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

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

Follicle-Stimulating Hormone-Secreting Pituitary Adenoma Inducing Spontaneous Ovarian Hyperstimulation Syndrome, Treatment Using In Vitro Fertilization and Embryo Transfer: A Case Report.

Objective: To describe the management of a patient with a pituitary adenoma secreting follicle-stimulating hormone (FSH) associated with spontaneous ovarian hyperstimulation syndrome (sOHSS) who was treated with in vitro fertilization and embryo transfer (IVF-ET). Methods: We report a clinical case of a woman of reproductive age with menstrual irregularity, infertility and ovarian hyperstimulation due to recurrent pituitary adenoma secreting FSH, which persisted after transsphenoidal surgery.She underwent the diagnosis by magnetic resonance imaging (MRI) and laboratory tests,and finally she was treated with IVF-ET. Results: The patient was plagued by a recurrent pituitary adenoma for many years and tried various treatments. After complete transsphenoidal surgery, sOHSS decreased, as shown by a reduction in oestradiol levels and an improvement in the ultrasonography parameters; however, secondary amenorrhea occurred. Finally, pregnancy was achieved through IVF-ET and the symptoms of ovarian hyperstimulation were relieved. Conclusions: IVF-ET was found to be effective for the treatment of recurrent pituitary adenoma, thus representing a therapeutic option that should be taken into consideration in such cases.

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.

Effect and Relationship of Seasons on the High Risk of Ovarian Hyperstimulation Syndrome After Oocyte Retrieval in Patients With Polycystic Ovary Syndrome.

Objective: To investigate the effect of seasons on the incidence of high risk of ovarian hyperstimulation syndrome (OHSS) after in oocyte retrieval in patients with polycystic ovarian syndrome (PCOS) and to establish a nomogram to predict the risk of OHSS. Design: Single-center, retrospective study. Setting: University-affiliated reproductive medicine center. Patients: A total of 2,030 infertility patients with PCOS underwent the follicular phase long-acting long protocol IVF/ICSI in the reproductive medicine center from January 2017 to December 2019. Interventions: None. Main outcome measures: Logistic regression analysis was used to analyze the factors associated with a high risk of OHSS. We established a nomogram to predict the risk of OHSS in infertility patients with PCOS after oocyte retrieval. Results: The incidence of patients at high risk of OHSS was significantly different from season-to-season and was especially higher in the summer and winter. Multivariate logistic analysis showed that gonadotropin dosage, number of retrieved oocytes, estradiol level, average bilateral ovarian diameter on the day human chorionic gonadotropin was administered, type of infertility, and average temperature were independent risk factors for OHSS after oocyte retrieval in PCOS patients. Based on the above independent risk factors, we constructed a prediction model for OHSS risk. To evaluate the efficiency of the prediction model, we calculated the C-index (0.849), area under the receiver operating characteristic curve (0.849), and internal validation C-index (0.846). Decision curve analysis suggested that the prediction model exhibited significant net benefits. Conclusions: The incidence of PCOS patients at high risk for OHSS after oocyte retrieval fluctuated with seasonal temperature changes, and was significantly higher in extreme climates. The prediction model had favorable predictive performance and clinical application value.

A borderline form of empty follicle syndrome treated with a double-trigger of gonadotropin-releasing hormone agonist and human chorionic gonadotropin: A case report.

RATIONALE: The borderline form of empty follicle syndrome (EFS) is a phenomenon where only a few mature or immature oocytes are retrieved despite adequate response to controlled ovarian hyperstimulation (COH). It is a rare phenomenon with an unclear underlying mechanism, and there is currently no effective treatment. PATIENT CONCERNS: The patient received 3 assisted reproductive technology cycles, and although her follicular development and estrogen levels were normal during COH, the outcome with respect to the oocytes obtained was unsatisfactory. DIAGNOSES: Borderline form of EFS. INTERVENTIONS: In the context of undergoing GnRH-antagonist protocol, we implemented a double-trigger with human chorionic gonadotropin (hCG) after 6 hours of gonadotropin-releasing hormone agonist (GnRH-a) administration. OUTCOMES: Eleven oocytes were obtained (M I × 3, M II × 8), which underwent in vitro fertilization (IVF). After 18 hours, 7 oocytes showed normal fertilization, with 2 embryos formed 72 hours later (embryo rating, 6C II × 1, 9C II × 1); the embryos were then frozen. LESSONS: Oocyte maturation and ovulation are time-dependent processes, and that different patients require different lengths/intervals of time for treatment. Therefore, the borderline form of EFS, in general, may be treatable, and our novel trigger method provides a new treatment option for such patients in the future.

