La diagnostica clinica della PCOS è estremamente eterogenea e variabile tale da complicare notevolmente l’iter diagnostico reso non meno difficoltoso da un altrettanto complicato corredo di dati di laboratorio. La sintomatologia è caratterizzata principalmente da disordini mestruali, iperandrogenismo ed alterazioni metaboliche. Le alterazioni ovariche funzionali e morfologiche, USG evidenziabili, saranno descritte in altri articoli.
Disordini mestruali: generalmente la presenza isolata di iperandrogenemia permette un’insorgenza normale del menarca seguito da cicli erratici (oligo-amenorrea), indolori e da anovulazione. Una modesta percentuale di pazienti con iperandrogenismo presenta cicli mestruali regolari o intermittenti e fertilità spontanea. L’associazione con l’obesità complica il quadro clinico, caratterizzandolo di cicli mestruali abbondanti, metrorragie disfunzionali, iperplasia endometriale a causa dell’aromatizzazione periferica dell’androstenedione in estrone. Occasionalmente si riscontra anche carcinoma occulto dell’endometrio. Inoltre nelle pazienti obese con iperandrogenismo c’e una maggiore resistenza all’induzione dell’ovulazione. Nelle pazienti PCOS magre si evidenzia una maggiore frequenza di iperstimolazione ovarica severa (OHSS) nei cicli PMA tale da richiedere un protocollo specifico per la iperstimolazione ovarica (COH).
Galattorrea: conseguenza di una iperprolattinemia quasi sempre modesta <100 ng/ml). La galattorrea è presente fino al 10 % delle pazienti con PCOS è probabilmente dovuta alla iperplasia delle cellule lattotrope ipofisarie ad opera dell’estrone a sua volta derivato dalla metabolizzazione periferica degli androgeni di origine ovarica e surrenalica. Spesso si associano abbassamento del tono dopaminergico e iperattivazione degli oppioidi endogeni.
Iperandrogenismo (HA): distinguiamo un un HA biologico: T>50 ng/ml e LH/FSH >2 ed un HA clinico che presenta virilizzazione, irsutismo, acne e obesità addominale.
La virilizzazione interessa circa il 10% delle pazienti con PCOS ed é caratterizzata da approfondimento del tono della voce, aumentata massa muscolare, atrofia delle ghiandole mammarie, alopecia androgena, aumento della libido, e clitoridomegalia. È espressione clinica dell’iperandrogenismo anche in assenza di alterazione dei dati di laboratorio.
L’obesità di tipo androgino: obesità con una distribuzione del grasso localizzato soprattutto a livello addominale e scapolare, identificabile da un rapporto circonferenza vita/circonferenza fianchi (WHR) >0.85. L’obesità influisce direttamente sul metabolismo glicidico innescando il circolo vizioso di insulino-resistenza/iperinsulinemia/diabete tipo II. E’ presente nel 50% delle donne con PCOS. Spesso si associa ad un aumento dei livelli sierici di trigliceridi, colesterolo LDL oltre che a iperinsulinemia come detto sopra.
Irsutismo: presenza di peli terminali, grossi, duri, lunghi, pigmentati in zone abitualmente glabre nelle donne o dotate di fine lanuggine viso, mento, torace, braccia, cosce. E’ correlato con alcuni parametri tipici della PCOS che costituisce l’80% circa delle cause di irsutismo nelle donne, La gravità dell’irsutismo è correlato con il grado di obesità, il tasso di testosterone sierico (T), il volume ovarico, l’ipoconcentrazione di FSH, l’alterato rapporto FSH/LH a favore di quest’ultimo. Il 60-65 % del testosterone circolante è legato alla TeGB (testosterone-binding globulin) denominata anche sex hormone-binding globulin (SHBG); il 35-40% è legato all’albumina con un legame a bassa affinità, e solo 1-2% del testosterone è libero. Nelle pazienti PCOS spesso si assiste ad una diminuita sintesi della SHBG epatica, a causa dell’obesità e della iperinsulinemia, per cui aumenta la percentuale di T sierico non legato (T free) e quindi prontamente disponibile per la sua attività androgenica. Non sempre però il grado di irsutismo è correlato con la concentrazione degli androgeni plasmatici che spesso risulta normale; c’è quindi una maggiore sensibilità agli androgeni da parte dell’unità pilo-sebacea ed in particolare una iperattività della 5-α-reduttasi, enzima che trasforma il T in DHT (diidrotestosterone) principale responsabile dell’irsutismo. L’aumentato metabolismo del T a livello dell’unità pilo-sebacea produce una diminuzione dei livelli plasmatici dell’ormone circolante e, per un fenomeno di feed-back positivo, un aumento della quantità totale prodotta creando così un circolo vizioso iperandrogenismo-irsutismo-iperandrogenismo. Da ricordare che l’attività della 5-α-reduttasi è amplificata anche da iperprolattinemia e iperestrogenemia quasi sempre presenti nelle PCOS.
Alopecia androgenetica: la perdita dei capelli tipicamente si riscontra a livello della sommità del capo e non sulla nuca. Facendo scorrere la mano sopra il cuoio capelluto, come ad accarezzare i capelli, “manovra della carezza”, é facile rendersi conto a vista di quanti sono i capelli corti e sottili (miniaturizzati). Un eccesso di capelli miniaturizzati indica un defluvio in anagen tipico dell’alopecia androgenetica.
