Future perspectives of PoseidOn stratification for clinical practice and research

A total of 50% of patients undergoing IVF treatment has previously been estimated to fulfill the POSEIDON classification criteria; importantly, although the reproductive prognosis differs between patients, POSEIDON patients share the same characteristic of a low ovarian response to exogenous gonadotropin stimulation\u2014independent of age. POSEIDON patients require focused attention as regards ovarian stimulation in order to increase the chances of having at least one euploid blastocyst for transfer\u2014the success criterion for stimulation set forth by the POSEIDON Group. The key to success seems to be individualization in all steps of treatment. In this perspective article we discuss the future impact of the POSEIDON stratification for daily clinical practice as well as for research

LH supplementation of ovarian stimulation protocols influences follicular fluid steroid composition contributing to the improvement of ovarian response in poor responder women.

Abstract In this prospective study, we evaluated the steroid levels in 111 follicular fluids (FF) collected from 13 women stimulated with FSH monotherapy and 205 FF collected from 28 women stimulated with FSH + LH because of a previous history of hypo-responsiveness to FSH. Steroid levels were measured by HPLC/MS–MS and related to ovarian stimulation protocol, oocyte maturity, fertilization and quality of blastocysts, after individually tracking the fate of all retrieved oocytes. 17-Hydroxy-Progesterone, Androstenedione, Estradiol and Estrone were significantly higher in the FSH + LH protocol. Progesterone, 17-Hydroxy-Progesterone and Estradiol were more expressed in FF yielding a mature oocyte (p < 0.01) in the FSH + LH protocol. FF Progesterone concentration was correlated with the rate of normal fertilization in the FSH protocol. None of the FF steroids measured were associated with blastocyst quality and achievement of pregnancy. Our results indicate that LH supplementation in hypo-responsive women modifies ovarian steroid production, mimicking physiological production better and likely contributing to an improved ovarian response. Employing a correct methodological procedure to evaluate the relationship between FF steroid hormones and assisted reproduction outcomes, our study reveals that some steroids in single follicles may be helpful in predicting oocyte maturity and fertilization

Recombinant human luteinizing hormone co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age: a systematic review and meta-analysis of randomized controlled trials

Introduction: Several studies suggest that luteinizing hormone (LH) could improve IVF outcome in women of advanced reproductive age by optimizing androgen production. In this review, we assessed the role of recombinant-human LH (r-hLH) and recombinant human follicle stimulating hormone (r-hFSH) co-treatment in ovarian stimulation for assisted reproductive technology in women of advanced reproductive age candidates for assisted reproduction. Material and methods: Using a preregistered protocol we systematically searched Medline/PubMed, Scopus and the ISI Web of Science databases to identify randomized controlled trials in which r-hFSH monotherapy protocols were compared with r-hFSH/r-hLH co-treatment in women ≥35 years undergoing fresh IVF cycles. We calculated the pooled odds ratio (OR) for dichotomous data and the weight mean difference (WMD) for continuous data with an associated 95% confidence interval (CI). The meta-analyses were conducted using the random-effect model. P values < 0.05 were considered statistically significant. Subgroup analyses of all primary and secondary outcomes were performed only in women aged 35–40 years. Results: Twelve studies were identified. In women aged between 35 and 40 years, r-hFSH/r-hLH co-treatment was associated with higher clinical pregnancy rates (OR 1.45, CI 95% 1.05–2.00, I2 = 0%, P = 0.03) and implantation rates (OR 1.49, CI 95% 1.10–2.01, I2 = 13%, P = 0.01) versus r-hFSH monotherapy. Fewer oocytes were retrieved in r-hFSH/r-hLH-treated patients than in r-hFSH-treated patients both in women aged ≥35 years (WMD -0.82 CI 95% -1.40 to − 0.24, I2 = 88%, P = 0.005) and in those aged between 35 and 40 years (WMD -1.03, CI − 1.89 to − 0.17, I2 = 0%, P = 0.02). The number of metaphase II oocytes, miscarriage rates and live birth rates did not differ between the two groups of women overall or in subgroup analysis. Conclusion: Although more oocytes were retrieved in patients who underwent r-hFSH monotherapy, this meta-analysis suggests that r-hFSH/r-hLH co-treatment improves clinical pregnancy and implantation rates in women between 35 and 40 years of age undergoing ovarian stimulation for assisted reproduction technology. However, more RCTs using narrower age ranges in advanced age women are warranted to corroborate these findings

Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation: a systematic review and meta-analysis

Genotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach to controlled ovarian stimulation (COS). However, the validity of such an approach remains to be established

