Incidence Of Severe Ovarian Hyperstimulation Syndrome Research Articles

The Incidence of Moderate and Severe Ovarian Hyperstimulation Syndrome in Hospitalized Patients in China.

Ovarian hyperstimulation syndrome (OHSS) occurs in women receiving fertility treatments. Moderate and severe OHSS cases are required to be admitted to hospital for treatment. The incidence of moderate and severe OHSS and the characteristics of these cases are unknown in China. We aimed to assess the incidence of moderate and severe OHSS in national databases from China between 2013 and 2017. We extracted moderate and severe OHSS cases from the Hospital Quality Monitoring System, the nationwide inpatient data collection system. We used ovum pick-up (OPUbaidu) cycle data from the annual report of China's National Health Commission, developed on the basis of OPU data collected by National ART Management Information System. Overall incidence of moderate and severe OHSS (women aged 20 to 50 years) and year-specific incidence by each calendar year in China were calculated. We also investigated the age distribution in OHSS and OHSS with different comorbidities. We extracted 18,022 eligible patients with moderate or severe OHSS and 1,581,703 OPU cycles. The overall incidence of moderate and severe OHSS between 2013 and 2017 was 1.14%. The year-specific moderate and severe OHSS incidence was 1.1% in 2013, 1.4% in 2014, 1.4% in 2015, 1.1% in 2016, 0.9% in 2017, respectively. Women aged 26 to 30 years accounted for 48.4% of OHSS cases, followed by women aged 31 to 35 years (30%) and 20 to 25 years (14.2%). The age distribution pattern was consistent across OHSS with different comorbidities. This study reported the incidence of moderate and severe OHSS in China using nationwide data for the first time. Our findings support that women aged under 35 years receiving assisted reproductive technology need more attention than other age groups in terms of OHSS risk control.

Clinical characteristics of severe late-onset ovarian hyperstimulation syndrome and its impact on the live birth outcome of IVF-ET

Objective: To investigate the correlation between different clinical features and live birth in patients with severe late-onset ovarian hyperstimulation syndrome (OHSS) after in vitro fertilization-embryo transfer (IVF-ET). Methods: The clinical information of 330 patients who were pregnant after IVF-ET and referred to medical treatments diagnosed as late-onset severe OHSS in Peking University Third Hospital from January 2016 to December 2020 was retrospectively analyzed. The patients were divided into live birth achieved group (n=287) and non-live birth achieved group (n=43) according to pregnancy outcomes, and live birth achieved group was further divided into two subgroups, full-term birth group (n=222) and early-term birth group (n=65) according to gestational week at delivery for better analysis. Single factor and multi-factor analysis were utilized to clarify the influencing factors of both live birth and early-term birth. Results: Among all the patients who received IVF-ET, the incidence of severe OHSS was 0.67% (673/100 758). Among 330 severe late-onset OHSS patients, 42.4% (140/330) had pleural effusion, the incidence of abnormal liver function was 69.4% (229/330), and the live birth rate was 87.0% (287/330). Among the 287 patients who achieved live birth, 55.4% (159/287) had no pleural effusion, 18.5% (53/287) had a small amount of pleural effusion, and 26.1% (75/287) had medium or massive pleural effusion; in the non-live birth achieved group, there were more patients without pleural effusion and less patients with a small amount of pleural effusion; the difference was statistically significant (χ2=6.213, P=0.045). The rate of selective fetal reduction in live birth achieved group was 16.0% (46/287), which was significantly higher than that in the non-live birth achieved group, which was 2.3% (1/43; χ2=5.749, P=0.017). Multivariate logistic regression analysis revealed that moderately abnormal liver function was an independent risk factor for live birth (OR=3.15, 95%CI: 1.60-6.19), while selective fetal reduction was an independent protective factor for live birth (OR=0.13, 95%CI: 0.02-0.96). Additionally, subgroup analysis suggested that twin birth was an independent risk factor for preterm birth (OR=8.54, 95%CI: 4.31-16.91). Conclusions: Moderate hepatic dysfunction may be associated with adverse pregnancy outcomes in patients with severe late-onset OHSS. Selective fetal reduction and singleton pregnancy are recommended to ameliorate live birth rate, full-term delivery rate, also the maternal and neonatal prognosis for patients with multiple pregnancies.

