RESUMEN
Background: Elective freezing of all embryos, followed by frozen-thawed ET cycles emerged to prevent risk of Ovarian Hyperstimulation Syndrome and to allow endometrium recovery after Controlled Ovarian Stimulation, leading to better IVF outcomes. Blastocyst Freeze-all policy can minimize the number of abnormal embryos and consequently failed ETs, but its efficacy in terms of cumulative rates has not been studied yet. Methods: A prospective cohort observational study was carried out in Assisting Nature, Center of Assisted Reproduction and Genetics, in Thessaloniki, Greece from January 2014 until December 2017. 244 patients- normal or high responders- underwent COS with recFSH and Freeze-all policy with blastocyst culture. The included patients were 18-39 years and achieved clinical pregnancy and/or live birth or had all their vitrified blastocysts transferred in subsequent frozen-thawed cycles. Women were divided into four groups (group A: 1-2 blastocysts frozen; group B: 3-4; group C: 5-6; group D ≥7 blastocysts frozen) or seven groups (group I: 1-2 blastocysts frozen, group II: 3, group III: 4, group IV: 5, group V: 6, group VI: 7; group VII: ≥8 blastocysts frozen), according to the numerical range or to the absolute number of vitrified blastocysts, respectively. Results: The main outcome of the study was the CLBR achieved by frozen-thawed ETs, according to the number of the vitrified blastocysts. Higher CLBR are expected, when at least 3 blastocysts are formed (group B: 65.2%) and at least 2 frozen-thawed ETs are performed, reaching highest rates (88%) by group D (≥7 vitrified blastocysts). Similarly, CLBR is significantly increasing with the absolute number of the vitrified blastocysts, ranging from 20%, when 1-2 blastocysts are vitrified (group I) to 82.4% when ≥8 blastocysts are available. Conclusions: A higher number of vitrified blastocysts is associated with higher CLBR in women <40 years old- normal/high responders- following Freeze-all policy. Adopting Freeze-all strategy after blastocyst culture can contribute to improve delivery outcome after IVF, in terms of CLBR. The number of the total cryopreserved blastocysts produced might reflect the quality of the oocyte and can successfully predict the pregnancy outcome. The blastulation rate can be a robust criterion to segment or not an IVF cycle.
RESUMEN
INTRODUCTION: A drawback of gonadotropin-releasing hormone (GnRH) antagonist protocols in in vitro fertilization (IVF) is that they have limited flexibility in cycle programming. This proof of concept study explored the efficacy of a single-dose, long-acting GnRH antagonist IVF protocol. Trial registration number is NCT03240159, retrospectively registered on March 08, 2017. MATERIALS AND METHODS: The efficacy of a single-dose long-acting antagonist, degarelix, was explored initially in healthy donors and subsequently in infertile patients. In the first part, five healthy oocyte donors underwent ovarian stimulation with this new protocol: in the late luteal phase, at day 24, a bolus injection of degarelix was administered subcutaneously to control the LH surge in the follicular phase. Ovarian stimulation with gonadotropins was initiated subsequently from day 7 to day 10. End points were first to inhibit the LH surge later in the follicular phase and, second, to retrieve mature oocytes for IVF. In the second part, five infertile women received the same bolus injection of degarelix administered during the luteal phase at day 24. Different gonadotropin starting days (day 2 through day 8) were tested in order to observe possible differences in ovarian stimulation. In these infertile patients, fresh embryo transfers were performed to assess the pregnancy efficacy of this protocol on pregnancy outcomes and to address any possible negative effects on endometrium receptivity. RESULTS: In the first part of the study, all donors were effectively downregulated with a single luteal dose of 0.5 ml of degarelix for up to 22 days until the final oocyte maturation triggering day. Mature oocytes were retrieved after 36 h from all patients and all produced 2-7 blastocysts. In the second part, all five infertile patients achieved sufficient LH downregulation and completed ovarian stimulation without any LH surge. All patients (except one with freeze all strategy) had blastocysts transferred and pregnancy occurred in three out of five women. CONCLUSION: A single dose of the long-acting antagonist degarelix during the luteal phase appears to be effective in downregulating hypophysis during ovarian stimulation. This represents a possible new protocol for IVF, which should be further elucidated in RCTs.
