Optimized personalized management approach for moderate/severe OHSS: development and prospective validation of an OHSS risk assessment index.

STUDY QUESTION: Can a simplified ovarian hyperstimulation syndrome (OHSS) risk assessment index be developed and validated with sufficient discrimination of moderate/severe OHSS from those without OHSS? SUMMARY ANSWER: This easy-to-use OHSS risk assessment index shows good discriminative power and high calibration accuracy in internal and external validation cohorts. WHAT IS KNOWN ALREADY: An early alert and risk stratification is critical to prevent the occurrence of OHSS. We have previously developed a multi-stage smartphone app-based prediction model to evaluate the risk of OHSS, but app use might not be so convenient in many primary institutions. A simplified OHSS risk assessment index has been required. STUDY DESIGN, SIZE, DURATION: This training and internal validation of an OHSS risk assessment index used retrospective cohort data from January 2016 to December 2020. External validation was performed with a prospective cohort database from January 2021 to May 2022. There were 15 066 cycles in the training cohort, 6502 cycles in the internal validation cohort, and 8097 cycles in the external validation cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was performed in the reproductive medicine center of a tertiary hospital. Infertile women who underwent ovarian stimulation were included. Data were extracted from the local database with detailed medical records. A multi-stage risk assessment index was constructed at multiple stages. The first stage was before the initiation of ovarian stimulation, the second was before the ovulation trigger, the third was after oocyte retrieval, and the last stage was on the embryo transfer day if fresh embryo transfer was scheduled. MAIN RESULTS AND THE ROLE OF CHANCE: We established a simplified multi-stage risk assessment index for moderate/severe OHSS, the performance of which was further evaluated with discrimination and calibration abilities in training and internal and external validation cohorts. The discrimination abilities of the OHSS risk assessment index were determined with C-statistics. C-statistics in training (Stages 1-4: 0.631, 0.692, 0.751, 0.788, respectively) and internal (Stages 1-4: 0.626, 0.642, 0.755, 0.771, respectively) and external validation (Stages 1-4: 0.668, 0.670, 0.754, 0.773, respectively) cohorts were all increased from Stage 1 to 3 with similar trends, and were comparable between Stages 3 and 4. Calibration plots showed high agreement between observed and predicted cases in all three cohorts. Incidences of OHSS based on diverse risk stratification (negligible risk, low risk, medium risk, and high risk) were 0%, 0.6%, 2.7%, and 8.3% in the training cohort, 0%, 0.6%, 3.3%, and 8.5% in the internal validation cohort, and 0.1%, 1.1%, 4.1%, and 7.2% in the external validation cohort. LIMITATIONS, REASONS FOR CAUTION: The influence from clinical interventions including cryopreservation of all embryos cannot be eliminated and thus certain risk factors like estrogen level on trigger day might be assigned with a lower risk score. Another weakness of the study is that several preventive treatments, for instance oral aspirin and letrozole, were not recorded and evaluated in the model. Despite the robust reliability of OHSS assessment index, this tool cannot be used directly for clinical decision-making or as a diagnostic tool. Its value lies in its capacity to evaluate the prognosis of various interventions and to facilitate clinician-patient communication. The combination of this tool and further symptoms and examinations should be all taken into consideration for accurate and personalized management of OHSS. WIDER IMPLICATIONS OF THE FINDINGS: The OHSS risk assessment index can be implemented to facilitate personalized counseling and management of OHSS. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by National Key R&D Program of China (2022YFC2702504), Medical Research Fund Guangdong Provincial (A2024003), and Xinjiang Support Rural Science and Technology (Special Correspondent) Program in Guangdong Province (KTPYJ 2023014). All authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

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.

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.

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.

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.

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.

