This study aimed to address the possible prediction of FT-ET results with regard to its previous fresh ET cycle from the same OPU. Our results showed consistent, significant differences between patients with a successful fresh ET cycle compared to those with an unsuccessful fresh ET with regard to the success of consecutive FT-ET cycles from the same OPU. This was also demonstrated in the first FT-ET cycle separately. Logistic regression showed this factor to be a significant independent factor, with an adjusted OR of 5.02.
This is the first study to evaluate this link in embryos cryopreserved using the vitrification method which is the prevalent method applied today in most IVF laboratories.
As previously reported by van Loendersloot et al. [3] and Lintsen et al. [4], our analyses demonstrated that the number of oocytes retrieved and use of ICSI are independent prognostic factors for successful ET. In addition to the previous studies mentioned, we showed a similar association between previous successful fresh cycle and successful ET. This further establishes these parameters as important prognostic factors that should be evaluated in predicting success of FT-ET.
Our finding of higher pregnancy rates for FT-ET cycles after successful fresh ET are in agreement with that reported by Molloy et al. [11] on 784 patients who had favorable pregnancy outcomes of FT-ET cycles depending on the outcome of the original fresh cycle.
El Toukhy et al. [12] similarly reported double implantation and pregnancy rates in FT-ET cycles using embryos originated from successful fresh ET cycles. Their data was based on 459 fresh cycles. However, both abovementioned studies were carried out prior to the introduction of the vitrification technique. Therefore, they did not assess this phenomenon in embryos frozen by vitrification, rendering them less relevant for IVF programs currently using this technique.
In order to address this issue, our study included only embryos frozen using vitrification. Frozen cycle success rate after vitrification reached 50% in patients with a previous successful fresh cycle compared with nearly 20% in patients with a failed fresh cycle.
A systematic review by Rienzy et al. [15] showed that the vitrification technique results in improved survival rates of cryopreserved oocytes and improved clinical pregnancy rates per cycle [16, 17]. Ultra-rapid cooling by vitrification enables solidification of cells and extracellular environment into a glass like state without formation of ice eliminating the mechanical injury which may occur during freezing of water particles. We hypothesize that the advantage of this technique over slow freezing may contribute to higher quality frozen-thawed embryos that preserve a "fresh embryo" potential with clinical outcomes as good as fresh embryos. Therefore, when the fresh cycle is successful, the consecutive vitrified frozen thawed embryos from same OPU are of a much higher potential for successful implantation and clinical pregnancy and are only minimally affected by vitrification. This hypothesis is supported by the major difference (~ 30%) in clinical pregnancy rate between our study groups, compared to smaller advantage in clinical pregnancy rates shown in similar studies that investigated this association in embryos frozen by slow freezing.
Besides its retrospective nature, this study has several limitations. During the study period only 122 blastocysts were transferred, Therefore, we were not able to separately analyze the groups according to cleavage stage and blastocysts transfers. Another limitation was the age difference of nearly a year in favor of the successful fresh cycle group. Though this may affect the subsequent frozen cycle's results, our logistic regression demonstrated that successful fresh cycle is an independent factor even when considering age at oocyte retrieval. Clinical pregnancy rates rather than live birth rates were used as the primary outcome due to lack of birth data for some (~ 20%) of the women included in the study. However, in most cases birth data was available and live birth rate was similarly higher in FT-ET following a successful fresh cycle.
In conclusion, this study shows that in addition to known factors such use of ICSI and number of retrieved oocytes, a successful fresh cycle is a positive independent prognostic factor for a successful FT-ET cycle of embryos derived from the same OPU. This data may assist physicians facing the challenge of counselling women planning a frozen thawed embryo transfer cycle.