Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product.

INTRODUCTION: In vitro or in vivo depletion of alloreactive T cells can facilitate haplo-identical hematopoietic stem cell transplantation (HSCT). Very satisfactory transplant outcomes were thus reported for TCRαß/CD19-depleted hematopoietic stem/progenitor cell (HSPC) grafts. The current semi-automatic manufacturing process on the CliniMACS Plus, although robust, still requires a significant amount of manual labor to be completed. Towards advancing and further facilitating large scale cell processing, a new TCRαß/CD19 depletion module combined with the previously described CD45RA depletion module (to serve as allo-reactivity attenuated donor lymphocyte infusion) was established on the CliniMACS Prodigy. METHODS: We evaluated six apheresis products from G-CSF-mobilized volunteer donors which were split automatically by the Prodigy, one portion each depleted of CD45RA+ or of TCRαß+ and CD19+ cells. We investigated critical quality attributes for both products. Products were assessed for recovery of HSPCs and mature subsets, as well as depletion efficiency of targeted cells using flow cytometry. Effects of apheresis and product age post 48 h storage at 2-6 °C as well as freeze-thawing on product viability and recovery of WBC and HPSCs were assessed by flow cytometry. RESULTS: Ten sequential automatic processes were completed with minimal hands-on time beyond tubing set installation. Depletion efficiency of CD45RA+ resp. TCRαß+ and CD19+ cells was equivalent to previous reports, achieving mean depletions of 4 log of targeted cells for both products. HSPC products retained TCRγδ+ and NK cells. 48 h storage of apheresis product was associated with the expected modest loss of HSPCs, but depletions remained efficient. Depleted products were stable until at least 72 h after apheresis with stem cell viabilities > 90%. Freeze-thawing resulted in loss of NK cells; post-thaw recovery of viable CD45+ and HSPCs was > 70% and in line with expectation. CONCLUSION: The closed, GMP-compatible process generates two separate medicinal products from the same mobilized apheresis product. The CD45RA-depleted products contained functional memory T cells, whereas the TCRαß/CD19-depleted products included HSPCs, TCRγδ+ and NK cells. Both products are predicted to be effectively depleted of GVH-reactivity while providing immunological surveillance, in support of haplo-identical HSCT.

Is nuchal translucency measurement feasible in early pregnancy?

BACKGROUND: To investigate whether early nuchal translucency measurement at 7+0 to 9+0 weeks (NT7-9w) is feasible, obtain normal values for different crown-rump lengths (CRL) in the above weeks and create percentile tables. METHODS: A prospective study was conducted in the Obstetrics and Gynecology Department of the University Hospital of Ioannina, including data from women with singleton pregnancies, examined in the early pregnancy unit between November 2010 and May 2015 at a CRL of 10-27 mm. The early pregnancy scan was performed vaginally, and the NT7-9w, CRL, fetal heart rate, and mean yolk sac diameter were measured. Demographic data, including body mass index and smoking, were recorded. RESULTS: NT7-9w was measured successfully in 192 fetuses out of 210 (91.4 %), with a CRL ranging from 10-27 mm. The median maternal age was 31 (range 18-43) years, and the median CRL was 19.9 (range 10.0-27.0) mm. Considering the above measurements, we created normal values and percentiles tables of NT at 7+0 to 9+0 weeks in relation to the corresponding CRL measurement. CONCLUSION: According to the literature, this is the first attempt to measure NT in such weeks of pregnancy. NT measurement as early as 7+0 to 9+0 is feasible and normal values can be created and correlated with CRL measurements. HIPPOKRATIA 2021, 25 (4):151-155.

"Follicular HCG endometrium priming for IVF patients experiencing resisting thin endometrium. A proof of concept study".

