Risk Of Ovarian Hyperstimulation Syndrome Research Articles

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2ng/mL or 3-day area under the curve > 4.5ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol 4000pg/mL had a greater likelihood of GBO compared to cycles < 1000pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000pg/mL versus 1000-1999pg/mL and 1000-1999pg/mL versus 2000-2999pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999pg/mL versus 3000-3999pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999pg/mL versus 4000pg/mL, aRR 0.96, 95% CI 0.9-1.04). In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.

Observation on efficacy and underlying mechanism of cheek acupuncture on ovulation induction for infertile women with PCOS: Case series.

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of childbearing age and is the primary cause of anovulatory infertility, accounting for 70% to 80% of cases. Ovulation induction is the main treatment approach for infertile patients with PCOS. Commonly utilized medications for this purpose are clomiphene citrate (CC) and letrozole (LE). Clomiphene citrate administration results in an ovulation rate ranging from 60% to 85%, while the pregnancy rate is limited to 35% to 40%, and a further reduction is observed in live birth rates. Letrozole demonstrates a slightly higher pregnancy rate and live birth rate compared to clomiphene citrate, although challenges persist in terms of longer stimulation cycles, multiple pregnancies, and the risk of ovarian hyperstimulation syndrome (OHSS). Clinical reports indicate that acupuncture therapy shows promising efficacy in treating patients with PCOS-related infertility, despite a partially unclear understanding of its underlying mechanisms. In this study, one patient did not achieve pregnancy despite more than a year of ovulation induction using clomiphene citrate and letrozole. However, after 3 months of receiving cheek acupuncture therapy, she successfully conceived and gave birth to a liveborn baby. Another patient achieved natural conception and live birth after 2 months of exclusive cheek acupuncture therapy. PCOS. Cheek acupuncture therapy. Both of them successfully conceived and gave birth to a liveborn baby. These findings suggest that cheek acupuncture therapy can effectively stimulate follicle development and ovulation, potentially improving endometrial receptivity. According to holographic theory, there is a biologically holographic model within the cheek region that shares a homology with the human body structure. This model provides an explanation for the regulatory effects of cheek acupuncture point stimulation on the Hypothalamic-Pituitary-Ovarian axis (HPO), which subsequently influences follicle development and ovulation in patients. Consequently, when cheek acupuncture therapy is applied alone or in combination with ovulation induction medication, patients have the ability to achieve successful pregnancy and experience a smooth delivery.

Risk factors for poor oocyte yield and oocyte immaturity after GnRH agonist triggering.

What are the potential risk factors for poor oocyte recuperation rate (ORR) and oocyte immaturity after GnRH agonist (GnRHa) ovulation triggering? Lower ovarian reserve and LH levels after GnRHa triggering are risk factors of poor ORR. Higher BMI and anti-Müllerian hormone (AMH) levels are risk factors of poor oocyte maturation rate (OMR). The use of GnRHa to trigger ovulation is increasing. However, some patients may have a suboptimal response after GnRHa triggering. This suboptimal response can refer to any negative endpoint, such as suboptimal oocyte recovery, oocyte immaturity, or empty follicle syndrome. For some authors, a suboptimal response to GnRHa triggering refers to a suboptimal LH and/or progesterone level following triggering. Several studies have investigated a combination of demographic, clinical, and endocrine characteristics at different stages of the treatment process that may affect the efficacy of the GnRHa trigger and thus be involved in a poor endocrine response or efficiency but no consensus exists. Bicentric retrospective cohort study between 2015 and 2021 (N = 1747). All patients aged 18-43 years who underwent controlled ovarian hyperstimulation and ovulation triggering by GnRHa alone (triptorelin 0.2 mg) for ICSI or oocyte cryopreservation were included. The ORR was defined as the ratio of the total number of retrieved oocytes to the number of follicles >12 mm on the day of triggering. The OMR was defined as the ratio of the number of mature oocytes to the number of retrieved oocytes. A logistic regression model with a backward selection method was used for the analysis of risk factors. Odds ratios (OR) are displayed with their two-sided 95% confidence interval. In the multivariate analysis, initial antral follicular count and LH level 12-h post-triggering were negatively associated with poor ORR (i.e. below the 10th percentile) (OR: 0.61 [95% CI: 0.42-0.88]; P = 0.008 and OR: 0.86 [95% CI: 0.76-0.97]; P = 0.02, respectively). A nonlinear relationship was found between LH level 12-h post-triggering and poor ORR, but no LH threshold was found. A total of 25.3% of patients suffered from oocyte immaturity (i.e. OMR < 75%). In the multivariate analysis, BMI and AMH levels were negatively associated with an OMR < 75% (OR: 4.34 [95% CI: 1.96-9.6]; P < 0.001 and OR: 1.22 [95% CI: 1.03-1.12]; P = 0.015, respectively). Antigonadotrophic pretreatment decreased the risk of OMR < 75% compared to no pretreatment (OR: 0.72 [95% CI: 0.57-0.91]; P = 0.02). Our study is limited by its retrospective design and by the exclusion of patients who had hCG retriggers. However, this occurred in only six cycles. We were also not able to collect information on the duration of pretreatment and the duration of wash out period. In clinical practice, to avoid poor ORR, GnRHa trigger alone should not be considered in patients with higher BMI and/or low ovarian reserve, balanced by the risk of ovarian hyperstimulation syndrome. In the case of a low 12-h post-triggering LH level, practicians must be aware of the risk of poor ORR, and hCG retriggering could be considered. None. N/A.

