Explore the vast range of titles available.

Background The 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. Methods This 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. Results Women 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). Conclusions In 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 registration U1111-1247-3260 (Brazilian Register of Clinical Trials, available at https://ensaiosclinicos.gov.br/rg/RBR-2kmyfm ).

IntroductionWomen with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) protocols are typically characterised by an increased number of oocytes retrieved. The oocytes are often of poor quality, leading to lower pregnancy rates, higher miscarriage rates and an increased risk of developing ovarian hyperstimulation syndrome (OHSS). Since our previous preliminary study showed that a novel progestin-primed ovarian stimulation (PPOS) protocol blocked the luteinising hormone (LH) surge during IVF and achieved a higher pregnancy rate with a lower incidence of OHSS, we designed a prospective randomised controlled trial to compare the efficacy and safety of this PPOS protocol with the flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS who are undergoing IVF procedures.Methods and analysisPatients with PCOS will be randomised to one of two controlled ovarian stimulation regimens—GnRH antagonist or PPOS—using a computer-generated random number. A freeze-all strategy using embryo vitrification techniques and frozen embryo transfer will be performed in both groups. The primary outcome is the live-birth rate per transfer. Secondary outcomes include the incidence of premature LH surges, the duration and total dose of human menopausal gonadotropin stimulation, the number of oocytes retrieved, the incidence of moderate or severe OHSS, the number of embryos available for transfer, implantation rates, clinical pregnancy rates, pregnancy loss rates, ectopic pregnancy rates, pregnancy and neonatal complications, and congenital anomalies. The necessary sample size for this trial was estimated as 392 participants, with 196 participants in each group. Intention-to-treat analysis was used in processing our experimental data.Ethics and disseminationThis study was approved by the Institutional Review Board of the hospital (2016-133-T82). The trial will be conducted according to the principles of the World Medical Association’s Declaration of Helsinki and in accordance with Good Clinical Practice standards. The findings of this trial will be published in a peer-reviewed journal.Trial registration numberChiCTRIPR16009580.

IntroductionMultimodal anticancer therapies greatly damage the fertility of breast cancer patients, which raises urgent demand for fertility preservation. The standard options for fertility preservation are oocyte and embryo cryopreservation; both require controlled ovarian hyperstimulation (COH). However, there are safety concerns regarding breast cancer relapse due to the elevated serum estradiol levels during COH. Serum estradiol levels can be effectively decreased with the highly specific aromatase inhibitor letrozole. Letrozole is still uncommonly used during COH for fertility preservation, which has only been reported in a few studies, and the evidence of oocyte retrieval during ovarian stimulation and short-term safety from the perspective study is insufficient. As a result, this study will compare the efficacy of ovarian stimulation and the short-term safety of letrozole COH and non-letrozole COH protocols for preserving fertility in patients with breast cancer.Methods and analysisThis is an open-label, multicentre RCT being conducted in five Chinese reproductive medical centres. 64 eligible patients diagnosed with breast cancer will be randomly assigned (1:1) to the letrozole or non-letrozole group during their COH cycles. The primary outcome is the number of mature oocytes. The secondary outcomes are the number of high-quality embryos, incidence of ovarian hyperstimulation syndrome(OHSS) and recurrence rate of breast cancer.Ethics and disseminationEthical approval was obtained from the Ethics Review Committee of Guangdong Provincial People’s Hospital (KY-Q-2023-840-02). Written informed consent will be obtained from each participant. Findings will be disseminated to patients, clinicians and commissioning groups through peer-reviewed publications.Trial registration numberChiCTR2300078625

