Incidence Of Ovarian Hyperstimulation Syndrome Research Articles

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).

Follitropin delta combined with menotropin in patients at risk for poor ovarian response during in vitro fertilization cycles: a prospective controlled clinical study

BackgroundThe maximum daily dose of follitropin delta for ovarian stimulation in the first in vitro fertilization cycle is 12 μg (180 IU), according to the algorithm developed by the manufacturer, and based on patient’s ovarian reserve and weight. This study aimed to assess whether 150 IU of menotropin combined with follitropin delta improves the response to stimulation in women with serum antimullerian hormone levels less than 2.1 ng/mL.MethodsThis study involved a prospective intervention group of 44 women who received 12 μg of follitropin delta combined with 150 IU of menotropin from the beginning of stimulation and a retrospective control group of 297 women who received 12 μg of follitropin delta alone during the phase 3 study of this drug. The inclusion and exclusion criteria and other treatment and follow-up protocols in the two groups were similar. The pituitary suppression was achieved by administering a gonadotropin-releasing hormone (GnRH) antagonist. Ovulation triggering with human chorionic gonadotropin or GnRH agonist and the option of transferring fresh embryos or using freeze-all strategy were made according to the risk of developing ovarian hyperstimulation syndrome.ResultsWomen who received follitropin delta combined with menotropin had higher estradiol levels on trigger day (2150 pg/mL vs. 1373 pg/mL, p < 0.001), more blastocysts (3.1 vs. 2.4, p = 0.003) and more top-quality blastocysts (1.8 vs. 1.3, p = 0.017). No difference was observed in pregnancy, implantation, miscarriage, and live birth rates after the first embryo transfer. The incidence of ovarian hyperstimulation syndrome did not differ between the groups. However, preventive measures for the syndrome were more frequent in the group using both drugs than in the control group (13.6% vs. 0.6%, p < 0.001).ConclusionsIn women with serum antimullerian hormone levels less than 2.1 ng/mL, the administration of 150 IU of menotropin combined with 12 μg of follitropin delta improved the ovarian response, making it a valid therapeutic option in situations where ovulation triggering with a GnRH agonist and freeze-all embryos strategy can be used routinely.Trial registrationU1111-1247-3260 (Brazilian Register of Clinical Trials, available at https://ensaiosclinicos.gov.br/rg/RBR-2kmyfm).

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.

Prevention of OHSS

Ovarian hyperstimulation syndrome (OHSS), perhaps the most serious complication arising from in vitro fertilization (IVF), is rare but life-threatening in some cases. In this lecture, we will first delve into the pathophysiology of OHSS and hallmark features such as hemoconcentration, hypercoagulability, electrolyte imbalances, fluid loss into third space, and renal insufficiency. In addition, clinical vignettes will illustrate some of the most severe cases of OHSS. Next, various methods for identifying patients at high risk of OHSS will be discussed. Available literature indicates that younger age and polycystic ovarian syndrome (PCOS) may be associated with the incidence of OHSS. Ovarian reserve markers such as anti-müllerian hormone (AMH) and antral follicle counts (AFC) have been suggested as useful screening tools. Also, stimulation cycle profiles, such as developing multiple follicles, peak serum estradiol levels, and the number of retrieved oocytes, may aid in identifying those at high risk. To lower the incidence of OHSS, modifying controlled ovarian stimulation (COS) protocols is essential. Evidence suggests that gonadotropin-releasing hormone (GnRH) antagonist protocol is beneficial in reducing the risk of OHSS. Medications such as dopamine agonists, aspirin, and metformin may be associated with lower risk while using clomiphene citrate remains controversial. “Coasting,” which is holding gonadotropins for several days to decrease the OHSS risk, has been suggested as another strategy. Triggering could be done differently using a GnRH agonist. Cycle segmentation by cryopreserving oocytes and embryos is also a feasible option. Close monitoring and early detection of symptoms are essential for prompt intervention and management of OHSS. By implementing preventative measures and closely monitoring patients, physicians may reduce the incidence and severity of OHSS and ensure safer fertility treatments.