Patients with IVF complicated by moderate-to-critical OHSS experience increased thrombosis, GDM and neonatal NICU admission but slightly shorter gestation compared with matched IVF counterparts: A retrospective Chinese cohort study.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a common disease during controlled ovarian hyperstimulation treatment. However, the obstetric and neonatal outcomes of this group of patients are unknown. The aim of this study was to explore the effects of late moderate-to-critical OHSS on obstetric and neonatal outcomes. METHODS: This prospective observational study included 17,537 patients who underwent IVF/ICSI-fresh embryo transfer (ET) between June 2012 and July 2016 and met the inclusion criteria, including 7,064 eligible patients diagnosed with clinical pregnancy. Ultimately, 6,356 patients were allocated to the control group, and 385 patients who were hospitalized and treated at the center for late moderate-to-critical OHSS were allocated to the OHSS group. Then, propensity score matching analysis was performed, matching nine maternal baseline covariates and the number of multiple gestations; 385 patients with late moderate-to-critical OHSS were compared with a matched control group of 1,540 patients. The primary outcomes were the live birth rate, preterm delivery rate, miscarriage rate, gestational age at birth (weeks), obstetric complications and neonatal complications. RESULTS: The duration of gestation in the matched control group was significantly higher than that in the OHSS group. The live birth delivery rate did not significantly differ between the OHSS and matched control groups. The incidence rates of the obstetric complications venous thrombosis (VT) and gestational diabetes mellitus (GDM), neonatal complications and the number of neonates admitted to the NICU were significantly higher in the OHSS group than in the matched control group. CONCLUSIONS: Pregnant women undergoing IVF with fresh ET whose course is complicated by late moderate-to-critical OHSS appear to experience shortened gestation and increased obstetrical and neonatal complications compared with matched controls whose course is not complicated by OHSS. However, the live birth rate, average neonatal weight, and incidence rates of premature delivery, miscarriage, early abortion, hypertensive disorder of pregnancy (HDP), placenta previa (PP), intrahepatic cholestasis of pregnancy (ICP), and low neonatal birth weight (LBW) did not differ significantly between the two groups.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

BACKGROUND: Monitoring of in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) is necessary to detect as well as reduce the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the optimal ovarian response needed for assisted reproduction treatment. Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation IVF and ICSI treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered.  OBJECTIVES: To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. SEARCH METHODS: In this update conducted in March 2020, two review authors searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the National Research Register, and web-based trial registers. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. SELECTION CRITERIA: Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. DATA COLLECTION AND ANALYSIS: Two review authors (IK, AW) independently selected the studies, extracted data and assessed risk of bias. We resolved disagreements by discussion. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. MAIN RESULTS: We did not identify any new eligible studies in this update in 2020. The evidence based on the six trials identified in 2014 remained unchanged. They included 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment. None of the six studies reported our primary outcome of live birth rate. Two studies presented pregnancy rate per initiated cycle and per embryo transfer, respectively. Four studies reported pregnancy rate per woman with pooled data; we are uncertain of the effect of monitoring with TVUS only versus combined monitoring on clinical pregnancy rate per woman (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests in women with a 36% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate using TVUS only would be between 31% and 46%. We are uncertain of any effect in the mean number of oocytes retrieved per woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence).  We are uncertain whether monitoring with TVUS only versus combined monitoring affected the incidence of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that in women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate monitored by TVUS only would be between 2% and 8%. The cycle cancellation rate was similar in both arms of two studies (0/34 versus 1/31, 1/25 versus 1/25; OR 0.57; 95% CI 0.07 to 4.39; N = 115; I² = 0%; low quality evidence).  The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. AUTHORS' CONCLUSIONS: This review update found no new randomised trials. Evidence from the six studies previously identified did not suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. The choice of one or the other method may depend upon the convenience of its use, and the associated costs. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Insulin Resistance and Free Androgen as Predictors for Ovarian Hyperstimulation Syndrome in Non-PCOS Women.

We evaluated the effect of insulin resistance and free androgen index (FAI) in non-PCOS (polycystic ovary syndrome) infertile women following controlled ovarian hyperstimulation. A prospective study was done on 144 infertile non-PCOS women with regular menstrual cycle. At first, insulin resistance (IR), free androgen index (FAI), PCOM (polycystic ovary morphology), AFC (antral follicle count), and AMH (anti-Müllerian hormone) were assessed. The patients underwent assisted reproductive technology (ART), and then preovulatory follicles and oocytes retrieved were recorded. The variables of the study were compared between two groups of patients with ovarian hyperstimulation syndrome (OHSS) (n=66) and non-OHSS patients (n=78). Of the 9 variables: BMI, HOMA-IR, FAI, AFC, AMH, PCOM, and preovulatory follicles were risk factors, while the age and retrieved oocytes were not. The 7 variables that showed significance in the univariate analyses were determined as independent variables included in the multivariable logistic regression analysis, as a result, a total of 5 risk factors, BMI, HOMA-IR, FAI, PCOM, and preovulatory follicles entered the equation. The maximum contribution was HOMA-IR followed by PCOM, FAI, preovulatory follicles and BMI. Patients with OHSS had higher chance to have ovaries with polycystic morphology (74%), about three times more than patients who did not develop OHSS (29%) (p<0.001). The best cut-points for IR, FAI, AFC, AMH, and preovulatry follicles were 2.36, 3.9, 8, 3.3 ng/ml, and 10, respectively. Patients with a higher value of BMI, FAI, HOMA-IR, and preovulatory follicles and the presence of PCOM are more likely to develop OHSS, which are not confined to PCOS patients.