Acne: gli androgeni stimolano l’attività mitotica delle ghiandole pilo-sebacee e la sintesi intracellulare dei lipidi (tab. 3). Alla iperproduzione di sebo, in mancanza di adeguata pulizia, consegue abnorme cheratinizzazione, colonizzazione batterica e flogosi locale. Anche il progesterone ha un’azione favorente l’acne; infatti l’acne aumenta nella fase luteinica e all’inizio della gravidanza. Gli estrogeni invece esplicano un’attività anti-acne (63-65).
Un profilo particolare presenta la Pre-PCOS che oltretutto offre un’altra teoria etiologica: LBW-early-life sequence.
- Armar N.A., Holownia P., McGarrigle HHG., Jacobs H. S., Honour J., Lachelin G.C.L.: Diatermia ovarica laparoscopica nel trattamento della sterilità anovulatoria in donne con ovaio policistico: variazioni endocrine e esito clinico. (University College, Middlesex School of Medicine, London) Fertil. Steril. 53:49,1990.
- Adashi EY, Rock JA, Guzick D, Wentz AC, Jones GS, Jones HW Jr. Fertility following bilateral ovarian wedge resection: a critical analsysis of 90 consecutive cases of the polycystic ovary syndrome. Fertil Steril 1981; 36:320 – 5.
- Toaff R, Toaff ME, Peyser MR. Infertility following wedge resection of the ovaries Am J Obstet Gynecol 1976; 124:92 – 6. Comparison of the effects of ovarian cauterization and gonadotropin-releasing hormone agonist and oral contraceptive therapy combination on endocrine changes in women with polycystic ovary disease. Fertil Steril 1996; 65:1115 –1118
- Insler V, Lunenfeld B. Polycystic ovarian disease: a challenge and controversy. Gynecol Endocrinol 1990; 5:51 – 69.
- Greenblatt E, Casper RF. Endocrine changes after laparoscopic ovarian cautery in polycystic ovary syndrome. Am J Obstet Gynecol 1987; 156:279 – 85.
- Kamrava MM, Seibel MM, Berger MJ, Thompson I, Taymor ML. Reversal of persistent anovulation in polycystic ovariandisease by administration of chronic low-dose follicle-stimulating hormone. Fertil Steril 1982; 37:520 – 3
- Parisi L., Tramonti M., Casciano S., Zurli A., Gazzarini O.: The role of ultrasound in the study of polycystic ovarian disease. J. Clin. Ultrasound 10:167,1982.
- Barreca A; Del Monte P; Ponzani P; Artini PG; Genazzani AR; Minuto F: “Intrafollicular insulin-like growth factor-II levels in normally ovulating women and in patients with polycystic ovary syndrome”. Fertil Steril. 1996 Apr. 65(4). P 739-45.
- Orvieto R; Ben-Rafael Z TI:Etiology of ovarian hyperstimulation syndrome? [letter; comment] SO:Fertil Steril. 1995 Oct. 64(4). P 871-2.
- Utiger R.D.: Insulin and the polycystic ovary sindrome. The New England J. of Medic., Vol. 335, n. 9, Agosto 1996.
- Cook C et al: “Relatioship between serum müllerian-inhibiting substance and other reproducyive hormones in untreated women with polycystic ovary syndrome and normal women. Fertil Steril 2002 Jan, 77,1:141-146.
- Yen SSC: “Polycystic ovary syndrome: hyperandrogenic chronic anovulation. In: Yen SSC, Jaffe RB, Barbieri RL, eds Reproductive endocrinology, physiology, pathophysiology and clinical management, 4th ed. Philadelphia; WBSaunders, 1999;436-478
- Ueno S et al: “Müllerian-inhibiting substance in the adult rat ovary during various stages of the estrous cycle”. Endocrinology 1989;125:1060-1066.
- Takakura K et al: “Follicle-stimulating hormone receptor gene mutations are rare in Japanese women with premature ovarian failure and polycystic ovary syndrome”. Fertil Steril 2001;75,1:207-209.
- Ovalle F and Azziz R: “Insulin resistance, polycystic ovary syndrome and type diabetes mellitus”. Fertil Steril 2002;77,6:1095-1105.
- Le Roith D, Zick Y: “Recent advances in our understanding of insulin action and insulin resistance”. Diabetes Care 2001; 24:588-597.
- Alberti K, Zimmet P: “Consultation Group. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus, provisional report of a WHO consultation”. Diabet Med 1998;15:39-53.
- Glueck CJ et al: “Continuing metformin throughout pregnancy in women with polycystic ovary syndrome appears to safely reduce first-trimester spontaneous abortion: a pilot study”. Fertil Steril 2001;75,1:46-52.
- Selma F et al: “Candidate gene analysis in premature pubarche and adolescent hyperandrogenism”. Fertil Steril 2001;75,4:724-730.
- Bale A.H: “Hypersecretion of luteinizing hormone and the polycystic ovary sindrome”. Human Reprod 1993;8 suppl 2:123-128.
