Eli Geva

The effect of antioxidant treatment on human spermatozoa and fertilization rate in an in vitro fertilization program

OBJECTIVE To study the possible influence of antioxidant treatment on human spermatozoa and the fertilization rate in an IVF program. DESIGN Prospective study. SETTING In Vitro Fertilization Unit, Serlin Maternity Hospital, and the Laboratory of Male Fertility, Bar-Ilan University, Ramat-Gan, Israel. PATIENTS Fifteen fertile normospermic male volunteers who had low fertilization rates in their previous IVF cycles. INTERVENTIONS Vitamin E (alpha-tocopherol) 200 mg daily by mouth for 3 months. MAIN OUTCOME MEASURES Lipid peroxidation potential (amount of malondialdehyde [MDA]), quantitative ultramorphologic analysis of spermatozoa, and fertilization rate per cycle. RESULTS The high MDA levels significantly decreased from 12.6 +/- 9.4 nmol/10(8) spermatozoa to normal levels of 7.8 +/- 4.2 nmol/10(8) spermatozoa after 1 month of treatment. The fertilization rate per cycle increased significantly from 19.3 +/- 23.3 to 29.1 +/- 22.2 after 1 month of treatment. No additional effects on MDA levels and fertilization rate were observed after completion of treatment. With regard to the quantitative ultramorphologic analysis, none of the sperm cell subcellular organelles were affected significantly by vitamin E treatment. CONCLUSION Vitamin E may improve the fertilization rate of fertile normospermic males with low fertilization rates after 1 month of treatment, possibly by reducing the lipid peroxidation potential, and with no change of the quantitative ultramorphologic analysis of subcellular organelles.

Circulating autoimmune antibodies may be responsible for implantation failure in in vitro fertilization

OBJECTIVE To investigate the role of autoimmune factors as a possible cause for implantation failure as manifested by chemical pregnancy after IVF and ET. DESIGN Anticardiolipin, anti-double-stranded DNA (dsDNA), antinuclear antibody, lupus anticoagulant, and rheumatoid factor serum levels were examined in patients with chemical pregnancies and in matched controls. SETTING An IVF unit, university-based IVF program. PATIENTS The study group included 21 patients who had one or more chemical pregnancies and no deliveries. The control group consisted of 21 patients who had conceived and delivered after IVF-ET treatment, without any history of fetal wastage, matched for age, type and duration of infertility, and number of previous IVF cycles. RESULTS The incidence of circulating autoimmune antibodies in the study group was 33.3% (7/21). Three patients (14.2%) were positive for anticardiolipin, two (9.5%) were positive for antidsDNA, one (4.7%) for antinuclear factor, and one (4.7%) for rheumatoid factor. Autoimmune antibodies were not detected in any of the control group. CONCLUSION Autoimmunity may play a role in implantation failure in IVF-ET. Circulating autoimmune antibody screening is therefore recommended after chemical pregnancy.

Patients with stages III and IV endometriosis have a poorer outcome of in vitro fertilization- embryo transfer than patients with tubal infertility

OBJECTIVE To evaluate the outcome of IVF in patients with stages III and IV endometriosis. DESIGN Retrospective study. SETTING The Sara Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Israel. PATIENT(S) Fifty-eight patients with stages III and IV endometriosis and 60 patients with tubal infertility. INTERVENTION(S) IVF-ET for all couples. MAIN OUTCOME MEASURE(S) Fertilization, pregnancy, and birth rates. RESULT(S) The comparison between patients with endometriosis and those with tubal infertility indicated that the former had a poor IVF outcome in terms of reduced fertilization rate (40% vs. 70%), reduced pregnancy rate per cycle (10.6% vs. 22.4%), and reduced birth rate per cycle (6.7% vs. 16.6%). The differences were statistically significant. CONCLUSION(S) The results show an unfavorable outcome of IVF-ET in patients with endometriosis when compared with those who have tubal infertility.

Autoimmunity and reproduction

OBJECTIVE To review the association between autoimmunity and reproductive failure. DESIGN A MEDLINE search done from 1965 to 1996. More than 300 original and review articles were evaluated, from which the most relevant were selected. RESULT(S) Autoimmune processes now are accepted widely as one of the possible mechanisms of many human diseases. The presence of autoimmune disorders has been associated repeatedly with reproductive failure. On the other hand, reproductive failure may be the first manifestation of autoimmune disorders. CONCLUSION(S) When abnormal autoantibody levels are present in women with reproductive failure, the reproductive failure alone should be considered as one of the possible clinical expressions of autoimmune disorders. Two relevant questions of whether these patients should be treated for autoimmunity remain unsolved. A prospective, placebo-controlled trial is necessary to evaluate the importance of any treatment.

Prednisone and aspirin improve pregnancy rate in patients with reproductive failure and autoimmune antibodies : A prospective study

PROBLEM: The study was conducted to investigate the efficacy of prednisone and aspirin in autoantibody seropositive patients with repeated in vitro fertilization–embryo transfer (IVF–ET) failure. METHODS OF STUDY: The study group comprised 52 consecutive patients seropositive for non‐organ‐specific autoantibodies, i.e., anti‐cardiolipin antibodies (ACA), anti‐nuclear antibodies (ANA), anti‐double‐stranded (ds) DNA, rheumatoid factor (RF), and lupus anti‐coagulant (LAC). These patients were treated with prednisone, 10 mg per day, and aspirin, 100 mg per day, starting 4 weeks before induction of ovulation in 52 IVF cycles. RESULTS: The clinical pregnancy rate per cycle was 32.7% (17/52). No increased incidence of pregnancy complications, including premature labor, gestational diabetes mellitus, and pregnancy‐induced hypertension, were found. CONCLUSIONS: Combined treatment of prednisone for immunosupression and aspirin as an anti‐thrombotic agent, starting before ovulation induction, may improve pregnancy rate in autoantibody seropositive patients who have had repeated IVF–ET failures.

