Moderate Ovarian Hyperstimulation Syndrome Research Articles

Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial.

There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

P-715 outcomes of in vitro fertilization and embryo transfer among ethnic Tibetan, Yi and Han Chinese women

Abstract Study question Does difference exist in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) among ethnic Tibetan, Yi and Han Chinese women? Summary answer We report that the outcomes of IVF-ET were poorer among ethnic Yi women compared with ethnic Han and Tibetan women. What is known already It has been reported that the outcomes of IVF-ET are correlated with ethnicity/race in Europe and the United States as an independent factor. Sichuan is the only province in China where all 56 ethnic groups reside, with ethnic Han, Yi and Tibetan Chinese having the highest proportions. In Chengdu city (the capital of Sichuan province, basin), the majority ethnic group is Han, whilst in Liangshan and Aba Prefectures (plateau), the major ethnic groups are Yis and Tibetans. The living environment, diet, custom, medical condition and genetic backgrounds are different among different ethnic groups. Study design, size, duration In this multi-center retrospective cohort study, a total of 58374 Chines women aged 20 ∼ 45 had undergoing the first IVF or intracytoplasmic sperm injection (ICSI) ET treatment cycle with non-donor gametes from January 2014 to December 2022 were enrolled. Participants/materials, setting, methods The patients were enrolled from two University Affiliated Hospitals and one Reproductive Hospital in Chengdu. The controlled ovarian stimulation protocols were gonadotropin releasing hormone (GnRH) agonist protocol or GnRH antagonist protocol. The patients were divided into three groups based on their ethnic origins: Tibetans (n = 1069), Yis (n = 2273) and Hans (n = 55032). The outcomes of IVF-ET were compared, with the primary outcome being the live birth rate. Main results and the role of chance The proportion of GnRH agonist protocol and IVF fertilization, the rates of moderate and severe ovarian hyper-stimulation syndrome (OHSS), and cleavage embryo formation in ethnic Han women were significantly higher than in the ethnic Yis and Tibetans (P &amp;lt; 0.05). The rates of implantation, clinical pregnancy and live birth (35.5% vs. 42.4%) were significantly lower, whereas the late abortion rate was significantly higher in Yi women than that in Han women (P &amp;lt; 0.05). The live birth rate was significantly lower in Yi women (35.5%) than in Tibetan (43.3%) and Han women (42.2%) (P &amp;lt; 0.05). Adjustment was made for age, duration, type and etiology of infertility, history of spontaneous abortion, smoking, alcohol, tuberculosis infection, body mass index, antral follicle count, antimüllerian hormone, and so on, by multivariate logistic regression analysis. Yi women had significantly lower rates of moderate and severe OHSS (OR = 0.69, 95% CI = 0.49-0.94, P = 0.024) and clinical pregnancy (OR 0.8, 95% CI 0.70-0.93, P = 0.002) compared with ethnic Hans. Yi women had significantly lower live birth rate compared with ethnic Hans (OR = 0.79, 95% CI = 0.68-0.92, P = 0.002) and Tibetans (OR 0.73, 95% CI 0.58-0.92, P = 0.007). Limitations, reasons for caution The limitations are related with the retrospective study and lack of some demographic characteristics of the patients which may influence the outcomes of IVF-ET, including diet habits, educational level, and economic status. Wider implications of the findings The ethnic group is an independent factor for the outcomes of IVF-ET among ethnic Tibetan, Yi and Han women. Among the three ethnic groups, the Yis had lower live birth rate and moderate and severe OHSS, whilst ethnic Han women had more moderate and severe OHSS. Trial registration number ChiCTR2300070269

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Efficacy of Dan'e Fukang Soft Extract in Moderate Ovarian Hyperstimulation Syndrome for Concurrent Treatment of Blood and Fluid Guided by the "Triple Prevention" Principle.

This study aimed to evaluate the therapeutic efficacy and safety of Dan'e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of "triple prevention". This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan'e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators. There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group. Based on the traditional Chinese medicine principle of "triple prevention", the use of Dan'e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.

Efficacy and safety of follitropin delta versus follitropin alpha/beta in infertility treatment: A systematic review and meta-analysis.

