Moderate Ovarian Hyperstimulation Syndrome Research Articles

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.

Severe ovarian hyperstimulation syndrome after letrozole-gonadotropin stimulation: a case report

Ovarian hyperstimulation syndrome (OHSS) results from an exaggerated response to ovulation induction, characterized by a fluid shift from the intravascular space to third space compartments. The incidence of moderate OHSS is approximately 3–6% and severe OHSS occurs in 0.1–3% of treatment cycles [1, 2]. A number of causal mechanisms have been investigated, involving estradiol (E2), human chorionic gonadotropin (hCG), and vascular endothelial growth factor (VEGF). A strong association between E2 concentrations and risk for developing OHSS has been observed consistently [3]. A growing awareness and interest in treatments aimed at fertility preservation (FP) has led many women to pursue urgent oocyte or embryo cryopreservation. Those with estrogen-sensitive cancers often receive adjunctive treatment with letrozole, in efforts to limit exposure to elevated estrogen concentrations that typically result from exogenous gonadotropin stimulation; letrozole inhibits estrogen production by binding competitively to the cytochrome P450 component of the aromatase enzyme. Combination stimulation regimens yield results comparable to those achieved with standard gonadotropin stimulation protocols, but are associated with significantly lower E2 levels [4]. The risk of OHSS for women receiving adjunctive treatment with letrozole generally is considered low, because E2 levels are markedly lower than in cycles stimulated with gonadotropins alone. In fact, no cases of severe OHSS have been reported in a patient receiving combined treatment with letrozole and gonadotropins. Here, we report a case of severe OHSS arising in a woman with breast cancer after stimulation with exogenous gonadotropins, despite treatment with letrozole and having only moderately elevated E2 concentrations.

The Diagnosis and Management of Ovarian Hyperstimulation Syndrome

ObjectiveTo review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its diagnosis and clinical management OutcomesThese guidelines will assist in the early recognition and management of ovarian hyperstimulation. Early recognition and prompt systematic supportive care will help avert poor outcomes EvidenceMedline, Embase, and the Cochrane database were searched for relevant articles, using the key words “ovarian hyperstimulation syndrome” and “gonadotropins,” and guidelines created by other professional societies were reviewed. ValuesThe quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care Recommendations for practice were ranked according to the method described in that report (Table 1). Recommandations1.Once the diagnosis of ovarian hyperstimulation syndrome is made, disease severity should be classified as mild, moderate, severe, or critical. (III-B)2.The physician prescribing gonadotropins should inform each woman of her personal risk for ovarian hyperstimulation syndrome. (III-A)3.In areas where patients do not have ready access to physicians familiar with the diagnosis and management of ovarian hyperstimulation syndrome, the physician prescribing gonadotropins should ensure that women are made aware that they should contact a physician or a member of the team within the hospital unit who has relevant experience, should the need arise. (III-B)4.Outpatient management is recommended for women with mild and moderate ovarian hyperstimulation syndrome. If outpatient management for more severe ovarian hyperstimulation syndrome is to be undertaken, the physician should ensure that the woman is capable of adhering to clinical instructions and that there is a system in place to assess her status every 1 to 2 days. (III-A)5.Paracentesis should be performed in admitted patients with tense ascites to alleviate their discomfort. (II-2B)6.Outpatient culdocentesis should be considered for the prevention of disease progression in moderate or severe ovarian hyperstimulation syndrome. (II-2B)7.Women with severe and critical ovarian hyperstimulation syndrome should be admitted to hospital for intravenous hydration and observation. (III-A)8.Intravenous hydration should be initiated with a crystalloid solution to prevent hemoconcentration and provide adequate end-organ perfusion. If end-organ perfusion is not maintained with a crystalloid solution, an alternate colloid solution should be administered. (II-2B)9.Pain relief in admitted patients should be managed with acetaminophen and/or opioid analgesics. (III-B) Non-steroidal anti-inflammatory drugs with antiplatelet properties should not be used (III-B)10.Women with severe ovarian hyperstimulation syndrome should be considered for treatment with prophylactic doses of anticoagulants. (II-2B)11.Critical ovarian hyperstimulation syndrome should be managed by a multidisciplinary team, according to the end organ affected (III-C)

