Preimplantation genetic diagnosis: present and future

Purpose: Preimplantation genetic diagnosis (PGD) was developed more than a decade ago and aims to identify embryos free of genetic disease attributed either to gene mutations or chromosome errors. The purpose of this article is to provide an update on the current status and future prospects of PGD. Methods: Review of studies employing different strategies for the detection of single gene defects, and chromosome abnormalities, both structural and numerical in the context of PGD. Results: Amplification of several DNA fragments is feasible via multiplex PCR for the PGD of single gene disorders, whilst current FISH protocols employ up to 10 probes to identify embryos with a normal chromosome complement. New methods are being developed which will enable the assessment of the entire chromosome complement of embryonic blastomeres. Conclusions: PGD has come a long way since its first application, and has become very accurate and reliable. Technical advances in the field of preimplantation genetics mean that PGD holds great promise for the future.     

Epidemiological characteristics in women with and without endometriosis in the Yale series

Objective The association between demographic factors, menstrual and reproductive characteristics, and clinical profile for women with endometriosis was analyzed in a retrospective case-control study. Methods Over a 6-year period, 535 women with endometriosis and 200 infertile women without endometriosis, studied by laparoscopy or laparotomy, were evaluated. Information was then collected in a uniform manner from the patients’ medical records. Statistical methods included χ ² and Mann–Whitney U test. Results The factors associated with an increased risk for endometriosis include lower body weight, alcohol use (χ ² = 8.8; P < 0.003), early menarche (χ ² = 5.08; P < 0.024), shorter cycle length (χ ² = 13.06; P < 0.001), and heavier menstrual cycles. Pelvic pain was present in 79.1% of women with endometriosis, dysmenorrhea in 70.2%, and dyspareunia in 49.5%. These symptoms were statistically significantly higher in comparison with the infertile women without endometriosis (P < 0.001). Moreover, we found that women with endometriosis had fewer prior pregnancies, elective abortions and ectopic pregnancies compared to women seeking care for infertility, who did not have endometriosis. Interestingly, women with endometriosis were significantly more likely to report a family history of cancer compared to women in control group (χ ² = 78.2; P < 0.001). Conclusions Body habitus, personal habits and menstrual characteristics are all strongly associated with the development of endometriosis. There may also be an association between family history of cancer and the development of endometriosis.     

The efficacy and tolerability of iron protein succinylate in the treatment of iron-deficiency anemia in pregnancy

The aim of this study was to evaluate the efficacy and tolerability of iron protein succinylate in the treatment of iron-deficiency anemia in pregnancy. One hundred and thirty anemic pregnant women were studied. Inclusion criteria were iron-deficiency type of anemia, and hemoglobin levels below of 11.5, 10.9 and 10.3 g/dl for the three trimesters of pregnancy, respectively. Twenty-five women who presented pregnancy-related complications were excluded during treatment. The remaining 105 were treated with 1600-mg iron protein succinylate per os daily for a period of four months. A group of anemia-related clinical signs and symptoms, and hematological parameters were recorded at the beginning of treatment, as well as two and four months later. They included epidermis and mucosal paleness, skin and nail lesions, glossitis, heart pulse, sickness, anorexia, apathy, ataxia, polypnea, insomnia, nervousness, paresthesias and other neurological symptoms; the hematological parameters included Hgb, hct, RBCs, WBCs, MCV, MCH, MCHC, PLTs, serum Fe and ferritin. Possible side or adverse effects were considered during treatment. The majority of symptoms and signs of anemia were gradually improved. There was a statistically significant increase in the means of Hgb, hct, WBCs, MCV, MCH, PLTs and serum ferritin (p < 0.05). Anemia was effectively treated in 100/105 (95.2%) women, but not in five patients (4.8%) who displayed poor compliance to the therapeutic protocol. There were transient and mild side-effects in seven (6.6%) treated women, namely diarrhea, epigastralgia, vomiting, and nausea, which however, did not necessitate discontinuation of the therapeutic protocol. Iron protein succinylate is an effective and well tolerated treatment of iron-deficiency anemia in pregnancy.     

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 Tukey's 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, Klinefelter's 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.     

Increased human placental growth hormone at midtrimester pregnancies may be an index of intrauterine growth retardation related to preeclampsia

OBJECTIVE: To evaluate the relationship between maternal serum and amniotic fluid levels of human Placental Growth Hormone (hPGH) with the fetal intrauterine growth retardation (IUGR) related to preeclampsia. DESIGN: We analyzed samples in pairs of serum and amniotic fluid retrospectively from 25 women, who manifested preeclampsia and IUGR in the late second or the third trimester of gestation. The samples were obtained at 16-22 weeks' gestation during amniocentesis for fetal karyotyping. At this time, there was no clinical or sonographic evidence of preeclampsia or IUGR, respectively. Sixty-two serum samples were used as controls which were obtained at 16-22 weeks' gestation from women with singleton, uncomplicated pregnancies, with normal outcome, and appropriate for gestational age neonatal birth weight. Forty-seven amniotic fluid samples were also used as controls which were obtained at 16-22 weeks' gestation from the women that were included in the control group who underwent an amniocentesis. hPGH levels were measured by a solid phase immunoradiometric assay. RESULTS: The mean hPGH values in the serum and the amniotic fluid of the IUGR related to preeclampsia affected pregnancies were significantly higher (P<0.05) than those of the normal pregnancies at 16-22 weeks' gestation: mean+/-SD in the serum was 13.16+/-10.52 ng/ml vs. 4.39+/-2.23 ng/ml; mean+/-SD in the amniotic fluid 2.49+/-1.6 ng/ml vs. 0.82+/-0.67 ng/ml. CONCLUSION: hPGH levels in maternal serum and amniotic fluid were found to be higher at 16-22 weeks' gestation in pregnancies that will be complicated subsequently by IUGR related to preeclampsia. Our findings suggest that the evaluation of the changes of hPGH levels at midtrimester should be further investigated for the possibility to provide a potential predictive index of IUGR and preeclampsia.     

