Joseph B. Lessing

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.

Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia

OBJECTIVE To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty‐two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P < .01), more multiple infarcts (P < .05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P < .05). CONCLUSION Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.

Low-molecular-weight heparin for the prevention of obstetric complications in women with thrombophilias.

OBJECTIVE To evaluate the benefit of combined low-molecular-weight (LMW) heparin and aspirin for prophylaxis in women carriers of thrombophilia who had previously suffered from severe obstetric complications. METHODS The 33 studied women had an earlier pregnancy complicated by severe preeclampsia, abruptio placentae, intrauterine growth retardation, or intrauterine fetal death. All were subsequently diagnosed as carrying inherited thrombophilias. In their subsequent pregnancy, prophylactic therapy consisting of LMW heparin 40 mg/day (Enoxaparin, Rhone-Poulenc-Rorer, France) and aspirin was administered. Patients who were found to be homozygotes for the methylenetetrahydrofolate reductase mutation also received folic acid supplementation throughout their pregnancy. RESULTS Low-molecular-weight heparin was well tolerated and none of the women or the newborns developed any hemorrhagic complications. Only three (9.1%) of the women developed pregnancy complications. The mean gestational age and the mean birth weight at delivery in the previously complicated pregnancies were 32.1 +/- 5.0 weeks and 1175 +/- 590 g, respectively, compared to 37.6 +/- 2.3 weeks and 2719 +/- 526 g, respectively, in the treated pregnancies (p < 0.001). CONCLUSIONS This uncontrolled trial suggests that patients with obstetric complications and an inherited thrombophilia may benefit from treatment with combined LMW heparin and aspirin in subsequent pregnancies. However, this needs to be verified by controlled trials before considering clinical application.

Vascular endothelial growth factor is increased in patients with preeclampsia.

PROBLEM: This study was conducted to determine whether altered levels of vascular endothelial growth factor (VEGF) may play a role in the pathogenesis of preeclampsia.

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.

Combined genitourinary prolapse repair and prophylactic tension-free vaginal tape in women with severe prolapse and occult stress urinary incontinence : Preliminary results

OBJECTIVES Continent patients with a positive stress test demonstrated on repositioning of severe genitourinary prolapse are considered to be at high risk of developing postoperative symptomatic stress urinary incontinence (SUI). Our aim was to evaluate in a prospective study whether a prophylactic, tension-free vaginal tape (TVT) procedure, performed during prolapse repair, may prevent the development of postoperative SUI in these women. METHODS Thirty consecutive, clinically continent women (mean age 64.5 +/- 9.04 years) with severe genitourinary prolapse and occult SUI were prospectively enrolled. Occult SUI was defined as a positive stress test with repositioning of the prolapse during the preoperative urodynamic studies. All patients had urethral hypermobility; none had intrinsic sphincter deficiency. In addition to genitourinary prolapse repair, these patients underwent concomitant TVT to prevent postoperative SUI. Patients were followed up for at least 1 year. Repeated urodynamic studies were performed at 3 to 6 months postoperatively. The main outcome measures were postoperative SUI, persistent or de novo detrusor instability, and recurrence of prolapse. RESULTS The mean duration of follow-up was 14.25 +/- 3.08 months (range 12 to 24). None of the patients developed postoperative symptomatic SUI. However, three asymptomatic patients (10%) had a positive stress test during their postoperative urodynamic evaluation. Nine patients (30%) had detrusor instability before surgery, which persisted in six (66%) postoperatively. Postoperative de novo detrusor instability was diagnosed in four other patients (13.33%). None of the patients had recurrent urogenital prolapse, nor did they have clinical evidence of bladder outlet obstruction. CONCLUSIONS The preliminary results of TVT as a prophylactic procedure in clinically continent women with severe prolapse and occult SUI are encouraging. Long-term follow-up is required to confirm the durability of these results.

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.

Nifedipine versus ritodrine for suppression of preterm labour

Objective To compare the efficacy of tocolysis with specific regimens of nifedipine and ritodrine. Maternal side effects and neonatal outcome also were evaluated.

ARP, a peptide derived from the stress-associated acetylcholinesterase variant has hematopoietic growth promoting activities

BackgroundPsychological stress induces rapid and long-lasting changes in blood cell composition, implying the existence of stress-induced factors that modulate hematopoiesis. Here we report the involvement of the stress-associated “readthrough” acetylcholinesterase (AChE-R) variant, and its 26 amino acid C-terminal domain (ARP) in hematopoietic stress responses.Materials and MethodsWe studied the effects of stress, cortisol, antisense oligonucleotides to AChE, and synthetic ARP on peripheral blood cell composition and clonogenic progenitor status in mice under normal and stress conditions, and on purified CD341 cells of human origin. We employed in situ hybridization and immunocytochemical staining to monitor gene expression, and 5-bromo-2-deoxyuridine (BrdU), primary liquid cultures, and clonogenic progenitor assays to correlate AChE-R and ARP with proliferation and differentiation of hematopoietic progenitors.ResultsWe identified two putative glucocorticoid response elements in the human ACHE gene encoding AChE. In human CD341 hematopoietic progenitor cells, cortisol elevated AChE-R mRNA levels and promoted hematopoietic expansion. In mice, a small peptide crossreacting with anti-ARP antiserum appeared in serum following forced swim stress. Ex vivo, ARP was more effective than cortisol and equally as effective as stem cell factor in promoting expansion and differentiation of early hematopoietic progenitor cells into myeloid and megakaryocyte lineages.ConclusionsOur findings attribute a role to AChE-R and ARP in hematopoietic homeostasis following stress, and suggest the use of ARP in clinical settings where ex vivo expansion of progenitor cells is required.

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.