- Genazzani AR et al: “Opioid control of gonadotrophin secretion in humans”. Human Reprod 1993;8 suppl 2:151-153.
- Scheele F et al: “Pulsatile gonadotrophin releasing hormone stimulation after medium-term pituitary suppression in polycystic ovary syndrome”. Human Reprod 1993;8 supplem
- Filicori M, Campaniello E, Michelacci L, Pareschi A, Ferrari P, Bolelli GT, Flamigni C: “Gonadotrophin-releasing hormone analog suppression render polycystyc ovarian disease patients more susceptible to ovulation induction with pulsatile Gn-RH”. J Clin Endocrinol Metab 1988;66:327-333.
- Keslie S et al.: « Effect of oral micronized progesterone on androgen levels in women with polycystic ovary syndrome ». Fertil Steril 2002; 77,6:1125-27.
- Azziz R et al: “Screening for 21-Hydroxylase deficient non classic adrenal hyperplasia among hyperandrogenic women: a prospective study”. Fertil Steril 1999;72:915-925.
- Kahsar-Miller MD et al: “Prevalence of Polycystic ovary syndrome in first-degree relatives of patients with PCOS”. Fertil Steril 2001;75,1:53-58.
- Efstathiadou Zand Tsatsoulis A: “Long-term remission of ovarian hyperandrogenism after short-term treatment with a gonadotropin-releasing hormone agonist”. Fertil Steril 2001;75,1:59-62.
- Glueck CJ et al: “Metformin therapy throughout pregnancy reduces the development of gestational diabetes in women with polycystic ovary syndrome”. Fertil Steril 2002;77,3:520-525.
- Townsend RR, Dipette DJ, Lyeux TR, Wolfe RR: “The role of the renin-angiotensin System in insulin sensitivity in normotensive subjects”. Am J Med Sci 1993;305:67-71.
- Do YS et al: “Human ovaria theca cells are a source of renin”. Proc Nat Acad Sci USA;1988;85:1957-1961.
- Heard M, Pierce A, Carson S, Buster JE: “Pregnancy following use of metformin for ovulation induction in patients with polycystic ovary syndrome”. Fertil Steril 2002;77,4:669-673.
- Legro RS: “Polycystic ovary syndrome. Phenotype to genotype”. Endocrinol Metab Clin North Am 1999;28:379-396.
- Gharani FS, McCarthy M: “Genetic abnormalities in polycystic ovary syndrome”. Ann Endocrinol (Pris) 1999;60:131-133.
- Mastorakos G, Koliopoulos C and Creatsas G : « Androgen and lipid profiles in adolescents with polycystic ovary syndrome who were treated with two forms of combined oral contraceptives ». Fertil Steril 2002;77,5:919-927.
- Robinson S et al: “Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries”. Clin Endocr (Oxford) 1996;44:277-284.
- Telli MH, Yildrim M and Noyan V: “Serum leptin levels in patients with polycystic ovary syndrome”. Fertil Steril 2002;77,5:932-935.
- Waldstreicher J, Santoro NF, Hall JE, Filicori M, Croley WF jr: “Hyperfunction of the hypotalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence of a partial gonadotroph desensitization”. J Clin Endocrinol Metab 1988;66:165-172.
- Cozzolino D et al: “The involvment of the opioid system in human obesità: a study in normal weight relatives of obese people”. J Clin Endocrinol Metab 1996;81:713-718.
- Bates GW and Whitworth NS: “Effects of body weigth reduction on plasma androgens in obese, infertile women”. Fertil Steril 1982;38:406-409.
- Fruzzetti F, Bersi C, Parrini D, Ricci C and Genazzani AR: “Effect of long-term naltrexone treatment on endocrine profile, clinical features, and insulin sensitivity in obese women with ovary syndrome”. Fertil Steril 2002;77,5:936-944.
- Amer SA, Banu Z, Li TC, Cooke ID.: “Long-term follow-up of patients with polycystic ovary syndrome after laparoscopic ovarian drilling: endocrine and ultrasonographic outcomes”. Hum Reprod 2002 Nov;17(11):2851-7.
- Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L.: “Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin”. Hum Reprod 2002 Nov;17(11):2858-64.
- Costello MF, et al: “A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome”. Fertil Steril 2003,79,1-13.
- Dunaif A: “Insulin resistance and the polycystic ovary syndrome : mechanism and implications for pathogenesis. Endocr. Rev. 1997,18:774-800.
- Dunaif A: “Molecular mechanisms of insulin resistance in the polycystic ovary syndrome “. Semin Reprod Endocrinol 1994;12:15-20.
- Nestler JE et6 al: “A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome”. J Clin Endocrin Metab 1991;72:83-89.
- Utiger R: „Insulin and polycystic ovary syndrome“. N Engl J Med 1996;335:657-658.
- Futterweit W: “Polycystic ovary syndrome: clinical perspectives and management”. Obstet Gynaecol Surv 1999;54:403-413.
- Carmina E and Lobo RA: “Treatment of hyperandrogenic alopecia in women”. Fertil Steril 2003;79,1:91-95.
