The present study showed that OPR in women with advanced endometriosis is significantly higher in the group of frozen embryo transfer compared to the fresh embryo transfer group (67.6% vs. 34% respectively). Regarding the secondary outcomes, there was a statistically significant higher implantation and clinical pregnancy rates also in the frozen embryo transfer group. To best of our knowledge, only few studies have addressed the issue of freeze all policy in women with advanced endometriosis.
In agreement with the findings of the current study, Wu et al.,(18) conducted a retrospective study that encompassed 1651 women with advanced stages of endometriosis performing ICSI. After matching, 506 women and 255 women were eligible in the freeze-all group in fresh group, respectively. In their matched cohort study, the implantation, CPR and LBR were significantly higher in the FET group in comparison to the fresh groups. Those results coincide with the current study in all perspectives except for the LBR as it was not included in the outcomes for the study.
However, the present study differs from Wu et al., where in their study, the development of the embryo was accessed on day 3, and the embryos selected to be transferred were high-quality cleavage-stage embryos only (at least six blastomeres with ≤ 20% fragmentation based on the Cummins' Criteria). In the fresh embryo transfer group, patients were arranged for a day 3 fresh embryo transfer, and vitrification of the extra embryos. For the FET, vitrification on day 3 of the entire cohort of good quality embryos. While in the present study, embryo development was assessed on day 5 and patients performing fresh transfer were scheduled for a day-5 ET, while in the frozen group, the embryos were vitrified on day 5, and embryo transfer was not exclusively for high quality embryos, but in some cases average or low quality embryos were transferred either alone or in combination with a high quality embryo.
Again the results of the present study coincided with a matched cohort prospective study conducted by Bourdon et al. (19),they compared the results of FET to fresh ET in women having endometriosis, where the FET group involved 135 women and the fresh group involved 424 matched women. CPR was of higher significance toward the FET group in comparison to the fresh group, also the ongoing pregnancy rate showed greater statistical significance in the FET group (34.8%) in comparison to the fresh-ET group (17.8%) (p = 0.005), and the live birth rate as well was of higher significance in FET in comparison to fresh embryo transfer group.
Another interesting study conducted by Mohamed et al. (20), a retrospective, database-searched cohort study. The study included two groups, the first group had freshly transferred embryos while the second group performed frozen embryo transfer. The primary outcome for the study was the live birth rate, while the secondary outcomes included the clinical pregnancy rate and the miscarriage rate. Out of the total number of cases, 415 (5.7%) had infertility attributed to endometriosis, in whom frozen ET cycles were associated with a relatively similar clinical pregnancy rate and live birth rate, in comparison to the clinical pregnancy rate and live birth rate of fresh ET cycles, showing no significant difference. Nevertheless, the study of Mohamed et al. differs from the present study as they considered other causes of infertility rather than endometriosis alone as a sole factor of infertility, it also concluded that there was no significant difference between FET over the fresh ET in cases of endometriosis concerning CPR (18.2 vs. 20.2% respectively) and LBR (16.9% vs. 15.5% respectively).
In accordance, a recent systematic review and meta-analysis conducted by Chang et al. (21), aimed at evaluating if FET has the ability to reimpose optimal receptivity targeting better ART results in patients with endometriosis. A total of six studies with moderate methodological quality were included in the meta-analysis. Three thousands and ten patients with endometriosis who underwent ICSI were included in the studies; 1777 performed FET, and 1233 performed fresh ET. LBR was significantly higher in the FET group in comparison to the fresh group. Although that CPR was similar between the two study groups, there was a significantly higher miscarriage rate in the fresh group.
The endometrium of endometriosis-affected women is different from that of healthy, unaffected women (8), which could be the main reason for the decline in endometrial receptivity quality. Thus, it is crucial to select the right embryo transfer technique, particularly for women who have severe endometriosis. The effects of ovarian stimulation in fresh ET cycles on the early peri-implantation uterine milieu have been documented in a number of studies, three-dimensional power Doppler ultrasonography measurements have revealed that stimulated cycles have reduced endometrial and subendometrial blood flow in comparison to normal cycles (9). Furthermore, certain pathologic alterations of the stimulated endometrium have been verified, such as the progression of endometrial maturation (10), as well as the early establishment of nucleolar channel systems (11).
Additionally, a number of researchers have demonstrated that during fresh embryo transfer cycles, there are abnormalities in the transcriptional activity of genes related to endometrial receptivity (22–24). The alterations indicated above are linked to the hyperestrogenic environment created during fresh IVF, which might subsequently hinder early embryonic adhesion (18, 25), and consequently, the embryos' capacity to implant. It follows that the current study's findings regarding implantation, clinical pregnancy, and ongoing pregnancy are better in FET cycles.
Our study has the advantage of being one of the few studies that addressed the role FET in endometriosis affected women and was conducted for a fair number of patients, moreover, this study focused on advanced endometriosis being the sole factor of infertility in the studied patients, excluding any other infertility related factors, however the main study limitation was being a retrospective analysis depending on the availability of complete medical records and the follow up stopped at 14 weeks of gestation.