An epidemiological survey of Mycoplasma hominis and Ureaplasma urealyticum in gynaecological outpatients, Rome, Italy.

The objective of this study was to assess the prevalence of Ureaplasma urealyticum and Mycoplasma hominis infections and to investigate associations between their presence in the lower female genital tract and lifestyle characteristics. The study was performed on a population of 3115 women, comparing the demographic and behavioural characteristics of 872 women with U. urealyticum infection and 142 women with M. hominis with uninfected women, using univariate and multiple logistic regression analysis. The prevalence of infection with U. urealyticum was 28% and M. hominis was 4.6%. In multivariate logistic regression analysis, intrauterine device, number of sexual partners and age (<35 years) were significantly associated with U. urealyticum while previous induced abortion, condom use and young age at first intercourse (<16 years) were associated with M. hominis infection. U. urealyticum infection presents the same demographic and behavioural characteristics of a sexually transmitted disease. The unprotective role of condom use suggests a non-sexual mode of transmission of M. hominis infection.

In vitro fertilization stimulation protocol for normal responder patients.

The aim of this prospective observational study is to determine the different outcomes of IVF/ICSI treatments after using antagonists or agonists of gonadotrophin-releasing hormone (GnRH) for controlled ovarian hyperstimulation (COH) in normal responder patients. Two hundred forty-seven patients undergoing IVF treatment at the Centre of Reproductive Medicine, Rome (CERMER), from January 2005 to December 2008, were included in the study. Patients were stimulated either with a standard long protocol with GnRH agonists (n = 156) or with GnRH antagonists (n = 91). The use of GnRH antagonists resulted in a significant reduction in the duration of the stimulation (Agonist Group 14.10 ± 2.25 vs Antagonist Group 11.34 ± 2.11; p < 0.001) and in the amount of gonadotrophin (IU of r-FSH) needed (Agonist Group 1878 ± 1109 vs Antagonist Group 1331 ± 1049; p = 0.0014). Moreover a lower number of cycles were cancelled with the antagonist protocol (4.39 vs 6.41%). The GnRH antagonist protocol, when compared to the GnRH agonist one, is associated with a similar clinical pregnancy rate, similar implantation rate, significantly lower gonadotrophin requirement and shorter duration of stimulation. For this reason, GnRH antagonists might be a good treatment even for normal responder patients undergoing IVF.

Methylenetetrahydrofolate reductase gene promoter hypermethylation in semen samples of infertile couples correlates with recurrent spontaneous abortion.

STUDY QUESTION: Is the methylation status of the methylenetetrahydrofolate reductase (MTHFR) promoter region in semen samples associated with 'recurrent spontaneous abortion' (RSA)? SUMMARY ANSWER: MTHFR promoter hypermethylation is more frequent in semen samples from RSA couples than in semen samples from infertile couples with no history of RSA (NRSA) and affects the whole sperm population significantly more often. WHAT IS KNOWN ALREADY: Modifications to the MTHFR gene such as polymorphisms and promoter methylations are associated with male infertility. STUDY DESIGN, SIZE AND DURATION: Retrospective cohort study of semen samples from 20 RSA couples, 147 NRSA couples and 20 fertile men between 2011 and 2012. MATERIALS, SETTING AND METHODS: DNA from the semen samples of RSA, NRSA and fertile men were analyzed by methylation-specific PCR amplification using primers which anneal to the methylated or unmethylated cytosine-phosphodiester bond guanine (CpG) islands within the promoter region of MTHFR. The specificity of the PCR products was assessed by DNA sequencing. MAIN RESULTS AND THE ROLE OF CHANCE: The methylated MTHFR epigenotype (including samples where it co-existed with unmethylated MTHFR epigenotypes) was detected in 75% of RSA men, 54% of NRSA men and 15% of fertile men. MTHFR methylation was observed in the whole sperm population in semen samples from 55% of RSA men compared with 8% in NRSA men (P < 0.05) and 0% in fertile men (P < 0.05). DNA sequencing analysis was fully concordant with the PCR results and revealed that when MTHFR methylation occurred, CpG islands within the promoter region were 100% methylated (hypermethylation of MTHFR promoter). LIMITATIONS, REASONS FOR CAUTION: The relatively small sample size of RSA infertile couples. WIDER IMPLICATIONS OF THE FINDINGS: The hypermethylation of the MTHFR gene promoter should be taken into consideration as a novel putative risk factor in RSA etiology. STUDY FUNDING/COMPETING INTEREST(S): Our institution has received an FAR research grant from the University of Ferrara, Ferrara, Italy. No competing interests declared.

