Fertility Blaze
Fertility Blaze 2014 › Fertility Blaze Vol-2, No-1, 2014

Prevention of OHSS

Background

Ovarian hyperstimulation syndrome (OHSS), an iatrogenic complication of controlled ovarian stimulation (COS) with follicle-stimulating hormone (FSH) medications, first came into the limelight in 1943 while the initial evidence of fatal consequences of the condition surfaced in 1951.1   Assisted reproduction techniques (ART) have gained popularity in recent times and the benefits and risks of the technology come with the package. OHSS is the most serious risk of ART. Klemetti and colleagues2   had reported in a study that 14 per 1000 women reported with a serious case of OHSS following first in vitro fertilization (IVF) treatment cycle. The risk of OHSS may be highest after the first and the fifth or more IVF treatment cycles.2   The total rate of hospitalization due to OHSS per initiated IVF treatment cycle ranged from 0.9% (210 cases/24,318 cycles) to 1.4% (330 cases/24,318 cycles) and the mean length of hospital stay due to OHSS and potential OHSS was 4.1 and 3.3 bed days respectively.2   This possibly provides an insight into the magnitude of the problem OHSS can pose.

Pathophysiology of OHSS

Despite extensive investigations, the pathophysiology of OHSS still remains obscure. When ovaries stimulated with FSH/leuteinizing hormone (LH) are subsequently exposed to human chorionic gonadotropin (hCG), OHSS ensues. The fundamental feature underlying OHSS includes increased vascular permeability that leads to a shift in fluid from the intravascular space to third space compartments.1,3     The various factors implicated in the pathophysiology of OHSS are summarized below.

Estradiol

Serum estradiol, initially believed to be significantly associated with OHSS pathogenesis, has now taken a backseat as far as the pathophysiology of OHSS is concerned. Although high levels of estradiol are noted in most OHSS patients, cases with low estradiol levels have also been reported.4   However, circulating estradiol levels carry predictive significance for OHSS.

Inflammatory mediators

Several cytokines and growth factors including interleukins (IL)-2, IL-6, IL-8, IL-10 and IL-18 have been implicated in the pathogenesis of OHSS.5   Their role has been suggested in the inflammatory processes associated with late follicular maturation, ovulation, corpus luteum function and embryo implantation. A recent study by Wei and colleagues6   revealed that IL-6 trans-signaling is activated during the ovarian stimulation process and this may induce vascular leakage in OHSS. IL-8 also plays a major role in OHSS. Chen et al7   demonstrated both vascular endothelial growth factor (VEGF) and IL-8 of follicular fluid (FF) to increase endothelial permeability via VEGF receptor 2 (VEGFR-2)-mediated Rho/Rock activation, actin polymerization and phosphorylations of VE-cadherin and occludin, thereby opening the adherens junctions and tight junctions.

Renin-angiotensin-aldosterone system

Derck et al8   had reported long back that FF from IVF patients stimulated with human menopausal/human chorionic gonadotropin had 40-fold increase in prorenin levels than plasma and 10-fold increase in renin levels than plasma when compared to unstimulated controls.Lightman and colleagues had also reported elevated FF levels of renin, angiotensin II, and angiotensin III among stimulated vs. unstimulated controls.9   The renin-angiotensin system has implications in new vessel formation while angiogenesis is associated with an increase in capillary permeability. Therefore, high plasma renin-like activity in human FF suggests a role of the renin-angiotensin system in ovarian enlargement and extracellular fluid accumulation in OHSS.10

Vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is crucial for the development of OHSS. The expression of VEGF and VEGFR-2 mRNA has been noted to increase significantly following hCG administration. The maximum levels have been noted to coincide with peak vascular permeability.3   Villasante and colleagues11   reported that hCG and VEGF produced a significant increase in vascular endothelial (VE)-cadherin release, an interendothelial adhesion molecule. hCG and VEGF also caused changes in the actin fibers that suggested increased capillary permeability. Figure 1 is an illustration of VEGF-mediated pathogenesis of OHSS.

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Symptoms of OHSS

The shift of fluid into the third space and the resulting hemoconcentration result in the following symptoms:12

  • Mild abdominal distention due to enlarged ovaries alone or with an accompanying fluid shift into the abdomen
  • Cystic ovaries, in advanced stages, lead to abdominal distension, pain, nausea, vomiting and diarrhea
  • Ascites
  • Oliguria
  • Cardiovascular effects – arterial hypotension, reduced fluid volume, low central venous pressure, tachycardia, increased cardiac output, low peripheral resistance, increased vascular stasis, hemoconcentration and hypercoagulation
  • Renal failure and death owing to hemoconcentration and hypoperfusion of organs including kidneys, heart and brain
  • Respiratory problems arising due to ascites with associated paralytic ileus.

