Jacob Levron

Prognostic value of the clinical and laboratory evaluation in patients with nonmosaic Klinefelter syndrome who are receiving assisted reproductive therapy

OBJECTIVEnTo characterize clinical and laboratory findings in nonmosaic 47,XXY patients that may help to predict spermatogenetic activity in their testicles.nnnDESIGNnProspective study.nnnSETTINGnAssisted reproductive technology program.nnnPATIENT(S)nTwenty patients with nonmosaic Klinefelter syndrome who underwent testicular sperm retrieval for IVF.nnnMAIN OUTCOME MEASURE(S)nThe correlation between basal FSH, LH and testosterone levels, mean testicular volume, and results of the hCG test and presence or absence of sperm after testicular sperm extraction (TESE).nnnRESULT(S)nSperm was found in nine patients (45%). The mean testicular volume was 7.8 +/- 2.5 mL in men with sperm after TESE and 5.6 +/- 1.2 mL in those without sperm after TESE; corresponding testosterone levels were 3.5 +/- 1.2 ng/mL and 1.7 +/- 0.8 ng/mL. Serum levels of FSH and LH did not significantly differ between groups. After the hCG test, the mean serum testosterone level was 16.0 +/- 6.3 ng/mL in men with sperm after TESE and 6.7 +/- 5.6 ng/mL in those without sperm.nnnCONCLUSION(S)nTesticular volume, testosterone levels, and results of the hCG test are important predictive factors of spermatogenesis in patients with nonmosaic Klinefelter syndrome.

Zygote intrafallopian transfer may improve pregnancy rate in patients with repeated failure of implantation

OBJECTIVEnTo evaluate the efficacy of zygote intrafallopian transfer (ZIFT) on implantation rates and pregnancy rates (PRs) in patients with repeated failure of implantation in IVF-ET cycles.nnnDESIGNnA case-control study.nnnPATIENT(S)nCriteria for patient selection included male factor or unexplained infertility, normal uterine cavity, and at least three failures of implantation in IVF-ET cycles in which at least three embryos were placed per transfer. Data on 70 patients who underwent 92 ZIFT cycles are presented. A control group consisted of patients with the same selection criteria who underwent an additional standard IVF-ET cycle during the same time period.nnnINTERVENTION(S)nOvulation induction consisted of down-regulation with GnRH analogue followed by ovarian stimulation with FSH and hMG. Intracytoplasmic sperm injection was performed on the oocytes of all patients with male factor infertility. Zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after oocyte retrieval.nnnMAIN OUTCOME MEASURE(S)nImplantation rates and PRs in the ZIFT and control groups were compared.nnnRESULT(S)nThe PRs and implantation rates were significantly higher in the ZIFT group than in the control group: 34.2% (24/70) and 8.7% (29/333) versus 17.1% (12/70) and 4.4% (13/289), respectively (P = 0.002 and P = 0.04). The cumulative conception rate for two ZIFT cycles was 59.3%.nnnCONCLUSION(S)nZygote intrafallopian transfer should be considered a beneficial mode of treatment for patients with repeated failure of implantation in IVF and transcervical ET. More prospective randomized studies are needed to support this observation.

The effect of prolonged cryopreservation on embryo survival

The purpose of this study was to assess the effects of long-term cryopreservation on the survival and implantation rates of embryos. We performed a matched case–control study comparing 101 women whose embryos were transferred after cryopreservation for 2–9 years, with 101 control women whose embryos were transferred after 6 months or less of cryopreservation. A multiple step-wise logistic regression was performed to determine the independent effect of the duration of cryopreservation, patient age and embryo quality on pregnancy and live birth rates. In the study group, 673 embryos were frozen for 24–108 months and of these 451 were thawed. In the control group, 513 embryos were cryopreserved for up to 6 months and 456 were thawed. The implantation rate was similar (4.5% vs. 5.5%) in both groups. We concluded that the duration of cryopreservation did not adversely affect embryo survival, and prolonged cryopreservation appeared to be a safe treatment option.

Sequential transfer of day 3 embryos and blastocysts after previous IVF failures despite adequate ovarian response.

The purpose of this study was to compare IVF outcome following sequential embryo transfer (ET) with that following the transfer of early cleavage embryos among patients with previous multiple IVF failures but adequate ovarian response. A retrospective matched case-control analysis was made of the medical files of 66 women who underwent sequential transfer of day 3 embryos and blastocysts in the Chaim Sheba Medical Centre between January 1999 and May 2004. The control group included 117 matched women who underwent embryo transfer on day 3 only. Sequential transfer of embryos in women resulted in a pregnancy rate of 30.3% (20/66) compared with 17.1% (20/117) following day 3 ET (P < 0.05). Multiple pregnancies (most of them twins) were significantly more common in women undergoing sequential transfer (10/20 versus 2/20; P < 0.02). Sequential transfer of embryos may be indicated for women with repeated IVF cycles, but the number of embryos transferred must be limited in order to prevent multifetal gestations. More data are needed to support this approach.

Should zygote intrafallopian transfer be offered to all patients with unexplained repeated in-vitro fertilization cycle failures?