Age at menarche and risk of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI cycles: a retrospective cohort study

ObjectivesWe aimed to explore the association between age at menarche (AAM) and ovarian hyperstimulation syndrome (OHSS) in fresh in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles.DesignA retrospective cohort study.SettingData were...

Personalizing the first dose of FSH for IVF/ICSI patients through machine learning: a non-inferiority study protocol for a multi-center randomized controlled trial

BackgroundAdequately selecting the initial follicle-stimulating hormone (FSH) dose during controlled ovarian stimulation (COS) is key for success in assisted reproduction. The objective of COS is to obtain an optimal number of oocytes to increase the chances of achieving a pregnancy, while avoiding complications for the patient. Current clinical protocols do achieve good results for the majority of patients, but further refinements in individualized FSH dosing may reduce the risk of poor ovarian response while also limiting the risk of ovarian hyperstimulation syndrome (OHSS) risk. Models to select the first FSH dose in COS have been presented in literature with promising results. However, most have only been developed and tested in normo-ovulatory women under the age of 40 years.MethodsThis is a randomized, controlled, multicenter, single blinded, clinical trial. This study will be performed in 236 first cycle in vitro fertilization (IVF) and/or ICSI (intracytoplasmic sperm injection) patients, randomized 1:1 in two arms. In the intervention arm, the dose of FSH will be assigned by a machine learning (ML) model called IDoser, while in the control arm, the dose will be determined by the clinician following standard practice. Stratified block randomization will be carried out depending on the patient being classified as expected low responder, high responder, or normo-responder. Patients will complete their participation in the trial once the first embryo transfer result is known. The primary outcome of the study is the number of metaphase II (MII) oocytes retrieved at ovarian pick up (OPU) and the hypothesis of non-inferiority of the intervention arm compared to the control. Secondary outcomes include the number of cycle cancelations (due to low response or no retrieval of mature oocytes), risk of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancy and live birth rates per first transfer.DiscussionTo our knowledge, this is the first randomized trial to test clinical performance of an all-patient inclusive model to select the first dose of FSH for COS. Prospective trials for machine learning (ML) models in healthcare are scarce but necessary for clinical application.Trial registrationClinicalTrials.gov, NCT05948293. Registered on 14 July 2023.

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).

Dealing with specialist pathology: an unusual case of ovarian hyperstimulation syndrome managed in the emergency department with point of care ultrasound

Ovarian hyperstimulation syndrome (OHSS) is a well-known complication of assisted reproduction. The hyperstimulated ovaries release vasoactive substances that can increase capillary permeability, resulting in volume shift to the extravascular space and leading to hypovolemia, ascites and, in complicated cases, pleural and pericardial effusions, kidney and liver failure, shock. Point Of Care UltraSound (POCUS) can help the emergency physician to detect many of these complications, as well as guide their treatment. In this case report we present a patient at low risk for OHSS who recently underwent a successful in vitro fertilization, coming to the emergency department with an unusual complication of OHSS (an isolated pleural effusion), that has been safely and promptly diagnosed and treated in the emergency room with the help of POCUS, without any unnecessary exposition to ionizing radiations.