Classification of symptoms

OHSS is generally categorized as early OHSS and late OHSS. Early OHSS ensues immediately following ovulation triggering (luteal phase of COS) while late, more severe, OHSS occurs in case of pregnancy following ART (increase in endogenous hCG).13,14     Table 1 enlists the classification of OHSS symptoms.14

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Risk factors and biomarkers for OHSS

There are many well-known and clearly-documented risk factors for the development of OHSS including: young age, low body mass index (BMI), polycystic ovarian syndrome (PCOS), allergic history, high antral follicle count (AFC), high basal anti-müllerian hormone (AMH), high doses of gonadotropins, high or rapidly rising estradiol levels, large numbers of large and medium-sized follicles, large numbers of oocytes retrieved, elevated inhibin B levels, high or repeated doses of hCG, pregnancy, and prior OHSS.1,5,14  

In a cohort of 262 IVF cycles, basal serum AMH level had a sensitivity of 90.5% and specificity of 81.3% for predicting OHSS and was a better predictor than age and BMI. Both the basal serum AMH level and serum estradiol level on the day of hCG administration were significant predictors of OHSS by logistic regression analysis.15  >   Miao and Huang16     reported that high serum inhibin B levels may predict OHSS. Lyon et al17   had reported that early OHSS is predicted by the number of oocytes retrieved (range 18-46) and estradiol concentration on the day of hCG administration (range 12,122-24,454 pmol/l) while late OHSS is predicted by the number of gestational sacs (range 2-3) on ultrasound 4 weeks after embryo transfer. A decreased dopaminergic tone and deregulated dopamine receptor 2 (Drd2) signaling account for higher VEGF and vascularization leading to increased OHSS risk in PCOS.18   According to a study conducted in women with moderate/severe OHSS and age-matched women without OHSS, AMH (AUC = 0.87) and AFC (AUC = 0.74) had moderate accuracy for predicting OHSS while inhibin B (AUC = 0.58) and LH (AUC = 0.61) had low accuracy (Figure 2). The cut-off value for AMH 3.3 ng/mL had the highest sensitivity of 90% and specificity of 71% for predicting OHSS. The positive (PPV) and negative predictive values (NPV) for AMH were 61% and 94%, respectively. The cut-off value for AFC was 8 with 78% sensitivity, 65% specificity, 52% PPV and 86% NPV.19

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Prevention of OHSS

Prevention with iCOS

Once the risk factors for OHSS have been identified, the primary step towards the prevention of OHSS involves individualization of the ovarian stimulation protocol, i.e. iCOS. Since the introduction of COS, pregnancy rates with IVF have escalated; however, several protocols may be used to accomplish ovarian stimulation and any single approach may not be suited to all the patients in a given population. Therefore, the approach should be individualized as per patients’ requirements through iCOS.20

The factors that generally affect the IVF outcome include patient age, hormonal status, PCOS, endometriosis and previous response to COS. There are several biomarkers in addition to the aforementioned factors that may help characterize every patient in order to decide the best COS protocol. These include FSH, AMH, inhibin B hormone levels, and AFC.21   The utility of these markers to predict ovarian reserve has been dealt with in detail in the previous article.

Yates et al22   evaluated the advantages of using novel, stratified ovarian hyperstimulation protocols, adapted as per individual AMH levels, and compared the same with conventional stimulation. Data were accumulated for 769 women undergoing first cycle of IVF, using fresh embryos. Three hundred and forty six women were subjected to conventional stimulation protocols while 423 women were treated under new AMH-tailored protocols. Following results were obtained:

  • Embryo transfer rates increased to 79-87% with AMH-tailored stimulation protocols
  • Pregnancy rate per cycle started and live birth rate also increased significantly in comparison with conventionally treated women (17.9-27.7% and 15.9-23.9%, respectively)
  • The incidence of OHSS was significantly reduced (6.9-2.3%) in the AMH group and failed fertilization also declined from 7.8 to 4.5% in this group
  • The cost of fertility drug treatment plunged by 29% per patient and the overall cost of clinical management of OHSS fell by 43% in the AMH group.

