De Rosa, Pasquale (2018) Anomalie della risposta alla stimolazione ovarica in cicli PMA di II livello: ruolo di variabili ambientali, genetiche ed endocrino-metaboliche. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: Italiano
Title: Anomalie della risposta alla stimolazione ovarica in cicli PMA di II livello: ruolo di variabili ambientali, genetiche ed endocrino-metaboliche
Creators:
CreatorsEmail
De Rosa, Pasqualederosap85@gmail.com
Date: 10 December 2018
Number of Pages: 86
Institution: Università degli Studi di Napoli Federico II
Department: Neuroscienze e Scienze Riproduttive ed Odontostomatologiche
Dottorato: Neuroscienze
Ciclo di dottorato: 31
Coordinatore del Corso di dottorato:
nomeemail
Taglialatela, Mauriziomtaglial@unina.it
Tutor:
nomeemail
Alviggi, CarloUNSPECIFIED
Date: 10 December 2018
Number of Pages: 86
Uncontrolled Keywords: PMA
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/40 - Ginecologia e ostetricia
Date Deposited: 19 Dec 2018 11:28
Last Modified: 23 Jun 2020 09:59
URI: http://www.fedoa.unina.it/id/eprint/12558

Abstract

A recent review conducted in 2014 (Direkvand-Moghadam et al), estimated that primary and secondary female infertility, affects about 15% of the world's female population. The main cause of female infertility is the woman's age. Maximum fertility peak is reached around 25 years; a slow but constant decline of reproductive potential is observed in women aged between 30 and 35 years, then the reduction of the reproductive potential increase in the women over 35 years. Therefore, age of the woman, is the main risk factor for infertility as well as the most important prognostic factor for the ART cycles. The outcome of the data recorded about the impact of different factors of infertility by the ART National Registry are: • Male infertility: 29.3%; • Female infertility: 37.1%; • Male and female infertility: 17.6%; • Idiopathic infertility: 15.1%; • Genetic factor: 0.9%. The main causes of female infertility are: uterine or cervical abnormalities, ovulation disorders, endometriosis, as well as factor tubal / peritoneal, immunological alterations and idiopathic causes. With regards to the causes of infertility and the ART outcomes, we have evaluated three different lines of research: 1. Environmental pollution related to fertility 2. Diagnostic Approach to anovulation in patients with Polycystic ovarian syndrome 3. The role of Genetic Polymorphisms of FSH Receptor in the ART prognosis Several lines of evidence suggest that exposure to environmental contaminants is involved in the pathobiology of adverse reproductive health effects. A lot of studies have shown that exposure to benzene is associated to menstrual disorders, miscarriages and other disorders of the reproductive system. We performed an observational prospective pilot study to evaluate if levels of benzene in follicular fluid were correlated with response to controlled ovarian stimulation. We divided the study population in two groups: Group A with a “low” intra-follicular benzene concentration (n=19, benzene <0.54 ng/mL) and Group B with a “high” intra-follicular benzene concentration (n=15, benzene≥0.54 ng/mL). The ovarian response to gonadotrophins and the outcome of IVF were analyzed in the two groups. It was found that ovarian response to endogenous and exogenous gonadotrophins appeared to be influenced by intra-follicular benzene levels. In particular, Group B, with high” intra-follicular benzene concentration, had significantly higher basal FSH levels, lower estradiol peak concentration, and fewer oocytes retrieved and embryos transferred. Polycystic ovary syndrome (PCOs) is an endocrine disease clinically characterized by anovulation, hyperandrogenism and oligomenorrhea. It affects from 5% to 10% of women in reproductive age. Ultrasound evaluation represents one of the major criteria in PCOs definition. Insulin resistance is found in a high percentage of PCOs although neither insulin resistance nor the metabolic syndrome are included in the diagnostic criteria of Rotterdam Consensus Workshop (ESHRE/ASRM, 2004). 5 Interestingly, there is evidence that the pathogenic mechanisms of insulin resistance-related PCOs differs from other mechanisms that cause hyperandrogenism-related PCOs. At present, there isn't correlation between PCOs pattern and insulin resistance. Our study was designed to assess the impact of hyperinsulinism on ovarian ultrasonographic parameters in patients with PCOs. Our results show that the presence of hyperinsulinism in PCOS patients, diagnosed according to the Rotterdam criteria, is associated to an ultrasound pattern that differs from the PCO pattern without hyperinsulinism. This observation, if confirmed by larger studies, supports the concept that the PCOS contains several entities that could be distinguishable by a complete metabolic evaluation and also by an accurate ultrasound definition. It has been reported that 10% to 15% of young, normogonadotrophic women show suboptimal response to standard gonadotropin-releasing hormone—a long protocol. These patients require higher doses of exogenous follicle-stimulating hormone (FSH). This phenomenon could be associated with genetic characteristics. In our study, FSH receptor polymorphism was retrospectively evaluated in 42 normoresponder young women undergoing an in vitro fertilization/intracytoplasmic sperm injection cycle; patients were stratified according to recombinant human FSH (r-hFSH) consumption. We retrospectively selected 17 normoresponder young patients undergoing a standard IVF/ICSI cycle, who required a cumulative dose of r-FSH >2500 UI (group A). A control group was selected randomly (ratio 1:2) among normoresponder young patients undergoing a standard IVF/ICSI cycle, who required a cumulative dose of r-FSH <2500 UI (group B). Our study confirms that the FSH-R genotype may interfere with physiological responsiveness of the target organ to FSH stimulation. The presence of the FSH-R Ser680 variant seems to result in a significant decrease in ovarian response to r-hFSH during ART cycles and, therefore, in a significant increase in drug consumption. More specifically, among patients requiring a higher cumulative dose of r-hFSH (group A), the expression of Ser/Ser genotype was significantly higher compared to the subgroups carryng variants Asn/Ser and Asn/Asn of FSH-R.

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