Follicular-Phase GnRH Agonist Protocol Is Another Choice for Polycystic Ovary Syndrome Patients With Lower LH/FSH and Lower AMH Levels Without Increasing Severe OHSS Risk.

PurposeTo explore another choice for a controlled ovarian stimulation (COS) protocol that does not increase severe ovarian hyperstimulation syndrome (OHSS) risk among polycystic ovarian syndrome (PCOS) patients with specific clinical features.MethodsA retrospective study was performed. Two hundred and fifty-nine participants were divided into two groups, group 1 (fixed GnRH antagonist protocol, n = 295) and group 2 (follicular-phase GnRH agonist protocol, n = 69) according to COS protocols. The basic characteristics and laboratory indicators between these two groups were compared. The severe OHSS rate and clinical pregnancy rate were selected as indicators to evaluate the risks and benefits of the two COS protocols. Subgroup analyses for the severe OHSS rate and clinical pregnancy rate were performed based on baseline luteinizing hormone/follicle-stimulating hormone (bLH/FSH) and anti-Mullerian hormone (AMH) levels.ResultsThe severe OHSS rate was statistically higher in group 2 than in group 1 (11.6% vs. 3.7%, p = 0.008), but the biochemical pregnancy rate and clinical pregnancy rate showed no statistical difference between the groups (71.9% vs. 60.3% and 62.5% vs. 54.3%). In the higher bLH/FSH subgroup (≥1.33) and the higher serum AMH level subgroup (>3.4 ng/ml), severe OHSS incidence was statistically higher in group 2 compared to group 1, but this incidence was lower in the bLH/FSH subgroup (<1.33) and the subgroup with lower serum AMH levels (≤3.4 ng/ml); a difference in severe OHSS risk was not observed. There was no statistical difference between the two groups regarding clinical pregnancy rate in any subgroup.ConclusionThe limited evidence from this study indicates that in PCOS patients with lower bLH/FSH levels (<1.33) and lower serum AMH levels (≤3.4 ng/ml), a follicular-phase GnRH agonist protocol may be another choice that does not increase the risk of severe OHSS.

Severe ovarian hyperstimulation syndrome with GnRH agonist trigger during the COVID pandemic: lessons learned from an unusual case

Background: Injectable gonadotropins stimulate multi-follicular recruitment and allows retrieval of multiple oocytes for assisted reproduction. The widespread utilization of gonadotropin releasing hormone agonist (GnRHa) to induce oocyte maturation for oocyte retrieval has nearly eliminated the risk of severe ovarian hyperstimulation syndrome (OHSS), and only a few cases have been reported in the literature. The rarity of severe OHSS may lead to the mistaken conclusion that gonadotropin stimulation can be safely administered with limited monitoring, even in high-risk patients. We present an unusual case of a woman with limited monitoring due to the COVID pandemic who developed severe OHSS before GnRH agonist trigger and oocyte. Case Presentation: A 29-year-old nulliparous woman with polycystic ovarian syndrome (PCOS) initiated ovarian stimulation for oocyte retrieval. She had a robust initial response, and developed worsening abdominal pain, bloating, nausea, vomiting, and decreased appetite before retrieval. GnRH agonist was given to “trigger ovulation and retrieval scheduled due to the low reported incidence of severe OHSS. Symptoms progressed, and on the morning of retrieval, ultrasound demonstrated bilaterally enlarged ovaries &gt;10cm and 48 oocytes were retrieved for a planned cryo-all cycle. She was hospitalized on the day of retrieval for severe OHSS and had two large-volume paracenteses. She was stable and discharged home by day 5, and symptoms markedly improved with the onset of menses. She has an ongoing pregnancy from her first frozen embryo transfer. Conclusion: We add a rare case of severe OHSS with a GnRHa trigger and cryo-all protocol with the onset of symptoms before GnRH agonist administration. Although rare, severe OHSS may still occur with a GnRHa trigger, and caution is needed when an initial robust response is identified. Here we also provide an opportunity to review the important patient risk factors for the development of OHSS and measures to reduce the risk in excessive responders.