Therefore, it is clearly evident that individualized, AMH-guided, COS protocols improve positive clinical outcomes, reduce the incidence of complications and reduce the costs associated with assisted reproduction to a considerable extent.

A systematic review identified AFC and AMH as the most sensitive markers of ovarian reserve that may be best suited to individualize COS protocols. The review also concluded that personalized IVF helps clinicians in counseling their patients especially in cases of extremes of ovarian response. Therapeutic strategies based on selective use of GnRH analogues and the adjustment of gonadotrophin dose on the basis of potential ovarian response in every single woman aids safer and effective IVF practice.23

Canceling ovulation induction

hCG is known to be associated with OHSS. Therefore, abrogating ovulation induction by not giving hCG when several risk factors of OHSS are present seems to be the best approach to prevent OHSS.24     It was in the 1970s that the preliminary evidence of OHSS prevention by withholding hCG stimulus surfaced.24     However, this approach is generally considered for patients at high risk of OHSS and total loss of cycle control.14

Benadiva and colleagues reported that withholding gonadotropin administration appeared to be an effective approach to prevent the development of severe OHSS in a high-risk population. This strategy yielded a high pregnancy rate without the need to repeat multiple frozen-thawed cycles.25

It is not feasible to apply this approach in an IVF scenario where the primary goal is to increase the number of oocytes as withholding hCG administration prevents OHSS at the expense of losing the cycle.24,26

Coasting – Suspending gonadotropin administration

Coasting refers to postponement of hCG administration in women who respond to ovarian stimulation with high plasma levels of estradiol until serum estradiol declines to a safe level.27   Coasting should be considered when the estradiol level is >3000 pg/mL in the setting of immature follicles.28   The duration of coasting should be limited to <4 days.27,29     This may help avoid the decrease in implantation and pregnancy rates that may ensue longer periods of coasting. Administration of hCG should be withheld until serum estradiol falls below 3000 pg/ml. This may help attain a low incidence of severe OHSS (<2%) and provide fertilization rate ranging from 55-71% and pregnancy rate of 36.5-63%.29

Nardo and colleagues27   determined the impact of length of coasting on the reproductive outcome in women at risk of developing OHSS. Coasting was undertaken at serum estradiol levels ≥17000 pmol/L but <21000 pmol/L. hCG was administered when hormone levels decreased to <17000 pmol/L. Eighty-one women with coasted stimulation cycles were grouped according to the number of coasting days. Severe OHSS occurred in one case, which represented 1.2% of patients who underwent coasting because of an increased risk of developing the syndrome. There was no difference between cycles coasted for 1-3 days and cycles coasted for ≥4 days as far as oocyte maturity, fertilization and embryo cleavage rates were concerned. Women in whom coasting lasted for ≥4 days had significantly fewer oocytes retrieved and decreased implantation rate compared to those coasted for 1-3 days. Coasting thus appeared to decrease the risk of OHSS without compromising the IVF cycle pregnancy outcome. Prolonged coasting reduced implantation rates. Internal coasting, i.e. interruption of the early stage of stimulation, appears safe for women at a high risk of OHSS and does not negatively affect fertilization, implantation or pregnancy rates.30   However, evidence is also there in the literature that suggests no benefit of using coasting to prevent OHSS compared with no coasting or other interventions.31

Reducing the hCG trigger dose

It is speculated that a reduction in the standard dose of hCG administered to trigger oocyte maturation might prevent OHSS.14   Infertile patients at high risk of developing OHSS given 2500 IU hCG did not report the development of moderate or severe OHSS. A majority of these women conceived (Figure 3) and there were three twin pregnancies. Therefore, low-dose of hCG appears to prevent the development of OHSS without compromising success rates.32     A meta-analysis of 9 trials published between 2002 and 2007 revealed that ovarian hyperstimulation was less significant in the GnRH antagonist (GnRHa) low-dose hCG protocol compared with the non-supplemented agonist protocol (OR 0.30; 95% CI 0.09-0.96).33

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A recent study by Chen and colleagues34   sought to determine the minimum dose of hCG sufficient to effectively trigger maturation of oocytes and prevent OHSS in a series of hyper-responders treated with a long GnRHa protocol. Pregnancies and births were achieved in 3 patients out of 5 in vitro fertilization-embryo transfer (IVF-ET) cycles. There was no evidence of moderate or severe OHSS. Triggering with 2000U hCG was effective in preventing OHSS in unpredicted hyper-responders undergoing IVF in a long GnRHa protocol.

