Prevention of moderate and severe ovarian hyperstimulation syndrome: a guideline.

Ovarian hyperstimulation syndrome is a serious complication associated with assisted reproductive technology. This systematic review aims to identify who is at high risk for developing ovarian hyperstimulation syndrome, along with evidence-based strategies to prevent it and replaces the document of the same name last published in 2016.

Normal and Abnormal Appearances of the Ovaries during Assisted Reproduction: Multimodality Imaging Review.

Infertility is a common diagnosis that prompts many couples and individuals to seek assisted reproductive technology (ART) for assistance with conception. These technologies have become increasingly used in the United States in the past several decades, with 326 468 ART cycles performed in 2020, resulting in 75 023 live births. This ubiquity of ART also increases the likelihood that radiologists will encounter both normal and abnormal imaging findings associated with these treatments. Thus, radiologists of all subspecialties should be familiar with the multimodality appearance of the ovaries and pelvis in patients undergoing ART treatments. Furthermore, it is imperative that radiologists understand the appearance expected during different stages of the ART process. During stimulated ovulatory cycles, it is normal and expected for the ovaries to appear enlarged and to contain numerous cystic follicles, often with a small to moderate volume of pelvic free fluid. After oocyte retrieval, hemorrhagic ovarian follicles and a small to moderate volume of blood products in the cul-de-sac can be expected to be seen. Multiple nonemergency and emergency complications are related to ART, many of which can be seen at imaging. The most encountered emergency complications of ART include ovarian hyperstimulation syndrome, ectopic pregnancy, heterotopic pregnancy, multiple gestations, ovarian torsion, and procedural complications related to oocyte retrieval. These complications have important clinical implications, thus necessitating accurate and timely detection by the radiologist and the clinical team. ©RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.

Severe early ovarian hyperstimulation syndrome following GnRH agonist trigger and freeze-all strategy in GnRH antagonist protocol; case report and literature review.

Ovarian hyperstimulation syndrome (OHSS) is characterized by increased vascular permeability, hemoconcentration and fluid leakage to the third space. The vast majority of OHSS cases occur following ovarian stimulation for IVF. This potentially lethal iatrogenic condition is one of the most serious complications of assisted reproductive technologies. We report one case of severe early OHSS after GnRH agonist trigger in a GnRH antagonist protocol and freeze-all approach without the administration of any hCG for luteal-phase support in a 34-year-old case of PCO with 7 years primary infertility. After oocyte retrieval the patient was seen at the emergency unit of the hospital with abdominal distension, pain, anuria, dyspnea, and OHSS symptoms. The diagnosis was OHSS with severe ascitis. She was admitted to the Intensive care unit (ICU). She was managed with oxygen by mask, intravenous fluids, anticoagulant and albumen, we performed a two-time vaginal ascites puncture, resulting in the removal of 7800mL of clear fluid in Intensive Care Unit with full recovery. This case study presents the clinical manifestations, investigation, progress, management, outcome and preventive measures. The patient was managed with no complications. Clinicians have to be aware that even the sequential approach to ovarian stimulation with a freeze-all approach and GNRH analog triggering does not completely eliminate OHSS in all patients.

Ovarian Hyperstimulation Syndrome: A Case Report.

BACKGROUND: Ovarian hyperstimulation syndrome is a rare, life-threatening obstetric emergency. Early recognition and prompt treatment of ovarian hyperstimulation syndrome are essential owing to the risk of long-term complications associated with this condition. CASE PRESENTATION: A 30-year-old female presented to the emergency department with a chief complaint of abdominal pain. After assessment and diagnostic testing, she was diagnosed as having ovarian hyperstimulation syndrome. The patient was admitted for 24-hour observation. The patient was discharged home with instructions to follow up with an outpatient reproductive medicine clinic. One month after her visit to the emergency department, the patient has not had any complications related to the diagnosis. CONCLUSION: This manuscript outlines the case of a patient presenting to the emergency department with ovarian hyperstimulation syndrome that was promptly recognized and treated. It is important for emergency nurses to quickly identify the risk factors and clinical presentation of ovarian hyperstimulation syndrome to decrease the risk of long-term complications.