Follitropin δ may be an alternative to conventional follitropin α/β for controlled ovarian stimulation (COS) within assisted reproductive treatment (ART), but its efficacy and safety remain unknown. We performed a random-effects meta-analysis to compare the efficacy and safety of follitropin δ and follitropin α/β. We searched randomized controlled trials comparing follitropin δ and follitropin α/β using MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO-ITCRP on December 14, 2022. The primary outcomes were the live birth rate and the incidence of moderate or severe ovarian hyperstimulation syndrome (OHSS). The certainty of the evidence was assessed using the grading of recommendations assessment, development, and evaluation approach. The protocol was registered on the Open Science Framework. Three studies involving 2682 participants were included in our meta-analysis. The results indicated that follitropin δ may result in little to no difference in live birth rates (risk ratio [RR], 1.12; 95% confidence interval [CI], 0.91-1.38; low certainty) and the incidence of moderate or severe OHSS (RR, 0.78; 95% CI, 0.48-1.26; low certainty) compared with follitropin α/β. Follitropin δ may result in little to no difference in COS compared with follitropin α/β, especially in terms of live births and safety.

Cocktail treatment by GnRH-antagonist, letrozole, and mifepristone for the prevention of ovarian hyperstimulation syndrome: a prospective randomized trial

Objective This study is aimed to determine the efficacy of a cocktail style treatment by combining GnRH-antagonist, letrozole, and mifepristone on the prevention of ovarian hyperstimulation syndrome (OHSS) in high-risk women. Methods This prospective, randomized controlled clinical trial was performed between January 2018 and December 2018. A total of 170 women who identified as high risk of OHSS during the ovarian hyperstimulation and underwent cryopreservation of whole embryos. On the day of oocyte retrieval, the combination group received 0.25 mg Cetrorelix for 3 d, 5 mg letrozole for 5 d, and 50 mg mifepristone for 3 d, the mifepristone group received 50 mg mifepristone for 3 d. A total of 156 cases were included in final analysis. All the frozen embryo transfer (FET) cycles were followed up until December 2021. Results The combination group showed significantly decreased incidence of moderate and severe OHSS than mifepristone group (20.5% vs. 42.3%), with remarkably reduced serum estradiol level on hCG + 3 and + 5 d, decreased ovarian diameter, and shortened luteal phase. Oocyte retrieval number, levels of estradiol on hCG + 0 and VEGF, and ovarian diameter on hCG + 5 were associated with the severity of the symptoms. There was no significant difference in cumulative live birth rates (LBRs) between the combination and mifepristone group (74.4% vs. 76.9%). Conclusions The combination treatment effectively reduces the incidence of moderate/severe OHSS in high-risk women.

Pregnancy Outcomes of Assisted Reproductive Technology (ART) Cycle Complicated by Ovarian Hyperstimulation Syndrome (OHSS): Case Series Study.

Ovarian hyperstimulation syndrome (OHSS) is a frequent, potentially lethal side effect of assisted reproductive technology (ART), distinguished by symptoms such as ovarian enlargement, ascites, and pleural effusion. This study is designed to study the effect of assisted reproductive technology (ART) cycle complicated by OHSS on pregnancy outcomes. A case series study at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia, was executed to examine the pregnancy outcomes in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. Fifteen patients were admitted to the IVF unit between January 2015 and December 2021. Data were retrieved from patients' medical records, and descriptive statistical methods were employed to analyze participants' data. The study assessed pregnancy outcomes for 15 female participants (mean age=31.1 years, SD=3.46) with a BMI range of 20-40 (mean BMI=29.6, SD=6.4), of whom 33.3% were classified as obese. The primary factor of infertility was anovulation (66.7%), followed by male factors (20%). About 26.7% of those affected by OHSS had moderate OHSS, and 73.3% had severe OHSS, with 100% of those with severe OHSS having undergone three embryo transfers. None of the participants developed gestational diabetes mellitus (DM), but one participant had high blood sugar levels (6.67% of total participants), with a mean glucose of 6.3±2.0. There were no instances of preeclampsia, gestational hypertension, abnormal placentas, or congenital abnormalities in newborns among the participants. Preterm deliveries were common, with 33.3% delivering between 32 and 37 weeks, 6.7% before 28 weeks, and 33.3% within 28-32 weeks. Overall, 73.3% of the participants experienced pregnancy, and the birth mode was almost evenly split between vaginal and cesarean birth. In conclusion, this research provides an exploration into the outcomes of pregnancies in women undergoing assisted reproductive technology treatments complicated by ovarian hyperstimulation syndrome. It shows anovulation as a prevalent cause of infertility and a noteworthy incidence of severe OHSS. Despite these challenges, a significant number of women were able to experience pregnancy, although preterm deliveries and abortions were common. The delivery methods were fairly balanced between vaginal birth and cesarean section. These findings underscore the necessity for more effective strategies to manage OHSS and improve pregnancy outcomes in ART procedures.

