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      Predicting and preventing ovarian hyperstimulation syndrome (OHSS): the need for individualized not standardized treatment

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          Abstract

          Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of controlled ovarian stimulation (COS) as part of assisted reproductive technologies (ART). While the safety and efficacy of ART is well established, physicians should always be aware of the risk of OHSS in patients undergoing COS, as it can be fatal. This article will briefly present the pathophysiology of OHSS, including the key role of vascular endothelial growth factor (VEGF), to provide the foundation for an overview of current techniques for the prevention of OHSS. Risk factors and predictive factors for OHSS will be presented, as recognizing these risk factors and individualizing the COS protocol appropriately is the key to the primary prevention of OHSS, as the benefits and risks of each COS strategy vary among individuals. Individualized COS (iCOS) could effectively eradicate OHSS, and the identification of hormonal, functional and genetic markers of ovarian response will facilitate iCOS. However, if iCOS is not properly applied, various preventive measures can be instituted once COS has begun, including cancelling the cycle, coasting, individualizing the human chorionic gonadotropin trigger dose or using a gonadotropin-releasing hormone (GnRH) agonist (for those using a GnRH antagonist protocol), the use of intravenous fluids at the time of oocyte retrieval, and cryopreserving/vitrifying all embryos for subsequent transfer in an unstimulated cycle. Some of these techniques have been widely adopted, despite the scarcity of data from randomized clinical trials to support their use.

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          Ovarian hyperstimulation syndrome in novel reproductive technologies: prevention and treatment.

          To overview the world literature on ovarian hyperstimulation syndrome (OHSS) and modes of prevention and treatment of OHSS. All the pertinent literature on OHSS, its prevention, and strategies for treatment were reviewed. Key to prevention is proper identification of the population at risk, which includes women with either the hormonal or the morphological signs of polycystic ovarian disease, high serum estradiol (E2) before human chorionic gonadotropin (hCG) administration (E2 greater than 4,000 pg/mL), multiple follicular response (greater than 35), younger age, and lean habitus. When a high risk situation is recognized, ovulatory dose of hCG may be reduced, avoided (with cycle cancellation), or substituted by gonadotropin-releasing hormone or its agonist. Luteal support with hCG is to be bypassed. To minimize risk of OHSS, endogenous pregnancy-drived hCG may be eluded by judicious cryopreservation of all embryos. Last, follicular aspiration will allow higher levels of E2 and larger number of follicles to be matured with lesser risk of OHSS than conventional ovulation induction without follicular aspiration. In-house for the severe and intensive care for the critical form. Meticulous fluid and electrolyte balance using both crystalloids and colloids (albumin) until hemoconcentration abates. Paracentesis is indicated for tight ascites, deteriorating kidney functions, and symptomatic relief. Diuretics may be prudently used once hemodilution is achieved. Dopamine drip may be used as a renal rescue, whereas heparin is indicated for thromboembolic phenomena and surgery reserved for abdominal catastrophies. Therapeutic interruption of an early gestation may be lifesaving when all other measures have failed. Although severe and critical OHSS may not be completely avoided, early recognition of high-risk factors, judicious prevention schemes, and treatment strategies should reduce the complication and long-term sequelae of this iatrogenic syndrome.
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            Assisted reproductive technology in Europe, 2006: results generated from European registers by ESHRE.

            In this 10th European IVF-monitoring (EIM) report, the results of assisted reproductive techniques from treatments initiated in Europe during 2006 are presented. Data were mainly collected from existing national registers. From 32 countries, 998 clinics reported 458 759 treatment cycles including: IVF (117 318), ICSI (232 844), frozen embryo replacement (FER, 86 059), egg donation (ED, 12 685), preimplantation genetic diagnosis/screening (6561), in vitro maturation (247) and frozen oocytes replacements (3498). Overall this represents a 9.7% increase in activity since 2005, which is partly due to an increase in registers (seven more countries with complete coverage). European data on intrauterine insemination using husband/partner's (IUI-H) and donor (IUI-D) semen were reported from 22 countries. A total of 134 261 IUI-H and 24 339 IUI-D cycles were included. In 20 countries, where all clinics reported to the IVF register, a total of 359 110 assisted reproductive technology (ART) cycles were performed in a population of 422.5 million, corresponding to 850 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 29.0 and 32.4%, respectively. For ICSI, the corresponding rates were 29.9 and 33.0%. After IUI-H the delivery rate was 9.2% in women below 40. After IVF and ICSI the distribution of transfer of one, two, three and four or more embryos was 22.1, 57.3, 19.0 and 1.6%, respectively. Compared with 2005, fewer embryos were replaced per transfer, but significant national differences in practice were apparent. The proportion of singleton, twin and triplet deliveries after IVF and ICSI combined was 79.2, 19.9 and 0.9%, respectively. This gives a total multiple delivery rates of 20.8% compared with 21.8% in 2005 and 22.7% in 2004. IUI-H in women below 40 years of age resulted in 10.6% twin and 0.6% triplet pregnancies. Compared with previous years, the reported number of ART cycles in Europe has increased, pregnancy rates have increased marginally, even though fewer embryos were transferred and the multiple delivery rates have declined.
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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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                Author and article information

                Journal
                Reprod Biol Endocrinol
                Reprod. Biol. Endocrinol
                Reproductive Biology and Endocrinology : RB&E
                BioMed Central
                1477-7827
                2012
                24 April 2012
                : 10
                : 32
                Affiliations
                [1 ]Kinderwunsch Centrum München (KCM) (Fertility Center Munich), Lortzingstr. 26, D-81241, Munich, Germany
                [2 ]Merck Serono S.A. – Geneva (an affiliate of Merck KGaA, Darmstadt, Germany), 9 Chemin des Mines, Geneva, CH-1202, Switzerland
                Article
                1477-7827-10-32
                10.1186/1477-7827-10-32
                3403873
                22531097
                e5728385-93e1-4110-8ad1-d8749368931b
                Copyright ©2012 Fiedler and Ezcurra; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 December 2011
                : 24 April 2012
                Categories
                Review

                Human biology
                ovarian hyperstimulation syndrome,risk factors,prevention,individualized controlled ovarian stimulation,vascular endothelial growth factor

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