Acute Lymphoblastic Leukemia in Pregnant Ovarian Hypersensitivity Syndrome.

ABSTRACT: Ovarian hyperstimulation syndrome (OHSS) is characterized by cystic enlargement of the ovaries and a fluid retention. This syndrome is sometimes caused after in vitro fertilization. We treated a 37-year-old woman with OHSS after in vitro fertilization, coincidentally complicated with acute lymphoblastic leukemia. Her clinical course of acute lymphoblastic leukemia was aggressive with the manifestation of OHSS, such as massive pleural effusion and massive ascites. The leukemic cells broadly infiltrated to the peritoneum, ovary, central spine fluid, and pleura. We speculated that this hyperpermeability of leukemic cells could be associated with the cytokine milieu caused by OHSS.

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the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data.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.

Strangulated internal hernia following severe ovarian hyperstimulation syndrome: a case report.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication of ovarian stimulation. Herein, we report a rare case of strangulated internal hernia in a woman with severe OHSS following ovulation induction. A delay in the diagnosis and management of acute abdominal pain can lead to serious problems. The aim of this case report was to highlight the diagnostic difficulties of abdominal pain in women with OHSS, and emphasize the positive effects of imaging and a timely differential diagnosis in clinical practice.

Spontaneous ovarian hyperstimulation syndrome in a nonpregnant female patient: a case report and literature review.

Spontaneous ovarian hyperstimulation syndrome (sOHSS) usually occurs in patients with a spontaneous ovulation cycle, especially in those with multiple pregnancies combined with hypothyroidism and polycystic ovary syndrome. sOHSS rarely occurs in women who are not pregnant. A 23-year-old woman with obvious abdominal distension visited our hospital. The patient was not pregnant and had not undergone controlled superovulation. Apart from abdominal distension, the patient denied any symptom of obvious incentives, abdominal pain, abnormal vaginal bleeding, or drainage. Biochemical analysis showed a high carbohydrate antigen-125 level and low total protein and albumin levels. Abdominal ultrasound and computed tomography showed a large amount of ascites and cystic uneven masses with an irregular shape in the area of the ovaries and fallopian tubes. Post-surgical histopathology indicated the diagnosis of sOHSS. Wedge resection of both ovaries was performed. Symptomatic treatment was further performed and the patient recovered well. Our findings indicate that sOHSS can occur in women who are not pregnant. Additionally, besides the follicle-stimulating hormone receptor gene mutation hypothesis, the pathogenesis of sOHSS should be further studied.

Point of Care Ultrasound in the Diagnosis and Management of Severe Ovarian Hyperstimulation Syndrome.

Presentation A 32year old woman, presented with a 5-day history of non-productive cough, chest pain, shortness of breath andabdominal bloating. She had undergone Embryo Transfer Treatment 6 days previously. Diagnosis A point of care ultrasound (POCUS) exam was performed as part of her initial investigations which showed right pleuraleffusion, ascites and cystic ovaries. Treatment She received Oxygen, IV Fluids and Antibiotics and was referred to the Obstetricians. Discussion Point of care ultrasound (POCUS) aided the prompt diagnosis of ovarian hyperstimulation syndrome (OHSS) in thispatient, making it possible for her to receive appropriate resuscitation and referral and an excellent outcome despitethis being a case of severe ovarian hyperstimulation syndrome.

Multimodality imaging of acute locoregional and systemic complications in the setting of assisted reproduction.

Over the past 40 years since the first in vitro fertilization was performed, both the role of assisted reproductive technology (ART) in establishing viable pregnancy as well as the available treatment options have expanded enormously. Annually in the USA, nearly 2% of pregnancies now employ some form of ART assistance, with in vitro fertilization (IVF) being the most commonly utilized methodology. Both maternal and fetal risks are elevated in ART pregnancies, the latter including adverse outcome due to both increased gestational number as well as advanced maternal age. Maternal risks may be divided into locoregional and systemic complications. Adverse pelvic complications include those relating to gamete harvesting and transfer, ovarian hyperstimulation, the sequela of ectopic and heterotopic pregnancies, as well as ovarian torsion, all of which are elevated in the ART cohort. Ovarian hyperstimulation syndrome is the most commonly encountered complication, with both systemic and pelvic features relating to increased vascular permeability, hemoconcentration, and ascites. While life-threatening cases are relatively rare, moderate and severe manifestations may occur in up to 10% of ART cycles and, as such, are a not infrequent cause for ER visitation. Familiarity with the clinical and imaging manifestations of ART complications as well as their prognostic implications will facilitate a timely diagnosis and assist the interpreting radiologist in best expediting appropriate clinical care. In this article, we will briefly discuss the current methodology of ART then present an imaging-based multimodality review of the potentially encountered adverse maternal sequela, highlighting key diagnostic features and differential considerations as well as potential prognostic implications.

