on the in vitro embryo development.

Time-dependent O2 consumption patterns determined optimal time ranges for selecting viable human embryos.

OBJECTIVE: To evaluate correlations between metabolic activity and implantation potential of transferred embryos in a study based on oxygen (O(2)) consumption (OC) measurements, because O(2) uptake is directly related to the capacity of an embryo to produce energy via adenosine triphosphate. DESIGN: Retrospective cohort study. SETTING: Infertility institute. PATIENT(S): Five hundred seventy-five injected oocytes in 56 first oocyte donation cycles with embryo transfer on day 3. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We analyzed embryo destination viability and implantation depending on the embryo OC rate obtained from 47,741 measurements (up to 85 measurements per embryo, 2-3 measurements per hour). OC patterns were analyzed in relation to the time elapsed from sperm microinjection, to the final destination of the embryos (transferred, frozen, or discarded), to ongoing pregnancy, and by successful implantation. RESULT(S): OC was found to decrease during embryonic development. OC patterns from 52 hours onward showed the strongest correlation with implantation success. Regarding embryo destination, the same patterns were observed. CONCLUSION(S): OC from individual embryos revealed significant differences, mainly close to the time of transfer, when OC pattern was associated with successful implantation. Therefore, measuring the OC pattern of human embryos culture up to 72 hours could be used to select the embryo with best developmental potential.

Report of results obtained in 2,934 women using donor sperm: donor insemination versus in vitro fertilization according to indication.

OBJECTIVE: To demonstrate that the use of donor sperm leads to varying outcome rates and that its use has evolved. DESIGN: Retrospective observational cohort study. SETTING: University-affiliated private IVF setting. PATIENT(S): Women (2,934) undergoing donor insemination (DI) or IVF with donor sperm (IVF-D). INTERVENTION(S): None. MAIN OUTCOME MEASUREMENT(S): We evaluated the distribution of the clinical indications for the use of donated sperm, studying the reproductive outcome. RESULT(S): A total of 1,663 DI (57%) and 1,271 IVF-D (43%) were performed. There were significant differences in the indications for the use of donated sperm (DI vs. IVF-D). Regarding pregnancy rates (PR), cases of nonobstructive azoospermia presented the highest rate (29.1%), whereas cases of intracytoplasmic sperm injection (ICSI) failures and single women showed rates of 27.6% and 22.6%, respectively. Meanwhile, patients with ICSI failures achieved the highest PRs in IVF cycles (48.7%), whereas nonobstructive azoospermia and single women showed rates of 42.0% and 38.2%, respectively. There have been significant increases in the use of donated sperm in single women. CONCLUSION(S): Single women, which also represented the oldest group, show a lower probability of achieving pregnancy, and thus represent a subfertile population. Associated factors could include advanced maternal age.

Cigarette smoking affects specific sperm oxidative defenses but does not cause oxidative DNA damage in infertile men.

OBJECTIVE: To evaluate the effects of tobacco consumption on the oxidative defenses of sperm, the glutathione system (GS), and sperm DNA oxidation. DESIGN: Double-blind experimental study. SETTING: Andrology laboratory in a university-affiliated private setting. PATIENT(S): One hundred seventeen semen samples from infertile males. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): (a) sperm GS enzymatic activity with respect to glutathione peroxidase isoforms GPx-1 and GPx-4, glutathione reductase (GR), and cellular glutathione (GSH) content (n = 29); (b) GPx-1, GPx-4, and GR mRNA expression analysis (n = 33); (c) oxidative DNA damage quantification using OXIDNA assay kit (n = 55). Two groups were established: nonsmoking and smoking males. The t tests were employed to detect significant differences between groups. RESULT(S): We identified a significant decrease in sperm GPx-4 activity but not in GPx-1 and GSH activity in smokers compared with nonsmokers. A significant decrease was also observed in GPx-1, GPx-4, and GR mRNA expression in the former group. Interestingly, we did not observe any significant variation in the percentage of cells with oxidative damage of the DNA or in the average level of oxidation of affected cells with respect to the smoking condition of the male. CONCLUSION(S): We demonstrate that smoking has a negative impact on intracellular antioxidant enzymes but that effect does not increase oxidative DNA damage. Thus, the effects of reduced oxidative defenses in sperm as a result of cigarette smoking are yet to be elucidated.

Impact of chromosomal abnormalities on preimplantation embryo development.

OBJECTIVES: To evaluate the influence of numerical chromosomal abnormalities on preimplantation embryo development. METHODS: This study includes 6936 embryos from 1245 women undergoing preimplantation genetic diagnosis (PGD). Indications for aneuploidy screening were: recurrent miscarriages, implantation failure, severe male factor, advanced maternal age, and mixed causes. Embryo biopsy was performed on day 3, and embryos were co-cultured until day 5, when embryo transfer was performed. RESULTS: In the aneuploidy screening regimen, normal euploid embryos showed significantly higher blastocyst rates (68.2%) compared to chromosomally abnormal (42.8%, p < 0.0001) and mosaic (53.7%, p < 0.0001) embryos. Among aneuploid embryos for autosomes, higher blastocyst rates were observed in trisomies than monosomies, although only statistically significant in patients over 36 years of age (50.8 vs 38.9%; p < 0.0001). In contrast, in embryos with sex chromosomes aneuploidy, similar blastocyst rates were observed between trisomies and monosomy X. CONCLUSION: Embryos with certain types of chromosomal abnormalities were negatively selected during preimplantation embryo development. Despite this selection, a remarkable percentage of chromosomally abnormal embryos can develop normally to blastocyst stage with high probability of implantation and pregnancy.

Sperm selection by swim-up in terms of deoxyribonucleic acid fragmentation as measured by the sperm chromatin dispersion test is altered in heavy smokers.

Toxic habits and their relationship with male factor infertility have been a matter of investigation in recent years, and smoking is one of the most common lifestyle toxic exposures to harmful substances. The analysis of sperm deoxyribonucleic acid fragmentation after capacitation detected a detrimental effect produced by tobacco, and this deleterious effect alters the sperm swim-up selection process in smokers, although the molecular and cellular basis of this phenomenon remain to be elucidated.