Explore the vast range of titles available.

Cycles with progesterone elevation during controlled ovarian stimulation (COS) for IVF/ICSI are commonly managed with a \"freeze-all\" strategy, due to a well-recognized detrimental effect of high progesterone levels on endometrial receptivity. However, also a detrimental effect of elevated progesterone on day-3 embryo quality has recently been found with regards to top quality embryo formation rate. Because blastocyst culture and cryopreservation are largely adopted, we deemed relevant to determine whether this detrimental effect is also seen on blastocyst quality on day 5-6. This issue was investigated through a large two-center retrospective study including 986 GnRH antagonist IVF/ICSI cycles and using top quality blastocyst formation rate as the main outcome. Results showed that on multivariate analysis sperm motility (p<0.01) and progesterone levels at ovulation triggering (p = 0.01) were the only two variables that significantly predicted top quality blastocyst formation rate after adjusting for relevant factors including female age, BMI, basal AMH and total dose of FSH used for COS. More specifically, progesterone levels at induction showed an inverse relation with top quality blastocyst formation (correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis identified P level >1.49 ng/ml as the best cut-off for identification of patients at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study is the first to investigate the top quality blastocyst formation rate in relation to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone is associated with lower rates of top quality blastocyst. Hence, the advantages of prolonging COS to maximize the number of collected oocytes might eventually be hindered by a decrease in top quality blastocysts available for transfer, if increasing progesterone levels are observed. This observation extends the results of two recent studies focused on day-3 embryos and deserves further research.

Background Currently, there is no consensus on the optimal management of women with low prognosis in ART. In this Delphi consensus, a panel of international experts provided real-world clinical perspectives on a series of literature-supported consensus statements regarding the overall relevance of the POSEIDON criteria for women with low prognosis in ART. Methods Using a Delphi-consensus framework, twelve experts plus two Scientific Coordinators discussed and amended statements and supporting references proposed by the Scientific Coordinators (Round 1). Statements were distributed via an online survey to an extended panel of 53 experts, of whom 36 who voted anonymously on their level of agreement or disagreement with each statement using a six-point Likert-type scale (1 = Absolutely agree; 2 = More than agree; 3 = Agree; 4 = Disagree; 5 = More than disagree; 6 = Absolutely disagree) (Round 2). Consensus was reached if > 66% of participants agreed or disagreed. Results The extended panel voted on seventeen statements and subcategorized them according to relevance. All but one statement reached consensus during the first round; the remaining statement reached consensus after rewording. Statements were categorized according to impact, low-prognosis validation, outcomes and patient management. The POSEIDON criteria are timely and clinically sound. The preferred success measure is cumulative live birth and key management strategies include the use of recombinant FSH preparations, supplementation with r-hLH, dose increases and oocyte/embryo accumulation through vitrification. Tools such as the ART Calculator and Follicle-to-Oocyte Index may be considered. Validation data from large, prospective studies in each POSEIDON group are now needed to corroborate existing retrospective data. Conclusions This Delphi consensus provides an overview of expert opinion on the clinical implications of the POSEIDON criteria for women with low prognosis to ovarian stimulation.

PurposeThis systematic review and meta-analysis aimed to compare pregnancy outcomes between immediate frozen embryo transfer (FET) performed within the first menstrual cycle after oocyte retrieval and delayed FET following subsequent cycles.MethodsPubMed, EMBASE, and Web of Science were searched for eligible studies through January 2020. The main outcome measures were clinical pregnancy rate (CPR), live birth rate (LBR), and pregnancy loss rate (PLR). The effect size was estimated as risk ratio (RR) with 95% confidence interval (CI) using a random effects model. Inter-study heterogeneity was assessed by the I2 statistic.ResultsTwelve retrospective cohort studies involving 18,230 cycles were included. The pooled results revealed no significant differences between delayed and immediate FET in CPR (RR 0.94, 95% CI 0.87–1.03; I2 = 67.9%), LBR (RR 0.94, 95% CI 0.85–1.03; I2 = 67.5%), and PLR (RR 1.05, 95% CI 0.87–1.26; I2 = 42.7%). Subgroup analyses of freeze-all cycles showed a marginal decrease of CPR in delayed FET (RR 0.93, 95% CI 0.86–1.00; I2 = 53.6%), but no significant changes were observed regarding LBR (RR 0.93, 95% CI 0.85–1.02; I2 = 65.2%) and PLR (RR 1.09, 95% CI 0.84–1.41; I2 = 59.1%). No statistical differences were found in effect estimates among other subgroup analyses by ovarian stimulation protocol, trigger agent, endometrial preparation regimen, and embryo stage.ConclusionTiming of the first FET after oocyte retrieval was not significantly associated with pregnancy outcomes. This finding refutes the current common practice to delay FET after oocyte retrieval and reassures patients who wish to proceed with FET at their earliest convenience. Due to the high heterogeneity and observational nature of included studies, further randomized controlled trials are needed to confirm the results.

