Association of 'normal' early follicular FSH concentrations with unexpected poor or suboptimal response when ovarian reserve markers are reassuring: a retrospective cohort study.

RESEARCH QUESTION: Are basal FSH measurements, when elevated within its normal range, useful for assessing overall ovarian response and predicting unexpected poor or suboptimal ovarian response? DESIGN: Retrospective cohort study of ovarian stimulation cycles. RESULTS: A total of 1058 ovarian stimulation cycles (891 first, 167 repeated) were included. Anti-Müllerian hormone (AMH) values were categorized into four (0 to ≤0.6, >0.6 to ≤1.2, >1.2 to ≤3.0, >3.0 to ≤6.25 ng/ml) and basal FSH levels into four groups (<25th percentile: >3.5 to 6.1 IU/ml; 25-75th percentile: >6.1 to ≤8.5 IU/ml; >75-90th percentile: >8.5 to ≤9.9 IU/ml; >90th percentile: >9.9 to ≤12.5 IU/ml). Including only first cycles, a significant independent effect of basal FSH on retrieved cumulus-oocyte complex (COC) count was seen for all basal FSH categories (>90th, >75 to ≤90th, >25 to ≤75th compared with ≤25th percentile, P < 0.001, P = 0.001 and P = 0.007, respectively), when adjusted for age, body mass index (BMI), AMH, antral follicle count (AFC), starting dose and gonadotrophin type. Including only first cycles, patients aged 35 years or older with AFC of 5 or above and AMH 1.2 ng/ml or above, showed significantly higher odds of unexpected poor or suboptimal response if they had higher basal FSH values. Most prominently in the above 90th percentile group (OR 8.64, 95% CI 2.84 to 28.47 compared with <25th percentile) but lower categories (>25th to ≤75th percentile: OR 3.04, 95% CI 1.42 t 6.99; >75th to ≤90th percentile: OR 3.47, 95% CI 1.28 to 9.83 compared with ≤25th percentile) also showed a significant association after adjusting for age, AMH, BMI, AFC, dose, and gonadotrophin type. In patients with a second cycle, an increase in FSH levels in the second round compared with the first was associated with fewer retrieved COCs (estimate: -0.44, 95% CI -0.44 to -0.05, P = 0.027). This effect was adjusted for changes in age, FSH, AFC, starting dose, stimulation duration and change in medication type. CONCLUSIONS: Basal FSH is independently associated with overall ovarian response. Moreover, it is associated with unexpected poor or suboptimal response in patients, who would fulfill POSEIDON group 2 criteria after oocyte retrieval.

Assessment of embryo implantation potential with a cloud-based automatic software.

RESEARCH QUESTION: Is embryo selection by Dana (automatic software for embryo evaluation) associated with a higher implantation rate in IVF treatments? DESIGN: A three-phase study for Dana system's validation: creation of a data-cloud of known implantation data (KID) embryos from 1676 transferred embryos; embryo evaluation by Dana considering manual annotations and embryo development videos (389 transferred embryos); and validation of Dana automatic selection, without embryologist's intervention (147 transferred embryos); RESULTS: The implantation rate of the 1021 KID embryos from phase 1 served to set four grades of embryos referring to implantation rate: A = 34%, B = 25%, C = 24%, and D = 19%. Phase 2: a classification ranking according to the unit average distance (UAD) and implantation potential was established: top (UAD ≤0.50), high (UAD = 0.51-0.66), medium (UAD = 0.67-1.03) and low (UAD >1.03). Pregnancy rates were 59%, 46%, 36% and 28%, respectively (P < 0.001). Phase 3: embryos were automatically categorized according to Dana's classification ranking. Most implanted embryos were found in groups top, high and medium (UAD ≤1.03), whereas the implantation rate in group low (UAD >1.03) was significantly lower: 46% versus 25%, respectively (P = 0.037). The twin gestation rate was higher when number of top embryos (UAD ≤0.5) transferred were two (52%) versus one (25%) (P < 0.001). CONCLUSIONS: Embryo selection based on Dana ranking increases the success of IVF treatments at least in oocyte donation programmes. The multicentre nature of the study supports its applicability at different clinics, standardizing the embryo development's interpretation. Dana's innovation is that the system increases its accuracy as the database grows.

An artificial intelligence model based on the proteomic profile of euploid embryos and blastocyst morphology: a preliminary study.