Cabergoline successfully prevented the incidence of severe OHSS

Ovarian hyperstimulation syndrome (OHSS) is one of serious complications in ovarian stimulation for IVF/ICSI. Recently dopamine receptor agonist cabergoline is reported to prevent OHSS by modulationg VEGF receptor activity. We investigated if administration of cabergoline reduces the risk of severe OHSS on a retrospective basis. Retrospective controlled study. Sixty one women had prophylactic intervention of cabergoline. They had controlled ovarian hyperstimulation for IVF or ICSI. Serum estrogen level in them on the HCG day showed more than 3500 pg/ml, so they had all embryos frozen instead of fresh transfer after OPU. Cabergoline 0.5mg was administered every two days 3 times from the OPU day. Total of 126 control cases had same treatment as intervention group other than cabergoline administration. Two group's characteristics are matched in age, number of picked up eggs, serum E2 level on the HCG day, and serum AMH. Both groups had screening tests of CBC and ultrasound monitoring on the 7th day after OPU. The grade of OHSS is classified in 3 groups as mild, moderate, or severe. The classification was according to patients' complaints, ovarian sizes, volume of ascites, and CBC findings. The volumes of ovaries are estimated by (longest diameter) x (shortest diameter)2. We analyzed the data using Fisher's exact test. The average age, number of obtained eggs by OPU, serum E2 (pg/ml), and AMH (pmol/L) were 35.4 vs. 35.3, 18.8 vs. 19.2, 5358 vs. 5185, and 31.0 vs. 34.3 in cabergoline group (n = 61) vs. control group (n = 126) respectively. There was no statistical difference between them. The incidence of all OHSS was 60% vs. 75% (P=0.109). The combined incidence of moderate and severe OHSS was 9% vs. 24% (P=0.04). The volume of ovaries after OPU was significantly shrunk in cabergoline group (98.4cm3 vs. 138.3cm3 P=0.0039). Prophylactic administration of cabergoline reduced the incidence of moderate and severe OHSS, although total incidence of OHSS was not different.

Gonadotropin stimulation of the patient with polycystic ovarian syndrome: a comparison of oral contraceptive pill/dual suppression lupron protocol versus oral contraceptive/antagonist protocol

To evaluate in vitro fertilization (IVF) cycle outcomes in polycystic ovarian syndrome (PCOS) patients with an oral contraceptive pill (OCP)/Lupron protocol versus an OCP/Antagonist protocol. Retrospective cohort study. The study included 309 patients who underwent 395 cycles of controlled ovarian hyperstimulation and IVF from January of 2004 to December of 2010. All patients met Rotterdam criteria for diagnosis of PCOS. Primary outcome measures include clinical pregnancy rate, percent cycles coasted, cancelled, and resulting in cryopreservation secondary to risk of ovarian hyperstimulation syndrome (OHSS), as well as occurrence of moderate or severe OHSS. Secondary outcome measures include length of stimulation, number of oocytes retrieved, number of mature oocytes, and implantation rate. Paired t tests and chi square test were used in analysis. P<0.05 was considered statistically significant. Results are shown in Table 1.Tabled 1OCP/AntagonistOCP/LupronP valueNumber of cycles81314Age31.9 ± 4.731.5 ± 4.1NSBMI23.7 ± 7.624.7 ± 6.8NSDays of stimulation10.2 ± 2.212.7 ± 2.60.02Coasts (%/cycle)1(1.2)31(9.8)0.02Cancelled due to risk of hyper response (%/cycle)2(2.5)17(5.4)NSEggs/retrieval16.8 ± 9.914.4 ± 7.10.02Mature eggs/retrieval13.8 ± 8.611.8 ± 6.10.02Frozen upfront for risk of OHSS(% per cycle)1(1.3)10(3.4)NSImplantation rate day 3 ET*43.1 ± 3639.4 ± 41.6NSImplantation rate day 5 ET*56.8 ± 49.552.1 ± 44.0NSTotal pregnancies (%/ET, %/cycle)195(69.7,62.1)56(75.7,69.1)NSClinical pregnancies (%/ET, %/cycle)168(60.2,53.5)49(66.2,60.0)NSLive birth/Ongoing pregnancies (%/ET, %/cycle)143(51.2,45.5)41(55.4,50.6)NSModerate OHSS(%)05(1.9)NSTable 1. * Embryo transfer (ET). Open table in a new tab Table 1. * Embryo transfer (ET). When compared to a dual suppression OCP/Lupron protocol, use of an OCP/Antagonist protocol in patients with PCOS results in more eggs retrieved, fewer days of stimulation, a lower rate of coasting, and less risk of OHSS. No cases of severe OHSS were identified in either group.

