E. Vaquero

Mild thyroid abnormalities and recurrent spontaneous abortion: diagnostic and therapeutical approach.

PROBLEM: The aim of this study is to evaluate the role of mild thyroid abnormalities in recurrent spontaneous abortion, and to assess the effects of two different therapeutical protocols.
 METHOD: A prospective study in the population of recurrent aborters with mild thyroid abnormalities, evaluating the obstetric outcome in 42 patients. Sixteen thyroid autoantibodies positive patients were treated with thyroid replacement therapy, while 11 patients received intravenous immunoglobulins (IVIG). Fifteen patients, characterized by negative antithyroid antibodies, and having underlying thyroid pathology, were treated with thyroid replacement therapy.
 RESULTS: Among patients with thyroid antibodies, 6 out of the 11 pregnancies (54.5%) treated with IVIG ended in live birth. In the thyroid supplementation group, 13 out of 16 pregnancies (81.2%) ended in live birth. Only one pregnancy loss occurred among patients with a mild underlying thyroid pathology treated with thyroid replacement therapy.
 CONCLUSIONS: Mild thyroid abnormalities are associated with an increased rate of miscarriage. This poor obstetrical prognosis seems to be related to an impaired thyroid adaptation to pregnancy. Thyroid replacement therapy appears to be more effective than IVIG in preventing a new miscarriage.

Pregnancy outcome in recurrent spontaneous abortion associated with antiphospholipid antibodies : A comparative study of intravenous immunoglobulin versus prednisone plus low-dose aspirin

PROBLEM: To compare the use of intravenous immunoglobulins (IVIG) with prednisone plus low‐dose aspirin (LDA) in treating pregnant women with a history of recurrent fetal loss having the antiphospholipid antibody (aPL), in terms of live‐birth rate and maternal and perinatal morbidity.
 METHOD: A prospective, two‐centers trial study included 82 recurrent aborters with aPL syndrome. Twenty‐nine were treated with prednisone and LDA in one center, 53 received IVIG in the other center. Maternal and fetal outcomes and pregnancy complications were compared between groups.
 RESULTS: Live‐birth rates were equivalent between groups (78 vs 76%). Mean birth weight was higher in the IVIG group than in the prednisone plus LDA group. In the prednisone‐ plus LDA‐treated patients, gestational hypertension and gestational diabetes were found significantly more often than in the IVIG‐treated group (14 vs 5% and 14 vs 5%, respectively).
 CONCLUSION: In patients with aPL syndrome, IVIG treatment improved pregnancy outcome, with significantly lower pregnancy complication rates, when compared with prednisone plus LDA therapy.

Hysteroscopic Findings in 344 Women with Recurrent Spontaneous Abortion

STUDY OBJECTIVE To evaluate the prevalence of different anatomic factors in women with recurrent spontaneous abortion (RSA). DESIGN Retrospective analysis over 9 years (Canadian Task Force classification II-2). SETTING University hospital-affiliated endoscopic unit. PATIENTS Three hundred forty-four consecutive patients with RSA and 922 controls referred for abnormal uterine bleeding. INTERVENTION Diagnostic hysteroscopy. MEASUREMENTS AND MAIN RESULTS Major and minor uterine mullerian abnormalities (septate, unicornuate uteri) were found significantly more often in women with RSA than in controls (32% vs 6%, p <0.001). The frequency of acquired uterine anomalies (submucous myomas, polyps) was significantly higher in controls (32% vs 9%, p <0.001). No significant differences were observed between groups in frequency of adhesions (4% vs 2%). CONCLUSION Major mullerian uterine abnormalities are associated with RSA, and minor uterine anomalies may be correlated with an increased risk of recurrent miscarriage.