Relation of allergy to HIV infection

In this retrospective study on 141 HIV-positive subjects, allergy was studied by a specific questionnaire and the Phadia-Top-Test, an in vitro screening test detecting specific IgE; both were correlated to the patient's history, clinical symptoms and the treatment used. Allergy was studied in reference to HIV-negative controls and in relation to the clinical and biological subgroups of HIV patients.
The application of the x² test demonstrated a high incidence of allergy and a specific relation to the HIV infection compared to the controls as well as in relation to the clinical stage of the infection. Atopy was not specifically related to the HIV infection despite the higher frequency found in the AIDS-IKEL group.
A significant number (21%) of patients with T4 > 300/μ1 considered immunocompetent presented clinical manifestations of AIDS-IKEL and 100% of these patients were allergic. A significant number (19%) of patients with T4 < 300/μ1 considered immunodeficient were asymptomatic and 75% of them were allergic.
Thus allergic symptoms may transiently be the only clinical manifestations in HIV infection and possibly a co-factor for the evolution of the disease due to the immunomodulatory function of the mediators, the cytokines and the proteases released during allergic reaction.     

Nocturnal blood pressure fall and metabolic syndrome score in patients with white coat hypertension

BACKGROUND: Accumulating data report that white coat hypertension (WCH) is associated with target organ damage. Metabolic syndrome (MS), and nondipping pattern is also associated with increased cardiovascular risk. The purpose of this study was to explore the nocturnal blood pressure fall in WCH patients according to their MS score. METHODS: The study comprised 2300 patients with WCH who attended our outpatient clinics. All underwent repeated office blood pressure measurements, 24-h ambulatory blood pressure monitoring, full clinical and laboratory evaluation. The diagnosis of MS was made according to the Adult Treatment Panel III criteria and patients were classified into five groups: group I (hypertension), group II (hypertension and any one component), group III (hypertension and any two components), group IV (hypertension and any three components), and group V (all five components). Dipping pattern was defined as 'dippers' with nocturnal systolic blood pressure (NSBP) fall greater than or equal to 10% but less than 20%, 'nondippers' with NSBP fall greater than or equal to 0% but less than 10%, 'extreme dippers' with NSBP fall greater than or equal to 20%, and 'reverse dippers' with NSBP increase. RESULTS: Patients were divided into two groups according to the presence (n=522) and absence (n=1778) of MS. The overall prevalence of MS in the study population was 22.7%. Comparing the non-MS group with the MS we observed significant differences for nondippers (24.5% vs. 38.9%, P<0.001), dippers (54.4% vs. 43.5%, P<0.001), extreme dippers (17.8% vs. 11.3%, P<0.001), and reverse dippers (3.3% vs. 6.3%, P=0.007). CONCLUSION: Patients with WCH and increased number of MS components present with elevated nighttime SBP levels. This observation is of a great significance in the assessment of the cardiovascular risk in these patients.     

Mandibular radiomorphometric measurements as indicators of possible osteoporosis in postmenopausal women

OBJECTIVE: The use of mandibular anatomic indicators on panoramic radiographs, i.e. the number of lost teeth, mandibular cortical width at the mental region (MCW), panoramic mandibular index (PMI), alveolar crest resorption degree (M/M ratio) and morphologic classification of the mandibular inferior cortex (MIC grade) can be useful in the evaluation of bone resorption in different age groups of women to determine the presence of osteoporosis. The purpose of this study was to assess the validity of mandibular radiomorphometric measurements and to determine the frequency of tooth loss in postmenopausal women. SUBJECTS AND METHODS: An assessment of the number of lost teeth, MCW, PMI, M/M ratio and MIC grade was performed on dental panoramic radiographs in a group of 133 postmenopausal women 38-80 years-of-age. BMD at the lumbar spine was measured by dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or osteoporosis (T-score less than -2.5) according to the World Health Organization classification. RESULTS: In our study when the T-score at the lumbar spine is decreased, the age of menopause is increased, and the MCW is decreased to a point of statistical significance. A decrease in MCW by 1mm increases the likelihood of osteopenia or osteoporosis to 43%, having taken into consideration the effect of the years elapsed since menopause. It was also shown that age, years since menopause, MCW value, and the number of teeth lost have a statistically important effect on the incidence of moderate or severe cortical erosion. Moreover, when the MCI is C2 or C3 (mild or severe erosions) the age is increased, the years since menopause are increased and the MCW is decreased to a point of statistical significance. As far as tooth loss is concerned, an increase by 1 unit in the number of teeth lost, increase the likelihood of moderate or severe erosion to 6%, having taken into account the years elapsed since menopause. Our study also demonstrated that postmenopausal women tend to lose their teeth at an age older than 50 years. They usually lose the 1st and 2nd mandibular molars and the 1st and 2nd maxillary premolars. Loss of front teeth and canines occurs at an age older than 60 years (except for the lateral maxillary incisors). At a younger age they tend to lose the 2nd maxillary premolars more frequently than their mandibular counterparts. CONCLUSIONS: In conclusion, panoramic radiographs constitute an integral part of almost every routine dental evaluation and can be useful for the early diagnosis of osteoporosis in postmenopausal women. Dentists have sufficient clinical and radiographic information that enables them to play a significant role in patient screening for osteoporosis.