- Haas DA, Carr BR, Attia GR: “Effects of metformin on body mass index, menstrual cyclicity, and ovulation induction in women with polycystic ovary sindrome”. Fertl Steril 2003,79,3:468-481.
- Fulghesu AMet al: “A new ultrasound criterion for the diagnosis of polycystic ovary syndrome: the ovarian stroma/total area ratio”. Fertil Steril 2001;76:326-331.
- Paula A. Radon, MD, Michael J. Mcmahon, MD, Mph And William R. Meyer, MD: “Impaired Glucose Tolerance in Pregnant Women With Polycystic Ovary Syndrome” Obstetrics & Gynecology
- Ibanez L et al, J Clin Endocrinol Metab 2003; 88:2600-2606
- Sahin Y, Yirmibes U, Kelestimur F, Aygen E.: “The effects of metformin on insulin resistance, clomiphene-induced ovulation and pregnancy rates in women with polycystic ovary syndrome”. European Journal of Obstetrics & Gynecology and Reproductive Biology, Volume 113, Issue 2, Pages 214 – 220.
- Stein IF, Leventhal ML: “Amenorrea associated with bilateral polycystic ovaries”. Am J Ostet Ginecol 1935;29:181-191.
- Futterweit W. Polycystic ovary syndrome: clinical perspectives and management. Obstet Gynecol Surv 1999 Jun;54(6):403-13.
- Lanzone et al: “Gli iperandrogenismi e la sindrome dell’ovaio policistico”. Endocrinologia Ginecologica; Editeam editore; Cento (FE); 2004; pagg193-210.
- Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome”. Fertil Steril
- Dunaif A: “Insulin resistance in women with polycystic ovary syndrome” Fertil Steril 2006;86,suppl 1:13-14
- de Zegher F, Ibañez L: “Prenatal growth restraint followed by catch-up of weight: a hyperinsulinemic pathway to polycystic ovarysyndrome”. Fertil Steril 2006;86,suppl 1:S4-S5.
- Droegemueller W, Herbert AL, Mishell DR and Stenchaver MA. Hyperandrogenism. In Comprehensive Gynecology. Second ed. 1992.
- Lobo RA. Hirsutism in polycystic ovary syndrome: current concepts. Clin Obst & gyne 34: 817-826; 1991.
- Rosenfeld RL. Hyperandrogenism in prepubertal girls. Current Issues in Pedia & Adolescent Endocrinology 37: 1333-1358; 1990.
Queste pagine fanno parte del sito fertilitycenter.it in internet da marzo 2011. I testi, le tabelle, i disegni e le immagini pubblicati in queste pagine sono coperte da copyright ma a disposizione di tutti per copia e riproduzione purchè venga citata la fonte con link al sito www.fertilitycenter.it.
Ringrazio i lettori per la loro cortese attenzione e li prego di voler comunicare le loro osservazioni e consigli su eventuali errori o esposizioni incomplete.
Good day very cool site!! Guy .. Excellent .
. Amazing .. I’ll bookmark your website and take the feeds also? I am glad to seek out a lot of useful info right here in the post, we need work out extra techniques in this regard, thank you for sharing. . . . . .
Write more, thats all I have to say. Literally, it seems as
though you relied on the video to make your point.
You clearly know what youre talking about, why waste your intelligence on
just posting videos to your blog when you could be
giving us something informative to read?
J’ai appris beaucouop de chose sur ce sujet grace à vous.
If some one desires to be updated with most up-to-date technologies then he must be pay a
quick visit this web site and be up to date every day.
Here is my web page; rokajmusic.com
Many thanks for an amazing publish, may read your particular others posts. thank you your thinking on this, I soon became a lttle bit made an impact to by this article. Thanks again! You earn a good time. Has wonderful data here. I believe if more people thought of it doing this, they
This Blog deserves far more attention than it is getting right now
Hello! This is my first comment here so I just wanted to give a quick shout out and say I genuinely enjoy reading your articles. Can you recommend any other blogs/websites/forums that cover the same topics? Many thanks!
An impressive share! I have just forwarded this onto a co-worker who was conducting a little
research on this. And he in fact bought me breakfast simply because I
stumbled upon it for him… lol. So allow me to reword this.
… Thank YOU for the meal!! But yeah, thanks for spending the time to talk about this issue here on
your internet site.
Hello this is kind of of off topic but I was wondering if blogs use
WYSIWYG editors or if you have to manually code with HTML. I’m starting a blog soon but have no coding skills so I wanted to get guidance from someone with experience. Any help would be enormously appreciated!
I’ve been surfing online more than 2 hours today, yet I never found any interesting article like yours. It is pretty worth enough for me. In my view, if all web owners and bloggers made good content as you did, the net will be much more useful than ever before.
I think this is among the such a lot important information for me.
And i am happy studying your article. However want to observation on some common issues, The site style is ideal,
the articles is truly excellent : D. Just right activity, cheers
I need to to thank you for this good read!! I definitely loved every bit of it.
I have you saved as a favorite to look at new things you post…
After I originally commented I seem to have clicked on the -Notify me
when new comments are added- checkbox and now each time
a comment is added I get 4 emails with the same comment.
Perhaps there is a way you can remove me from that service?
Thank you for the auspicious writeup. It in truth was a amusement account it.
