Ester Polak de Fried

Low-dose aspirin treatment improves ovarian responsiveness, uterine and ovarian blood flow velocity, implantation, and pregnancy rates in patients undergoing in vitro fertilization: a prospective, randomized, double-blind placebo-controlled assay

OBJECTIVE To determine the effects of low-dose aspirin on ovarian response, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in patients undergoing IVF. DESIGN Prospective, randomized, double-blind placebo-controlled assay. SETTING Department of Reproductive Medicine, CER Medical Institute, Buenos Aires, Argentina. PATIENT(S) Two hundred ninety-eight infertile patients (mean [+/- SDI age, 35.6+/-4.09 years) undergoing IVF cycles. INTERVENTION(S) In the treatment group, 149 patients underwent controlled ovarian hyperstimulation and received a daily dose of 100 mg of aspirin. In the control group, 149 patients underwent controlled ovarian hyperstimulation in association with placebo. MAIN OUTCOME MEASURE(S) Number of follicles, number of oocytes retrieved, serum E2 levels, uterine and ovarian pulsatility index, cancellation rate, number of embryos transferred, and implantation and pregnancy rates. RESULT(S) There were statistically significant differences between the treatment group and the control group, respectively, in the number of follicles (19.8+/-7.2 versus 10.2+/-5.3), number of oocytes retrieved (16.2+/-6.7 versus 8.6+/-4.6), serum E2 levels (2,923.8+/-1,023.4 versus 1,614.3+/-791.7 pg/mL), uterine pulsatility index (1.22+/-0.34 versus 1.96+/-0.58), ovarian pulsatility index (1.18+/-0.31 versus 1.99+/-0.56), pregnancy rate (45% versus 28%), and implantation rate (17.8% versus 9.2%). CONCLUSION(S) Low-dose aspirin treatment significantly improves ovarian responsiveness, uterine and ovarian blood flow velocity, and implantation and pregnancy rates in IVF patients.

Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone receptors and steroidogenesis in ovarian cells *

OBJECTIVE To examine the effect of a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide acetate (LA), on human chorionic gonadotropin/luteinizing hormone (LH) receptors content and progesterone (P) and estradiol (E2) production in cultured granulosa or luteal cells. DESIGN Prospective. SETTING Private Fertility Clinic and National Research Institute. PATIENTS Twenty patients undergoing in vitro fertilization or gamete intrafallopian transfer programs. RESULTS Human chorionic gonadotropin/LH receptors in human granulosa cells increased after 48 hours of culture, and LA inhibited such effect. Leuprolide acetate, 1 ng/mL, in the cultures produced an increase in P production. On the contrary, LA inhibited E2 production. Additionally, the in vivo effect of LA (2 micrograms/rat per 7 days) was studied in corpus luteum of superovulated rats. Luteal cells from LA-treated rats in culture produced lower P than the controls but showed an increase in aromatase activity. Luteal LH receptors declined after 48 hours of culture with LA. CONCLUSION The high doses of gonadotropin necessary to induce ovarian hyperstimulation when GnRH-a is administered could be related with an inhibitory effect of these agonists on LH receptors and aromatase activity.

Male immunologic infertility: Sperm performance on in vitro fertilization

Abstract Objective : To analyze sperm performance in a group of patients with male immunologic infertility treated with IVF-ET. Design : Retrospective clinical study. Setting : Patients attending a private IVF clinic. Patient(s) : The study group comprised seven men with significant levels of surface-bound antisperm antibodies treated in nine IVF cycles. The control group comprised nine couples with female tubal infertility and no indication of male factor infertility treated on the same cycle. Intervention(s) : None. Main Outcome Measure(s) : Fertilization rate, early embryonic development, implantation, and clinical pregnancy rate (PR). Result(s) : Forty-six (44.2%) of 104 inseminated oocytes were fertilized in the study group compared with 65 (84.4%) of 77 in the control group, which was a significant difference. Surfacebound antisperm antibodies significantly inhibited early embryonic cleavage in the study group (13 [28.3%] of 46 embryos with at least 3 blastomeres) compared with the control group (41 [63.1%] of 65 embryos, with at least 3 blastomeres). The percentage of good-quality embryos (grades 1 and 2) was similar in the study and control groups (71.7% and 78.5%, respectively). The percentage of poor-quality embryos (grade 4 and two pronuclei) was higher in the study group compared with the control group (13.9% versus 9.2%, respectively); however, the difference was not significant. The implantation rate and clinical PR were lower in the study group (3% and 11%, respectively) compared with the control group (9.5% and 44%, respectively), but the difference was not statistically significant. Conclusion(s) : The fertilization rate and early embryonic cleavage of human embryos was found to be reduced significantly in patients with high levels of surface-bound antisperm antibodies. Moreover, embryonic quality and the PR may be compromised by the presence of significant levels of surface-bound antisperm antibodies.

