Late Ovarian Hyperstimulation Syndrome Research Articles

Spontaneous dichorionic diamniotic twin pregnancy following a leuprolide acetate trigger and freeze all cycle for OHSS risk: A case report

Introduction: Gonadotropin-releasing hormone (GnRH) agonist triggers are increasingly used in antagonist in vitro fertilization (IVF) cycles to prevent ovarian hyperstimulation syndrome (OHSS) following a robust ovarian response. The luteolytic effects of GnRH agonists inhibit implantation or spontaneous pregnancy, warranting freezing available blastocysts for future transfer after the risk of OHSS subsides. Case Report: A 33-year-old G1P1 with secondary infertility due to polycystic ovarian syndrome underwent IVF with a GnRH antagonist cycle. A leuprolide acetate trigger for final oocyte maturation was prescribed given her risk of OHSS. A spontaneous dichorionic/diamniotic twin pregnancy ensued. Conclusion: This case reinforces the importance of advising abstinence during the stimulation phase of an IVF cycle and that, although rare, the endometrium may allow for spontaneous conception following a leuprolide acetate trigger, which may further potentiate the risk of late OHSS.

Treatment algorithms for high responders: What we can learn from randomized controlled trials, real-world data and models.

A high ovarian response to conventional ovarian stimulation (OS) is characterized by an increased number of follicles and/or oocytes compared with a normal response (10-15 oocytes retrieved). According to current definitions, a high response can be diagnosed before oocyte pick-up when >18-20 follicles ≥11-12mm are observed on the day of ovulation triggering; high response can be diagnosed after oocyte pick-up when >18-20 oocytes have been retrieved. Women with a high response are also at high risk of early ovarian hyper-stimulation syndrome (OHSS)/or late OHSS after fresh embryo transfers. Women at risk of high response can be diagnosed before stimulation based on several indices, including ovarian reserve markers (anti-Müllerian hormone [AMH] and antral follicle count [AFC], with cutoff values indicative of a high response in patients with PCOS of >3.4ng/mL for AMH and >24 for AFC). Owing to the high proportion of high responders who are at the risk of developing OHSS (up to 30%), this educational article provides a framework for the identification and management of patients who fall into this category. The risk of high response can be greatly reduced through appropriate management, such as individualized choice of the gonadotropin starting dose, dose adjustment based on hormonal and ultrasound monitoring during OS, the choice of down-regulation protocol and ovulation trigger, and the choice between fresh or elective frozen embryo transfer. Appropriate management strategies still need to be defined for women who are predicted to have a high response and those who have an unexpected high response after starting treatment.

Determinants of Severe Late Ovarian Hyperstimulation Syndrome in Fresh Embryo Transfer Cycles Based on Integration of Decision Tree Classification and Conditional Logistic Regression

Background: To explore possible predictors of severe late ovarian hyperstimulation syndrome (SL-OHSS) in fresh embryo transfer cycles. Methods: We conducted a historical cohort study in a Chinese tertiary hospital from January 2017 to December 2019, with a total of 6931 women who had the first fresh embryo transfer included. SL-OHSS was defined as severe symptoms of OHSS occurring 12–17 days after ovulation triggering. Possible determinants of the occurrence of SL-OHSS were identified by a detection decision tree, effects of which were estimated by conditional logistic regression and restricted cubic spline. Results: Elevated estradiol (E2) on the day of ovulation triggering and elevated Anti-Mullerian hormone (AMH) were associated with an increased risk of SL-OHSS (p < 0.001). Women with an E2 on trigger day of ≥3320.2 pg/mL (odds ratio (OR): 2.20; 95% confidence interval (CI): 1.03–4.68), or with an E2 on trigger day of <3320.2 pg/mL and an AMH of ≥4.62 ng/mL (OR: 5.44; 95% CI: 2.29–12.90), had an increased risk of SL-OHSS compared to their counterparts. Women with E2 on trigger day of >3320.2 pg/mL and AMH of >4.62 ng/mL had the highest risk of SL-OHSS (OR: 13.20; 95% CI: 3.87–45.02) when compared with E2 on trigger day of ≤3320.2 pg/mL and AMH of ≤4.62 ng/mL. This association was not linear. Conclusions: Serum E2 concentration on trigger day and AMH levels at baseline may predict SL-OHSS occurrence in fresh embryo transfer cycles. These biomarkers may be valuable in determining the optimum transfer strategy to limit the occurrence of SL-OHSS.