Lipid Metabolic Disorders and Ovarian Hyperstimulation Syndrome: A Retrospective Analysis.

ObjectivesTo evaluate the effect of dyslipidemia on the incidence of moderate and severe Ovarian hyperstimulation syndrome (OHSS) in the duration of assisted reproduction technique (ART).MethodsThe study included 233 moderate and severe OHSS patients who received hospitalization after in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles to avoid severe complications. They were divided into dyslipidemia group and normal lipid metabolism group to evaluate whether dyslipidemia contributes to the development of severe OHSS. Subgroup analysis was set to avoid deviation including the freeze-all group and fresh embryo transfer (ET) group according to whether the eligible women chose fresh embryo transfer immediately after their IVF or ICSI cycles. The main outcome measures included the incidence of moderate OHSS and severe OHSS, total gonadotropin dose, number of oocytes retrieved, age and body mass index (BMI). In the ET groups, the rate of pregnancy is also included for analysis.ResultsIn the freeze-all group, lipid metabolism was ultimately identified as the factor affecting the morbidity of severe OHSS and the ones with dyslipidemia were more likely to develop to severe OHSS (P < 0.05), while the incidence of severe OHSS among the ET groups had no statistical significance (P > 0.05).ConclusionThe findings of this study suggested that dyslipidemia might contribute to the development of OHSS, especially for those patients who chose the cryopreservation of all embryos. It is essential to consider the risk of OHSS in patients with dyslipidemia although they required cryopreservation of all embryos.

Early onset of cabergoline therapy for prophylaxis from ovarian hyperstimulation syndrome (OHSS): A potentially safer and more effective protocol

Vascular endothelial growth factor (VEGF) is the most important angiogenic mediator in ovarian hyperstimulation syndrome OHSS. Studies proved that cabergoline administration blocks the increase in vascular permeability via dephosphorylation of VEGF receptors and hence can be used as prophylactic agent against OHSS. This study aimed at evaluating the effectiveness of early administration of cabergoline in the prevention of OHSS in high risk cases prepared for ICSI. This case series study was conducted on 126 high risk patients prepared for ICSI using the fixed antagonist protocol. High risk patients were defined as having more than 20 follicles >12 mm in diameter, and/or E2 more than 3000 pg/ml when the size of the leading follicle is more than 15 mm. When the size of the leading follicle reached 15 mm, cabergoline was administered (0.5 mg/day) for 8 days. Patients were followed up clinically, ultrasonographically and hematologically. The final E2 was 6099.5 ± 2730 and the mean number of retrieved oocytes was 19.7 ± 7.8. The clinical pregnancy rate was 62/126 (49.2%). There were no significant changes (p > 0.05) comparing hematological parameters, renal function tests and liver function tests between the day of HCG and the day of blastocyst transfer. The incidence of severe OHSS in this group was 1/126 (0.9%), while moderate OHSS was 12 (9.5%) and there were no cases of critical OHSS. We concluded that early administration of cabergoline is a safe and potentially more effective approach for prophylaxis against OHSS in high risk cases.

Laparoscopic ovarian drilling versus GnRH antagonist combined with cabergoline as a prophylaxis against the re-development of ovarian hyperstimulation syndrome

