Cases Of 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.

Cryopreservation as a strategy for prevention of ovarian hyperstimulation syndrome in a public assisted reproduction service in São Paulo - Brazil.

This study aimed to evaluate the prevalence of ovarian hyperstimulation syndrome (OHSS) and associated risk factors in patients undergoing fertilization cycles at risk of OHSS (≥15 antral follicles or ≥15 oocytes aspirated) and submitted to cryopreservation of all embryos in the Human Reproduction Service of the Pérola Byington Hospital (Referral Center for Women's Health) in São Paulo, SP, Brazil. This cross-sectional, institutional, descriptive study of secondary data from patients' charts enrolled in the Assisted Reproduction Service of the Pérola Byington Hospital at risk of OHSS after controlled ovarian stimulation and submitted to cryopreservation of all embryos was conducted between January 2015 and September 2017. OHSS occurred in 47.5% of cycles, all with mild severity, and there were no moderate or severe cases of OHSS. The cryopreservation of all embryos is associated with a reduction in moderate and severe forms of OHSS. Risk factors for OHSS should be evaluated prior to initiation of treatment, with less intense stimulation protocols accordingly.

Ovarian hyperstimulation syndrome complicating spontaneous molar pregnancy: a case report

Ovarian hyperstimulation syndrome (OHSS) is a rare finding that occurs in early pregnancy. There is a rapidly increasing ovarian size secreting vasoactive substances that lead to fluid shift into third spaces. It can be associated with a spectrum of other clinical findings, including ascites, hemoconcentration, hypercoagulability, and electrolyte imbalances. OHSS most commonly occurs as a complication of treatment with in vitro fertilization medications, such as human chorionic gonadotropin (hCG) or gonadotropin-releasing hormone agonists. OHSS has infrequently been reported to be caused by high hCG levels in molar pregnancies. We present a case of OHSS complicating spontaneous molar pregnancy. A 25‑year gravida 3, para 2+0, living 2 lady presented with complaints of continuous vaginal bleeding for 2 weeks and lower abdominal pain at 17 weeks' gestation. A bulky uterus containing a large hyperechoic structure with multiple cystic spaces suggestive of complete molar gestation and enlarged ovaries containing multiple cysts were seen on ultrasound imaging. She was managed successfully with conservative and supportive treatment.

Ovarian Hyperstimulation Syndrome (OHS): A Rare Cause of Acute Renal Failure: A Case Report

We report in this work, the evolution and management of a case of ovarian hyperstimulation syndrome (OHS) complicated by severe acute renal failure (ARI). A young 31-year-old patient pregnant with twins after 17 weeks of amenorrhea was admitted to nephrology department for rapidly progressive acute renal failure (AKI) (creatinine increases in 48 hours from 28mg/l to 55mg/l) and was complicated by major hydro-electrolyte disorders and multi-organ failure. Her past medical history revealed an ovulation induction before her last pregnancy and a spontaneous abortion seven years ago before her hospitalization which occurred in the 2nd trimester of her 1st twin pregnancy obtained by medically assisted reproduction. Despite optimal care, the patient improves her renal function and her multiorgan failure after abortion in gynecological intensive care. Because of worldwide increase of infertility cases and the use of new ovulation induction techniques with these risks of serious complications, we report this interesting clinical case of OHS.

Ovarian hyperstimulation syndrome in assisted reproductive technology programs in the ­Republic of Bashkortostan