Pancreatic cancer with liver metastases in a pregnant patient: case report and review of the literature.

In this case report, the authors discuss clinical presentation, surgical procedure and early results of chemotherapy of pancreatic carcinoma with liver metastases diagnosed a few days after delivery. Pancreatic adenocarcinoma occurs infrequently in pregnant and childbearing women: only ten cases have been reported in the literature. The early diagnosis of pancreatic cancer is difficult because symptoms appear when cancer is about to reach an advanced stage. In pregnancy, it is even more difficult because symptoms like dyspepsia, vomiting and epigastric pain may result confusing. The authors outline the difficulties in diagnosis and treatment of this kind of disease during pregnancy.

Pregnancy in patients with undifferentiated connective tissue disease: a prospective case-control study.

OBJECTIVES: To assess the outcome of pregnancy and disease flare or differentiation into well-defined connective tissue disease (CTD), in a cohort of pregnant patients with undifferentiated connective tissue disease (UCTD) and to compare these findings with those obtained from a population of non-pregnant women with UCTD. METHODS: In total, 55 pregnancies (in 50 UCTD patients) were monitored from the positive pregnancy test until the sixth month after delivery. Likewise, during a 15-month timeframe, the incidence of flares or evolution into a major CTD was also recorded in a population of 53 non-pregnant women with UCTD. The Student t-test was applied for unpaired, continuous variables and chi-square was applied when percentages were compared. RESULTS: The mean duration of the successful pregnancies was 38.6 weeks (range 28-42) while the mean birth weight was 3190 g (range 1200-4600 g). Three pregnancies (5.4%) ended in miscarriage. The following obstetric complications were found: five premature membrane ruptures, two preeclampsia and two intra-uterine growth restrictions. In a total of 16 patients (32%) the disease flared during pregnancy or during the 6-month post-delivery period. Of these, five developed well-defined CTD after delivery. In the control population, six patients flared (11%) and, of these, only one developed a well-defined CTD. CONCLUSIONS: If pregnancy is properly treated, the outcome in UCTD patients is generally good while, considering disease activity, pregnancy appears to be a clear risk factor for flare up or evolution into well-defined CTD.

Betamethasone, progesterone and RU-486 (mifepristone) exert similar effects on connexin expression in trophoblast-derived HTR-8/SVneo cells.

Connexins (Cx) are membrane proteins able to influence cell trophoblast responses, such as proliferation, differentiation, migration and invasiveness. Likewise, glucocorticoids are also known to modulate many factors involved in implantation, including trophoblast gap-junction intercellular communication, although their influence on pregnancy is controversial. In order to investigate the effects of betamethasone, a synthetic glucocorticoid, on Cx and glucocorticoid receptor (GR) expression and localisation, as well as on cell proliferation, the extravillous trophoblast-derived HTR-8/SVneo cell line was used as a model. The results, confirmed by means of immunofluorescence, demonstrate that betamethasone selectively modifies GR and Cx expression, enhancing the GRα isoform without affecting GRß, and inhibiting Cx40 expression whilst increasing that of Cx43 and Cx45. Furthermore, betamethasone was shown to exert an inhibitory action on cell proliferation. In this model the abortion drug RU-486 (mifepristone), reported to be a GR antagonist, did not counteract this effect of betamethasone. On the contrary, it induced responses similar to those of the hormone. Knowing that RU-486 is also a potent progesterone-receptor antagonist, the effect of progesterone alone and in combination with the drug on Cx expression and cell proliferation was then tested. Progesterone showed the same effect as betamethasone on Cx expression, but it did not affect proliferation. Based on these results, neither the abortion effects of RU-486 nor the protective action of betamethasone and progesterone are exerted by modulation of Cx. RU-486 did not antagonise the progesterone effect, suggesting that its abortive action does not involve alteration of trophoblast Cx expression.