Electroacupuncture facilitates implantation by enhancing endometrial angiogenesis in a rat model of ovarian hyperstimulation.

Controlled ovarian hyperstimulation (COH) impairs the synchronized development of endometrium and embryo, resulting in the failure of embryo implantation. Here, we investigated what effects electroacupuncture had on embryo implantation in COH rats. Female rats were randomly assigned to four groups: normal (N), model (M), electroacupuncture (EA), and electroacupuncture pretreatment (PEA). Rats in groups M, EA, PEA were injected with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin to establish the COH model. Rats in group EA received electroacupuncture treatment from the PMSG injection day to the 3rd day of pregnancy (D3), while those in group PEA received electroacupuncture treatment for 3 days before the PMSG day and continuing to D3. Furthermore, another 30 female rats who received the same treatment as the rats in group PEA were injected with siVEGFR2 into uterine lumen. The endometrial microvascular density (MVD) and the expression levels of vascular endothelial growth factor-A, angiopoietin-1, and fibroblast growth factor-2 were significantly lower in groups M than in groups N and PEA. The percentage of dolichos biflorus agglutinin positive uterine natural killer cells in groups N, EA and PEA was higher than that in group M. After the siVEGFR2 injection, the protein expression levels of vascular endothelial growth factor receptor 2 (VEGFR2), PI3K, p-AKT and p-ERK, the embryo number and the MVD were significantly reduced. In conclusion, electroacupuncture can facilitate embryo implantation in COH rats by activating the VEGFR2/PI3K/AKT and VEGFR2/ERK signaling pathways which have a positive relationship with endometrial angiogenesis.

Effects of acupuncture on the levels of serum estradiol and pituitary estrogen receptor beta in a rat model of induced super ovulation.

AIMS: Acupuncture is frequently recommended as a complementary therapy for infertility. However, whether acupuncture can prevent early ovarian hyperstimulation syndrome has not been examined and its potential mechanisms are not well understood. MAIN METHODS: Forty rats were randomized into four groups: Control, Ovarian Stimulation Model, Acupuncture, and Human Chorionic Gonadotropin (HCG). Serum estradiol, progesterone, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were measured by enzyme-linked immunosorbent assay. Pituitary ER mRNA and ERß expression were detected by real-time PCR and western blotting respectively. The pathology of rat ovaries were observed by light microscopy. KEY FINDINGS: We observed significantly lower estradiol levels in the Acupuncture group than in the Model group and increased LH levels in the HCG group than in Model and Acupuncture groups. Testosterone and FSH levels were significantly lower in the Acupuncture group than in the HCG group. Western blotting showed significantly lower pituitary ERß expression in the Model group than in the Control group and higher expression in the Acupuncture group than in the Model group. Real-time PCR showed lower pituitary ER mRNA expression in the Acupuncture group than in the Model group. Hematoxylin and eosin staining showed a lower proportion of atretic follicles in Acupuncture and HCG groups than in Model and Control groups. Instead, Acupuncture and HCG groups showed growing and mature follicles. SIGNIFICANCE: Our results demonstrate a relationship between acupuncture and the hypothalamic-pituitary-gonadal axis, and the potential mechanism underlying the preventative effects of acupuncture on the incidence of early ovarian hyperstimulation syndrome.

Outpatient management of severe ovarian hyperstimulation syndrome: a systematic review and a review of existing guidelines.

Ovarian hyperstimulation syndrome (OHSS) is a potentially serious complication of assisted reproductive treatment. Management of women with severe OHSS has traditionally included hospitalisation for close monitoring and supportive treatment. The aim of this review is to assess the evidence for safety and efficacy of outpatient management of severe OHSS. A systematic review of studies describing outpatient management options was performed. Current guidance from advisory bodies was also reviewed. Outpatient management has been found in observational studies to be safe and cost-effective compared to inpatient management. Paracentesis of ascitic fluid seems to be effective treatment for severe OHSS along with supportive management including maintenance of fluid balance and preventative measures against thrombo-embolism. GnRH antagonist was shown in few studies to be effective in treatment of early severe OHSS although further research is required to assess its role in this context. Appropriate outpatient set up and protocols are essential to provide safe outpatient management for women with severe OHSS.

Severe ovarian hyperstimulation syndrome after combined GnRH-agonist and low-dose human chorionic gonadotropin trigger in a patient with a single kidney.

