H. Nahum

Estradiol supplementation during the luteal phase may improve the pregnancy rate in patients undergoing in vitro fertilization-embryo transfer cycles

OBJECTIVE To evaluate the effect of adding E(2) to progestin supplementation during the luteal phase on pregnancy and implantation rates in patients undergoing IVF cycles. DESIGN Prospective, randomized study. SETTING An IVF unit in a university hospital. PATIENT(S) Patients who were undergoing IVF with controlled ovarian hyperstimulation using a GnRH analog and who had E(2)2,500 pg/dL at the time of hCG administration. INTERVENTION(S) Serum concentrations of E(2) and progesterone were measured in all patients on days 7, 10, and 12 after ET. MAIN OUTCOME MEASURE(S) The E(2) and progesterone profiles of the luteal phase and the pregnancy and implantation rates were documented. Data were analyzed for the entire study population and further stratified according to the GnRH analog protocol used (short or long). RESULT(S) Significantly higher E(2) levels were found during the luteal phase in the group that received E(2) supplementation. This effect was more pronounced in the patients who were treated with the long GnRH analog protocol. Significantly higher pregnancy and implantation rates were recorded in the patients who received E(2) supplementation and were treated with the long GnRH analog protocol. CONCLUSION(S) For patients who are treated with the long GnRH analog protocol for controlled ovarian hyperstimulation and for whom luteal support with hCG is contraindicated, the addition of E(2) to the progestin support regimen may have a beneficial effect on pregnancy and implantation rates.

Pregnancies and live births following ICSI with testicular spermatozoa after repeated implantation failure using ejaculated spermatozoa.

The use of testicular spermatozoa for IVF/intracytoplasmic sperm injection (ICSI) is currently indicated exclusively for patients with azoospermia, since a favourable outcome is expected even when very few spermatozoa are present in the ejaculate. Here, a series of four couples with long-standing male factor infertility and multiple failed IVF/ICSI cycles are described. In all couples, the use of ejaculated spermatozoa for ICSI resulted in poor embryo quality and repeated implantation failure. Testicular sperm aspiration was performed in subsequent cycles, and testicular spermatozoa were used for ICSI. Embryo implantation and ongoing pregnancies/deliveries were achieved in all four couples. It is postulated that spermatozoa are subjected to post-testicular damage during sperm transport between the seminiferous tubules and epididymis, with the injection of damaged spermatozoa being the cause for repetitive IVF/ICSI failures. In selected patients, the use of testicular spermatozoa for IVF/ICSI should be considered, even when motile spermatozoa can be identified in the ejaculate.

Prospective evaluation of blastocyst stage transfer vs. zygote intrafallopian tube transfer in patients with repeated implantation failure

OBJECTIVE To compare extended culture with blastocyst stage transfer and zygote intrafallopian transfer (ZIFT) in the management of IVF patients with repeated implantation failure. DESIGN Prospective, nonrandomized study. SETTING An IVF unit at a university hospital. PATIENT(S) Sixty-four infertile patients with more than three previous failed IVF-ET attempts. INTERVENTION(S) Patients were allocated to undergo either blastocyst stage transfer (Group 1; n = 32) or ZIFT (Group 2; n = 32). MAIN OUTCOME MEASURE(S) Implantation, clinical pregnancy, and live birth rates. RESULT(S) Patient characteristics and response to stimulation were comparable for both groups. Totals of 84.3% and 97% of the patients underwent blastocyst transfer and ZIFT, respectively. Significantly more embryos were transferred through ZIFT (5.5+/-0.8) as compared with blastocyst transfer (2.3+/-1.4), and there were significantly more cycles with embryo cryopreservation in the ZIFT group as compared to the blastocyst transfer group (15/32 vs. 4/32, respectively). Implantation rate (13.6% vs. 1.4%), clinical pregnancy rate (40.6% vs. 3.1%), and live birth rates (38.7% vs. 0%) were all significantly higher in the ZIFT group as compared to the blastocyst transfer group, respectively. CONCLUSION(S) Zygote intrafallopian transfer is a powerful clinical tool in the management of patients with RIF. In contrast, blastocyst stage transfer fails to improve the outcome in this poor-prognosis group. The pathophysiology of RIF should be the subject of intense investigation to allow the introduction of appropriate therapeutic measures earlier in the course of treatment.