Background. Ovarian hyperstimulation syndrome is a fatal complication of unknown etiology. In connection with the increase in the frequency of this complication, it is necessary to identify prognostically significant markers to discover the risk of its development.
 Aim. To analyze the frequency of ovarian hyperstimulation syndrome and search for the association of genes for differential growth factor 9, luteinizing hormone/horiogonadotropin receptor, and follicle-stimulating hormone receptor with different responses to ovulation stimulation.
 Material and methods. A retrospective single-center cohort study of the frequency and clinical parameters of early ovarian hyperstimulation syndrome was carried out in 147 patients, the average age was 36.5 [3338] years, who underwent an in vitro fertilization program in the period 20062021 in the Department of Assisted Reproductive Technologies of the Republican Medical Genetic Center in Ufa. The study of polymorphic loci of the genes for differential growth factor 9, luteinizing hormone/choriogonadotropin receptor, and follicle-stimulating hormone receptor was performed using TaqMan technology and real-time polymerase chain reaction. Deoxyribonucleic acid was isolated from peripheral blood samples. Statistical analysis was performed using the KruskalWallis criteria, median test, Pearson's 2 test, using the Statistica 12 software package.
 Results. 7577 procedures of assisted reproductive technologies were performed. 147 (2.3%) cases of ovarian hyperstimulation syndrome were registered, 53 (0.8%) cases of moderate and severe degree, 84 (1.3%) cases of mild degree. The *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene was associated with a poor ovarian response 15 (0.75); (2=4.00; p=0.02; odds ratio 3.4; 95% confidence interval 1.1310.27). The distribution of allele and genotype frequencies of the other studied genes did not differ statistically significantly in all the studied groups.
 Conclusion. The frequency of ovarian hyperstimulation syndrome in the Republic of Bashkortostan was 2.3%; the *CT genotype of the rs254286 polymorphic locus of the differential growth factor 9 gene, as well as the level of anti-Mllerian hormone, can serve as markers of a poor response and ovarian hyperstimulation to ovulation stimulation.

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.

Obstetric outcomes following ovarian hyperstimulation syndrome in IVF – a comparison with uncomplicated fresh and frozen transfer cycles

BackgroundWe aimed to assess the correlation between ovarian hyperstimulation syndrome (OHSS) in the early course of in vitro fertilization (IVF) pregnancies and obstetric outcomes.MethodsWe identified records of patients admitted due to OHSS following IVF treatment at our institution between 2008 and 2020. Cases were included if pregnancy resulted in a live singleton delivery (OHSS group). OHSS cases were matched at a 1:5:5 ratio with live singleton deliveries following IVF with fresh embryo transfer (fresh transfer group) and frozen embryo transfer (FET group), according to maternal age and parity. Computerized files were reviewed, and maternal, obstetric and neonatal outcomes compared.ResultsOverall, 44 OHSS cases were matched with 220 fresh transfer and 220 FET pregnancies. Patient demographics were similar between the groups, including body mass index, smoking and comorbidities. Gestational age at delivery, the rate of preterm births, preeclampsia and cesarean delivery were similar between the groups. Placental abruption occurred in 6.8% of OHSS pregnancies, 1.4% of fresh transfer pregnancies and 0.9% of FET pregnancies (p=0.02). On post-hoc analysis, the rate of placental abruption was significantly higher in OHSS pregnancies, compared with the two other groups, and this maintained significance after adjustment for confounders. Birthweights were 3017 ± 483, 3057 ± 545 and 3213 ± 542 grams in the OHSS, fresh transfer and FET groups, respectively (p=0.004), although the rate of small for gestational age neonates was similar between the groups.ConclusionsOHSS in the early course of IVF pregnancies is associated with an increased risk of placental abruption.

P-698 Pituitary functioning gonadotroph adenomas (FGA)-induced ovarian hyperstimulation syndrome (OHSS): results from tertiary neuroendocrine centres in the UK