PURPOSE: A thin endometrium is one of the most difficult problems encountered in assisted reproduction every day practice. Whether a daily dose of 150 IU HCG for 7 days concomitant with estrogen administration in estrogen replacement cycles can increase the endometrial thickness and improve pregnancy outcome, was the objective of the current study. METHODS: Seventeen infertile patients with successive implantation failures and resisting thin endometrium, being recipients of fresh donor or frozen embryos were recruited. This was a prospective cohort, proof of concept study, NCT01768247. On day-8 or 9 of the estrogen administration, and continuing 8 mg estrogen per day, subcutaneous injections of 150 IU HCG were initiated daily for 7 days. After a week on HCG priming, (day-14 or 15) endometrial thickness was controlled with ultrasound, and progesterone was initiated. RESULTS: Mean endometrial thickness was increased from 5.2 mm to 6 mm (p = 0.008). 35.3 % of the patients had more than 20 % improvement of their endometrial thickness after HCG priming. 17 % achieved an endometrial thickness more than 7 mm, and 29.4 % did not improve their thickness at all. Interestingly, from the later two became pregnant. Overall, 41 % of them (7/17) finally delivered. CONCLUSIONS: One hundred fifty IU HCG endometrial priming for 7 days in the proliferative phase of estrogen substituted cycles for frozen embryos is highly promising, as not only the thickness of the endometrium improves but also eventually the receptivity appears normalized.

Towards more successful gene therapy clinical trials for ß-thalassemia.

ß-thalassemias constitute hereditary blood disorders characterized by reduced or absence of ß-globin synthesis resulting in mild to severe anemia, depending on the genotype. More than 200 mutations in the ß-globin gene are responsible for their specific features leading to a very heterogeneous phenotype. Current therapies for ß-thalassemia include blood transfusions, usually along with iron chelation and in selected cases with bone marrow transplantation (BMT) of HLA-matched hematopoietic stem cells (HSCs). However, these approaches are limited by factors, such as iron overload and donor availability, respectively. Since 2000, when globin lentiviral vectors (LVs) were first successfully tested for transfer efficiency of the therapeutic transgene, which led to disease amelioration in murine models, attention was drawn towards the improvement of such vectors for ß-thalassemia gene therapy. Constantly improving vector design and efficient HSC manipulation led recently to the first successful clinical trial in France, which further proved that this genetic approach can be curative. Furthermore, improved new efficient vectors and methods to safely monitor integration sites and therapeutic transgene position effects, promise a new era for ß-thalassemia gene therapy, with more and safer clinical trials yet to come.

GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients.

STUDY QUESTION: Does a GnRH agonist (GnRHa) trigger followed by a bolus of 1.500 IU hCG in a group of patients at risk of ovarian hyperstimulation syndrome (OHSS) reduce the OHSS incidence compared with hCG trigger? SUMMARY ANSWER: A GnRHa trigger followed by early luteal hCG support with one bolus of 1.500 IU hCG appears to reduce OHSS in patients at risk of OHSS; however, in a low-risk group a second bolus of 1.500 IU hCG induced two cases of late onset OHSS. WHAT IS KNOWN ALREADY: A GnRHa trigger is an alternative to hCG in GnRH antagonist co-treated cycles. STUDY DESIGN, SIZE, DURATION: Two RCTs were performed in four Danish IVF units. A total of 446 patients were assessed for eligibility and 390 patients were enrolled in the study from January 2009 until December 2011. The primary outcome of the study was OHSS incidence in the group at risk of OHSS. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients received a fixed dose of recombinant human FSH for the first 4 days. On the day of triggering, patients were assessed for their risk of OHSS based on the total number of follicles ≥11 mm diameter, and were classified as being at risk of OHSS when the total number of follicles ≥11 mm was between 15 and 25 and at low risk of OHSS when the total number of follicles ≥11 mm was ≤14. Two separate randomization lists were used for each of the OHSS risk groups. Women at risk of OHSS were allocated (RCT 1) to either: Group A (n = 60), ovulation triggering with a bolus of 0.5 mg buserelin (GnRHa) s.c. followed by a single bolus of 1.500 IU hCG s.c. after the oocyte retrieval-or: Group B (n = 58): 5.000 IU hCG. Similarly, women at low risk of OHSS were allocated (RCT 2) to receive either: Group C (n = 125), a bolus of 0.5 mg buserelin s.c., followed by a bolus of 1.500 IU hCG s.c. after oocyte retrieval and a second bolus of 1.500 IU hCG on the day of oocyte retrieval +5-or: Group D (n = 141), 5.000 IU hCG. Groups C and D were included in order to obtain preliminary data. MAIN RESULTS AND THE ROLE OF CHANCE: In women at risk of OHSS (RCT 1) (15-25 follicles) no OHSS case was seen in Group A (GnRHa trigger and one bolus of 1.500 IU hCG), whereas two cases of moderate late-onset OHSS occurred in group B (3.4%), (P = 0.24). In contrast, in women at a low risk of OHSS (RCT 2) (≤14 follicles) two cases of late-onset OHSS occurred in Group C (GnRHa trigger and two boluses of 1.500 IU hCG), whereas no OHSS case was encountered in Group D (P = 0.22). LIMITATIONS, REASONS FOR CAUTION: Although the first RCT was powered to include 168 patients at risk of OHSS (15-25 follicles ≥11 mm) randomized to either GnRHa trigger or hCG trigger, the trial was prematurely discontinued when a total of 118 patients at risk of OHSS were randomized. In addition the second RCT in the OHSS low-risk group was designed as a feasibility study to assess the incidence of OHSS after GnRHa trigger and dual hCG administration versus 5.000 IU hCG. No power calculation was performed for this trial. In addition, there was a lack of blinding in the RCTs. WIDER IMPLICATIONS OF THE FINDINGS: Although a non-significant result, one bolus of 1.500 IU hCG after GnRHa trigger tended to reduce the OHSS rate in patients with 15-25 follicles ≥11 mm as well as secure the ongoing pregnancy rate. In contrast, in patients at low risk of OHSS the administration of two boluses of 1.500 IU hCG after GnRHa trigger should be avoided as it may induce OHSS.