Objective: The aim of this work was to investigate the value of laparoscopic ovarian drilling (LOD) compared with GnRH antagonist flexible protocol combined with cabergoline (Cb), as a prophylaxis against the re-development of ovarian hyperstimulation syndrome (OHSS) in women with clomiphene citrate-resistant polycystic ovary disease (CCR-PCOD) who had severe OHSS before in a previous ICSI cycle. Study design: It is a prospective controlled study, where 250 CCR-PCOD women (n = 250) with a history of severe OHSS before, had been recruited for the study. LOD had been performed for 120 (n = 120) of the recruited women before ovarian induction, and considered as group A. GnRH antagonist (Cetrotide 0.25 mg) was added when a leading follicle reaches 14–16 mm combined with oral Cb in a dose 0.5 mg a day before hCG, and for 8 d for another 130 (n = 130) women, and considered as group B. Pregnancy was diagnosed with BhCG level ≥25 IU/L, ± 14 d after embryo transfer, followed with transvaginal ultrasound scanning (TVS) 2 weeks later to confirm intra-uterine pregnancy (IUP). Women were followed up weekly for 3 months for the possible development of any signs and symptoms of OHSS. Results: None of the participants in group A developed severe OHSS, and only six women (5%) developed mild to moderate OHSS. The incidence of severe OHSS was significantly higher (n = 3, 15%) in group B compared with group A (p < .001). Another (n = 17, 13.3%) women in group B developed mild to moderate OHSS. The probability of developing severe OHSS was also significantly higher in group B as well (p = .031). Pregnancy rate (PR) was significantly higher in group A more than group B (67% versus 39%, respectively), and all were single intrauterine pregnancies (IUP) and all developed after fresh embryo transfer (ET), compared with frozen embryo transfer (FET) which was performed in 42 cases in group B after postponing ET due to significantly severe OHSS developed. Conclusion: LOD could be considered a good prophylactic measure against OHSS, in addition to improving the total outcome of IVF cycles in women with CCR-PCOS.

Comparison of Cabergoline and Quinagolide in Prevention of Severe Ovarian Hyperstimulation Syndrome among Patients Undergoing Intracytoplasmic Sperm Injection.

BackgroundThe aim of the current study is to compare quinagolide with cabergoline in prevention of ovarian hyperstimulation syndrome (OHSS) among high risk women undergoing intracytoplasmic sperm injection (ICSI).Materials and MethodsThis randomized clinical trial study was performed from March 2015 to February 2017. One hundred and twenty six women undergoing ICSI who were at high risk of developing OHSS (having over 20 follicles of >12 mm), were randomized into two groups. The first group received cabergoline 0.5 mg and the second group received quinagolide 75 mg every day for 7 days commencing on the day of gonadotropin-releasing hormone (GnRH) agonist administration. Then OHSS symptoms as well as their severity were assessed according to standard definition, 3 and 6 days after GnRH agonist administration. Ascites were determined by trans-vaginal ultrasound. Other secondary points were the number of oocytes and the number of embryos and their quality. Quantitative and qualitative data were analyzed using Student’s t test, and Chi-square or fisher’s exact test, respectively. A P<0.05 was considered statistically significant.ResultsThe incidence of severe OHSS in the quinagolide-treated group was 3.1% while it was 15.8% in cabergolinetreated subjects (P<0.001). Ascites were less frequent after treatment with Quinagolide as compared to cabergoline (21.9 vs. 61.9%, respectively) (P=0.0001). There was no significant statistical deferences between the two groups in terms of mean age, number of oocytes, metaphase I and metaphase II oocytes, and germinal vesicles. There was a significant difference between cabergoline and quinagolide groups regarding the embryo number (P=0.037) with cabergoline-treated group showing a higher number of embryos. But, the number of good quality embryo in quinagolide-treated individuals was significantly higher than that of the cabergoline-treated group (P=0.001).ConclusionQuinagolide seems to be more effective than Cabergoline in prevention of OHSS in high-risk patients undergoing ICSI (Registration number: IRCT2016053128187N1).

Severe ovarian hyperstimulation syndrome: Can we eliminate it through a multipronged approach?

BackgroundPrevention of severe Ovarian Hyperstimulation Syndrome (OHSS), a potentially fatal complication of controlled ovarian hyperstimulation has been the aim of all fertility experts. Various pharmacologic and non-pharmacologic interventions have been instituted but the results have been conflicting. These preventive strategies were administered in isolation or as a combination of few aiming to eliminate this iatrogenic sequel. This study aimed to eliminate severe OHSS by multipronged approach incorporating almost all preventive modalities available in patients at high risk for this dreadful complication. MethodsIt was a prospective observational study wherein 112 high risk patients planned for IVF were studied. The multipronged approach was in the form administering calcium gluconate infusion, cabergoline, albumin infusion, GnRH antagonist in luteal phase in addition to elective cryopreservation of embryos. The primary outcome measure was incidence of severe OHSS in the study group and the rate of hospitalisation. The secondary outcome measure was the number of days required for complete recovery and resolution of signs and symptoms. ResultsOut of the 112 high risk patients only one patient (1/112; 0.9%) developed severe OHSS with an overall incidence of 0.095% of severe OHSS in all the cycles. There was no biochemical or haematological derangement in any of the high risk patients. ConclusionAlthough this is the first study evaluating the multipronged approach in preventing the dreaded complication of severe OHSS, it does add to the knowledge that targeting the various pathophysiological pathways at different time frames will bring about prevention of OHSS but further randomised studies may reveal superiority of one intervention over the other.

