Severe Ovarian Hyperstimulation Syndrome Research Articles

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

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

Efficacy of gonadotropin-releasing hormone antagonists in the management of patients with severe early-onset ovarian hyperstimulation syndrome

Objective. To study the efficacy of gonadotropin-releasing hormone (GnRH) antagonists in the treatment of patients with severe early-onset ovarian hyperstimulation syndrome (OHSS). Patients and methods. This study including 60 women was conducted between January 2021 and January 2023 at Al-Azhar University Maternity Hospitals and private ART centers. Approval from the Research Ethics Committee was obtained to conduct the study. Patients were randomly divided into two groups: group I (n = 30; control group) received only standard therapy for severe OHSS, group II (n = 30; study group) received standard therapy and cetrorelix. Results. The percentage of patients who required paracentesis, the mean serum creatinine level 48 hours after GnRH antagonist injection, and the percentage of patients who had persistent oliguria 48 hours after GnRH antagonist injection were significantly lower in the study group (cetrorelix group) compared with the control group. Patients in the cetrorelix group had a significantly shorter mean length of hospital stay and mean recovery time than patients in the control group. Conclusion. The therapeutic efficacy of the GnRH antagonist cetrorelix for the treatment of patients with severe early-onset OHSS was demonstrated. Key words: gonadotropin releasing-hormone antagonist; severe early-onset ovarian hyperstimulation syndrome

Ovarian Hyperstimulation Syndrome (OHSS) requiring Intensive Care Unit (ICU) admission between 1996-2020 in England, Wales, and Northern Ireland.

Ovarian Hyperstimulation Syndrome (OHSS) is a life-threatening iatrogenic complication of In vitro fertilisation (IVF). This study aimed to quantify rates of Ovarian Hyperstimulation Syndrome (OHSS) requiring intensive care unit (ICU) admission and assess whether trends have changed between 1996-2020 commensurate with the introduction of safer IVF practices. Data regarding Intensive Care Unit (ICU) admission across England, Wales and Northern Ireland was gathered retrospectively from the Intensive Care National Audit and Research Centre (ICNARC) database. 38,957 female patients aged between 18-55 years were admitted to ICU for OHSS or related conditions between 1996-2020. The primary outcome was the rate of OHSS requiring ICU admission expressed as a proportion of the number of fresh IVF cycles conducted in that year according to Human Fertility and Embryology Authority (HFEA) records. Baseline characteristics (for example, age, ethnicity, BMI), biochemical parameters (such as renal function, serum electrolytes), length of ICU stay and duration and need for organ support, were also compared between ICU patients with 'confirmed OHSS' and those 'without OHSS'. There were 238 cases of 'confirmed OHSS' requiring ICU admission recorded between 1996-2020. Rates of OHSS requiring ICU admission declined over the study period (P=0.006); the annual rate of severe OHSS requiring intensive care admission halved when comparing those occurring between 1996-2007 and 2008-2020 (OR=0.37, 95% CI 0.37-0.45; P<0.0001). Patients spent a mean of 3.5 days in the ICU, with 86.3% of patients with 'confirmed OHSS' requiring at least 2 days of higher level (i.e., level 2 or 3) care. Patients with 'confirmed OHSS' required a shorter duration of renal, advanced cardiovascular, and advanced respiratory support than patients 'without OHSS' (P<0.0001 for all comparisons). There was no significant difference in BMI or ethnicity between those with 'confirmed OHSS' and those 'without OHSS', however women with 'confirmed OHSS' were younger (34 versus 41 years old, p<0.0001). Although absolute rates of OHSS requiring ICU admission recorded in this study are likely to represent a significant underestimate of all clinically significant OHSS, rates of OHSS requiring ICU admission have decreased since 1996 in concordance with the introduction of modern IVF practices.