Ovarian Hyperstimulation Syndrome: A Simulation Case for Emergency Medicine Residents.

Introduction: Ovarian hyperstimulation syndrome (OHSS) is a complication of assisted reproductive technology (ART) for infertility. Given the potential for significant morbidity, it is important for emergency medicine (EM) residents to be able to recognize and initiate treatment for this disorder. Methods: A high-fidelity human patient simulator was used, with availability of bedside ultrasound. PGY 1-4 EM residents participated in this case of a 28-year-old female patient undergoing treatment for infertility who presented to the emergency department with shortness of breath and near syncope. Workup revealed a diagnosis of OHSS. After the simulation, we surveyed residents on their knowledge of OHSS prior to participation in the simulation. We also asked about their confidence in caring for a patient with OHSS pre- and postsimulation based on a 5-point Likert scale. Results: A total of 24 EM residents completed this simulation case. Prior to participating in the simulation experience, 62% of residents reported that they had heard of OHSS, and 17% of residents had previously managed a patient with OHSS. After participating in the simulation, residents' comfort with managing a patient with OHSS increased from 1.7 to 3.7 points (1 = not at all comfortable, 5 = extremely comfortable; p < .001). Discussion: OHSS is a rare but important complication of ART that many EM residents have not treated in the clinical environment. As the presenting symptoms may mimic other diagnoses, obtaining a detailed history and utilizing bedside ultrasonography are essential to diagnosing and correctly treating these patients.

A Personalized Management Approach of OHSS: Development of a Multiphase Prediction Model and Smartphone-Based App.

Objective: This study aimed to develop multiphase big-data-based prediction models of ovarian hyperstimulation syndrome (OHSS) and a smartphone app for risk calculation and patients' self-monitoring. Methods: Multiphase prediction models were developed from a retrospective cohort database of 21,566 women from January 2017 to December 2020 with controlled ovarian stimulation (COS). There were 17,445 women included in the final data analysis. Women were randomly assigned to either training cohort (n = 12,211) or validation cohort (n = 5,234). Their baseline clinical characteristics, COS-related characteristics, and embryo information were evaluated. The prediction models were divided into four phases: 1) prior to COS, 2) on the day of ovulation trigger, 3) after oocyte retrieval, and 4) prior to embryo transfer. The multiphase prediction models were built with stepwise regression and confirmed with LASSO regression. Internal validations were performed using the validation cohort and were assessed by discrimination and calibration, as well as clinical decision curves. A smartphone-based app "OHSS monitor" was constructed as part of the built-in app of the IVF-aid platform. The app had three modules, risk prediction module, symptom monitoring module, and treatment monitoring module. Results: The multiphase prediction models were developed with acceptable distinguishing ability to identify OHSS at-risk patients. The C-statistics of the first, second, third, and fourth phases in the training cohort were 0.628 (95% CI 0.598-0.658), 0.715 (95% CI 0.688-0.742), 0.792 (95% CI 0.770-0.815), and 0.814 (95% CI 0.793-0.834), respectively. The calibration plot showed the agreement of predictive and observed risks of OHSS, especially at the third- and fourth-phase prediction models in both training and validation cohorts. The net clinical benefits of the multiphase prediction models were also confirmed with a clinical decision curve. A smartphone-based app was constructed as a risk calculator based on the multiphase prediction models, and also as a self-monitoring tool for patients at risk. Conclusions: We have built multiphase prediction models based on big data and constructed a user-friendly smartphone-based app for the personalized management of women at risk of moderate/severe OHSS. The multiphase prediction models and user-friendly app can be readily used in clinical practice for clinical decision-support and self-management of patients.

Are anthropometric data a tool for determining the severity of OHSS? Yes, it could be!