RESEARCH QUESTION: The study aimed to develop an artificial intelligence model based on artificial neural networks (ANNs) to predict the likelihood of achieving a live birth using the proteomic profile of spent culture media and blastocyst morphology. DESIGN: This retrospective cohort study included 212 patients who underwent single blastocyst transfer at IVI Valencia. A single image of each of 186 embryos was studied, and the protein profile was analysed in 81 samples of spent embryo culture medium from patients included in the preimplantation genetic testing programme. The information extracted from the analyses was used as input data for the ANN. The multilayer perceptron and the back-propagation learning method were used to train the ANN. Finally, predictive power was measured using the area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: Three ANN architectures classified most of the embryos correctly as leading (LB+) or not leading (LB-) to a live birth: 100.0% for ANN1 (morphological variables and two proteins), 85.7% for ANN2 (morphological variables and seven proteins), and 83.3% for ANN3 (morphological variables and 25 proteins). The artificial intelligence model using information extracted from blastocyst image analysis and concentrations of interleukin-6 and matrix metalloproteinase-1 was able to predict live birth with an AUC of 1.0. CONCLUSIONS: The model proposed in this preliminary report may provide a promising tool to select the embryo most likely to lead to a live birth in a euploid cohort. The accuracy of prediction demonstrated by this software may improve the efficacy of an assisted reproduction treatment by reducing the number of transfers per patient. Prospective studies are, however, needed.

Effect of Sperm Concentration and Storage Temperature on Goat Spermatozoa during Liquid Storage.

The use of cooled semen is relatively common in goats. There are a number of advantages of cooled semen doses, including easier handling of artificial insemination (AI) doses, transport, more AI doses per ejaculate, and higher fertility rates in comparison with frozen AI doses. However, cooled semen has a short shelf life. The objective of this study was to examine the effect of temperature and sperm concentration on the in vitro sperm quality during liquid storage for 48 h, including sperm motility and kinetics, response to oxidation, mitochondrial membrane potential (MMP) and DNA fragmentation in goats. Three experiments were performed. In the first, the effects of liquid preservation of semen at different temperatures (5 °C or 17 °C), durations (0, 24 and 48 h) and sperm concentrations (250 × 106 sperm/mL (1:2 dilution rate), 166.7 × 106 sperm/mL (1:3 dilution rate) or 50 × 106 sperm/mL (1:10 dilution rate)) on sperm motility and kinetics were studied. In the second experiment, the effect of temperature, sperm washing and concentration on sperm motility and DNA fragmentation was studied. Finally, the effect of sperm concentration and duration of storage at 5 °C on sperm motility, response to oxidative stress and MMP was examined. We found that refrigerated liquid storage of goat sperm impaired sperm quality, such as motility, MMP and response to oxidation, as storage time increased; however, sperm DNA fragmentation index was not significantly affected. Liquid storage at 5 °C preserved higher total motility than at 17 °C. Moreover, we observed that the reduction of sperm concentration below 500 × 106 sperm/mL did not seem to improve the quality of spermatozoa conserved in milk-based extender in the conditions tested.

Novel noninvasive embryo selection algorithm combining time-lapse morphokinetics and oxidative status of the spent embryo culture medium.

OBJECTIVE: To develop a noninvasive embryo selection algorithm consisting of time-lapse morphokinetics and the oxidative status of the spent embryo culture medium determined using the Thermochemiluminescence (TCL) Analyzer. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): From women participating in the oocyte donation program, data from 505 samples of spent embryo culture media samples from 292 intracytoplasmic sperm injection cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Morphokinetic parameters assessed during incubation in the time-lapse system Embryoscope. Oxidative parameters (H1sm, H2sm, and H3sm) from the spent culture medium on day 5 of incubation measured using the TCL assay; and a combined assessment algorithm, including morphology, morphokinetics, and the embryo's culture medium oxidative status, developed as a tool for embryo selection, based on implantation success and confirmed ongoing pregnancy. RESULT(S): The levels of the oxidative parameters H1sm, H2sm, and H3sm on day 5 of incubation were statistically significantly higher in transferred and vitrified embryos compared with discarded embryos and in successfully implanted embryos compared with those that did not result in pregnancy. The assessment algorithm resulted in a hierarchical classification with six embryo quality categories (A to F), associated with implantation rates of between 76.5% and 29.2%. CONCLUSION(S): An assessment algorithm combining morphology, morphokinetics and the embryo's culture medium oxidative status may help to improve current embryo selection methods criteria and in vitro fertilization success.