Sexual Intercourse for Induction of Spontaneous Onset of Labor: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

INTRODUCTION: Sexual intercourse during pregnancy is commonly believed to trigger the onset of contractions and, therefore, labor. However, in low-risk pregnancies, there is neither association with preterm birth, premature rupture of membranes, or low birth weight, nor with spontaneous onset of labor at term. AIM: To evaluate the effectiveness of sexual intercourse for spontaneous onset of labor at term in singleton pregnancies. METHODS: The systematic search was conducted using electronic databases from inception of each database to June 2019. Review of articles also included the abstracts of all references retrieved from the search. Inclusion criteria were randomized controlled trials comparing sexual intercourse in singleton low-risk pregnancies at term with controls (either reduced number of coitus or no coitus) for spontaneous onset of labor. Estimates were pooled using random-effects meta-analysis. MAIN OUTCOME MEASURES: The primary outcome was the incidence of spontaneous onset of labor. The summary measures were reported as summary relative risk with 95% CI using the random-effects model of DerSimonian and Laird. RESULTS: Data extracted from 3 trials, including 1,483 women with singleton pregnancy at term and cephalic presentation, were analyzed. Women who were randomized in the sexual intercourse group had similar incidence of spontaneous onset of labor compared with control subjects (0.82% vs 0.80%; relative risk 1.02, 95% CI 0.98-1.07). CLINICAL IMPLICATION: Sexual intercourse should not be restricted in low-risk term pregnancies. Further studies are needed to properly evaluate the impact of orgasm, penetration, condom use, frequency of intercourse and other factors on induction of labor at term. STRENGTH & LIMITATIONS: Our study has several strengths. The three included trials had low risk of allocation bias; intention-to-treat analysis was used; this is the first meta-analysis on this issue so far. Limitations mainly depend on the design of the included studies. Firstly, compliance to the protocol relied on self-reporting by patients; in addition, not all the features of sexual intercourse could be adequately assessed (orgasm, nipple stimulation, sexual positions, etc.). CONCLUSION: In women with singleton, cephalic, low-risk pregnancies, sexual intercourse at term does not significantly increase the incidence of spontaneous onset of labor

Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker—The Follicle-To-Oocyte (FOI) Index

Hypo-responsiveness to controlled ovarian stimulation is an undervalued topic in reproductive medicine. This phenomenon manifests as a low follicles output rate (FORT) with a discrepancy between the relatively low number of pre-ovulatory follicles which develop following ovarian stimulation as compared to the number of antral follicles available at the start of stimulation. The pathophysiology mechanisms explaining the ovarian resistance to gonadotropin stimulation are not fully understood, but the fact that both hypo-responders and normal responders share similar phenotypic characteristics suggests a genotype-based mechanism. Indeed, existing evidence supports the association between specific gonadotropin and their receptor polymorphisms and ovarian hypo-response. Apart from genotypic trait, environmental contaminants and oxidative stress might also be involved in the hypo-response pathogenesis. The ratio between the number of oocytes collected at the ovum pick up and the number of antral follicles at the beginning of OS [Follicle to oocyte index (FOI)] is proposed as a novel parameter to assess the hypo-response. Compared with traditional ovarian reserve markers, FOI might reflect most optimally the dynamic nature of follicular growth in response to exogenous gonadotropin. In this review, we contextualize the role of FOI as a parameter to identify this condition, discuss the underlying mechanisms potentially implicated in the pathogenesis of hypo-response, and appraise possible the treatment strategies to overcome hyper-responsiveness to gonadotropin stimulation

Z boson production in Pb+Pb collisions at √Snn = 5.02 TeV measured by the ATLAS experiment

The production yield of Z bosons is measured in the electron and muon decay channels in Pb+Pb collisions at √S = 5.02 TeV with the ATLAS detector. Data from the 2015 LHC run corresponding to an integrated luminosity of 0.49 nb are used for the analysis. The Z boson yield, normalised by the total number of minimum-bias events and the mean nuclear thickness function, is measured as a function of dilepton rapidity and event centrality. The measurements in Pb+Pb collisions are compared with similar measurements made in proton-proton collisions at the same centre-of-mass energy. The nuclear modification factor is found to be consistent with unity for all centrality intervals. The results are compared with theoretical predictions obtained at next-to-leading order using nucleon and nuclear parton distribution functions. The normalised Z boson yields in Pb+Pb collisions lie 1-3σ above the predictions. The nuclear modification factor measured as a function of rapidity agrees with unity and is consistent with a next-to-leading-order QCD calculation including the isospin effect. nn -