Jacob Farhi

Prospective evaluation of two stimulation protocols for low responders who were undergoing in vitro fertilization–embryo transfer

OBJECTIVEnTo compare two stimulation protocols designed for low responders undergoing IVF.nnnDESIGNnRandomized, prospective study.nnnSETTINGnUniversity hospital IVF unit.nnnPATIENT(S)nSixty low responders who were recruited on the basis of results in previous cycles.nnnINTERVENTION(S)nModified flare protocol in which a high dose of GnRH agonist was administered for the first 4 days, followed by a standard agonist dose, or a modified long protocol in which a standard agonist dose was used until pituitary down-regulation, after which the agonist dose was halved during stimulation.nnnMAIN OUTCOME MEASURE(S)nNumber of oocytes retrieved.nnnRESULT(S)nTwenty-nine cycles were performed with the modified flare protocol and 31 were performed with the modified long protocol. Significantly more oocytes were obtained with the modified long protocol than the modified flare protocol (4.42 +/- 2.6 vs. 3.07 +/- 2.15). The number and quality of embryos available for transfer was similar in both groups. One clinical pregnancy (3.4%) was achieved with the modified flare protocol, and 7 pregnancies (22.5%) were achieved using the modified long protocol.nnnCONCLUSION(S)nThese preliminary results substantiate the poor prognosis and outcome for low responders undergoing IVF. A modified long mini-dose protocol appears to be superior to a modified mega-dose flare protocol in terms of oocyte yield and cycle outcome.

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

OBJECTIVEnTo compare extended culture with blastocyst stage transfer and zygote intrafallopian transfer (ZIFT) in the management of IVF patients with repeated implantation failure.nnnDESIGNnProspective, nonrandomized study.nnnSETTINGnAn IVF unit at a university hospital.nnnPATIENT(S)nSixty-four infertile patients with more than three previous failed IVF-ET attempts.nnnINTERVENTION(S)nPatients were allocated to undergo either blastocyst stage transfer (Group 1; n = 32) or ZIFT (Group 2; n = 32).nnnMAIN OUTCOME MEASURE(S)nImplantation, clinical pregnancy, and live birth rates.nnnRESULT(S)nPatient 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.nnnCONCLUSION(S)nZygote 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

OBJECTIVEnTo 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.nnnDESIGNnRetrospective analysis of ZIFT cycles.nnnSETTINGnAn IVF unit in a university hospital.nnnPATIENT(S)nCriteria 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.nnnINTERVENTION(S)nFour to six zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval.nnnMAIN OUTCOME MEASURE(S)nImplantation 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).nnnRESULT(S)nThe 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.nnnCONCLUSION(S)nZIFT 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.

Coarse granulation in the perivitelline space and IVF-ICSI outcome.

AbstractPurpose: To study the effect of the presence of coarse granules in the perivitelline space (PVS) of oocytes on embryonic development, and on implantation and pregnancy rates in IVF.nMethods: The study population included 24 patients treated during the period 1995–2000. The majority or all of their oocytes exhibited repeatedly coarse granulation in the PVS. Clinical and laboratory cycle characteristics of their 65 IVF-ICSI cycles and the resulting implantation and pregnancy rates were compared to a matched control group of 65 IVF- ICSI cycles without granulation in the PVS.nResults: A total of 623 oocytes were retrieved, 418 oocytes fertilized, and 246 embryos were transferred in the study group. No difference was detected between the study and control group with regard to patients clinical data, IVF cycle characteristics, mean number of oocytes retrieved and fertilized, and mean number of embryos transferred. Only seven pregnancies were achieved in the study group, leading to pregnancy and implantation rates of 10.7 and 5.7%, respectively. Pregnancy and implantation rates were significantly higher in the control group of matched IVF-ICSI cycles without granulation in the PVS (32.5 and 11.5%, respectively).nConclusions: The presence of coarse granules in the PVS correlates with low implantation and pregnancy rates in IVF-ICSI cycles and might be regarded as a distinct entity, part of the yet poorly defined condition of “egg factor infertility.”

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

OBJECTIVEnTo 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.nnnDESIGNnProspective randomized controlled study.nnnSETTINGnThe IVF Unit, Wolfson Medical Center, Holon, Israel.nnnPATIENT(S)nAll women in whom oocytes were retrieved at the germinal vesicle stage between December 1995 and March 1996.nnnINTERVENTION(S)nOocytes 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.nnnMAIN OUTCOME MEASURE(S)nMaturation rate from the germinal vesicle to M2 stage and fertilization rate.nnnRESULT(S)nEach 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.nnnCONCLUSION(S)nBoth 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

OBJECTIVEnTo 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.nnnDESIGNnRetrospective study.nnnSETTINGnAn IVF clinic in a university hospital.nnnPATIENT(S)nForty-seven IVF-ICSI cycles using testicular spermatozoa in 28 couples with the male partner suffering from nonobstructive azoospermia.nnnINTERVENTION(S)nSperm 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.nnnMAIN OUTCOME MEASURE(S)nThe presence of motile spermatozoa at the time of ICSI and fertilization and clinical pregnancy rates.nnnRESULT(S)nA 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.nnnCONCLUSION(S)nTesticular 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.

Human chorionic gonadotropin serum levels following ovulation triggering and IVF cycle outcome

PurposeThe clinical significance of serum hCG levels after ovulation triggering was studied previously with conflicting results. Our aim was to study the correlation of hCG levels on the day after ovulation triggering using recombinant hCG (r-hCG) with treatment outcome.MethodsA prospective observational study of all fresh IVF/ICSI cycles in a single medical center, between January 2015 and June 2016, was performed. hCG serum levels were obtained 10–12xa0h following ovulation triggering with 250xa0mcg r-hCG. Clinical and laboratory outcome parameters were compared between cycles with serum hCG above and below median level. A multivariate regression analysis was performed in order to study the association between hCG levels and live birth rate, after controlling for confounders.ResultsOverall, 326 cycles were included. Median serum hCG level was 91.35xa0IU/L. hCG levels were lower as age and BMI were higher (pu2009=u20090.004, pu2009<u20090.001, respectively). The study groups did not differ with regard to clinical pregnancy rate (pu2009=u20090.14), live birth rate (pu2009=u20090.09), fertilization rate (pu2009=u20090.45), or metaphase II oocyte rate (pu2009=u20090.68). On multivariate regression analysis, hCG level was not associated with live birth (aOR 0.99, 95% CI 0.98–1.005), after controlling for patient’s age and BMI.ConclusionshCG levels on the day after ovulation triggering with 250xa0mcg r-hCG are inversely correlated with patient age and BMI. However, they are not correlated with any clinical or laboratory outcome parameter. Therefore, testing for hCG levels after ovulation induction seems futile and cannot be recommended.

OC093: Uterine contractility throughout ART cycles

significantly (p = 0.12). Furthermore, more conspicuous results were revealed by the qualitative analysis: eight subjects (44.44%) presented ‘‘abnormal’’ spectra according to Goswamy and Steptoe’s waveform classification i.e. type A (n = 1), type B (n = 3) and type O (absent diastolic blood flow) (n = 4); all of them recovered type C waveforms (normal spectrum) during the hour following nifedipine dispensation. Conclusions: Nifedipine induced a reversible enhancement of uterine arterial blood flow. Restoring diastolic blood flow provides a compelling evidence that nifedipine is a potent drug which may improve embryonic implantation in case of abnormal uterine vascularization.