Pathophysiology Of Ovarian Hyperstimulation Syndrome Research Articles

Prevention of OHSS

Ovarian hyperstimulation syndrome (OHSS), perhaps the most serious complication arising from in vitro fertilization (IVF), is rare but life-threatening in some cases. In this lecture, we will first delve into the pathophysiology of OHSS and hallmark features such as hemoconcentration, hypercoagulability, electrolyte imbalances, fluid loss into third space, and renal insufficiency. In addition, clinical vignettes will illustrate some of the most severe cases of OHSS. Next, various methods for identifying patients at high risk of OHSS will be discussed. Available literature indicates that younger age and polycystic ovarian syndrome (PCOS) may be associated with the incidence of OHSS. Ovarian reserve markers such as anti-müllerian hormone (AMH) and antral follicle counts (AFC) have been suggested as useful screening tools. Also, stimulation cycle profiles, such as developing multiple follicles, peak serum estradiol levels, and the number of retrieved oocytes, may aid in identifying those at high risk. To lower the incidence of OHSS, modifying controlled ovarian stimulation (COS) protocols is essential. Evidence suggests that gonadotropin-releasing hormone (GnRH) antagonist protocol is beneficial in reducing the risk of OHSS. Medications such as dopamine agonists, aspirin, and metformin may be associated with lower risk while using clomiphene citrate remains controversial. “Coasting,” which is holding gonadotropins for several days to decrease the OHSS risk, has been suggested as another strategy. Triggering could be done differently using a GnRH agonist. Cycle segmentation by cryopreserving oocytes and embryos is also a feasible option. Close monitoring and early detection of symptoms are essential for prompt intervention and management of OHSS. By implementing preventative measures and closely monitoring patients, physicians may reduce the incidence and severity of OHSS and ensure safer fertility treatments.

The investigation of cholinergic receptor muscarinic 1 activity in the rat ovary with induced ovarian hyperstimulation.

We look at the immunoreactivity of cholinergic receptor muscarinic 1 (CHRM1) in the ovarian tissues of rats with ovarian hyperstimulation syndrome (OHSS) considering the possibility that the muscarinic activity may contribute to the pathophysiology of OHSS. In this study, 14 immature female Wistar Albino rats were divided into two groups at random. The rats were 22 days old. Rats in the control group (n=7) were 22 days old, while those in the OHSS group (n=7) received 10 IU follicle-stimulating hormone subcutaneously over the course of four days and 30 IU human chorionic gonadotropin (hCG) on the fifth day to induce ovarian hyperstimulation. All the rats were sacrificed after all the groups' ovaries and blood samples were collected at the conclusion of the experiment. The left ovarian tissues were kept in aluminum foil at -80 °C, while the right ovarian tissues were kept in 10% formalin. Tissue vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α and malondialdehyde (MDA) levels were measured by The Enzyme Linked Immunosorbent Assay technique in the ovarian tissues. CHRM1 immunoreactivity was scored immunohistochemically. Ovarian weight, tissue IL-10, TNF-α, VEGF and MDA levels, and CHRM1 immunoreactivity were significantly increased in the OHSS group. Increased levels of CHRM1 activity may play a role in the pathophysiology of OHSS. With further studies, the effect of luteinizing hormone and hCG on the ovarian and hypothalamic cholinergic system can be further investigated, and useful information can be obtained in determining OHSS prevention strategies.

Global Transcriptional Profiling of Granulosa Cells from Polycystic Ovary Syndrome Patients: Comparative Analyses of Patients with or without History of Ovarian Hyperstimulation Syndrome Reveals Distinct Biomarkers and Pathways.