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

ObjectivesTo 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 designA 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. ResultsA 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. ConclusionAlthough 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.

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.

A qualitative study on couples’ attitudes and concerns regarding a freeze all strategy in ART treatment

The freeze all strategy has become a promising alternative to fresh embryo transfer in fertility treatment almost eliminating late ovarian hyperstimulation syndrome (OHSS) in the segmented cycle. There is a lack of in-depth knowledge regarding patients’ attitudes towards the freeze all strategy. The aim of this study was to explore the attitudes towards a freeze all strategy compared with fresh embryo transfer in assisted reproductive technology (ART) treatment among couples in a public health care setting. We conducted semi-structured qualitative interviews with ten couples already participants in a randomised controlled trial (RCT) and undergoing ART treatment. The couple’s responses showed five themes: (i) Starting treatment provides needed relief; (ii) Treatment must be provided with humanity; (iii) Provision of information instigates positive attitudes towards treatment; (iv) Fresh treatment – ‘The normal way’; and (v) Freeze all treatment – ‘The new black’. When thorough information about treatment procedures and safety aspects regarding both the freeze all and fresh embryo transfer strategy is given prior to initiation of treatment, couples feel secure and content, regardless of which treatment strategy is finally applied. This qualitative study found that starting treatment could prompt longed-for relief, as professionals would now ‘take over’ and assist in meeting the couple’s family building goals.

Luteal Support and Risk of Ovarian Hyperstimulation in Assisted Reproduction (A Review)

Background. Gonadotropin-releasing hormone agonist as an ovulation trigger effectively reduces the ovarian hyperstimulation risk in in vitro fertilisation protocols, at the same time requiring an effective luteal phase support in embryo transfer cycles.Objectives. A review of modern approaches to luteal support after the ovulation trigger switch in in vitro fertilisation/intracytoplasmic sperm injection protocols; assessment of feasibility and safety of gonadotropin-releasing hormone agonist in the post-transfer period.Methods. Literature sources were mined in the PubMed, eLibrary, Web of Science, Cochrane Library, Cyberleninka databases at a depth of 10 years. The query keywords were: gonadotropin-releasing hormone agonist, luteal phase support, ovulation trigger, in vitro fertilisation, ovarian hyperstimulation syndrome.Results. The review included 35 records selected from the 96 analysed total. The analysis reveals a sensible efficiency of gonadotropin-releasing hormone agonist for the luteal phase support, improved success of in vitro fertilisation/intracytoplasmic sperm injection and embryo transfer strategies, improved pregnancy outcomes. Microdosing of chorionic gonadotropin to supplement standard progesterone luteal support also improves the pregnancy outcome rate in assisted reproduction, however, at the risk of late ovarian hyperstimulation syndrome and should be applied with caution.Conclusion. Administration of gonadotropin-releasing hormone agonist for luteal support may improve pregnancy outcomes in in vitro fertilisation/intracytoplasmic sperm injection protocols in patients with the ovarian hyperstimulation risk after the ovulation trigger switch. Nevertheless, further research is necessary into the efficacy and safety of gonadotropin-releasing hormone agonist for luteal support in embryo transfer cycles.

Pregnancy Rate in Frozen Cycles Transfer After Freeze-All Policy to Prevent Ovarian Hyper Stimulation Syndrome

Background: Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic state, potentially lethal, and still one of the major complications encountered during controlled ovarian stimulation (COS) in IVF. It occurs in approximately 1–14 % of assisted reproductive technique (ART) cycles and is related to increased vascular permeability. There are two forms of (OHSS) early and late form. Objectives: The aim of the study was to evaluate the pregnancy rate from frozen thawed embryo transfer after freeze-all policy for patient with high risk for OHSS. Patients and methods: This is cohort study conducted at Genetics and Infertility Unit, Department of Obstetrics and Gynecology, Zagazig University and a private center (retro- prospective and record-based data). The study was carried out on 150 infertile cases. They were divided into three groups. Group A: Frozen thawed embryo transfer after freeze-all policy for cases of high risk to OHSS, group B: frozen thawed embryo transfer for cases with normal ovarian response and group C: Fresh embryo transfer in cycles with 6 or more oocytes with antagonist protocol. Results: The main results of the study revealed that there was high statistically significant difference between groups regarding pregnancy outcomes. Pregnancy rate in frozen cycles is better than fresh cycles in normal responders with no late OHSS and less severe early OHSS. Conclusion: Freeze-all policy improves pregnancy rate in high and normal responders. Also, it prevents late OHSS.

A decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for ovarian hyperstimulation syndrome after triggering final oocyte maturation with hCG.

STUDY QUESTIONCan the grade of ascites, haematocrit (Ht), white blood cell (WBC) count and maximal ovarian diameter (MOD) measured on Day 3 be used to construct a decision-making algorithm for performing or cancelling embryo transfer in patients at high risk for severe ovarian hyperstimulation syndrome (OHSS) after an hCG trigger?SUMMARY ANSWERUsing cut-offs of ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm on Day 3, a decision-making algorithm was constructed that could predict subsequent development of severe OHSS on Day 5 with an AUC of 0.93, a sensitivity of 88.5% and a specificity of 84.2% in high-risk patients triggered with hCG.WHAT IS KNOWN ALREADYDespite the increasing popularity of GnRH agonist trigger for final oocyte maturation as a way to prevent OHSS, ≥75% of IVF cycles still involve an hCG trigger. Numerous risk factors and predictive models of OHSS have been proposed, but the measurement of these early predictors is restricted either prior to or during the controlled ovarian stimulation. In high-risk patients triggered with hCG, the identification of luteal-phase predictors assessed post-oocyte retrieval, which reflect the pathophysiological changes leading to severe early OHSS, is currently lacking.STUDY DESIGN, SIZE, DURATIONA retrospective study of 321 patients at high risk for severe OHSS following hCG triggering of final oocyte maturation. High risk for OHSS was defined as the presence of at least 19 follicles ≥11 mm on the day of triggering of final oocyte maturation.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study includes IVF/ICSI patients at high risk for developing severe OHSS, who administered hCG to trigger final oocyte maturation. Ascites grade, MOD, Ht and WBC were assessed in the luteal phase starting from the day of oocyte retrieval. Outcome measures were the optimal thresholds of ascites grade, MOD, Ht and WBC measured on Day 3 post-oocyte retrieval to predict subsequent severe OHSS development on Day 5. These criteria were used to construct a decision-making algorithm for embryo transfer, based on the estimated probability of severe OHSS development on Day 5.MAIN RESULTS AND THE ROLE OF CHANCEThe optimal Day 3 cutoffs for severe OHSS prediction on Day 5 were ascites grade>2, Ht>39.2%, WBC>12 900/mm3 and MOD>85 mm. The probability of severe OHSS with no criteria fulfilled on Day 3 is 0% (95% CI: 0–5.5); with one criterion, 0.8% (95% CI: 0.15–4.6); with two criteria, 13.3% (95% CI: 7.4–22.8); with three criteria, 37.2% (95% CI: 24.4–52.1); and with four criteria, 88.9% (95% CI, 67.2–98.1). The predictive model of severe OHSS had an AUC of 0.93 with a sensitivity of 88.5% and a specificity of 84.2%.LIMITATIONS, REASONS FOR CAUTIONThis is a retrospective study, and therefore, it cannot be excluded that non-apparent sources of bias might be present. In addition, we acknowledge the lack of external validation of our model. We have created a web-based calculator (http://ohsspredict.org), for wider access and usage of our tool. By inserting the values of ascites grade, MOD, Ht and WBC of high-risk patients on Day 3 after oocyte retrieval, the clinician instantly receives the predicted probability of severe OHSS development on Day 5.WIDER IMPLICATIONS OF THE FINDINGSThe present study describes a novel decision-making algorithm for embryo transfer based on ascites, Ht, WBC and MOD measurements on Day 3. The algorithm may be useful for the management of high-risk patients triggered with hCG and for helping the clinician’s decision to proceed with, or to cancel, embryo transfer. It must be emphasized that the availability of the present decision-making algorithm should in no way encourage the use of hCG trigger in patients at high risk for OHSS. In these patients, the recommended approach is the use of GnRH antagonist protocols, GnRH agonist trigger and elective embryo cryopreservation. In addition, in patients triggered with hCG, freezing all embryos and luteal-phase GnRH antagonist administration should be considered for the outpatient management of severe early OHSS and prevention of late OHSS.STUDY FUNDING/COMPETING INTEREST(S)NHMRC Early Career Fellowship (GNT1147154) to C.A.V. No conflict of interest to declare.TRIAL REGISTRATION NUMBERN/A.