Prognostic role of follicular fluid tumor necrosis factor alpha in the risk of early ovarian hyperstimulation syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition characterized by capillary hyperpermeability which can be predicted by preovulatory ovarian responses such as number of follicles. A variety of cytokines are thought to be involved in pathophysiology of this syndrome. METHODS: A prospective cohort study invloving sixty intracytoplasmic sperm injection (ICSI) patients. On the day of hCG injection, we explored the threshold of larger follicles ≥11 mm diameter with a count of ≥18 follicles for the high-risk moderate-to-severe OHSS and 13-18 follicles for the low-risk moderate-to-severe OHSS. Whereas larger follicles count of less than 13 were classified as normoresponders. Pooled follicular fluid (FF) samples of each patient were collected on the day of oocyte retrieval. Magnetic multiplex immunoassay was explored to measure the concentrations of some intrafollicular cytokines including: GM-CSF, INF-γ, TNF-α, IL-10, CXCL8/IL-8, IL-6, IL-5, IL-4, IL-2, and IL-1ß. All sixty patients underwent controlled ovarian hyperstimulation (COH) with either GnRH agonist or antagonist protocols. RESULTS: Intrafollicular TNF-α concentration was significantly different (p < 0.05) in the high-risk moderate-to-severe OHSS patients compared to low-risk moderate-to-severe OHSS patients and normoresponders. TNF-α in FF had a negative correlation with the chance of high-risk moderate-to-severe OHSS. The differences in the risk of OHSS between patients who received GnRH agonist or antagonist were not significant (p > 0.05). CONCLUSIONS: In accordance to the negative correlation of TNF-α and high risk of early OHSS, we did not expect TNF-α to play a role in increasing vascular permeability in ovarian tissues. In addition, the risk of early moderate-to-severe OHSS was not affected by different GnRH superovulation protocols.

Ovarian hyperstimulation syndrome following GnRH agonist trigger for final follicular maturation in a patient undergoing random start ovarian stimulation for egg-donation cycle with an inadvertent concomitant early pregnancy.

We report the first case of OHSS following GnRH agonist trigger for final follicular maturation in random start ovarian stimulation for egg-donation cycles during inadvertent concomitant early pregnancy. As an additional note, the sustained activity exerted by the increasing endogenous hCG production seemed to be responsible for the suboptimal performance in terms of oocyte yield in the current case. OHSS can occur in random-start stimulations protocols even after the use of a GnRH agonist for triggering in case of concomitant unnoticed early pregnancy especially if stimulation is commenced in the periovulatory/luteal phase. The present case report introduces a note of extreme caution when proceeding with this protocol in an otherwise fertile population (egg-donors, elective or oncologic oocyte cryopreservation).

GnRH triggering may improve euploidy and live birth rate in hyper-responders: a retrospective cohort study.

PURPOSE: Despite the increasing use of GnRHa to trigger final oocyte maturation in segmented IVF cycles, the effects of trigger modality on chromosomal competence and embryo quality remain controversial. Hence, the purpose of this study was to compare euploidy rates and pregnancy outcomes among hyper-responding women using hCG versus GnRHa trigger. METHODS: This retrospective study included 333 hyper-responders, defined as >15 oocytes retrieved, who underwent preimplantation genetic testing (PGT-A) in segmented IVF cycles using either GnRHa or urinary hCG trigger. Live birth rate (LBR) was the primary outcome of interest. Implantation rate (IR), clinical pregnancy rate (CPR), and euploidy rate were secondary outcomes. RESULTS: GnRH triggering was associated with improved IR (70.5 vs. 53.2%, p = 0.0475), LBR (51.3 vs. 33.8%, p = 0.0170) compared to hCG. A greater number of oocytes were retrieved (21.9 vs 18.4%, p < 0.001) and euploid embryos produced (2.8 vs. 2.1, p = 0.0109) after GnRHa triggering, while higher euploidy rates were only observed among women <35-years-old (62.0 vs. 51.7%, p = 0.0307) using GnRHa trigger. Higher OHSS rates were observed after hCG triggering (10.6 vs. 2.1%, p = 0.0009). CONCLUSION: Hyper-responders who received GnRHa trigger experienced improved pregnancy outcomes and lower rates of OHSS compared to hCG triggering. The higher number of oocytes retrieved and euploid embryos produced may reflect an improved developmental competence using GnRHa triggering due to physiologic induction of both LH and FSH surge or other undefined mechanisms that improve embryo development. However, higher overall euploid rates were only observed among women <35-years-old using the GnRHa trigger. Further prospective studies are required to validate this observation and evaluate the specific influence of different ovulation triggers on gamete developmental competence among hyper-responder women.

