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.

BackgroundOculocerebrorenal syndrome of Lowe is an X-linked disorder with very low prevalence in the general population. The OCRL gene encodes the protein phosphatidylinositol 4,5-bisphosphate-5-phosphatase, a lipid phosphatase, located in the trans-Golgi network. Point mutations in the OCRL gene cause Lowe syndrome and Dent disease, which are characterized as a multisystemic disorder. The symptoms of Lowe syndrome are expressed primarily as dysfunction of the eyes, kidneys, and the central nervous system.Case presentationThis report describes a case of a 31-year-old Georgian woman with a de novo pathogenic mutation causing oculocerebrorenal syndrome of Lowe, who was a volunteer in an oocyte donation program for in vitro fertilization purposes, and the outcome of the treatments of this particular donor’s oocyte receivers, describing the implications of the mutation for the children born as a result of the treatments. It raises important medical and ethical issues about the necessity of genetic testing of oocyte donors and the possibility of rare genetic disorders being inherited by the offspring of donors.ConclusionThis particular case indicates the legal, medical, and emotional risks of utilizing donor oocytes from phenotypically healthy women, whose genetic constitution is unknown in terms of being silent carriers of rare diseases. In addition, all the necessary actions were followed; the further examinations that are required are mentioned. The donor and the offspring should be further tested. The remaining cryopreserved embryos should be destroyed or preimplantation genetic testing should be performed before they are utilized. Finally, all the people involved, the treated couples and the donor, alongside her family, should follow genetic and psychological counselling.

Objective: In order to help make the dream of parenthood come true for oocyte acceptors, it is essential that the procedure is not dangerous or unpleasant for oocyte donors. The aim of this study was to identify differences in safety, efficacy and patient acceptability between a traditional stimulation antagonist protocol with recombinant-FSH (rFSH) with hCG-triggering, compared with an innovative antagonist protocol with corifollitropin alfa (Elonva ® ) plus GnRH agonist triggering in oocyte donors. Methods: A prospective longitudinal study was conducted at an in vitro fertilization center in Greece. The same eighty donors underwent two consecutive antagonist stimulation schemes. Primary outcomes were patient satisfaction (scored by a questionnaire) and delivery rate per donor. Secondary outcomes were mean number of cumulus-oocyte-complexes, metaphase II (MII) oocytes and ovarian hyperstimulation syndrome (OHSS) rate. Results: Donors reported better adherence and less discomfort with the corifollitropin alpha + GnRH agonist-triggering protocol ( p <0.001). No significant differences were identified in the clinical pregnancy rate per donor ( p =0.13), the delivery rates, the number of oocytes ( p =0.35), the number of MII oocytes ( p =0.50) and the number of transferred embryos, between the two protocols. However, the luteal phase duration was significantly shorter ( p <0.001) in the corifollitropin alpha + GnRH agonist-triggering protocol. Moreover, three cases of moderate OHSS (3.75%) were identified after hCG triggering, whereas no case of OHSS occurred after GnRH agonist ovulation induction ( p =0.25). Conclusion: The use of corifollitropin alpha combined with a GnRH agonist for triggering is a safe, effective and acceptable protocol for oocyte donors.

Oocyte donation programs involve young and healthy women undergoing heavy ovarian stimulation protocols in order to yield good-quality oocytes for their respective recipient couples. These stimulation cycles were for many years beset by a serious and potentially lethal complication known as ovarian hyperstimulation syndrome (OHSS). The use of the short antagonist protocol not only is patient-friendly but also has halved the need for hospitalization due to OHSS sequelae. Moreover, the replacement of beta-human chorionic gonadotropin (b-hCG) with gonadotropin-releasing hormone agonist (GnRH-a) triggering has reduced OHSS occurrence significantly, almost eliminating its moderate to severe presentations. Despite differences in the dosage and type of GnRH-a used across different studies, a comparable number of mature oocytes retrieved, fertilization, blastulation, and pregnancy rates in egg recipients are seen when compared to hCG-triggered cycles. Nowadays, GnRH-a tend to be the triggering agents of choice in oocyte donation cycles, as they are effective and safe and reduce OHSS incidence. However, as GnRH-a triggering does not eliminate OHSS altogether, caution should be practiced in order to avoid unnecessary lengthy and heavy ovarian stimulation that could potentially compromise both the donor’s wellbeing and the treatment’s efficacy.

IntroductionA 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 methodsThe 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.ResultsIn 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.ConclusionA 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.