A Cochrane review compared the safety and effectiveness of subcutaneous recombinant hCG (rhCG) and high dose recombinant LH (rLH) with that of intramuscular urinary hCG (uhCG) for inducing final oocyte maturation triggering in IVF and ICSI cycles. In all, 14 randomized controlled trials were included in the analysis. rhCG and uhCG did not demonstrate any significant difference with regard to the ongoing pregnancy or live birth rate. Furthermore, the incidence of OHSS did not differ significantly between the rhCG and uhCG groups. Similarly, ongoing pregnancy or live birth rate and incidence of OHSS were not different between rhLH and uhCG. It could therefore be deduced that uHCG could still be the best choice for final oocyte maturation triggering in IVF and ICSI treatment cycles owing to its effectiveness and ease of availability.35

Luteal phase support

A defective corpus luteum function as a result of the relatively short endogenous LH surge may have deleterious effects on endometrial receptivity. Aggressive luteal phase support is thus required. Estradiol and progesterone supplementation in the luteal phase and the first trimester can help attain this. Adjuvant low-dose hCG is also a potential alternative.36

Castillo and colleagues37   evaluated the efficacy and safety of luteal support using hCG after triggering ovulation with GnRH agonist in IVF/ICSI antagonist cycles. One hundred and ninety two OHSS-at risk patients, following a GnRH antagonist protocol (0.25mg/day cetrorelix) during recombinant FSH stimulation, were triggered with 1.5mg s.c. leuprorelin for ovulation. Group A (n=44) received 1000IU, group B (n= 115) received 500IU while group C (n=33) received 250IU hCG for luteal support every third day, starting the day after oocyte retrieval. Overall pregnancy rate was 51.8% and clinical pregnancy rate was 43.4%. Nearly 4.2% subjects developed moderate and 3.6% reported severe OHSS. About 85.7% of the severe cases were late-onset OHSS, related to pregnancy. Therefore, GnRH agonist single dose for triggering ovulation and low doses of hCG used as luteal-phase support helped secure a normal pregnancy outcome without increasing the OHSS risk.

Dopamine agonist administration

Dopamine agonists (DAs) have been used with varying success during the ovarian stimulation phase when there are early signs of OHSS. Of 1646 women undergoing assisted reproduction, 914 received a DA. In the treated group, 9.41% developed OHSS as compared to 21.45% in the non-treated group. The use of DAs certainly prevented OHSS.38   DAs block the expression of the VEGF receptor, thereby preventing the development of OHSS.39

Bromocriptine, an ergot alkaloid dopamine receptor agonist, has a strong agonist action at the D2 receptor while a weak antagonist action at the D1 receptor. It has the potential to stimulate both pre- and post-synaptic receptors.40   The efficacy of bromocriptine in reducing the incidence and severity of OHSS was evaluated in patients undergoing assisted reproduction through a prospective study. The impact of bromocriptine administration on pregnancy rates was also investigated. The study was conducted over a 1-year period and enrolled 40 patients at high risk for developing OHSS. Bromocriptine was administered for a period of 16 days starting from the day of ovum pick up. The study end-points included incidence of moderate and severe OHSS, timing of onset of OHSS (early/late), hospitalization rate, pregnancy rates and tolerability of medication. The participants were compared with a historical group of high responders matched for age and BMI. A significant reduction in the incidence of moderate OHSS, early OHSS and the number of admissions was clearly evident. Average duration of hospitalization was significantly reduced. The incidence of clinically significant OHSS was 17.5% in the study group as compared to 40.9% in the control group. Figure 4 depicts the incidence of OHSS in the two groups. There appeared to be no significant difference between the groups in clinical pregnancy rates.40

A recent study determined the effects of bromocriptine on vascular endothelial growth factor (VEGF) levels in serum, kidney function and OHSS in women undergoing IVF. Twenty-eight women were randomly divided into two groups (Group A – folic acid, Group B – Bromocriptine) and were administered therapy for 14 days, starting on the day of hCG administration. Physical exams, pelvic ultrasounds and laboratory evaluations were performed on the day of hCG administration and 7 days later. Bromocriptine did not alter blood levels of VEGF and kidney function. It further did not affect the incidence of OHSS in high-risk patients subjected to IVF.41

