Moreover there is a third possible GnRH agonist target
Moreover, there is a third possible GnRH agonist target – the endometrium. The human endometrium has been shown to express high levels of both GnRH and GnRH receptors (Maggi et al., 2016), and GnRH agonists affect the function of the urokinase-type plasminogen activator/plasminogen activator inhibitor system in human decidual stromal carnosic acid australia (Chou et al., 2003) and regulate the motility of human decidual endometrial stromal cells (Wu et al., 2015).
Availability of data and materials
Ethics approval and consent to participate
Consent for publication
Introduction Three types of endometriosis have been described – peritoneal endometriosis (61% of patients), deep infiltrating endometriosis (DIE, about 6% of patients), and endometrioma (17–50% of patients) – associated or not with adenomyosis , . However, one woman can have more than one type of endometriosis. The severity of endometriosis has been classified into four stages by the American Society of Reproductive Medicine (ASMR): minimal (stage I), mild (stage II), moderate (stage III) and severe (stage IV). However, this classification does not take into account the presence of DIE. Subsequently, additional classifications, such as ENZIAN staging or scoring systems, such as the Endometriosis Fertility Index (EFI) have been advocated to assess the extent of the disease and to estimate the chances of pregnancy . Although the impact of endometriosis on fertility is well established, the exact pathophysiology remains unclear. It has been suggested that inflammation and oxidative stress might impact the quality of the oocyte , the ovarian reserve and the quality of the embryo , . The implantation process might also be altered in endometriosis  although this hypothesis has been challenged by good results obtained in oocyte recipients with endometriosis , . Two options are available for women with endometriosis-associated infertility: surgery or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). In certain types of endometriosis, surgery can be effective in enhancing spontaneous pregnancies but with a risk of complications, especially in women with DIE , , . Conversely, although pregnancy and implantation rates in stage III/IV are lower compared to women without endometriosis , , first intention IVF/ICSI is an option for patients who refuse surgery or after failure of spontaneous pregnancy. Clinical pregnancy rates comprised between 29% and 68% , ,  can be obtained with IVF/ICSI that is similar to those obtained in women with tubal infertility , . Once IVF/ICSI decided, the choice of the controlled ovarian hyperstimulation (COH) protocol remains debatable. A Cochrane meta-analysis has demonstrated that prolonged pituitary downregulation with a gonadotropin releasing hormone (GnRH) agonist for at least three months before starting a GnRH-agonist long protocol (ultra-long protocol) increases the pregnancy rate by at least four-fold in women with endometriosis . De Ziegler et al. used oral estro–progestin contraception (OC) at least six weeks before the beginning of the COH to suppress ovarian function and found an improvement in the pregnancy rate . Finally, Pabuccu et al. reported no difference in the pregnancy rate between GnRH-agonist and GnRH-antagonist protocols, but more mature oocytes after GnRH-agonist protocol .
Materials and methods
Discussion These results are similar to those of the first meta-analysis published by Al-Inany and Aboulghar comparing GnRH-antagonists to GnRH-agonists in the general population . The authors found the GnRH-antagonist protocol less advantageous, with an overall OR for clinical pregnancy per woman of 0.79 [CI 0.63–0.99], per oocyte retrieval of 0.77 [CI 0.61–0.96] and per embryo transfer of 0.76 [CI 0.60–0.97]. However, several recent meta-analyses ,  comparing the two protocols in the general population did not find any difference either in clinical pregnancy or live-birth rates. The last meta-analysis published in 2016  confirmed the absence of difference with an OR of 0.92 [CI 0.83–1.01] for the clinical pregnancy rate and an OR of 1.02 [CI 0.85–1.23] for the live-birth rate.