Yvoni Fragouli

Increased IL-18 levels in seminal plasma of infertile men with genital tract infections.

Interleukin (IL)‐18 is a novel cytokine, previously known as interferon (IFN)‐γ inducing factor. We evaluated the levels of IL‐18 and IFN‐γ in seminal plasma (SP) of fertile and infertile men.

Increased levels of interleukin‐8 in human seminal plasma

Summary The role of cell‐mediated immunity in the aetiopathogenesis of male infertility is far from being defined. The cytochemokine interleukin‐8 (IL‐8) has a key role in T‐cell mediated immune responses. The aim of this study was to confirm the presence of IL‐8 in human seminal plasma, to show differences between IL‐8 concentrations in fertile and infertile subjects, and to show the potential relationship between IL‐8 amounts in semen and spermiogram parameters. IL‐8 levels were determined in the seminal plasma of 77 men divided as follows: (a) into seven groups according to the aetiological diagnosis of fertility and (b) into two groups on the basis of a normal or abnormal spermiogram. The mean value of IL‐8 in the seminal plasma was 31.5 times higher than the upper limit in normal serum. There is a borderline statistical significant difference among the means of the various groups (P<0.051). The Tukeys HSD test for multiple comparisons indicated no two groups as being significantly different, whereas the less conservative test LSD showed significant differences between the group with infection and groups with normal controls, Klinefelters syndrome, mumps orchitis, cryptorchidism, or varicocele. There was no significant difference in IL‐8 levels between men with normal and those with abnormal spermiograms. Furthermore, there was no correlation between IL‐8 levels and the variables of the spermiogram. Even though the conclusions of this study have to be tempered by the sample size, IL‐8 concentration in seminal plasma may be considered as a potential marker for the diagnosis of male accessory gland infection.

Apoptosis and Differential Expression of Apoptosis-Related Proteins in Endometriotic Glandular and Stromal Cells

Objective: Apoptosis is an important regulator of eutopic endometrial function. Endometriosis, the growth of endometrial tissue outside the uterus, could result from increased cellular proliferation or decreased apoptosis in response to appropriate stimuli. The objective of this study was to evaluate the rate of apoptosis and the expression of apoptosis-related Bcl-2 and Bax proteins in endometriotic tissues within the glandular and stromal compartments, according to the phase of the menstrual cycle and the stage of disease. Methods: Ovarian endometriosis samples were evaluated in 75 women who had surgery at a university hospital. Apoptotic cells were detected with the use of the dUTP nick-end labeling (TUNEL) assay. Bcl-2 and Bax expression were assessed by immunohistochemical techniques. Results: The percentage of apoptotic cells was significantly higher in endometriotic stormal cells (73.3%) compared with glandular cells (48%; P = .002). In contrast, the expression of the apoptosis-related proteins Bcl-2 and Bax was significantly lower in the endometriotic stroma (17.3% for both) than in the glandular epithelium (38.6% and 41.3%, respectively; P < .004). No significant menstrual cycle phase-dependent changes or endometriosis stage-related changes were observed in TUNEL, Bcl-2, or Bax positivity within ovarian endometriotic tissues. Conclusion: Apoptosis occurs in ovarian endometriots lesions at significantly higher levels in the stroma than the glandular epithelium. However, Bcl-2 and Bax proteins are distributed preferentially in glandular epithelial cells. the apoptotic rate as well as Bcl-2 and Bax expression in ovarian endometriotic cells were not affected by the stage of endometriosis or the phase of thhe menstrual cycle.

Endometriosis related to family history of malignancies in the Yale series.

OBJECTIVE Recent studies reported that endometriosis could behave as a neoplasmatic process. The purpose of this study is to investigate the family risk of ovarian, colon and prostate cancer in women with endometriosis. STUDY DESIGN A search of medical records at the Yale New Haven Hospital from 1996 to 2002 identified 348 women with endometriosis and 179 women without endometriosis. All the cases were diagnosed by laparoscopy. Demographic characteristics were evaluated in women with positive or negative family history of cancers in women with endometriosis. RESULTS The overall risk of patients with endometriosis and positive family history of cancers was 7.7 (95% confidence interval 3.8-15.7) (chi(2)=39.8, P<0.001). Significant excess was observed for ovarian cancer in first- and second-degree relatives (OR=10.5, 95% CI (2.5-44.2), chi(2)=14.3, P<0.001), colon cancer (OR=7.5, 95% CI (2.7-21.1), chi(2)=18.2, P<0.001) and prostate cancer (OR=4.5, 95% CI (14-15.3), chi(2)=6.1, P<0.001). We found similar results in first- and second-degree relatives with ovarian and colon cancer. Moreover, we found similar results regarding the demographic characteristics in women with positive family history of cancers and in women with negative history. CONCLUSIONS These data suggest a familial association of endometriosis with ovarian, colon and prostate cancers. This evidence could support the genetics and molecular similarities between endometriosis and cancer. Future studies will be important to determine a clear genetic link between endometriosis and cancer.