Ovarian hyperstimulation syndrome (OHSS) is often a complication of polycystic ovarian syndrome (PCOS), the most frequent disorder of the endocrine system, which affects women in their reproductive years. The etiology of OHSS is multifactorial, though the factors involved are not apparent. In an attempt to unveil the molecular basis of OHSS, we conducted transcriptome analysis of total RNA extracted from granulosa cells from PCOS patients with a history of OHSS (n = 6) and compared them to those with no history of OHSS (n = 18). We identified 59 significantly dysregulated genes (48 down-regulated, 11 up-regulated) in the PCOS with OHSS group compared to the PCOS without OHSS group (p-value < 0.01, fold change >1.5). Functional, pathway and network analyses revealed genes involved in cellular development, inflammatory and immune response, cellular growth and proliferation (including DCN, VIM, LIFR, GRN, IL33, INSR, KLF2, FOXO1, VEGF, RDX, PLCL1, PAPPA, and ZFP36), and significant alterations in the PPAR, IL6, IL10, JAK/STAT and NF-κB signaling pathways. Array findings were validated using quantitative RT-PCR. To the best of our knowledge, this is the largest cohort of Saudi PCOS cases (with or without OHSS) to date that was analyzed using a transcriptomic approach. Our data demonstrate alterations in various gene networks and pathways that may be involved in the pathophysiology of OHSS. Further studies are warranted to confirm the findings.

Anorexigenic peptide (leptin, obestatin, nesfatin-1) levels and their impact on assisted reproductive technology treatment outcomes in patients with polycystic ovary syndrome.

ObjectiveIn this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes.MethodsA prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses.ResultsIn the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients.ConclusionsBaseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.

Investigation on the risk factors for late-onset OHSS: a retrospective case-control study.

The pathophysiology of ovarian hyperstimulation syndrome (OHSS) is largely unknown. High ovarian response is acknowledged as a risk factor. However, in our clinical practice, the incidence of OHSS is not necessarily linked to the degree of such response among women. Here, we aimed to screen for potential risk factors other than those associated with ovarian response. A total of 21,222 ovarian stimulation cycles were collected among women undergoing assisted reproductive technology, among which 84 patients with late-onset OHSS were identified as cases; corresponding matched control cases were obtained from the remaining 21,138 cycles. A multivariable logistic regression with the best subset method was performed to screen for significant risk factors. First, control samples were obtained with a case-to-control ratio of 1:4. The matching criteria were mainly ovarian response-related factors including age, body mass index, number of oocytes retrieved, standard or mild ovarian stimulation, and specific ovarian stimulation protocols. After matching the five ovarian response-related factors, 81 cases and 318 controls were obtained. The best model was selected after analysis as above. Basal serum low-density lipoprotein cholesterol (LDL-C), basal total cholesterol (TC), and estradiol (E2) concentrations on the day of triggering ovulation were included in the model, with odds ratios of 0.3410 (95% confidence interval, CI, 0.1618-0.7186), 2.2008 (95% CI 1.1192-4.3275) and 1.0000 (95% CI 1.0000-1.0001), respectively. Basal LDL-C was a risk factor negatively associated with late-onset OHSS, while basal TC and triggeringE2 levels during ovarian stimulation were positive risk factors.

Plasma and follicular fluid osteopontin levels during ovarian cycle and their correlation with follicular fluid vascular endothelial growth factor levels

Osteopontin (OPN) is a multifunctional secreted glycoprotein. We evaluated OPN concentrations in blood and follicular fluid (FF) during the ovarian cycle and their relationship with the production of vascular endothelial growth factor (VEGF), which is involved in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). Twenty-two women undergoing in vitro fertilization (minimal stimulation protocol with clomiphene citrate) were enrolled. Samples were collected (a) on the third day of withdrawal bleeding, (b) 2 days before oocyte retrieval, and (c) on the day of oocyte retrieval. FF was collected during oocyte retrieval. The OPN concentration in each specimen and the VEGF concentration in FF was measured by enzyme-linked immunosorbent assays. Plasma OPN concentrations were (in ng/mL): (a) 416 ± 37.2, (b) 378 ± 35.8, and (c) 390 ± 40.0, with no significant differences between the groups. The OPN concentration in FF was 106 ± 13.4 ng/mL. A positive correlation was found between OPN concentrations in FF and plasma samples. A positive correlation was also found between plasma OPN and FF VEGF concentrations, irrespective of the blood-sampling period. Plasma OPN concentration is suggested to reflect the FF VEGF level at oocyte retrieval and maybe a novel clinical marker for predicting the risk for OHSS.

Substantial Effect of Fenugreek Seeds Aqueous Extract on Serum Estradiol Level in Ovarian Hyperstimulation Syndrome Rat Model.