BACKGROUND: All management guidelines of ovarian hyperstimulation syndrome (OHSS) recommend daily monitoring of women's body weight, waist circumference and note that as indicators increase, the severity OHSS also increases. However, the dynamics of abdominal size and its relationship with markers of OHSS severity have not been highlighted. The purpose of this study is to assess the usefulness of various anthropometric indicators for determining the degree of OHSS severity as well as paracentesis indications. METHODS: Observational study including 76 women complaining with OHSS. Clinical history, physical examination, laboratory tests, and ultrasound measurement of the ovarian volume (OV) and ascites index (AsI) were done in all cases. Intra-abdominal pressure (IAP) was assessed using an intravesical manometer. The anteroposterior diameter of the abdomen (APD) and transverse diameter of the abdomen (TS) were measured with a pelvimeter. The APD/TS ratio was calculated. RESULTS: The APD/TS ratio increased progressively and tended to be the highest in the most symptomatic stage of OHSS (Kruskal-Wallis test, p < 0.001). The median APD/TS was significantly lower in patients with mild OHSS (0.55 [IQR, 0.44-0.64]) compared with severe OHSS (0.87 [IQR, 0.80-0.93]; p < 0.001) or critical OHSS (1.04 [IQR, 1.04-1.13]; p < 0.001). Similarly, the median APD/TS of the moderate OHSS group (0.65 [IQR, 0.61-0.70]) was significantly lower than that of the severe (p < 0.001) and critical OHSS group (p = 0.001). There was a strong positive correlation between APD/TS and IAP (Spearman's r = 0.886, p < 0.01). The APD/TS ratio showed a significant positive correlation with AsI (Spearman's r = 0.695, p < 0.01) and OV (Spearman's r = 0.622, p < 0.01). No significant differences were observed in age, height, weight, body mass index, hip circumference or waist circumference between moderate, severe and critical OHSS groups. CONCLUSIONS: The APD/TS ratio is related to the severity of OHSS. Monitoring APD/TS dynamics could be a method of indirectly controlling intra-abdominal volume, compliance of the abdominal wall and IAP. In conjunction with clinical and laboratory data, APD/TS might be an indicator for paracentesis.

Predictive performance of peritoneal fluid in the pouch of Douglas measured five days after oocyte pick-up in predicting severe late-onset OHSS: A secondary analysis of a randomized trial.

OBJECTIVES: To investigate if the amount of peritoneal fluid (PF) in the Pouch of Douglas at oocyte pick-up (OPU) or OPU + 5 days predict severe late-onset ovarian hyperstimulation syndrome (OHSS) in women undergoing ovarian stimulation for assisted reproductive technology (ART). STUDY DESIGN: A secondary analysis of a dual-centre RCT on 1050 women referred for their first ART treatment in two public fertility clinics in Denmark and randomized 1:1 to GnRH-antagonist or GnRH-agonist protocol. All women from the two arms who were examined on day of OPU and OPU + 5 days were included in this study (n = 940). The ability of PF in the pouch of Douglas to predict severe late-onset OHSS was assessed by multivariate logistic regression analyses and receiver operator characteristics (ROC) curve analyses and compared with other known predictors of OHSS. The final models were cross-validated by the leave-one-out method to assess the models' generalizability. RESULTS: A total of 28 (3%) women developed severe late-onset OHSS. PF in the pouch of Douglas measured on OPU + 5 days predicted severe late-onset OHSS. The optimal cut-off value was 17.5 mm at OPU + 5 days with a 61% sensitivity and 71% specificity (Area under the curve = 0.70 95% CI 0.61-0.80). PF on the day of OPU was not predictive of late on-set OHSS as the adjusted multivariate logistic regression analyses showed insignificant results. CONCLUSION: Although PF in the pouch of Douglas could predict late-onset severe OHSS, the low sensitivity underlines that it is not useful as a sole marker to decide whether to perform blastocyst transfer or to use a freeze-all strategy.