The ovarian hyperstimulation that truly matters: Admissions, severity and prevention strategies.

Ovarian hyperstimulation syndrome (OHSS) is a common but serious complication of in vitro fertilisation. Despite available strategies to reduce OHSS incidence, a small proportion of patients will develop the clinically significant disease with substantial morbidity. Efforts toward better understanding and the prevention of severe disease are required to improve patient outcomes. The aims are to: (1) formulate clinically relevant OHSS classification for inpatient settings and data collection/reporting; (2) estimate OHSS prevalence requiring hospital admission in Victoria; and (3) determine the extent of OHSS preventability with clinical strategies. This retrospective cohort study included all OHSS admissions in a tertiary referral centre, January 2016-December 2021, which included approximately 40% of all cases of hospitalisation for OHSS in the State of Victoria. Patient characteristics, treatment regimes, fertility treatment outcomes, timing classification, and clinical markers of disease severity were studied. Patients were classified as having mild, moderate, or severe OHSS with a novel inpatient classification system. Of 199 OHSS cases presenting to the tertiary institution, 107 were classified as moderate/severe, with no significant difference between age, body mass index, length of stimulation and follicle number between mild/moderate and severe groups. There were more cases of early hyperstimulation (137) compared to late (62) presentation, of which 53% were severe. The average length of stay overall was 3.1 days, and 5.2 days for severe presentations. In 15% of severe cases, an agonist trigger was used. The overall prevalence of OHSS requiring hospital admission appears to be low (approximately 0.6% of all stimulated cycles). Established risk factors may not accurately predict clinically relevant OHSS risk. Further monitoring, clinician and patient education are required to minimise the risk of significant OHSS that results in hospital admissions.

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications.

To explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset. This was a single-center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three-degree, five-level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate-to-severe OHSS were divided into two groups. A control group included 3427 (96.54%) non-OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores. There was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P< 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P< 0.05). In patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.

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.

Hormonal profile in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

The major limitations associated with gonadotropin-releasing hormone agonist (GnRHa) triggering are inferior clinical outcomes in fresh embryo transfer cycles caused by luteal phase insufficiency following the GnRHa triggering. We included 153 high-risk patients in this study. In group I, the patients received gonadotropin-releasing hormone agonist (GnRHa) trigger + 1,500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day; in group II, the patients had a dual trigger (GnRHa + 1,500 IU hCG); and in group III (control), 10,000 IU hCG trigger was prescribed for the final oocyte maturation. The levels of LH, estradiol, and progesterone were evaluated in serum on the stimulation starting day, day 6 of stimulation, on the day of the trigger administration, OPU day, days 3 and 5 post-OPU, and day 14 post-ET, as well as in follicular fluid. Progesterone concentration was significantly lower in group I on OPU+5 compared to the hCG group (I vs. III, р = 0.0065). Progesterone levels were significantly lower in group II in serum on OPU+5 compared to groups I and III (I vs. II, р = 0.0068; II vs. III, р = 1.76 × 108). The progesterone levels were significantly higher in follicular fluid in group III compared to the study groups (I vs. III, р = 0.002; II vs. III, p = 0.009). However, no significant differences in clinical outcomes were found between the groups. Then, we divided all women into pregnant and non-pregnant groups and found that estradiol (p = 0.00009) and progesterone (p = 0.000036) on the day of the pregnancy test were significantly higher in the pregnant women group. Also, progesterone on OPU day was significantly higher in the non-pregnant group (p = 0.033). Two cases of moderate ovarian hyperstimulation syndrome (OHSS) late-onset occurred in group I (3.5%, 2/56), no case of moderate/severe OHSS late-onset in group II, and three cases of moderate late-onset in group III (5.7%, 3/53). The low-dose hCG supplementation improves the luteal phase insufficiency after GnRHa triggering, which is confirmed by the comparable pregnancy rates in fresh transfer cycles between the groups. However, low-dose hCG carries a similar risk of OHSS as the full dose of hCG in high-responder patients.