ODP430 Unusual Complication after a controlled ovarian stimulation presenting as ascites

Abstract Assisted Reproductive Technologies have become an integral element of care for women suffering from infertility. These comprise all interventions that include in vitro handling of both human oocytes and sperm, or of embryos for the purposes of reproduction. Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of controlled ovarian hyperstimulation (COH) for assisted reproduction technologies (ART). Hereby we are describing the case of a patient who developed severe OHSS presenting prominent ascites who benefitted from early onset cabergoline therapy and paracentesis. Case of 28 y/o female with past medical history of hypothyroidism and hyperprolactinemia admitted after presenting worsening abdominal pain and distention, nausea, vomiting and decreased urine output 3 days after receiving treatment before a planned follicular extraction. She initially was started on intramuscular follistim and Menopur, exogenous gonadotropins, preceded by intramuscular progesterone in preparation for said extraction. On physical examination, there was a pronounced abdominal ascites with positive fluid wave accompanied by abdominal discomfort at palpation, tachycardia of 103bpm, oliguria (less than 0.5cc/kg/hr) but no palpable masses or visceromegaly. Evaluation showed leukocytosis of 23. 0K/uL, hematocrit level of 43.5 g/dl (N: 36-48% in females), hypotonic hyponatremia with sodium level: 134 (136-145mmol/L), serum osmolality of 268 mOsm/L (N: 269-295mOsm/L), estradiol level of 3,057 pg/ml and progesterone level of 253.3 ng/ml; hormones both well above normal range compatible with response to ovarian stimulation therapy received. Afterwards, the patient underwent an abdominal ultrasound reporting small to moderate amount of ascites and findings highly suggestive of OHHS. Endovaginal Ultrasound was done which showed a prominent endometrium measuring 6.5×5. 0x 3.2 cm with bilateral large ovaries containing numerous complex cysts. Patient was started with intravenous hydration with normal saline to maintain adequate intravascular volume and cabergoline 0.25mg intravaginally daily, a dopamine agonist associated with a significant reduction in the incidence of symptoms and signs of moderate to severe OHSS. Her symptoms improved initially, but three days later she complained of worsening abdominal distention, to which abdominal ultrasound was repeated to localize a pocket for abdominal paracentesis. Paracentesis was performed: 1.8 liters of yellow fluid were aspirated and ascites resolved. Although the most severe form of OHSS is rare as in our patient, the incidence observed over time is less than 1% reported in literature. This case is an example of women with low risk factors who develop severe OHSS who had a good response to dopamine agonist therapy. As strategies to reduce the incidence of OHSS and its severity, clinical trials are needed to study the efficacy as well as safety of different doses and durations of cabergoline administration for both prophylactic and therapeutic purposes. Presentation: No date and time listed

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

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

A novel GnRH antagonist protocol based on LH levels versus traditional flexible GnRH antagonist protocol in PCOS patients undergoing in vitro fertilization: study protocol for a randomized controlled, non-inferiority trial

BackgroundThe gonadotropin-releasing hormone (GnRH) antagonist protocol is advantageous given that it can avoid severe ovarian hyperstimulation syndrome (OHSS), especially for patients with polycystic ovary syndrome (PCOS). Basic and clinical evidence has shown that a threshold of luteinizing hormone (LH) stimulation is required for adequate follicular development and oocyte maturation. Ultra-low or high levels of LH are detrimental to pregnancy outcomes. We previously demonstrated that LH could be an indicator for the timing and dosage of antagonist administration in a retrospective study.Methods/designIn this randomized, single-center, non-inferiority trial, we aim to test the hypothesis that there is no significant difference in cumulative ongoing pregnancy rates between PCOS patients stimulated with LH-based flexible protocol versus traditional flexible GnRH antagonist protocol. The primary efficacy endpoint will be the cumulative ongoing pregnancy rate per cycle. The secondary outcomes will be clinical pregnancy rate, cancelation rate, serious OHSS rate, and cost-efficiency. The cumulative ongoing pregnancy rate per cycle in PCOS women was 80%. Considering that a non-inferiority threshold should retain 80% of the clinical effect of a control treatment, a minimal clinical difference of 16% (two-sided: α, 2.5%; β, 20%) and a total of 196 patients were needed. Anticipating a 10% dropout rate, the total number of patients required was 216.DiscussionThe results of this study will provide evidence for the efficacy and safety of the LH-based flexible GnRH antagonist protocol in PCOS patients. Moreover, it evaluates the cost-efficiency of both protocols.Trial registrationChinese Clinical Trial Registry ChiCTR1800018129. Date assigned: 31 August 2018. Protocol version: 1.0 (18 July 2017)

Luteinizing hormone-based modified GnRH antagonist protocol in normal responders undergoing in vitro fertilization treatment: A multi-center randomized controlled trial.