GnRH agonists to sustain the luteal phase in antagonist IVF cycles: a randomized prospective trial.

BACKGROUND: The addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone. METHODS: The primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions. RESULTS: A total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reached p < 0,01. No increase of OHSS risk was observed. CONCLUSIONS: From this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).

Oligosypthomatic ovarian hyperstimulation syndrome in a spontaneous uneventful pregnancy. A case report.

Spontaneous hyperstimulation syndrome (spOHSS) is a rare event in pregnancies following natural conception. Only a few cases are reported in the scientific literature and result associated with massive ovarian enlargement with multiple cysts, dehydration, and fluid accumulation in the "third space". We report a novel case of spOHSS in a naturally conceived singleton pregnancy. The spOHSS was characterized by massive ovarian enlargement with multiple cysts. No dehydration and no signs of ascites were observed. The pregnancy uneventful evolved up to term.

Clinical characteristics of preterm ovarian hyperstimulation syndrome: seven cases from China and 14 cases from the literature.

Preterm ovarian hyperstimulation syndrome (POHS) is a rare condition with only a few reported cases. The objective of this study is to investigate the clinical characteristics of 21 POHS cases (seven from China and 14 from the literature). Suspected patients (n = 7) were referred for further confirmation and data on demographics, family history, clinical manifestations (edema developed in the vulva, the hypogastric site and the upper leg), serum and sonographic assessments (ovarian cyst/cysts, gonadotropins, and estradiol levels), the natural course of patients were documented. We did not observe substantial differences in clinical manifestations among POHS patients from China relative to that from the literature. Preterm female newborns developed edema in the vulva, the hypogastric site and the upper leg at 30-39+6 weeks of post-conception age (PCA) as the major clinical manifestations. The characteristic also included high gonadotropins and estradiol, and ovarian cysts. This condition can self-resolve. Clinical manifestations of POHS patients from China are similar to those from the literature. The pathognomonic signs of POHS include vulvar, hypogastric, and upper leg edema developed at 30-39+6 PCA along with high gonadotropins and E2 values and the presence of ovarian cysts in preterm female newborns and the syndrome can self-resolve.

Ovarian hyperstimulation syndrome. A new look at an old problem.

To analyze the management of severe ovarian hyperstimulation syndrome based on aspects of its etiology and pathogenesis a systematic review of the literature was done. An evaluation of clinical trials, meta-analysis, case-reports and reviews assessing the management of different conditions related to ovarian hyperstimulation syndrome was made using the following data sources: MEDLINE Pubmed (from 1966 to July 2018) and the Cochrane Controlled Clinical Trials Register, Embase (up to July 2018). The role of intra-abdominal hypertension in the development of the severe forms of ovarian hyperstimulation syndrome and its complicated outcomes was assessed. The pathophysiology and clinic of intra-abdominal hypertension syndrome are almost identical to moderate and severe forms of ovarian hyperstimulation syndrome and associated organ dysfunction. The classic triad (respiratory disorders, reduction in venous return, and restriction of perfusion in internal organs) is present in severe ovarian hyperstimulation syndrome as well as in intra-abdominal hypertension syndrome. This review provides recommendations for the management of ovarian hyperstimulation syndrome and insight into the different medical complaints of this syndrome. The principles of therapy for intra-abdominal hypertension syndrome might be considered in the treatment of severe forms of ovarian hyperstimulation syndrome.

Anti-Müllerian Hormone and Its Predictive Utility in Assisted Reproductive Technologies Outcomes.

Anti-Müllerian hormone (AMH) has become one of the most informative biochemical markers of the ovary and is considered the earliest and most sensitive marker of reproductive aging. The accuracy of AMH in predicting ovarian response to controlled ovarian stimulation has led to AMH-based prognostication counseling and individualization of assisted reproductive technology (ART) stimulation protocols to optimize ovarian response and minimize hyperstimulation risks. Although AMH is considered a good predictor of quantitative ART outcomes, its correlation with qualitative ART outcomes is still controversial. The aim of this review is to provide an updated overview of the clinical utility of AMH in predicting ART outcomes.