Background The E-Freeze trial is a multi-centre randomised controlled trial of fresh versus frozen embryo transfer for women undergoing in vitro fertilisation. This paper describes the statistical analysis plan for the E-Freeze trial. Methods and design E-Freeze is a two-arm parallel-group, multi-centre, individually randomised controlled trial to determine if a policy of freezing embryos, followed by thawed frozen embryo transfer, results in a higher healthy baby rate when compared with the current policy of transferring fresh embryos. Couples undergoing their first, second or third cycle of in vitro fertilisation at fertility centres in the UK were randomised to either fresh or frozen embryo transfer. The primary outcome is a healthy baby, defined as a live singleton baby born at term with an appropriate weight for gestation. This paper describes the statistical analysis plan for the trial, including the analysis principles, definitions of outcomes, methods for primary analysis, pre-specified subgroup analysis and sensitivity analysis. This plan was finalised prior to completion of recruitment to the trial. Trial registration ISRCTN registry: ISRCTN61225414 . Registered on 29 December 2015.

Background Infertility affects one in seven couples; many of these need in vitro fertilisation (IVF). IVF involves external hormones to stimulate a woman’s ovaries to produce eggs which are harvested surgically. Embryos, created in the laboratory by mixing eggs with sperm, are grown in culture for a few days before being replaced within the uterus (fresh embryo transfer). Spare embryos are usually frozen with a view to transfer at a later point in time – especially if the initial fresh transfer does not result in a pregnancy. Despite improvements in technology, IVF success rates remain low with an overall live birth rate of 25–30% per treatment. Additionally, there are concerns about health outcomes for mothers and babies conceived through IVF, particularly after fresh embryo transfer, including maternal ovarian hyperstimulation syndrome (OHSS) and preterm delivery. It is believed that high levels of hormones during ovarian stimulation could create a relatively hostile environment for embryo implantation whilst increasing the risk of OHSS. It has been suggested that freezing all embryos with the intention of thawing and replacing them within the uterus at a later stage (thawed frozen embryo transfer) instead of fresh embryo transfer, may lead to improved pregnancy rates and fewer complications. We aim to compare the clinical and cost effectiveness of fresh and thawed frozen embryo transfer, with the primary aim of identifying any difference in the chance of having a healthy baby. Methods E-Freeze is a pragmatic, multicentre two-arm parallel group randomised controlled trial where women aged ≥18 and < 42 years, with at least three good quality embryos are randomly allocated to receive either a fresh or thawed frozen embryo transfer. The primary outcome is a healthy baby, defined as a term, singleton, live birth with appropriate weight for gestation. Cost effectiveness will be calculated from a healthcare and societal perspective. Discussion E-Freeze will determine the relative benefits of fresh and thawed frozen embryo transfer in terms of improving the chance of having a healthy baby. The results of this pragmatic study have the potential to be directly transferred to clinical practice. Trial registration ISRCTN registry: ISRCTN61225414 . Date assigned 29/12/2015.

The use of Gonadotrophin releasing hormone agonist (GnRHa), with freeze-all strategy followed by frozen embryo transfer (FET) has been found to eliminate the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovarian syndrome (PCOS) undergoing IVF cycles. However, physicians still hesitate to routinely use GnRHa as a trigger, replacing human chorionic gonadotrophin (hCG), for concerns of compromised cycle outcome. We aimed to evaluate outcomes following the transfer of embryos in FET cycles obtained from GnRHa trigger in comparison with hCG trigger in PCOS patients of Asian origin. Prospective observational cohort study. 210 PCOS patients undergoing IVF in an antagonist protocol who were randomized in the previous study (to evaluate if GnRHa trigger is a better alternative than hCG in PCOS patients to prevent OHSS; Group A: GnRHa trigger (n=92)] and Group B: hCG trigger (n=101)], were followed up in FET cycles to assess the outcomes. The odds of cumulative live birth rate per stimulation cycle favors GnRHa trigger against the hCG trigger [OR=2.15; (CI 1.2-3.83); p=0.008]. A significantly higher number of mature oocytes (19.1±11.7 versus 14.1±4.3; p<0.001) and blastocysts (4.2±1.63 versus 3.26±1.22; p<0.001) were available in the GnRHa group as compared to the hCG group. The cumulative live birth rate was better following transfer of frozen-thawed embryos generated from GnRHa-triggered cycles compared to hCG trigger. Hence, in PCOS undergoing IVF, as a good practice point, hCG trigger should be replaced by a GnRHa trigger with vitrification of all embryos followed by FET.