Follicule stimulating hormone (FSH) administer with trigger dose human chorionic gonadotropin (hCG) completely prevents ovarian hyperstimulation syndrome (OHSS). Randomised controlled study

Complete prevention of OHSS has only being possible with avoidance of HCG trigger. Excessive administration of FSH to susceptible patients has being considered an attributing factor to OHSS. FSH peaks just before LH surge in the natural cycle without OHSS. This study examines a similar role for FSH in patients at risk of OHSS. 102 patients undergoing IVF/ICSI cycles at risk of OHSS with serum oestradiol (E2) = />3500 pg/ml, = />15 follicles in each ovary and 2 leading follicles of size = />18mm were prospectively randomised to two strategies groups (gp1&2) for the prevention of OHSS. All patients had received GnRH agonist long protocol and starting dose of 225 iu of HMG. The HMG was withheld in gp1(51 patients) until the E2 levels fell below 1500 pg/ml when trigger dose of HCG was administered. In the gp2 (51 patients) pure FSH was administered with the trigger dose of HCG irrespective of the E2 levels = />3500 pg/ml. The pure FSH dose was the equivalent in the last HMG dose. IVF or ICSI performed according to semen paramter. Three cleaved D3 or two D5 blastocyst embryos were transfered. OHSS was identified according the revised classification. Comparing gp1vsgp2 mean total dose of HMG (3322.5+/-1005vs3465+/-937.5), total number of follicles (38.5+/-3.1vs37.4 +/-4.2), serum E2 on the day of randomisation (4455.5+/-541.5vs4527,5 +/-682.5) were similar. Mean serum E2 on trigger day was significantly higher in gp2 (910+/-385.6vs4527.5+/-682, P<0.001) following mean duration of coasting (4.8+/ = 1.4 days) in gp1. Fertilisation, cleavage rates and mean quality of embryos was similar. Mean no oocytes (8.6+/-2.9vs26.4+/-3.5) and D5 blastocyst (3.5+/-1.2vs10.6+/-2.7) were significantly higher in gp2, P<0.001. Incidence of OHSS (10 moderate, 4 severe 1 critical) was signficantly higher in gp 1. No moderate, severe or critical OHSS in gp 2, P<0.001. Similar clinical pregnancy rates (48.6vs51.8%). Pure FSH blocks and completely prevents the initiation of OHSS by HCG trigger.

Intravenous administration of calcium in ovarian hyperstimulation syndrome (OHSS) prevention

Evaluation of the effectiveness of intravenous administration of calcium gluconate in preventing the development of clinical symptoms of OHSS. Prospective double-blind clinical trial. 108 in vitro fertilization patients were administered intravenously either 10 mL 10% calcium gluconate (62 women) or 1,000 mL of 6% hydroxyethyl starch (46 women) on the day of oocyte retrieval (OR) and Days 1, 2, and 3 post-OR. The principal inclusion criteria were symptoms of the high risk of OHSS (development of ≥20 follicles >10 mm on Day 6 of controlled ovarian hyperstimulation, estradiol level on the day of OR ≥3,000 pg/mL, age < 30 years old and body mass index (BMI) < 25 kg/m2). Symptoms of OHSS (lower abdominal discomfort, abdominal distension, nausea and/or vomiting, rapid weight gain, dyspnoea, and progressive oliguria), volumes of ovaries and ascites were observed. The differences in the clinical symptoms of OHSS among the groups were statistically significant (P<0.0001). The ovarian volume did not differ (P>0.07) between the groups until Day 10 post-OR; later was observed the significant (P<0.0001) decrease of the ovarian volume in the calcium group. The ascites volume was significantly lower in the calcium group from Day 3 post-OR onwards (P<0.0001). Intravenous administration of calcium effectively prevents development of moderate or severe OHSS with no detrimental effect on the pregnancy rate, which confirms our proposed model of OHSS, in which the membrane depolarization leads to development of OHSS clinical manifestations and calcium-induced membrane stabilization is expected to alleviate OHSS symptoms.

