Severe Early Ovarian Hyperstimulation Syndrome Research Articles

Pregnancy Rate in Frozen Cycles Transfer After Freeze-All Policy to Prevent Ovarian Hyper Stimulation Syndrome

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic state, potentially lethal, and still one of the major complications encountered during controlled ovarian stimulation (COS) in IVF. It occurs in approximately 1–14 % of assisted reproductive technique (ART) cycles and is related to increased vascular permeability. There are two forms of (OHSS) early and late form. Objectives: The aim of the study was to evaluate the pregnancy rate from frozen thawed embryo transfer after freeze-all policy for patient with high risk for OHSS. Patients and methods: This is cohort study conducted at Genetics and Infertility Unit, Department of Obstetrics and Gynecology, Zagazig University and a private center (retro- prospective and record-based data). The study was carried out on 150 infertile cases. They were divided into three groups. Group A: Frozen thawed embryo transfer after freeze-all policy for cases of high risk to OHSS, group B: frozen thawed embryo transfer for cases with normal ovarian response and group C: Fresh embryo transfer in cycles with 6 or more oocytes with antagonist protocol. Results: The main results of the study revealed that there was high statistically significant difference between groups regarding pregnancy outcomes. Pregnancy rate in frozen cycles is better than fresh cycles in normal responders with no late OHSS and less severe early OHSS. Conclusion: Freeze-all policy improves pregnancy rate in high and normal responders. Also, it prevents late OHSS.

Plasma pentraxin 3 is higher in early ovarian hyperstimulation syndrome than in uncomplicated in vitro fertilization cycle of high-risk women

PurposePentraxin 3 (PTX3) is a locally secreted, quicker responsive pro-inflammatory protein than C-reactive protein (CRP). We evaluated the value of PTX3 in the prediction of ovarian hyperstimulation syndrome (OHSS), a severe complication of in vitro fertilization (IVF).MethodsThis two-year prospective follow-up study included 27 women with uncomplicated IVF-cycles (IVF group) and 31 patients diagnosed with moderate or severe early OHSS (OHSS group). PTX3 was analysed from follicular fluid (FF) and serial blood samples with enzyme-linked immunoassay and CRP with particle-enhanced immunoturbidimetric assay. The value of PTX3 and CRP in detecting OHSS was examined with receiver operating characteristic (ROC) curve analysis and expressed as the area under the curve (AUC).ResultsThe circulating PTX3 level peaked at two days after oocyte pick-up (OPU2), and in the OHSS group the level was 1.9 times higher (P = 0.006) than in the IVF group. However, in ROC curve analysis PTX3 (AUC 0.79, best cut off 1.1 µg/L) was not superior to CRP (AUC 0.87; best cut off 9.5 mg/L) in predicting early OHSS. In the IVF group, the FF-PTX3 concentration was 15–20 times higher than in the plasma. PTX3 level at OPU2 correlated with the number of punctured follicles (r = 0.56, n = 22, P = 0.006). Triggering with human chorionic gonadotrophin or early pregnancy had no effect on PTX3 level.ConclusionThe elevated PTX3 concentration in OHSS at OPU2, when freeze-all embryos strategy is still possible to consider, indicates that PTX3 level could provide additional benefit in the risk assessment for early OHSS.

A decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for ovarian hyperstimulation syndrome after triggering final oocyte maturation with hCG.