Background The aim of this study was to compare the efficacy of antagonist rescue protocol (replacing GnRH agonist with GnRH antagonist and reducing the dose of gonadotropins) combined with cabergoline versus cabergoline alone in the prevention of ovarian hyperstimulation syndrome (OHSS) in patients pretreated with GnRH agonist long protocol who were at high risk for OHSS. Methods Two hundred and thirty six patients were randomized in a 1:1 ratio to the cabergoline group or the antagonist rescue combined with cabergoline group. Both groups received oral cabergoline (0.5 mg/day) for eight days beginning on the day of HCG administration. In the antagonist rescue combined with cabergoline group, when the leading follicle reached 16 mm, GnRH agonist (triptorelin) was replaced with GnRH antagonist (cetrorelix acetate) and the dose of HP-uFSH was reduced to 75 IU/day. HCG (5,000 IU/I.M) was administered when the serum estradiol level dropped below 3500 pg/ml. The study was open label and the outcome assessors (laboratory staff and the doctor who performed oocyte retrieval) were blind to treatment allocation. Results The incidence of moderate/severe OHSS was significantly lower in the antagonist rescue combined with cabergoline group [5.08 % Vs 13.56 %, P value =0.025, OR = 0.342, 95 % CI, 0.129–0.906]. Four cycles were cancelled in the cabergoline group. There were no significant differences between the groups with respect to the number of retrieved oocytes, metaphase II oocytes, high quality embryos and fertilization rate. Moreover, the implantation and pregnancy rates were comparable between both groups. Conclusion GnRH antagonist rescue protocol combined with cabergoline is more effective than cabergoline alone in the prevention of OHSS. Trial registration Clinical trial.gov ( NCT02461875 ).

A great deal of literature has recently evaluated the prevention and management of ovarian hyperstimulation syndrome (OHSS) in the outpatient setting, but there remains a dearth of research evaluating OHSS in the emergency department (ED) and its management. This narrative review evaluates the underlying pathophysiology and clinical manifestations of OHSS and discusses approaches to patient care in the ED based on current literature. OHSS is an iatrogenic complication caused by an excessive response to controlled ovarian stimulation during assisted reproductive cycles (ART). OHSS complicates up to 30% of ART cycles, and many of these patients seek initial care in the ED. Risk factors for the development of OHSS include age < 35, history of polycystic ovarian syndrome or previous OHSS, and pregnancy. Emergency physicians will be faced with several complications including ascites, abdominal compartment syndrome, renal dysfunction, acute respiratory distress syndrome, thromboembolic disease, and hemodynamic instability. Critical patients should be evaluated in the resuscitation bay, and consultation with the primary obstetrics/gynecology team is needed, which improves patient outcomes. This review provides several guiding principles for management of OHSS and associated complications. OHSS occurs in up to 30% of IVF cycles and carries a high morbidity. Effective care of the OHSS patient begins with early diagnosis while evaluating for other diseases and complications. Understanding these complications and an approach to the management of OHSS is essential to optimizing patient care.

