This was a study showing the cumulative live birth in patients with low prognosis by using POSEIDON criteria. In the present study, we constructed and validated a nomogram to predict CLBR, consist of age, BMI, type and causes of infertility, bFSH, and usable embryos number at day 3.
The usable embryos number at day 3 was the most important variable in the nomogram. According to the Fig. 2, we could see a huge weight of embryos number in the scoring, furthermore the predictor capability of it alone was also high (AUC 0.737 in Table 2). The variable reflecting quality or quantity of embryos were different among studies, such as number of embryos transferred[10,11], or good-quality embryos.In this study, we have chosen the usable embryos number at day 3 because it was not only a routine data in our center that could be most completely retrieved, and also it is a factor strongly related with CLBR or other clinical outcomes[13,14]. The usable embryos number at day 3 take account of both the high-quality and low-quality embryos, that the later ones were potential of live birth in subsequent transfer when the first transfer failed. It is more suitable for studies using CLBR as an endpoint. The number of embryos played such an important role in POSEIDON population, indicated that the treatment protocol should be carefully chosen as the other factors were less influential or hard to adjust in clinical. Several more embryos might be a decisive change for some couples.
Among reset six variables, age were always reported as important predictors in previous studies[16,17]. It is not surprising that age could affect the clinical outcome, but the detailed results showed that only > 35 year old will significantly impact the CLBR. The exact threshold of age to affect the live birth was still not established, but more and more studies choose the 35 years old as the threshold, and also it had been accept in the POSEIDON criteria. The causes of infertility were also common in CLB prediction studies, especially the male factor which was quite reasonable as the application of ICSI technical. In this study, we also found uterine factors could be a disadvantage factor in IVF. But it need to mention that the predictor capability of infertility cause was not satisfactory in the validation set. It imply that the factors need further verification.
For BMI, it is interesting to see that overweight (24kg/m2 ≤ BMI < 28 kg/m2) achieved a better live birth rate than those with normal BMI. It is commonly believed that the BMI, or fat cells, is critical in estrogen secretion. But the results in previous studies were inconsistent with common sense. One large scale study focus on BMI found the overall live birth rate was decreased in women with BMI > 30 kg/m2 , but no differences were seen in other groups. Other studies also indicated there was no correlation between BMI and live birth rate, or even negatively correlated with live birth rate. But few study focus on POSEIDON patients had reported the relationship between CLBR and BMI, we suppose the endocrine changing were more sensitive in these patients and it might be a reason that BMI became one of the variables in the nomogram.
The management of POSEIDON patients was a challenging issue, the main reason was poor prognosis and it was the common cause of dropout. In a recent studies in China, the POSEIDON patients got an approximate 24% of CLBR, significantly lower than that in non-POSEIDON patients, which was 44.5%. In our study, the CLBR was about 26%, similar to that in the reference. The characteristics of the patients in several POSEIDON population were all similar. It indicated that the conclusion in our study could be applied and also validated by most POSEIDON population.
Treatment regimen decision might affect the clinical outcome, so it was always included in the multivariate analysis. In the Chinese experts’ opinions, antagonist protocol were recommended in both younger patients (< 35 years old) and elder patients (> 35 years old), as it could achieve good clinical outcomes in fresh cycle, and also reduce the Gn usage or shorten the treatment duration. Even after the recommendation, an opinion was given that the protocol should be applied according to the situation of center and patients. But the treatment regimen was not included in the nomogram, as some further analyses would be applied to directly compare the effectiveness of different treatment protocols in POSEIDON population, and also in each subgroups. The comparison could directly reflect the difference of CLBR under both dimension of treatment regimens and dimension of POSEIDON subgroup, which is the first step for clinical application of the nomogram.
It was a retrospective and single center study, bias could not be fully avoided. As shown in table 2, several variables showed different predict capability in training and validation set. The nomogram could be more accurate by expansion more samples. And the clinical outcome was chosen CLB only, some other common outcomes such as live birth in single cycle, clinical pregnancy rate were not shown in this study. One reason was the definition of CLB fits the criteria of POSEIDON best, another was that there were already extensive results by CLB.