STUDY QUESTIONCan the grade of ascites, haematocrit (Ht), white blood cell (WBC) count and maximal ovarian diameter (MOD) measured on Day 3 be used to construct a decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for severe ovarian hyperstimulation syndrome (OHSS) after an hCG trigger?SUMMARY ANSWERUsing cut-offs of ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm on Day 3, a decision-making algorithm was constructed that could predict subsequent development of severe OHSS on Day 5 with an AUC of 0.93, a sensitivity of 88.5% and a specificity of 84.2% in high-risk patients triggered with hCG.WHAT IS KNOWN ALREADYDespite the increasing popularity of GnRH agonist trigger for final oocyte maturation as a way to prevent OHSS, ≥75% of IVF cycles still involve an hCG trigger. Numerous risk factors and predictive models of OHSS have been proposed, but the measurement of these early predictors is restricted either prior to or during the controlled ovarian stimulation. In high-risk patients triggered with hCG, the identification of luteal-phase predictors assessed post-oocyte retrieval, which reflect the pathophysiological changes leading to severe early OHSS, is currently lacking.STUDY DESIGN, SIZE, DURATIONA retrospective study of 321 patients at high risk for severe OHSS following hCG triggering of final oocyte maturation. High risk for OHSS was defined as the presence of at least 19 follicles ≥11 mm on the day of triggering of final oocyte maturation.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study includes IVF/ICSI patients at high risk for developing severe OHSS, who administered hCG to trigger final oocyte maturation. Ascites grade, MOD, Ht and WBC were assessed in the luteal phase starting from the day of oocyte retrieval. Outcome measures were the optimal thresholds of ascites grade, MOD, Ht and WBC measured on Day 3 post-oocyte retrieval to predict subsequent severe OHSS development on Day 5. These criteria were used to construct a decision-making algorithm for embryo transfer, based on the estimated probability of severe OHSS development on Day 5.MAIN RESULTS AND THE ROLE OF CHANCEThe optimal Day 3 cutoffs for severe OHSS prediction on Day 5 were ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm. The probability of severe OHSS with no criteria fulfilled on Day 3 is 0% (95% CI: 0–5.5); with one criterion, 0.8% (95% CI: 0.15–4.6); with two criteria, 13.3% (95% CI: 7.4–22.8); with three criteria, 37.2% (95% CI: 24.4–52.1); and with four criteria, 88.9% (95% CI, 67.2–98.1). The predictive model of severe OHSS had an AUC of 0.93 with a sensitivity of 88.5% and a specificity of 84.2%.LIMITATIONS, REASONS FOR CAUTIONThis is a retrospective study, and therefore, it cannot be excluded that non-apparent sources of bias might be present. In addition, we acknowledge the lack of external validation of our model. We have created a web-based calculator (http://ohsspredict.org), for wider access and usage of our tool. By inserting the values of ascites grade, MOD, Ht and WBC of high-risk patients on Day 3 after oocyte retrieval, the clinician instantly receives the predicted probability of severe OHSS development on Day 5.WIDER IMPLICATIONS OF THE FINDINGSThe present study describes a novel decision-making algorithm for embryo transfer based on ascites, Ht, WBC and MOD measurements on Day 3. The algorithm may be useful for the management of high-risk patients triggered with hCG and for helping the clinician’s decision to proceed with, or to cancel, embryo transfer. It must be emphasized that the availability of the present decision-making algorithm should in no way encourage the use of hCG trigger in patients at high risk for OHSS. In these patients, the recommended approach is the use of GnRH antagonist protocols, GnRH agonist trigger and elective embryo cryopreservation. In addition, in patients triggered with hCG, freezing all embryos and luteal-phase GnRH antagonist administration should be considered for the outpatient management of severe early OHSS and prevention of late OHSS.STUDY FUNDING/COMPETING INTEREST(S)NHMRC Early Career Fellowship (GNT1147154) to C.A.V. No conflict of interest to declare.TRIAL REGISTRATION NUMBERN/A.