Ascites ultrafiltration and concentration-reinfusion in severe ovarian hyperstimulation syndrome

Mild forms of ovarian hyperstimulation syndrome are common in women undergoing in-vitro fertilization, affecting up to 33% of in-vitro fertilization cycles; 3-8% of cycles are complicated by moderate or severe ovarian hyperstimulation syndrome (Royal College of Obstetricians and Gynaecologists, 2006). To treat severe ovarian hyperstimulation syndrome, albumin and other colloid solutions are used intravenously to increase the perfusion pressure (Manaka et al, 1995; Balasch et al, 1996), heparin to restore coagulation (Balasch et al, 1996) and dopamine to increase renal blood flow (Brinsden et al, 1995), but these all have limited effects.

Endocrine gland–derived vascular endothelial growth factor concentrations in follicular fluid and serum may predict ovarian hyperstimulation syndrome in women undergoing controlled ovarian hyperstimulation

To assess the predictive value of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) concentrations in follicular fluid (FF) and serum for ovarian hyperstimulation syndrome (OHSS) in patients undergoing controlled ovarian hyperstimulation. Retrospective, case-control study. University hospital, IVF center. Seventeen women with OHSS and 61 controls. None. FF and serum EG-VEGF and VEGF concentrations, IVF outcome. FF and serum EG-VEGF concentrations showed a significant negative correlation with serum E(2) concentration on the day of hCG administration. FF, but not serum, VEGF concentrations also showed a significant negative correlation with serum E(2) concentrations on hCG day. The FF EG-VEGF, FF VEGF, and serum EG-VEFG concentrations were significantly lower in the OHSS group than in the non-OHSS group. There was no significant difference in serum VEGF concentrations. Among FF and serum EG-VEGF and VEGF concentrations, only FF EG-VEGF concentrations were significantly lower in patients with moderate OHSS than in those with mild OHSS. FF and serum EG-VEGF concentrations may predict OHSS occurrence. Furthermore, FF EG-VEGF concentrations were significantly correlated with OHSS severity; thus, EG-VEGF appears to be more valuable than VEGF for predicting OHSS.

Treatment of Ovarian Hyperstimulation Syndrome

Mild forms of ovarian hyperstimulation syndrome (OHSS) do not require treatment. Moderate OHSS should be followed up on an outpatient basis with no specific treatment. Severe OHSS requires proper evaluation. Investigations are done to evaluate hematocrit, electrolytes, and kidney and liver function. Conservative treatment with intravenous (i.v.) fluids and close monitoring is usually done. Intensive care admission is indicated in cases with severe respiratory distress or major electrolyte imbalance with elevated serum creatinine. Crystalloids in the form of i.v. saline and colloids as albumin or hydroxyethyl starch are commonly used to expand intravascular volume. Dopamine can be used to improve diuresis, and prophylactic heparin is administered to prevent venous thrombosis. Diuretics are generally contraindicated because they may further contract intravascular volume. Abdominal or vaginal aspiration of ascitic fluid results in marked improvement of symptoms, improved diuresis, and shortened hospital stay. The current trend to treat patients with i.v. fluids, albumin, and to perform aspiration of ascitic fluid on an outpatient basis has been found to be a more cost-effective protocol of treatment.

