Endometrial receptivity following early start and single dose of GnRH antagonists in patients with PCOS

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To compare the effects of 2 GnRH antagonist protocols (Fixed and single dose) on endometrial receptivity using immunohistochemical criteria of epithelial integrin expression in PCOS patients. Prospective randomized clinical study. Infertile PCOS women who were randomized to fixed (0.25 started on day 6, n:4), and single dose(3mg started when the leading follicle>15 mm, n:5) regimens of GnRH antagonist(cetrorelix 0.25 and 3). All received rFSH(follitropin alpha) 150 IU starting on menstrual day 2. Endometrial biopsy was obtained 3 days after oocyte retrieval. Immunohistochemical staining intensity and distribution (HSCORE) of αvβ3 subunit integrins and traditional histologic endometrial dating were compared. There were no significant differences among the groups with respect to baseline characteristics. Although both protocols produced similar folliculogenesis, the changes in endometrial receptivity as determined by integrin positivity and HSCORE were better in the fixed protocol (integrin positivity 4 vs 2 respectively). The androgen levels and progesterone on day of HCG and later were greater in the single dose protocol. Eight of the 9 endometrial samples were in phase histologically, distributed similarly through the 2 patient groups(all advanced 1–2 days). Integrin αvβ3 expression was not predicted by in-phase histology, with integrin staining low in all three groups). Just as presence of integrin was not associated with in-phase histology, neither was intensity of integrin staining as measured by the mean HSCORE. Although both protocols were similar in follicular recruitment in PCOS, endometrial receptivity and luteal hormonal mileu were not similarly enhanced. High LH levels at initiation of the cycle and increased androgens may be better suppressed earlier by fixed protocol than single dose. The above changes together with increased exposure to FSH in the single dose group may be the cause of suboptimal endometrium and implantation in PCOS. Although data with antogonist and PCO are limited further trials may outline the exact interaction between the hormonal characteristics of PCO and use of antagonists. Thus may explain the observation of reduced implantation or high miscarriage rates in PCOS patients who conceive with conventional COH with or without GnRH-a.