Endometriosis is an estrogen dependent inflammatory disease classically characterized by infertility and secondary progressively dysmenorrhea, which is becoming more prevalent in childbearing-age women. Endometriosis is closely related to infertility, about 10–25% of women with endometriosis have undergone IVF/ICSI, however whether minimal and mild endometriosis are associated with infertility and the outcomes of IVF/ICSI are still unclear. So more assisted reproductive technology for effectively improving the pregnancy rate for minimal and mild endometrios women are still needed. Though previous studies about the two major endometrial preparation protocols analyzed the correlations between fresh embryo transfer or FET and pregnancy outcomes in the population, their results are inconsistent. Therefore, in this study we aimed to compare the effects of natural cycle endometrial preparation versus long-term GnRH-a down regulation cycle endometrial preparation of FET on the live birth rate in minimal and mild endometriosis women.
In this study, all subjects were pathologically confirmed as I-II endometriosis of ASRM after laparoscopic or open surgery, and they were assigned to the natural cycle and GnRH-a down regulation cycle groups according to specific endometrial preparation protocols. Their baseline characteristics were comparable. The biochemical pregnancy rate, clinical pregnancy rate, implantation rate and live birth rate were significantly higher in the natural cycle group than those in the GnRH-a down regulation cycle group. Besides, there were nonsignificant differences in the multiple pregnancy rate, miscarriage rate, ectopic pregnancy rate, premature birth rate, normal delivery rate and cesarean section rate between the two groups. By contrast, van de Houwen LE et al. concluded that GnRH-a down regulation cycle of FET improved ongoing pregnancy rates compared with natural cycle of FET in severe endometriosis patients. However,another study has assessed the influence of endometrial peristalsis on embyros/blastocysts implantation and has reported that natural cycle of FET is instrumental to a high pregnancy rate. Nevertheless, they did not take into consideration different endometrial preparations. Levron et al. demonstrated that the implantation rate and clinical pregnancy rate were improved after natural cycle of FET, which is consistent with our findings. In addition, in long-term GnRH-a down regulation cycle, minimal and mild endometriosis patients in the present study were supplemented with exogenous estrogens before the placental function was established. Due to no using of exogenous estrogens, natural cycle of FET do not alter endometrial receptivity, and there were a more natural effect of luteal support for blatocyst development; moreover, it is cost-saving during a short period of treatment.
Embryo quality and endometrial receptivity are the major factors that influence outcomes following FET. In our study, both blastocyst culture and cryopreservation during the controlled ovarian hyperstimulation cycle contribute to a high pregnancy rate and live birth rate after FET. To obtain higher developmental potential, we eliminated blastocysts with poor quality or chromosomal abnormalities, and we kept high-quality blastocysts during blastocyst culture, and then performed the vitrification for good quality blastocysts. And we discover that more high-quality transplanted blastocysts is what matters to a higher live birth rate after FET, rather than the number of transplanted blastocysts, which is also supported by the study by Bourdon M et al.
In the present study we confirmed that age and AMH levels were associated with the live birth rate following FET. Evidences show that age is an independent risk for the live birth rate. With the increasing age, diminished quality of oocytes alongside mitochondrial dysfunction and oxidative stress increases the risk of embryo chromosome abnormalities, often manifesting as the presence of aneuploid embryo and a low blastulation rate. Decreases in AMH levels and the AFC indicate a reduced ovarian reserve, which further influences the numbers of eggs, embryos and high-quality embryos.
It is reported that minimal and mild endometriosis may have a certain impact on low newborn birth weight. Although no significant differences in newborn birth weight and length were identified between the natural cycle and GnRH-a down regulation cycle groups, a higher premature rate and lower newborn birth weight in both groups were consistent with previous studies[19, 25]. As a result, further research is required to clarify the correlation between minimal and mild endometriosis and low newborn birth weight. It is reported that IVF treatment in severe minimal and mild endometriosis patients may enhance susceptibilities to congenital cardiovascular and skeletal muscle diseases in neonates. After we screened fetal malformation, although there were early and late abortions in both groups during pregnancy, no birth defects were detected, which can be explained by the inclusion of minimal and mild endometriosis patients, high-quality blastocysts transplantation, comprehensive prenatal examinations of the abnormal fetus, or a small sample size.
This is a retrospective non-randomized controlled trial, so a potential selection bias may influence the research quality. A prospective randomized controlled trial at multi-centers is required to validate our findings. Summarily, this study demonstrates that natural cycle endometrial preparation is superior to GnRH-a down regulation cycle endometrial preparation in terms of the implantation rate, clinical pregnancy rate and live birth rate, which also improves the cost-effectiveness of FET for women with minimal and mild endometriosis. A large sample size is still required to re-verify the influence of endometrial preparations on pregnancy outcomes of Chinese minimal and mild endometriosis women undergoing FET.