Zygote intrafallopian transfer in patients with tubal factor infertility after repeated failure of implantation with in vitro fertilization–embryo transfer

OBJECTIVE To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) in terms of implantation and pregnancy rates in patients with tubal factor infertility and repeated implantation failure in IVF-ET cycles. DESIGN Retrospective analysis of ZIFT cycles. SETTING An IVF unit in a university hospital. PATIENT(S) Criteria for patient selection for ZIFT included at least four failures of implantation in IVF-ET cycles in which at least 3 embryos were replaced per transfer and a cause of infertility diagnosed as male, unexplained, or tubal factor with proof of one patient tube. INTERVENTION(S) Four to six zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval. MAIN OUTCOME MEASURE(S) Implantation and pregnancy rates were determined in 112 ZIFT cycles performed in 81 patients with repeated failure of implantation. Results were further stratified for patients with tubal factor (n = 15) and patients without tubal factor (n = 66). RESULT(S) The pregnancy and implantation rates for all ZIFT cycles were 35.1% and 11.1%, respectively. Pregnancy and implantation rates per cycle in patients with tubal factor versus patients without tubal factor were 26.6% versus 37.1% and 9.4% versus 11.4%, respectively. CONCLUSION(S) ZIFT can be considered as a mode of treatment for patients with repeated failure of implantation in IVF-ET and with tubal factor with proved patency of one tube.

Incubation with sperm enhances in vitro maturation of the oocyte from the germinal vesicle to the M2 stage

OBJECTIVE To evaluate the effect of sperm in the culture medium on the rate of oocyte maturation in vitro from the germinal vesicle to the M2 stage. DESIGN Prospective randomized controlled study. SETTING The IVF Unit, Wolfson Medical Center, Holon, Israel. PATIENT(S) All women in whom oocytes were retrieved at the germinal vesicle stage between December 1995 and March 1996. INTERVENTION(S) Oocytes retrieved at the germinal vesicle stage were divided prospectively and randomly into four groups of incubation conditions: group 1, intact germinal vesicle with cumulus; group 2, intact germinal vesicle with sperm cells in the culture medium; group 3, stripped germinal vesicle; and group 4, stripped germinal vesicle with sperm cells. Oocytes were observed 24 hours after retrieval, and the stage of maturation was recorded. Oocytes that reached the M2 stage underwent the intracytoplasmic injection procedure, and the fertilization rate in each group was recorded at 48 hours. MAIN OUTCOME MEASURE(S) Maturation rate from the germinal vesicle to M2 stage and fertilization rate. RESULT(S) Each group contained 20 germinal vesicle oocytes. In groups 1 and 2, 2 (10%) and 9 (45%) oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 1 (5%) and 8 (40%) embryos developed, respectively. The results in group 2 were significantly higher than in group 1. In groups 3 and 4, 6 (30%) and 16 (80%) oocytes, respectively, reached the M2 stage at 24 hours; at 48 hours, 5 (25%) and 14 (70%) embryos developed, respectively. Results in group 4 were significantly higher than those in groups 1, 2, and 3. CONCLUSION(S) Both methods of oocyte activation (i.e., addition of sperm to the culture medium or removal of the cumulus) enhance oocyte maturation in vitro, but the sperm-incubation method has a more pronounced effect. A combination of both methods leads to an exceptionally high rate of oocyte maturation, followed by a high fertilization rate.

Timing of testicular sperm retrieval procedures and in vitro fertilization–intracytoplasmic sperm injection outcome

OBJECTIVE To compare the outcome of IVF-intracytoplasmic sperm injection (ICSI) using testicular spermatozoa obtained on the day of ovum pick-up (OPU) or on the day before OPU. DESIGN Retrospective study. SETTING An IVF clinic in a university hospital. PATIENT(S) Forty-seven IVF-ICSI cycles using testicular spermatozoa in 28 couples with the male partner suffering from nonobstructive azoospermia. INTERVENTION(S) Sperm retrieval was performed either on the OPU day (23 cycles in 19 patients; group A) or on the day before OPU (24 cycles in 15 patients; group B). Testicular sperm aspiration (TESA) was performed and followed by testicular sperm extraction (TESE) if no spermatozoa could be found. MAIN OUTCOME MEASURE(S) The presence of motile spermatozoa at the time of ICSI and fertilization and clinical pregnancy rates. RESULT(S) A similar proportion of motile spermatozoa (60.9% vs. 62.5%), fertilization rate (61.7% vs. 58.9%), and clinical pregnancy rate per transfer (34.8% and 29.2%) were obtained for groups A and B, respectively. CONCLUSION(S) Testicular sperm retrieval can be performed on the day before OPU without compromising success. Considerable medical and practical advantages may be offered by further advancement of testicular sperm retrieval procedures to 48 hours before OPU. This approach should thus be further evaluated.