Look complex to more introduced agreeable from you!
By the way, how could we communicate?
Saved as a favorite, I like your site!
I all the time used to read paragraph in news papers
but now as I am a user of web so from now I am using net for articles or reviews, thanks to web.
It’s going to be ending of mine day, but before ending I
am reading this impressive article to increase my experience.
This piece of writing gives clear idea in favor of the new viewers
of blogging, that genuinely how to do blogging.
Hi, after reading this remarkable article i am also happy to share my
familiarity here with colleagues.
It’s remarkable designed for me to have a web site, which
is beneficial in favor of my know-how. thanks admin
I am not sure where you’re getting your information, but great topic.
I needs to spend some time learning much more or understanding more.
Thanks for great info I was looking for this info for my mission.
There is definately a great deal to find out abou this topic.
I like all the points you have made.
Howdy! This blog post couldn’t be written any better!
Looking at this post reminds me of my previous roommate!
He constantly kept preaching about this. I will forward this article to him.
Fairly certain he’s going to have a good read. I appreciate you for sharing!
Have you ever considered publishing an e-book or
guest authoring on other blogs? I have a blog centered on the same ideas you discuss and would love
to have you share some stories/information. I know
my visitors would appreciate your work. If you’re even remotely interested, feel
free to shoot me an email.
Hello there, I found your website by way of Google at the same time as looking for a related matter,
your web site came up, it appears good. I have bookmarked it in my google
Hello there, just become alert to your blog via Google, and located that it is really informative.
I am going to watch out for brussels. I will be grateful in the event you proceed this in future.
Many other folks can be benefited from your writing.
Hi there, constantly i used to check web site posts here early in the dawn,
since i enjoy to learn more and more.
Right here is the perfect blog for everyone who wishes to understand this topic.
You realize a whole lot its almost hard to argue with
you (not that I really will need to…HaHa). You certainly put a new spin on a subject that’s been discussed for years.
Excellent stuff, just great!
Very nice post. I simply stumbled upon your weblog and wished to mention that I’ve truly enjoyed surfing
around your weblog posts. After all I will be subscribing in your rss feed and I’m hoping you write again soon!
Whats up this is kind of of off topic but I was wanting to know
if blogs use WYSIWYG editors or if you have to manually code with HTML.
I’m starting a blog soon but have no coding expertise
so I wanted to get advice from someone with experience. Any help would be greatly appreciated!
As the admin of this web page is working, no hesitation very soon it will be renowned,
due to its quality contents.
I’m really enjoying the design and layout of your blog.
It’s a very easy on the eyes which makes it much more pleasant
for me to come here and visit more often. Did you hire out a developer to create your theme?
Good day! I could have sworn I’ve been to this website before but after browsing through some of the post I realized it’s new to
me. Nonetheless, I’m definitely glad I found it and I’ll be bookmarking
and checking back frequently!
This article provides clear idea designed for the new users of blogging, that actually how to do blogging and site-building.
great isѕues altogethеr, you simploy gained a new reader.
What could yyou sugցest about your post thаt yoou sіmply made ѕome daƴs
in thе past? Any sure?
Hi, I do think this is an excellent blog. I stumbledupon it 😉 I’m
going to return yet again since I book-marked
it. Money and freedom is the greatest way to change,
may you be rich and continue to guide others.
With havin so much content do you ever run into any issues of plagorism or copyright violation? My blog has a lot
of exclusive content I’ve either authored myself or outsourced but it looks like a lot of it
is popping it up all over the internet without my permission. Do
you know any solutions to help stop content from being ripped off?
I’d certainly appreciate it.
I like it when folks come together and share views.
Great blog, keep it up!
Valuable information. Fortunate me I found your website accidentally, and I am surprised why this coincidence
didn’t happened earlier! I bookmarked it.
Hello, i think that i saw you visited my weblog so i came to “return the favor”.I am attempting to
find things to improve my web site!I suppose its ok to use
some of your ideas!!
Hi there! Wouldd you mind if I share your blog with
myy zynga group? There’s a lot of folks that I think would really enjoy your content.
Please let me know. Thank you
Hello to all, how is the whole thing, I think every
one is getting more from this web page, and your views are nice in favor of new visitors.
Depending upon the experience of thee traders, the use of thee indicators could be made.
Feel free to surf to my web-site start a website
Hello, i think that i noticed you visited my web site thus
i came to return the want?.I’m attempting to in finding issues to improve my website!I assume its ok to use some of
I seriously love your blog.. Pleasant colors & theme. Did you develop this website yourself?
Please reply back as I’m wanting to create my own personal site and would love to know where you got this from or
what the theme is named. Thanks!
I really like looking through an article that can make people think.
Also, many thanks for permitting me to comment!
I am special innovations that are such can get updated into Boom Seashore eventually,
but today it’s really a touch bare.
It’s hard to find educated people for this subject, but you seem like
you know what you’re talking about! Thanks
Good way of explaining, and pleasant article to obtain data on the topic of my presentation focus,
which i am going to present in college.
Hi to all, it’s truly a fastidious for me to visit
this website, it consists of helpful Information.
Hello There. I discovered your weblog using msn. This is an extremely neatly written article.