The effect of luteal GnRH antagonist on moderate and severe early ovarian hyperstimulation syndrome during in vitro fertilization treatment: a prospective cohort study.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of assisted reproductive technology (ART) treatment. However, there are limited data regarding the ability of the luteal GnRH antagonist cetrorelix to reduce the incidence of moderate and severe OHSS, and the mechanism remains unclear. Thus, we designed a study to assess the effectiveness of cetrorelix to prevent early moderate and severe OHSS in high-risk patients undergoing controlled ovarian stimulation for IVF/ICSI. In this prospective cohort study, 105 patients with high-risk OHSS undergoing cryopreservation of all embryos were divided into two groups according to their personal choice. The cetrorelix group (n = 65) received 0.25mg of cetrorelix by subcutaneous injection daily, from days 3 to 5 post-oocyte retrieval (POR); the control group (n = 40) received no drug. The primary outcome measures were the incidence and severity of early moderate and severe OHSS. Secondary measures included serum estradiol levels, ovarian volume, ascites volume, hematocrit values, and WBC count on days 3, 6, and 9 POR. VEGF and EGR-1 levels were assessed, and binary logistic regression analysis was applied to predict associations between clinical variables and OHSS. Ninety-six patients were examined. The incidence of moderate and severe OHSS was significantly lower in the cetrorelix group than in the control group (18.03% and 37.14%, respectively; P = 0.037). Serum estradiol (P = 0.013), white blood cell count (P = 0.031), ascites volume (P = 0.036), EGR-1 (P = 0.025), and VEGF levels (P = 0.015) were significantly higher in the control group on day 6 POR than on day 3 POR, while no increase was observed between day 3 POR and day 6 POR in the cetrorelix group, indicating a faster regression of OHSS symptoms. Cetrorelix intervention was associated with the incidence and severity of OHSS (OR 0.29, 95% CI 0.11-0.78, P = 0.014). Cetrorelix effectively reduces the incidence of early moderate and severe OHSS in high-risk women and decreases serum VEGF levels.

A Second Dose of GnRHa in Combination with Luteal GnRH Antagonist May Eliminate Ovarian Hyperstimulation Syndrome in Women with ≥30 Follicles Measuring ≥11 mm in Diameter on Trigger Day and/or Pre-trigger Peak Estradiol Exceeding 10 000 pg/mL.

This observational study included 21 patients at remarkably high risk of ovarian hyperstimulation syndrome (OHSS), characterized by more than 30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL, which was also the feature of women with established severe early OHSS followed by gonadotrophin-releasing hormone agonist (GnRHa) trigger and freeze-all policy that previously have been reported. All patients received a second dose of GnRHa 12 h after the first GnRHa trigger combined with administration of GnRH antagonist at 0.25 mg/day for a period of 3 days from the day of oocyte retrieval onwards. The in vitro fertilization (IVF) outcomes may be preferable compared with a bolus of GnRHa trigger and none of the included patients developed moderate-to-severe OHSS. Moreover, patients' symptoms, reproductive hormone levels and ultrasound findings were improved significantly. This new strategy seems to be efficacious and could be a further supplement of GnRHa trigger with or without applying freeze-all strategy to completely prevent early-onset moderate to severe OHSS, especially for the patients characterized by ≤30 follicles measuring ≥11 mm in diameter on trigger day and/or pre-trigger peak estradiol exceeding 10 000 pg/mL. Further studies should be performed to compare this regimen with conventional methods of OHSS prevention.

Severe early ovarian hyperstimulation syndrome after spontaneous pregnancy and despite GnRH-agonist trigger during controlled ovarian stimulation in an oocyte donor cycle: a case report

Severe early ovarian hyperstimulation syndrome after spontaneous pregnancy and despite GnRH-agonist trigger during controlled ovarian stimulation in an oocyte donor cycle: a case report

Ultrasound and hematological changes during early luteal phase in women at high risk for developing ovarian hyperstimulation syndrome.