ObjectiveTo study the clinical efficacy and cost-effectiveness of a modified gonadotrophin-releasing hormone (GnRH) antagonist protocol based on luteinizing hormone (LH) levels through one complete assisted reproductive technology (ART) cycle in normal responders.DesignNon-inferiority, multicenter randomized controlled trial.SettingUniversity-based hospitals and an academic medical center.PatientsA total of 372 patients fulfilled the inclusion criteria and were eligible to participate.Intervention(s)Participants were randomized at a 1:1 ratio and stimulated with the conventional flexible GnRH antagonist protocol (control group) or LH-based modified GnRH antagonist protocol (study group).Main Outcome MeasuresThe primary outcome was the cumulative ongoing pregnancy rate per aspiration. The secondary outcomes were number of oocytes retrieved, number of good quality embryos, cumulative positive βhCG rate, cumulative clinical pregnancy rate, pregnancy loss rate, moderate and severe ovarian hyperstimulation syndrome (OHSS), and financial expenditure.ResultsThe cumulative ongoing pregnancy rate was 65.1% in the study group and 70.1% in the control group (odds ratio, 0.79; 95% confidence interval, 0.50–1.26; P = 0.33). The multivariate regression analyses results showed that the number of retrieved oocytes was positively associated with the odds for a higher cumulative ongoing pregnancy rate (adjusted odds ratio, 1.11, 95% confidence interval, 1.06–1.17, P < 0.001). The treatment protocol, female age, and body mass index were not independent predictors. The incremental cost-effectiveness ratio for luteinizing hormone-based gonadotrophin releasing hormone antagonist protocol versus the conventional flexible gonadotrophin releasing hormone antagonist protocol was estimated at 3568.6 USD for each additional ongoing pregnancy.ConclusionThe luteinizing hormone-based gonadotrophin releasing hormone antagonist protocol had clinical efficacy similar to the conventional flexible gonadotrophin releasing hormone antagonist protocol in normal responders undergoing in vitro fertilization treatment but was more cost-effective considering the cumulative ongoing pregnancy rate in the entire assisted reproductive technology cycle.Clinical Trial Registration www.chictr.org.cn, identifier: ChiCTR1800018077URL of the registration site http://www.chictr.org.cn/edit.aspx?pid=27389&htm=4.Trial registration date29 August 2018.Date of first patient enrollment1 September 2018.

Recombinant LH supplementation improves cumulative live birth rates in the GnRH antagonist protocol: a multicenter retrospective study using a propensity score-matching analysis

BackgroundLuteinizing hormone (LH) is critical in follicle growth and oocyte maturation. However, the value of recombinant LH (r-LH) supplementation to recombinant follicle stimulating hormone (r-FSH) during controlled ovarian stimulation in the gonadotrophin releasing hormone (GnRH) antagonist regimen is controversial.MethodsThis multicenter retrospective cohort study recruited 899 GnRH antagonist cycles stimulated with r-LH and r-FSH in 3 reproductive centers and matched them to 2652 r-FSH stimulating cycles using propensity score matching (PSM) for potential confounders in a 1:3 ratio. The primary outcome was the cumulative live birth rate (CLBR) per complete cycle.ResultsThe baseline characteristics were comparable in the r-FSH/r-LH and r-FSH groups after PSM. The r-FSH/r-LH group achieved a higher CLBR than the r-FSH group (66.95% vs. 61.16%, p = 0.006). R-LH supplementation also resulted in a higher 2-pronuclear embryo rate, usable embryo rate, and live birth rate in both fresh embryo transfer cycles and frozen-thawed embryo transfer (FET) cycles. No significant differences were found in the rate of moderate and severe ovarian hyperstimulation syndrome (OHSS), or cycle cancellation rate in the prevention of OHSS.ConclusionsR-LH supplementation to r-FSH in the GnRH antagonist protocol was significantly associated with a higher CLBR and live birth rate in fresh and FET cycles, and improved embryo quality without increasing the OHSS rate and cycle cancellation rate.