Optimising Ovulation Induction in PCOS

Biochemical, Metabolic and Endocrine changes in PCOS result in reproductive impairment in women with PCOS. Controlled ovarian stimulation (COS) may be associated with • Unpredictable response • Response may be slow • Hyper-response - OHSS • Risk of Cyst Formation • Poor oocyte quality • Miscarriage • Cycle cancellation So, the ovulation induction protocol should be efficacious and safe resulting in a singleton live birth, minimising complications, and risks like ovarian hyperstimulation syndrome (OHSS), multiple pregnancies and cancellation of cycles. For this special consideration should be given to prediction of response, pre-treatment, choosing the right ovulation induction (OI) protocol with right dose and analogue, using GnRH agonist trigger instead of hCG, preventing late follicular phase rise in progesterone, or following the segmentation protocol. We can maximize the success rates by stimulation individualization based on age, AMH, AFC and amended further for BMI. AMH is considered as more sensitive marker to define follicle excess than AFC as it appraises more follicle classes - preantral and early antral. One should probably use mild stimulation protocols where gonadotropins are given in combination with oral ovulogens or the low dose step up protocol. It is essential that we use GnRH antagonist protocol and administer GnRH agonist if there is risk of OHSS. If segmentation protocol is used one could also use the progesterone primed ovarian stimulation instead of GnRG antagonist. One could reduce the incidence of OHSS by laparoscopic ovarian drilling and use of Metformin and aspirin before assisted reproduction. If the patient is at risk of developing OHSS during stimulation then one could administer cabergoline, intravenous infusion of calcium gluconate or albumin and methylprednisolone. But freezing all embryos and transferring them in a subsequent cycle increase the efficacy and reduce complications of ART in PCOS women. Elective single embryo transfer(eSET) should be the norm to reduce the multiple pregnancy rate. Conclusion Thus, in all ART cycles individualised COS with freeze all and eSET could help in increasing the success of ART and reducing stress and anxiety and complications in these women.

#210 : The Comparison of Agonist Trigger and Dual Trigger in Our IVF Population - A Single Center Retrospective Study

Background: For years, human chorionic gonadotropin (hCG) has been the trigger of choice for oocyte maturation due to its molecular and biological similarity with LH, but its longer half-life compared to LH contributes to the ovarian hyperstimulation syndrome (OHSS) in hyper responders. Besides, hCG lacks FSH activity, which plays a role in the in vitro maturation of oocytes. Gonadotropin-releasing hormone (GnRH) agonists which can bring endogenous release of both FSH and LH and have a shorter mean duration of LH surge, and effectively reduce the incidence of OHSS in high responders. However, the substitution of agonist as trigger is associated with the risk of empty follicle syndrome, increased early pregnancy loss and decreased rates of ongoing pregnancy. The idea of a dual trigger where hCG component could serve as a rescue in case of poor response to GnRH-agonist, occurring in about 2.71% of ART population, and agonist bringing FSH &amp; LH surge simultaneously leading to improved oocyte quality was the basis for present study. Aim &amp; objective: To observe the difference between agonist trigger and dual trigger in various ovarian reserve groups. Materials &amp; Methods: Retrospective cohort study in patients attending Eva fertility clinic &amp; IVF center between 2021-2022. Total patients =157 agonist trigger =57 dual trigger = 100 Age: 24 years to 41 years Average BMI 26 AMH :2.0 ng-6.6 ng/ml Primary outcome: Clinical pregnancy rate &amp; ongoing pregnancy rate Secondary outcome: Blastocyst formation rate Total M2 achieved. Result: Pregnancy’ in (AMH: &lt;2 ng/mL)- no significant difference between the various groups in terms of distribution of Pregnancy ([Formula: see text]2= 0.209, p = 1.000). (Table 1) Pregnancy’ in (AMH: 2-5 ng/mL)- no significant difference ([Formula: see text]2= 0.023, p = 0.880). (Table 2) Pregnancy’ in (AMH: &gt;5 ng/mL)- no significant difference ([Formula: see text]2= 0.286, p = 0.711). (Table 3) Limitation of the study- small sample size, lack of plain hCG trigger group to compare as an arm 3. Conclusion: Dual trigger treatment with GnRH agonist and hCG is not inferior in terms of live birth rate, blastocyst, &amp; M2 oocytes compared to GnRH agonist &amp; hCG trigger apart from avoiding the danger of OHSS.

