There were 1100 patients who underwent IVF/ICSI cycles and had at least one poor ovarian response recorded in the database during the study period. From these, we enrolled 812 eligible patients and divided them into five groups according to the Bologna criteria; however, 41 of these patients were not included in any of the Bologna subgroups because they had only one cycle of less than four retrieved oocytes after standard ovarian stimulation and no other risk factors for POR. The number of patients in groups III and IV was higher than the other groups. Phenotype III (58.9%, n= 478) comprised the majority of patients according to Bologna criteria.
Comparison of different poor ovarian responder (POR) patient groups based on Bolognacriteria
We compared baseline characteristics among different POR groups according to Bologna criteria (Table 1). There were significant differences among the groups in terms of age, number of previous IVF/ICSI cycles, serum AMH levels, and AFC before starting stimulation; however, this was expected because these variables are determinative factors according to Bologna criteria. Bologna group IV had the highest rate of secondary infertility compared to the other groups (p<0.001). Bologna group V patients had a significant difference compared with the other groups regarding the causes of infertility. Patients in this group had a lower rate of the ovulatory factor for infertility compared with the other groups (p<0.001). The numbers of patients with a previous history of no oocytes and no response in Bologna groups I (p<0.001) and II (p=0.02) were significantly lower than the other groups. No significant difference was found among groups regarding the other baseline characteristics (Table 1).
The outcomes of the last cycle of ovarian stimulation and embryo transfer (ET) were compared among different POR groups according to Bologna criteria (Table 2). The ovarian stimulation protocol in Bologna group IV patients differed from the other groups; the majority of protocols in this group were antagonists and double-stimulation protocols. In our institute, the COH protocol was selected based on the age of the woman, ovarian reserve, and history of previous cycles. Therefore, in patients with advanced age and low ovarian reserve or previous history of POR, the antagonist or double-stimulation protocol was used more frequently. However, the duration of ovarian stimulation, dose of gonadotropin (rFSHand/or human menopausal gonodatropin [hMG]), and number of follicles ≥15 mm on the day of oocyte triggeringin the last cycle were not different among the groups. Tukey analysis demonstrated that the number of retrieved and MIIoocytes in Bologna group III was different from the other groups; consequently, the number and quality of obtained embryos, and the number of embryos transferred was different from the other groups (p<0.001).However, the stage of the transferred embryo (blastocyst or cleavage) did not differ between the groups. The cancellation (p<0.001) and no oocyte (p=0.007) rates in Bologna groups IV and V were significantly higher than the other groups. Endometrial thickness on the trigger day showed a significant difference between groups and the results of the Bonferroni test showed that endometrial thickness in Bologna group IV was significantly higher compared with Bologna groups II (p=0.03) and III (p=0.01).Finally, the clinical pregnancy and LBR in Bologna groupsIIandIIIwere significantly higher than the other groups (p=0.006).
Comparison of different poor ovarian responder (POR) patients according toPatient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) group classification
Patients classified on the basis of POSEIDON group criteria were mostly in group 4 (57%, n=463). Table 3 shows the baseline characteristics of the patients in the different groups based on the POSEIDON group classification.
There were also significant differences among groups in terms of women’s age, basal FSH and serum AMH levels, and AFC before starting stimulation; however, this was expected because these variables are main factors in the POSEIDON group classification. Women in POSEIDON group 4 had a significant secondary infertility type in comparison to the other groups. Also, there was a significant difference in the cause of infertility between POSEIDON group 1 and the other groups (p<0.001). The majority of patients in POSEIDON group 1 were with male factor diagnosis, whereas most patients were diagnosed with ovarian factor in the other groups. No significant difference was found among groups in terms of the other baseline characteristics (Table 3).
Table 4 shows the outcomes of the last treatment cycle of the studied patients in the different groups based on POSEIDON group classification. In a similar way, the COH protocol was selected on the basis of age, ORT, and previous history; therefore, the antagonist and double-stimulation COH protocols were used more frequently in patients from POSEIDON group 4 (p<0.001).
However, the mean values of the ovarian stimulation day and dose of gonadotropins, and the number of follicles ≥15 mm on the day of oocyte triggering were not significantly different among the groups. Tukey analysis showed that the number of retrieved (p=0.002) and MII (p=0.001) oocytes in POSEIDON group 3 were greater than those of POSEIDON group 4. Meanwhile, the differences between the other groups were not statistically significant. The number of embryos obtained and the number of embryos transferred were not in line with the total retrieved oocytes; these were significantly lower in POSEIDON group 1 compared with the other three groups (p=0.002, p=0.003, and p=0.008). In addition, the quality of obtained embryos and the rates of fertilization, cancellation, and no oocyte cases did not significantly differ between the groups. Endometrial thickness on the trigger day in POSEIDON group 3 was significantly higher than in POSEIDON group 4 (p=004). Finally, the clinical pregnancy and LBR in POSEIDON group 3 were significantly higher than the other groups (p=0.006).
Table 5 shows the association between possible related factors and the LBR according to the univariate logistic regression test. The analysis indicated that women’s age, duration of infertility, serum TSH levels, number of oocytes obtained and MII oocytes, the number of embryos obtained, the number and quality of transferred embryos, and the POSEIDON classification group showed a significant unilateral relationship with the LBR.
All of the significant possible variables related to the LBR were entered in multivariate logistic regression model. The analysis revealed that the significant independent variables that remained in the model as important predictive factors for live births in the study population were the number and quality (good and excellent) of the transferred embryos, and POSEIDON classification group 3. In other words, the likelihood of a live birth after transferring excellent embryos was approximately 5.9 times higher than the transfer of fairquality embryos.Also by increasing the number of transferred embryos, the likelihood of a live birth increased by 1.6 times.In this regression model, the likelihood of a live birth in a patient in POSEIDON group 3 was three times higher than that of a patient in POSEIDON group 4 (Table 6).