Background The objective was to present a new ovarian response prediction index (ORPI), which was based on anti-Müllerian hormone (AMH) levels, antral follicle count (AFC) and age, and to verify whether it could be a reliable predictor of the ovarian stimulation response. Methods A total of 101 patients enrolled in the ICSI programme were included. The ORPI values were calculated by multiplying the AMH level (ng/ml) by the number of antral follicles (2–9 mm), and the result was divided by the age (years) of the patient (ORPI=(AMH x AFC)/Patient age). Results The regression analysis demonstrated significant ( P <0.0001) positive correlations between the ORPI and the total number of oocytes and of MII oocytes collected. The logistic regression revealed that the ORPI values were significantly associated with the likelihood of pregnancy (odds ratio (OR): 1.86; P =0.006) and collecting greater than or equal to 4 oocytes (OR: 49.25; P <0.0001), greater than or equal to 4 MII oocytes (OR: 6.26; P <0.0001) and greater than or equal to 15 oocytes (OR: 6.10; P <0.0001). Regarding the probability of collecting greater than or equal to 4 oocytes according to the ORPI value, the ROC curve showed an area under the curve (AUC) of 0.91 and an efficacy of 88% at a cut-off of 0.2. In relation to the probability of collecting greater than or equal to 4 MII oocytes according to the ORPI value, the ROC curve had an AUC of 0.84 and an efficacy of 81% at a cut-off of 0.3. The ROC curve for the probability of collecting greater than or equal to 15 oocytes resulted in an AUC of 0.89 and an efficacy of 82% at a cut-off of 0.9. Finally, regarding the probability of pregnancy occurrence according to the ORPI value, the ROC curve showed an AUC of 0.74 and an efficacy of 62% at a cut-off of 0.3. Conclusions The ORPI exhibited an excellent ability to predict a low ovarian response and a good ability to predict a collection of greater than or equal to 4 MII oocytes, an excessive ovarian response and the occurrence of pregnancy in infertile women. The ORPI might be used to improve the cost-benefit ratio of ovarian stimulation regimens by guiding the selection of medications and by modulating the doses and regimens according to the actual needs of the patients.

Purpose This retrospective study was carried out to evaluate whether increasing the starting dose of FSH stimulation above the standard dose of 150 IU/day in patients with low predicted ovarian reserve can improve IVF outcomes. Method A total of 122 women aged less than 36 years in their first cycle of IVF were identified as having likely low ovarian reserve based on a serum AMH measurement below 14 pmol/l. Thirty five women were administered the standard dose of 150 IU/day FSH, while the remaining 87 received a higher starting dose (200–300 IU/day FSH). There were no significant differences in age, BMI, antral follicle count, serum AMH, FSH or aetiology of infertility between the two dose groups. Results No significant improvement in oocyte and embryo yield or pregnancy rates was observed following an upward adjustment of FSH starting dose. While increasing the dose of FSH above 150 IU/day did not produce any adverse events such as OHSS, it did consume an extra 1,100 IU of FSH per IVF cycle. Conclusion The upward FSH dose adjustment in anticipation of low ovarian reserve can not be advocated as it is both expensive and of no proven clinical value.

Introduction Mild ovarian stimulation has been conceived, proposed and implemented in clinical practice as a safer and cheaper alternative to conventional strategies of controlled ovarian hyperstimulation in preparation for in vitro fertilization (IVF). Our aim was to summarize the key evidence on this topic and explore its possible role as the standard treatment option for women undergoing IVF. Materials and Methods A short narrative review of the existing literature, with emphasis on mild ovarian stimulation clinical and cost effectiveness, as well as treatment limitations. Results Numerous studies highlight mild ovarian stimulation’s favorable characteristics with respect to oocyte/embryo quality, reduced patient risk, and ease of intervention. There is, however, a need for high-quality laboratory environment. Limitations regarding poor responders, older women, or those seeking ovarian stimulation for non-infertility indications should also be considered. Finally, outcomes on the cumulative success rates and the cost effectiveness of mild ovarian stimulation remain inconclusive. Conclusion Mild ovarian stimulation protocols for IVF should currently be implemented only in carefully selected populations. Further research is needed to clarify the remaining controversies in this IVF approach.