Use of glucocorticoids in pregnancy.

For many years glucocorticoids have been used world-wide in pregnant women for treatment of a variety of medical disorders, from bronchial asthma to systemic lupus erythematosous, to renal transplant. More recently their administration has been successfully addressed to the prevention of congenital fetal diseases. In some of these, such as for instance the 21-hydroxylase deficiency leading to congenital adrenal hyperplasia, the pathogenic mechanism is well known, while in others, such as the cystic adenomatoid malformation of the lung, it is not yet understood. Besides these types of diseases, there are acquired inflammatory conditions impairing the physiologic evolution of pregnancy that benefit from glucocorticoid administration. This is the case in recurrent miscarriage due to increased concentration of decidual Natural Killer cells, as well as in the Romero's syndrome, leading to premature parturition and related life threatening fetal complications. However, in spite of its prominent efficacy, the therapy is generally viewed with some suspicion because of possible fetal and maternal adverse effects. With the aim to contribute to a better knowledge of the basic mechanisms of glucocorticoid protection, we reviewed the regulation of their trans-placental passage, their biological effects on gestational environment, their possible 'programming' and teratogenic action, and their accepted use for prevention and cure of pregnancy complications. We believe that a more qualified and liberal use of these compounds will lead in many cases to a significant improvement of fetal and maternal prognosis.

[Cervical cerclage and evidence-based medicine: if, how and when]. / Il cerchiaggio cervicale e la medicina basata sull'evidenza: se, come e quando.

Cervical cerclage has always been the main treatment option in cases of so-called cervical insufficiency, a condition that is notoriously associated with a high risk of second trimester abortion and/or preterm delivery. We can distinguish between a prophylactic cerclage, to be performed electively, usually at 13-16 weeks gestation, only when the woman has a history extremely suggestive for cervical incompetence (3 or more mid-trimester abortions or preterm deliveries) and a therapeutic cerclage. This last cerclage is recommended either for women who have ultrasonographic changes consistent with a short cervix or the presence of funneling after the 16-20 weeks gestation (urgent cerclage) and for women who present the asymptomatic dilation of the uterine cervix of at least 2 cm and/or a prolapse of the amniochorial membranes (emergent cerclage). So far there is still a lack of controlled and randomized trials that can unquestionably demonstrate the advantages of the cervical cerclage in comparison with a ''wait and see'' aptitude. The cerclage can be performed either transvaginally, usually according to the McDonald technique, or transabdominally. This last approach is recommended when a transvaginal cerclage has to be avoided because of technical difficulties depending on the conditions of the cervix or when the pregnant woman has a history of one or more failed transvaginal cerclages. Interesting perspectives are currently offered by the laparoscopic cerclage, a method that has been effective and unexpectedly safe till now.

Intravaginal gemeprost and second-trimester pregnancy termination in the scarred uterus.

OBJECTIVE: To investigate the effectiveness and complication rate of intravaginal gemeprost, a prostaglandin E(1) analogue, for second-trimester pregnancy termination in women with a scarred uterus. METHODS: Of 439 women undergoing induced abortion between the 13th and the 23rd week of pregnancy, 67 had a scarred uterus because of 1 or more cesarean sections or myomectomy. All women received a 1 mg dose of gemeprost intravaginally every 3 h, up to 5 times over 24 h. Those who did not respond received further cycles of gemeprost treatment. RESULTS: The rate of successful abortions among women with uterine scars was not different from that observed in the nulliparous controls, but previously vaginal delivery was associated with a shorter induction to abortion interval. The rate of severe complications did not differ between the groups, and was about 1%. CONCLUSION: The rate of complications following intravaginal administration of a PGE(1) analogue for second-trimester pregnancy termination was similar in women with a scarred or unscarred uterus.