Abstract Study question There are no published series of OHSS due to FGA. What FGA features should clinicians look for during OHSS, and what treatments are effective? Summary answer FGA tumour size is always &amp;gt;10mm. Other pituitary hormones may be deficient. Surgical resection of FGA is an effective treatment for OHSS. What is known already Pituitary adenomas affect 1:1000 adults and are classified as functioning or non-functioning. Non-functioning pituitary adenomas do not secrete hormones, but most commonly stain histologically gonadotroph cells. Functional pituitary adenomas secrete hormones such as prolactin causing prolactinoma. However, it is rare for a pituitary tumour to cause clinical features of excessive gonadotrophins (functioning gonadotroph adenoma; FGA). Single case reports, but no case series, have been published on the presentation of FGA-induced OHSS in women. Surgical excision of adenomas has been reported to cause remission of symptoms, though systematic data are lacking owing to rarity of these tumours. Study design, size, duration National case series from tertiary neuroendocrine units in England, Wales and Scotland. Participants/materials, setting, methods Eight high-volume pituitary endocrine tertiary units within England, Wales and Scotland audited their records for any cases of FGA-induced OHSS; only seven patients have been identified to date. In all cases, there had been no recent exposure to assisted reproductive technologies (ART) or drugs known to induce OHSS including gonadotrophins or selective oestrogen receptor modulators (SERMS). Main results and the role of chance Seven cases of FGA were identified with mean age 31.6 years (range 16-48) at diagnosis. Two-of-seven women presented acutely unwell with abdominal pain, distention and palpable mass requiring oophorectomy for ovarian torsion/ruptured ovarian cyst. The remaining five women presented with abdominal pain (n = 2), thyrotoxicosis (n = 1), menstrual irregularities/galactorrhoea (n = 1) and visual disturbances (n = 1). All women experienced intermittent pelvic pain during medical attendance. Pelvic ultrasound demonstrated enlarged multiseptated ovaries (volume ranging 27-442cm3). Ascites was noted in one woman. Six women had visual field defects due to optic chiasm compression on formal assessment. Median FSH was 26.10 u/L (8.3-33), but LH was &amp;lt;2.5 u/L in all cases. Estradiol (E2) far exceeded the reference range in 5/7 women (2990 to &amp;gt; 18000pmol/L);E2 was at the upper limit of normal in the remaining 2/7 women (960-1450pmol/L). Hyperprolactinaemia, hyperthyroidism and other pituitary hormones deficiency were noted in 6/7, 1/7 and 4/7 women respectively. All FGAs were macroadenomas with diameters ranging 16-48mm. Two patients were administered a somatostatin analogue prior to surgery, but FSH, E2 and tumour size did not change. Transsphenoidal surgery was performed in 6/7 women, and always improved symptomatic and biochemical features of OHSS; however, residual FGA tumour was present post-operatively in all cases studied. Limitations, reasons for caution It is possible that some ‘non-functioning’ gonadotroph adenomas cause subclinical problems including menstrual irregularity and mild OHSS which were never diagnosed. We have insufficient data to determine the prognosis for future pregnancy after FGA-induced OHSS. This study utilised historical case-notes, so some data is missing. Wider implications of the findings The ‘spontaneous’ presentation of OHSS may be confusing for clinicians. We report that FGA is an important cause of spontaneous OHSS which has well-defined biochemical and radiological characteristics, which may be treated effectively in the short-to-medium with pituitary surgery. Results of this study may provide greater awareness of FGA-induced OHSS. Trial registration number N/A

IVF Lite: a smart IVF programme based on mild ovarian stimulation for good prognosis patients

Research questionThe IVF Lite programme is based on mild ovarian stimulation including up to three fresh/frozen embryo transfers within 12 months. Is it effective and safe in good prognosis patients? DesignSingle-centre prospective study on infertile patients at their first IVF attempt (female age ≤38 years, anti-Müllerian hormone concentrations >1.5 ng/ml and/or FSH ≤10 mIU/ml). Induction of multiple follicular growth was based on a fixed protocol consisting of clomiphene citrate (100 mg/day) from day 3 to 7 of the menstrual cycle and 150 IU of recombinant FSH on days 5, 7 and 9. In case of low follicular recruitment (fewer than four follicles), the cycle was cancelled. The IVF Lite programme was considered complete after a live birth delivery or up to three embryo transfers within 12 months. The primary outcome was the cumulative live birth rate (cLBR) per couples that completed the programme. ResultsA total of 369 patients completed the IVF Lite programme, with 239 live births; 132 patients delivered after one embryo transfer (35.8%), 70 after a second embryo transfer (cLBR 54.7%), and 37 after a third attempt (cLBR 64.8%). No cases of ovarian hyperstimulation syndrome or clinical complications occurred. Spontaneous dropout rate from the programme was 4.5%. The cLBR per intention to treat was 46.8%. ConclusionsThe IVF Lite programme proved to be effective and safe in good prognosis patients with a good response to clomiphene citrate stimulation. It was well tolerated and implied low gonadotrophin consumption. Two-thirds of the patients achieved a live birth at the completion of the programme.