Physiology and Pathology of Ovarian Hyperstimulation Syndrome

Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries primed with follicle-stimulating hormone/leuteinizing hormone (LH) are subsequently exposed to human chorionic gonadotropin (hCG). The ultimate pathophysiological step underlying this clinical picture is increased vascular permeability (VP). With the administration of hCG, the expression vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2) mRNA increases significantly rising to a maximum coinciding with peaked VP. Immunohistochemistry shows the presence of VEGF and VEGFR-2 proteins in the granulosa-lutein and endothelial cells of the entire corpus luteum. These findings suggest that the syndrome can be prevented by inducing ovulation with LH or gonadotropin-releasing hormone analogs, which prevent VEGF overexpression. Also, coadministration of a dopamine agonist inhibits phosphorylation of the receptor VEGFR-2. In a trial of 69 oocyte donors, the incidence of moderate OHSS was 20% with the dopamine agonist cabergoline and 44% with a placebo ( P = 0.04). Another dopamine agonist, quinagolide, was also effective in nonpregnant patients, but those pregnant did not benefit from dopamine agonist administration. In conclusion, the pathophysiological mechanisms involved in OHSS show that targeting VEGF/VEGFR2 is an effective preventive approach to treat the syndrome. Pharmaco-prevention through dopamine agonists is effective only in nonpregnant high-risk OHSS women. Embryo cryopreservation plus dopamine agonist administration might be the most appropriate way to prevent OHSS in high-risk patients.

103 A SUCCESSFUL MANAGEMENT OF A PATIENT WITH SUBCLAVIAN VEIN THROMBOSIS AFTER IVF

The incidence of thromboembolic disease associated with the assisted reproductive techniques is considered to be rare. The aim of the report is to present a case of successful management of woman with subclavian vein thrombosis after IVF and embryo transfer. A 29-year-old smoking woman was refered to our programme for IVF and ICSI because of infertility associated with the male factor. Her past medical history didn’t report any serious disease. The treatment procedure consisted of a long protocol included administration of Diferelinum and Gonal F 75U/day. After 10 days of stimulation she received 6000 IU of hCG. At that point there were 16 follicles between 18 20mm in diameter. Oocyte recovery took place 36 hours later. 14 oocytes were collected and 9 were mature and underwent ICSI resulting in 6 embryos. Three embryos were transferred to the uterus 3 days later and three embryos were frozen. A dose of 40mg Dufaston per os, 600mg Utrozestan per vaginum and 1500U Pregnil in a day were given for luteal phase support. One day before embryo transfer the patent complained of slight shortness of breath, flatulence. Haematocrit was normal, ovaries were moderately enlarged at 85× 54 and 77x53mm. A diagnosis of moderate ovarian hyperstimulation syndrome was made and intravenous hydratation with HAES-sterile was administered. In two weeks triplets pregnancy was diagnosed. At 5th week of gestation (w.g.) the patient experienced pain and swelling of left arm and neck. Ultrasonography revealed thrombus in left internal jugular, subclavian and brachiocephalic veins. The patient started low molecular weight heparin (LMWH) and remained on therapeutic doses of LMWH until postpartum. Thrombophilia work-up (antiphospholipid antibody, lupus anticoagulant, total homocysteine, proteins C, S, antithrombin III, plasminogen, prothrombin G20210A, factor V Leiden and methyleneteterahydrofolatreductase (MTHFR) C677T) revealed high titer of antib2-GPI IgM (twice 14 weeks apart) and homozygosity for MTHFR C677T. At 11w.g. the patient passed prenatal ultrasound screening for Dawn syndrome and reduction of one fetus of triplets was made by method of Berkovich at 11 weeks of gestation. The procedure of reduction was simple. Patient’s pregnancy course was otherwise uncomplicated. Patient delivered female twins with Apgar 6 7 weighing 2200 and 1900 g via caesarian section at 37w.g. The pregnancy was ended via caesarian section at 37w.g. Female twins were born with Apgar 6 7 weighing 2200 and 1900. This case illustrates serious complication of assisted reproductive treatment. Early recognition and treatment of OHSS and thrombophilia is critical for prevention and effective therapy of thromboembolic complications in patients undergoing ovarian stimulation. 104 CLINICAL SIGNIFICANCE OF HIDDEN THROMBOPHILIA BEFORE IN VITRO FERTILIZATION AND EMBRYO TRANSFER A.M. Harutyunyan, Zh.K. Isentayeva. Moscow Centre of Urology, Andrology and Reproductive Gynecology, Moscow, Russia