Can steroidal ovarian suppression during the luteal phase after oocyte retrieval reduce the risk of severe OHSS?

BackgroundOvarian stimulation in IVF cycle results in luteal supraphysiological steroid concentrations especially for high response patients. The aim of this study was to evaluate the efficacy of ovarian steroid hormone suppression in luteal phase after oocyte retrieval for preventing severe ovarian hyperstimulation syndrome (OHSS) in high-risk patients with embryo cryopreservation.Methods281 patients with high risk of OHSS were enrolled in this study among 4735 infertile women undergoing their first IVF treatment. The subjects were allocated into treatment and control group. The treatment group (n = 161) received letrozole (n = 43), mifepristone (n = 51), cetrotide (n = 39) and three-drug combinations (n = 28) during the luteal phase after oocyte retrieval, respectively. The control group (n = 120) received no medicine. Fertilization rate, good embryo rate, serum steroid concentration, clinical outcome, and incidence of severe OHSS were compared between the two groups.ResultsOn days 2, 5 and 8 after oocyte retrieval, serum estradiol levels in the letrozole and three-drug combination therapy group were significantly lower than in the other three groups at the same time (P < 0.001, respectively). There were no significantly difference of serum luteinizing hormone concentration on days 2, 5 and 8 and progesterone concentration on day 8 after oocyte retreival among the five groups (P > 0.05, respectively). Compared with the control group, the incidence of severe OHSS, the paracentesis rate, the duration of hospitalization and the days of luteal phase in each subgroup of treatment groups was not significantly decreased (P > 0.05, respectively).ConclusionsOur findings indicate that steroidal ovarian suppression in luteal phase after oocyte retrieval seems to be unable to prevent severe OHSS in high-risk patients with embryo cryopreservation.

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.

A large, multicentre, observational, post-marketing surveillance study of the 2:1 formulation of follitropin alfa and lutropin alfa in routine clinical practice for assisted reproductive technology

BackgroundFollicle-stimulating hormone (FSH) and luteinizing hormone (LH) both have a role to play in follicular development during the natural menstrual cycle. LH supplementation during controlled ovarian stimulation (COS) for assisted reproductive technology (ART) is used for patients with hypogonadotropic hypogonadism. However, the use of exogenous LH in COS in normogonadotropic women undergoing ART is the subject of debate. The aim of this study was to investigate characteristics of infertile women who received the 2:1 formulation of follitropin alfa and lutropin alfa (indicated for stimulation of follicular development in women with severe LH and FSH deficiency) in German clinical practice.MethodsA 3-year, multicentre, open-label, observational/non-interventional, post-marketing surveillance study of women (21-45 years) undergoing ART. Primary endpoint: reason for prescribing the 2:1 formulation of follitropin alfa and lutropin alfa. Secondary variables included: COS duration/dose; oocytes retrieved; fertilization; clinical pregnancy; ovarian hyperstimulation syndrome (OHSS).ResultsIn total, 2220 cycles were assessed; at least one reason for prescribing the 2:1 formulation was given in 1834/2220 (82.6%) cycles. Most common reasons were: poor ovarian response (POR) (39.4%), low baseline LH (17.8%), and age (13.8%). COS: mean dose of the 2:1 formulation on first day, 183.1/91.5 IU; mean duration, 10.8 days. In 2173/2220 (97.9%) cycles, human chorionic gonadotrophin was administered. Oocyte pick-up (OPU) was attempted in 2108/2220 (95.0%) cycles; mean (standard deviation) 8.0 (5.4) oocytes retrieved/OPU cycle. Fertilization (≥1 oocyte fertilized) rates: in vitro fertilization (IVF), 391/439 (89.1%) cycles; intracytoplasmic sperm injection (ICSI)/IVF + ICSI, 1524/1613 (94.5%) cycles. Clinical pregnancy rate: all cycles, 25.9%; embryo transfer cycles, 31.3%. OHSS: hospitalization for OHSS, 8 (0.36%) cycles, Grade 2, 60 (2.7%), and Grade 3, 1 (0.05%).ConclusionsIn German routine clinical practice, the most common reasons for using the 2:1 formulation of follitropin alfa and lutropin alfa for women undergoing ART were POR, low baseline LH, and age. Severe OHSS incidence was low and similar to that reported previously.Trial registrationClinicaltrials.gov NCT01112618