BackgroundOne of the suggest strategy for patients with repeated implantation failure (RIF) is zygote intrafallopian transfer (ZIFT). However, no data exist regarding to the issue of when and under which circumstances should ZIFT be offered to patients with RIF? We therefore aimed to examine whether repeated implantation failure (RIF) patients characteristics or their previous controlled ovarian hyperstimulation (COH) variables may differentiate between those who will conceive following a ZIFT cycle and those who will not.MethodsForty seven consecutive women admitted to our IVF unit during a 7 year period, who underwent ZIFT for RIF, were included. Ovarian stimulation characteristics, number of oocytes retrieved and number and quality of zygotes/embryos transferred were assessed and compared between the ZIFT cycle and the previous IVF/ICSI cycle and between those who conceived following the ZIFT cycle and those who did not.ResultsTwelve clinical pregnancies (clinical pregnancy rate- 25.5%) were recorded following the ZIFT cycle. Those who benefit from ZIFT were young patients (≤31xa0yrs), who underwent ≤6xa0cycle attempts, yielding over eight 2PN embryos with low (≤0.4) ratio of number of top-quality embryos to total 2PN embryos. Moreover, in those destined for a ZIFT cycle, only those with >7 2PN embryo should undergo a transfer of at least five 2PN embryos.ConclusionsFurther large prospective studies are needed to identify the specific characteristics of RIF women who may benefit from ZIFT.

IVF outcome in azoospermic cancer survivors

OBJECTIVEnTo assess clinical outcome among infertile couples treated by in vitro fertilization (IVF) and intra cytoplasmic sperm injection (ICSI) using testicular sperm from azoospermic cancer survivors.nnnSTUDY DESIGNnThis clinical retrospective study included infertile couples treated in a single tertiary referral center between 1996 and 2013. All male partners were cancer survivors who were diagnosed with azoospermia due to previous gonadotoxic treatments and referred to testicular sperm extraction (TESE). Retrieved sperm was used for IVF-ICSI among patients spouses. Sperm retrieval rate and IVF-ICSI outcome were evaluated.nnnRESULTSnSperm was successfully retrieved in 12 out of 36 patients (33.3%) on initial TESE, with an overall sperm retrieval rate of 38.6% (17 of 44). Female patients were 29.8±5.1 years old. The average number of retrieved oocytes was 14.0±4.0 per cycle, with clinical pregnancy and live birth rates per successful TESE of 64% (11 of 17) and 58.8% (10 of 17), respectively. Age, serum FSH, testicular volume and time from chemotherapy to TESE were not significantly different between patients with successful TESE to those without. Patients suffering from seminomas had significantly higher sperm retrieval rate, as compared to patients who had Hodgkins lymphoma (P=0.024).nnnCONCLUSIONSnPost-chemotherapy azoospermia can be successfully treated with TESE and ICSI, and should be offered to azoospermic cancer survivors who did not cryopreserve sperm prior to their gonadotoxic treatments.

Fish based preimplantation genetic diagnosis to prevent DiGeorge syndrome

PurposeTo report the performance of fluorescence in-situ hybridization in the setting of preimplantation genetic diagnosis in order to diagnose embryos affected by DiGeorge syndrome.DesignCase report.SettingAcademic referral center.PatientA 32xa0year-old female affected by DiGeorge syndrome.Intervention(s)History and physical examination, karyotyping, amniocentesis, preimplantation genetic diagnosis, fluorescence in-situ hybridization.Main outcome measure(s)Avoidance of pregnancy with embryo affected by DiGeorge syndrome.Result(s)Termination of pregnancy with an affected embryo followed by fluorescence in-situ hybridization based preimplantation genetic diagnosis and delivery of healthy offspring.Conclusion(s)The combination of preimplantation genetic diagnosis with fluorescence in-situ hybridization is recommended to prevent pregnancies with DiGeorge syndrome affected embryos in properly selected patients.

Pre-implantation genetic diagnosis—should we use ICSI for all?

ObjectiveIntracytoplasmic sperm injection (ICSI) is commonly used during pre-implantation genetic diagnosis (PGD) in vitro fertilization (IVF), aiming to eliminate the risk of contamination from extraneous sperm DNA. Recently, ICSI “overuse” in non-male infertility has been doubted, since it does not offer an advantage over IVF. Prompted by the aforementioned observations, we sought to assess the accuracy of IVF vs ICSI in PGD cases, as might be reflected by a difference in the prevalence of discarded embryos as a consequent of parental contamination.MethodsCohort-historical study of all consecutive patients admitted to the IVF-PGD program in a large tertiary center. The percentages of complete, incomplete diagnosis, PCR failure, abnormal embryos, and the contamination rate with paternal DNA in the IVF-only and the ICSI-only groups. We reviewed the computerized files of all consecutive women admitted to our IVF for a PGD-PCR cycle. Patients were divided accordingly into three groups: an IVF group—where all the oocytes underwent IVF only, an ICSI group—where all oocytes underwent ICSI, and a mixed group—where sibling oocytes underwent both IVF and ICSI. The laboratory data and the genetic diagnostic results were collected and compared between the different insemination groups.ResultsNine-hundred and twenty-seven patients underwent IVF-PGD cycles in our program, 315 in the IVF group, 565 in the ICSI group, and 47 in the mixed group. No differences were observed in fertilization rates, the percentage of embryos available for biopsy, and the percentages of complete, incomplete diagnosis, PCR failure, or abnormal embryos, between the IVF-only and the ICSI-only groups and between the IVF and the ICSI of sibling oocytes in the mixed group. Moreover, contamination with paternal DNA, through contamination with sperm cells, was negligible. Not one single case of misdiagnosis was encountered during the study period.ConclusionIt might be therefore concluded that IVF should be the preferred insemination methods in PGD cycles, and ICSI should be indicated only in cases of male-factor infertility.