Successful birth following transfer of frozen–thawed embryos produced from in-vitro matured oocytes

It is well established that ovarian hyperstimulation syndrome (OHSS) is more frequent in patients with polycystic ovarian syndrome. In-vitro maturation (IVM) of immature oocytes presents a potential alternative for the fertility treatment and prevention of OHSS for these patients. This report describes the case of a 26-year old woman with a successful pregnancy and delivery following the transfer of frozen-thawed embryos derived from in-vitro matured oocytes. She had three failed cycles of ovarian stimulation (using low-dose step-up gonadotrophin protocol) with or without intrauterine insemination cycles, an ovulation-induction cycle with luteal long protocol, two fresh IVM cycle and one frozen-thawed IVM cycle. During the IVF cycle, she developed moderate OHSS and required hospitalization for 3 weeks. Following four unsuccessful IVF or IVM cycles, 15 months after the last cryopreservation, six fertilized oocytes were thawed for a scheduled embryo transfer. Following thawing, four fertilized oocytes survived and cleaved. Four frozen-thawed embryos were transferred. Six weeks after embryo transfer an ongoing intrauterine single pregnancy with fetal heartbeat was confirmed by transvaginal ultrasound. An uneventful pregnancy and delivery via Caesarean section at 39 weeks resulted in the birth of a normal healthy infant.

C-reactive protein as the indicator of severity in ovarian hyperstimulation syndrome

Background. To establish correlations between laboratory findings and clinical symptoms of moderate and severe ovarian hyperstimulation syndrome (OHSS).Design. A retrospective study.Setting. Department of obstetrics and gynecology, public clinical hospital.Patients. Nineteen women admitted to the public hospital with a diagnosis of OHSS. The procedure of controlled ovarian stimulation (COH) was performed in the private assisted reproductive technology centre.Methods. Blood samples were collected, ultrasound examination of ovaries, abdominal circumference measurement were performed, intravenous crystalloids, plasma expanders such colloids and albumin were given. Correlations between mean laboratory results (haematocrit, c-reactive protein (CRP), white blood count, serum protein, serum albumin), ovarian size in ultrasound examination, abdominal circumference, and amount of albumin and hydroxyethyl starch transfused to the patient were assessed.Results. Significant correlation was observed between CRP concentration and abdominal circumference measured when the patient was admitted to the department, between CRP concentration and ovarian size measured during ultrasound examination at admission and between CRP concentration and body weight.Conclusions. CRP can be a potential candidate to an indicator of OHSS severity.

Effect of bromocriptine on the severity of ovarian hyperstimulation syndrome and outcome in high responders undergoing assisted reproduction

CONTEXT:Ever since ovarian hyperstimulation syndrome (OHSS) was recognized as a clinical entity, various treatment modalities have been tried to prevent its occurrence and reduce its severity. Many recent studies have evaluated the role of dopamine agonists in reducing the incidence of OHSS.OBJECTIVES:To assess the effectiveness of dopamine agonist bromocriptine in reducing the incidence and severity of OHSS in patients undergoing assisted reproduction and its effect on pregnancy rates.SETTINGS AND DESIGN:It was a prospective study in which patients at high risk of developing OHSS undergoing assisted reproduction were recruited.MATERIALS AND METHODS:The study was carried out from August 2008 to August 2009 in patients undergoing assisted reproduction and included 40 patients at high risk for developing OHSS. Tablet bromocriptine 2.5 mg was prescribed for a period of 16 days starting from day of ovum pick up. Patients were analyzed on the basis of incidence of moderate and severe OHSS, timing of onset of OHSS (early/late), hospitalization rate, pregnancy rates and tolerability of medication and were compared with a historical group of high responders matched for age and BMI.STATISTICAL ANALYSIS:Student’s t test and proportion test were used.RESULTS:There was a significant reduction in the incidence of moderate OHSS (P=0.037), early OHSS (P=0.012) as well as the number of admissions (P=0.030). Average duration of hospitalization was also significantly reduced (P=0.036). In the study group, the incidence of clinically significant OHSS was 17.5% as compared to 40.9% in the control group. No difference was detected between the groups in clinical pregnancy rates (P=0.0054).CONCLUSION:Bromocriptine reduced the incidence and severity of clinically significant OHSS in high risk patients without affecting the pregnancy rates.