Gonadotropin releasing hormone (GnRH) antagonist administration to decrease the risk of ovarian hyperstimulation syndrome in GNRH agonist cycles triggered with human chorionic gonadotropin.

In Gonadotropin releasing hormone(GnRH) agonist IVF, after administration of human chorionic gonadotropin(HCG) triggering, there is a risk of ovarian hyperstimulation syndrome(OHSS). Few methods exist to prevent OHSS in these cases. Therefore, we investigated the use of a GnRH antagonist to decrease the risk of OHSS, due to its ability to decrease VEGF production and function. A retrospective cohort study of 171-IVF patients at risk for developing OHSS after a GnRH agonist cycle with HCG trigger was performed from 2011 to 2019. The patient population consisted of women with an unexpected exuberant response to stimulation based on ovarian reserve testing and were triggered with hCG. Women were converted to a freeze-all cycle and received either cabergoline 0.5mg orally alone for 7days from the collection(Group 1, n = 123) or received cabergoline 0.5mg orally and ganirelix, 250 mcg SC for 7-10days(Group 2, n = 48). Group 1 had more cases of moderate and severe OHSS than group 2-(25% vs. 10% p = 0.03, and 52% vs. 25% p = 0.001 respectively). Group 1 reported more abdominal discomfort and bloating than group 2(91% vs. 65% p < 0.001) and the presence of free fluid was more frequent in group 1 than group 2(74% vs. 35% p < 0.001). Hemoconcentration and electrolyte disturbances were less severe in group 2 than in group 1 (p < 0.001 all cases). In patients at high risk for developing OHSS after hCG trigger in a GnRH agonist cycle, the addition of GnRH antagonists in the luteal phase may reduce the risk of developing moderate and severe OHSS. The GnRH antagonist likely leads to more rapid luteolysis and down regulation of VEGF production and receptor response, thereby decreasing the hallmark increased vascular permeability.

Polycystic Ovary Syndrome Develops the Complications of Assisted Reproductive Technologies.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication that remains a threat to every patient experiencing stimulation of ovulation. Polycystic ovary syndrome (PCOS) appears to be the most important predisposing factor for OHSS. The severity of OHSS is associated with the degree of the follicular response to the ovulation inducing agents. The objective of this study was to investigate the relationship between PCOS with the risk of moderate-to-severe OHSS in intracytoplasmic sperm injection treatment patients. Sixty patients in the reproductive ages (20-38), including OHSS patients and age-matched normoresponders were included in this study. Patients who had larger follicle counts on the day of hCG injection were considered at risk for developing moderate-to-severe OHSS. In addition, oocyte quality was assessed about 20-30 min after oocyte pickup. The incidence of OHSS in PCOS patients increased significantly up to 13.9 times higher than in patients without PCOS (OR=13.900; P=0.007). Moreover, moderate-to-severe OHSS increased significantly (OR=3.860; P=0.043) in patients with primary infertility than those with secondary infertility. In addition, oocyte quality was not affected with the severity of OHSS. In conclusion, the risk of moderate-to-severe OHSS is correlated with PCOS and primary infertility without affecting oocyte quality.

Effectiveness, safety and cost of urinary follicle stimulating hormone in controlled ovarian stimulation in China: multi-center retrospective cohort study of 102 061 in vitro fertilization cycles

Objective: To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China. Methods: Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use. Results: Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol (OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol (OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased (OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased (OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant (P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient (P<0.01). Conclusion: For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Risk of Higher Blood Pressure in 3 to 6 Years Old Singleton Born From OHSS Patients Undergone With Fresh IVF/ICSI

