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      Ovarian hyperstimulation syndrome: a clinical report on 4894 consecutive ART treatment cycles

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          Abstract

          Background

          Although a large number of studies have been dedicated to ovarian hyperstimulation syndrome (OHSS) none gave full embryological and clinical outcomes comparing oocyte trigger with human chorionic gonadotrophin (HCG) versus with a gonadotrophin-releasing hormone (GnRH) agonist (Buserelin) in cases with suspicious OHSS. The aim of the present study was thus to analyze 4894 consecutive assisted reproductive treatment cycles to undercover associated risk factors for development of OHSS, and the effects of the use of Buserelin as ovulation trigger on embryological and clinical outcomes.

          Methods

          In the 51 cases that developed OHSS, ovulation trigger was performed with HCG as indicators were not suspicious for OHSS. These were compared against two types of groups: 71 cases where Buserelin was used for ovulation induction due to suspicious development of OHSS; and those remaining 4772 cases where ovulation trigger was currently performed with HCG (control).

          Results

          Of the cases treated with Buserelin the oocyte maturation rate and the ongoing pregnancy rate were significantly lower, with higher rates of ectopic pregnancy and newborn malformations, but none developed OHSS. Of the OHSS cases, 23 needed hospitalization, with no major complications.

          Conclusions

          Young age, lower time of infertility, lower basal follicle stimulating hormone levels, higher number of cases with female factor and polycystic ovarian syndrome, high number of follicles and higher estradiol concentrations were the risk factors found associated with OHSS. Cases with OHSS also presented higher follicle count but the estradiol levels were within the normal range. It thus remains to develop more strict criteria to avoid all cases with OHSS.

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          Most cited references25

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          Incidence and prediction of ovarian hyperstimulation syndrome in women undergoing gonadotropin-releasing hormone antagonist in vitro fertilization cycles.

          To determine the incidence of ovarian hyperstimulation syndrome (OHSS) in a large series of GnRH antagonist-stimulated cycles and to assess the predictive value of E2 and the number of follicles on the day of hCG administration. Prospective cohort study of women undergoing IVF treatment with a GnRH antagonist protocol over a 2-year period. Tertiary university hospital. One thousand eight hundred one patients who underwent 2,524 cycles. Multifollicular ovarian stimulation with recombinant FSH and GnRH antagonist for IVF-ICSI treatment. Incidence of OHSS in GnRH antagonist cycles, predictive value of E2, and number of follicles on the day of hCG for OHSS occurrence. Fifty-three patients were hospitalized because of OHSS (2.1%; 95% confidence interval [CI]:1.6-2.8). Early OHSS presented in 31 patients (1.2%; 95% CI: 0.9-1.8), whereas the late type was a complication in 22 patients (0.9%; 95% CI: 0.5-1.3). Late OHSS cases compared with the early OHSS cases always occurred in a pregnancy cycle (100% vs. 40%); had higher probability of being severe (72.7% vs. 42%), and more often were related to a multiple pregnancy (40% vs. 0). Receiver operating characteristic curve analysis for several E2 concentrations and number of follicles with a diameter of > or =11 mm revealed that the predictive value of the optimal threshold of > or =13 follicles (85.5% sensitivity; 69% specificity) was statistically significantly superior to the optimal threshold of 2,560 ng/L for E2 concentrations (53% sensitivity, 77% specificity) in identifying patients at risk for OHSS. Considering that severe OHSS represents the most clinically significant pattern, the combination of a threshold of > or =18 follicles and/or E2 of > or =5,000 ng/L yields a 83% sensitivity rate with a specificity as high as 84% for the severe OHSS cases. Clinically significant OHSS still remains a limitation of multifollicular ovarian stimulation for IVF even with the use of GnRH antagonist protocols. The number of follicles can discriminate the patients who are at risk for developing OHSS, whereas E2 concentrations are less reliable for the purpose of prediction. There is more than ever an urgent need for alternative final oocyte maturation-triggering medication.
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            GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

            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. 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. 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)]. 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.
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              1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction: a prospective, randomized, controlled study.

              To prospectively assess the reproductive outcome with a small bolus of hCG administered on the day of oocyte retrieval after ovulation induction with a GnRH agonist (GnRHa). Prospective, randomized trial. Three hospital-based IVF clinics. Three hundred five IVF/intracytoplasmic sperm injection patients after a GnRH antagonist protocol. Ovulation induction was performed with either 10,000 IU hCG or 0.5 mg GnRHa (buserelin) supplemented with 1,500 IU hCG on the day of oocyte retrieval. Reproductive outcome in the two groups. No significant differences were seen regarding positive hCG/ET rate (48% and 48%), ongoing pregnancy rate (26% and 33%), delivery rate (24% and 31%), and rate of early pregnancy loss (21% and 17%) between the GnRHa and 10,000 IU hCG groups, respectively. A small bolus of hCG in the GnRHa group secured the luteal phase, resulting in a comparable reproductive outcome in the two groups. However, a nonsignificant difference of 7% in delivery rates justifies further studies to refine the use of GnRHa for ovulation induction. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                msousa@icbas.up.pt
                marianacunha@hotmail.com
                jmsts8@gmail.com
                cristianojoliveira@hotmail.com
                joaquinapsilva@gmail.com
                paulo.viana@gmail.com
                abarros@med.up.pt
                Journal
                Reprod Biol Endocrinol
                Reprod. Biol. Endocrinol
                Reproductive Biology and Endocrinology : RB&E
                BioMed Central (London )
                1477-7827
                23 June 2015
                23 June 2015
                2015
                : 13
                : 66
                Affiliations
                [ ]Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
                [ ]Multidisciplinary Unit for Biomedical Research-UMIB, ICBAS-UP, Rua Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
                [ ]Centre for Reproductive Genetics Alberto Barros, Av. do Bessa, 240, 1° Dto. Frente, 4100-012 Porto, Portugal
                [ ]Department of Genetics, Faculty of Medicine, University of Porto (FMUP), Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
                [ ]Institute of Health Research an Innovation, University of Porto, Porto, Portugal
                Article
                67
                10.1186/s12958-015-0067-3
                4477314
                26100393
                3303bbf3-f9ad-4a7f-8f1e-6d7bc3bccb57
                © Sousa et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 March 2015
                : 17 June 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Human biology
                gonadotrophin-releasing hormone agonist,icsi,ivf,ovarian hyperstimulation syndrome,embryological,clinical and newborn outcomes

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