ObjectivesEstradiol (E2) plays an important role in the pathophysiology of ovarian hyperstimulation syndrome (OHSS). This study aimed to evaluate the effect of fenugreek seed aqueous (FSA) extract on serum E2 levels in a rat model of OHSS.MethodsA total of 34 female Sprague Dawley rats, aged 18 days old, weighing 40 to 45 g, were randomly divided into negative control, positive control, and treatment groups. A daily dose of 1500 mg/kg per body weight of FSA extract was administrated orally to rats in the treatment group for 13 days. On day eight of the study, OHSS was induced in both positive control and treated groups by subcutaneous injection of pregnant mare’s serum gonadotropin 50 IU for four consecutive days, followed by human chorionic gonadotropin 25 IU on the fifth day. The effect of FSA extract was evaluated by measuring the concentration of serum E2 using the enzyme-linked immunosorbent assay.ResultsFSA extract reduced serum E2 level significantly in the treated OHSS model (p-value < 0.050) compared to the positive control group.ConclusionsThe finding has important implications on the development of female infertility adjuvant drugs for safe assisted reproduction technology cycles in terms of OHSS prevention.

Concentration of soluble urokinase plasminogen activator receptor (suPAR) in the pre-ovulatory follicular fluid is associated with development of ovarian hyperstimulation syndrome during ovarian stimulation.

Investigating whether pre-ovulatory follicular fluid (FF) levels of selected proteins differ between women who do or do not develop severe ovarian hyperstimulation syndrome (OHSS) and evaluate whether they potentially could guide a "freeze-all" strategy. FF was collected during a randomized controlled trial comparing OHSS in antagonist versus agonist protocol including 1050 women in their first assisted reproductive technology (ART) cycle during year 2009-2013. The present sub-study is a matched case-control study comparing FF levels of soluble urokinase plasminogen activator receptor (suPAR), C-reactive protein, placental growth factor, vascular endothelial growth factor, and angiopoietins 1 and 2 in OHSS cases (n = 25, severe OHSS, and ≥ 15 oocytes), high-risk controls (n = 25, no OHSS, and ≥ 15 oocytes), and low-risk controls (n = 25, no OHSS, and 5-8 oocytes). FF level of suPAR differed significantly between the three groups (p = 0.018) with mean (SD) levels of 2.3 (0.4) μg/L, 2.6 (0.8) μg/L, and 2.8 (0.6) μg/L in OHSS cases, high-risk controls, and low-risk controls, respectively. Receiver operating characteristic curve analysis demonstrated that suPAR levels could predict severe OHSS (AUC 0.678; 95% CI 0.553-0.803) with a sensitivity of 64% and a specificity of 66%. None of the other investigated proteins differed between the three groups or between OHSS cases and combined controls. The pre-ovulatory FF level of suPAR was significantly lower in women developing severe OHSS, indicating that the plasminogen activator system could be involved in the pathophysiology of OHSS. However, suPAR did not provide a satisfying predictive value for the prediction of OHSS.

Diosmin versus cabergoline for prevention of ovarian hyperstimulation syndrome

Abstract Background OHSS (Ovarian Hyperstimulation Syndrome) is the most serious iatrogenic complication of ovulation induction. The pathophysiology of OHSS is characterised by increased capillary permeability, leading to leakage of fluid from the vascular compartment, with third space fluid accumulation and intravascular dehydration. Objective This study aimed to evaluate the effectiveness of diosmin in comparison to the dopamine agonist cabergoline in preventing OHSS in high risk patients undergoing assisted reproductive technique cycles. Methods In this study, 200 women who were at high risk for developing OHSS were randomly allocated into two groups. Group A (Diosmin group, 100 women) and group B (Cabergoline group, 100 women). All patients were assessed every two weeks after retrieval and for 8 weeks to determine early clinical or ultrasound evidence of OHSS. Results There was a statistically significant reduction (P = 0.005) in the incidence of OHSS in the diosmin group (12%) compared to cabergoline group (28%). The number of severe OHSS cases in the cabergoline group (n = 13) was significantly higher (P = 0.003) than the diosmin group (n = 2). There was no difference in clinical pregnancy rate. Conclusion Our results concluded that diosmin was more effective in preventing severe OHSS and decreasing OHSS occurrence rates than cabergoline when used in high-risk patients. Trial registration: Clinical trial.gov ( NCT02134249 ).