Acute ascites and abdominal pain from ovarian hyperstimulation syndrome (OHSS).

A healthy 30 year old female G1P1 presented to the ED with a chief complaint of abdominal pain, shortness of breath and bloating 72 hours after an egg retrieval out of state. She states she had two injections of an unknown hormone therapy and that the retrieval was uncomplicated. On arrival, heart rate is is 130-140s and her blood pressure is soft (99/76). Her abdomen is distended and non-focally tender but not peritoneal. Point-of-care FAST exam was immediately performed showing free fluid (Fig. 1) and enlarged, cystic appearing ovaries (Fig. 2).

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

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

Cesarean Delivery in a Case of Persistent Second Trimester Ovarian Hyperstimulation Syndrome.

Background Ovarian hyperstimulation syndrome develops as an iatrogenic complication related to ovulation induction. It is usually self-limiting with complete resolution expected within 10-14 days. Case The current case is a report of an unusually prolonged course of ovarian hyperstimulation syndrome persisting until 22 weeks of gestation, accidentally discovered and managed by cesarean section due to an obstetric indication. Conclusion Clinicians should be aware of this possibility when managing cases of IVF pregnancy.

Intravenous neutralization of vascular endothelial growth factor reduces vascular function/permeability of the ovary and prevents development of OHSS-like symptoms in rhesus monkeys.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a disorder associated with elevated serum VEGFA following chorionic gonadotropin (hCG) exposure in controlled ovarian stimulation (COS) cycles in women. In this study, we tested the effect of intravenous VEGFA neutralization on OHSS-like symptoms and vascular function in rhesus macaques during COS cycles. METHODS: Monkeys (n = 8) were treated with 3 COS protocols and assigned randomly to groups as follows: 1) COS alone (Control, n = 5); 2) COS + VEGF mAb Avastin 19 ± 5 h before hCG (Avastin pre-hCG; n = 6); 3) COS + Avastin 3-4 days post-hCG (Avastin post-hCG; n = 4); 4) COS + Simulated Early Pregnancy (SEP n = 3); or 5) COS + SEP + Avastin (SEP + Avastin n = 3). Follicles were aspirated 36 h post-hCG, fluid was collected from one follicle for analysis of steroid and vascular hormone content. Remaining follicles were aspirated, and luteinized granulosa cells (LGCs) cultured for 24 h. Ovarian/uterine vascular flow (VF) and blood volume (BV) were analyzed by contrast enhanced ultrasound (CEUS) before hCG bolus and 6-8 days post-hCG bolus/time of peak SEP response. Ovarian permeability to albumin was analyzed by Dynamic Contrast Enhanced-MRI (DCE-MRI) post-hCG. RESULTS: Abdominal fluid was present in 4/5 Control, 2/6 Avastin pre-hCG, and 3/4 Avastin post-hCG females. Neutralization of VEGFA before hCG reduced ovarian VF, BV, and permeability to albumin (P < 0.05), while only ovarian VF and permeability were reduced in Avastin-post hCG group (P < 0.05). There was no effect of Avastin on ovarian vascular function during COS + SEP. VEGF levels in follicular fluid were reduced 78-fold by Avastin pre-hCG, and LGCs exposed to Avastin in vivo also released 4-fold less VEGF into culture media (P < 0.05). Culture medium of LGCs exposed to VEGFA neutralization in vivo had lower levels of P4 and ANGPT1, and an increased ratio of ANGPT2/1 (P < 0.05). Uterine VF was reduced by SEP + Avastin in the basalis/junctional zone (P < 0.05). CONCLUSIONS: Avastin treatment before hCG prevents the development of symptoms associated with ovarian hyperstimulation syndrome. In vitro data suggest neutralization of VEGFA alters expression of other vascular factors typically induced by hCG in the luteinizing follicle. Neutralization of VEGFA action alters the vascular function of the basalis zone of the uterus during simulated early pregnancy, indicating a potential effect on embryo implantation.

Effect of letrozole on moderate and severe early-onset ovarian hyperstimulation syndrome in high-risk women: a prospective randomized trial.