Determination of cervicovaginal microorganisms in women with abnormal cervical cytology: the role of Ureaplasma urealyticum.

OBJECTIVE: To evaluate the existence of an association between cervicovaginal infections and precancerous lesions of the uterine cervix, through determination of prevalent cervicovaginal micro-organisms, alone and in association with human papillomavirus (HPV), in patients with abnormal and normal vaginal cytology. PATIENTS AND METHODS: Patients with abnormal vaginal cytology were divided into three study groups according to cytological findings: ASC-US, L-SIL and H-SIL. All patients underwent colposcopic examination and exoendocervical and vaginal sampling for microbiological and molecular analysis for detection of HPV-DNA, Ureaplasma urealyticum, Chlamydia trachomatis, Trichomonas vaginalis, mycetes and common bacteria. Results were compared with the patient group asymptomatic for cervicovaginal inflammation with negative vaginal cytology and colposcopy. RESULTS: A high association between Ureaplasma urealyticum infection and the grade of cytological cervical lesion (27% for ASC-US, 35% for L-SIL and 45% for H-SIL) was found. Furthermore, 19% of the control group samplings were positive for Ureaplasma urealyticum, significantly less than that observed in the positive cytology groups. An interesting association of HPV with Ureaplasma urealyticum in patients with H-SIL vaginal cytology (83%), much higher than that observed in patients with slightly abnormal or normal vaginal cytology (56% for ASC-US, 49% for L-SIL, 40% for normal cytology) was also identified. In contrast, the association between Papillomavirus and multiple microorganisms seemed to decrease with the level of cellular dysplasia in 30% of controls, 33% of ASC-US, 32% of L-SIL and 17% of H-SIL. CONCLUSION: The presence of a high Ureaplasma urealyticum level seems to be a cofactor of HPV infection, a necessary cause of precancerous lesions of the uterine cervix. The presence of Ureaplasma urealyticum may play a role both in initiating viral cellular anomalies and in viral persistence. It can be hypothesized that these initial processes are helped by a state of cervical inflammation, also supported by multiple microorganisms. It would, thus, be suggested for all patients who present with an abnormal PAP test to undergo a cervicovaginal microbiological examination to detect potentially pathogenic microbes for correct diagnosis and treatment, as well as a more complete follow-up of cervical cytological lesions.

Breast density changes associated with hormone replacement therapy in postmenopausal women. Effects on the specificity and sensitivity of mammographic screening.

Postmenopausal HRT use is associated with an increase of mammographic density and reduction of sensitivity and specificity of mammography results and an increase of false-positive and false-negative outcomes. The increased density does not allow a good evaluation of the exam. Mammographic density is an independent risk factor for breast cancer, but the link between changes in breast density and difference in breast cancer risk, remain uncertain. On the other hand, today specific guidelines and protocols to optimize the screening of neoplastic breast pathology in HRT users do not exist and it is unknown if short-term suspension of therapy improves mammographic sensitivity. More information is required to define this important risk factor.

Microsurgery versus laparoscopy in distal tubal obstruction hysterosalpingographically or laparoscopically investigated.

OBJECTIVE: To compare pregnancy rates after laparotomic microsurgical or laparoscopic distal tuboplasty. DESIGN: Two hundred and twenty-four women with infertility due to distal tubal occlusion were randomized to be treated with either laparotomy or laparoscopy from 1987 to 2001 at the Institute of Gynaecology and Obstetrics, University of Rome, "La Sapienza". RESULTS: The results were evaluated taking into account the type of surgical approach, the severity of tubal damage and of adhesions. After a 24-month follow-up period, the overall pregnancy rate obtained with microsurgery was 43.7%, of which 33.3% were term pregnancies, 5.0% abortions, and 5.0% ectopic pregnancies. After laparoscopy, the overall pregnancy rate was 41.6%, of which 29.1% were term pregnancies, 8.3% abortions and 3.9% ectopic pregnancies. No significant differences was observed between the two groups in terms of fertility rate (chi-square 0.016, p = 0.9003). CONCLUSIONS: Laparotomy plus microsurgery and laparoscopy were equally effective in restoring fertility in women with comparable tubal damage. The severity of the damage is a critical factor for the results.