Ovarian hyperstimulation syndrome (OHSS) following gonadotropin-releasing hormone agonist (GnRH-a) trigger is rare. Here, we report a case of severe OHSS after combined GnRH-a and low-dose human chorionic gonadotropin (hCG) trigger in a patient with a single kidney. The patient is a 32-year-old women with a two-year history of infertility. The patient's history was significant for a single kidney, that is, she had donated a kidney to a family member three years ago. The patient underwent controlled ovarian stimulation (COS) for in vitro fertilization (IVF) and received a combined 2 mg GnRH-a and 1500 IU hCG ovulatory trigger. Estradiol (E2) levels on the day of and after the trigger were 3800 pg/mL and 4001 pg/mL, respectively. Four days after the trigger, the patient began experiencing nausea, abdominal distention and dyspnea, and her blood testing revealed hemoconcentration (hemoglobin: 16.9 g/dL; hematocrit: 51.0%) and an elevated creatinine level (1.16 mg/dL). Fresh embryo transfer was deferred. The patient was admitted to the hospital for fluid monitoring and prophylactic anticoagulation. Following inpatient management, her hemoglobin, hematocrit and creatinine levels normalized. The current report highlights that the systemic effects of OHSS can be accentuated in patients with preexisting renal disease or a single kidney.

Prevention and management of ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) is a serious iatrogenic complication of ovarian stimulation. It is feasible to identify patients at risk, modify stimulation strategies to ameliorate risk, and initiate out-patient treatments that alter disease pathophysiology to reduce disease severity. Mitigation of OHSS risk and severity, through innovative approaches prior to treatment, during treatment and after treatment should now be standard care. This review summarizes recent developments and provides recommendations on the prevention and treatment of OHSS.

Interventions for the prevention of OHSS in ART cycles: an overview of Cochrane reviews.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) in assisted reproductive technology (ART) cycles is a treatment-induced disease that has an estimated prevalence of 20% to 33% in its mild form and 3% to 8% in its moderate or severe form. These numbers might even be higher for high-risk women such as those with polycystic ovaries or a high oocyte yield from ovum pickup. OBJECTIVES: The objective of this overview is to identify and summarise all evidence from Cochrane systematic reviews on interventions for prevention or treatment of moderate, severe and overall OHSS in couples with subfertility who are undergoing ART cycles. METHODS: Published Cochrane systematic reviews reporting on moderate, severe or overall OHSS as an outcome in ART cycles were eligible for inclusion in this overview. We also identified Cochrane submitted protocols and title registrations for future inclusion in the overview. The evidence is current to 12 December 2016. We identified reviews, protocols and titles by searching the Cochrane Gynaecology and Fertility Group Database of Systematic Reviews and Archie (the Cochrane information management system) in July 2016 on the effectiveness of interventions for outcomes of moderate, severe and overall OHSS. We undertook in duplicate selection of systematic reviews, data extraction and quality assessment. We used the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool to assess the quality of included reviews, and we used GRADE methods to assess the quality of the evidence for each outcome. We summarised the characteristics of included reviews in the text and in additional tables. MAIN RESULTS: We included a total of 27 reviews in this overview. The reviews were generally of high quality according to AMSTAR ratings, and included studies provided evidence that ranged from very low to high in quality. Ten reviews had not been updated in the past three years. Seven reviews described interventions that provided a beneficial effect in reducing OHSS rates, and we categorised one additional review as 'promising'. Of the effective interventions, all except one had no detrimental effect on pregnancy outcomes. Evidence of at least moderate quality indicates that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Metformin treatment before and during an ART cycle for women with PCOS (moderate-quality evidence).• Gonadotrophin-releasing hormone (GnRH) antagonist protocol in ART cycles (moderate-quality evidence).• GnRH agonist (GnRHa) trigger in donor oocyte or 'freeze-all' programmes (moderate-quality evidence). Evidence of low or very low quality suggests that clinicians should consider the following interventions in ART cycles to reduce OHSS rates.• Clomiphene citrate for controlled ovarian stimulation in ART cycles (low-quality evidence).• Cabergoline around the time of human chorionic gonadotrophin (hCG) administration or oocyte pickup in ART cycles (low-quality evidence).• Intravenous fluids (plasma expanders) around the time of hCG administration or oocyte pickup in ART cycles (very low-quality evidence).• Progesterone for luteal phase support in ART cycles (low-quality evidence).• Coasting (withholding gonadotrophins) - a promising intervention that needs to be researched further for reduction of OHSS.On the basis of this overview, we must conclude that evidence is currently insufficient to support the widespread practice of embryo cryopreservation. AUTHORS' CONCLUSIONS: Currently, 27 reviews in the Cochrane Library were conducted to report on or to try to report on OHSS in ART cycles. We identified four review protocols but no new registered titles that can potentially be included in this overview in the future. This overview provides the most up-to-date evidence on prevention of OHSS in ART cycles from all currently published Cochrane reviews on ART. Clinicians can use the evidence summarised in this overview to choose the best treatment regimen for individual patients - a regimen that not only reduces the chance of developing OHSS but does not compromise other outcomes such as pregnancy or live birth rate. Review results, however, are limited by the lack of recent primary studies or updated reviews. Furthermore, this overview can be used by policymakers in developing local and regional protocols or guidelines and can reveal knowledge gaps for future research.

