Micha Baum

End tidal carbon monoxide levels are lower in women with gestational hypertension and pre-eclampsia.

BACKGROUND: The possible role of heme oxygenase and its byproduct carbon monoxide (CO) in the regulation of blood pressure is under investigation. The aim of this study was to compare end tidal breath CO (ETCO) levels in women with gestational hypertension (GH) or pre-eclampsia to the levels in healthy pregnant and nonpregnant women.MATERIALS AND METHODS: We prospectively performed ETCO measurements corrected for ambient CO (ETCOc) in two medical centers (Stanford, CA and Cleveland, OH). A Natus® CO-Stat® End Tidal Breath Analyzer (Natus Medical Inc., San Carlos, CA) was used. The study group included a convenience sample of 31 women with GH/pre-eclampsia (PE). Control groups included 46 nonpregnant healthy women, 44 first-trimester and 48 third-trimester pregnant healthy women.RESULTS: Mean±SD ETCOc measurements were significantly lower in the GH/PE group compared to first-trimester (p=0.004) and third-trimester (p=0.001) normotensive pregnant and nonpregnant women (p=0.002) (1.36±0.30 vs 1.76±0.47, 1.72±0.42 and 1.78±0.54 ppm, respectively). The ETCOc values were ≤1.6 ppm in 89% of GH/PE women compared with, respectively, only 45, 54, and 46% of nonpregnant, first- and third-trimester normotensive pregnant women (p<0.05). ETCO measurements were not influenced by maternal age, parity, ethnicity, body mass index, gestational age or presence of household smokers. In the two centers, the controls had a similar mean ETCOc and the differences found remained significant when results for each center were analyzed separately.CONCLUSIONS: ETCOc levels were found to be significantly lower in women with GH/PE. Further investigation is required to determine if the lower CO levels reflect a deficient compensatory response to the increase in blood pressure or whether these are primary changes of significance to our understanding of the pathogenesis of GH/PE.

Role of embryo quality in predicting early pregnancy loss following assisted reproductive technology

Early pregnancy loss (EPL) significantly reduces the initial success rate of assisted reproduction treatments and increases the psychological burden on the patient. The aim of the current study was to investigate the association between embryo quality and EPL in IVF. A retrospective study of 1471 women undergoing IVF between July 2000 and October 2004 was performed. Multivariate logistic regression models evaluated the effect on EPL of the womans age, type and cause of infertility, endometrial thickness on the day of oocyte retrieval, performance of intracytoplasmic sperm injection, number of transferred embryos, embryo quality as assessed by the number of blastomeres in the leading transferred embryo at day 3, and the percentage of fragmentation. The 2902 oocyte retrieval-embryo transfer cycles resulted in 816 pregnancies (28.1%; 705 women) constituting the study cohort. Of these, 259 pregnancies (31.7%) ended in EPL and 557 (68.3%) in ongoing pregnancies. EPL risk was significantly associated with advanced (>35 years) maternal age (OR=1.53; 95% CI 1.12-2.09) and five or fewer blastomeres in the leading embryo transferred at day 3 (OR=1.82; 95% CI 1.16-2.85). In conclusion, the quality of transferred embryos, as assessed by the total number of blastomeres in the leading transferred embryo, and maternal age are predictors of EPL.

Does local injury to the endometrium before IVF cycle really affect treatment outcome? Results of a randomized placebo controlled trial

Aim: To evaluate the effect of local injury to the endometrium during spontaneous menstrual cycles before in vitro fertilization (IVF) treatment on implantation and pregnancy rates in women with recurrent implantation failure (RIF). Methods: In a prospective randomized controlled trial (RCT), a total of 36 patients, with RIF undergoing IVF, were randomized to two groups. In 18 patients, endometrial biopsies were performed using a pipelle curette on days 9–12 and 21–24 of the menstrual cycle preceding IVF treatment. In 18 control patients, a cervical pipelle was performed. Results: The implantation rate (2.08% versus 11.11%; p = 0.1), clinical (0% versus 31.25%; p < 0.05) and live births rates (0% versus 25%; p = 0.1) were lower in the experimental group compared with controls. Conclusion: Our RCT did not find any benefit from local injury to the endometrium in women with a high number of RIFs. Further studies are warranted to better define the target population of patients who may benefit from this procedure.

Recurrence of empty follicle syndrome with stimulated IVF cycles

Aim: To determine the incidence of recurrent empty follicle syndrome (EFS) and to analyse the factors associated with this phenomenon. Methods: Retrospective analysis comparing all EFS cycles with cycles in which oocytes were retrieved in our in vitro fertilization (IVF) unit between 1998 and 2006. Results: Of 8292 IVF cycles, 163 (2.0%) resulted in empty follicles. Risk factors for EFS included advanced age (37.7 ± 6.0 years vs. 34.2 ± 6.0 years, p < 0.001), longer infertility (8.8 ± 10.6 years vs. 6.3 ± 8.4 years, p < 0.05), higher baseline follicle-stimulating hormone levels (8.7 ± 4.7 IU/L vs. 6.7 ± 2.9 IU/L, p < 0.001) and lower E2 levels before the human chorionic gonadotropin injection (499.9 ± 480.9 pg/mL vs. 1516.3 ± 887.5 pg/mL, p < 0.001) compared with cases in which ova were retrieved. Among patients with EFS, recurrent EFSs occurred in 15.8% of subsequent cycles. Conclusion: The EFS is a sporadic event in the majority of patients. However, in about 16% of the patients, EFS may recur. These cases may be a variant form of poor response and patients with repetitive EFS syndrome should be counseled concerning their chances to conceive.

