ABT888 br Acknowledgments br Introduction Oocyte donation ha
Introduction Oocyte donation has increasingly been used as an option for infertile women with preserved ovarian function but expected poor outcomes, e.g. low responders to standard ovarian stimulation and women who have experienced repeated implantation failure. Transfer of embryos to the recipient in the temporal period of maximal endometrial receptivity is achieved by synchronizing donor and recipient, usually by administration of a single long-acting gonadotrophin releasing hormone (GnRH) agonist injection in the mid-luteal phase of the previous ABT888 followed by unopposed oestrogen administration until the donor is ready for oocyte retrieval (Remohi et al., 1994, Borini et al., 1995, Glujovsky et al., 2010) Devroey and Pados, 1998. Accidental exposure to GnRH agonist coinciding with an implanting spontaneous pregnancy is infrequent (0.6–6%) among these patients (Platteau et al., 2000a, Platteau et al., 2000b, Tan et al., 2006); however, according to the US Food and Drug Administration, this drug belongs to category X (Food and Drug Administration 1980, Cahill et al., 1994). Although no increased risk of teratogenic effects of GnRH agonists compared with the general population (1.67–2.1%) have been reported, nor an increase in miscarriage rates (22–28%) (; Platteau et al., 2000), some studies have shown a slightly increased incidence of ectopic pregnancies (5.86–9%) (Cahill et al., 1994, Platteau et al., 2000b, Tan et al., 2006). Long-term follow-up of children born after inadvertent administration of an agonist during early pregnancy suggests a possible increased incidence of neurodevelopmental abnormalities, such as epileptic disorder, attention deficit hyperactivity disorder, dyslexia, motor difficulties and speech difficulties (Lahat et al., 1999, Papanikolaou et al., 2005, Tan et al., 2006). Use of GnRH antagonists allows an immediate suppression of the pituitary–gonadal axis, with a rapid reversible suppression and the lack of an initial stimulatory effect seen in agonists (). Furthermore, its short half-life avoids the occurrence of undesirable effects of GnRH agonists if a cycle is cancelled after the start of endometrial priming. Administration of GnRH antagonist reduces endometrial priming time, does not induce cyst formation, does not result in symptoms of oestrogen deprivation and also allows self-administration (). Different studies have explored multiple antagonist administration in the early follicular phase (Sagnella et al., 2009, Blockeel et al., 2011, Garcia-Velasco et al., 2012), achieving a delay in follicular growth caused by the suppression of FSH and LH concentrations (). Moreover, our studies comparing agonists and antagonists on endometrial development in terms of gene expression profiles during the window of implantation have shown that the similarity of the endometrium to the natural cycle is closer in antagonist than in agonist cycles (). With this background in mind, we questioned whether an antagonist, instead of an agonist, could be used to synchronize donors and recipients. This approach would permit the administration of the antagonist GnRH beginning after menses rather than in the mid-luteal phase, avoiding many inconveniences such as delayed menstruation, inadvertent exposure to a pregnancy, flare up, longer treatment, menopause-related symptoms and persistent follicular cysts (). Therefore, our aim was to test the hypothesis that administration of a GnRH antagonist in the very early stages of the follicular phase for a pituitary blockade and simultaneous endometrial priming to synchronize donors and recipients in oocyte donation programmes would result in improved oocyte donation outcome. To this end, a prospective, randomized study was designed.
Materials and methods
Results A flowchart of patient participation is presented in . After receiving the GnRH analogue, a percentage of cycles were cancelled in both groups without statistically significant differences (16.5% in group A and 11.4% in group B). The most frequent cause of cycle cancellation was endometrial bleeding before donation (6.8% in antagonist group and 3.7% in agonist group; not significantly different). In group A, patients who were not delayed took oestrogen therapy from day 1 of their cycle until day 3, and initiated patches on day 1 at the same time as antagonist GnRH administration; similar endometrial bleeding (11/278 [4%]) was observed to those taking agonist suppression. Another reason for cycle cancellation was inadequate endometrium, which included polyps, insufficient endometrial thickness, synechia, submucosal myoma and Müllerian defects diagnosed during endometrial priming, none of which are related to the type of GnRH administered.