Analysis and prediction of risk factors of ovarian hyperstimulation caused by Long-acting GnRH agonist protocol in follicular phase.

OBJECTIVE: The aim of the study was to explore the risk factors of ovarian hyperstimulation in patients undergoing long-acting gonadotropin-releasing hormone (GnRH) agonist protocol in follicular phase of ovulation induction therapy and to establish a predictive model. PATIENTS AND METHODS: A total of 1289 patients who received Long-acting GnRH agonist protocol in follicular phase for ovulation induction in the Fujian Provincial Maternity and Child Health Hospital from July 1, 2018, to July 31, 2019, were selected. Among them, 33 patients developed moderate/severe ovarian hyperstimulation syndrome. The relevant indicators of the two groups were followed up for comparison, and Lasso regression was used to screen independent risk factors and construct a nomogram prediction model.  A receiver operating characteristic (ROC) curve and calibration curve were used to evaluate the discrimination and calibration of the prediction model. RESULTS: Univariate analysis suggested that the woman's age, basal antral follicle number (AFC), total gonadotropin (Gn) dose, Gn starting dose, basal estradiol (E2) level, basal anti-Müllerian hormone (AMH) value, number of follicles obtained, Gn start day E2, the difference in follicle-stimulating hormone (FSH) value and Gn starting day were statistically significant. Significant indicators of univariate analysis and clinical significance were included in the Lasso regression model, and AFC, woman's age, polycystic ovary syndrome, Gn starting dose and number of follicles obtained were finally screened as final predictors. The ROC curve indicated that the area under the curve (AUC) was 0.812. CONCLUSIONS: Ovarian hyperstimulation caused by long-acting GnRH agonist protocol in follicular phase for ovulation stimulation has a certain predictability. Paying attention to the patient's age, AFC, Gn starting dose, number of follicles obtained, and whether PCOS is evident may lead to early detection of ovarian hyperstimulation syndrome, which has clinical guiding significance.

Fluidothorax as an atypical symptom of late ovarian hyperstimulation syndrome.

OBJECTIVE: To present a case of isolated fluidothorax as a symptom of atypical late ovarian hyperstimulation syndrome. METHODS: Review of available information and presentation of our case observed at the Department of Obstetrics and Gynaecology, 1st Faculty of Medicine, Charles University and University Hospital Bulovka. GnRH antagonist protocol was used to stimulate the patient and fresh embryo transfer was performed. Sixteenth day after the oocyte retrieval the patient was examined due to dyspnoea and lab exam proved ovarian hyperstimulation syndrome. CONCLUSION: Late ovarian hyperstimulation syndrome can lead to isolated fluidothorax in case of additional favourable conditions.

Neutrophil:lymphocyte and estradiol:progesterone ratios as predictive markers for ovarian hyperstimulation syndrome (OHSS).

This study was based on the pathophysiology of the disease and aimed at predicting ovarian hyperstimulation syndrome (OHSS) by determining the importance of ratios obtained from the inflammatory process associated with oestradiol and progesterone in recent years. Out of 242 infertile women who underwent assisted reproductive therapy, 59 patients who developed OHSS were taken as the study group, while the remaining 122 normo-responder (NR) and 61 hyper-responder (HR) patients constituted the control group. The neutrophil to lymphocyte (NLR) and oestradiol/progesterone (EPR) ratios were found to be statistically significantly higher in the OHSS group (P <0.001). A multivariate logistic regression analysis revealed that the NLR (OR=2.410, P =0.001) and EPR (OR=1.701, P =0.028) were independent predictors for the development of OHSS. In conclusion, in OHSS inadequate progesterone levels may inhibit suppression of the exaggerated inflammatory process caused by high E2 levels, and NLR and EPR can be used to predict the development of OHSS in patients undergoing controlled ovarian hyperstimulation during in vitro fertilisation cycles.

An unusually prolonged course of late onset severe OHSS with successful outcome - a rare but avoidable complication.