Gestational Pattern of Heme Oxygenase Expression in the Rat

Fetal growth is influenced by many intrinsic and extrinsic factors. Our objective was to determine the pattern of heme oxygenase (HO) expression in the pregnant rat and to study its association with fetal growth and growth factors. Uterine tissues were obtained from nonpregnant and from time-mated rats at 7, 13, 16, 19, and 21 d of pregnancy. Placental tissue was obtained on d 13, 16, 19 and 21 of pregnancy. Tissues were evaluated for HO activity, HO-1, HO-2, leptin and vascular endothelial growth factor protein, and HO-1 and HO-2 mRNA. HO activity in both the uterus and placenta peaked on d 21 of pregnancy. In the uterus, HO-1 and HO-2 protein and total mRNA levels peaked on d 16 of pregnancy, whereas, in the placenta, HO-1 and HO-2 protein levels peaked on d 19. Additionally, placental HO-1 mRNA peaked on d 16, but placental HO-2 mRNA declined toward the end of pregnancy. Placental leptin and vascular endothelial growth factor protein levels followed a similar pattern to placental HO-1 and peaked on d 16. We conclude that there is a clear uterine and placental gestational pattern of HO expression in the rat. This pattern is comparable to that of vascular endothelial growth factor and leptin.

Why do couples discontinue unlimited free IVF treatments

Abstract Worldwide, IVF is often discontinued before a live birth is achieved due to high costs. Even when partial financial coverage is provided, often medical providers advise treatment discontinuation. In Israel, unlimited IVF is offered free of charge for a couples’ first two children. Our objective was to assess the reasons couples discontinue IVF treatments before achieving two children in a completely unlimited cost-free environment. This cohort study included all primary infertile women, <35 years, referred for their first IVF cycle to Sheba IVF unit between 2001 and 2002. Patients were followed until February 2012. Those who ceased treatments for 12 months were interviewed to assess the main reason they ceased treatments. Of the 134 couples included, only 46 ceased IVF treatments without achieving two children, after performing an average of 6.2 IVF cycles to achieve their first birth. The reasons given were: lost hope of success (13), psychological burden (18), divorce (6), medical staff recommendation (5), bureaucratic difficulties (3) and general medical condition (1). The main reasons for “drop out” in our cost-free environment were as follows: psychological burden and lost hope of success. Due to high availability of treatments, medical staff recommendation was a less significant factor in our study.

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.

Is severe OHSS associated with adverse pregnancy outcomes? Evidence from a case-control study.

Ovarian hyperstimulation syndrome (OHSS) is a serious and potentially life-threatening complication of fertility treatment. This study evaluated pregnancy outcomes of women hospitalized for severe OHSS. A case-control study was performed of 125 women who were hospitalized due to severe OHSS compared with a control group, consisting of 156 women matched by age and aetiology of infertility, who conceived via IVF and did not develop OHSS. Among women with singleton pregnancies, patients with severe OHSS delivered significantly earlier (37.96 versus 39.11 weeks) and had smaller babies (2854 g versus 3142 g) compared with the matched controls. Similarly, rates of preterm delivery (<34 weeks of gestation: 8.9% versus 0%, P < 0.01; <37 weeks of gestation: 20.5% versus 5.1%, P < 0.01) were significantly increased among patients in the study group. There were no between-group differences in the rates of gestational diabetes, gestational hypertension and intrauterine growth restriction. In contrast, twin pregnancies following OHSS were not significantly different from matched control twins, with regard to the rates of delivery <34 weeks and <37 weeks of gestation, gestational diabetes, gestational hypertension and intrauterine growth restriction. In conclusion, severe OHSS at early gestation is associated with adverse pregnancy outcome only in singleton gestations.

Sperm preservation by electroejaculation in adolescent cancer patients.

The increasing prevalence of cancer survivors who are infertile due to gonadal failure highlights the importance of fertility preservation prior to gonadotoxic treatments. Adolescent cancer patients may not be mature enough to produce sperm by masturbation, leading to the use of alternative methods for obtaining sperm for cryopreservation. The aim of the current study was to evaluate the safety and efficacy of electroejaculation (EEJ) for cryopreservation among adolescent cancer patients.

ICSI increases ongoing pregnancy rates in patients with poor response cycle: multivariate analysis of 2819 cycles.

The objective of this study was to evaluate the prognosis of patients with a first treatment cycle that was defined as a poor ovarian response cycle according to the new ESHRE consensus criteria. The first documented cycle of poor response for a patient and all the cycles that followed were retrospectively analysed. Factors that were associated with ongoing pregnancy rates were assessed using multivariate analysis. In total, this study evaluated 1014 patients that underwent 2819 consecutive IVF cycles. As expected, patients with poor response cycles were older and had less oocytes retrieved and less embryos transferred. Multivariate analysis for ongoing pregnancy rates adjusted for patient and the cycle characteristics revealed that the intracytoplasmic sperm injection (ICSI) procedure was associated with a significant increase of 40% in ongoing pregnancy rate (adjusted success ratio 1.40, 95% CI 1.00-1.96). Age over 41 years and additional cycles with poor response, were associated with significantly less ongoing pregnancy rate. However, the cumulative pregnancy rates were 29.5% and 36.4% following five and seven cycles, respectively. In conclusion, performing ICSI may improve the ongoing pregnancy rates in poor responders. Further studies are needed to establish the number of cycles recommended in these patients. Patients with poor ovarian response cycles are currently the most challenging group of fertility patients. We are yet far from understanding the factors which cause reduced ovarian response and further away from finding a solution to this painful problem. In this work, we present that with current available treatment modalities, the results can be improved. We show that performing intracytoplasmic sperm injection and implementation of additional number of treatment cycles may improve the ongoing pregnancy rates of patients with a first treatment cycle that is defined as a poor ovarian response cycle. In addition, we investigated the cumulative pregnancy rates in this group and the effect of performing a number of treatment cycles.