Levels of vascular endothelial growth factor are elevated in patients with ectopic pregnancy: is this a novel marker?

OBJECTIVE To determine serum levels of vascular endothelial growth factor (VEGF) and evaluate their capacity to serve as a marker for the diagnosis of ectopic pregnancy (EP). DESIGN Prospective, case-controlled study. SETTING A tertiary care center. PATIENT(S) Twenty women with EP, 10 women with normal intrauterine pregnancy, and 10 women with abnormal intrauterine pregnancy, all at comparable stages of gestation. INTERVENTION(S) Serum samples were obtained from all women. MAIN OUTCOME MEASURE(S) All samples were analyzed for VEGF, progesterone, and beta-hCG by specific methods. RESULT(S) Women with EP had higher serum levels of VEGF than women with normal intrauterine pregnancy and women with abnormal intrauterine pregnancy (median levels, 226.8 pg/mL, 24.4 pg/mL, and 59.4 pg/mL, respectively). With a cutoff level of 200 pg/mL, serum VEGF could distinguish intrauterine from extrauterine pregnancy with a sensitivity of 60%, specificity of 90%, and positive predictive value of 86%. CONCLUSION(S) The increased serum VEGF levels in women with EP may facilitate this challenging diagnosis and reduce maternal morbidity and mortality.

Role of angiopoietins in reproductive tract angiogenesis.

UNLABELLED Components of the female reproductive system undergo a number of programmed angiogenic processes coupled with cyclic evolution and decline of ovarian, endometrial, and placental structures. The development of a new vascular network requires a remarkable degree of coordination between different cell types undergoing complex changes. This implies that the expression of the inciting angiogenic factors are hormone dependent. Recently, a second family of vascular endothelial growth factors was identified, the angiopoietins. Angiopoietins are vascular endothelial cell-specific growth factors that play important roles principally during the later stages of angiogenesis, after the induction of new capillaries by vascular endothelial growth factor (VEGF). There are four known angiopoietins, and their specificity for the vascular endothelium results from the restricted expression pattern of their tyrosine kinase receptor, Tie2. In this review, we discuss the molecular characterization and mechanism of action of angiopoietin-1 and angiopoietin-2 in reproductive tract angiogenesis. TARGET AUDIENCE Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES After completion of this article, the reader will be able to describe the angiogenic process and specifically explain the role of angiopoietics in reproductive tract angiogenesis and compare the differences between the various proteins that are involved in angiogenesis.

Recombinant luteinizing hormone induces increased production of ovarian follicular adiponectin in vivo: implications for enhanced insulin sensitivity

OBJECTIVE To determine in vivo whether LH supplementation during the late follicular phase induces increased production of ovarian follicle adiponectin in humans. DESIGN Randomized, double-blind, placebo-controlled study. SETTING Academic tertiary care medical center. PATIENT(S) Twenty infertile, healthy women (aged 18-39 years) undergoing IVF. INTERVENTION(S) Administration of recombinant FSH after down-regulation and equal randomization of subjects to receive recombinant LH 75 IU/day or placebo when two or more follicles reached a mean diameter of 14 mm. MAIN OUTCOME MEASURE(S) Follicular fluid (FF) adiponectin levels were measured. RESULT(S) Adiponectin FF levels were significantly higher in the recombinant LH group compared with the placebo group, and these differences were unaltered after correction to estrogen (E) levels and number of follicles in each cycle. CONCLUSION(S) This is the first demonstration of in vivo induction of adiponectin by gonadotropins in the human ovary. The addition of recombinant LH during the late follicular phase may enhance follicular insulin sensitivity, resulting in decreased androgen levels through a cascade mediated by increased production of adiponectin.

High Levels of Anticardiolipin Antibodies in Patients with Abnormal Embryo Morphology Who Attended an In Vitro Fertilization Program

PROBLEM: Recently, it has been suggested that anticardiolipin antibodies (ACAs) may serve as possible markers for reproductive failure. The association between ACAs and embryo morphology in patients undergoing in vitro fertilization (IVF) was investigated.

Evaluation of fetal echogenic bowel in the second trimester

Previous studies cite different possible etiologies for fetal echogenic bowel (FEB). The purpose of this study was to evaluate the possible etiologies for second-trimester FEB, and to provide clinical guidelines for evaluation of this finding. The study included 79 patients diagnosed with FEB in the second trimester. Fifteen cases (19%) were associated with maternal vaginal bleeding. Of these, 12 patients underwent amniocentesis, 9 of which had visible blood products in the amniotic fluid. Seven cases (8.9%) had associated severe malformation. Seven other cases (8.9%) were noted in multifetal pregnancies. Five fetuses (6.3%) had evidence of bowel obstruction or perforation not associated with cystic fibrosis (CF). Chromosomal aberrations were found in 5 fetuses (6.3%). Intrauterine infection with cytomegalovirus, herpes simplex virus, varicella-zoster virus, or parvovirus B-19 was documented in 5 patients (6.3%). Three cases (3.8%) were associated with subsequent unexplained stillbirth. Two fetuses (2.5%) were found to be affected by CF. Finally, in 30 cases (38%), no obvious reason for FEB was found. We conclude that the evaluation of second-trimester FEB should include targeted ultrasound for associated malformations, infectious studies, DNA analysis for CF mutations, amniocentesis for chromosomal analysis and evaluation of the amniotic fluid for degraded blood products, and an autopsy in cases of stillbirth. Even when no apparent reason is found, pregnancies should be considered at high risk for poor outcome.