Effect of GnRH agonist trigger with or without low-dose hCG on reproductive outcomes for PCOS women with freeze-all strategy: a propensity score matching study.

This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy. A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2mg GnRHa) and dual-trigger group (0.2mg GnRHa plus 1000/2000IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes. After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05). For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.

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.

Beyond the Umbrella: A Systematic Review of the Interventions for the Prevention of and Reduction in the Incidence and Severity of Ovarian Hyperstimulation Syndrome in Patients Who Undergo In Vitro Fertilization Treatments.

Ovarian hyperstimulation syndrome (OHSS) is the main severe complication of ovarian stimulation for in vitro fertilization (IVF) cycles. The aim of the current study was to identify the interventions for the prevention of and reduction in the incidence and severity of OHSS in patients who undergo IVF not included in systematic reviews with meta-analyses of randomized controlled trials (RCTs) and assess and grade their efficacy and evidence base. The best available evidence for each specific intervention was identified, analyzed in terms of safety/efficacy ratio and risk of bias, and graded using the Oxford Centre for Evidence-Based Medicine (CEBM) hierarchy of evidence. A total of 15 interventions to prevent OHSS were included in the final analysis. In the IVF population not at a high risk for OHSS, follitropin delta for ovarian stimulation may reduce the incidence of early OHSS and/or preventive interventions for early OHSS. In high-risk patients, inositol pretreatment, ovulation triggering with low doses of urinary hCG, and the luteal phase administration of a GnRH antagonist may reduce OHSS risk. In conclusion, even if not supported by systematic reviews with homogeneity of the RCTs, several treatments/strategies to reduce the incidence and severity of OHSS have been shown to be promising.

The efficacy of GnRH agonist trigger followed by hCG add-back in normal responders for fresh embryo transfer: a case-control analysis from Vietnam

Aim: to assess the effects of a dual trigger by gonadotrophin-releasing hormone (GnRH) agonist and low-dose human chorionic gonadotropin (hCG) on in vitro fertilization (IVF) outcomes in women with normal ovarian response.Materials and Methods. This case-control analysis comprised 118 patients who responded normally to ovarian stimulation with a GnRH antagonist protocol at Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between January 2018 and October 2019. Recruitment was achieved through case-control matching: a case (with Dual trigger – group A) was paired with control (with hCG trigger – group B) in a 1:1 ratio. The primary markers of success were the retrieval of oocytes and embryological data, the pregnancy rate, and the incidence of ovarian hyperstimulation syndrome (OHSS).Results. 59 patients in group A and 59 women in group B were recruited. Two groups had comparable patient characteristics and ovarian reserve. The initial dose, total dose, duration of gonadotropin administration, and peak of estradiol level were not statistically different across groups. The number of recovered oocytes (10.3 ± 4.2 vs. 10.0 ± 3.3; p = 0.663), mature oocytes (8.6 ± 3.7 vs.8.1 ± 2.8; p = 0.346), and high-quality embryos (56.2 ± 28.9 vs. 59.8 ± 35.9; p = 0.555) was equivalent. Fertilization, clinical pregnancy, and live birth rates were comparable between the dual trigger and hCG groups. In neither group were any occurrences of OHSS seen.Conclusion. Dual trigger may substitute hCG for final oocyte maturation and fresh embryo transfer in patients with normal responses to GnRH antagonist protocol-induced ovarian stimulation without compromising IVF outcomes.