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 Case of Ovarian Hyperstimulation Syndrome with Diffuse Cortical Necrosis

Ovarian hyperstimulation syndrome is an iatrogenic, serious complication of controlled ovarian hyperstimulation, usually self-limited, but occasionally life threatening and typically occurs with gonadotropin. A 32-year-old married female [Para 0+1, 30 weeks (intra-uterine death)—2016], who underwent ovum pick up procedure for secondary infertility, presented to the Department of Nephrology, Apollo Hospital, Guwahati with the complaints of pain in the abdomen, anuria, breathing difficulty, bleeding per vagina on the next day. On investigating the case, the patient had thrombocytopenia, leucocytosis, anemia, normal morphology in peripheral blood smear, raised inflammatory markers, hepatic transaminases, lactate dehydrogenase, and rapidly progressive renal failure, metabolic acidosis with negative serological markers for connective tissue disease. Radio imaging suggested bilaterally enlarged ovaries with multiple hemorrhagic cysts, pleural effusion, and ascites. Ultrasound showed normal sized kidneys with increased echotexture and hypoechoeic cortical rim. Renal biopsy showed diffuse renal cortical necrosis. Supportive management started with a target to correct volume depletion, monitoring, and electrolyte abnormalities. Patient was hemodynamically stabilised and discharged on thrice weekly maintenance dialysis.

Low dose hCG supplementation in a Gn-RH-agonist trigger protocol is associated with worse pregnancy outcomes: a retrospective cohort study

BackgroundA number of studies have looked at dual triggers with hCG and GnRH agonist (GnRHa) in varying doses, but the question remains: what is the optimal dose of hCG to minimize ovarian hyperstimulation syndrome (OHSS) and still offer adequate pregnancy rates? The purpose of this study was to compare pregnancy and OHSS rates following dual trigger for oocyte maturation with GnRHa and a low-dose hCG versus hCG alone. A secondary objective was the assess pregnancy outcomes in subsequent frozen cycles for the same population.MethodsA total of 963 women < 41 years old, with a BMI 18–40 kg/m2 and an AMH > 2 ng/mL who underwent fresh autologous in vitro fertilization (IVF) with GnRH antagonist protocol at a University-based fertility center were included in this retrospective cohort study. Those who received a low dose dual trigger with hCG (1000u) and GnRHa (2 mg) were compared to those who received hCG alone (10,000u hCG/250-500 μg Ovidrel). Differences in implantation rates, pregnancy, live birth, and OHSS were investigated.ResultsThe dual trigger group was younger (mean 33.6 vs 34.1 years), had a higher AMH (6.3 vs 4.9 ng/mL,) more oocytes retrieved (18.1 vs 14.9) and a higher fertilized oocyte rate (80% vs 77%) compared with the hCG only group. Yet, the dual trigger group had a lower probability of clinical pregnancy (gestational sac, 43.4% vs 52.8%) and live birth (33.4% vs 45.8%), all of which were statistically significant. There were 3 cases of OHSS, all in the hCG-only trigger group. In subsequent frozen cycles, pregnancy rates were comparable between the two groups.ConclusionsThe dual trigger group had a better prognosis based on age and AMH levels and had better stimulation outcomes, but significantly worse pregnancy outcomes, suggesting the low dose hCG (1000u) in the dual trigger may not have provided adequate luteal support, compared to an hCG-only trigger (10,000u hCG/250-500 μg Ovidrel). Interestingly, the pregnancy rates were comparable in subsequent frozen cycles, further supporting the hypothesis that the issue lies in inadequate luteal phase support, rather than embryo quality. Based on these findings, our program has changed the protocol to 1500u of hCG in a dual trigger.

Dual trigger protocol is an effective in vitro fertilization strategy in both normal and high responders without compromising pregnancy outcomes in fresh cycles