The Effect of Dual Trigger of Oocyte Maturation with Gonadotropin-Releasing Hormone Agonist and Low-Dose Human Chorionic Gonadotropin on Pregnancy Rate in Women at Risk of Ovarian Hyperstimulation Syndrome

Background: the purpose of this study was to compare rates of ovarian hyperstimulation syndrome (OHSS) and the pregnancy outcome after using gonadotropin-releasing hormone agonists (GnRHa) alone and GnRHa in combination with low-dose human chorionic gonadotropin (hCG, dual trigger) for final oocyte maturation in women undergoing controlled ovarian hyperstimulation (COH). Patients and Methods: the study included 150 female patients with high risk of OHSS occurrence who were allocated by the Computer-based randomization method into two groups with 75 patients in each arm, Group I received GnRHa trigger and Group II received dual trigger (GnRHa + low-dose (1500 IU) hCG trigger). Results: Our study showed that the incidence of OHSS was higher after dual trigger than GnRHa trigger but with no statistically significant difference (8.0 vs 1.33 %, p >0.05). There were 6 cases of OHSS developed with dual trigger group (Group II) (3 were mild early OHSS, 2 were moderate early and one case was severe late OHSS). In contrast, there was only one case of severe late OHSS seen in Group I. Conclusion: Dual trigger for final oocyte maturation using GnRHa and low-dose hCG is associated with increased the incidence of early OHSS compared to GnRH alone. However, dual trigger appears to be a safe approach with a satisfactory pregnancy outcome. Also, the dual trigger improves the oocyte maturation, the number of yield embryos and the quality of embryos.

Case Report of Ectopic Pregnancy during Controlled Ovarian Stimulation without Oocytes Harvested and Late Ovarian Hyperstimulation Syndrome

Here we reported a rare case of misdiagnosed ectopic pregnancy (EP) due to unintended ovulation during controlled ovarian stimulation (COS) in GnRH agonist cycle, resulting in no oocytes harvested and late hyper-stimulation syndrome (OHSS). The patient was a 33-year old primary infertile woman due to male’s factors and underwent her second in vitro fertilization (IVF) cycle using GnRH agonist protocol, and no oocytes harvested on ovum picked-up (OPU) day. The start of gonadotropin usage was on day 8th of her period, and the P level increased rapidly and strangely high from day 8th after gonadotropin usage. The E2 level and follicles grew normally but finally no oocytes harvested. She was diagnosed as late ovarian hyper-stimulation syndrome (OHSS) 7 days after OPU. 20 days after OPU, no menstruation come and a positive urine test of hCG were reported. And the patient was diagnosed as EP by laparoscopy. In conclusion, rapidly increased P level, no oocyte retrieval and late onset of OHSS should be very important clues to diagnose this misdiagnosed EP.

A case report on severe ovarian hyperstimulation syndrome in a pregnancy with torsion of bilateral enlarged ovaries with acute abdomen

