Prevention of Ovarian Hyperstimulation Syndrome: A Review

Hindawi Publishing Corporation Obstetrics and Gynecology International Volume 2015, Article ID 514159, 10 pages http://dx.doi.org/10.1155/2015/514159 Review Article Prevention of Ovarian Hyperstimulation Syndrome: A Review Vinayak Smith,1 Tiki Osianlis,2 and Beverley Vollenhoven2,3,4 1 Alice Springs Hospital, Department of Obstetrics and Gynaecology, Alice Springs, NT 0870, Australia Monash IVF, 252 Clayton Road, Clayton, VIC 3168, Australia 3 Monash Health, Women’s and Children’s Program, Monash Medical Centre, Clayton Road, Clayton, VIC 3168, Australia 4 Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3168, Australia 2 Correspondence should be addressed to Vinayak Smith; Received 27 January 2015; Accepted 29 April 2015 Academic Editor: Curt W. Burger Copyright © 2015 Vinayak Smith et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The following review aims to examine the available evidence to guide best practice in preventing ovarian hyperstimulation syndrome (OHSS). As it stands, there is no single method to completely prevent OHSS. There seems to be a benefit, however, in categorizing women based on their risk of OHSS and individualizing treatments to curtail their chances of developing the syndrome. At present, both Anti-Müllerian Hormone and the antral follicle count seem to be promising in this regard. Both available and upcoming therapies are also reviewed to give a broad perspective to clinicians with regard to management options. At present, we recommend the use of a “step-up” regimen for ovulation induction, adjunct metformin utilization, utilizing a GnRH agonist as an ovulation trigger, and cabergoline usage. A summary of recommendations is also made available for ease of clinical application. In addition, areas for potential research are also identified where relevant. 1. Introduction Ovarian hyperstimulation syndrome (OHSS) is encountered in practice as an iatrogenic complication of controlled ovarian stimulation (COS). COS is aimed at producing multiple ovarian follicles during assisted conception cycles in hope of increasing the number of oocytes available for collection. OHSS, however, is characterised by an exaggerated response to this process [1, 2]. The incidence of moderate to severe OHSS is between 3.1 and 8% of in vitro fertilization (IVF) cycles but can be as high as 20% in high risk women [3, 4]. Typically, OHSS is a phenomenon which is associated with gonadotrophin use during COS. There are instances, however, where OHSS has been documented to arise spontaneously either in conjunction with clomiphene or with gonadotrophin releasing hormone use [2, 5]. This review aims to examine the pathophysiology of OHSS and the evidence behind the various methods employed by clinicians to prevent its occurrence. 2. Methods A literature search was carried out on the following electronic databases (until December 2014): MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials. Only articles in English were taken into consideration and abstracts were excluded. A combination of text words or Medical Subject Headings (MeSH) terms were subsequently utilized to generate a list of citations: (“OHSS” OR “ovarian hyperstimulation syndrome”) AND (“prevention”). Articles and their references were then examined in order to identify other potential studies which could provide perspective for the following review. Systematic reviews, meta-analyses, and randomized controlled trials (RCTs) were then preferentially selected over other forms of data where feasible in order to formulate the following review and recommendations. 3. Results and Discussion 3.1. Pathophysiology. OHSS is theorized to manifest systemically as a result of vasoactive mediators being released from hyperstimulated ovaries. As a result, capillary permeability is increased which causes the extravasation of fluid from the intravascular compartment into the third space. The haemoconcentration which ensues results in complications such as hypercoagulability and reduced end organ perfusion [6, 7]. 2 Obstetrics and Gynecology International Pathophysiology of OHSS “Early” OHSS, due to exogenous hCG Overstimulated ovarian follicle “Late” OHSS, due to endogenous hCG Hyperstimulated ovary ↑ Intraovarian RAS activation ↑ VEGF secretion ↑ Capillary leakage resulting in OHSS Blood vessel Figure 1: Graphical representation of the pathophysiology of ovarian hyperstimulation syndrome (OHSS). There is currently no consensus on the exact cause of OHSS. Human Chorionic Gonadotrophin (hCG) exposure, however, is thought to be a critical mediator of the syndrome. This is based on the findings that OHSS does not develop when hCG is withheld as an ovulatory trigger during COS and also that increased hCG exposure is associated with an increased risk of OHSS [8, 9]. The role of hCG can be further elucidated via the two distinct clinical presentations observed in OHSS: the “early” and “late” forms. “Early” OHSS occurs within 9 days of hCG being administered as an ovulatory trigger and reflects the effect of exogenous hCG on ovaries that have already been hyperstimulated by gonadotrophins. “Late” OHSS, on the other hand, occurs more than 10 days after the use of hCG as an ovulatory trigger (in the absence of luteal hCG support) and demonstrates the ovarian response to endogenous hCG produced by the trophoblast [9]. hCG is thought to play a key role in the pathophysiological mechanism of OHSS by mediating the release of vascular endothelial growth factor-A (VEGF-A). VEGF-A, through its interactions with the VEGF receptor-2 (VEGFR-2), promotes angiogenesis and vascular hyperpermeability. Its overexpression, therefore, characterises the increased vascular permeability observed in OHSS [10, 11]. VEGF-A concentrations have been demonstrated to be elevated after hCG administration and in women with or at risk of OHSS [12, 13]. Another pathophysiological mechanism implicated in OHSS is the intraovarian renin angiotensin system (RAS). The ovarian RAS is involved in regulating vascular permeability, angiogenesis, endothelial proliferation, and prostaglandin release. hCG causes a strong activation of the RAS, evidenced by high renin activity in the follicular fluid of women with OHSS [11, 14]. Overstimulation of this cascade, together with increasing VEGF levels, is postulated to synergistically potentiate OHSS (Figure 1) [15, 16]. 3.2. Prevention of OHSS. As the old adage goes, prevention is better than cure. As it stands, there is no perfect strategy which completely eliminates OHSS. There are factors however which we can take into consideration in order to reduce its incidence. 3.2.1. Identifying the “At Risk” Woman. Being aware of the risk factors for OHSS will allow clinicians to preempt its occurrence and t (...truncated)