Ovarian hyperstimulation syndrome (OHSS) is an entity associated with controlled ovarian stimulation (COS) in assisted reproduction. It presents a great challenge for clinicians concerning a timely diagnosis and intervention, because it is a life-threatening condition. We came across a rare case of late onset severe OHSS, which lasted till 19 weeks of gestation (POG) with diagnostic challenge in which the patient had hemorrhagic ascites post embryo transfer, and transaminitis. The case was managed effectively with repeated paracentesis along with replacement therapy, and the transaminitis was also gradually resolved. Severe OHSS may follow an unusually prolonged course associated with transaminitis. Our case suggests that it is crucial to distinguish between the nature and etiology of transaminitis along with OHSS, and other pathologies like drug induced transaminitis should also be kept in mind.

Imaging of complications following treatment with assisted reproductive technology: keep on your radar at each step.

Since the advent of assisted reproductive technology (ART), the utilization of ART procedures has become increasingly popular among women seeking to establish pregnancy. Radiologists are therefore likely to encounter the various complications of ART therapy. The most common is ovarian hyperstimulation syndrome; others are multiple, ectopic, and heterotopic pregnancies. Ultrasonography is considered the initial modality to investigate ART complications, However, nonspecific symptoms might need the use of an additional imaging modality, such as computed tomography or magnetic resonance imaging, as a problem-solving tool. This article briefly discusses the steps involved in assisted reproduction. Its aim is to help radiologists become familiarized with the multimodality imaging features of the spectrum of ART-related complications. Their key imaging features and differential considerations are emphasized. This will facilitate the provision of precise and timely diagnoses, and aid the avoidance of fatal consequences.

Ovarian Hyperstimulation: Diagnosis, Prevention, and Management.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication of controlled ovarian stimulation (COS). Pathogenesis of the disease is based on massive transudation of protein-rich fluid from the vascular compartment into the peritoneal, pleural and pericardial spaces, with a variable picture of clinical manifestations depending on its severity. Nowadays OHSS can easily be avoided by several prevention methods, ranging from identification of high-risk patients, choice of a correct protocol stimulation, trigger with gonadotropin-releasing hormone (GnRH) agonists or, finally, the freeze-all strategy. When OHSS occurs, it can usually be managed as outpatient care. Only if severe/critical cases are diagnosed hospitalization is necessary for appropriate rehydration, monitoring of fluid balance and eventual drainage of ascitic fluid. One of the most dangerous complications of OHSS is venous thromboembolism (VTE). Thromboprophylaxis has shown to be cost effective and widely used, while there are controversies regarding the usage of low dose aspirin (LDA) as a preventive measure.

Nomogram Model to Predict the Probability of Ovarian Hyperstimulation Syndrome in the Treatment of Patients With Polycystic Ovary Syndrome.

Objective: The objective of this study was to explore the risk factors of ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and to establish a nomogram model evaluate the probability of OHSS in PCOS patients. Methods: We retrospectively analyzed clinical data from 4,351 patients with PCOS receiving IVF/ICSI in our reproductive medical center. The clinical cases were randomly divided into a modeling group (3,231 cases) and a verification group (1,120 cases) according to a ratio of about 3:1. The independent risk factors correlation with the occurrence of OHSS was identified by logistic regression analysis. Based on the selected independent risk factors and correlated regression coefficients, we established a nomogram model to predict the probability of OHSS in PCOS patients, and the predictive accuracy of the model was measured using the area under the receiver operating curve (AUC). Results: Univariate and multivariate logistic regression analyses showed that FSH (OR, 0.901; 95% CI, 0.847-0.958; P<0.001), AMH (OR, 1.259; 95% CI, 1.206-1.315; P<0.001), E2 value on the day of hCG injection (OR, 1.122; 95% CI, 1.021-1.253; P<0.001), total dosage of Gn used (OR, 1.010; 95% CI, 1.002-1.016; P=0.041), and follicle number on the day of hCG injection (OR, 0.134; 95% CI, 1.020-1.261; P=0.020) are the independent risk factors for OHSS in PCOS patients. The AUC of the modeling group is 0.827 (95% CI, 0.795-0.859), and the AUC of the verification group is 0.757 (95% CI, 0.733-0.782). Conclusion: The newly established nomogram model has proven to be a novel tool that can effectively, easily, and intuitively predict the probability of OHSS in the patients with PCOS, by which the clinician can set up a better clinical management strategies for conducting a precise personal therapy.