Finding of the optimal preparation and timing of endometrium in frozen-thawed embryo transfer: a literature review of clinical evidence.

Frozen-thawed embryo transfer (FET) has been a viable alternative to fresh embryo transfer in recent years because of the improvement in vitrification methods. Laboratory-based studies indicate that complex molecular and morphological changes in endometrium during the window of implantation after exogenous hormones with controlled ovarian stimulation may alter the interaction between the embryo and endometrium, leading to a decreased implantation potential. Based on the results obtained from randomized controlled studies, increased pregnancy rates and better perinatal outcomes have been reported following FET. Compared to fresh embryo transfer, fewer preterm deliveries, and reduced incidence of ovarian hyperstimulation syndrome were found after FETs, yet there is a trend of increased pregnancy-related hypertensive diseases in women receiving FET. Despite the increased application of FET, the search for the most optimal priming protocol for the endometrium is still undergoing. Three available FET protocols have been proposed to prepare the endometrium: i) natural cycle (true natural cycle and modified natural cycle) ii) artificial cycle (AC) or hormone replacement treatment cycle iii) mild ovarian stimulation (mild-OS) cycle. Emerging evidence suggests that the optimal timing for FET using warmed blastocyst transfer is the LH surge+6 day, hCG administration+7 day, and the progesterone administration+6 day in the true natural cycle, modified natural cycle, and AC protocol, respectively. Although still controversial, better clinical pregnancy rates and live birth rates have been reported using the natural cycle (true natural cycle/modified natural cycle) compared with the AC protocol. Additionally, a higher early pregnancy loss rate and an increased incidence of gestational hypertension have been found in FETs using the AC protocol because of the lack of a corpus luteum. Although the common clinical practice is to employ luteal phase support (LPS) in natural cycles and mild-OS cycles for FET, the requirement for LPS in these protocols remains equivocal. Recent findings obtained from RCTs do not support the routine application of endometrial receptivity testing to optimize the timing of FET. More RCTs with rigorous methodology are needed to compare different protocols to prime the endometrium for FET, focusing not only on live birth rate, but also on maternal, obstetrical, and neonatal outcomes.

The value of LH maximum level in predicting optimal oocyte yield following GnRH agonist trigger.

Risk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone. We retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle. Following confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035-47.274). Group 1 (b = -12.72; 95% CI -20.9 to -4.55) and BMI (b = -0.25; 95% CI -0.5 to -0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS. The maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes.

The therapeutic effects of rFSH versus uFSH/uHMG on ovarian stimulation in women undergoing assisted reproductive technology: a meta-analysis of randomized controlled trials.

This systematic review and meta-analysis aimed to compare the therapeutic effects of rFSH versus uFSH/uHMG on ovarian stimulation in women undergoing assisted reproductive technology. The databases of PubMed, Embase, and the Cochrane Library were systematically searched to retrieve data on eligible trials from inception until July 2022. The relative risks (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs) were applied to assess categorical and continuous outcomes, and the pooled results were calculated using the random-effects model. Sensitivity, subgroup, and publication bias analyses were also performed. Forty-eight trials that enrolled 10,127 women were included in this quantitative meta-analysis. There were no significant differences between rFSH and uFSH/uHMG in the clinical pregnancy rate (RR: 1.01; 95% CI 0.95-1.07; P = 0.760), live birth rate (RR: 0.98; 95% CI 0.91-1.06; P = 0.665), multiple pregnancy rate (RR: 0.92; 95% CI 0.77-1.09; P = 0.320), miscarriage rate (RR: 1.17; 95% CI 0.94-1.46; P = 0.151), and the incidence of ovarian hyperstimulation syndrome (RR: 1.25; 95% CI 0.91-1.70; P = 0.164). In addition, the administration of rFSH was associated with a higher number of oocyte retrieval compared with that of uFSH/uHMG (WMD: 0.61; 95% CI 0.03-1.20; P = 0.038), while no significant differences were found between rFSH and uFSH/uHMG in the dosage of gonadotrophin (WMD: 14.80; 95% CI -136.97 to 166.57; P = 0.848) and the duration of ovarian stimulation (WMD: -0.26; 95% CI -0.62 to 0.10; P = 0.152). Thus, the exploratory analyses revealed several potential differences in the effects of rFSH versus uFSH/uHMG on ovarian stimulation. The administration of rFSH significantly increased the number of oocytes retrieved, whereas there were no significant differences between the efficacies of rFSH and uFSH/uHMG for pregnancy outcomes.