ObjectiveTo study the birth rates of normal vs. high responders after dual trigger of final oocyte maturation with gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin in fresh in vitro fertilization (IVF) cycles in which ovarian stimulation was achieved by a flexible GnRH antagonist protocol.DesignRetrospective cohort study.SettingUniversity hospital.Patient(s)In women <35 years of age, 290 fresh IVF cycles using the dual trigger protocol with day 5 embryo transfers from January 2013 to July 2018 were included. Cycles excluded were those with preimplantation genetic testing, gestational carriers, donor oocytes, and fertility preservation.Intervention(s)IVF with dual trigger.Main Outcome Measure(s)Clinical pregnancy rate, live birth rate.Result(s)Comparing normal responders, defined as <30 oocytes retrieved, and high responders, defined as ≥30 oocytes retrieved, the clinical pregnancy rates (67.0% vs. 69.3%, respectively) and live birth rates (60.5% vs. 60.0%, respectively) were not significantly different. No cases of ovarian hyperstimulation syndrome were reported in either group.Conclusion(s)Ovarian stimulation by a flexible GnRH antagonist protocol followed by dual trigger yields comparable outcomes between normal and high responders in fresh IVF cycles.

Severe ovarian hyperstimulation syndrome with GnRH agonist trigger during the COVID pandemic: lessons learned from an unusual case

Background: Injectable gonadotropins stimulate multi-follicular recruitment and allows retrieval of multiple oocytes for assisted reproduction. The widespread utilization of gonadotropin releasing hormone agonist (GnRHa) to induce oocyte maturation for oocyte retrieval has nearly eliminated the risk of severe ovarian hyperstimulation syndrome (OHSS), and only a few cases have been reported in the literature. The rarity of severe OHSS may lead to the mistaken conclusion that gonadotropin stimulation can be safely administered with limited monitoring, even in high-risk patients. We present an unusual case of a woman with limited monitoring due to the COVID pandemic who developed severe OHSS before GnRH agonist trigger and oocyte. Case Presentation: A 29-year-old nulliparous woman with polycystic ovarian syndrome (PCOS) initiated ovarian stimulation for oocyte retrieval. She had a robust initial response, and developed worsening abdominal pain, bloating, nausea, vomiting, and decreased appetite before retrieval. GnRH agonist was given to “trigger ovulation and retrieval scheduled due to the low reported incidence of severe OHSS. Symptoms progressed, and on the morning of retrieval, ultrasound demonstrated bilaterally enlarged ovaries &gt;10cm and 48 oocytes were retrieved for a planned cryo-all cycle. She was hospitalized on the day of retrieval for severe OHSS and had two large-volume paracenteses. She was stable and discharged home by day 5, and symptoms markedly improved with the onset of menses. She has an ongoing pregnancy from her first frozen embryo transfer. Conclusion: We add a rare case of severe OHSS with a GnRHa trigger and cryo-all protocol with the onset of symptoms before GnRH agonist administration. Although rare, severe OHSS may still occur with a GnRHa trigger, and caution is needed when an initial robust response is identified. Here we also provide an opportunity to review the important patient risk factors for the development of OHSS and measures to reduce the risk in excessive responders.

Fresh embryo transfer versus freeze-only after in vitro maturation with a pre-maturation step in women with high antral follicle count: a randomized controlled pilot study.

In vitro maturation (IVM) is an alternative to in vitro fertilization (IVF) for women at high risk of developing ovarian hyperstimulation syndrome (OHSS). This study determined the effectiveness and safety of a freeze-only strategy versus fresh embryo transfer (ET) after IVM with a pre-maturation step (CAPA-IVM) in women with a high antral follicle count (AFC). This randomized, controlled pilot study (NCT04297553) was conducted between March and November 2020. Forty women aged 18-37 years with a high AFC (≥24 follicles in both ovaries) undergoing one cycle of CAPA-IVM were randomized to a freeze-only strategy with subsequent frozen ET (n = 20) or to fresh ET (n = 20). The primary endpoint was ongoing pregnancy resulting in live birth after the first ET of the started treatment cycle. The ongoing pregnancy rate in the freeze-only group (65%) was significantly higher than that in the fresh ET group (25%; p = 0.03), as was the live birth rate (60% versus 20%; p = 0.02). Clinical pregnancy rate was numerically, but not significantly, higher after frozen versus fresh ET (70% versus 35%; p = 0.06), while the number of day 3 or good quality embryos, endometrial thickness on the day of oocyte pick-up, implantation rate, and positive pregnancy test rate did not differ significantly between groups. No cases of OHSS were observed, and miscarriage and multiple pregnancy rates were similar in the two groups. These findings suggest that the effectiveness of CAPA-IVM could be improved considerably by using a freeze-only strategy followed by frozen ET in subsequent cycles. NCT04297553 ( www.clinicaltrials.gov ).