I’ll make sure to bookmark it and return to read extra of your helpful information. Thank you for
the post. I will certainly return.
Link exchange is nothing else but it is just placing the other person’s webpage link on your page at appropriate place and other person will also do similar in support of you.
Valuable information. Lucky me I discovered your site by chance, and
I am shocked why this coincidence did not happened in advance!
I bookmarked it.
You actually make it seem really easy together with your presentation however I
in finding this matter to be actually something that I think
I might never understand. It seems too complex and extremely broad for me.
I am having a look forward in your next put up, I will try to
get the hold of it!
despues de consultar varios sitios la verdad es que tu sitio es el mas util.
Feel free to surf to my weblog: http://www.108.co.nz/profile.php?id=146469
Woah! I’m really enjoying the template/theme of this site.
It’s simple, yet effective. A lot of times it’s very difficult to get that “perfect balance” between user friendliness and visual appearance.
I must say you’ve done a excellent job with this.
In addition, the blog loads extremely fast for me on Safari.
Hello, Neat post. There’s a problem along with your site in web explorer, mjght check this?
IE still iis the marketplace chief and a large component off pwople will miss your wonderful writing
because of thiis problem.
If you ever feel like you cannot succeed at making money online, take a look at Ewen Chia.
All this without ever meeting ANY of your clients face-to-face.
Some time ago, it wasn’t such a big problem, because only few people did
Hello my family member! I wish to say that this article is awesome, nice written and come with almost all vital infos.
I’d like to see more posts like this .
Thanks for your personal marvelous posting! I definitely enjoyed reading it, you’re a great
author.I will remember to bookmark your blog and may come back sometime soon. I want
to encourage one to continue your great work, have
a nice weekend!
Awesome issues here. I’m very satisfied to look your post.
Thanks so much and I am looking forward to touch you.
Will you please drop me a mail?
Thanks very interesting blog!
No matter if some one searches for his vital thing, thus he/she wishes to be
available that in detail, thus that thing is maintained over here.
I was recommended this web site by my cousin. I’m not sure whether this post is written by him
as no one else know such detailed about my difficulty. You are wonderful!
It’s wonderful that you are getting ideas from this
piece of writing as well as from our discussion made here.
Greetings! I know this is kind of off topic but I was wondering
which blog platform are you using for this website?
I’m getting fed up of Wordpress because I’ve had problems with hackers and I’m
looking at alternatives for another platform. I would be fantastic if you
could point me in the direction of a good platform.
Yes! Finally someone writes about free online.
whoah this blog is wonderful i really like reading your posts.
Stay up the great work! You recognize, many people are
hunting round for this information, you can help them greatly.
Hurrah, that’s what I was looking for, what a data! existing here at this web site,
thanks admin of this web page.
Hi, I do think this is an excellent site. I stumbledupon it 😉 I
am going to return once again since i have book marked it.
Money and freedom is the greatest way to change, may you be rich
and continue to guide other people.
Hi, its pleasant article concerning media print, we all understand media is a
great source of data.
My spouse and I stumbled over here different website and thought I should check things out.
I like what I see so i am just following you. Look forward to exploring your web page yet again.
I’m gone to say to my little brother, that he should also visit this blog
on regular basis to get updated from most up-to-date reports.
If you desire to get a great deal from this post then you have
to apply these strategies to your won webpage.
I don’t know whether it’s just me or if perhaps everybody else encountering problems with your
site. It looks like some of the written text within your posts are running off the screen. Can somebody else please comment and
let me know if this is happening to them as well? This may be
a problem with my internet browser because I’ve had this happen previously.
Hi Dear, are you actually visiting this website on a regular basis, if so then you will definitely
take pleasant experience.
Fantastic beat ! I wish to apprentice while
you amend your website, how could i subscribe for a blog site?
The account aided me a acceptable deal. I were a little bit acquainted of this your broadcast offered
vibrant transparent concept
You need to be a part of a contest for one of the most useful sites on the web.
I am going to recommend this blog!
Wow, amazing blog format! How lengthy have you been running a blog
for? you make running a blog look easy. The total
look of your website is wonderful, let alone the content!
Asking questions are actually fastidious thing if you are not
understanding anything entirely, except this post offers pleasant
This is my first time pay a visit at here and i am truly impressed to
read all at single place.
Hello to all, tthe copntents present at this website are genuinely aawesome
ffor people knowledge, well, keep up the nice work fellows.
This post provides cleaqr idea in favor of the new users off blogging,
that inn factt how to do blogging.
Awesome blog! Is your theme custom made or
did you download it from somewhere? A theme like yours with a few
simple tweeks would really make my blog shine. Please let me know where
you got your theme. With thanks
What’s up to every one, it’s in fact a good for me
to visit this site, it contains priceless Information.
Here are several tips in the truth about abs review. An effective and balanced diet is
required for your body to function efficiently and you will probably also feel more energetic.
Sleep deprivation is additionally connected to several health problems,
including heart problems.
Hi everyone, it’s my first pay a quick visit at this web page, and article is
really fruitful in favor of me, keep up posting these content.
I really like reading an article that will ake men and women think.
Also, many thanks for permitting me to comment!
