Emilio Piccione

Macrophage Migration Inhibitory Factor in Human Pregnancy and Labor

PROBLEM: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in reproduction. Presently there is no information on the possible involvement of MIF in the onset of labor.

The influence of BMI, smoking, and age on vaginal erosions after synthetic mesh repair of pelvic organ prolapses. A multicenter study

Objective. To study the influence of body mass index (BMI), smoking, and age on the risk of vaginal erosions after mesh repair of pelvic prolapses. Design. Retrospective study. Setting. Three university and community hospitals. Population and sample. Patients that underwent mesh correction of prolapses between 2002 and 2007. Excluded were those with stress urinary incontinence, ongoing clinical infections, with a complete antibiotic course in the last six months and with systemic diseases affecting tissue oxygenation. Methods. Revision of medical notes. Main outcome measures. Risk contributions for age, smoking, and BMI on the occurrence of vaginal erosions. Results. Data were collected from 460 patients. Postoperative erosions were present in 7%. BMI greater than 30 conferred a 10.1‐fold increase in the risk of developing erosions, smoking a 3.7‐fold increase, and age greater than 60 years a 2.2‐fold increase. A cut‐off value of seven pack years was determined for smoking where the risk associated with light smokers was similar to that of non‐smokers. Conclusions. BMI, smoking, and age are important risk factors for pelvic organ prolapse surgery. Our data could be used to stratify patients according to their risk so that preventative measures can be taken in high‐risk patients.

Functionally active complement is present in human ovarian follicular fluid and can be activated by seminal plasma

Human ovarian preovulatory follicular fluids (FF) from 10 women were analysed for their complement contents. Functionally active complement was detected in all the fluids studied in amounts similar to those present in normal human serum. Pooled FF was challenged by seminal plasma in order to determine whether seminal plasma could activate FF complement, the pattern of such an activation and the possible consequences on the reproductive function. FF complement activation occurred during the incubation with seminal plasma with features including alternative pathway activation, factor B and C3 conversion and reduction in total haemolytic complement, as well as an inhibition by seminal plasma of the FF complement response to a new activating challenge. Possible consequences for fertilization, implantation of a fertilized ovum and local defence mechanisms against viruses and bacteria are discussed.

The role of serum anti-Müllerian hormone (AMH) in the hormonal diagnosis of polycystic ovary syndrome

Abstract Background: The study was performed to validate the threshold for anti-Müllerian hormone (AMH) that suggests the presence of polycystic ovaries in women with polycystic ovary syndrome (PCOS). Methods: This prospective observational study included 59 infertile women: (A) 22 PCOS with hyperandrogenism (HA) and oligo-anovulation, (B) 15 suspected PCOS with either HA or oligo-anovulation and (C) 22 asymptomatic control women. The diagnosis of PCOS was made according to the NIH classification. Results: For serum AMH and follicle number, respectively, the areas under the receiver operating characteristic curve (A versus C) were 0.97 and 0.93. The best compromise between specificity (95% and 91%) and sensitivity (95% and 82%) was obtained with threshold values of 33 pmol/l and 13 follicles, respectively. Using a serum AMH > 33 pmol/l as a surrogate for either HA or oligo-anovulation in group B would lead to the diagnosis of PCOS in seven (46.6%) patients from this group. Conclusions: Our data confirms that the AMH assay has a high diagnostic potential, providing that an appropriate threshold is used. AMH measurement may be included as an ultimate diagnostic criterion for the diagnosis of PCOS when either HA or anovulation is missing and/or when no reliable antral follicle count can be obtained.

A comparison of vaginal, laparoscopic-assisted vaginal, and minilaparotomy hysterectomies for enlarged myomatous uteri.

To compare the operative data and early postoperative outcome of vaginal hysterectomy (VH), laparoscopic‐assisted vaginal hysterectomy (LAVH), and minilaparotomy hysterectomy (MiniLPT).

Thyroid autoimmunity and recurrent miscarriage

Citation Ticconi C, Giuliani E, Veglia M, Pietropolli A, Piccione E, Di Simone N. Thyroid autoimmunity and recurrent miscarriage. Am J Reprod Immunol 2011; 66: 452–459

Role of type I collagen C telopeptide, bone-specific alkaline phosphatase and osteocalcin in the assessment of bone status in postmenopausal women.

Aim:  To investigate the clinical role of the bone turnover markers type I collagen C telopeptide (CTX), osteocalcin (OC) and bone‐specific alkaline phosphatase (BAP) in the assessment of bone status in women with postmenopausal osteoporosis.