Misoprostol prior to hysteroscopy in premenopausal and post-menopausal women. A systematic review and meta-analysis.

BACKGROUND: Although several randomized controlled trials (RCTs) have examined the effect of misoprostol prior to hysteroscopy for cervical dilatation, no solid conclusion has been reached. We therefore set out to perform a meta-analysis of RCTs. METHODS: We searched MEDLINE, the ISI Web of Science and the Cochrane Library to identify RCTs comparing misoprostol versus placebo or control prior to hysteroscopy. No restrictions on language or time were applied. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for all dichotomous outcomes, whereas mean differences (MDs) and 95% CIs were calculated for continuous outcomes using the Mantel-Haenszel or DerSimonian-Laird model according to the heterogeneity. RESULTS: Of the initial 141 potentially relevant articles that were retrieved, 21 RCTs involving 1786 patients were included in the meta-analysis. Subgroup analyses were performed according to menopausal status and according to whether diagnostic or operative hysteroscopy was performed. Premenopausal women treated with misoprostol had a significantly lower risk for further cervical dilatation in the diagnostic setting [RR (95% CI): 0.56 (0.34-0.92)] and a significantly lower risk for cervical laceration in the operative setting [RR (95% CI): 0.22 (0.09-0.54)], compared with placebo. In contrast, post-menopausal patients did not experience any clear benefit from misoprostol compared with placebo regarding the need for further cervical dilatation [RR (95% CI): 0.99 (0.76-1.30)] and the cervical laceration rate [RR (95% CI): 1.15 (0.40-3.29)]. In addition, the mean cervical width prior to hysteroscopy was significantly higher in premenopausal women treated with misoprostol compared with placebo [MD (95% CI): 2.47 mm (1.81-3.13)] but did not differ among post-menopausal patients [MD (95% CI): 0.39 mm (-0.42 to 1.21)]. CONCLUSIONS: Misoprostol prior to hysteroscopy appears to facilitate an easier and uncomplicated procedure only in premenopausal women.

GnRH-agonist versus GnRH-antagonist IVF cycles: is the reproductive outcome affected by the incidence of progesterone elevation on the day of HCG triggering? A randomized prospective study.