Link exchange is nothing else but it is only placing the other
person’s webpage link on your page at suitable place and other person will also do same in favor of you.
This design is wicked! You obviously know how to keep a reader amused.
Between your wit and your videos, I was almost
moved to start my own blog (well, almost…HaHa!) Wonderful job.
I really enjoyed what you had to say, and more than that, how you presented
it. Too cool!
I got this site from my pal who told me concerning this site and at the moment this
time I am browsing this web site and reading very informative content at this
Thanks for another informative blog. Where else could I am getting that kind of information written in such a perfect manner?
I’ve a venture that I am simply now working on, and I have been on the look out for such
What’s up, just wanted to tell you, I loved this article.
It was helpful. Keep on posting!
Feel free to visit my weblog :: clash of clans hack
It really is supported by iOS and Google android platforms and gets results on iPhone, iPad and Android mobile phones
Wonderful blog! I found it while browsing on Yahoo
News. Do you have any tips on how to get listed
in Yahoo News? I’ve been trying for a while but I never seem to get there!
Fabulous, what a webpage it is! This website provides
valuable facts to us, keep it up.
When someone writes an article he/she retains the idea of a user in his/her brain that how a user can be aware of
it. Therefore that’s why this paragraph is amazing. Thanks!
Tengo aprenda alguna justo cosas aquí. Definitivamente precio marcadores para volver a visitar.
I extrañar cómo mucho coloca a crear tal magnífico Página web.
Hey I know this is off topic but I was wondering if you knew of any widgets I could add to my blog that automatically tweet my newest twitter updates.
I’ve been looking for a plug-in like this for quite some time and was hoping maybe you would have some experience with something like this.
Please let me know if you run into anything. I truly enjoy reading
your blog and I look forward to your new updates.
Here is a list of all unique Home Depot ZIP codes,
in case anyone wants to double check my work.
Hi there this is somewhat of off topic but I was wondering if blogs use WYSIWYG editors
or if you have to manually code with HTML. I’m starting a blog soon but have no coding expertise so
I wanted to get guidance from someone with experience.
Any help would be greatly appreciated!
Oh my goodness! Incredible article dude! Many thanks, However I am having
difficulties with your RSS. I don’t understand the reason why I am unable
to subscribe to it. Is there anybody else getting the same RSS problems?
Anyone that knows the solution can you kindly
Hello to every one, as I am actually eager of reading this weblog’s post to be updated regularly.
It carries good data.
Hi to every body, it’s my first go to see of
this webpage; this blog carries amazing and genuinely excellent stuff for readers.
Hi, I read your blog daily. Your humoristic style is witty, keep it up!
I don’t even know how I ended up here, however I believed this post
was once good. I don’t understand who you’re however certainly you’re going to a famous blogger in case you are not already.
After I initially commented I seem to have clicked
the -Notify me when new comments are added- checkbox and now every
time a comment is added I receive 4 emails with the exact same comment.
There has to be a way you can remove me from that service?
Hi, everything is going fine here and ofcourse every one is sharing facts, that’s really good,
keep up writing.
Truly when someone doesn’t understand then its up to other people that
they will assist, so here it occurs.
In fact when someone doesn’t understand after that its up to other visitors that they will assist, so here
Excellent beat ! I wish to apprentice while you amend your
website, how can i subscribe for a blog site? The
account aided me a acceptable deal. I had been tiny bit
acquainted of this your broadcast provided bright
Hello my loved one! I want to say that this post is awesome, great
written and come with approximately all vital infos.
I would like to look more posts like this .
Hence you may not be getting any recognition for your work.
So, what other factors come into play to determine relevance.
Since the successful launch of the Automatic Backlink Creator,
the team realizes there are just a few minor flaws inside the first version and so they are releasing ABC version 2 that promises more features and higher reliability.
Once it passes through glass or plastic, the UV is filtered out.
When setting up the aquarium it is important to use an external heat
source to maintain a temperature range of 75 -85 F.
Ideally it becomes good to have an interior and
an outdoor cage if possible.
Responsible lenders are not working to clean out your bank account.
She wants potential buyers to save at least 20% for
a down payment’and that’s on top of having an 8-month
emergency fund saved up. The borrowers if desire can also seize supplementary
time for arrangement but will then are obliged to forfeit further sum in the form of very
Hi to every one, the contents existing at this site
are actually awesome for people experience, well, keep up the nice work fellows.
Ne cliquez pas en allant sur leurs vidéos qui sont capables contenir kklk virus donnés pour vous-même voler
vos ne vos informations.
Appreciating the dedication you put into your site and in depth
information you offer. It’s great to come across a blog every once in a while that isn’t the same unwanted rehashed material.
Great read! I’ve bookmarked your site and I’m including your RSS feeds to my Google account.
I like the helpful information you provide in your articles.
I’ll bookmark your weblog and check again here regularly.
I am quite certain I will learn many new stuff right here! Good
luck for the next!
My relatives all the time say that I am wasting my time here at net, but I know
I am getting know-how all the time by reading such pleasant articles or reviews.
These are truly impressive ideas in on the topic
of blogging. You have touched some nice points here.
Any way keep up wrinting.