To assess ultrasound and hematological changes during the early luteal phase following triggering of final oocyte maturation with human chorionic gonadotropin (hCG) in women at high risk for developing ovarian hyperstimulation syndrome (OHSS). This was a retrospective cohort study of 319 women undergoing in-vitro fertilization who were at high risk for OHSS following administration of hCG for the triggering of final oocyte maturation. Patients were treated with a gonadotropin-releasing hormone agonist or antagonist protocol and were monitored for 5 days post-oocyte retrieval (early luteal phase). Severe OHSS was diagnosed in the presence of at least moderate ascites and two or more of the following: maximum ovarian diameter (MOD) > 100 mm, hematocrit (Ht)> 45%, white blood cell count (WBC) >15 000/mm3 , hydrothorax, dyspnea and oliguria. Outcome measures included change in Ht, ascites grade, WBC and MOD, as well as the association between these changes during the early luteal phase. Ascites grade, Ht and WBC increased significantly (P ≤ 0.001) during the early luteal phase, both in patients who developed and in those who did not develop severe early OHSS. MOD increased significantly (P = 0.001) only in patients who developed severe early OHSS. On multivariable analysis, both time following oocyte retrieval and whether severe early OHSS developed were significantly associated with ascites grade, Ht, WBC and MOD; furthermore, there was also a significant interaction between time and development of severe early OHSS for all four variables (P ≤ 0.001). In women at high risk of OHSS, ascites grade, Ht and WBC significantly increased with time over the 5-day observation period, in line with the pathophysiology of the syndrome. Our data support the use of MOD in the diagnosis of severe early OHSS, and provide novel evidence for the role of change in Ht as a patient-specific hemoconcentration marker during development of OHSS. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Vascular endothelial growth factor antagonist reduces the early onset and the severity of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of controlled ovarian stimulation (COH) during assisted reproductive technology (ART) protocols. This syndrome is a result of ovarian expression of vascular endothelial growth factor (VEGF), which increases vascular permeability. To evaluate the efficiency of prophylactic and therapeutic use of cabergoline in women with higher risk of developing OHSS. In this prospective randomized study, 146 women undergoing in vitro fertilization (IVF) cycles with GnRH agonist protocols with a higher risk of OHSS diagnosed during the HCG day administration (more than 18 follicles observed larger than 12mm in diameter during COH and/or estradiol levels of 3000-3500pg/ml, previous episodes of OHSS). Women were randomly divided in two groups. The first group included 78 women who received 0.5mg per day of cabergoline (Dostinex®) orally for 7 days starting from hCG administration day. The second group included 68 women who received no medication treatment. Overall, in each group 25 patients have developed OHSS. This defines subgroup 1 that includes 25 cases of OHSS obtained in group 1 and subgroup 2 where 25 cases of OHSS obtained in group 2. Early OHSS was defined as being when the onset of the syndrome was initiated during the first 9 days after hCG administration and late OHSS was defined as being when the onset of the syndrome was initiated from 10 days after hCG administration. Outcome measures of this study were the incidence of moderate and severe OHSS, early or late OHSS and pregnancy rates. There was no evidence of a statistically significant reduction in the incidence of OHSS in cabergoline group (32.05% vs. 36.76%; P>0.05). Late OHSS was observed in 60.6% of cases in cabergoline group while 39.4% of cases in the other group (P=0.036). Early OHSS decreased significantly (P<0.05) in the cabergoline group. Severe OHSS cases were more common within subgroup 2 than subgroup 1 (32% vs. 8%, P=0.000). There was no difference in clinical pregnancy rates (PR) and miscarriages rates between the two subgroups. The cabergoline administration (Dostinex®) for patients with high-risk of OHSS can reduce the rate of early OHSS and its severity in GnRH agonist IVF cycles, but cannot prevent the incidence of OHSS.

Cetrotide administration in the early luteal phase in patients at high risk of ovarian hyperstimulation syndrome: A controlled clinical study.

The aim of the present pilot study was to assess the feasibility and efficacy of Cetrotide administration in the early luteal phase in patients at high risk of ovarian hyperstimulation syndrome (OHSS), undergoing embryo cryopreservation following superovulation. A total of 135 patients at high risk of OHSS and undergoing embryo cryopreservation were divided into two groups. In the treatment group (n=39), the patients received daily subcutaneous injections of 0.25 mg Cetrotide between days 1 and 5 following ooctye retrieval, and volume expansion and symptomatic treatment were also provided. In the control group (n=96), the patients received routine treatments, including volume expansion therapy. The serum steroid hormone concentrations of the patients were measured on days 2, 5 and 8 following ooctye retrieval, while the incidence of moderate or severe OHSS, self-evaluated clinical symptoms and various clinical indicators were recorded. The serum estradiol (E2), luteinizing hormone and progesterone levels in the treatment group on days 2, 5 and 8 following oocyte retrieval were not found to differ significantly when compared with the patients in the control group (P>0.05). The incidence of severe OHSS did not differ significantly between the two groups (P>0.05). The average length of hospital stay and length of luteal phase were not found to be significantly different between the treatment and control groups (P>0.05). In conclusion, Cetrotide injections in the early luteal phase did not alter the serum steroid levels of patients at high risk of OHSS undergoing embryo cryopreservation, and were unable to reduce the incidence of severe early OHSS. However, further randomized studies are required to evaluate the effectiveness of Cetrotide in the prevention of OHSS.