Life-threatening Medical Complications Due to Ovarian Hyperstimulation Syndrome: A Hidden Etiology.

Ovarian hyperstimulation syndrome is usually an iatrogenic complication in women taking ovulation induction medications during assisted reproduction. We hereby report the case of a 25 years old female who presented with hypertension, polyserositis with tense ascites and large cystic ovaries. She developed sigmoid and transverse sinus thrombosis. She had undergone a clandestine ovulation induction therapy as a commercial ovum donor. She fitted in severe category of ovarian hyperstimulation syndrome.

Severe ovarian hyperstimulation syndrome in a naturally conceived singleton pregnancy after ovulation induction: a case report.

OBJECTIVE: To present a case of severe ovarian hyperstimulation syndrome (OHSS) in a naturally conceived singleton pregnancy after ovulation induction. CASE: A 31-year-old woman with polycystic ovarian syndrome (PCOS) underwent ovulation induction therapy. Six days later, she was admitted to the present hospital with the symptoms of OHSS. Ultrasonography confirmed the single live intrauterine pregnancy, as well as enlarged multicystic ovaries and marked ascites that required abdominal paracentesis. The woman was treated with intravenous infusion, exogenous colloid supplementation, essentiale liver treatment, rocephin anti-infective therapy for skin lymphangitis of left lower limb, and drainage of the ascites. She recovered by day 45 of admission. CONCLUSION: Severe OHSS may develop in women with PCOS who undergo ovulation induction therapy. Serious complications may develop rapidly and therefore OHSS must be treated urgently and with multidisciplinary management.

Pathophysiology, treatment and prevention of ovarian hyperstimulation syndrome.

PURPOSE OF REVIEW: Severe ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that affects 1% of women that undergo treatment with assisted reproductive technology. The review aims to summarize recent evidence on pathophysiology, treatment, and prevention of OHSS. RECENT FINDINGS: The pathophysiology is still not completely understood; however, vascular endothelial growth factor is likely to be an important mediator. Human chorionic gonadotropin was previously thought to be necessary for OHSS to occur; however, recent case reports have proven otherwise. The contribution of an attenuated anti-Mullerian hormone signalling pathway and CD11c + HLA-DR + dendritic cells and associated interleukins has been explored recently as contributors to pathogenesis.Treatment is largely supportive and is based mainly on consensus statements rather than evidence. Therefore, it is important to prevent this condition by identifying women at risk, allowing the clinician to implement preventive strategies, including the use of GnRH antagonist cycles with agonist triggers. SUMMARY: More research is required to elucidate the pathophysiology behind the condition. Clinicians should employ strategies to prevent OHSS.

Diginyc partial hydatidiform mole with increased fetal nuchal translucency and ovarian hyperstimulation syndrome.

PURPOSE OF INVESTIGATION: Hydatidiform mole (HM) is an abnormal pregnancy characterized by proliferation of cytotrophoblast and syncytiotrophoblast and vesicular swelling of placental villi. The fetus or embryo can be absent or abnormal. HMs can be complete or partial. CASE REPORT: A case of diginyc partial HM at 12 weeks of gestational age was referred to the present center of prenatal diagnosis. The patient showed ovarian hyperstimulation syndrome. At ultrasonography, increased fetal nuchal translucency (NT) with fetal anomaly was evident, without sonographic signs of placental mole. Pregnancy was terminated with legal abortion. RESULTS: Partial HM (PHM) was suspected by ultrasonographic fetal markers with ovarian hyperstimulation syndrome, but the diagnosis was performed only with fluorescent in situ hybridization. In particular fetal NT appeared increased also in diginyc mole. CONCLUSION: In order to improve the detection rate of PHM, routine histological examinations may be associated to fluorescent in situ hybridization in all cases of fetal anomalies.