Several studies have shown high variability in clinical outcome among women undergoing follicle-stimulating hormone treatment. Pharmacogenetic studies have revealed a series of genetic markers involved in controlled ovarian hyperstimulation (COH) response. gene-associated SNPs, including the N680S missense variant, are the most promising genetic markers available to date. In this paper the state of the art pharmacogenetic analysis of COH outcome is reviewed and a meta-analysis is conducted with available data that confirms that the N680S marker is associated with poor response during COH. Thus, we propose that by pooling together available information, it is possible to go one step further with this biomarker to definitively validate its utility in the clinical field. We propose to conduct clinical trials, to look for algorithms integrating the N680S genotype and to test if such clinical protocols can optimize recombinant follicle-stimulating hormone dose and detect women at risk of a poor response during a COH cycle.

Purpose To determine whether there is a superior treatment modality for ‘poor’ responders. Method Retrospective analysis of three stimulation regimens, with patients stratified based on age, stimulation regime and response in previous cycles (“poor’ responder or “non poor” responder). Fertilisation, embryo utilisation and clinical pregnancy rates were assessed. There were a total of 1,608 cycles in the ‘poor’ responder and 8,489 cycles in the ‘non poor’ responder groups. Results In ‘poor’ responders there was no significant difference in fertilisation rate, nor utilisation rate between the three stimulation regimes and no differences in the pregnancy rate/initiated cycle irrespective of age and stimulation regimen in any of the groups. ‘Non poor’ responders had a significantly greater pregnancy rate/initiated cycle for all stimulation regimens in both age groups compared with ‘poor’ responders. Conclusion This large retrospective study of ‘poor’ responders has not shown a difference in pregnancy rates/initiated cycle between stimulation regimens.

Background Human follicle-stimulating hormone (hFSH; follitropin alfa) can be employed therapeutically to induce ovarian follicular development in assisted reproduction treatments. Current recombinant hFSH (r-hFSH) preparations available for clinical use are labeled either in terms of the bioactivity expressed in international units (IU) or in mass (μg). Several clinical trials have tried to assess the clinical implications of the physicochemical improvements in the dosing of follitropin alfa filled by mass (FbM). The aim of this study was to perform a meta-analysis of previous studies in order to assess the efficacy and safety of ovarian stimulation using follitropin alfa FbM compared with follitropin alfa filled by international units (FbIU). Methods A literature search was carried out in scientific databases to find published articles and abstracts comparing both hormone preparations. A fixed effects model meta-analysis was performed. The variables studied include the average dose (IU), days of treatment, estradiol peak, follicles >14 mm, number of extracted oocytes, number of embryos obtained, number of cases of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancies. Results A total of six studies met the stated criteria and were included in the meta-analysis. In these studies, the average r-hFSH dose per patient was 230.29 IU less with administration of follitropin alfa FbM compared with FbIU, and the number of days of treatment was reduced by 0.48. In addition, a significantly greater number of oocytes (0.84) were extracted, more embryos (0.88) were obtained, and a higher peak level of estradiol (613.08 pmol/L) was achieved in the patients undergoing ovarian stimulation with follitropin alfa FbM. However, no statistically significant differences were observed in the number of follicles >14 mm, clinical pregnancies, or OHSS cases. Conclusion Follitropin alfa FbM, a technologically modified formulation of r-hFSH, is as safe as follitropin alfa FbIU but requires a smaller dose over a shorter period to produce more oocytes and final embryos.

Our purpose was to evaluate the relationship between the initial follicle count during gonadotropin stimulation after gonadotropin-releasing hormone (GnRH) agonist suppression and the efficiency of controlled ovarian hyperstimulation (COH) in patients receiving treatment with assisted reproductive technologies (ARTs). A total of 338 COH procedures in 291 couples was performed with cycles that reached the stage of oocyte retrieval. The ovarian antral follicle number was measured using transvaginal ultrasonography at the folliculometry during gonadotropin stimulation by GnRH agonist suppression in patients undergoing ARTs. Controlled ovarian hyperstimulation was accomplished using GnRH agonist down-regulation combined with FSH and menotropin stimulation. The characteristics of oocytes after retrieval and embryos after in vitro culture and the pregnancy rates were assessed. The procedures performed included 195 ET cycles, 129 TET cycles, and 14 incomplete cycles. The treatment cycles were divided into four categories according to the antral follicle number (i.e., < or = 5, 6-10, 11-15, and > or = 16) at the first folliculometry to evaluate the influence of various factors. The antral follicle count correlated significantly with the patient age, dosage of gonadotropins, serum estradiol concentration, number of antral follicles (> or = 13 mm) while receiving hCG injections, number of oocytes retrieved, and, later, number of embryos transferred. There was a trend toward an increasing number of pregnancies per cycle as the number of antral follicles increased (14.7, 26.5, 44, and 45%, respectively). We were able to predict the efficiency of COH and outcome of ARTs based on the follicle count during the first folliculometry during gonadotropin stimulation after GnRH agonist suppression. The results of the folliculometry significantly predicted the ovarian response to COH and the outcome of ARTs in the current treatment cycle.