BACKGROUND: Ovarian hyperstimulation syndrome is an iatrogenic complication of controlled ovarian stimulation. Early ovarian hyperstimulation syndrome occurs during luteal phase of controlled ovarian stimulation within 9 days after human chorionic gonadotropin trigger and reflects an acute consequence of this hormone on the ovaries. Late ovarian hyperstimulation syndrome occurs 10 or more days after human chorionic gonadotropin trigger and reflects increased endogenous human chorionic gonadotropin levels following pregnancy. Human chorionic gonadotropin stimulates granulosa-lutein cells to produce vascular endothelial growth factor messenger RNAs, which in turn raises serum vascular endothelial growth factor concentration and increases vascular permeability in women with ovarian hyperstimulation syndrome. Efforts to reduce the incidence and severity of ovarian hyperstimulation syndrome after oocyte retrieval, and in particular primary prevention efforts, are vital to prevent thrombogenesis and other serious complications. OBJECTIVE: The objective of the study was to compare the efficacy of letrozole, an aromatase inhibitor, with aspirin in primary prevention of early ovarian hyperstimulation syndrome and to compare vascular endothelial growth factor levels between groups. STUDY DESIGN: Participants in this prospective randomized trial included 238 participants undergoing cryopreservation of the whole embryos after oocyte retrieval with at least 1 of the following high-risk factors for ovarian hyperstimulation syndrome: oocyte retrieval ≥25; estradiol level ≥5000 pg/mL on the day of human chorionic gonadotropin administration; and clinical or ultrasonographic evidence of ovarian hyperstimulation syndrome on the day of oocyte retrieval, such as ultrasonographic evidence of ascites. After human chorionic gonadotropin triggering, experimental (119 cases) and control (119 cases) groups received letrozole and aspirin, respectively, for 5 days. The 5 categories of ovarian hyperstimulation syndrome include no, yes-mild, yes-moderate, yes-severe, and yes-critical. The primary outcome was the incidence and severity of early ovarian hyperstimulation syndrome. The secondary outcome included vascular endothelial growth factor level both on the second and seventh day after the human chorionic gonadotropin trigger, and clinical and laboratory features of ovarian hyperstimulation syndrome symptoms. RESULTS: The incidence of ovarian hyperstimulation syndrome was significantly higher in women receiving aspirin, compared with letrozole (90.2% vs 80.4%, P = .044). Moderate and severe ovarian hyperstimulation syndrome was also higher in the aspirin group, 45.1%, compared with the letrozole group, 25.0% (P = .002). Moreover, the duration of luteal phase was shortened in letrozole group compared with aspirin group (8.1 ± 1.1 days vs 10.5 ± 1.9 days, P < .001). The vascular endothelial growth factor level was significantly higher in the letrozole-treated group than aspirin-treated group (0.49 ± 0.26 vs 0.42 ± 0.22, P = .029). CONCLUSION: Letrozole was more effective than aspirin in decreasing the incidence of moderate and severe early-onset ovarian hyperstimulation syndrome. Our results indicate that ovarian hyperstimulation syndrome might be caused through a luteolytic effect rather than through modulation of vascular endothelial growth factor, racing by a decline in estradiol and termination of early-onset ovarian hyperstimulation syndrome in advance in high-risk women with cryopreservation of the whole embryos.

Use of Point-of-Care Ultrasound for the Diagnosis of Ovarian Hyperstimulation Syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) occurs when ovaries are overstimulated and enlarged due to fertility treatments resulting in a shift of serum from the intravascular space to the third space, mainly the abdominal cavity. It is the most serious complication of ovarian hyperstimulation for assisted reproduction. CASE REPORT: We present the case of a 40-year-old woman who presented with abdominal bloating and nausea 2 weeks after undergoing in vitro fertilization (IVF); she was diagnosed by an outside radiology ultrasound as having a ruptured ovarian cyst. A point-of-care emergency ultrasound performed by the emergency physician made the diagnosis of ovarian hyperstimulation syndrome. This led to more expedient management and obstetrical consultation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Abdominal bloating and nausea are common presenting complaints in pregnant women. OHSS is a rare but potentially fatal complication of IVF. Recognition and early diagnosis by the emergency physician can lead to appropriate intervention and consultation.

Young Ischemic Stroke in Association with Ovarian Hyperstimulation Syndrome.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially fatal complication of medical ovarian stimulation. Uncommonly, it is associated with thromboembolic complications with venous thrombosis being more common than arterial thromboembolic events. We present a case of cerebral infarction in the setting of severe OHSS secondary to in vitro fertilization treatment with no residual neurological deficits. MATERIALS AND METHODS: We also performed a review of previously published ischemic cerebral infarction and cerebral venous sinus thrombosis (CVST) cases associated with OHSS to evaluate common patterns in presentations, commonly affected central nervous system sites, trends for therapeutic options in these cases, and outcomes. CONCLUSION: We have included 27 cases of ischemic cerebral infarction and 7 cases of CVST previously published in English literature. We have included cases of central retinal artery occlusion in the ischemic cerebral infarction group, and central retinal vein occlusion in the CVST group. Mean ages of presentation were 31 ± 4.84 and 34 ± 4.90 years for ischemic cerebral infarction and CVST, respectively. Ischemic strokes commonly affect large cortical areas with unilateral weakness, aphasia, unilateral sensory changes, and visual field deficits being the common presentations. Middle cerebral artery (n = 7) is the common site of vascular occlusion where vascular imaging has been reported, followed by internal carotid artery occlusion (n = 5). OHSS cannot be considered a direct risk for pathogenesis, but OHSS is frequently associated with hyperviscosity, which may add to the risk factors.