Ovarian hyperstimulation syndrome is a complication of fertility treatment, which uses pharmacological ovarian stimulation to increase the number of oocytes and therefore embryos available during assisted reproductive technology. Ovarian hyperstimulation syndrome is invariably associated with increased volume of ovaries which is itself a threat to undergo torsion, and it may cause an additional threat requiring prompt surgical intervention in many situations. Simple release of torsion, sacrificing the devitalized ovarian tissue in part and complete can have effect in continuation of pregnancy; and something like this happened in our case. The patient, 29-year-old, a known case of polycystic ovary syndrome (PCOS), conceived through ovulation induction; came with an episode of acute pain abdomen with abdominal distension toward the later part of her first trimester. Ultrasonography was done. Bilateral enlarged ovaries of around 23 cm × 11.8 cm each were seen meeting at the pouch of Douglas with ascites. It was a case of ovarian hyperstimulation syndrome, more specifically, a case of late ovarian hyperstimulation syndrome. Serum E2 level was 3263 pg/ml. Laparotomy was then done. Intraperitoneally bilateral ovarian torsion was seen with areas of necrosis. The right oophorectomy was done, while on the left side some portion of normal ovarian tissue was preserved. Following the operation, her symptoms were improved. The pregnancy continued uneventfully. Exposure of ovaries to human chorionic gonadotropin or luteinizing hormone following controlled ovarian stimulation by follicle-stimulating hormone underlies most cases of ovarian hyperstimulation syndrome. The risk of ovarian hyperstimulation syndrome is smaller when using gonadotropin-releasing hormone antagonist (GnRH) antagonist protocol instead of GnRH agonist protocol for suppression of ovulation during ovarian hyperstimulation. To avoid ovarian hyperstimulation syndrome, the best trigger is GnRH agonists. In PCOS patients, metformin is an important aid in reducing ovarian hyperstimulation syndrome.

Vascular endothelial growth factor antagonist reduces the early onset and the severity of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of controlled ovarian stimulation (COH) during assisted reproductive technology (ART) protocols. This syndrome is a result of ovarian expression of vascular endothelial growth factor (VEGF), which increases vascular permeability. To evaluate the efficiency of prophylactic and therapeutic use of cabergoline in women with higher risk of developing OHSS. In this prospective randomized study, 146 women undergoing in vitro fertilization (IVF) cycles with GnRH agonist protocols with a higher risk of OHSS diagnosed during the HCG day administration (more than 18 follicles observed larger than 12mm in diameter during COH and/or estradiol levels of 3000-3500pg/ml, previous episodes of OHSS). Women were randomly divided in two groups. The first group included 78 women who received 0.5mg per day of cabergoline (Dostinex®) orally for 7 days starting from hCG administration day. The second group included 68 women who received no medication treatment. Overall, in each group 25 patients have developed OHSS. This defines subgroup 1 that includes 25 cases of OHSS obtained in group 1 and subgroup 2 where 25 cases of OHSS obtained in group 2. Early OHSS was defined as being when the onset of the syndrome was initiated during the first 9 days after hCG administration and late OHSS was defined as being when the onset of the syndrome was initiated from 10 days after hCG administration. Outcome measures of this study were the incidence of moderate and severe OHSS, early or late OHSS and pregnancy rates. There was no evidence of a statistically significant reduction in the incidence of OHSS in cabergoline group (32.05% vs. 36.76%; P>0.05). Late OHSS was observed in 60.6% of cases in cabergoline group while 39.4% of cases in the other group (P=0.036). Early OHSS decreased significantly (P<0.05) in the cabergoline group. Severe OHSS cases were more common within subgroup 2 than subgroup 1 (32% vs. 8%, P=0.000). There was no difference in clinical pregnancy rates (PR) and miscarriages rates between the two subgroups. The cabergoline administration (Dostinex®) for patients with high-risk of OHSS can reduce the rate of early OHSS and its severity in GnRH agonist IVF cycles, but cannot prevent the incidence of OHSS.

Ovarian Hyperstimulation Syndrome Due to Exogenous Human Chorionic Gonadotropin (hCG) Presenting More Than 7 Days After hCG Administration

We present a case of ovarian hyperstimulation syndrome (OHSS) occurring 8 days after human chorionic gonadotropin (hCG) administration. OHSS is classified as late type if it occurs 12 to 17 days after hCG administration and early type if it occurs within 7 days. Thus, the condition in this patient did not fit the definition of early or late OHSS. The OHSS was mild, and she recovered in approximately 10 days without requiring admission. The patient was not pregnant, and the OHSS was shown to be induced by exogenous hCG administration not endogenous hCG. In conclusion, OHSS can occur 8 to 11 days after hCG administration and it is important to distinguish whether OHSS is induced by endogenous or exogenous hCG.

Current Medical Strategies in the Prevention of Ovarian Hyperstimulation Syndrome

The purpose of this review is to analyze current medical strategies in the prevention of ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation for in vitro fertilization. Owing to contemporary preventive measures of OHSS, the incidence of moderate and severe forms of the syndrome varies between 0.18% and 1.40%. Although none of medical strategies is completely effective, there is high-quality evidence that replacing human chorionic gonadotropin (hCG) by gonadotropin-releasing hormone (GnRH) agonists after GnRH antagonists and moderate- quality evidence that GnRH antagonist protocols, dopamine agonists and mild protocols reduce the occurrence of OHSS. Among various GnRH agonists, buserelin 0.5 mg, triptorelin 0.2 mg and leuprolide acetate (0.5-4 mg) have been mostly utilized. Although GnRH trigger is currently regarded as the best tool for OHSS prevention, intensive luteal support with exogenous administration of estradiol and progesterone or low-dose hCG on the day of oocyte retrieval or on the day of GnRH agonist trigger are required to achieve optimal conception rates due to early luteolysis. Among currently available dopamine agonists, cabergoline, quinagolide and bromocriptine are the most common drugs that should be used for prevention of both early and late OHSS. Mild stimulation protocols offer attractive option in OHSS prevention with satisfactory pregnancy rates.

Quinagolide compared with cabergoline in the prevention of ovarian hyperstimulation syndrome

Objective The aim of the present study was to compare quinagolide with cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in at-risk patients undergoing in-vitro fertilization (IVF) treatments and to compare the pregnancy rate, the tolerability and the complication rate of the two drugs. Study design A randomized controlled trial. Patients and methods A total of 112 patients undergoing IVF/intracytoplasmic sperm injection long luteal GnRH agonist procedure considered at risk of OHSS were randomized into two groups. Group I patients received quinagolide 75 µg and group II patients received cabergoline 0.5 mg for 8 days starting from the day of human chorionic gonadotrophin injection. Results The total number of patients who developed OHSS in our study was similar in the two groups, with nine (16.1%) patients in the quinagolide group compared with 11 (19.6%) in the cabergoline group (P=0.81). However, the majority of these patients developed only mild OHSS comprising 55.6% in the quinagolide group and 63.6% in the cabergoline group. There was no statistical difference between the two groups regarding the incidence of early OHSS (P=0.77) or late OHSS (P=1.0). Severe/critical grades of OHSS occurred in only 3.6% of the cases in the quinagolide group and 1.8% of the cases in the cabergoline group, whereas the incidence of moderate OHSS was 3.6 and 5.4% in the quinagolide and the cabergoline groups, respectively. Quinagolide was responsible for significantly more nausea (P=0.03) and vomiting (P=0.009) than cabergoline, but there was no statistically significant difference between the two groups regarding other side effects. Conclusion Quinagolide seems to be just as effective as cabergoline in the prevention of OHSS in at-risk patients undergoing IVF treatments.

C-reactive protein response is higher in early than in late ovarian hyperstimulation syndrome

ObjectivesMany in vitro fertilization (IVF) complications are inflammatory by nature, some of which are even life-threatening. We evaluated the response of C-reactive protein (CRP) in IVF complications, especially in early and late ovarian hyperstimulation syndrome (OHSS), to support clinical decision making in gynecological emergency policlinics. Study designIn a prospective two-year study at Helsinki University Hospital, Finland, we recruited patients with IVF complications including moderate or severe OHSS (n=47 patients: 36 early and 14 late OHSS cases), or other IVF complications (n=13). As controls, we recruited women in an uncomplicated IVF cycle (n=27). Serial blood samples (CRP, blood count, platelets, albumin, estradiol, creatinine, and electrolytes) were collected from patients upon admission to the emergency polyclinic and during and after treatment on the ward, and from the controls prior, during, and after the IVF protocol. All samples were categorized according to oocyte pick-up (OPU). The statistics included comparisons between and within the study groups, and receiver-operating characteristic (ROC) curve analysis for diagnostic accuracy of CRP for early OHSS at emergency polyclinics. ResultsOn admission, CRP did not differentiate OHSS from other IVF complications, but CRP was higher in early (median 21; IQR 8–33mg/L) than in late (6; 3–9mg/L, p=0.001) OHSS. In ROC analysis for CRP (12mg/L), the area under the curve (AUC) was 0.74 (p=0.001) with sensitivity of 69% and specificity of 71% for early OHSS. CRP was significantly higher (28; 10–46mg/L) in patients with early OHSS two days after oocyte pick-up (OPU) than in the controls (5; <3–9mg/L, p<0.001). The level normalized by 12 days, similarly to the controls. On the ward, the peak CRP was higher if early OHSS was complicated with infection (108; 49–166mg/L) than without infection (20; 8–32mg/L, p=0.001). Late OHSS was associated with hypoalbuminemia (19.6; 16.2–23.1g/L, p<0.001) and thrombocytosis (494; 427–561 E9/L, p=0.004; comparisons to early OHSS). ConclusionsEarly OHSS associates with a distinct rise in CRP level beyond that induced by uncomplicated oocyte pick-up, whereas the CRP levels in late OHSS are comparable to those in the control cycles. CRP identifies, but cannot distinguish IVF complications.