Hysteroscopic Metroplasty Improves Gestational Outcome in Women with Recurrent Spontaneous Abortion

STUDY OBJECTIVE To compare the reproductive outcome in women with recurrent spontaneous abortion (RSA) associated with septate uterus after hysteroscopic metroplasty compared with patients who did not undergo surgery. DESIGN Longitudinal evaluation (Canadian Task Force classification II-2). SETTING University of Rome, Tor Vergata-affiliated endoscopic unit. PATIENTS Forty-eight consecutive women with septate uterus and RSA were enrolled in the study. INTERVENTIONS Hysteroscopic metroplasty. MEASUREMENTS AND MAIN RESULTS Reproductive outcome in terms of term pregnancy was significantly improved after hysteroscopic metroplasty compared with controls (76% vs. 20%). No differences were found in the prevalence of preterm delivery between groups (4% vs. 5%). CONCLUSION Our data suggest that hysteroscopic septum incision can improve pregnancy outcome in patients with RSA associated with septate uterus.

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.

Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: A pilot study

BackgroundAim of this pilot study is to examine the effects of myo-inositol administration on ovarian response and oocytes and embryos quality in non PolyCystic Ovary Syndrome (PCOS) patients undergoing multiple follicular stimulation and in vitro insemination by conventional in vitro fertilization or by intracytoplasmic sperm injection.MethodsOne hundred non-PCOS women aged <40 years and with basal FSH <10 mUI/ml were down-regulated with triptorelin acetate from the mid-luteal phase for 2 weeks, before starting the stimulation protocol for oocytes recovery. All patients received rFSH, at a starting dose of 150 IU for 6 days. The dose was subsequently adjusted according to individual response. Group B (n = 50) received myo-inositol and folic acid for 3 months before the stimulation period and then during the stimulation itself. Group A (n-50) received only folic acid as additional treatment in the 3 months before and through treatment.ResultsTotal length of the stimulation was similar between the two groups. Nevertheless, total amount of gonadotropins used to reach follicular maturation was found significantly lower in group B. In addition, the number of oocytes retrieved was significantly reduced in the group pretreated with myo-inositol. Clinical pregnancy and implantation rate were not significantly different in the two groups.ConclusionsOur findings suggest that the addition of myo-inositol to folic acid in non PCOS-patients undergoing multiple follicular stimulation for in-vitro fertilization may reduce the numbers of mature oocytes and the dosage of rFSH whilst maintaining clinical pregnancy rate. Further, a trend in favor of increased incidence of implantation in the group pretreated with myo-inositol was apparent in this study. Further investigations are warranted to clarify this pharmacological approach, and the benefit it may hold for patients.

Glutathione S-transferase genes and the risk of recurrent miscarriage in Italian women.

OBJECTIVE To investigate the role of glutathione S-transferases (GSTs) in the pathogenesis of recurrent miscarriage (RM). DESIGN Genetic association study. SETTING University of Rome, Tor Vergata and San Giovanni Calibita, Fatebenefratelli Hospital. PATIENT(S) One hundred twenty-one women with RM and 113 women without pregnancy complications. INTERVENTION(S) Genomic DNA extracted from buccal cells and screening of positive/null genotypes of GSTM1 and GSTT1 genes and single nucleotide polymorphisms of GSTA1, GSTO2, and GSTP1 genes. MAIN OUTCOME MEASURE(S) Occurrence of GST polymorphisms. RESULT(S) Women with at least one GSTA1*-69T allele are more frequent in the RM group than in the control group: 67% vs. 48%, respectively. Significant outcomes were obtained considering different genetic models: codominant, dominant, and log-additive. In addition, the combined analysis suggests that GSTA1 and GSTM1 variants have a significant interaction in RM risk. CONCLUSION(S) Our study highlighted a significant association between the GSTA1 gene and an increased risk of RM. In particular, the -69T allele in the GSTA1 gene may be considered as a predisposing factor of RM.

Further Evidence on the Role of Thyroid Autoimmunity in Women with Recurrent Miscarriage

It has been twenty years since the first paper reporting the association between thyroid antibodies (TAIs) and spontaneous miscarriage was published. Following this observation, several studies have clearly demonstrated an increased prevalence of TAI in patients with recurrent miscarriage (RM). However, the exact mechanism underlying this association remains a matter of debate. The aim of the present study was to evaluate the thyroid function, throughout a specific test, in patient with RM and TAI focusing on the hypothesis that TAI should be an indirect sign of a mild thyroid dysfunction. 46 patients with RM and TAI were included in the study. All patients underwent short TRH stimulation test showing an abnormal response in the vast majority of cases (65%). Normal FT4 and FT3 mean values were found whereas TSH values were in the upper normal range (2.64 ± 1.3 mUI/L). Our data support the hypothesis that in patients with RM the presence of TAI is an indirect sign of a subtle thyroid dysfunction detectable by a specific test. This test give the possibility to identify women with RM in which specific therapeutic approaches could effectively improve the possibility for a successful pregnancy.

Cystic ovaries in women affected with hereditary angioedema.

Polycystic ovary (PCO) syndrome is biochemically characterized by abnormal gonadotropin secretion and polycystic ovaries associated with increase in size and functional activity of stromal tissue; multifollicular ovaries (MFO) are defined by the presence of multiple cysts with no increase in stromal tissue. A central (hypothalamic‐pituitary) abnormality, including high plasma /?‐endorphin (BE) concentrations without simultaneous elevation of ACTH, was reported for subjects with PCO syndrome. Since we have found the presence of high plasma BE concentrations in hereditary angioedema (H ANE) during attacks as well as during symptom‐free periods, we studied, by means of pelvic ultrasound scanning employed to determine the prevalence of PCO and of MFO, 13 women of reproductive age affected with HAN E who were not on oral contraceptives. We have found PCO in 5/ 13 (38.4%) and MFO in 7/13 (53.8%) HANE patients. Nine patients had oligomenorrhoea (five with PCO, three with MFO, one with normal ovaries), five (three with PCO, two with MFO) were hirsute and only one (with MFO) had weight loss. No patient was obese. Mean plasma LH, testosterone, prolactin, cortisol and ACTH concentrations were normal, while FSH was significantly reduced and LH/FSH ratio increased. BE concentrations were significantly high in all the patients studied. Our results clearly demonstrate that women with HANE frequently have cystic ovaries (polycystic or multifollicular) in the presence of high BE concentrations.

IVF pregnancies: Neonatal outcomes after the new Italian law on assisted reproduction technology (law 40/2004)

Objective. To compare maternal and neonatal outcome of pregnancies achieved by assisted reproduction technique (ART) according to the guidelines of the newly established Italian ART law 40/2004, with that of naturally conceived. Design. Three hundred and sixty‐four ART pregnancies and 304 naturally conceived pregnancies were analyzed in terms of the incidence of obstetric complications and perinatal outcome. Control group was enrolled prospectively after being matched for an extensive number of maternal characteristics. Results. Among singletons, ART pregnancies when compared to naturally conceived pregnancies showed a higher incidence of pregnancy loss (23.4% versus 10.5%) and a lower mean birth weight. A higher but not significant incidence of small for gestational age fetuses was observed in ART pregnancies, compared to those from normally conceived pregnancies (7.2% versus 2.7%). Moreover, the ART pregnancies showed a slightly, but nonetheless significantly shorter mean gestational age (38.6 versus 39.3 weeks) and more frequent preterm deliveries (11%) than the control group (2.7%). No difference was found in terms of other obstetric complications such as pregnancy‐induced hypertension, gestational diabetes and placental abruption. Neonatal outcome was similar in both groups. Conclusion. Although the obstetric outcome among singleton ART pregnancies was good, these patients should be considered obstetric risk cases. The different frequency of complications is not related to maternal age or parity and could be the consequence of infertility or the procedures by which these women conceived. The reasons are, however, unclear and further studies are necessary.