This respective study did not find obvious effecy of GnRH-a in pregnancy outcomes for patient with adenomyosis. The result of comparable clinical pregnancy rates seemed conflicted with GnRH-a increasing the chance of pregnancy for female with adenomyosis[13-14]. Preterm rates and full-term rates happened almost in the same level between the two groups, which was different from the previous epidemiological studies.
Meta-analysis explored the association between the endometrium thickness and pregnancy outcomes, thinner endometrium(＜7mm) resulting in negative ongoing pregnancy rates and live birth rates[19-20]. In this study, the difference of endometrium thickness between two groups had statistical significance; however, mean values of both were more than 9mm. So it was debatable to detect whether the different endometrium thickness impaired pregnancy outcomes in this study.
A randomized controlled trial indicated that embryo transfer conducted at day 5 was more likely to obtain higher ongoing or cumulative pregnancy rates compared with the result at day 3. Another meta-analysis demonstrated that clinical pregnancy rates and live birth rates were significantly higher following day 5 compared to day 6 blastocyst transfers. Both Group A and Group B covered the day 3, day 5 and day 6 of embryo transfer and the variation between two groups was no statistical significance even if the proportion of day 3 was relatively low. The embryos of day 5 covered the vast majority in both groups, which can improve the pregnancy rates in a way.
The proportion of primary infertility in Group A was more than that of Group B, although the difference of the ratio of primary and secondary infertility between two groups did not have statistical significance. Studies demonstrated that pregnancy performance of the secondary infertility was significantly better than that of the primary infertility[23-24]. The higher percentage of primary infertility in group A may be a key factor to decreasing rates.
As for the number of transferring embryos, a study indicated that two elective single embryo can obtain better reproductive outcomes than one double embryo transfer using blastocysts. In our study, single embryo transfer protocol was also regarded as the major protocol to ensure the better pregnancy outcomes. In addition, it was easy to find the total clinical pregnancy rates and live birth rates of patients still stayed at low level regardless what measures had been taken.
In this study, GnRH-a did not show obvious effect of improving pregnancy outcomes. We came up with several reasons to explain this phenomenon. Firstly, the current cycles of GnRH-a was not enough for patients with adenomyosis so that the effects of the drug did not work. We failed to get the information of the degree of adenomyosis between the two groups, maybe many patients did not suffer from severe adenomyosis, and it may be another reason leading to the negative result in GnRH-a improving pregnancy outcomes. Furthermore, we can consider whether patients was not sensitive to GnRH-a resulting in uterus not changing much, or GnRH-a did not work at all.
One advantage of our study was that the number of women with adenomyosis was relatively large, including patients in a time span of six years. In addition, according to 2018 specialist consensus published in Journal of Reproductive Medicine, the number of embryo transfer was no more than two under 40 years and single embryo transfer was recommended. In our study, single embryo transfer constitutes the vast majority and the others were double embryo transfer, which was consistent with consensus. This two advantages made this study applicative for more population with adenomyosis. Apart from that, we also found that good reproductive outcomes still stayed at a low level although different measures had been taken, which meant many new explorations needed to be done to improve reproductive outcomes for women with adenomyosis.
Two obvious defects existed in this study. Firstly, this study did not analysis the duration of GnRH-a for women with adenomyosis. If patients could get enough duration of GnRH-a down-regulation, the attachment of high quality follicles will be affected as most of our patients only underwent only once GnRH-a down-regulation. In addition, the severity of adenomyosis did not be discussed, which may be influence therapeutic effect in a way. These questions both needed to be studied in the future.
Although many studies thought that administrating GnRH agonists was very beneficial for patients of adenomyosis in improving reproductive outcomes of IVF-ET, our study did not demonstrate advantages of adding GnRH agonists based on hormone replacement therapy cycle. Similiar negative conclusions were also shown in endometriosis[10-12]. In addition, Movahedi S et al. did a study that Endometrial preparation for FET using GnRH agonists appeared to be as effective as FET without administrating these agonists. The other two articles also did not think that GnRH-a down-regulation showed any significant advantages of IVF-ET[27-28]. Those all provided some supportive evidence for our study result.
In conclusion, patients with adenomysis carried out GnRH-a down regulation or not based on hormone replacement therapy cycle had similar reproductive outcomes. Adding GnRH-a based on hormone replacement therapy cycle may not increase the rates of clinical pregnancy and live birth.