Severe hypoplasia of the right femur, ipsilateral agenesia of the fibula and twisted right foot in a 24-week-old fetus with proximal femoral focal deficiency (PFFD).

A case of a 24-week-old fetus of non consanguineous parents with an ultrasonographic diagnosis of a short right femur, ipsilateral agenesia of the fibula and a twisted right foot is described. Cordocentesis revealed a normal 46XY karyotype. The parents were informed on treatment options and after psychological counselling they decided to undergo an abortion. Post mortem examination confirmed the diagnosis of a severe right limb malformation.

[Placental chorioangioma]. / Il corionangioma placentare.

Chorioangioma is a primary benign tumour with predominantly vascular involvement. It is found in 1% of all placentas undergoing careful and systematic histopathological examination. A rarer form is the clinically relevant chorioangioma which is likely to be associated with complications like polyhydramnios, pre-term birth, IUGR, anemia, fetal congested heart decompensation, non-immune fetal hydrops, perinatal mortality. Chorioangioma generally presents an increased consistency compared to adjacent tissues; it tends to be single, rounded and reddish-brown in colour. The preferred localisation is on the fetal side of the placental disk and it may protrude into the amniochorial cavity; the volume is variable (but rarely exceeds a maximum diameter of 4-5 cm). Of the known 3 histotypes of chorioangioma (angiomatous, cellular, degenerative), the first is the most insidious: the intratumoral vascular bed represents an arteriovenous shunt in the systematic circulation of the fetus #150; sometimes causing dramatic hemodynamic consequences #150; as well as a functional empty space (blood short-circuited through the neoplasm circulation would be deprived of the possibility of adequate gaseous and metabolic exchanges at the level of the terminal villi). Having been identified as early as 1798, chorioangioma has recently been the subject of renewed interest for the following reasons: 1) the possibility of prenatal diagnosis, prohibited to earlier generations of authors, following the development of instrumental techniques like ultrasonography and flowmetry; 2) the acquisition of new knowledge regarding the physiopathology of the tumour and the etiopathogenesis of its main complications; 3) improved prognostic capacity accompanied by better prospects for correct management; 4) wider awareness of the range of therapeutic options available.

Postchemotherapy late recurrence of non metastatic gestational trophoblastic disease following a partiale mole. A case report.

The authors describe a case of a 35-year-old woman who showed elevation of betahCG 13 months after the complete regression of betahCG values following chemotherapy for an incomplete mole. This case outlines the necessity for careful monitoring of betahCG levels in low risk gestational trophoblastic diseases for a period of time longer than one year after achieving the first clinical remission.

[Ovulation induction and the risk of ovarian tumors]. / Induzione dell'ovulazione e rischio di neoplasie ovariche.

In the last years it has been observed a more and more increasing number of women submitted to therapies for induction of ovulation (disorders of the ovulation represent 33% of the causes of female infertility). In 1998, these therapies had been administrated to approximately two million of USA women. Various Authors have assumed a possible relationship between induction of ovulation and ovarian tumors. Between 1982 and 1997, at least 43 cases of ovarian tumors have been published (among these, there were also 25 cases of epithelial tumors) occurring in women previously treated with ovulation induction. The mean age of patient was 30.3 years, approximately 20 years younger than normal patient population for the same tumors. Among the possible causes of epithelial ovarian tumors, there is the trauma of the ovary surface caused by the continuous repeating of the ovulation phenomenon (incessant ovulation). Gynecologist should be aware of this potential risk for their patients. Multicentric studies should be evaluated in order to establish the risk of ovarian cancer in women treated for infertility problems. A survey of the international literature is made in order to analyse the epidemiological studies and to discuss the relationship between ovulation inducing agents and ovarian tumors.