Ovarian Hyperstimulation Syndrome Is Associated with a High Secondary Sex Ratio in Fresh IVF Cycles with Cleavage-Stage Embryo Transfer: Results for a Cohort Study.

The sex ratio at birth is defined as the secondary sex ratio (SSR). Ovarian hyperstimulation syndrome (OHSS) is a serious and iatrogenic complication associated with controlled ovarian stimulation (COS) during assisted reproductive technology (ART) treatments. It has been hypothesized that the human SSR is partially controlled by parental hormone levels around the time of conception. Given the aberrant hormonal profiles observed in patients with OHSS, this retrospective study was designed to evaluate the impact of OHSS on the SSR. In this study, all included patients were divided into 3 groups: non-OHSS (n=2777), mild OHSS (n=644), and moderate OHSS (n=334). Our results showed that the overall SSR for the study population was 1.033. The SSR was significantly increased in patients with moderate OHSS (1.336) compared to non-OHSS patients (1.002) (p=0.048). Subgroup analyses showed that increases in the SSR in patients with moderate OHSS were observed in the IVF group (1.323 vs 1.052; p=0.043), but not in the ICSI groups (1.021 vs 0.866; p=0.732). In addition, the elevated serum estradiol (E2) and progesterone (P4) levels in OHSS patients were not associated with SSR. In this study, for the first time, we report that a high SSR is associated with OHSS in patients who received fresh IVF treatments. The increases in SSR in OHSS patients are not attributed to the high serum E2 and P4 levels. Our findings may make both ART clinicians and patients more aware of the influences of ART treatments on the SSR and allow clinicians to counsel patients more appropriately.

Association of ovarian response with picoAMH in women undergoing controlled ovarian hyperstimulation.

OBJECTIVE: Our study aims to evaluate the diagnostic performance of a high-sensitivity picoAnti-Müllerian Hormone (picoAMH) for predicting ovarian response in women undergoing controlled ovarian hyperstimulation and occurrence of ovarian hyperstimulation syndrome. METHODS: Retrospective cohort study at a single academic fertility center including all patients with picoAMH ELISA who underwent controlled ovarian hyperstimulation. The primary outcome was the number of oocytes retrieved, and secondary outcomes included cycle cancellation and ovarian hyperstimulation syndrome. Patients were grouped into poor, normal, and hyper-responders based on number of oocytes retrieved. RESULTS: The mean AMH and antral follicle count (AFC) were significantly different between normal response vs. hyper response group (p < 0.0001). Only serum AMH and not AFC was significantly increased in patients diagnosed with ovarian hyperstimulation syndrome (OHSS). For prediction of OHSS, receiver operating characteristic (ROC) analysis revealed that AMH (area under the ROC curve [AUC] = 0.85) was significantly better than the AFC (AUC = 0.64). The serum AMH cut-off at sensitivity of 80% for predicting OHSS among hyper responders from ROC curve was 3.67 ng/ml. Serum AMH measured by picoAMH ELISA showed superior correlation to number of oocytes retrieved when compared to AFC in the age group over 40 years old (r2 = 0.74 and r2 = 0.4, respectively) CONCLUSION: This study shows great utility of picoAMH ELISA for predicting ovarian response to controlled ovarian hyperstimulation (COH). Diagnostic performance of picoAMH for prediction of OHSS is superior to the AFC in our cohort.