Cycles triggered with GnRH agonist: exploring low-dose HCG for luteal support

The aim of this study in patients at risk of ovarian hyperstimulation syndrome (OHSS) was to determine the efficacy and safety of luteal support using human chorionic gonadotrophin (HCG) after triggering ovulation with gonadotrophin-releasing hormone (GnRH) agonist in IVF/intracytoplasmic sperm injection antagonist cycles. A total of 192 OHSS-risk patients, following a GnRH antagonist protocol (0.25mg/day cetrorelix) during recombinant FSH stimulation, were triggered with 1.5mg s.c. leuproreline for ovulation. A total of three boluses of HCG were used for luteal support, 1000IU (group A, n=44), 500IU (group B, n=115) or 250IU (group C, n=33) every third day, starting the day after oocyte retrieval. For the reproductive outcome, main variables were biochemical and clinical pregnancy rates, and for OHSS, the variables were the numbers of moderate and severe OHSS cases. Overall pregnancy rate was 51.8% and clinical pregnancy rate was 43.4%. This study observed eight cases of moderate (4.2%) and seven of severe OHSS (3.6%). Six out of the seven (85.7%) severe cases were late-onset OHSS, related to pregnancy. In conclusion, GnRH agonist single dose for triggering ovulation and low doses of HCG used as luteal-phase support seem to secure a normal pregnancy outcome without increasing the OHSS risk.

High dose cabergoline in management of ovarian hyperstimulation syndrome

To describe a case of moderate ovarian hyperstimulation syndrome (OHSS) that was treated with high dose cabergoline. Case report. Private assisted reproduction center. A 29-year-old woman who developed early moderate OHSS despite preventive cabergoline administration (0.5 mg/day) following controlled ovarian hyperstimulation for IVF treatment. Cabergoline dose was increased to 1 mg/day upon diagnosis of OHSS on the second day after oocyte collection and embryo transfer was postponed to the fifth day after oocyte collection. Resolution of OHSS and achievement of healthy live birth. OHSS resolved rapidly despite occurrence of pregnancy and patient delivered a healthy boy at term. The higher cabergoline dose might have prevented an increase in the severity of OHSS and its prolongation following occurrence of pregnancy. Randomized controlled trials assessing the efficacy and safety of different doses and durations of cabergoline administration in both prophylactic and therapeutic settings are required.

Can quantitative three‐dimensional power Doppler angiography be used to predict ovarian hyperstimulation syndrome?

To test the hypothesis that ovarian vascularity is increased in women developing ovarian hyperstimulation syndrome (OHSS) and to assess its value as a predictor of OHSS during in-vitro fertilization (IVF). 118 subjects undergoing their first cycle of IVF had a three-dimensional (3D) transvaginal ultrasound scan in the early follicular phase of the menstrual cycle preceding IVF treatment. 18 of them developed moderate or severe OHSS and 100 subjects had normal ovarian response. Antral follicle count, ovarian volume, and ovarian vascularity (vascularization index (VI), flow index (FI) and vascularization flow index (VFI)) were compared between OHSS and control groups. Multiple regression analysis was used to assess the predictive value of these variables against age, body mass index and basal follicle-stimulating hormone level for the development of OHSS. The ovarian blood flow indices VI (11.1 +/- 11.6 vs. 8.6 +/- 7.3%; P = 0.23), FI (38.0 +/- 4.8 vs. 38.0 +/- 5.5; P = 0.95) and VFI (4.2 +/- 3.3 vs. 3.5 +/- 3.1; P = 0.40) were similar in the OHSS group and the normal responders. While antral follicle count was significantly higher in women developing OHSS (33.0 +/- 15.1) than in the control group (19.2 +/- 9.9, P < 0.001), ovarian volume did not differ between the two groups (10.6 +/- 3.8 vs. 8.9 +/- 4.8 cm(3), respectively, P = 0.11). On multiple regression analysis, antral follicle count was the only significant predictor of OHSS (P < 0.01). Women developing OHSS during IVF do not demonstrate an increased ovarian blood flow as measured by 3D ultrasound but do have a significantly higher antral follicle count, which is the only significant predictor of OHSS.