BACKGROUND: In view of the current debate concerning possible differences in efficacy between the two GnRH analogues used in IVF stimulated cycles, the current study aimed to explore whether progesterone control in the late follicular phase differs when GnRH antagonist is used as compared with GnRH agonist, and if so, to what extent the progesterone rise affects the probability of pregnancy. METHODS: Overall 190 patients were randomized: 94 in the GnRH-agonist group and 96 in the GnRH-antagonist group. The GnRH-agonist long protocol started on Day 21 of the preceding cycle with intranasal buserelin (600 mg per day). The GnRH-antagonist protocol started on Day 6 of the stimulation with ganirelix or cetrorelix (each 0.25 mg). All blood samples were analysed with the Elecsys analyzer. An intention-to-treat analysis was applied. RESULTS: A progesterone rise >1.5 ng/ml was noticed in 23.0% of the antagonist group, comparable with 24.1% incidence within the agonist group. Per patient randomized, delivery rates were also comparable: 28.1% in the antagonist group and 24.5% in the agonist group (odds ratio = 1.21, 95% confidence interval: 0.63-2.31, P= 0.56). However, there was a reduction in delivery rates when progesterone exceeded the threshold of 1.5 ng/ml, both in the agonist group (9.5 versus 31.8%, P= 0.03) and in the antagonist group (14.3 versus 34.3%, P= 0.07). CONCLUSIONS: Although the incidence of a progesterone rise was similar between the two analogues, our findings reconfirm previous observations that insufficient progesterone control (>1.5 ng/ml) on the day of ovulation triggering is related to poor delivery rates in both protocols. The current study has shown that the reproductive outcomes with the two GnRH analogues are comparable. Possible modes of action to circumvent late follicular progesterone rise should be explored. TRIAL REGISTRATION NUMBER: NCT01191710.

The relationship of premature progesterone rise with serum estradiol levels and number of follicles in GnRH antagonist/recombinant FSH-stimulated cycles.

OBJECTIVE(S): To investigate the relationship between premature progesterone (P) rise and serum estradiol (E(2)) levels and the number of follicles in GnRH antagonist/rec-FSH stimulated cycles. STUDY DESIGN: Two hundred and seven patients treated by IVF/ICSI at the Centre for Reproductive Medicine of the Dutch-Speaking Brussels Free University were included in this observational study. They received 200 IU/day rec-FSH from day 2 of the cycle and daily GnRH antagonist starting on day 6 of stimulation. The criteria for hCG administration included the presence of ≥3 follicles of ≥17 mm diameter. Serum P, E(2) and LH were determined on the day of hCG administration. The outcome measure was to identify a threshold of E(2) and number of follicles on the day of hCG administration which would define a progesterone rise on the day of hCG administration (cut-off value of 1.5 ng/ml). RESULT(S): Patients with a P >1.5 ng/ml had significantly higher concentrations of E(2) and increased number of follicles on the day of hCG administration compared to those with P ≤1.5 ng/ml. However, patients with a P >1.5 ng/ml the day of hCG showed lower pregnancy rates than those with P <1.5 ng/ml (17.8 vs. 32.7%, respectively; p<0.05). A ROC curve was employed in order to estimate a cut-off for E(2) on day of hCG >1790.5 pg/ml and more than 9.5 follicles of ≥11 mm in diameter for progesterone rise over 1.5 ng/ml. CONCLUSION(S): A significant impact is shown on progesterone rise by E(2) and number of follicles on the day of hCG administration in GnRH antagonist/rec-FSH-stimulated cycles. With this knowledge, an upcoming progesterone rise during follicular phase can be anticipated and prevented.

The luteal phase after GnRH-agonist triggering of ovulation: present and future perspectives.

In stimulated IVF/intracytoplasmic sperm injection cycles, the luteal phase is disrupted, necessitating luteal-phase supplementation. The most plausible reason behind this is the ovarian multifollicular development obtained after ovarian stimulation, resulting in supraphysiological steroid concentrations and consecutive inhibition of LH secretion by the pituitary via negative feedback at the level of the hypothalamic-pituitary axis. With the introduction of the gonadotrophin-releasing hormone-(GnRH) antagonist, an alternative to human chorionic gonadotrophin triggering of final oocyte maturation is the use of GnRH agonist (GnRHa) which reduces or even prevents ovarian hyperstimulation syndrome (OHSS). Interestingly, the current regimens of luteal support after HCG triggering are not sufficient to secure the early implanting embryo after GnRHa triggering. This review discusses the luteal-phase insufficiency seen after GnRHa triggering and the various trials that have been performed to assess the most optimal luteal support in relation to GnRHa triggering. Although more research is needed, GnRHa triggering is now an alternative to HCG triggering, combining a significant reduction in OHSS with high ongoing pregnancy rates.