Increased rate of endometriosis and spontaneous abortion in an in vitro fertilization program: No correlation with epidemiological factors

Background. There are conflicting data concerning endometriosis and spontaneous abortion (SAB). The aim of the present study was to evaluate if there was any association between endometriosis and SAB. Moreover, we investigated risk factors in women with endometriosis and SAB. Methods. The medical files of 457 married women with endometriosis and 200 infertile women without endometriosis were studied retrospectively. All cases were diagnosed by laparoscopy. Data concerning demographic variables and menstrual characteristics were recorded from 226 women with endometriosis, which were divided into two groups. Group 1 included 126 cases with endometriosis and SAB, and Group 2 comprised 100 parous women with endometriosis and without SAB. Statistical comparisons between groups were made using the χ2 test and odds ratios (OR) and 95% confidence intervals (CI). Results. The proportion of SAB was significantly higher in women with endometriosis than in infertile women without endometriosis (126/457 (27.6%) vs. 36/200 (18.0% ); OR = 1.7, 95% CI 1.1 = 2.6; p = 0.01). The frequency of nulligravid women was significantly higher in women with endometriosis than in the control group (OR = 1.9, 95% CI 1.4 – 2.81; p = 0.001). Mean age, age at onset of endometriosis, race, height, weight, body mass index, medical history of allergies, and family histories of endometriosis and cancer were similar in women with endometriosis and SAB and in parous women with endometriosis but without SAB. Moreover, the two groups were similar in age at menarche, length of cycle, duration and amount of flow, and the severity of disease. The incidence of infertility was significantly higher in women with SAB (p < 0.001). Conclusion. These data suggest but do not prove that the risk of SAB is increased in women with endometriosis. The epidemiological risk factors of endometriosis are not associated with an increase in the abortion rate.

Epidemiological factors influencing IVF outcome : Evidence from the Yale IVF program

Summary Age, BMI, lifestyle, menstrual status and obstetric history can modulate the endocrine system and, therefore, have been hypothesised to play a role in in-vitro fertilisation (IVF) outcome. We designed a retrospective study, set in a medical school hospital. We evaluated the medical files of 297 infertile women who underwent laparoscopy and consecutive IVF-ET treatment in the Yale IVF unit between 1996 and 2002. The study group consisted of 151 women who conceived after IVF-ET and the control group of 146 women who underwent 288 IVF-ET cycles without pregnancy. The main outcome measure was the impact of epidemiological factors on the IVF outcome. There was no association between IVF outcome and race, BMI, age at menarche, length of cycle, duration and amount of flow, menstrual symptoms, other medical problems, medical history of allergies, and family history of endometriosis and cancer. We found that the degree of smoking and alcohol use was not a factor when comparing women with and without pregnancy after IVF (34.5% vs 29.5%, and 33.7% vs 27%, respectively). The rate of duration of infertility tended to be lower in pregnant women (35.9±23.4 months) vs (42.3±30.2) non-pregnant women. As expected, we also confirmed the inverse association between the age of women and IVF outcome. Overall, body attributes, lifestyle, family history, menstrual and reproductive factors were not related to IVF-ET outcome.

Human Placental Growth Hormone Is Increased in Maternal Serum in Pregnancies Affected by Down Syndrome

Objective: To evaluate the relationship between maternal serum levels of human placental growth hormone (hPGH) and fetal Down syndrome at gestational midtrimester. Methods: We retrospectively analyzed samples of serum from 21 women with Down syndrome pregnancies detected at gestational midtrimester. The samples were obtained at 16–23 weeks’ gestation during amniocentesis for fetal karyotyping. Sixty-two serum samples were used as controls, which were obtained at 16–23 weeks’ gestation from women with singleton, uncomplicated pregnancies, who gave birth to healthy neonates with a birth weight appropriate for gestational age. The hPGH levels were measured by a solid-phase immunoradiometric assay using 2 different epitopes. Results: The median hPGH values in the serum of the Down-syndrome-affected pregnancies were significantly higher (p < 0.05) than those of the normal pregnancies at 16–23 weeks’ gestation: the median value in the serum was 9.4 ng/ml (5th to 95th percentiles = 1.49–39.03) versus 4.7 ng/ml (0.53–7.88). Conclusion: The hPGH levels in maternal serum were found to be higher at 16–23 weeks’ gestation in pregnancies affected by fetal Down syndrome. Further investigation is needed to examine if maternal serum hPGH could be used as an additional marker in prenatal screening of Down syndrome at gestational midtrimester.

Increased pregnancy-associated plasma protein-A (PAPP-A) concentrations in peritoneal fluid of women with endometriosis.

PROBLEM:  Pregnancy‐associated plasma protein‐A (PAPP‐A) belongs to a group of glycoproteins isolated from extracts of human placenta. Healthy ovarian and uterine tissues are also known to express PAPP‐A. We hypothesized that PAPP‐A levels might also be elevated in the peritoneal fluid (PF) of women with endometriosis, and examined variations in PF PAPP‐A during the menstrual cycle and with the severity of the disease.

Immunohistochemical Expression of p53, MDM2, and p21Wafi Oncoproteins in Endometriomas But Not Adenomyosis

Objective: p53, MDM2, and p21Wafi are oncoproteins that regulate the cell cycle. The purpose of this study was to examine the distribution ofp53, MDM2, and p21 Wafl oncoprotein expression in endometriomas and in adenomyosis. Methods: Tissue samples from 25 women with pathologically confirmed endometriomas and 31 women with pathologically confirmed adenomyosis were analyzed. Expression of p53, MDM2, and p21Waf1 oncoproteins was assessed by immunohistochemical nuclear staining. Results: p53, MDM2, and p21Waf1 expression were detected in 20%, 60%, and 80% of endometrioma tissue samples, respectively. All endometrioma tissue samples expressing p53 also tested positive for both MDM2 and p21Waf1 MDM2 expression was signnficantly higher in the proliferative than in the secretory phase of the cycle. In contrast,all 31 adenomyosis tissue samples were negativeforp53, MDM2, and p21 Wafl expression. Conclusion: The expression of p53, MDM2, and p2JWaf1 suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not in adenomyosis.