Rescue in vitro fertilization using a GnRH antagonist in hyper-responders from gonadotropin intrauterine insemination (IUI) cycles

To evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to "rescue" in vitro fertilization (IVF) using a Gonadotropin-Releasing Hormone (GnRH) antagonist, with regards to implantation rates, pregnancy rates, cost, and ovarian hyperstimulation syndrome (OHSS) as compared to matched, hyper-responder, IVF controls. This prospective cohort study was conducted between January 2007 and December 2009 at our institution. In order to decrease high-order multiple pregnancy, minimize the incidence of OHSS, and avoid cycle cancellation, high-response stimulated-IUI patients opted to convert to "rescue" IVF using the GnRH antagonist cetrorelix acetate. We then compared their clinical outcomes with matched patients from high-response IVF cycles of the standard long mid-luteal GnRH agonist protocol (14 or more collected oocytes). Only cases of conventional IVF without intra-cytoplasmic sperm injection (ICSI) were included in the control group. Out of 184 patients undergoing stimulated-IUI cycles with gonadotropins, 87 patients developed a hyper-response, and 20 opted to convert to "rescue" IVF. These patients were compared with 157 matched, hyper responder IVF controls from our registry. The implantation rate was 25.6 % in the "rescue" IVF group and 20.7 % in the control IVF group (p < 0.0047). The ongoing clinical pregnancy rate per embryo transfer was 45.0 % and 33.6 % in the "rescue" IVF and the control IVF groups, respectively (p < 0.0001). The mean duration of stimulation was comparable between cohorts (10.0 vs.10.4 days, p = 0.6324). The mean dose of gonadotropin used per cycle was higher in the control group, 2664 international units (IU) of follicle stimulation hormone (FSH) compared to 1450 IU of FSH in the "rescue" IVF group (p < 0.0001). The incidence of severe OHSS is also higher in the control group, 5.1 % versus no cases in the "rescue" IVF group (p < 0.0001). Our study demonstrates that conversion of high-response gonadotropin-IUI cycles to "rescue" IVF using a GnRH antagonist is a cost-effective strategy that produces better results than regular IVF with relatively minimal morbidity, and shorter duration to achieve pregnancy. Implantation and ongoing clinical pregnancy rates tend to be higher than those from hyper-responder regular IVF patients.

Combination of cabergoline and embryo cryopreservation after GnRH agonist triggering prevents OHSS in patients with extremely high estradiol levels—a retrospective study

Embryo cryopreservation after triggering oocyte maturation with GnRH agonist (GnRHa) in GnRH antagonist protocols has been proposed to prevent ovarian hyperstimulation syndrome (OHSS). However, a small percentage of patients still developed severe OHSS. The purpose of the study was to investigate the efficacy of preventing OHSS in patients at very high risk when cabergoline was given in addition to elective cryopreservation after GnRHa triggering. This is a retrospective observational study. The patients were stimulated with GnRH antagonist protocol. When serum E2 concentration was >6,000 pg/ml and there were more than 20 follicles ≥11 mm on the day of final oocyte maturation, GnRHa was used to trigger oocyte maturation. Cabergoline was given to augment the effect of preventing OHSS. The embryos were electively cryopreserved by vitrification and thawed in subsequent cycles. The primary outcome measure was the incidence of severe OHSS. The secondary outcome measure was the clinical pregnancy rate in the first frozen-thawed embryo transfer cycle. One hundred and ten patients underwent 110 stimulated cycles were included for analysis. No patients developed moderate/severe OHSS. Mean E2 concentration on the day of final oocyte maturation was 7,873 pg/ml, and an average of 22.7 oocytes was obtained from each patient. One hundred and ten thawing cycles were performed, resulting in 69 clinical pregnancies (62.7 %). Combining cabergoline and embryo cryopreservation after GnRHa triggering in GnRH antagonist protocol could prevent OHSS in patients at very high risk.