Serum vascular endothelial growth factor levels following luteal gonadotrophin‐releasing hormone antagonist administration in women with severe early ovarian hyperstimulation syndrome

To investigate the kinetics of serum vascular endothelial growth factor (VEGF) following gonadotrophin-releasing hormone (GnRH) antagonist administration in the luteal phase in women with established severe early ovarian hyperstimulation syndrome (OHSS). Pilot observational cohort study. Private in vitro fertilisation (IVF) Unit. Twelve IVF women diagnosed with established severe early OHSS 5 days post oocyte retrieval (POR). Women undergoing IVF diagnosed with severe early OHSS 5 days POR were given 0.25 mg GnRH antagonist for 4 days, from day 5 until and including day 8 POR, combined with elective blastocyst cryopreservation. Serum VEGF was measured from the day of oocyte retrieval until day 11 POR. Ovarian volume, ascites, serum estradiol and progesterone, haematocrit and white blood cells were monitored during the same period. Kinetics of VEGF following luteal GnRH antagonist administration in women with established severe early OHSS. The concentration of VEGF was highest (390.9 ± 137.4 pg/ml) 5 days POR, coinciding with the day of diagnosis of severe OHSS. There was a significant decline of VEGF on day 7 (302.8 ± 104.9 pg/ml; P = 0.026), day 9 (303.3 ± 148.3 pg/ml; P = 0.007), and day 11 (252.6 ± 182.7 pg/ml; P = 0.010) compared with day 5 POR. This decline was associated with an improvement of ultrasound and laboratory parameters, indicating regression of severe OHSS. All women were managed at an outpatient level. GnRH antagonist administration in the luteal phase is associated with a significant decline of VEGF and with regression of established severe early OHSS.

Risk factors for ovarian hyperstimulation syndrome: relevance of the number of follicles, serum estradiol levels and the number of oocytes collected

13:1901–1906. SeyhanA, Ata B, PolatM, SonWY, Yarali H,DahanMH. Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG. Hum Reprod 2013. doi:10.1093/det124. Triwitayakorn A, Suwajanakorn S, Pruksananonda K, Sereepapong W, Ahnonkitpanit V. Correlation between human follicular diameter and oocyte outcomes in an ICSI program. J Assist Reprod Genet 2003; 20:143–147.

Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger with the addition of 1500 IU hCG

Is severe early ovarian hyperstimulation syndrome (OHSS) completely prevented with the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol? Severe early OHSS can occur even after the GnRH agonist trigger and 1500 IU hCG luteal rescue protocol. Prior studies including over 200 women who received the GnRH agonist trigger and 1500 hCG luteal rescue protocol have reported complete prevention of severe early OHSS. Only a few late OHSS cases have been reported and it has been suggested that this protocol can be safely applied to any women under risk. This retrospective cohort study included all women who were at high risk of OHSS and were given the GnRH agonist trigger plus hCG luteal rescue protocol between December 2008 and August 2012 in the two participating centers. There were 23 women with a mean estradiol level of 4891 ± 2214 pg/ml and a mean number of >12 mm follicles of 20 ± 6 on the day of ovulation triggering. OHSS was categorized according to the Golan criteria. Overall 6 of the 23 (26%) women developed severe OHSS. Five women had severe early OHSS requiring ascites drainage and hospitalization and three of these women did not undergo embryo transfer. The number of follicles measuring 10-14 mm on the day of triggering was significantly different between women who developed severe early OHSS and those who did not. The small number of women with severe early OHSS may have prevented identification of other significant risk factors. Although the GnRH agonist plus 1500 IU hCG luteal rescue protocol significantly decreases the risk of severe OHSS, this life threatening complication can still occur in high-risk patients. It would be prudent to avoid hCG luteal rescue and freeze all embryos for future transfer in such women particularly when there are ≥18 follicles with 10-14 mm diameters even with few larger follicles.