Background Ovarian hyperstimulation syndrome is the most severe and life-threatening iatrogenic complication of controlled ovarian stimulation during assisted reproductive technology procedures. Its diagnosis and severity grading are complex. Despite its debilitating and sometimes fatal consequences, there is a paucity of data on early predictors of ovarian hyperstimulation syndrome. Objective This study aimed to identify early predictors of ovarian hyperstimulation syndrome among women undergoing controlled ovarian stimulation for assisted reproductive technology treatment. Methods This prospective cohort study included 46 women undergoing assisted reproductive technology treatment from 1 April to 30 November 2023 at Hallmark Medicals, Kumasi, Ghana. Participants were conveniently recruited and received a standard controlled ovarian stimulation protocol. A structured questionnaire was used to collect sociodemographic and clinical data. Approximately 10 mL of venous blood was collected for laboratory analysis of fibrinogen and cytokine markers as well as hepatic and renal function tests. Statistical analyses were performed using R version 4.3.2 and Statistical Package for the Social Sciences version 26.0. A p-value of <0.05 was considered significant. Results The incidence of ovarian hyperstimulation syndrome among the study cohort was 10.9%, with a higher prevalence (60%) among the 18–24 year age group (p > 0.05) than among other age groups. Fibrinogen and cytokine levels did not differ significantly between the ovarian hyperstimulation syndrome and non-ovarian hyperstimulation syndrome groups; moreover, there was no significant difference in their levels measured before and after controlled ovarian stimulation (p > 0.05). However, receiver operating characteristic analysis revealed that elevated baseline (pre-controlled ovarian stimulation) levels of fibrinogen (area under the curve = 0.567, p = 0.604), interleukin-8 (area under the curve = 0.628, p = 0.337), tumour necrosis factor-alpha (area under the curve = 0.615, p = 0.337) and interleukin-10 (area under the curve = 0.633, p = 0.334) were associated with an increased risk of ovarian hyperstimulation syndrome. Women with elevated baseline interleukin-10 (≥33.5 ng/L) were at higher risk of ovarian hyperstimulation syndrome, with a sensitivity of 80.0%, specificity of 71.8%, area under the curve of 63.3% and an accuracy of 72.7%. Conclusion Interleukin-10 may serve as an early predictor of ovarian hyperstimulation syndrome among women undergoing controlled ovarian stimulation, with high sensitivity, specificity and accuracy. Further large-scale studies are warranted to confirm these findings.

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threating iatrogenic complication of the early luteal phase and/or early pregnancy after in vitro fertilization (IVF) treatment. The aim of the current study was to identify the most effective methods for preventing of and reducing the incidence and severity of OHSS in IVF patients. A systematic review of systematic reviews of randomized controlled trials (RCTs) with meta-analysis was used to assess each potential intervention (PROSPERO website, CRD 268626) and only studies with the highest quality were included in the qualitative analysis. Primary outcomes included prevention and reduction of OHSS incidence and severity. Secondary outcomes were maternal death, incidence of hospital admission, days of hospitalization, and reproductive outcomes, such as incidence of live-births, clinical pregnancies, pregnancy rate, ongoing pregnancy, miscarriages, and oocytes retrieved. A total of specific interventions related to OHSS were analyzed in 28 systematic reviews of RCTs with meta-analyses. The quality assessment of the included studies was high, moderate, and low for 23, 2, and 3 studies, respectively. The certainty of evidence (CoE) for interventions was reported for 37 specific situations/populations and resulted high, moderate, and low-to-very low for one, 5, and 26 cases, respectively, while it was not reported in 5 cases. Considering the effective interventions without deleterious reproductive effects, GnRH-ant co-treatment (36 RCTs; OR 0.61, 95% C 0.51 to 0.72, n  = 7,944; I 2  = 31%) and GnRH agonist triggering (8 RCTs; OR 0.15, 95% CI 0.05 to 0.47, n  = 989; I 2  = 42%) emerged as the most effective interventions for preventing OHSS with a moderate CoE, even though elective embryo cryopreservation exhibited a low CoE. Furthermore, the use of mild ovarian stimulation (9 RCTs; RR 0.26, CI 0.14 to 0.49, n  = 1,925; I 2  = 0%), and dopaminergic agonists (10 RCTs; OR 0.32, 95% CI 0.23 to 0.44, n  = 1,202; I 2  = 13%) coadministration proved effective and safe with a moderate CoE. In conclusion, the current study demonstrates that only a few interventions currently can be considered effective to reduce the incidence of OHSS and its severity with high/moderate CoE despite the numerous published studies on the topic. Further well-designed RCTs are needed, particularly for GnRH-a down-regulated IVF cycles.