BackgroundA large registry-based study found the increasing disorders of cardiovascular and metabolism in IVF children but underlying mechanism is still unknown. Few studies have investigated any association between OHSS and cardiovascular or metabolic function in subsequent children.ObjectiveTo evaluate the effect of ovarian hyperstimulation syndrome (OHSS) on blood pressure of singletons after in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI).Study DesignThe singlet-center corhort study included 1780 singletons born with IVF/ICSI and 83 spontaneously conceived children from 2003 to 2014. Follow-up has lasted more than 10 years, and is still ongoing. This study analyzed data from follow-up surveys at 3 to 6 years of age.Participants, Setting and MethodsWe recruited 83 children (Group E) spontaneously conceived (SC) as control group and 1780 children born with IVF/ICSI including 126 children born to OHSS-fresh embryo transfer (ET) women (Group A), 1069 children born to non OHSS-ET women (Group B), 98 children conceived by women who developed into moderate or severe OHSS after oocyte retrieval and selected the frozen-thawed embryo transfer (FET) (Group C), 487 children conceived with non OHSS-FET (Group D). We evaluated cardiometabolic function, assessed BP in mmHg, heart rate, anthropometrics, and metabolic index including glucose, serum lipid (triglyceride, total cholesterol, low density lipoprotein, high density lipoprotein), thyroid function, of those children. The BP and heart rate were measured twice on the same day. We applied several multiple regression analyses to investigate the effect of OHSS in the early pregnancy.Main FindingsBy the single factor analysis, the SBP and DBP in the SC group (SBP: 99.84 ± 8.9; DBP: 55.27 ± 8.8) were significantly lower than OHSS-ET group’s, while the blood pressure was similar between the SC group and other three ART groups. Children had higher BP in the OHSS-ET group (SBP: 101.93 ± 8.17; DBP: 58.75 ± 8.48) than in the non OHSS-ET (SBP: 99.49 ± 8.91; DBP: 56.55 ± 8.02) or OHSS-FET group (SBP: 99.38 ± 8.17; DBP: 55.72 ± 7.94). After using multiple regression analysis to adjust current, early life, parental and ART characteristics, the differences in the SBP and DBP (B (95% confidence interval)) between OHSS-ET and non OHSS-ET remained significant (SBP: 3.193 (0.549 to 2.301); DBP: 3.440 (0.611 to 2.333)). And the BP showed no significant difference complementarily when compared non OHSS-FET group with non OHSS-ET group. In addition, the anthropometrics, fast glucose, serum lipid, and thyroid index did not differ among the ART groups.Principal ConclusionsOHSS might play an independent key role on offspring’s BP even cardiovascular function. Electing frozen-thawed embryo transfer for high risk of OHSS population may reduce the risk of the high BP trend.Wider Implications of the FindingsIt is a large sample study to investigate the effect of OHSS on offspring’s health. These findings provide a clinic evidence of the impact of early environment (embryo even oocyte stage) on the offspring’s cardiovascular health. Our study emphasis the importance of the accuracy of IVF clinic strategy and preventing the OHSS after fresh embryo transfer.

P-661 dydrogesterone as an alternative to supress LH surge in single stimulus protocols with follitropin delta