A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening, iatrogenic complication that occurs during assisted reproduction. Polycystic ovarian syndrome (PCOS) significantly increases the risk of OHSS during controlled ovarian stimulation. Therefore, a more effective early prediction technique is required in PCOS patients. Quantitative proteomic analysis of serum proteins indicates the potential diagnostic value for disease. In the present study, the authors revealed the differentially expressed proteins in OHSS patients with PCOS as new diagnostic biomarkers. The promising proteins obtained from liquid chromatography-mass spectrometry were subjected to ELISA and western blotting assay for further confirmation. A total of 57 proteins were identified with significant difference, of which 29 proteins were upregulated and 28 proteins were downregulated in OHSS patients. Haptoglobin, fibrinogen and lipoprotein lipase were selected as candidate biomarkers. Receiver operating characteristic curve analysis demonstrated all three proteins may have potential as biomarkers to discriminate OHSS in PCOS patients. Haptoglobin, fibrinogen and lipoprotein lipase have never been reported as a predictive marker of OHSS in PCOS patients, and their potential roles in OHSS occurrence deserve further studies. The proteomic results reported in the present study may gain deeper insights into the pathophysiology of OHSS.

Calcium Dobesilate versus Cabergoline for Prevention of Ovarian Hyper Stimulation Syndrome

Background: OHSS (Ovarian Hyper stimulation Syndrome) is the most serious iatrogenic complication of ovulation induction. The pathophysiology of OHSS is characterized by increased capillary permeability, leading to leakage of fluid from the vascular compartment, with third space fluid accumulation and intravascular dehydration. Objective: This study aimed to evaluate the effectiveness of Calcium dobesilate (CaD) in comparison to the dopamine agonist cabergoline in preventing OHSS in high-risk patients undergoing assisted reproductive technique cycles. Methods: In this study, 200 women who were at high risk for developing OHSS were randomly allocated into two groups. Group A (Calcium dobesilate group, 100 women) and group B (Cabergoline group, 100 women). All patients were assessed weekly after retrieval and for 8 weeks to determine early clinical or ultrasound evidence of OHSS. Results: There was a statistically significant reduction (P=0.005) in the incidence of OHSS in the Calcium dobesilate (CaD) group (12%) compared to cabergoline group (28%). The number of severe OHSS cases in the cabergoline group (n=13) was significantly higher (P=0.003) than the CaD group (n=2). There was no difference in clinical pregnancy rate. Conclusion: Our results concluded that Calcium dobesilate (CaD) was more effective in preventing severe OHSS and decreasing OHSS occurrence rates than cabergoline when used in highrisk patients.

Prevention of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of ovarian stimulation for fertility treatment. Risk factors include polycystic ovaries, high ovarian reserve, and excessive ovarian response to stimulation. It is important to be aware of the risk of OHSS, even in so called low-risk situations. An understanding of the pathophysiology of OHSS may help clinicians to target preventative measures in women who are at risk. Ovarian stimulation regimes based on an individualized reserve assessment may help reduce the incidence of OHSS. Gonadotropin-releasing hormone (GnRH) antagonist regimes are associated with a lower risk than GnRH agonist regimes and the risk may be further reduced if a GnRH agonist trigger is used in place of human chorionic gonadotropin (hCG). Other methods of reducing hCG exposure include avoiding hCG luteal support, cryopreservation of all embryos, and avoidance of multiple pregnancy. However, the only method that guarantees avoidance of OHSS in high-response cycles is cycle cancellation. Clinicians should be aware of the potential value of coasting and dopamine agonists, as measures to reduce risk in the presence of an excessive ovarian response.

The role of osmoregulation in the pathophysiology and management of Severe Ovarian Hyperstimulation Syndrome

Severe Ovarian Hyperstimulation Syndrome (OHSS), with an incidence of 1–2% of superovulation cycles, remains one of the most important complications of gonadotrophin use in assisted reproductive technologies because of its associated morbidity and rarely, mortality. Despite the wealth of scientific and clinical interest that this iatrogenic complication has generated, its pathophysiology is still not adequately elucidated and its management has thus remained empirical. Disorders of salt and water balance are two very important features that have been reported during severe OHSS. Some of the clinical and biochemical changes resulting from this disorder of salt and water balance are similar to those previously reported in pregnancy and liver cirrhosis. The pathophysiology of these clinical changes has been explained in part in pregnancy and liver cirrhosis by changes in osmoregulation function. It is this similarity in the clinical and biochemical changes in OHSS, pregnancy and liver cirrhosis that has prompted the investigation of the role of osmoregulation function in the pathophysiology of OHSS. The current article has been written to provide further details in support of recent excellent articles and guidelines, highlighting the physiological basis and rationale governing some aspects of, and the role of osmoregulation in the management of the OHSS syndrome.