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.

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.

Ovarian hyperstimulation syndrome and its relation to pregnancy

Vytautas Abraitis1, Saulė Kržčonavičiūtė1, Marija Vaitkevičiūtė2 1 Department of Obstetrics and Gynecology, Medical Academy, Lithuanian University of Health Sciences, Eivenių g. 2, LT-50161 Kaunas, Lithuania 2 Medical Academy, Lithuanian University of Health Sciences, A. Mickevičiaus g. 9, LT-44307 Kaunas, Lithuania Abstract Introduction: Ovarian Hyperstimulation Syndrome (OHSS) is an iatrogenic complication manifested by suprafysiological ovarian stimulation. This syndrome is commonly related to assisted reproduction. OHSS has been associated with an increased risk of miscarriage, multiple pregnancies, and more severe clinical course of the syndrome. However, there are few studies examining the relationship between OHSS and pregnancy, and more consistent studies are needed. The aim – to discuss the characteristics of OHSS and it‘s possible links with pregnancy. Research method: systematic literature review was conducted. Articles, describing OHSS and its links to pregnancy, were selected. The review was done using the electronic database Pub-Med (Medline). Results: OHSS prevention is selected individually based on risk factors, anti-müllerian hormone concentration, and number of tertiary follicles. Mild to moderate OHSS may regress spontaneously and treatment is not always necessary. Patients who develop signs of severe OHSS should be hospitalized and treated with medication and (or) surgery. In case of unclear pathogenesis of the disease, only symptomatic treatment is possible. A correlation was observed between OHSS and an increased risk of miscarriage, preterm birth, gestational hypertension and low birth weight. Conclusions: OHSS is an iatrogenic complication that can occur at different stages and degrees due to variety of risk factors and prevention. Mild to moderate OHSS is often a transient condition, however, severe OHSS can be potentially life-threatening. The complications associated with OHSS are miscarriage and preterm birth, although there are also associations between this syndrome and gestational hypertension as well as low birth weight. Keywords: ovarian hyperstimulation syndrome, OHSS treatment, pregnancy.

Calcium gluconate infusion is not as effective as dopamine agonists in preventing ovarian hyperstimulation syndrome.

The aim of the study was to compare the effectiveness of calcium gluconate and cabergoline therapy in the prevention of ovarian hyperstimulation syndrome (OHSS). Eight hundred and forty-five women who underwent GnRH antagonist protocol and at high risk for developing OHSS were divided into two groups, those given cabergoline (n=435) or calcium gluconate (n=410). In cabergoline group, 0.5 mg of cabergoline was administered once daily p.o. starting on the day of ovulation trigger and continued until the following 8 days. In calcium gluconate group, intravenous calcium gluconate was administered daily for four days starting on the day of oocyte pickup (OPU). 10 ml of 10% calcium gluconate solution was dissolved in 200 ml of physiological saline and administered by intravenous route within 40 minutes. Infusion was started within the first 30 minutes following the OPU and continued on the 1st, 2nd and 3rd days after OPU. Mild OHSS was developed in 367 (89%) patients receiving calcium gluconate infusion, while 251 patients (57%) in the cabergoline group developed mild OHSS. The frequency of mild OHSS in the calcium group was significantly higher than the cabergoline group (p<.001). Moderate OHSS was observed in 32 people (7.8%) in the calcium gluconate group, while it was observed in 184 people in the cabergoline group (42.3%). Calcium gluconate infusion significantly reduced the development of moderate OHSS compared to cabergoline therapy (p<.001). Severe OHSS developed in 11 patients (2.7%) in the calcium gluconate group, while severe OHSS did not develop in those given cabergoline (0%, p<.001). Clinical pregnancy, live birth and abortion rates were similar in the two groups. When logistic regression analysis was performed, a significant correlation was found between age, BMI, AMH, the number of antral follicle count, OHSS history, paracentesis, progesterone on the day of hCG, 2 PN zygotes, and HbA1c levels and the development of OHSS. No correlation was found between the use of metformin or cetrotide and the development of OHSS. Calcium gluconate treatment is not effective in the prevention of OHSS.