#86 : Use of Triptorelin Versus Human Chorionic Gonadotropin as Ovulation Trigger

Background and Aims: Gonadotropin releasing hormone agonist (GnRH-a) trigger has been shown to be associated with significantly lower risk of moderate or severe ovarian hyperstimulation syndrome (OHSS) when compared among women at high risk of OHSS. However, trigger failure has been shown to occur in 2% of cycles using GnRH-a as trigger. This study aims to review the use of GnRH-a as ovulation trigger. Method: Retrospective review of records in antagonist cycles from an ART unit in a tertiary hospital from 2017-2021 was performed. Follicles were considered mature when they reach [Formula: see text] 15 mm. Ovulation triggered with urinary human chorionic gonadotropin (uhCG) (5000-10000 IU), recombinant hCG (rhCG) 250 mcg, or triptorelin 0.2 mg when there were [Formula: see text] 3 mature follicles. All embryos obtained from cycles using triptorelin were cryopreserved. Outcome including the number of oocytes retrieved, the follicle to oocyte index, ovarian hyperstimulation syndrome were reviewed. Results: 1378 cycles were included. 1089 cycles had uhCG or rhCG as trigger, while 284 cycles had triptorelin as trigger. Women in the triptorelin group were significantly younger with a lower basal follicle stimulating hormone level and a higher antral follicle count (Table 1). In the triptorelin group, the total number of mature sized follicles, estrogen level at trigger, oocytes retrieved, number of blastocysts were significantly higher compared to the hCG group (Table 2). Follicle to oocyte index was significantly higher in the triptorelin group but the proportion of mature oocytes were similar in both groups. There were no cases of trigger failure and OHSS in the triptorelin group, but 30 cases of OHSS, with18 cases early onset, 12 cases late onset, amongst them 10 cases (1%) were severe OHSS) in the hCG group. Conclusion: GnRH-a trigger is a good candidate as ovulatory trigger in women at risk of OHSS without hampering the laboratory outcome.

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.

#394 : The Efficacy of an Individualized Dose of Follitropin Delta on Ovary Reproductive Stimulation and Clinical Outcomes

Background and Aims: Follitropin delta is the third recombinant human follicle-stimulating hormone (r-hFSH) expressed in a host cell line of human fetal retinal origin that currently emphasizes that the actual tendency of administration is a personalized dosing algorithm based on the anti-Mullerian hormone (AMH) and body mass index (BMI) for ovarian stimulation. Methods: In this present manuscript, we aimed to gather all available data published between 2018–2022 regarding the co-administration and administration of follitropin delta and the clinical outcomes reported following an in vitro fertilization (IVF). Results: Follitropin delta is non-inferior in contrast to its previously launched agents for ovarian stimulation, enhancing a similar-to-superior response reflected by both the reproductive and pregnancy outcomes in parallel with a low risk of ovarian hyperstimulation syndrome (OHSS), being well tolerated. The body weight and AMH level are factors that may influence the outcome in a patient. Despite controversy and results that refute these arguments on several occasions, follitropin delta exceeds the benefits of conventional dosing with either follitropin alfa or follitropin beta. Therefore, all post hoc derived analyzes and subgroups of patients who participated in subsequent studies support this statement. Conclusion: Despite the relatively limited range of data in the current literature, most authors provide strong evidence to support the later use of this drug according to patient profiles and overcoming ethnic limitations. Others disagree with these observations, but this topic and this drug have great potential. As such, additional research is needed to fill existing knowledge gaps and extend this experience to a larger scale. Demonstrate overcoming all limitations.

Optimising IVF Outcomes

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, with an overall prevalence of 5% to 15%, and a frequent cause of infertility. Ovulation disorders are the main cause of infertility for the couples. A range of endocrine and metabolic traits are also associated with PCOS and these include obesity, dyslipidemia, insulin resistance, hyperinsulinism and an increased risk of type 2 diabetes mellitus and cardiovascular disease. Studies have found that women with PCOS had a higher live birth rate, clinical pregnancy rate and implantation rate, as well as an increased risk of ovarian hyperstimulation syndrome (OHSS), pregnancy complications including miscarriage, preterm delivery, gestational diabetes mellitus and pregnancy-induced hypertension in their first IVF treatment when compared with non-PCOS controls. During the past three decades, applying IVF for infertility treatment PCOS women has increased significantly, and the landscape of treatment strategies has changed dramatically. GnRH agonist triggering oocyte maturation combined with freeze-all embryos is an effective and commonly used protocol nowadays to achieve good success rate as well as to minimize the risk of OHSS in women with PCOS. Recently, there has been an increasing use of oocyte in-vitro maturation (IVM) for treating infertility in women with PCOS. IVM technique could be considered as an alternative to IVF in centers where it is available. However, strategies to minimize pregnancy complications in women with PCOS remain further studied.

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.

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats

Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries. These effects were similar to those of hCG, although in some cases they were less pronounced. TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis.