The Role of Pigment Epithelium-Derived Factor in the Pathophysiology and Treatment of Ovarian Hyperstimulation Syndrome in Mice

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of assisted reproduction. OHSS is induced by an ovarian release of vasoactive, angiogenic substances that results in vascular hyperpermeability, leakage, and shift of fluids from blood vessels into the extravascular space with consequent ascites and edema that are attributed to vascular endothelial growth factor (VEGF). Our objective was to examine a physiological approach for preventing and treating OHSS, based on negating the VEGF network. We used a mouse OHSS model and cultured granulosa cells. Changes in pigment epithelium-derived factor (PEDF) and VEGF were measured by quantitative PCR and Western blot analysis. OHSS was recorded by changes in body weight and in peritoneal vascular leakage, quantified by the modified Miles vascular permeability assay. Granulosa cells produced and secreted the anti-angiogenic factor, PEDF, in an inverse fashion to VEGF. The physiological PEDF-VEGF counterbalance was found to be impaired in the mouse OHSS model. Treatment of OHSS-induced mice with low doses of recombinant PEDF (rPEDF) alleviated OHSS signs including edema (P < .001) and vascular leakage (P < .001) and reduced the level of ovarian VEGF mRNA. Low doses of rPEDF also reduced VEGF mRNA levels in granulosa cells in vitro. However, these effects were not seen at higher doses of rPEDF, suggesting a hormetic mechanism of rPEDF action. These observations provide a new perspective into the pathophysiology of OHSS, namely, high expression level of VEGF together with a nearly undetectable level of PEDF. A replacement therapy with rPEDF is suggested as an innovative physiological treatment for OHSS. Finally, control of the PEDF-VEGF reciprocal relationship could open new therapeutic avenues for other angiogenic-related fertility pathologies.

Ovarian Hyperstimulation Syndrome

ABSTRACTART is proven of great help to all the infertile couples anxious to get pregnant, but is not free of side effects and complications. OHSS one of the most important complication especially in cases of PCOS. Ovarian hyperstimulation syndrome (OHSS) is a potentially fatal complication of ovarian stimulation. The incidence has been estimated at 3 to 6% for moderate and 0.1 to 2% for severe OHSS. The trigger for initiation of OHSS appears to be human chorionic gonadotropin (hCG). In conception cycles symptoms may persist longer due to endogenous hCG stimulus. Vascular endothelial growth factor (VEGF), a member of the transforming growth factor superfamily, has emerged as one of the factors most likely involved in the pathophysiology of OHSS. There are various risk factors which increases the risk of developing OHSS during the stimulation like PCOS, low body weight, previous history of OHSS, etc. Primary and secondary preventive measures are been tried to reduce the risk of developing OHSS. GnRHa trigger in patients at risk revealed that incidence OHSS was reduced or totally eliminated. Use of antagonist cycle with an agonist trigger and elective vitrification of all embryos allows us to aim for an ‘OHSS Free’ clinic today.How to cite this articleMahajan N. Ovarian Hyperstimulation Syndrome. Int J Infertility Fetal Med 2013;4(3):71-78.

Prevention and management of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome is a relatively common complication of ovarian stimulation and can be life-threatening. The pathophysiology of ovarian hyperstimulation syndrome is characterised by increased capillary permeability, leading to leakage of fluid from the vascular compartment, with third space fluid accumulation and intravascular dehydration. The combined use of a gonadotrophin-releasing hormone antagonist protocol with gonadotrophin-releasing hormone agonist triggering and oocyte and embryo freezing has considerable promise in preventing ovarian hyperstimulation syndrome. Women with severe ovarian hyperstimulation syndrome require hospitalisation for more careful monitoring and treatment. Transvaginal paracentesis can be used as an outpatient treatment to prevent the need for hospitalisation. The inhibition of vascular permeability seems to be a novel therapeutic approach to preventing and treating ovarian hyperstimulation syndrome.