Abstract Study question Is oral dydrogesterone (DYG) 30 mg daily efficient on prevention of premature luteinizing hormone (LH) surge in ART cycles? Summary answer Oral dydrogesterone demonstrated to be as safe and effective as GnRH-ant in IVF/ICSI cycles intended to freeze-all / PGT-A, oocyte preservation and embryo banking programs What is known already The use of progesterone (PG) to inhibit pituitary LH surge during ovarian stimulation have been described over the last decades. Due to its harmful effect on the endometrium, PG suppression is mainly reserved for freeze-all cycles. Dydrogesterone (DYG), a known and safe synthetic progesterone, has been tested for this purpose based on the concept of its more selective PG receptors activity, which could reduce the inconveniences of side effects with less relevant androgenic, estrogenic, glyco or mineralocorticoid activity. Accordind to some recent work, DYG would be an effective tool both in cycles intended to freeze-all or in oocyte preservation strategies. Study design, size, duration Observational, comparative single center study, comparing the effect of DYG and gonadotropin releasing hormone (GnRH) antagonists on prevention of premature luteinizing hormone (LH) surge as well as to evaluate the number of metaphase II oocytes. From January 2019 to January 2020, 143 no age restrictions patients underwent both IVF/ICSI or oocyte preservation, all of them receiving the same single stimulus protocol with follitropin delta (Rekovelle). Participants/materials, setting, methods 92 IVF/ICSI plus 51 oocyte cryopreservation cycles underwent deltafollitropin (Rekovelle®, Ferring Pharmaceuticals) in a fixed daily and individualized SC-dose. Clinical decision led to a GnRH-antagonist (CTA-Cetrorelix acetate, Cetrotide®, Merck) 0,25 mg/d initiated in a flexible schedule in presence of one follicle ≥14 mm and continued throughout the stimulation period (48 cycles) or dydrogesterone (DYG), 10mg 8/8 hours (Duphaston®, Abbott) combined to gonadotrophin from the beginning of stimulation until the day after the trigger (95 cycles). Main results and the role of chance DYG-group had a mean age significantly higher (37.8 x 35.8-p 0.002) but there were no differences in mean parameters of BMI (24.08 x 24.81), days of stimulation (9.95 x 10.08), AMH (2.30 x 2.52), AFC (14.6 x 16.2). In the same way, no differences were observed between follicles 15 mm to 18 mm (3.06 x 3.68) and ≥ 18 mm (4.56 x 3.9), with a tendency for a greater number of larger follicles in the DYG-group. Metaphase II oocytes (7.48 x 7.33) was similar in both groups. One patient from each group experienced a premature LH surge (3.54 x 3.06) and one case in the DYG-group had no oocyte in a single 20mm aspirated follicle. There happened no cancelling. No patients experienced moderate to severe ovarian hyper stimulation syndrome, even when AMH&amp;gt;3 ng/mL. Cancelling criteria: no follicles with a diameter 17 mm by day 15. Oocyte retrieval took place 36 hours after trigging. Primary outcome was the incidence of premature LH surge. Secondary outcomes included follicles ≥ 15 mm and &amp;lt; 18 mm and ≥ 18 mm on hCG day, metaphase II oocytes, number of cancelled cycles and OHSS symptoms. Statistics were performed by Mann-Whitney test. Limitations, reasons for caution The main limitation point is the small number of patients. Despite having relative experience with the use of DYG, in this work we limited the sample to consider only one type of stimulus protocol, making the groups more homogeneous for the analysis. Wider implications of the findings Dydrogesterone is as effective as GnRH-ant in reducing premature LH surge. It can be considered for IVF/ICSI cycles intended to freeze-all / PGT-A, oocyte preservation and for embryo banking strategies, representing lower costs in these cases. Trial registration number not applicable

P-623 Outcomes of Ovarian Drilling

Abstract Study question Is it cost-effective performing laparoscopic ovarian drilling in patients with polycystic ovarian syndrome? Summary answer Laparoscopic ovarian drilling (LOD) is a cost-effective procedure and can potentially reduce the risk of ovarian hyperstimulation syndrome (OHSS) in subsequent IVF treatment What is known already LOD increases the chances of resumed regular menstruation as well as an increase in spontaneous ovulation when compared to patients treated with clomiphene citrate. An increase in spontaneous conception of pregnancy can be seen in LOD patients however this can be affected by the age of the patient but not necessarily by the BMI. In the 1980’s wedge resection was shown to be successful in ovulation induction, however this was abandoned with the emergence of urinary gonadotrophins and oral anti-oestrogens. Study design, size, duration This is a retrospective observational study performed in a single UK district general hospital. A total of 84 patients underwent laparoscopic ovarian drilling over a six-year period were identified from the hospital discharge code. All patients with a confirmed PCOS diagnosis according to the Rotterdam Criteria were included. Demographic details included age, body mass index, follicle-stimulating and luteinising hormone levels, Anti-Mullerian hormone (AMH) and antral follicle count and patient’s subsequent treatment details were analysed. Participants/materials, setting, methods We analysed the biochemical pregnancy, clinical pregnancy and livebirth rates of all patients who underwent LOD. We further evaluated the prognosis of the patients who did not achieve a live birth following LOD with subsequent fertility treatment such as ovulation induction treatment or in-vitro fertilisation (IVF). We also explored the rate OHSS after LOD. All data were obtained from the local hospital database system where patient’s demographic, treatment details and birth outcomes are recorded. Main results and the role of chance 38 out of the 84 (45%) patients had receive other forms of fertility treatment prior to the laparoscopic ovarian drilling, namely clomiphene or letrozole but failed to achieve a successful pregnancy. 26 (31%) of the patients ovulated spontaneously after the operation and conceived with 22 of them achieving a livebirth (26%). For patients who did not ovulate spontaneously or did not achieve a pregnancy after 6 months from the drilling, 28 patients then undergone further ovulation induction, with a 43% (13/28) clinical pregnancy and 29% (9/28) of livebirth rate. Further 35 patients went for IVF treatment with 21/35 (60%) achieving a livebirth. 6 out of the 35 (17%) had a ‘freeze all’ cycle due to high risk of development of moderate to severe OHSS. The OHSS rate in this high risk group of population was 8% (3/35). In conclusion, 61% (52/84) patients achieved a live birth of which, 26% was following laparoscopic drilling without any further treatment fertility treatment. For patients who underwent drilling and subsequently had IVF treatment, the development of OHSS is similar to the background rate quoted in literature rather than the much higher 20% in PCOS population (Delvigne et al, 2002) Limitations, reasons for caution The retrospective nature of the study with a relatively small sample size limited the generalisability of the results. There was a lack of strict inclusion criteria for patients who were offered drilling reflected by the wide range of AMH (18.9-176 pmol/l) and LH (0.8-33.4 iu/l) levels in our sample. Wider implications of the findings The response to treatment can also be dependent on the energy modality used. LOD has been shown to be cost effective when compared Gonadotrophin treatment which can lead to ovarian hyperstimulation. Some studies have reported similar pregnancy outcomes with both treatment options, however LOD has shown to be cost effective. Trial registration number not applicable