A modern classification of OHSS

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication of ovarian stimulation using fertility medications. OHSS classification presents the different severity categories and grades of OHSS and optimizes management schemes and prognosis. An initial classification system, which grouped OHSS into mild, moderate and severe categories, was based on patients' symptomatology plus manual estimation of ovarian enlargement and urinary excretion of sex steroids. A revised classification system then also incorporated the use of transvaginal sonography for both estimation of ovarian enlargement and detection of even small amounts of ascitic fluid. The detection of ascites establishes the diagnosis of moderate OHSS which may deteriorate to a severe form and is therefore of major importance. Subsequent modifications defined a group of critical or complicated OHSS in which grave complications have already developed. A consensus on the classification of OHSS should be reached by professional societies. As the revised classification system is very valid and widely used, it should form the basis for a modern classification, with the addition of critical or complicated OHSS to the severe category of the syndrome.

Influence of the ovarian hyperstimulation syndrome (OHSS) in embryo quality and in implantation and pregnancy rates

OBJECTIVE: Some studies suggest that ovarian hyperstimulation can compromise implantation rates in assisted fertilization treatment cycles. Other studies believe that OHSS does not affect implantation rates or the quality of both oocytes and embryo. The purpose of this study was to evaluate embryonic quality, the implantation and pregnancy rates of patients with OHSS by comparing them to a control group without OHSS. DESIGN: Retrospective. MATERIALS AND METHODS: The study included 1905 patients with an indication for Intracytoplasmic sperm injection (ICSI) of which 156 patients had OHSS and 1749 did not (control group). Both the short and the long protocols were used. HCG was administered when at least 3 follicles had reached 19 mm in diameter. M2 eggs were injected 4 hours after oocyte retrieval. Fertilization and embryo development were assessed at 20h, 44h and 68h after ICSI. Embryo transfer was performed on day 2 or 3. Patients were divided into six groups, namely G1 (patients ≤ 35 years and with mild OHSS), G2 (patients ≤ 35 years and moderate or severe OHSS), G3 (patients between 36 to 40 years and mild OHSS), G4 (patients between 36 and 40 years and moderate to severe OHSS), G5 (patients ≤ 35 years without OHSS) and G6 (patients between 36 and 40 without OHSS). Statistical analyses used one-Way ANOVA or the Fisher's exact tests at the level of P<0.05. RESULTS: With respect to embryo quality, there was no statistically significance between the total of obtained embryos and the transferred embryos. The percentage of good morphology embryos (A+B) were: 75%, 82%, 73%, 88%, 78% and 78% for G1, G2, G3, G4, G5 and G6 respectively, and transferred embryos were: 95.5%, 100%, 98.5%, 100%, 98% and 97% for G1, G2, G3, G4, G5 and G6, respectively. Implantation rates were: 23% (G1), 56% (G2), 25% (G3), 45% (G4), 21% (G5) and 13.5% (G6). Hence, it was verified an increased implantation rate in G2 and G4 i.e., patients with a moderate or severe OHSS, as well as in the pregnancy rates, which were: 52% (G1), 72% (G2), 44% (G3), 71% (G4), 46% (G5), 47% (G6). CONCLUSIONS: Since no difference between the various groups was identified, our results do corroborate the opinion of certain authors who believe that embryo quality is not affected by OHSS. However, an increase in implantation and pregnancy rates was observed in both groups with moderate to severe OHSS i.e., G2 and G4 (≤ 35 years and 36-40 years, respectively).