Guideline No. 315: Prevention of Ovarian Hyperstimulation Syndrome

Summary Statements1.The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I)2.Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III)3.Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2)4.The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I)5.There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III)6.Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2)7.Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2)8.Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations1.The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)2.Gonadotropin dosing should be carefully individualized, taking into account the patient’s age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B)3.Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C)4.Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B)5.A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C)6.Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E)7.Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C)8.Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A)9.Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B)

P-205 comparison of GnRH antagonist protocol versus progestin-primed protocol in high ovarian responders: a propensity score-matched study

Abstract Study question To compare the clinical outcomes and cost-efficiency between gonadotropin-releasing hormone (GnRH) antagonist and progestin-primed ovarian stimulation (PPOS) protocol in high ovarian responders. Summary answer Comparing with PPOS protocol, GnRH antagonist protocol was associated with shorter time to live birth, higher OHSS rate and less cost in high responders. What is known already For high ovarian responders prone to develop ovarian hyperstimulation syndrome (OHSS), the best option should be the GnRH antagonist, as it has been shown to significantly reduce the incidence of OHSS. By applying ovarian stimulation using the combination of antagonist with agonist trigger and embryos freezing, OHSS can be erased. PPOS protocol in combination with a freeze-all strategy has proved to be a valid alternative to the conventional stimulation protocols. Recent studies showed that comparing with antagonist protocol, a lower cumulative live birth rate (CLBR) was associated with PPOS in general population, with no data available in high responders. Study design, size, duration This was a propensity score-matched retrospective cohort study. From Jan. 2016 to Jan. 2023, 5810 patients with AMH &amp;gt; 3.67ng/ml undergoing IVF treatment with antagonist or PPOS protocol at the Sixth Affiliated Hospital of Sun Yat-sen University were screened. Participants/materials, setting, methods Two-to-one propensity score matching was performed with a caliper of 0.2. After matching, 540 patients in GnRH antagonist group and 270 patients in PPOS group were included. Generalized estimated equation regression was applied to evaluate the impact of independent variables on the CLBR. Main results and the role of chance No significant difference in baseline characteristics was found in two groups. The OHSS (moderate to severe) rate was significantly higher in the GnRH antagonist group than in the PPOS group (7% vs. 3%). The clinical pregnancy rate and live birth rate per transfer were comparable between the two groups. After excluding patients who didn't achieve live birth but had surplus embryos, the CLBR was comparable between the antagonist and PPOS group (67.4% vs. 61.0%; Risk ratio = 1.106; 95% confidence interval [CI], 0.973-1.256, P = 0.109), and the generalized estimated equation regression analysis also showed that protocol selection had no significant impact on CLBR. The average time to live birth (TTLB) in the antagonist group was significantly shorter than the PPOS group (11.45 months vs. 12.13 months, P &amp;lt; 0.05). Besides, the average cost in the antagonist group was about $4933, while it was about $5465 in the PPOS group. Limitations, reasons for caution Although we recruited a large sample size and the sophisticate statistical analysis method, this was a retrospective study with an intrinsic limitation, besides more patients in the PPOS group had surplus embryos than in the antagonist group (24.1% vs. 19.8%). Further prospective RCTs are required to confirm our findings. Wider implications of the findings For infertile patients with high ovarian reserve, the clinical outcomes were comparable between GnRH antagonist and PPOS group. The antagonist group was associated with a shorter TTLB and more cost-effective, while the PPOS was associated with a lower OHSS rate. Trial registration number Not Applicable

Retracted: Clinical Pregnancy and Incidence of Ovarian Hyperstimulation Syndrome in High Ovarian Responders Receiving Different Doses of hCG Supplementation in a GnRH-Agonist Trigger Protocol.