Intrafollicular melatonin concentration is elevated in patients with ovarian hyperstimulation syndrome (OHSS) and can serve as an important predictor of OHSS.

PURPOSE: Melatonin is an important factor in regulating numerous processes in human female reproduction. The aim of the present study was to compare melatonin levels in the follicular fluid (FF) of ovarian hyperstimulation syndrome (OHSS) women with those of non-OHSS women undergoing in vitro fertilization (IVF)-embryo transfer and to evaluate the relationship between FF melatonin levels and IVF outcomes in these women. METHODS: We determined FF melatonin levels in 20 OHSS women and 23 non-OHSS women on oocyte retrieval day. RESULTS: OHSS patients had significantly higher melatonin levels as compared to the non-OHSS women (P < 0.001). In addition, melatonin levels of the patients were significantly positively correlated with antral follicle count (AFC), serum anti-Müllerian hormone (AMH) levels, serum estradiol (E2) levels on human chorionic gonadotropin (HCG) administration day, number of retrieved oocytes, total fertilized oocytes, normally fertilized oocytes, cleaved zygotes, top quality embryos on day 3, blastocysts obtained and embryos suitable for transplantation (day 3 embryos + day 5/6 blastocysts) (P < 0.05). While, the intrafollicular melatonin levels were significantly negatively correlated with age, basal serum follicle-stimulating hormone (FSH) levels, serum FSH levels on HCG administration day (P < 0.01). Since younger women with more AFC, higher AMH levels, higher serum E2 levels and larger number of retrieved oocytes are much easier to encounter OHSS, while FF melatonin levels are significantly correlated with these five indices in our study, we propose that intrafollicular melatonin concentration can also be an important predictor of OHSS. CONCLUSIONS: This is the first demonstration that FF melatonin levels were significantly higher in OHSS patients than in non-OHSS group and FF melatonin levels may serve as an important predictor of OHSS.

Ovarian Hyperstimulation Syndrome as a Growing Diagnostic Problem in Emergency Department Settings: A Case Report.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a common complication of an in-vitro fertilization (IVF) procedure, which is usually clinically insignificant. However, without monitoring, it can progress into a life-threatening condition. With the increasing popularity of IVF technology, patients with OHSS may begin visiting emergency departments (EDs) more frequently. CASE REPORT: We report the case of a patient admitted to the ED presenting with severe abdominal pain, cough, and nausea. An ultrasound examination was inconclusive. Computer tomography revealed enlarged ovaries and fluid in the pleural cavities, around the liver and spleen, between the bowel loops, and in the pelvis. This prompted physicians to review the patient's fertility issues. Consequently, the diagnosis of OHSS was made. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: When the physician knows that the patient is undergoing IVF, the diagnosis of OHSS can be straightforward; without this information, it can be difficult. Having in mind the growing demand for infertility treatment, we present this case to increase awareness of possible clinical findings and complications of OHSS as a rare consequence of IVF. OHSS diagnosed via ultrasound can reduce the emotional, financial, and health burden of infertile couples and help them to fulfill their procreation plans without unnecessary delay.

Added value today of hormonal measurements in ovarian stimulation in gonadotropin-releasing hormone antagonist treatment cycle.

PURPOSE OF REVIEW: Traditional approach of ovarian stimulation monitoring for in-vitro fertilization involves transvaginal sonography and serum estradiol measurements. Accumulating evidence has shown that hormonal evaluations during ovarian stimulation allow individual cycle optimization, moving away from only predicting the risk of ovarian hyperstimulation syndrome, but in addition assessing the impact of ovarian stimulation on endometrial receptivity, quality of oocytes, and subsequently embryos. The purpose of this review is to discuss the relevance and added value of hormonal monitoring during ovarian stimulation in gonadotropin-releasing hormone antagonist cycles where most of the advances have occurred. RECENT FINDINGS: Basal hormonal status, particularly estradiol, progesterone, and luteinizing hormone are instrumental in prediction of the patients with poor prognosis. Estradiol levels on the day of trigger are less sensitive in predicting ovarian hyperstimulation syndrome then the number of follicles more than 11 mm in diameter. Progesterone elevation on the day of trigger is associated with lower pregnancy rates. The gold standard treatment for progesterone elevation is to adopt a freeze-all strategy when the threshold of 1.50 ng/ml is exceeded. The effect of progesterone elevation on embryo quality remains to be confirmed by more trials. SUMMARY: Endocrine monitoring during ovarian stimulation allows fine-tuning of the physiology of the stimulated cycle and thereby increases the chances of successful treatment outcome.