Predictive Factors for Recovery Time in Conceived Women Suffering From Moderate to Severe Ovarian Hyperstimulation Syndrome.

ObjectiveThis study aimed to evaluate potential predictors for recovery time in pregnant patients with moderate to severe ovarian hyperstimulation syndrome (OHSS).MethodsA total of 424 pregnant patients with moderate to severe OHSS who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) were retrospectively identified. The clinical features and laboratory findings within 24 h after admission were collected. Treatment for OHSS was carried out according to standard procedures, including fluid replacement therapy, human albumin, aspirin, low-molecular-weight heparin, and paracentesis, when necessary. Patients were discharged from the hospital when the tmorning hematocrit was <40% and no obvious clinically relevant symptoms existed, such as abdominal distension, abdominal pain, and shortness of breath. Meanwhile, ultrasound indicating little pleural or abdominal effusion and biochemical abnormalities returning to normal were required. Spearman’s correlation analysis was used to assess the association between the blood-related parameters and recovery time. Multiple linear regression models were used to assess the relationship between the clinical or laboratory parameters and recovery time.ResultsThe median recovery time of these patients was 11 days. In Spearman’s correlation test, leukocytes, hemoglobin, platelets, hematocrit, creatinine, prothrombin time (PT), fibrinogen (Fib), D-dimer, and fibrinogen degradation products (FDPs) were positively correlated with recovery time. On the other hand, albumin and thrombin time (TT) were negatively correlated with recovery time. Multiple linear regression analysis showed that polycystic ovary syndrome (PCOS), hemoglobin, platelets, albumin, and Fib were significantly associated with the recovery time of patients with OHSS (p = 0.023, p < 0.001, p = 0.007, p < 0.001, and p = 0.019, respectively).ConclusionsIn pregnant patients with OHSS, PCOS and hypoalbuminemia were associated with a significantly longer recovery time. Meanwhile, the recovery time was longer when patients have high levels of hemoglobin, platelets, and Fib.

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

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

Comparison of bromocriptine and hydroxyethyl starch in the prevention of ovarian hyperstimulation syndrome.

To evaluate the effectiveness of bromocriptine for prevention of ovarian hyperstimulation syndrome (OHSS). The retrospective study included women at risk of OHSS who were receiving gonadotropin-releasing hormone antagonist protocols, including 52 women given 2.5mg bromocriptine by rectal insertion, 52 women given 500 ml intravenous hydroxyethyl starch (HES), and 40 women who received no intervention. Treatments were administered daily for 5 days beginning on the day of oocyte retrieval. Baseline information and data related to OHSS were compared. No significant differences were found among groups in estradiol concentration on the day of trigger or in number of retrieved oocytes. Incidence of mild OHSS was not significantly different among groups, respectively 13.5%, 15.4%, and 17.5% (P> 0.05). The incidence of moderate to severe OHSS was significantly lower in the bromocriptine and HES groups compared with the control group, respectively 7.7%, 5.8%, and 22.5% (P< 0.05). D-dimer levels were significantly lower in the bromocriptine and HES groups compared with the control group on Day 5 after oocyte retrieval (P< 0.05). No differences in liver or renal function were found in the three groups. Bromocriptine was apparently as effective as intravenous HES in patients with high risk of 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.