Pregnancy and neonatal outcomes following luteal GnRH antagonist administration in patients with severe early OHSS

Do high-risk patients who develop severe early ovarian hyperstimulation syndrome (OHSS) and receive low-dose GnRH antagonist in the luteal phase have lower live birth rates compared with high-risk patients who do not develop severe early OHSS and do not receive GnRH antagonist in the luteal phase? Low-dose luteal GnRH antagonist administration in women with severe early OHSS is associated with similar live birth rates to that of high-risk patients who do not develop severe early OHSS and do not receive GnRH antagonist in the luteal phase. It has been reported that luteal GnRH antagonist administration in patients with established severe early OHSS appears to prevent patient hospitalization and results in quick regression of the syndrome on an outpatient basis. However, the effect of such treatment on pregnancy outcome has been investigated in only a small number of animal studies. This is a prospective cohort study of 192 IVF patients who were at high risk for OHSS and who did not wish to cancel embryo transfer and have all embryos cryopreserved. The study was conducted between January 2009 and December 2011 at Eugonia Assisted Reproduction Unit. Patients were <40 years of age, with polycystic ovaries, at high risk for OHSS (defined by the presence of at least 20 follicles ≥11 mm on the day of triggering of final oocyte maturation) and not willing to cancel embryo transfer and cryopreserve all embryos, if severe early OHSS was diagnosed by Day 5 of embryo culture. Patients who were diagnosed with severe early OHSS on Day 5 post-oocyte retrieval were administered 0.25 mg of ganirelix for 3 days, from Day 5 until and including Day 7 (OHSS + antag group, n = 22). High-risk patients who did not develop the severe early OHSS did not receive GnRH antagonist in the luteal phase (control group, n = 172). All patients underwent embryo transfer on Day 5. Live birth rates (40.9 versus 43.6%), ongoing pregnancy rates (45.5 versus 48.8%), clinical pregnancy rates (50 versus 65.1%), positive hCG (72.7 versus 75%), duration of gestation (36.86 ± 0.90 weeks versus 36.88 ± 2.38 weeks) and neonatal weight (2392.73 ± 427.04 versus 2646.56 ± 655.74 g) were all similar in the OHSS + antag and control groups, respectively. The incidence of major congenital malformations was 2.9% (3/103) in children born in the control group compared with no cases (0/14) in children born following luteal GnRH antagonist administration. No stillbirths or intrauterine deaths, and no cases of pregnancy-induced late OHSS were recorded in either group. None of the 22 patients with severe early OHSS required hospitalization following luteal antagonist administration. Ovarian volume, ascites, hematocrit, white blood cell count, serum estradiol and progesterone decreased significantly (P < 0.001) by the end of the monitoring period (Day 11 post-oocyte retrieval), indicating rapid resolution of the severe OHSS. This is a prospective cohort investigation with a very limited number of patients receiving the intervention and a larger number of control patients. Our findings suggest that low-dose luteal GnRH antagonist administration during the peri-implantation period may be safe, although larger studies with follow-up of the children born are required. Our study suggests for the first time that low-dose luteal GnRH antagonist administration in women with severe early OHSS is associated with a favourable IVF outcome, comparable to control high-risk patients without severe OHSS and not receiving the intervention. Regarding the wider implications on the concept of an OHSS-free clinic, administration of GnRH antagonist in the luteal phase may present a tertiary management level in patients with established severe OHSS, along with the use of GnRH antagonist protocols for primary prevention and the replacement of hCG with GnRH agonist for triggering final oocyte maturation for secondary prevention. However, at present, fresh embryo transfer combined with antagonist administration should only be used with caution by experienced practitioners, after carefully deciding which patients can have a fresh transfer or embryo cryopreservation, until the current data are confirmed by larger trials.

Ovarian hyperstimulation syndrome- an optimal solution for an unresolved enigma

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of controlled ovarian hyperstimulation (COH). The syndrome almost always presents either after hCG administration in susceptible patients or during early pregnancy. Despite many years of clinical experience, there are no precise methods to completely prevent severe OHSS, except by withholding the ovulation-inducing trigger of hCG. Recently, COH which combining GnRH antagonist co-treatment and GnRH agonist trigger has become a common tool aiming to eliminate severe early OHSS. However, the observed decrease in implantation and pregnancy rates following this approach has encouraged different modifications of luteal support aiming to improve outcome. One of the suggest approach is the 1500 IU hCG luteal rescue, which appears to be a promising protocol, aiming to reduce (rather than eliminating) severe early OHSS, without compromising outcome. In the present paper we discuss the different suggested strategies and offer a strict triage, aimed at eliminating the occurrence of severe OHSS based on several clinical observations, including the role of GnRH-antagonist in COH protocols, the use of different luteal rescue protocols and the ability to transfer embryos in the blastocyst stage.