Should Cochrane reviews be performed during the development of new concepts?

Cochrane reviews are internationally recognized as the highest standard in evidence-based health care. A Cochrane analysis conducts systematic reviews of primary research in human health care, and the analysis includes a comprehensive search of all potentially relevant studies and the use of explicit, reproducible criteria in the selection of studies for review. Thus, Cochrane reviews, undoubtedly provide many useful clinical guidelines. In this opinion paper, however, it is questioned at what level of clinical development of a new strategy a Cochrane review should be conducted in order not to draw premature conclusions that may not be sustained later on. Previous examples of this are debated together with the most recent Cochrane review regarding GnRH agonist triggering of final oocyte maturation, in which debatable conclusions are drawn from early studies, when the concept was still under development. We question the current policy of meta-analysis and recommend that in the future, the meta-analysts should await the results of a sufficient number of well-performed studies with an established new regime before an analysis is performed in order to avoid too early and possibly biased conclusions.

Autochthonous Plasmodium vivax malaria in Greece, 2011.

Between May and September 2011, twenty cases of Plasmodium vivax infection were reported in Greek citizens without reported travel history. The vast majority of those cases were confined to a delimited agricultural area of Evrotas, Lakonia. Conditions favouring locally acquired transmission of malaria, including the presence of competent vectors and migrants from endemic countries exist in Greece, underscoring the need for the development of an integrated preparedness and response plan for malaria prevention.

Ongoing outbreak of West Nile virus infection in humans, Greece, July to August 2011.

Between 16 July and 21 August 2011, 31 cases of West Nile neuroinvasive disease were reported from four regions in Greece. Of these, 17 occurred in districts that had not been affected in 2010. The reoccurrence of human cases in two consecutive years (following the large 2010 outbreak) and the spread of the virus in new areas suggest that West Nile virus is established in Greece, and its transmission may continue to occur in the future.

GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

BACKGROUND: GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering. METHODS: This narrative review is based on expert presentations and subsequent group discussions supplemented with publications from literature searches and the authors' knowledge. Moreover, randomized controlled trials (RCTs) were identified and analysed either in fresh IVF cycles with embryo transfer (ET), oocyte donation cycles or cycles without ET; risk differences were calculated regarding pregnancy rate and OHSS rate. RESULTS: In fresh IVF cycles with ET (9 RCTs) no OHSS was reported after GnRHa triggering [0% incidence in the GnRHa group: risk difference 5% (with 95% CI: -0.07 to 0.02)]. Importantly, the delivery rate improved significantly after modified luteal support [6% risk difference in favour of the HCG group (95% CI: -0.14 to 0.2)] when compared with initial studies with conventional luteal support [18% risk difference (95% CI: -0.36 to 0.01)]. In oocyte donation cycles (4 RCTs) the OHSS incidence is 0% [10% risk difference (95% CI: 0.02-0.40)]. CONCLUSIONS: GnRHa triggering is a valid alternative to hCG triggering, resulting in an elimination of OHSS. After modified luteal support there is now a non-significant difference of 6% in delivery rate in favour of hCG triggering.

Validation of a numerical code for the simulation of a short-term CO2 release in an open environment: effect of wind conditions and obstacles.

Carbon Capture and Storage (CCS) is one of the possible mitigation measures to reduce the CO(2) emissions produced from anthropogenic sources and thus help address the issue of global warming. Accidental CO(2) releases may occur at any of the CCS stages, having potentially harmful consequences on the people who work in the CCS facilities, the general public in their vicinity and the environment. CFD is an increasingly used tool to investigate the behavior of released substances and predict the consequences of hazardous scenarios. This information aids the development of mitigation methods to minimize the consequences of an accident. The validation of numerical codes and models is a necessary preliminary step before their application to safety and risk assessment analysis. In this context, numerical simulations of CO(2) release and dispersion field experiments were performed with a CFD code. The experimental data were taken from the Kit Fox CO(2) gas field experiments which were designed to investigate the effect of ground roughness of industrial process plants and of meteorological conditions on the formation and extent of the CO(2) gas cloud. This study presents a comparison between the simulation results and the experimental measurements in order to assess the accuracy of the code with different modeling approaches.