Association between hospital treatment volume and major complications in ovarian hyperstimulation syndrome

ObjectiveAn inverse relationship between hospital volume and adverse patient outcomes has been established for many conditions, but has not yet been examined in ovarian hyperstimulation syndrome (OHSS). Given the rarity of severe OHSS, but potential for high morbidity, this study aimed to elucidate the effect of hospital volume on inpatient OHSS-related complications. MethodsThis is a retrospective observational study querying the National Inpatient Sample, 1/2001–12/2011. Study population was 11,878 patients with OHSS treated at 735 hospitals. Annualized hospital OHSS treatment volume was grouped as: low-volume (1 case/year), mid-volume (>1 but < 3.5 cases/year), and high-volume (≥3.5 cases/year). Main outcome measure was major complication rates stratified by hospital treatment volume, assessed by multinomial regression and binary logistic regression models. ResultsA total of 2,415 (20.3%) patients were treated at low-volume centers, 5,023 (42.3%) at mid-volume centers, and 4,440 (37.4%) at high-volume centers. Patients treated at high-volume centers were more likely to be older and less comorbid with higher incomes and lower body mass index (P < 0.05). High-volume hospitals were more likely to be urban-teaching centers with large bed capacity (P < 0.001). Overall, 1,624 (13.7%) patients experienced a major complication during hospitalization. Patients treated at high-volume hospitals had lower rates of major complications (high: 11.0%, mid: 15.2%, low: 15.6%, P < 0.001). On multivariable analysis, treatment at high-volume hospitals was independently associated with a nearly 20% lower rate of major complications (odds ratio 0.82, 95% confidence interval 0.70–0.97, P = 0.021). ConclusionOur study suggests that higher hospital treatment volume for OHSS may be associated with improved outcomes.

Effect of GnRH agonist alone or combined with different low-dose hCG on cumulative live birth rate for high responders in GnRH antagonist cycles: a retrospective study

BackgroundThere is insufficient evidence regarding the impact of dual trigger on oocyte maturity and reproductive outcomes in high responders. Thus, we aimed to explore the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone or combined with different low-dose human chorionic gonadotropin (hCG) regimens on rates of oocyte maturation and cumulative live birth in high responders who underwent a freeze-all strategy in GnRH antagonist cycles.MethodsA total of 1343 cycles were divided into three groups according to different trigger protocols: group A received GnRHa 0.2 mg (n = 577), group B received GnRHa 0.2 mg and hCG 1000 IU (n = 403), and group C received GnRHa 0.2 mg and hCG 2000 IU (n = 363).ResultsThere were no significant differences in age, body mass index, and rates of oocyte maturation, fertilization, available embryo, and top-quality embryo among the groups. However, the incidence of moderate to severe ovarian hyperstimulation syndrome (OHSS) was significantly different among the three groups (0% in group A, 1.49% in group B, and 1.38% in group C). For the first frozen embryo transfer (FET) cycle, there were no significant differences in the number of transferred embryos and rates of implantation, clinical pregnancy, live birth, and early miscarriage among the three groups. Additionally, the cumulative ongoing pregnancy rate and cumulative live birth rate were not significantly different among the three groups. Similarly, there were no significant differences in gestational age, birth weight, birth height, and the proportion of low birth weight among subgroups stratified by singleton or twin.ConclusionsGnRHa trigger combined with low-dose hCG (1000 IU or 2000 IU) did not improve oocyte maturity and embryo quality and was still associated with an increased risk of moderate to severe OHSS. Therefore, for high responders treated with the freeze-all strategy, the single GnRHa trigger is recommended for final oocyte maturation, which can prevent the occurrence of moderate to severe OHSS and obtain satisfactory pregnancy and neonatal outcomes in subsequent FET cycles.