GnRH antagonist protocol versus progestin-primed ovarian stimulation in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

The aim of this meta-analysis was comparing the efficacy of GnRH antagonist (GnRH-ant) protocol and progestin-primed ovarian stimulation (PPOS) in polycystic ovarian syndrome (PCOS) women. A search was conducted from PubMed, Embase, The Cochrane library, Web of Science, and Scopus databases to collect clinical papers regarding GnRH-ant protocol and PPOS protocol from inception to September 2023. Subsequently, the retrieved documents were screened, and the content of the documents that conformed to the requirements was extracted. Moreover, statistical meta-analyses were conducted using the RevMan 5.4 software. Furthermore, with the use of a star-based system and the Cochrane handbook, the methodological quality of the covered papers was evaluated on the Ottawa-Newcastle scale. A total of eight papers were covered in the meta-analysis, with 2156 PCOS women enrolled (i.e., 1085 patients in the GnRH-ant protocol group and 1071 patients in the PPOS group). As indicated by the meta-analysis results, the PPOS group was correlated with a lower risk of ovarian hyperstimulation syndrome (OHSS) (SMD = 9.24, [95% CI: (2.50, 34.21)], P = 0.0009), more gonadotropin (Gn) dose (SMD = - 0.34, [95% CI: (- 0.56, - 0.13)], P = 0.002) compared with GnRH-ant group. No statistical difference was identified on the oocytes condition and pregnancy outcomes. As revealed by the data of this study, the progesterone protocol is comparable with the GnRH-ant protocol in oocytes condition and clinical outcomes. The progestin-primed ovarian stimulation could serve as an alternative for polycystic ovarian syndrome women who have failed in GnRH antagonist protocol. The above-described conclusions should be verified by more high-quality papers due to the limitation of the number and quality of included papers. PROSPERO registration: CRD42023411284.

Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from 2 randomized, placebo-controlled clinical tricals

Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 (KP54) can induce oocyte maturation during in vitro fertilization treatment, including in women at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported. ObjectiveTo determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (Phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (Phase-2a trial). DesignTwo randomized, placebo-controlled, parallel group, dose-finding trials. SettingClinical trials unit, Netherlands. ParticipantsHealthy women aged 18-35 years, either without (Phase-1; n=24), or with ovarian stimulation (Phase-2a; n=75). InterventionsPhase-1: Single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 μg) or placebo, (n=6 per dose).Phase-2a: Single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 μg; n=16-17 per dose), triptorelin 0.2 mg (n=5; active comparator), or placebo (n=5). Main Objectives and Outcome MeasuresPhase-1: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones).Phase-2a: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); time to ovulation assessed by transvaginal ultrasound. ResultsIn both trials, MVT-602 was safe and well-tolerated across the entire dose-range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours.In the Phase-2a trial, LH concentrations increased dose-dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3μg MVT-602 and remained above 15 IU/L for 33 hours. Time to ovulation following drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 μg), 88% (1μg), 82% (0.3μg), and 75% (0.1μg), of women after MVT-602, 100% after triptorelin, and 60% after placebo. ConclusionsMVT-602 induces LH concentrations of similar amplitude and duration as the physiological mid-cycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR. Trial RegistrationsEUDRA-CT: 2017-003812-38, 2018-001379-20

The Impact of Nutritional Therapy in the Management of Overweight/Obese PCOS Patient Candidates for IVF.

Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder, and it has two main pathological aspects: reproductive and metabolic. Overweight/obesity is a risk factor in terms of adverse effects during hormone stimulation, a reduced response to ovulation induction regimens, reduced success of IVF, and an increased risk of obstetric complications. To resolve this vicious cycle of pathological events, weight loss and lifestyle modifications are promising strategies. Among these possible approaches, the consumption of a very-low-calorie ketogenic diet (VLCKD) or Mediterranean diet (MD) represents a valid option. In our study, 84 obese/overweight PCOS patients were recruited to evaluate the effects induced by the VLCKD and MD on weight, hormonal, and metabolic parameters. BMI decreased significantly among the VLKCD patients compared to the MD patients (both presenting p values < 0.0001 at 90 and 120 days), and a significant reduction in body circumference was observed. At the same time, HOMA index values statistically decreased for the VLCKD patients compared to those on the MD (p value < 0.001 at 90 days and p value < 0.05 at 120 days), and this phenomenon was also observed for AFC at 90 and 120 days (both p values < 0.001) and AMH at 90 days (p value < 0.05). Interestingly, the ovarian hyperstimulation syndrome (OHSS) incidence was statistically lower in the VLKCD patients compared to the MD patients (p < 0.001). We state that these dietary regimes may improve anthropometric parameters (such as BMI) and women's reproductive health, restore menstrual regularity, and reduce the risk of OHSS. Regarding the different nutritional therapies, the results suggest that the VLCKD is an optimal choice for entry into IVF, especially in terms of the time range in which these results are achieved.

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.

Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial.

Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial.