Luteinizing hormone supplementation in women with hypogonadotropic hypogonadism seeking fertility care: Insights from a narrative review.

The management of infertile women affected by hypogonadotropic hypogonadism (HH) or conditions mimicking it is particularly challenging. In the present narrative review, we aimed to synthesize the available evidence on the benefit (if any) of exogenous luteinizing hormone (LH) supplementation in this group of patients. Available data support LH supplementation in women with organic or functional HH. On the contrary, the benefit of exogenous LH on reproductive outcomes both in advanced maternal age patients and in cases of depletion of FSH and LH levels induced by GnRH analogues has not been demonstrated. unfortunately, the inhomogeneous study populations as well as the methodological heterogeneity between studies focused on women affected by conditions mimicking HH do not allow reliable conclusions to be drawn.

Inflammatory Bowel Disease and Reproductive Health: From Fertility to Pregnancy-A Narrative Review.

Despite the fact that knowledge on obstetrical management of Inflammatory Bowel Diseases (IBDs) has greatly improved over the years, many patients still actively avoid pregnancy for fear of adverse maternal or neonatal outcomes, of adverse effects of pregnancy on the disease activity, of eventual IBD inheritance, or of an increased risk of congenital malformations. Indeed, though data prove that fertility is hardly affected by the disease, a reduced birth rate is nevertheless observed in patients with IBD. Misconceptions on the safety of drugs during gestation and breastfeeding may influence patient choice and negatively affect their serenity during pregnancy or lactation. Moreover, physicians often showed concerns about starting IBD medications before and during pregnancy and did not feel adequately trained on the safety of IBD therapies. IBD-expert gastroenterologists and gynecologists should discuss pregnancy and breastfeeding issues with patients when starting or changing medications in order to provide appropriate information; therefore, pre-conception counselling on an individualized basis should be mandatory for all patients of reproductive age to reassure them that maintaining disease remission and balancing the eventual obstetrical risks is possible.

Ovarian Hyperstimulation: Diagnosis, Prevention, and Management.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication of controlled ovarian stimulation (COS). Pathogenesis of the disease is based on massive transudation of protein-rich fluid from the vascular compartment into the peritoneal, pleural and pericardial spaces, with a variable picture of clinical manifestations depending on its severity. Nowadays OHSS can easily be avoided by several prevention methods, ranging from identification of high-risk patients, choice of a correct protocol stimulation, trigger with gonadotropin-releasing hormone (GnRH) agonists or, finally, the freeze-all strategy. When OHSS occurs, it can usually be managed as outpatient care. Only if severe/critical cases are diagnosed hospitalization is necessary for appropriate rehydration, monitoring of fluid balance and eventual drainage of ascitic fluid. One of the most dangerous complications of OHSS is venous thromboembolism (VTE). Thromboprophylaxis has shown to be cost effective and widely used, while there are controversies regarding the usage of low dose aspirin (LDA) as a preventive measure.

Morphokinetic analysis of cleavage stage embryos and assessment of specific gene expression in cumulus cells independently predict human embryo development to expanded blastocyst: a preliminary study.

To assess whether morphokinetic features at the cleavage stage together with specific gene expression in cumulus cells (CCs) may be used to predict whether human embryos are able to achieve the expanded blastocyst stage on day 5. Eighty-one embryos were cultured using the Geri plus® time-lapse system. Twenty-seven embryos progressing to the expanded blastocyst stage (BL group) were compared with thirty-five embryos showing developmental arrest (AR group) and nineteen reaching the stage of early or not fully expanded blastocyst (nBL group). The analyzed morphokinetic variables were pronuclear appearance (tPNa), pronuclear fading (tPNf), and completion of cleavage to two, three, four, and eight cells (t2, t3, t4, and t8). CCs were analyzed by RT-qPCR for bone morphogenetic protein 15 (BMP15), cytochrome c oxidase subunit II (COXII), ATP synthase subunit 6 (MT-ATP6), connexin 43 (Cx43), and heme oxygenase-1 (HO-1). Embryos of BL group showed a significantly faster kinetic. BMP15, COXII, and MT-ATP6 mRNA expression was significantly higher in CCs of BL group embryos, whereas Cx43 and HO-1 mRNA levels were higher in AR group. Kinetic parameters and gene expression were not significantly different between either the BL and nBL groups or the AR and nBL groups. ROC curves showed that the most predictive cut-offs were t2 < 26.25 for morphokinetics and COXII > 0.3 for gene expression. Multivariable logistic regression analysis showed that morphokinetic variables and gene expression were both valuable, independent predictors of embryo development to expanded blastocyst. Our results suggest the possibility of developing integrated prediction models for early embryo selection at the cleavage stage.