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GnRH agonist trigger

Gonadotropin-releasing hormone agonist (GnRHa) trigger has been used for more than 2 decades now in place of hCG to prevent OHSS. The introduction of GnRH antagonists helped eliminate OHSS completely as patients at high risk for OHSS could be triggered with GnRHa.42

The use of GnRHa to trigger final follicle maturation in stimulated cycles of hyper-responders is associated with a favorable reproductive outcome and no incidence of OHSS.43   GnRHa trigger, besides complete prevention of OHSS, also extends the advantages of the introduction of a surge of FSH in addition to the LH surge and the possibility to individualize luteal-phase supplementation based on ovarian response to stimulation.44

Griesinger et al45   assessed the incidence of OHSS, odds of live birth and neonatal outcome after GnRHa triggering of final oocyte maturation and vitrification of all pronucleate (2PN) oocytes for later frozen-thawed embryo transfer (FRET) in an OHSS-risk population. Forty OHSS-at risk patients undergoing ovarian stimulation in a GnRH-antagonist protocol were subjected to triggering with 0.2 mg triptorelin. No patient developed OHSS. Thirty-nine patients underwent 87 FRETs (mean number of FRETs per patient: 2.2±1.6; range: 1-7) with the cumulative live birth rate per patient coming out to be 35.0%. Mean time-to-conception resulting in live birth after agonist trigger was 24.2±17.1 weeks. Humaidan et al46   had also reported that there was 0% incidence of OHSS in fresh IVF cycles with ET as well as in oocyte donation cycles. Despite all the advantages, the rate of multiple pregnancies has been noted to be uncontrollably high. Therefore, the safety of this protocol in standard clinical practice in the context of IUI still needs investigation.43

Intravenous fluid administration at the time of oocyte retrieval

Several studies have investigated the ability of intravenous (IV) fluids including albumin, hydroxyethyl starch (HES), Haemaccel® and dextran in preventing severe form of OHSS, though the results have been inconsistent.47     One such review included randomized controlled trials (RCTs) comparing the effects of IV fluids with placebo or no treatment for the prevention of severe OHSS in high risk women undergoing IVF or ICSI treatment cycles. Statistically significant decrease in the incidence of severe OHSS was noted with administration of human albumin (8 RCTs, OR 0.67, 95% CI 0.45 to 0.99) as well as HES (3 RCTs, OR 0.12, 95% CI 0.04 to 0.40). However, there was no significant difference in the pregnancy rate between both groups.47     Venetis and colleagues,48   on the contrary, by means of 8 RCTs, reported that there was no significant difference in the incidence of severe OHSS in patients who received IV albumin (n=595) and those who did not (n=604). Treatment with IV albumin around the time of oocyte retrieval may also reduce pregnancy rates.49

Two hundred and fifty patients (cycles) considered at risk of developing OHSS in an IVF programme were randomized to receive either 20% human albumin 50 ml (n = 82); 6% HES (200/0.5) 500 ml (n = 85) or a placebo of 500 ml 0.9% NaCl solution (n = 83) over 30 min during oocyte collection. No severe OHSS was reported in patients receiving albumin and HES. Moderate OHSS was reported in 4 patients in the albumin group, 5 patients receiving HES and 12 patients receiving placebo. Both HES and albumin were able to significantly reduce the incidence of moderate, severe and overall incidence of OHSS. HES could therefore be used as a cheaper and safer alternative to human albumin in OHSS prevention.50

Cryopreservation of oocytes and embryos

In the position of ovarian hyper-response, cryopreservation of all embryos followed by transfer of thawed embryos seems an effective proposition to avoid OHSS without adversely affecting the pregnancy and live birth rates.51,52     A recent study determined the benefits of cryopreservation in patients at high risk of OHSS. Twenty four of the 66 recruited patients underwent cryopreservation of all the embryos due to high risk of OHSS (Group 1). The rest 42 patients formed group 2 and underwent fresh embryo transfer despite ovarian hyper-response (estradiol >4000/mL, hCG day). There was no case of OHSS in group 1 while 40.5% in group 2 developed OHSS. Group 2 had 12.9% implantation rate, 21.4% pregnancy rate per transfer and 22.2% spontaneous abortion. Live birth rates were significantly better in group 1 (15.4% vs. 67%) with a significant lower rate of spontaneous abortion (27% vs. 11.4%) following frozen ET cycles.51   Both elective cryopreservation of embryos with subsequent frozen embryo transfer and coasting seem to be effective ways of improving pregnancy rates and limiting severe OHSS.53     Ferraretti and colleagues54   recruited 125 patients at risk of OHSS in two groups: group 1, control group (n = 67), had fresh embryo transfers; group 2 (n = 58) had cryopreservation of all obtained pronucleate embryos.   Pregnancies per patient (46.3 vs. 48.3%) and live birth rates (38.8 vs. 39.6%) were not different in the two groups. However, no cases of OHSS occurred in group 2, while four patients developed OHSS in group 1. The implantation rate was slightly but not significantly lower in group 2.