Clinical outcome according to timing of cabergoline initiation for prevention of OHSS: a randomized controlled trial

Cabergoline, a dopamine receptor-2 agonist, is suggested to prevent ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. The aim of this study was to evaluate the influence of different timing of cabergoline administration on clinical outcome among patients at risk of developing OHSS. Among infertile women undergoing IVF treatment at risk of developing OHSS, 206 were enrolled in this study. The subjects were randomly allocated into two groups, i.e. the study group (n=100) receiving cabergoline beginning on the day of human chorionic gonadotrophin (HCG) injection and the control group (n=100) receiving cabergoline starting on the day of oocyte retrieval. Oocyte metaphase-II rate, fertilization rate, clinical outcome and incidence of severe OHSS were compared between the two groups. There were no significant differences in oocyte metaphase-II rate (0.86±0.16 versus 0.85±0.15) or fertilization rate (0.79±0.22 versus 0.76±0.20) or in the incidence of OHSS between two groups. Similarly, there were no significant differences in implantation or clinical pregnancy rate between the two groups. Cabergoline can be administered as soon as HCG injection to prevent early OHSS, without adverse effects on oocyte maturation, fertilization rate and clinical outcome.Cabergoline, a dopamine receptor-2 agonist, is suggested to prevent ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. Nevertheless, the most suitable timing of cabergoline administration has not yet been studied. The aim of this study was to evaluate the influence of different timing of cabergoline administration on final oocyte maturation, fertilization rate and clinical outcome among patients at risk of developing OHSS. Among infertile women undergoing IVF treatment at risk of developing OHSS, 206 were enrolled in this study. The subjects were randomly allocated into two groups, i.e. the study group (n=100) receiving cabergoline beginning on the day of human chorionic gonadotrophin (HCG) injection and the control group (n=100) receiving cabergoline starting on the day of oocyte retrieval. Oocyte metaphase II rate, fertilization rate, clinical outcome and incidence of severe OHSS were compared between the two groups. There were no significant differences in oocyte metaphase II rate (0.86±0.16 versus 0.85±0.15) or fertilization rate (0.79±0.22 versus 0.76±0.20) or in the incidence of OHSS (3/100 versus 1/100) between the control and study groups. Similarly, there were no significant differences in implantation rate (36.6% versus 34.0%) or clinical pregnancy rate (54.0% versus 51.0%) between the two groups. Among women at high risk of OHSS, cabergoline can be administered as soon as the HCG injection to prevent early OHSS, without adverse effects on oocyte maturation, fertilization rate and clinical outcome.

Can cabergoline prevent ovarian hyperstimulation syndrome in polycystic ovarian patients undergoing gonadotropin stimulation?

Can cabergoline prevent ovarian hyperstimulation syndrome in polycystic ovarian patients undergoing gonadotropin stimulation?

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.

Oocyte vitrification: influence of operator and learning time on survival and development parameters

