To our knowledge, there were few studies comparing the effects of the two regimens for elderly patients with DOR. In this study, our research subjects were women over the age of 35 with DOR undergoing IVF treatment. In terms of the effect of inhibiting the premature LH surge, PPOS regimen and antagonist regimen showed no difference. Although the final outcome of the frozen embryo transfer cycles of two regimens showed similarities,the antagonist regimen was better than the PPOS regimen in terms of ovulation induction outcome.
DOR is a difficult problem in the treatment of fertility. Because DOR patients do not respond well to ovarian stimulation, COS becomes a particularly critical step in ART cycles [14]. We selected the two most clinically used ovulation stimulation regimens to compare which regimen used by DOR patients would have better oocyte-obtained outcome and fertility outcome. Patients with DOR were more likely to experience premature LH surge [12]. One of the advantages of the PPOS regimen is that it can prevent premature LH surge [10]. Therefore, we first compared its effect with the antagonist regimen in suppressing premature LH surge. We found there was no difference which was different from other studies. In a study of patients with endometriosis, the LH level on trigger day of PPOS group patients was lower than that in the antagonist group [15]. Chen et al. proved that compared with the antagonist regimen, PPOS regimen could better prevent the appearance of premature LH surge for poor responders [16]. But we found similar conclusion in a study [17] that also targeted DOR patients. There was also no difference in the incidence of premature LH surge between the flexible PPOS group and antagonist group. Subsequently, the researcher also conducted subgroup analyses based on the AMH value and AFC, and no difference was found. Therefore, for patients with DOR, there was no difference in the effectiveness of the two regimens for pituitary suppression.
From the process of ovulation induction and the number of retrieved oocytes, the antagonist program may be more suitable for DOR patients over 35 years old. The proliferation and differentiation of endometrial cells depend on estrogen and progesterone. Levels of estradiol and progesterone play a key role in the preparation of the uterus before implantation [18]. There is still controversy as to whether estradiol and progesterone levels on trigger day are associated with IVF outcomes [18, 19]. Although the estradiol and progesterone levels on HCG administration days in the antagonist group were higher than those in the PPOS group in this study, the pregnancy outcome did not show any difference. Related studies [18] proved that the effect of serum estradiol on IVF pregnancy outcome might be related to concentration, and it was believed that the optimal concentration range for positive outcomes in patients over 38 years old is 2000–3000 pg/mL, and the range is higher for patients younger than 38 years old. A meta-analysis with a sample size of 55,000 [20] showed that there was a negative correlation between progesterone levels and pregnancy rate, and a decrease in pregnancy rate would be seen when the progesterone level reached the range of 0.8–1.1 ng/ml. In this study, the two groups of trigger-day estradiol levels did not reach 2000 pg/Ml, and the progesterone levels did not reach 0.8ng/ml. Therefore, we could only provide a reference that estradiol and progesterone levels on HCG administration day might be higher in patients with DOR from antagonist regimen than PPOS regimen.
In terms of retrieved oocytes results, the antagonist regimen was better than the PPOS regimen. No difference in the number of oocytes retrieved was observed between PPOS regimen and antagonist regimen in patients with low ovarian response or polycystic ovary syndrome (PCOS) [16, 21]. In a study comparing the PPOS regimen with the long regimen in DOR patients over 35 years of age, no difference was found in the number of oocytes retrieved either [22]. However, in this study, the number of follicles in different stages and the number of retrieved oocytes of the antagonist group were all higher than those of the PPOS group. Although the final clinical outcomes of the two groups were not statistically different, the key to promoting ovulation in patients with DOR is to reduce the rate of early ovulation and maximize the possibility of retrieving oocytes. And the older the patients get, the easier it is to ovulate prematurely [12]. Therefore, from the perspective of oocytes retrieving, in terms of the results of this study, the antagonist regimen might be more suitable for DOR patients over 35 years of age who received IVF-assisted pregnancy.
There were some limitations in our study. Firstly, this was a retrospective study, which proved that the purpose of the study was not as strong as a randomized controlled study. What’s more, the number of patients collected during the study period was relatively small. A larger sample size is needed for further research in the future. Since the embryos of patients using PPOS regimen were all frozen, we couldn’t compare the outcome of the fresh cycle of two regimens. So we compared their frozen embryo clinical outcomes. This was also a feature of this study.