[This retracts the article DOI: 10.1155/2021/2180933.].

Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial

BackgroundCurrently, optimal method of ovarian stimulation (OS) to in-vitro fertilization (IVF) in the patients with polycystic ovarian syndrome (PCOS) is unknown. The present research aims to study the efficiency of minimal-OS method in treatment of infertile patients with PCOS and also the effect of gonadotropin type (recombinant FSH (r-FSH) vs. urinary Human menopausal gonadotropin (u-HMG)) on treatment cycles with GnRH-antagonist.MethodsIn this randomized controlled trial, a total of 120 eligible patients were randomly allocated into four groups of OS to IVF: minimal-OS with r-FSH, minimal-OS with u-HMG, mild-OS with r-FSH and mild-OS with u-HMG. IVF outcomes of groups were analyzed statically.ResultsThe statistical analysis showed that there were significant differences among groups regarding stimulation duration (p < 0.0001), number of retrieved oocytes (p < 0.0001), number of obtained embryos (p < 0.0001). There were no statistically significant differences in fertilization rate (p = 0.289) and implantation rate (p = 0.757) among our participants. There were also significant differences among these four groups in terms of clinical pregnancy rate (/ET and /cycles) (p < 0.0001, p = 0.021, respectively) and live birth rate/cycles (p < 0.0001). Also cases of freeze all embryos due to prevention of ovarian hyper stimulation syndrome (OHSS) (p = 0.004).ConclusionsOn the basis of present results the minimal-OS with u-HMG may be one of optimal methods of control OS in the patients with PCOS in respect to serum levels of estradiol on the day of triggering final oocyte maturation, total dose of prescribed gonadotropin, the optimal number of oocytes and embryos obtained, rate of clinical pregnancy and the incidence of OHSS risk.Trial registrationNCT, NCT03876145. Registered 15/03/2019. Retrospectively registered, http://www.clinicaltrial.gov/ NCT03876145.

Fresh versus frozen embryo transfer in women with polycystic ovaries syndrome undergoing in vitro fertilisation

BackgroundPolycystic ovarian syndrome (PCOS) cases undergoing in vitro fertilisation (IVF) are widely at risk of ovarian hyperstimulation; therefore, elective freezing of all embryos to be transferred in a later cycle is preferred. We aimed to compare the pregnancy outcome between the fresh and the frozen embryo transfer (ET) in PCOS cases undergoing IVF with antagonist ovarian induction using human chorionic gonadotropin (HCG) as a trigger.MethodsIn this prospective randomised study, 110 infertile PCOS women underwent fresh ET (group A) or frozen ET (group B) with GnRH-antagonist protocol. The primary outcome was the chemical and clinical pregnancy rates. The secondary outcomes were the ongoing pregnancy rate, ovarian hyperstimulation syndrome (OHSS) rate, pregnancy loss rate, ectopic pregnancy rate, and congenital anomalies rate.ResultsThere was no significant difference between both groups regarding chemical pregnancy rate (44.23% vs 47.27%, P = 0.752), clinical pregnancy rate (42.31% vs 43.64%, P = 0.89), ongoing pregnancy rate (38.46% vs 41.82%, P = 0.723), pregnancy loss rate (17.39% vs 15.4%, P = 1), ectopic pregnancy rate (1.92% vs 0%, P = 0.486) and anomaly malformation rate (4.35% vs 3.85%, P = 1). On the other hand, the incidence of OHSS was significantly less in group B than in group A (3.64% vs 19.23%, P = 0.011), and the OHSS grade was less severe in group B than in group A (P = 0.033). However, there was no statistically significant difference between both regarding the need for hospitalisation (P = 0.111), ICU admission (P = 0.486), and ascites tapping (P = 0.486).ConclusionsUnder GnRH-antagonist protocol, frozen ET has the upper hand in PCOS undergoing IVF treatment for infertility, as it protects against OHSS and decreases its severity.Trial registrationIt was first registered at ClinicalTrials.gov on 22/12/2021 with registration number NCT05167838.