LATE ONSET OHSS AND PREGNANCY OUTCOME: A CASE REPORT

Ovulation induction has been an important mode of treatment of infertility.Ovarian stimulation may result in a supraphysiologic response leading to an iatrogenic complication known as the ovarian hyperstimulation syndrome(OHSS) . This syndrome is a potentially lethal condition,the pathophysiologic hallmark of which is the accumulation of massive extravascular exudate combined with profound intravascular volume depletion and hemoconcentration.we report a case of severe OHSS with very large ovaries in a 38yr old case of G2A1 with 4weeks 5days GA ,ICSI conception with TCTA triplets presented to the emergency department with abdominal pain,ascites and respiratory distress . The patient was managed symptomatically with no complications. Although ovarian hyperstimulation is a rare entity ,it is important that the physician recognizes this condition.prompt diagnosis and successful management is likely to avoid serious and rapid development of complications.

Individualized ovarian stimulation for in vitro fertilization: a multicenter, open label, exploratory study with a mixed protocol of follitropin delta and highly purified human menopausal gonadotropin

To evaluate the safety profile and the number of usable blastocysts on day 5 and on day 6 after treatment with an individualized dosing regimen of a follitropin delta and highly purified human menopausal gonadotropin (HP-hMG) for controlled ovarian stimulation. Multicenter, open label, exploratory study. Reproductive medicine clinics. A total of 110 patients (aged 18-40 years). Follitropin delta coadministered with HP-hMG, with follitropin delta dose fixed according to an established algorithm and HP-hMG dose at 75 IU when the follitropin delta starting dosage was <12 μg; 150 IU when follitropin delta dosage was 12 μg and weight <100 kg, and 225 IU when follitropin delta dosage was 12 μg and weight ≥100 kg (dosage adjustments confined to HP-hMG only). Mean number of good-quality blastocysts obtained at day 5 and day 6 as well as the proportion of women with ovarian hyperstimulation syndrome (OHSS). A cohort study was compared with the follitropin delta group from the Evidence-based Stimulation Trial with Human Recombinant Follicle-Stimulating Hormone in Europe and Rest of World 1 (ESTHER-1) study. Even when stratified by age, a statistically significantly higher mean in the number of oocytes retrieved and number of good-quality blastocysts was observed in this study compared with the ESTHER-1 trial in which follitropin delta was used alone. The rate of patients triggered with a gonadotropin-releasing hormone agonist was statistically significantly higher in our Menopur and Rekovelle Combined Study (MARCS) cohort (43%) when compared with the rates reported in the follitropin delta cohort in the ESTHER-1 study (2.3%). Incidence of any grade of OHSS was 9.3% in the present study compared to 2.6% in follitropin delta group from ESTHER-1 trial. No cases of moderate or severe OHSS were observed in our study compared with 1.4% in the follitropin delta group of ESTHER-1. Optimizing the ovarian response during invitro fertilization employing a mixed protocol of individualized dosing of follitropin delta and HP-hMG resulted in a statistically significant number of usable blastocysts on days 5 and 6 with an increased risk of mild OHSS, which did not require medical intervention or hospitalization. NCT03483545.

The Frequency of Ovarian Hyperstimulation Syndrome and Thromboembolism with Originator Recombinant Human Follitropin Alfa (GONAL-f) for Medically Assisted Reproduction: A Systematic Review.