Multiple transvaginal ascitic fluid aspirations improves the clinical and reproductive outcome in patients undergoing in vitro fertilisation treatment complicated by severe early ovarian hyperstimulation syndrome

The objective of this study is to examine the effect of repeated transvaginal ascitic fluid aspiration on the reproductive outcome in patients undergoing in vitro fertilisation treatment complicated with severe ovarian hyperstimulation syndrome. A total of 65 women with severe early OHSS were hospitalised and managed with transvaginal ascitic fluid aspiration either in < 3 occasions (control group; n = 29) or ≥ 3 occasions (multiple aspirations) (study group; n = 36). All patients in both groups received intravenous fluid, human albumin and thromboprophylaxis. Patients in the study group received significantly lower amounts of parenteral fluid (p < 0.05), human albumin (p < 0.01), and LMWH (p < 0.001). In addition, they had significantly lower days of hospitalisation (p < 0.01) as compared with the control group. There was no significant difference in the cancellation rate between the two groups, but patients who underwent multiple aspiration had a significantly higher pregnancy rate (82.8% vs 41.7%, p < 001) and significantly lower abortion rate (10.3% vs 40%, p < 0.05) compared with the control group. Repeated transvaginal asitic fluid aspiration even with large amounts is safe and effective in the treatment of symptomatic patients with severe OHSS. The pregnancy rate increased significantly along with a significant decrease in the abortion rate was observed after multiple aspirations compared with < 3 aspirations.

Agonist and antagonist coast

The use of GnRH-a in ovarian stimulation permitted stronger stimulation resulting in an increased incidence of OHSS. The first Cochrane review comparing GnRH agonist and GnRH antagonist protocols for ovarian stimulation showed no significant difference in OHSS rate between the two protocols, however, a recent Cochrane review showed a highly significant decrease in the incidence in OHSS rate in the antagonist protocol. Coasting is a commonly used procedure for preventions of OHSS. The optimum time to start coasting is when the lead follicle reaches 16 mm in diameter and hCG should be given when E2 level drops below 3000 pg/ml. Coasting may act by diminishing the functioning granulosa cell cohort. Administration of daily GnRH antagonist in high risk patients for OHSS who were down-regulated by GnRH-a resulted in rapid drop of E2 and decrease in incidence of OHSS. A series of patients who developed early OHSS were treated by daily GnRH antagonist injections, all embryos were cryopreserved. No progression to severe OHSS was observed.

Cabergoline and Ganirelix Therapy for Early Moderate to Severe Ovarian Hyperstimulation Syndrome (OHSS) Results in Faster Recovery than in Early Untreated OHSS