I have read several excellent stuff here. Certainly price bookmarking for revisiting.
I wonder how a lot effort you set to make any such wonderful informative web site.
It’s going to be end of mine day, however before ending I am reading this
fantastic piece of writing to improve my experience.
Great blog you have here.. It’s hard to find quality writing
like yours these days. I really appreciate people like
you! Take care!!
It’s great that you are getting thoughts from this
post as well as from our discussion made at this time.
Wow, this post is nice, my younger sister is analyzing such things, therefore I am going to let know her.
Nice weblog here! Also your web site loads up very fast!
What web host are you the usage of? Can I get your associate hyperlink on your host?
I desire my website loaded up as quickly as yours lol
It’s actually very complicated in this busy life to listen news on Television, so I only use web for that reason,
and get the most recent news.
Hi there, the whole thing is going sound here and ofcourse every one is sharing
information, that’s in fact good, keep up writing.
Excellent post. Keep writing such kind of information on your blog.
Im really impressed by it.
Hi there, You’ve done an incredible job. I’ll definitely
digg it and individually recommend to my friends.
I’m sure they will be benefited from this
Hi just wanted to give you a quick heads up and let you know a few of the pictures aren’t loading properly.
I’m not sure why but I think its a linking issue.
I’ve tried it in two different web browsers and both show the same outcome.
Thank you, I have recently been searching for
information approximately this subject for a long time and yours is
the best I’ve came upon so far. However, what in regards to the conclusion? Are you certain concerning
I was very happy to find this site. I wanted to thank
you for your time for this particularly wonderful read!!
I definitely enjoyed every part of it and i also have you book-marked
to look at new things in your web site.
I am in fact plеased to read this blog posts which includes lots of
valuable data, thanks for providing these statistics.
I like the helpful info you provide on your articles.
I’ll bookmark your weblog and test once more here frequently.
I’m quite sure I will learn lots of new stuff right right here!
Good luck for the following!
If you are going for finest contents like me,
just go to see this site every day for the reason that it provides
feature contents, thanks
My spouse and I stumbled over here different web address and thought I might check things out.
I like what I see so i am just following you. Look forward to finding out about your web
When I initially commented I clicked the “Notify me when new comments are added” checkbox and now each time a
comment is added I get three emails with the same comment.
Is there any way you can remove people from that service?
Hi everyone, it’s my first pay a visit at this website, and post is really fruitful
in support of me, keep up posting these articles or reviews.
Hey! This post could not be written any better! Reading through this post reminds me of my old room mate!
He always kept talking about this. I will forward this article to him.
Fairly certain he will have a good read. Thank you
I’d like to find out more? I’d want to find out some additional information.
What’s up to all, how is the whole thing, I think every one
is getting more from this site, and your views are pleasant
in support of new users.
Superb, what a web site it is! This web site provides
useful facts to us, keep it up.
I don’t even know how I ended up here, but I thought this post was great.
I do not know who you are but definitely you’re going to a famous blogger if you are not already
Hmm is anyone else having problems with the images on this blog loading?
I’m trying to figure out if its a problem on my end or if it’s the blog.
Any feedback would be greatly appreciated.
I like looking through an article that will make people think.
Also, thank you for allowing for me to comment!
constantly i used to read smaller articles that also clear their motive, and that is also happening with this paragraph which I am reading at this time.
Hello to all, how is all, I think every one is getting more from this web page,
and your views are pleasant designed for new users.
Hey there, You Һave ⅾone an incredible job.
I’ll ԁefinitely digg іt and personally ѕuggest
tօ mү friends. I
ɑm confident they ѡill ƅe
benefited from tҺіѕ site.
Your wɑү of telling аll in tɦіѕ post іѕ actually
fastidious, аll bе capable οf effortlessly қnoա іt, Ƭhanks a
Excellent blog you’ve got here.. It’s hard to find good quality writing like
yours nowadays. I truly appreciate individuals like you!
Howdy, I think your blog could be having browser compatibility issues.
Whenever I take a look at your website in Safari, it looks fine however, when opening in Internet Explorer, it has some overlapping issues.
I just wanted to provide you with a quick heads up! Besides that, wonderful website!
Hi, i feel that i saw you visited my web site thus i got here to return the
favor?.I am trying to to find things to enhance my web site!I assume
its ok to make use of a few of your ideas!!
Hi there to every one, the contents present at this site
are in fact remarkable for people experience, well,
keep up the nice work fellows.
Hey! I know this is somewhat off topic but I was wondering which blog platform are you using for
this site? I’m getting tired of Wordpress because I’ve had problems with hackers and I’m looking at
alternatives for another platform. I would be great if you could point me in the direction of a good platform.
Howdy, I do believe your web site may be having web
browser compatibility problems. Whenever I take a look at your blog in
Safari, it looks fine however, if opening in I.E.,
it’s got some overlapping issues. I just wanted to give you a
quick heads up! Aside from that, fantastic website!
I’d like to thank you for the efforts you’ve put in writing this site.
I am hoping to see the same high-grade blog posts by you in the future as
well. In truth, your creative writing abilities has motivated me to get my own website now 😉
I am actually delighted to read this blog posts which includes plenty of valuable data,
thanks for providing these data.