Does cessation of progesterone supplementation during early pregnancy in patients treated with recFSH/GnRH antagonist affect ongoing pregnancy rates? A randomized controlled trial.

BACKGROUND: The aim of this study was to assess whether the cessation of progesterone (P) supplementation during early pregnancy after GnRH antagonist cycles is not inferior to its continuation in terms of pregnancy rates beyond 12 weeks of gestation METHODS: There were 200 patients, with a positive ß-hCG test (followed by a doubling in ß-hCG levels 48 h later) after a fixed recombinant FSH (recFSH)/GnRH antagonist protocol for IVF/ICSI and a Day-3 fresh embryo transfer (ET), participated in this randomized controlled study. All patients received luteal support, with 200 mg vaginal P being administered three times daily for 14 days, beginning on the day of ET until the second ß-hCG test, 16 days post-ET. In the control group (n = 100) the administration of P was continued until 7 weeks of gestation. In the study group (n = 100), vaginal P was discontinued on the 16th day post-ET RESULTS: The ongoing pregnancy rate beyond 12 weeks, the primary outcome measure, did not differ between the study and control groups (82 versus 73%, P = 0.175; difference 9%, 95% CI: -2.6 to 20.3). There were also no significant differences observed between the study and control group in terms of abortion before or after 7 weeks of gestation [(9 versus 12%, P = 0.645) and (8 versus 10%, P = 0.806), respectively]. The same was true for bleeding episodes (14 versus 19%, P = 0.446). CONCLUSIONS: After recFSH/GnRH antagonist cycles, the withdrawal of P supplementation in early pregnancy, with normally increasing ß-hCG levels on the 16th day post-ET, had no significant clinical impact in terms of ongoing pregnancy rates beyond 12 weeks.

Endometrial advancement after triggering with recombinant or urinary HCG: a randomized controlled pilot study.

More than 3 days' luteal endometrial advancement in IVF has been related with no pregnancies. This study assessed the effect of recombinant and urinary human chorionic gonadotrophin (recHCG and uHCG) when administered for final oocyte maturation on the advancement of endometrial histology. Thirty patients were randomized to receive either 250 microg recHCG or 10,000 IU uHCG in an antagonist/recombinant FSH protocol. Endometrial biopsy was performed on the day of oocyte retrieval. All specimens were evaluated according to Noyes' criteria by one pathologist blinded to the allocation treatment groups. Single blastocyst transfer was performed. Overall, 13 patients in recHCG group and 14 patients in uHCG group underwent endometrial biopsy. The mean days of histological endometrial advancement were comparable between the two groups: 2.03 versus 2.17days, respectively. Nevertheless more patients (69%, 9/13) had less than 3 days' advanced endometrium in the recHCG arm as compared with 43% (6/14) patients in the uHCG group (OR 3.00, 95% CI 0.4-16.3). The delivery rate per patient was higher, although not significantly, in the recHCG group (38.5% versus 28.6%). Both recHCG and uHCG preparations induce advancement of endometrial maturation. Whether a subtle difference in endometrial maturation affects the reproductive outcome remains to be proven.

GnRHa to trigger final oocyte maturation: a time to reconsider.

Recently GnRH antagonist protocols for the prevention of a premature LH surge were introduced, allowing final oocyte maturation to be triggered with a single bolus of a GnRH agonist (GnRHa). GnRHa is as effective as hCG for the induction of ovulation, and apart from the LH surge a FSH surge is also induced. Until recently, prospective randomized studies reported a poor clinical outcome when GnRHa was used to trigger final oocyte maturation in IVF/ICSI antagonist protocols, presumably due to a luteal phase deficiency, despite standard luteal phase supplementation with progesterone and estradiol. As GnRHa triggering of final oocyte maturation could possess advantages over hCG triggering in terms of a reduced if not eliminated risk of ovarian hyperstimulation syndrome (OHSS) and the retrieval of more mature oocytes, the challenge has been to rescue the luteal phase. In the literature now several studies report a luteal phase rescue with a reproductive outcome comparable to that of hCG induced final oocyte maturation. Although more research is needed, GnRHa triggering is now a valid alternative with potential benefits.