Abstract
The POSEIDON group (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) has introduced “the ability to retrieve the number of oocytes needed to achieve at least one euploid embryo for transfer” as an intermediate marker of successful outcome in IVF/ICSI cycles. This study aimed to develop a novel calculator to predict the POSEIDON marker. We analyzed clinical and embryonic data of infertile couples who underwent IVF/ICSI with the intention to have trophectoderm biopsy for preimplantation genetic testing for aneuploidy. We used the negative binomial distribution to model the number of euploid blastocysts and the adaptive LASSO (Least Absolute Shrinkage and Selection Operator) method for variable selection. The fitted model selected female age, sperm source used for ICSI, and the number of mature (metaphase II) oocytes as predictors (p < 0.0001). Female age was the most important factor for predicting the probability of a blastocyst being euploid given each mature oocyte (loglikelihood of age [adjusted for sperm source]: 30.9; df = 2; p < 0.0001). The final predictive model was developed using logistic regression analysis, and internally validated by the holdout method. The predictive ability of the model was assessed by the ROC curve, which resulted in an area under the curve of 0.716. Using the final model and mathematical equations, we calculated the individualized probability of blastocyst euploidy per mature retrieved oocyte and the minimum number of mature oocytes required to obtain ≥1 euploid blastocyst—with their 95% confidence interval [CI]—for different probabilities of success. The estimated predicted probabilities of a mature oocyte turn into a euploid blastocyst decreased progressively with female age and was negatively modulated overall by use of testicular sperm across age (p < 0.001). A calculator was developed to make two types of predictions automatically, one using pretreatment information to estimate the minimum number of mature oocytes to achieve ≥1 euploid blastocyst, and another based on the actual number of mature oocytes collected/accumulated to estimate the chances of having a euploid blastocyst using that oocyte cohort for IVF/ICSI. The new ART calculator may assist in clinical counseling and individualized treatment planning regarding the number of oocytes required for at least one euploid blastocyst in IVF/ICSI procedures.
Highlights
Approximately 10% of the couples have difficulties to conceive, with the highest prevalence in Eastern Europe, North Africa, Middle East, and Oceania [1]
The mean female age of our selected cohort was 38.9 years (95% confidence interval [CI]: 32.4–42.4 years) with a mean number of mature oocytes retrieved per patient of 6.3
The primary goal of our prediction model was to allow the development of a calculator to provide individualized pretreatment estimates concerning the number of mature oocytes needed to achieve ≥1 euploid blastocyst for transfer in infertile couples undergoing IVF/ICSI treatment
Summary
Approximately 10% of the couples have difficulties to conceive, with the highest prevalence in Eastern Europe, North Africa, Middle East, and Oceania [1]. Assisted reproductive technology (ART) has become an essential element of care for many couples suffering from infertility [2]. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) reported over four million ART treatments worldwide between 2008 and 2010 [3], most of which using ICSI as the fertilization method [4]. Despite the notable developments in ART over the last decades, which improved live birth rates from 26% in the 90’s to about 40% nowadays [7], the incidence of male infertility has increased, in parallel with a decline in semen quality [8, 9]. The etiology and severity of male infertility seem to independently affect reproductive outcomes even under ART settings [7, 10]. In turn, poses enormous challenges for clinicians and researchers alike as female age seems to be the central factor for pregnancy success [11]
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