BackgroundRecombinant human follitropin alfa (r-hFSH) is used for ovarian stimulation as part of medically assisted reproduction. There is a risk for ovarian hyperstimulation syndrome (OHSS) with r-hFSH treatment, and an increased risk for thromboembolic events in the presence of pregnancy with OHSS.ObjectivesTo report the frequency of OHSS and thromboembolism with originator follitropin alfa (GONAL-f) based on the Global Safety Database of Merck KGaA, Darmstadt, Germany and a systematic review of published data.Data SourcesReports of OHSS and thromboembolism were obtained from the Global Safety Database of Merck KGaA, Darmstadt, Germany from 20 October 1995 to 19 October 2018. The systematic review was based on MEDLINE and Embase searches from inception to 19 October 2018.Study Eligibility CriteriaPatients receiving GONAL-f for ovulation induction or ART, with a starting dose within the range included in the prescribing information and providing information on the occurrence of OHSS and/or thromboembolism.Study Appraisal and Synthesis MatchesIn the Global Safety Database of Merck KGaA, Darmstadt, Germany there were an estimated 16,525,975 treatment cycles since 20 October 1995; 1110 reported cases of OHSS and 80 reported cases of thromboembolic events (reporting rates 6.7 and 0.48 per 100,000 treatment cycles, respectively). The systematic review identified 45 studies (5186 patients exposed to GONAL-f; 5240 treatment cycles). There were 272 reports of OHSS (5190 [5.19%] per 100,000 treatment cycles), including 10 cases of severe OHSS (191 [0.19%] per 100,000 treatment cycles).LimitationsThere may be the potential for under-reporting of safety outcomes in the literature, and under-reporting is a well-known phenomenon in spontaneous reporting databases.Conclusion and Implications of Key FindingsOur analyses demonstrate low rates of OHSS and thromboembolism with GONAL-f.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-020-01512-w) contains supplementary material, which is available to authorized users.

Assessing the Usefulness of Severity Markers in Women with Ovarian Hyperstimulation Syndrome.

The present study aims to assess the usefulness of severity markers in women with ovarian hyperstimulation syndrome (OHSS). An observational study was designed including 76 women with varying degrees of severity of OHSS. Clinical history, physical examination, laboratory tests, and ultrasound measurement of the ovarian size and ascites index were carried out in all patients. Intra-abdominal pressure (IAP) was measured using an intravesical Foley Manometer catheter. Ascites index and ovarian volume increased progressively being highest in the most severe stage of OHSS. The median IAP in mild OHSS was found to be lower than that in the moderate and severe OHSS (4.0mm, 12mm, and 16.0mm, respectively). Critical cases of OHSS presented the highest IAP (25.0mm). IAP did not reach the level of intra-abdominal hypertension in mild OHSS, whereas moderate and severe OHSS was associated with intra-abdominal hypertension grade I and grade II-III, respectively. Values of IAP in critical OHSS were found similar to those observed in abdominal compartment syndrome patients. The IAP showed a strong positive correlation with ovarian volume and ascites index. The reduction of IAP after paracentesis was greater among critical OHSS patients. The ovarian volume and the level of intra-abdominal hypertension are related to the severity of OHSS and are of particular importance in the initialization of the syndrome. Ascites index is simple and convenient and can serve as an indirect marker of the abdominal reserve volume. In conjunction with clinical and laboratory data, ascites index and IAP values might be indicators for paracentesis.

Rare genetic variants suggest dysregulation of signaling pathways in low- and high-risk patients developing severe ovarian hyperstimulation syndrome.

To investigate if rare gene variants in women with severe ovarian hyperstimulation syndrome (OHSS) provide clues to the mechanisms involved in the syndrome. Among participants in a prospective randomized study (Toftager et al. 2016), six women with predicted low and six women with predicted high risk of OHSS developing severe OHSS (grades 4 and 5, Golan classification) were selected. In the same cohort, six plus six matched controls developing no signs of OHSS (Golan grade 0) were selected. Whole-exome sequencing was performed. Analysis using a predefined in silico OHSS gene panel, variant filtering, and pathway analyses was done. We found no convincing monogenetic association with the development of OHSS using the in silico gene panel. Pathway analysis of OHSS variant lists showed substantial overlap in highly enriched top pathways (p value range p < 0.0001 and p > 9.8E-17) between the low- and high-risk group developing severe OHSS, i.e., "the integrin-linked kinase (ILK) signaling pathway" and the "axonal guidance signaling pathway," both being connected to vasoactive endothelial growth factor (VEGF) and endothelial function. Rare variants in OHSS cases with two distinct risk profiles enrich the same signaling pathways linked to VEGF and endothelial function. Clarification of the mechanism as well as potentially defining genetic predisposition of the high vascular permeability is important for future targeted treatment and prevention of OHSS; the potential roles of ILK signaling and the axonal guidance signaling need to be validated by functional studies.