Differences in Follicle Development and Hormone Dynamics Between Controlled Ovarian Stimulation (COS) Using Follitropin Delta and that Using Follitropin Alfa

Background: We compared the performance of follitropin delta and follitropin alfa in the gonadotropin-releasing hormone (GnRH) antagonist protocol for controlled ovarian stimulation (COS) and discussed the distinctive features of follitropin delta in COS. Methods: Patients underwent COS using the GnRH antagonist protocol with either recombinant follicle-stimulating hormone (FSH) and oocytes were retrieved. We compared the results of COS, oocyte pick up, fertilization, embryo culture, and clinical pregnancy between the follitropin alfa group and the follitropin delta group. Results: The serum estrogen level at trigger was significantly lower in the delta than in the alfa group (3,576.69 ± 1,775.60 vs. 2,833.19 ± 1,567.88) as was serum P4 level (2.14 ± 1.26 vs. 1.19 ± 0.85). The stimulation duration (in days) were longer (12.97 ± 2.38 vs. 13.96 ± 2.26) and total gonadotropin dose significantly lower (199.69 ± 54.47 vs. 114.27 ± 39.92), respectively, in the delta group than in the alfa group. The ovarian hyperstimulation syndrome (OHSS) rate was significantly lower in the delta than in the alfa group (48.1% vs. 58.6%). Fertilization, good blastocyst, and clinical pregnancy rates were not significantly different. COS using follitropin delta is characterized by significantly slower follicle development than COS using follitropin alfa. A comparison of developing follicles showed that the minimum follicle was significantly smaller in the delta group on days 6–8 of COS. The maximum follicle was significantly smaller in the delta group on days 6–8 and 11–13 of COS. The number of follicles larger than 14 mm was significantly lower in the delta group on days 6–8 of COS. Conclusions: Using follitropin delta is associated with slow follicular development, slow serum E2 elevation, and longer stimulation duration; however, excessive elevation of serum estrogen levels during COS is reduced and so is the incidence of mild OHSS.

The Effect of Follitropin Alfa in Controlled Ovarian Stimulation Protocol for In Vitro Fertilization Cycles.

Follitropin alfa (FA) is one of the most widely used exogenous gonadotropins in both agonist and antagonist protocols for controlled ovarian stimulation (COS) and in vitro fertilization (IVF). However, reports of its effectiveness are limited, particularly in terms of its impact on overall IVF outcomes and ovarian hyperstimulation syndrome (OHSS). Therefore, in this study, FA competency was investigated by evaluating its effect on IVF outcomes and OHSS, administering agonist and antagonist COS protocols. A retrospective study with 120 subjects was conducted. Outcomes comprising the number of retrieved and fertilized oocytes, quality of embryos, and clinical pregnancies were assessed. Statistical correlation between FA dose, IVF outcomes, and the incidence of OHSS was also analyzed. All statistical analyses were performed at 95% confidence level. There was no significant difference in both protocols regarding retrieved oocytes (p=0.604), fertilized oocytes (p=0.761), embryo quality including good, average, poor embryo (p=0.875, p=0.565, p=0.785), and clinical pregnancy (p= 0.844). However, FA doses in the agonist protocol were shown notably higher (p= 0.001). Negative correlations were also observed between FA dose and the number of retrieved oocytes (r=-0.255, p<0.01), fertilized oocytes (r=-0.296, p<0.01), and good quality embryos (r=-0.231, p<0.05). Our study suggested that FA yields similar outcomes in both COS protocols, but agonist protocols require higher doses of FA and evaluation of its effect on OHSS is an important area of research for further investigation.