OHSS-safe IVF practice: Dream or reality?

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening iatrogenic complication of ovarian stimulation. Severe forms complicate 1–3% of IVF cycles (1). It is characterized by a massive ovarian enlargement together with a fluid shift into extravascular compartments responsible for the development of ascites, sometimes pleural and/or pericardial effusion, hypovolemia, oliguria, and hydroelectrolytic disorders. Several factors such as histamine, serotonin, prostaglandins, prolactin, cytokines including the interleukins, tumor necrosis factor alpha, endothelin-1 and vascular endothelial growth factor (VEGF) are thought to be involved in triggering of increased vascular permeability after ovulation stimulation. Vascular endothelial growth factor (VEGF), which promotes angiogenesis and vascular permeability, is probably the principle factor involved in the pathogenesis of OHSS (2). VEGF was demonstrated to be secreted from progesterone-producing granulosa cells in the ovarian follicles, and the VEGF production is stimulated by HCG (3). So, it is evident that hCG is the main trigger for its development. Therefore, the ideal method to avoid OHSS occurrence is cancelation of the cycle, which unfortunately leads to a financial and psychological impact. How to reach an OHSS-safe IVF? In the last decades, there were several trials aiming at a more successful and OHSS-safe IVF. Since the pathophysiology of OHSS is poorly understood, scientific effort should search for a reliable predictive test for patients prone to OHSS before starting stimulation and testing its validity. Such as, a possible gene mutation in the FSH receptor gene, which displays an increased sensitivity to hCG and may be responsible for the development of spontaneous ovarian hyperstimulation syndrome (OHSS), (4). Another possible option is the pre-treatment measurement of

Etiology of OHSS and use of dopamine agonists

Vascular endothelial growth factor is the factor that causes increased capillary permeability and therefore the most serious manifestations of ovarian hyperstimulation syndrome. Dopamine agonists can both prevent and treat ovarian hyperstimulation syndrome by blocking expression of the vascular endothelial growth factor receptor.

Pharmacotherapy of ovarian hyperstimulation syndrome

Importance of the field: One of the main objectives in assisted reproduction techiques (ART) is the maturation of multiple follicles and the recovery of multiple good quality oocytes. To realize this, it is necessary to interfere with the mechanisms of selection and follicular dominance, characteristic of spontaneous mono-ovulatory cycles, by administering gonadotrophins. In 12 – 20% of the stimulation cycles, the response to ovarian stimulation in terms of follicular development is higher than expected, with the onset of the so-called ovarian hyperstimulation syndrome (OHSS). This is considered to be an exaggerated response: an iatrogenic – possibly life-threatening – complication of ovarian stimulation.Areas covered in this review: This review deals about reproductive, obstetric and gynecological aspects of OHSS.What the reader will gain: Understanding the pathophysiology of OHSS is the key to establishing a correct pharmacotherapy. However, the mechanisms underlying OHSS have not yet been completely clarified. Treatment of OHSS is empirical, so prevention is the most important aspect in its management. Several studies support the role of vascular endothelial growth factor in the development of OHSS in humans, so future studies about anti-angiogenetic molecules seem to be an important goal in ART.Take home message: Methods to prevent OHSS.

Ovarian hyperstimulation syndrome: pathophysiology and prevention

To review and discuss the pathophysiology and prevention strategies for ovarian hyperstimulation syndrome (OHSS), which is a condition that may occur in up to 20% of the high risk women submitted to assisted reproductive technology cycles. The English language literature on these topics were reviewed through PubMed and discussed with emphasis on recent data. The role of estradiol, luteinizing hormone, human chorionic gonadotropin (hCG), inflammatory mediators, the renin-angiotensin system and vascular endothelial growth factor is discussed in the pathophysiology of OHSS. In addition we consider the prevention strategies, including coasting, administration of albumin, renin-angiotensin system blockage, dopamine agonist administration, non-steroidal anti-inflammatory administration, GnRH antagonist protocols, reducing hCG dosage, replacement of hCG and in vitro maturation of oocytes (IVM). Among the many prevention strategies that have been discussed, the current evidence points to the replacement of hCG by GnRH agonists in antagonist cycles and the performance of IVM procedures as the safest approaches.