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

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. 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. 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. 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). 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.

Predictors of Paracentesis in Women with Severe Ovarian Hyperstimulation Syndrome: A Retrospective Cohort Study

Background: To identify predictors of paracentesis in women with severe ovarian hyperstimulation syndrome (OHSS). Methods: In a retrospective cohort study, we assessed patient characteristics and outcome measures of women with severe OHSS Golan grade II/III from 1996 to 2010 using univariate and multivariate analyses with the number of paracenteses as the main outcome. Results: Three hundred ninety four women with OHSS Golan grade II (n = 40) and grade III (n = 354) were included in the study. Paracentesis was performed in 108/394 (27%) of these women. One paracentesis was performed in 63 (16%), 2 paracenteses in 26 (6%), and ≥3 paracenteses 19 (5%) women, respectively. No thrombotic or cerebrovascular morbidity occurred. The mortality of the cohort was 0/394 (0%). In a univariate analysis, late onset OHSS (p = 0.02), pregnancy (p < 0.001), human chorionic gonadotropin use (p = 0.02), ovarian diameter (p = 0.006), and elevated serum levels of alanine aminotransferase (p < 0.001), hematocrit (p < 0.001), leucocytes (p < 0.001), thrombocytes (p < 0.001), and uric acid (p < 0.001) were associated with paracentesis. In a multivariate logistic regression analysis, only alanine aminotransferase (OR 1.006; 95% CI 1.001-1.01) and hematocrit (OR 1.16; 95% CI 1.05-1.27) were independently associated with paracentesis. Conclusion: Alanine aminotransferase and hematocrit at initial presentation are independent predictors of paracentesis.

Spontaneous Late Onset OHSS in Singleton Pregnancy in 2nd Trimester: A Rare Case.

Ovarian hyperstimulation syndrome (OHSS) is a potentially life‐threatening complication of pharmacological ovarian stimulation. It is seen in approximately 2 % of all IVF cycles. The prevalence of moderate to severe OHSS ranges from 1 to 10 % in major IVF programs. Severe forms complicate 1 % of IVF cycles and are characterized by massive ovarian enlargement together with a fluid shift into extravascular compartments responsible for the development of ascites, sometimes pleural and/or pericardial effusion, hypovolemia, oliguria, and hydroelectrolytic disorders. In the most marked cases, thromboembolic phenomena may occur as a result of hemoconcentration and coagulation disturbances (Hollemaert et al. [1]). Spontaneous ovarian hyperstimulation (spontaneous OHSS) is extremely rare in naturally conceived pregnancies. OHSS in the absence of exogenous gonadotropins is very rare, and only a few cases have been reported in the literature. Spontaneous OHSS likely to occur at 8–14 weeks of gestation, while iatrogenic OHSS usually occurs earlier at 3–8 weeks of gestation [2]. Human chorionic gonadotropin (hCG) is thought to play a crucial role in the development of the syndrome. Severe forms are indeed restricted to cycles with exogenous hCG to induce ovulation or as luteal phase support or with endogenous pregnancy‐derived hCG (Delbaere et al. [3]). Here, we report a rare case of spontaneous 2nd trimester OHSS in 22-year-old primigravida.