Progesterone production in cultured human granulosa cells: correlation with follicular fluid hormone levels *

STUDY OBJECTIVE To examine the progesterone (P) production by cultured granulosa cells and the hormonal content in the follicular fluid (FF) of ovarian-hyperstimulated women. DESIGN Retrospective. SETTING Private Fertility Clinic and National Research Institute. PATIENTS Eighteen patients undergoing in vitro fertilization or gamete intrafallopian transfer programs. RESULTS Progesterone levels Measured in the culture medium of granulosa cells decreased sixfold with culture time. Human luteinizing hormone (LH) increased P production only when basal P production was less than 1 microgram/mL. Granulosa cell P production in culture was negatively correlated with FF LH-human chorionic gonadotropin (hCG) levels. Follicular fluid follicle-stimulating hormone (FSH) levels were positively correlated with FF P and 17 beta-estradiol (E2) concentrations. Similar results were found between FF LH (hCG) and E2 levels, but there was no relationship between FF LH (hCG) and FF P values. CONCLUSION The high dose of hCG administered during gonadotropin treatment could induce a decrease in the in vitro granulosa cell P production.

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2) investigated the time of appearance of auto-antibodies with respect to CMV antigenemia in liver transplant recipients. In this study, AECAs were detected in coincidence with or immediately after the CMV antigenemia peak in most cases and were observed for at least 15 days. It is speculated that the CMVinduced endothelial damage and the presence of circulating cytomegalic endothelial cells may be a potent antigenic stimulus that leads to the production of AECAs. CMV antigenemia is considered as a possible indirect marker of endothelial cell infection and can reflect the state of the endothelial barrier. We reported the differences in the clinical outcomes between the recipients with mismatched and matched combinations of CMV glycoprotein H (gH) antibodies 3) . In our study, most acute rejection was diagnosed within one month after transplantation (mean 25±32 days of rejection after transplantation), and initial positive antigenemia was detected thereafter. On the other hand, the mean weeks of the initial antigenemia detection was 7 weeks after transplantation and its range was varied from 1 to 20 weeks after transplantation. Although this might indicate that most acute rejection was diagnosed prior to AECAs production, association between auto-antibodies and acute rejection could not be ruled out. In addition to measurement of the AECAs titers and their comparison between gH match and mismatch recipients, longer follow up data would be interesting to evaluate the AECAs as a predictor of acute renal allograft vascular rejection.

Interleukin-1β levels in human embryo culture supernatants and their predictive value for pregnancy

Interleukin 1 (IL-1) is possibly one factor produced by the embryo that might have a role in the maternal immunological recognition of pregnancy. The purpose of this study was to identify an embryo-related factor suitable for prediction of pregnancy during IVF procedures. For this purpose, IL-1 beta levels were measured in 21 samples of human embryo culture-conditioned media. The average number of embryos per sample was 5 +/- 1. Simultaneously, 16 cell culture media containing 10% autologous serum but no embryos were tested as controls. IL-1 beta levels were measured using the ELISA technique, and the biological activity of IL-1 was measured by means of a C3H/HeJ mice thymocyte proliferation assay. The average IL-1 beta level +/- S.E.M. was 49 +/- 7 pg/ml in embryo culture-conditioned media and 12 +/- 2 pg/ml in controls (P < 0.001). The average IL-1 beta level in embryo culture-conditioned media from viable pregnancy cycles was 82 +/- 6 pg/ml (n = 8), while in those cases that did not result in viable pregnancies the IL-1 beta level was significantly lower (28 +/- 4 pg/ml, n = 13, P < 0.001). The IL-1 activity of embryo culture-conditioned media, measured by [3H]thymidine incorporation in thymocytes was increased, compared with control media (442 +/- 51 counts/min vs. 337 +/- 13 counts/min, P < 0.05), and the highest values corresponded to media containing those embryos that resulted in pregnancies (589 +/- 41 counts/min, P < 0.01 vs. controls). We conclude that the determination of the levels of this cytokine in embryo culture-conditioned media might be a predictive parameter for pregnancies in patients undergoing IVF-ET.

Healthy girl born after cryopreservation of gametes and ICSI in a patient with seminoma

This study reports birth in a case of intracytoplasmic sperm injection with cryopreserved oocytes and spermatozoa banked after radiotherapy and prior to chemotherapy due the occurrence of two non-synchronous seminomas. A 30-year-old male with a diagnosis of seminoma cryopreserved six vials of spermatozoa. After oncological treatment was completed, his partner, a 24-year-old woman, underwent ovarian stimulation. Seventeen oocytes were retrieved; one was at the germinal vesicle stage and two were injected, resulting in two embryos. Fourteen metaphase II oocytes were frozen. The woman presented moderated ovarian hyperstimulation syndrome, and embryo cryopreservation was indicated. After endometrial preparation, two embryos were transferred and a pregnancy was achieved. The woman suffered eclampsia during week 28 of gestation. Caesarean section was performed and a preterm girl weighing 1000 g was born, but died 2 weeks after delivery. A year later, a second procedure was begun. Frozen oocytes and one vial of semen were thawed. Eight of the 14 oocytes survived and were microinjected; two became fertilized and one good quality cleaved embryo was transferred. Pregnancy was achieved and a healthy girl was born with a birth weight of 2800 g. Oocyte cryopreservation associated with sperm banking in cancer patients is a useful tool for couples seeking deferred parenthood.