OBJECTIVE(S): To determine whether early-onset OHSS patients treated with cabergoline and ganirelix have more rapid symptom improvement and require less urgent care when compared with those with untreated early OHSS. DESIGN: Retrospective cohort study. MATERIALS AND METHOD(S): Consecutive patients with moderate to severe early OHSS between retrieval and ET from August 2008 until the present were included (n = 6). Early OHSS was defined as the development of symptoms presenting within 10 days from βhCG injection. All embryos were frozen, and patients received cabergoline 0.5 mg daily for 7 days and ganirelix 250 μg daily for 2 days. Day 0 was defined as the first day of treatment. Serial weights, number of urgent visits, and days of hospitalization were recorded. Controls were historical patients (n = 11) diagnosed with early-onset OHSS before initiation of the cabergoline/ganirelix protocol. Potential controls were excluded if no serial weights were documented in the medical record. Day 0 was defined as the date of diagnosis. The groups were compared using the Wilcoxon rank-sum test. RESULT(S): The results are presented in the table. CONCLUSION(S): This is the first report comparing patients treated with cabergoline and ganirelix in early-onset OHSS with early OHSS patients who did not receive therapy. Treated patients had more rapid weight loss at each time point, fewer unscheduled visits, and no hospital admissions. This protocol may represent a rapid and cost-effective outpatient therapy for patients diagnosed with moderate to severe early-onset OHSS.TableTreatment, median (25%, 75%)Control, median (25%, 75%)PAge27.0 (25.3, 33.0)32.0 (29.0, 34.0).13Body mass index23.3 (19.9, 24.8)20.8 (20.4, 21.2).51FSH units used4125 (1663, 4425)1500 (1200, 1875).04a.Peak E2, pg/dL6430 (5065, 8970)3335 (2481, 3890).003a.Follicles at retrieval53.5 (49.3, 55.5)35.5 (30.8, 44.8).03a.Oocytes30.5 (18.0, 40.0)25.0 (17.0, 31.0).56Weight change at day 2, kg−0.7 (−0.9, −0.5)+1.8 (+0.9, +2.8).003a.Weight change at day 4, kg−1.4 (−1.8, −1.4)+0.7 (+0.5, +1.4).004a.Weight change at day 7, kg−2.7 (−3.1, −1.8)−0.4 (−0.9, +1.6).03a.Unscheduled visits0.0 (0.0, 0.3)2.0 (1.0, 3.0).001a.No. of days of hospitalization0.0 (0.0, 0.0)6.0 (5.0, 11.0)<.001a.a . Open table in a new tab

Management of severe OHSS using GnRH antagonist and blastocyst cryopreservation in PCOS patients treated with long protocol

Despite the fact that many methods have been proposed for the management of severe ovarian hyperstimulation syndrome (OHSS), its prevention is mainly achieved by withholding human chorionic gonadotrophin (HCG) administration and cycle cancellation. Currently no curative therapy is available. Three women diagnosed with polycystic ovarian syndrome underwent ovarian stimulation for IVF using a long gonadotrophin-releasing hormone (GnRH) agonist protocol. Six days after oocyte retrieval, severe early OHSS was diagnosed by analysis of haematocrit, white blood cell (WBC) count, serum urea, and ultrasonographic assessment of ovarian size and ascitic fluid. On the same day, antagonist administration was administrated and continued daily for 1 week, while resulting blastocysts were cryopreserved. Progression of severe early OHSS was inhibited in all three patients. A marked decrease of haematocrit, WBC, ascitic fluid, oestradiol, progesterone and ovarian volume was observed, during 1 week of follow-up suggesting a luteolytic effect of GnRH antagonist. None of the patients required hospitalization. In conclusion, GnRH antagonist administration combined with blastocyst cryopreservation 6 days post retrieval might represent a new approach for the effective management of patients with established severe OHSS. The flexibility of the approach allows the elongation of the monitoring period up to 8 days following HCG administration.

Management of severe early ovarian hyperstimulation syndrome by re-initiation of GnRH antagonist

Several approaches have been proposed for the management of OHSS that reduce, but do not completely eliminate the incidence of human chorionic gonadotrophin (HCG)-induced early severe OHSS. Three women diagnosed with polycystic ovarian syndrome underwent ovarian stimulation for IVF using a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Three days after oocyte retrieval, severe early OHSS was diagnosed by analysis of haematocrit (Ht), white blood cell (WBC) count, serum urea, and ultrasonographic assessment of ovarian size and ascitic fluid. On the same day, antagonist administration was re-initiated and continued daily for a week, while all embryos were cryopreserved. No progression of severe early OHSS was observed in any of the patients. A marked decrease of Ht, WBC count, ovarian volume and ascitic fluid was observed during 1 week of follow-up, and none of the patients required hospitalization. GnRH antagonist re-initiation might represent a new strategy for flexible management of patients with established severe early OHSS. Based on the flexibility of the approach, if severe OHSS does not occur, patients may proceed to embryo transfer, while if severe early OHSS ensues, antagonist administration combined with embryo cryopreservation appear to be associated with prevention of life-threatening OHSS, facilitation of regression of severe OHSS to a moderate form and avoidance of patient hospitalization.