The application of information-motivation-behavior skill model in patients with moderate to severe ovarian hyperstimulation syndrome

Ovarian Hyperstimulation Syndrome (OHSS) is a common complication of infertile patients underwent super ovulation treatment with assisted reproductive technology, which often occurs after the use of gonadotropin or in the first trimester. In this study, we investigated the effectiveness of the information-motivation-behavior skill model in patients with moderate to severe OHSS. After different nursing intervention, the score results showed that after 4 weeks of intervention, the two groups of patients’ self-efficacy scores, total scores and quality of life scores were higher than before intervention, and the intervention group was higher than the normal control (p &lt; 0.05). Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of 2 groups were lower than before intervention, and the score of the intervention group was lower than the normal control (p &lt; 0.05). In conclusion, the information-motivation-behavioral (IMB) skills model can significantly improve the cognitive level and the quality of life of patients with moderate and severe OHSS.

Clinical outcomes of potential high responders after individualized FSH dosing based on anti-Müllerian hormone and body weight

Research questionHow does the efficacy and safety of individualized follitropin delta dosing compare with conventional dosing for ovarian stimulation in potential high responders? DesignRetrospective analysis of 153 potential high responders identified on the basis of baseline serum anti-Müllerian hormone (AMH) levels above 35 pmol/l, who were originally randomized to an individualized fixed dose of follitropin delta based on AMH and body weight (n = 78) or to a daily starting dose of 150 IU follitropin alfa (n = 75). ResultsAt the end of stimulation, patients treated with individualized follitropin delta or conventional follitropin alfa had 12.1 ± 7.0 and 18.3 ± 7.0 (P < 0.001) follicles measuring 12 mm or wider, and 27.3% and 62.7% had serum progesterone levels higher than 3.18 nmol/l (P < 0.001), respectively. Overall number of oocytes in these two respective arms was 9.3 ± 6.7 and 17.9 ± 8.7 (P < 0.001), and the ongoing pregnancy rate per started cycle after fresh blastocyst transfer was 28.2% and 24.0%. The risk of ovarian hyperstimulation syndrome (OHSS) for all cases was three times higher in the conventional follitropin alfa arm at 16.0% versus 5.1% with individualized follitropin delta treatment (P = 0.025) and 26.7% versus 7.7% (P = 0.001) for early moderate or severe OHSS, preventive interventions for early OHSS, or both. ConclusionsTreatment with individualized follitropin delta provides an improved efficacy–safety balance in women with high ovarian reserve, as it normalizes the ovarian response and decreases the risk of OHSS without compromising the chance of pregnancy.

Coagulation and Fibrinolysis Biomarkers as Potential Indicators for the Diagnosis and Classification of Ovarian Hyperstimulation Syndrome