Hormonal regulation of cytokine release by human fetal membranes at term gestation: effects of oxytocin, hydrocortisone and progesterone on tumour necrosis factor-α and transforming growth factor-β 1 output

Inflammatory cytokines can play an important role in the biomolecular processes leading to labour by regulating prostaglandin production in intrauterine tissues. In the setting of intrauterine infection, an increased production of these cytokines by placenta, decidua and fetal membranes occurs and is responsible for the onset and maintenance of preterm labour. However, the factors involved in the control of cytokine release by these tissues in normal pregnancy at term are still largely unknown. We investigated the possibility that the synthesis and release of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) by human fetal membranes at term gestation is regulated by several hormones potentially involved either in the maintenance of pregnancy or in the parturitional process. In the present study, the effects of hydrocortisone, progesterone and oxytocin on TNF-alpha and TGF-beta1 release by explants of fetal membranes at term gestation were evaluated. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the effect of the above hormones on mRNA expression; TNF-alpha and TGF-beta1 release in culture medium was quantitifed by ELISA assays. Results show that both tissue mRNA expression for TNF-alpha and TNF-alpha release in culture medium were significantly increased by oxytocin, but not by hydrocortisone and progesterone. On the contrary, all the hormones tested increased both tissue TGF-beta1 mRNA expression and release in culture medium. These findings suggest that TNF-alpha and TGF-beta1 production by human fetal membranes in uncomplicated pregnancy at term is selectively modulated by oxytocin, hydrocortisone and progesterone.

Thrombin-activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.

OBJECTIVE To investigate the possible association between selected thrombin-activatable fibrinolysis inhibitor (TAFI) single nucleotide polymorphisms (SNPs) and recurrent pregnancy loss (RPL). DESIGN Case-control study. SETTING University hospital. PATIENT(S) One hundred fifty-eight women (86 cases and 72 controls). INTERVENTION(S) Determination of TAFI SNPs -438A/G, +505A/G, +1040T/C, +1542C/G, and +1583A/T by polymerase chain reaction (PCR) reactions and sequencing analysis performed on peripheral blood samples. MAIN OUTCOME MEASURE(S) Analysis of the genotype and allele frequencies of TAFI SNPs -438A/G, +505A/G, +1040T/C, +1542C/G, and +1583A/T in women with and without RPL. RESULT(S) Genotype and allele frequencies of TAFI +505 and +1583 SNPs were significantly different in women with RPL compared with control women. The frequencies of the +505A/A and +505G/G genotypes were 1.2% and 61.6% in women with RPL and 13.9% and 43.1% in control women, respectively. The frequencies of the +1583A/A and +1583T/T genotypes were 1.2% and 61.6% in women with RPL and 13.9% and 45.8% in control women, respectively. The genotype and allele frequencies at TAFI position -438, +1040, and +1542 were not significantly different between RPL and control women. CONCLUSION(S) The SNPs leading to increased TAFI levels are associated with a reduced risk of RPL. It is possible that TAFI is involved in RPL.

Regulation of phosphodiesterase 5 expression and activity in human pregnant and non-pregnant myometrial cells by human chorionic gonadotropin

Objectives: This study has a twofold aim: 1) to investigate whether protein expression and enzyme activity of phosphodiesterase 4 (PDE5) can be detected in human myometrium and undergo changes in relation to the presence of pregnancy and/or labor; 2) to evaluate whether PDE 5 expression and activity in myometrial cells can be influenced by human chorionic gonadotropin (HCG). Methods: Primary cultures of myometrial cells, obtained from non-pregnant women and from pregnant women at tem, either before or during labor, were carried out in the presence of HCG or dibutyryl-cyclic AMP (ad-cAMP), the non-hydrolizable analogue of cAMP. PDE5 expression in cultures of myometrial cells was detected by immunocytochemistry and western blot. PDE5 activity was detected in cell extracts by enzyme assay. Results: PDE5 is expressed and is functionally active in smooth myscle cells. Treatment of cell cultures with HCG and db-cAMP results in a reduction of PDE5 expression and activity. The effects of HCG and db-cAMP are exerted irrespective of the functional status of the myometrium (n0n-pregnant, pregnant not in labor, pregnant in labor). Conclusions: PDE5 protein is expressed in human non-pregnant and pregnant myometrium. HCG reduces PDE5 expression and enzyme activity in smooth muscle cells, possibly through a pathway involving cAMP