Ami Amit

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.

Endometrial receptivity: the age-related decline in pregnancy rates and the effect of ovarian function.

OBJECTIVE To assess the effect of age and ovarian function on endometrial receptivity. DESIGN Retrospective comparison between standard IVF and ovum donation in younger and older patients (< 40 and > or = 40 years of age, respectively). PATIENTS In standard IVF, there were 325 transfer cycles in older patients and 1,103 transfer cycles in younger ones. In ovum donation, there were 236 transfer cycles in older patients and 222 cycles in younger women. Ovum recipients were then redivided into two groups, according to ovarian function: ovarian failure group (219 cycles) and eugonadal group (239 cycles) in patients with retained ovarian function as manifested by regular menstrual cycles and normal gonadotropins. RESULTS In standard IVF, clinical pregnancy rates (PRs) were significantly lower in older patients (12.9% versus 23.8%, respectively). In ovum donation, clinical PRs were also significantly lower in older patients (21.2% versus 29.3%, respectively). A significantly higher clinical PR (31.1%) was noted in patients with ovarian failure, compared with both eugonadal patients undergoing ovum donation (19.7%) and standard IVF patients (21.3%). CONCLUSIONS The decrease in endometrial receptivity with age is responsible for the higher rate of implantation failure in older women. Patients with nonfunctioning ovaries do better than eugonadal patients in ovum donation programs.

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.

Patients with Turner’s syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation

OBJECTIVE To evaluate whether endometrial receptivity is compromised in patients with premature ovarian failure (POF) due to Turners syndrome who undergo oocyte donation. DESIGN Retrospective analysis. SETTING In vitro fertilization-ET units, anonymous oocyte donation program. PATIENTS The study included 53 patients with POF who underwent oocyte donation. These included 7 patients with Turners syndrome (45,X) who underwent 22 ET cycles, 15 women with Turner variants (mosaics, deletions, or isochromosomes) who underwent 36 ET cycles, and 31 other patients with POF and a normal karyotype who underwent 69 oocyte donation cycles. INTERVENTION All patients on standby for donation were treated with E2 valerate 6 mg/d until oocytes became available; then P 100 mg/d was added. Oocyte donors were healthy women < 34 years who underwent IVF themselves. MAIN OUTCOME MEASURES Clinical pregnancy rates (PRs), biochemical pregnancies, early abortions, and delivery rates were evaluated. RESULTS Turners syndrome patients had a significantly higher rate of biochemical pregnancies (22.7% versus 4.3%), a lower clinical PR (22.7% versus 33.3%), a significantly higher rate of early abortions (60% versus 8.7%), and a significantly lower rate of deliveries per pregnancy (20.0% versus 73.1%) compared with non-Turner patients. CONCLUSIONS Patients with a complete or partial deficiency of an X chromosome have reduced PRs and an increase in early implantation failure after oocyte donation. This may indicate an inherent endometrial abnormality, possibly associated with a deficiency of X-linked genes regulating endometrial receptivity.

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.

The hemizona assay is of good prognostic value for the ability of sperm to fertilize oocytes in vitro

OBJECTIVES To assess the prognostic value of hemizona assay (HZA) in predicting the success of IVF. DESIGN Samples from 133 patients, who were referred for semen evaluation, were tested by HZA. Thirty samples were tested twice to assess interassay variation. Seventy couples were also referred for IVF. Results of HZA were compared with standard parameters of sperm quality, fertilization rates, and pregnancies. RESULTS The intra-assay and interassay coefficient of variation were 8% and 14%, respectively. Hemizona assay results had the highest correlation with sperm morphology (r = 0.60). Of all parameters evaluated, fertilization rates were best predicted by hemizona index (HZI) (r = 0.75). The assay was found to have high sensitivity and specificity rates, at a threshold HZI of 23%. CONCLUSIONS The HZA is a valuable prognostic test for IVF. With a threshold HZI of 23%, it has a good predictive value for fertilization rates in IVF, and may thus be used for patient preselection before IVF.

High progesterone levels adversely affect embryo quality and pregnancy rates in in vitro fertilization and oocyte donation programs

OBJECTIVE To assess the effect of P levels on oocyte and embryo quality and pregnancy rates (PRs) in IVF and oocyte donation. DESIGN Retrospective analysis of PRs in ovum donors and their recipients with regard to P levels on day of hCG administration. SETTING In Vitro Fertilization Units, oocyte donation programs. PATIENTS In vitro fertilization patients who agreed to donate oocytes were treated by hMG alone (53 cycles) or in combination with a GnRH analog (122 cycles). INTERVENTIONS Uterine preparation in oocyte recipients consisted of 6 mg/d E2 valerate. Progesterone (100 mg/d) was added when oocytes became available. Hormonal treatment was continued until 12 weeks of gestation. RESULTS Using a series of Fishers Exact Tests, a critical threshold for P was identified at 1.9 ng/mL (conversion factor to SI units, 3.185). With elevated P levels (> 1.9 ng/mL), lower PRs were noted for the donors (7.1% versus 17%), as well for the recipients (8.3% versus 26.7%). CONCLUSIONS Exposure to elevated P levels resulted in lower PRs for the donors and significantly lower PRs in the recipients. Because the endometria in the recipients were prepared uniformly, we conclude that this is the result of detrimental effects of P on oocyte or embryo quality.