A Novel Predictive Model to Estimate the Number of Mature Oocytes Required for Obtaining at Least One Euploid Blastocyst for Transfer in Couples Undergoing in vitro Fertilization/Intracytoplasmic Sperm Injection: The ART Calculator

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.

Keywords: ART calculator; POSEIDON criteria; assisted reproductive technology; blastocyst; decision support models; female age; intracytoplasmic sperm injection; preimplantation genetic testing for aneuploidy.

Figure 1

Blastocyst euploidy probability per mature (MII) oocyte. The plots show the probability of a MII oocyte turn into a euploid blastocyst as a function of female age. The estimated probabilities (solid curves) and their 95% confidence interval (dotted curves) are presented according to sperm source to be used for IVF/ICSI, namely, ejaculated sperm (blue) and testicular sperm extracted from patients with non-obstructive azoospermia (NOA) (red). The relations are non-linear and characterized by a differential modulatory effect of sperm source across age (see text).

Figure 2

Online calculator to determine the minimum number of mature oocytes required to obtain at least one euploid blastocyst for transfer in infertile patients undergoing IVF/ICSI cycles. The figure shows how the online calculator can be used in an office-based setting. Pretreatment, clinicians should input the patient age and the sperm source to be used for IVF/ICSI. If the option “Testicle” is marked, then the type of azoospermia should be also defined. The probability of success is set by the user and indicates the chance of having ≥1 euploid blastocyst when the predicted number of mature oocytes is achieved. Its complement is the risk, that is, the chance of having no (zero) euploid blastocysts when the predicted number of oocytes is achieved. Once the button “calculate” is pressed, a text box will pop-up on the right side of the screen, indicating the predicted minimum number of mature oocytes needed for obtaining at least one euploid blastocyst, with its 95% confidence interval.

Figure 3

ART online calculator. The figure shows how the online calculator can be used posttreatment, i.e., when fewer than the predicted number of mature oocytes are obtained after one or more oocyte retrieval cycles. Clinicians should input the pretreatment information and the actual number of mature oocytes collected or accumulated. The probability of success is set by the user; it reflects the chance that the estimation is correct given the number of oocytes input. Once the button “calculate” is pressed, a text box will pop-up on the right side of the screen, indicating the predicted probability of achieving ≥1 euploid blastocyst with the number of mature oocytes available.

Figure 4

Predictive model output (Ejaculated sperm). The plots show the predicted probability of having ≥1 euploid blastocyst oocyte according to the number of mature oocytes. Each solid curve represents a female age category. The dotted reference lines indicate the 70, 80, and 90% bands for achieving the desired outcome.

Figure 5

Predictive model output (Testicular sperm from non-obstructive azoospermic [NOA] men). The plots show the predicted probability of having ≥1 euploid blastocyst oocyte according to the number of mature oocytes. Each solid curve represents a female age category. The dotted reference lines indicate the 70, 80, and 90% bands for achieving the desired outcome.