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]
Tipologia del documento: |
Tesi di dottorato
|
Lingua: |
Italiano |
Titolo: |
Anomalie della risposta alla stimolazione ovarica in cicli
PMA di II livello: ruolo di variabili ambientali, genetiche ed
endocrino-metaboliche |
Autori: |
Autore | Email |
---|
De Rosa, Pasquale | derosap85@gmail.com |
|
Data: |
10 Dicembre 2018 |
Numero di pagine: |
86 |
Istituzione: |
Università degli Studi di Napoli Federico II |
Dipartimento: |
Neuroscienze e Scienze Riproduttive ed Odontostomatologiche |
Dottorato: |
Neuroscienze |
Ciclo di dottorato: |
31 |
Coordinatore del Corso di dottorato: |
nome | email |
---|
Taglialatela, Maurizio | mtaglial@unina.it |
|
Tutor: |
nome | email |
---|
Alviggi, Carlo | [non definito] |
|
Data: |
10 Dicembre 2018 |
Numero di pagine: |
86 |
Parole chiave: |
PMA |
Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/40 - Ginecologia e ostetricia |
[error in script]
[error in script]
Depositato il: |
19 Dic 2018 11:28 |
Ultima modifica: |
23 Giu 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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