Vitrification is a simple and valuable technique being used extensively in the majority of IVF units, mainly for oocyte and blastocyst cryopreservation.55     Selman and colleagues56   ascertained the performance of embryo vitrification as an emergency procedure for patients at high risk of OHSS. A total of 69 embryos from 24 patients were vitrified and warmed for deferred embryo transfer. Surviving embryos were transferred, resulting in 10 clinical pregnancies. It has been reported that vitrified-warmed blastocyst transfer (BT) cycles yield statistically significantly higher clinical pregnancy and implantation rates compared with fresh BT cycles.57   Vitrification, thus, appears to be a promising method with favorable outcomes that can be recommended as a routine technique for cryopreservation of human embryos.

Treatment of OHSS

Conservative management is generally sufficient as the syndrome is self-limiting. Mild OHSS does not require any specific treatment. However, a close examination should be done and care should be taken since the case may progress to moderate or severe OHSS. Rest and adequate fluid intake defines the treatment for patients with moderate OHSS. Strenuous physical activity should be avoided.

Severe OHSS calls for close monitoring and immediate initiation of therapy. The aim of therapy is to mobilize fluid from the third space back to the vessels, maintaining circulatory hemodynamics and prevent hemoconcentration.12

Gong et al58   recently evaluated the efficacy of three treatment protocols for OHSS: 25 patients were given low-molecular dextran and albumin, 67 patients were treated with 6% medium molecular-weight HES, and 40 patients were treated with active aspiration of pleural effusion and ascites. All three therapies improved the symptoms of OHSS and various blood biochemical parameters. Patients with OHSS can be managed with outpatient transvaginal paracentesis effectively.59   Early outpatient paracentesis for moderate to severe OHSS represents the most cost-effective management strategy when compared with traditional conservative inpatient therapy.60   Paracentesis and albumin administration, the active outpatient interventions to manage OHSS, avoid hospitalizations and minimize the progression and complications of OHSS.61

Aboulghar and colleagues62   reported on the significance of IV fluid therapy and ascitic fluid aspiration in the management of severe OHSS by subjecting 42 women with severe OHSS to ultrasonically guided transvaginal aspiration of ascitic fluid and IV fluid infusion. Aspiration was followed by considerable improvement of symptoms and general condition. Hematocrit readings decreased by 22%, creatinine clearance increased by 79.3%, and urine output increased by 220.7%. An average of 3900 mL fluid was aspirated. The average duration of hospital stay was 3.8 days in the treated women. In patients treated conservatively, severe symptoms and electrolyte imbalance continued for an average of 9 days, and the average hospital stay was prolonged to 11 days.

There are several medications that may be used to curb the progression of OHSS and manage the symptoms. Infections are common during the procedures like paracentesis, urinary catheterization, pleural puncture undertaken to manage OHSS. Antibiotic prophylaxis is therefore recommended.12

Conclusion

OHSS is a serious, sometimes fatal complication of uncontrolled ovarian stimulation. The primary step in preventing this syndrome is tailoring/individualizing the stimulation protocol a patient is subjected to. Owing to the heterogeneity of the patient population, the outcomes of the various strategies adopted for the prevention of OHSS vary considerably. Withholding hCG and gonadotrophins and continuing GnRH agonist in down-regulated cycles appears a promising preventive strategy. Canceling the cycle, coasting, reducing the hCG trigger dose or employing a GnRH trigger in the setting of a GnRH antagonist protocol, use of IV fluids at the time of oocyte retrieval, and cryopreservation of all oocytes are several other strategies that may be used to prevent OHSS with varying results.

OHSS should be anticipated and studied as soon as hCG is administered and the clinician should not wait for the symptoms to appear. This may help develop prevention strategies before the onset of signs of severe OHSS.

References

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