Bisphenol A and the female reproductive tract: an overview of recent laboratory evidence and epidemiological studies.

Bisphenol A (BPA) is a high production volume monomer used for making a wide variety of polycarbonate plastics and resins. A large body of evidence links BPA to endocrine disruption in laboratory animals, and a growing number of epidemiological studies support a link with health disorders in humans. The aim of this review is to summarize the recent experimental studies describing the effects and mechanisms of BPA on the female genital tract and to compare them to the current knowledge regarding the impact of BPA impact on female reproductive health. In particular, BPA has been correlated with alterations in hypothalamic-pituitary hormonal production, reduced oocyte quality due to perinatal and adulthood exposure, defective uterine receptivity and the pathogenesis of polycystic ovary syndrome. Researchers have reported conflicting results regarding the effect of BPA on premature puberty and endometriosis development. Experimental studies suggest that BPA's mechanism of action is related to life stage and that its effect on the female reproductive system may involve agonism with estrogen nuclear receptors as well as other mechanisms (steroid biosynthesis inhibition). Notwithstanding uncertainties and knowledge gaps, the available evidence should be seen as a sufficient grounds to take precautionary actions against excess exposure to BPA.

Contribution of genome-wide association studies to scientific research: a pragmatic approach to evaluate their impact.

The factual value of genome-wide association studies (GWAS) for the understanding of multifactorial diseases is a matter of intense debate. Practical consequences for the development of more effective therapies do not seem to be around the corner. Here we propose a pragmatic and objective evaluation of how much new biology is arising from these studies, with particular attention to the information that can help prioritize therapeutic targets. We chose multiple sclerosis (MS) as a paradigm disease and assumed that, in pre-GWAS candidate-gene studies, the knowledge behind the choice of each gene reflected the understanding of the disease prior to the advent of GWAS. Importantly, this knowledge was based mainly on non-genetic, phenotypic grounds. We performed single-gene and pathway-oriented comparisons of old and new knowledge in MS by confronting an unbiased list of candidate genes in pre-GWAS association studies with those genes exceeding the genome-wide significance threshold in GWAS published from 2007 on. At the single gene level, the majority (94 out of 125) of GWAS-discovered variants had never been contemplated as plausible candidates in pre-GWAS association studies. The 31 genes that were present in both pre- and post-GWAS lists may be of particular interest in that they represent disease-associated variants whose pathogenetic relevance is supported at the phenotypic level (i.e. the phenotypic information that steered their selection as candidate genes in pre-GWAS association studies). As such they represent attractive therapeutic targets. Interestingly, our analysis shows that some of these variants are targets of pharmacologically active compounds, including drugs that are already registered for human use. Compared with the above single-gene analysis, at the pathway level GWAS results appear more coherent with previous knowledge, reinforcing some of the current views on MS pathogenesis and related therapeutic research. This study presents a pragmatic approach that helps interpret and exploit GWAS knowledge.

The influence of cigarette smoking on a population of infertile men and women.

PURPOSE: This study aimed at investigating the effect of cigarette smoking on semen parameters in infertile men and on antral follicle count (AFC) and reproductive hormone levels in infertile women. METHODS: In 648 men (200 smokers and 448 non-smokers) sperm concentration, motility and morphology were compared according to smoking status. In the female population, AFC and basal follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured in 296 women (102 smokers and 194 non-smokers). Statistical analysis of data was performed using t test, χ²-test and Spearman's correlation. RESULTS: Among the male population, smokers had significantly lower sperm concentration and motility than non-smokers. Sperm normal morphology was reduced in smokers, although this difference did not reach statistical significance. No significant correlation was found between sperm parameters and the intensity of smoking. In the female population, AFC was reduced in smokers compared with non-smokers. Women who smoked had significantly higher FSH levels. No significant difference was found in LH and estradiol levels according to smoking status. The number of pack-years was negatively correlated to AFC and positively correlated to FSH levels. CONCLUSION: Cigarette smoking is associated with damaging effects on sperm parameters in infertile men and with ovarian reserve alteration in infertile women, as reflected by reduced AFC and increased FSH levels. Every smoker should be encouraged to stop smoking to prevent the damage of the toxins contained in cigarette smoking and preserve their own reproductive potential.