Effect of cervical conization on pregnancy outcome of in-vitro fertilization/intracytoplasmic sperm injection treatment: a retrospective cohort study.

AIMS: To investigate the effect of cervical conization on the outcome of in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Materials andMethods: The authors performed a retrospective, database-searched cohort study based on patients undergoing controlled ovarian hyperstimulation and IVF/ICSI between 2009 and 2013 in the present hospital. Cervical intraepithelial neoplasia (CIN) or cervical cancer was carefully confirmed by transvaginal ultrasound, hysteroscopy, and biopsy. High-quality case-control study with strict inclusion criteria was conducted. The authors analyzed basic characters and main IVF/ICSI outcomes between both groups. RESULTS: The authors included 48 patients with a history of cervical conization who underwent IVF/ICSI and control group without cervical conization. No significant differences were found in IVF/ICSI outcomes between both groups. No obvious evidence was found indicating that cervical stenosis could impact IVF operation. CONCLUSIONS: The present results suggest that cervical conization does not affect IVF/ICSI outcomes. Patients can receive cervical conization before undertaking assisted reproductive technology.

A gonadotropin releasing hormone agonist trigger of ovulation with aggressive luteal phase support for patients at risk of ovarian hyperstimulation syndrome undergoing controlled ovarian hyperstimulation.

OBJECTIVE: The aim of this study was to determine the efficacy and safety of luteal phase support using human chorionic gonadotropin (hCG) in cycles that are triggered with a gonadotropin-releasing hormone (GnRH) agonist in a moderate-to-high risk population undergoing a GnRH antagonist protocol. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients undergoing an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycle with a GnRH antagonist protocol from September 2011 to August 2012. The patients were defined as at high risk for ovarian hyperstimulation syndrome (OHSS) in terms of anti-Müllerian hormone (AMH) and antral follicle counts (AFCs). The patients were divided into two groups depending on whether ovulation was triggered with hCG or a GnRH agonist. Modified luteal support was provided for the cycles triggered by the GnRH agonist via low dose hCG (1500∼5000 IU). For the cycles that were triggered by hCG, urinary hCG (5000 IU) following two doses of recombinant hCG (250 µg) were administered. The primary outcomes of this study were the clinical pregnancy rate and the OHSS rate of the two groups. The secondary outcomes were the number of oocytes retrieved and the number of good quality embryos obtained. RESULTS: The study group and the control group were similar in terms of the primary and secondary outcome measures. CONCLUSION: Aggressive luteal support with low dose hCG following a GnRH agonist trigger can result in a comparable pregnancy rate to that with the use of a traditional hCG ovulation trigger. However, OHSS can still occur in patients with risk factors. Therefore, other OHSS prevention strategies should be considered.

Ovarian hyperstimulation syndrome in the 21st century: the role of gonadotropin-releasing hormone agonist trigger and kisspeptin.

PURPOSE OF REVIEW: Ovarian hyperstimulation syndrome (OHSS) complicates a considerable part of stimulated in-vitro fertilization (IVF) cycles and is a potential iatrogenic cause of death in otherwise healthy women undergoing fertility treatment. The triggering factor of OHSS is the widespread use of human chorionic gonadotropin (hCG) to induce final oocyte maturation. The aim of this review is to summarize different approaches available, using alternative triggering protocols such as gonadotropin-releasing hormone agonist (GnRHa) or kisspeptin for final oocyte maturation. RECENT FINDINGS: According to the latest European Society of Human Reproduction and Embryology report, the incidence of OHSS ranges from 0.18 to 1.40% in European countries. However, OHSS is still subject to substantial underreporting. New triggering protocols using GnRHa have shown to be similar to the gold standard hCG-trigger with regard to the reproductive outcome, but with a significant decrease in - and almost elimination of - OHSS. Lately, promising results have been reported for the use of kisspeptin to induce final oocyte maturation. Although until now no study has been performed in an OHSS risk population, theoretically, the risk of OHSS development might be even further reduced after kisspeptin trigger. SUMMARY: GnRHa trigger is currently the best tool we have to prevent OHSS and at the same time maintain good reproductive outcomes. Future research will explore the safety and efficacy of kisspeptin trigger.