The threat of severe ovarian hyperstimulation syndrome (OHSS) and the increase in discomfort for the patient has limited the feasibility of maximizing the oocyte yield per treatment cycle. A gonadotrophin-releasing hormone (GnRH) antagonist protocol with agonist triggering and vitrification of all 2PN oocytes can eliminate the risk of OHSS. This prospective, single-centre, cohort study in 30 good-responder IVF patients ⩽36 years reports the feasibility of arbitrarily intensifying stimulation in a GnRH antagonist protocol in terms of tolerability, safety and efficacy. Ovarian stimulation was performed with 225–375 IU FSH, induction of final oocyte maturation with 0.2 mg GnRH agonist followed by vitrification of all 2 pronuclear (2PN) oocytes and repetitive vitrified–warmed embryo transfer cycles. Main outcomes were severe OHSS incidence, tolerability, assessed by a questionnaire, and cumulative live birth rate. On average, 17 oocytes were retrieved (range 4–42) and 8.4 oocytes at the 2PN stage were cryopreserved (range 3–22). No case of severe OHSS was observed (0%, 95 CI 0–11.4%). Tolerability was good. The cumulative live birth rate per patient undergoing at least one vitrified–warmed embryo transfer was 26.9% (7/26, 95% CI 13.7–46.1%). This approach can be explored in future larger-sized controlled studies.The more oocytes that are available after ovarian stimulation, the more often a patient can undergo an embryo transfer when frozen–thawed cycles using cryopreserved embryos are taken into account. However, the feasibility of retrieving a large number of oocytes has so far been hampered by the risk of ovarian hyperstimulation syndrome (OHSS). An approach combining a gonadotrophin-releasing hormone (GnRH) antagonist protocol stimulation with agonist triggering of final oocyte maturation and vitrification of all 2 pronuclear oocytes eliminates the risk of OHSS. Herein we report the feasibility of arbitrarily intensifying stimulation in a GnRH antagonist protocol in terms of tolerability, safety and efficacy. It was found in a small study on young patients that harvesting a large number of oocytes (on average 17) is not associated with poor tolerability or an increased risk of OHSS. The live birth rate after vitrified–thawed embryo transfers was 26.9%. Thus, this approach can be studied in larger-sized controlled trials.

Intensified ovarian stimulation in a GnRH antagonist protocol with agonist triggering: a prospective, clinical feasibility study

The threat of severe ovarian hyperstimulation syndrome (OHSS) and the increase in discomfort for the patient has limited the feasibility of maximizing the oocyte yield per treatment cycle. A gonadotrophin-releasing hormone (GnRH) antagonist protocol with agonist triggering and vitrification of all 2PN oocytes can eliminate the risk of OHSS. This prospective, single-centre, cohort study in 30 good-responder IVF patients ≤ 36 years reports the feasibility of arbitrarily intensifying stimulation in a GnRH antagonist protocol in terms of tolerability, safety and efficacy. Ovarian stimulation was performed with 225-375IU FSH, induction of final oocyte maturation with 0.2mg GnRH agonist followed by vitrification of all 2 pronuclear (2PN) oocytes and repetitive vitrified-warmed embryo transfer cycles. Main outcomes were severe OHSS incidence, tolerability, assessed by a questionnaire, and cumulative live birth rate. On average, 17 oocytes were retrieved (range 4-42) and 8.4 oocytes at the 2PN stage were cryopreserved (range 3-22). No case of severe OHSS was observed (0%, 95 CI 0-11.4%). Tolerability was good. The cumulative live birth rate per patient undergoing at least one vitrified-warmed embryo transfer was 26.9% (7/26, 95% CI 13.7-46.1%). This approach can be explored in future larger-sized controlled studies.

Ovarian Hyperstimulation Syndrome Prevention Strategies: Use of Gonadotropin-Releasing Hormone Antagonists

The most serious complication of ovarian stimulation for in vitro fertilization is severe ovarian hyperstimulation syndrome (OHSS), a rare but potentially life-threatening condition. The present review discusses the place of gonadotropin-releasing hormone antagonists (GnRH-ant) in primary, secondary, and tertiary prevention of OHSS. Sound evidence indicates that the routine use of GnRH-ant instead of GnRH agonists (GnRHa) during ovarian stimulation drastically reduces the relative risk of OHSS. GnRH-ant are therefore useful for primary OHSS prevention, and an increased use of antagonists should help reduce the overall incidence of severe OHSS with its associated risks and complications. In patients on antagonist protocols identified to be at risk of developing severe OHSS, replacing human chorionic gonadotropin with GnRHa as a trigger of final oocyte maturation has been proposed as an effective measure of secondary prevention. A concept of combining GnRHa triggering with cryopreservation of all oocytes or embryos has yielded promising results as far as total avoidance of OHSS is concerned while providing a good chance of pregnancy for the patient in later frozen-thawed embryo transfers. In patients with early onset of OHSS, reinitiation of GnRH-ant in the luteal phase as a measure of tertiary prevention might lead to rapid regression of the syndrome; however only limited data on this new concept are available in the literature.