[PGF2 and the induction of the trial of labor. The prognostic value of uterine contractions]. / PGE2 e induzione del travaglio di parto. Valore prognostico delle contrazioni uterine.

BACKGROUND: Uterine contractions during the first hour following intracervical application of dinoprostone would show the myometrial sensitivity to prostaglandins E2 (PGE2) and could be a good practical marker of the real prospects of success of an attempt to induce labor according to the above mentioned modalities. The verification of such an hypothesis is the principal aim of this work. METHODS: The study was carried out on a group of 90 cardiotocograms recorded soon after a sample of pregnant women at term underwent labor induction by intracervical application of a gel containing 0.5 mg of PGE2 (dinoprostone). Special attention was paid to some characteristics of the cardiotocograms obtained during the first hour following administration of the gel: regularity of uterine contractions, total number of contractions, number of contractions having an intensity equal or superior to 50 mmHg, mean number of contractions during a period of 10 minutes, mean number of "effective" contractions during a period of 10 minutes, presence or absence of "excessive uterine activity" (tachysystole and/or hypersystole). RESULTS: Some cardiotocographic patterns were associated with a higher percentage of successful inductions, but the observed differences, not statistically significant, do not seem to be clinically interesting. CONCLUSIONS: However, it's not possible to exclude that a longer period of uterine contractions monitoring, perhaps lasting 2 hours instead of only 60 minutes, could lead to more useful information for the management choices.

[Collection of autologous blood during pregnancy and fetal safety. Computer analysis of fetal heart rate]. / Predonazione di sangue autologo in corso di gravidanza e sicurezza fetale. Analisi computerizzata dell'attività cardiaca fetale.

BACKGROUND: This study aims at objectively evaluating the impact on the fetus of a sudden maternal blood withdrawal, through a computer analysis of the various aspects of the cardiotocographic pattern before and after one autologous blood unit predonation from near term pregnant women. METHODS: For the collection of cardiotocographic data, a Sonicaid Team fetal monitor was used; it is a monitoring system which uses Doppler ultrasound impulses and autocorrelates the received Doppler signals with varied signals of frequency, connected to Sonicaid System 8000, a program for "objective" cardiotocographic analysis according to the so-called Dawes-Redman criteria. RESULTS: From the statistic comparison of Non Stress Tests preceeding and following predonation, some statistically significant differences have sometimes emerged on the level of specific parameters. CONCLUSIONS: In particular, the general variation of fetal heart frequency and fetal reactivity resulted higher after predonation, even though they were within absolute normality, justifying the suspicion that the stress of autologous predonation practice might produce some indefinite disturbance to fetal activity/rest rhythm.

[Predictive factors of fetal macrosomia]. / Fattori predittivi di megalosomia fetale.

BACKGROUND: Fetal macrosomia is a condition which may increase the risk of mechanical and/or dynamic problems for the parturient. In the past, we have demonstrated that in more than half of the cases it is not possible to exclude a contribution of maternal pathology to the determination of fetal-macrosomia. The aim of this work is to verify whether our more recent experience regarding predictive factors of fetal macrosomia shows some noteworthy novelty. METHODS: The study was retrospectively carried out on pregnant women who, during the period January 1994-February 1996, delivered babies weighing at least 4 kg at the Midwifery School of Camerino. With regard to the frequency of the main risk factors of fetal macrosomia described in scientific literature, the sample was compared with a control group randomly selected. RESULTS: Advanced gestational age at the time of delivery, parental tallness, maternal overweight/obesity, gestational glucidic dysmetabolism, a distance between pubis and uterine fundus of at least 34 cm, male sex of the unborn child have proved to be predictive factors of fetal macrosomia. CONCLUSIONS: The differences in comparison with the past, on the other hand altogether negligible, are the consequence of changes in the management of some obstetric situations.