Background: Accurate diagnosis and classification of ovarian hyperstimulation syndrome (OHSS) is important for its management. We employed a new high-sensitivity chemiluminescence immunoassay to detect the thrombin-antithrombin complex (TAT), plasmin alpha2-plasmin inhibitor complex (PIC), soluble thrombomodulin (sTM), and tissue plasminogen activator-inhibitor complex (TPAI-C), and evaluated their diagnostic and classification performance for OHSS.Methods: A total of 106 women were enrolled, including 51 patients with OHSS (25 mild or moderate OHSS, 26 severe OHSS), and 55 without OHSS (control group). TAT, PIC, sTM, and TPAI-C levels were measured using the Sysmex HISCL5000 automated analyzer.Results: Compared to the control group, TAT, PIC, and TPAI-C levels were significantly higher (P < 0.001, P < 0.001, P < 0.001, respectively), whereas the sTM level was significantly lower (P < 0.001) in the patients with OHSS. The receiver operating characteristic was used to evaluate the diagnostic efficiency. For the diagnosis of OHSS, the area under the curves (AUCs) for TAT, PIC, sTM, and TPAI-C were 0.991, 0.973, 0.809, and 0.722, respectively. In particular, the sensitivity, specificity, positive predictive value, and negative predictive value for TAT and PIC were all above 90%. For the differential diagnosis of mild–moderate and severe OHSS, the AUCs for TAT, PIC, and TPAI-C were 0.736, 0.735, and 0.818, respectively. The cutoff values of TAT, PIC, and TPAI-C for the differential diagnosis of mild–moderate and severe OHSS were 11.5 ng/mL, 2.4 μg/mL, and 5.8 ng/mL, respectively. Based on these cutoff values, eight cases of mild–moderate OHSS exceeded the cutoff values, two of which developed to severe OHSS in the following days. However, of the remaining 17 cases of mild–moderate OHSS patients with negative biomarkers, none subsequently developed severe OHSS.Conclusions: TAT, PIC, sTM, and TPAI-C can be used as sensitive biomarkers in the diagnosis of OHSS. Meanwhile, TAT, PIC, and TPAI-C also displayed remarkable potential in the classification of OHSS. In addition, the levels of TAT, PIC, and TPAI-C above the cutoff values in patients with mild–moderate OHSS might predict a high risk of developing severe OHSS.

Cabergoline versus calcium infusion in the prevention of ovarian hyperstimulation syndrome: a randomised controlled study

The aim of this study was to compare the efficacy of calcium infusion versus cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in IVF patients at high risk for OHSS. One hundred and seventy patients who were stimulated using the long luteal GnRH agonist protocol and at high risk for developing OHSS were randomised in a 1:1 ratio to cabergoline group and calcium gluconate group. In cabergoline group, 0.5 mg of cabergoline was administered once daily p.o. for eight days starting on the day of HCG administration. In calcium gluconate group, intravenous calcium gluconate (10%, 10 ml in 200 ml of physiologic saline) was administered daily for four days starting on the day of ovum pickup. Six patients in cabergoline group and eight patients in calcium gluconate group developed moderate OHSS. One patient in each group developed severe OHSS. The incidence of moderate/severe OHSS was comparable between both groups (8.24% vs. 10.59%, p value = .599, OR = 0.76, 95% CI [0.269–2.138]). The implantation, clinical and ongoing pregnancy rates were similar in the two groups (16.91% vs. 15.84%, p = .771, 35.29% vs. 32.94%, p = .746, and 30.59% vs. 28.24%, p = .736, respectively). In conclusion, calcium infusion and cabergoline have comparable effectiveness in the prevention of OHSS. Both drugs are well tolerated, cheap and have no adverse effects on the reproductive outcomes of IVF cycle. Clinical trial registration: The trial was registered on clinical trials.gov database [NCT02875587]. Impact Statement What is already known on this subject? The effectiveness of cabergoline in the prevention of OHSS in IVF patients at high risk for OHSS is confirmed by overwhelming scientific evidence. Calcium infusion is a novel strategy for prevention of OHSS. Few studies reported the use of calcium infusion in the prevention of OHSS. A retrospective study and a randomised controlled study revealed that calcium infusion reduces the incidence of OHSS. Moreover, a quasi-randomised study revealed that calcium infusion is as effective as cabergoline in the prevention of OHSS. What the results of this study add? Calcium infusion and cabergoline have comparable effectiveness in the prevention of OHSS. Both drugs are well tolerated, cheap and have no adverse effects on the reproductive outcomes of IVF cycle. What the implications are of these findings for clinical practice and/or further research? Calcium infusion should be used to minimise the incidence of OHSS in IVF patients at high risk for OHSS.