The presence of high density small unmyelinated nerve fibers in the functional layer of the endometrium has been strongly associated with endometriosis. It has been suggested as a semi-invasive diagnostic test for minimal–mild endometriosis. Nerve fiber endings can be identified and quantified following simple endometrial biopsy. The presence of nerve fibers in the endometrium of women undergoing IVF treatment has not been previously assessed. Our aim was to assess the presence and density of nerve fiber endings in endometrium of women with various causes of infertility undergoing IVF, and to examine the correlation between the presence of nerve fiber endings in the endometrium and IVF success. Prospective observational study. Thirty-two IVF patients underwent Pipelle endometrial biopsy during days 21-23 of the menstrual cycle. Nerve fiber endings were identified by a specific immunohistochemical staining using anti-PGP9.5. Correlations between the presence of nerve fiber ending and their amount and between the various causes of infertility and between IVF success were assessed. Nerve fiber endings were identified in the endometrium of 10 out of 31 (32.2%) women with a satisfactory biopsy. No correlation was found between the presence of nerve fibers and the cause of infertility. A trend for higher density of nerve fiber endings was found in women with a diagnosis of endometriosis, unexplained infertility and patients with repeated implantation failure. Pregnancy was achieved in 14/32 (44%) of patients. No correlation was observed between the presence of nerve fiber endings in the endometrium and the likelihood of pregnancy. Nerve fiber endings can be identified in a substantial percentage of women undergoing IVF, possibly reflecting under-diagnosis of endometriosis in this population. Their presence does not seem to interfere with embryo implantation. The significance of nerve fiber endings in the endometrium of IVF patients warrants further research.

OBJECTIVE:To evaluate the risk for congenital malformations diagnosed at birth following assisted reproductive technology (ART) treatments compared with live births conceived spontaneously.METHODS:A retrospective cohort study including 9042 live births following ART and 213 288 spontaneously conceived (SC) live births during the period 1997-2004.The cohort was linked to the national live birth registry to determine the outcome of the pregnancies including congenital malformations.RESULTS:An increased adjusted risk for all congenital malformations was observed in ART compared with SC infants [2.4% versus 1.9%; ORadj = 1.45; 95% CI: 1.26, 1.68]. The increased risk was observed in singleton births [2.4% versus 1.8%; ORadj = 1.41; 95% CI: 1.14, 1.71] but not in the ART conceived multiple births [2.5% versus 2.6%.; ORadj = 1.15; 95% CI: 0.90, 1.46]. Significantly increased adjusted risks for nervous, circulatory, digestive and genital system malformations were evident in the ART singleton group compared to SC infants. In addition, increased risks were also observed in separate comparisons of IVF births versus SC [ORadj = 1.28; 95% CI: 1.00, 1.63] and ICSI births versus SC [ORadj = 1.56; 95% CI: 1.31, 1.84]. Data regarding pregnancy termination or congenital malformation diagnosed later in life were not included.CONCLUSION:Infants born following ART were at significantly increased risk for congenital malformations compared to live birth conceived spontaneously.

Fixed and flexible GnRH antagonist (GnRH-ant) protocols have been found comparable in clinical outcome and a significant reduction in GnRH-ant and gonadotropin consumption was observed with the flexible regimen. In reality, most patients on flexible regimens begin GnRH-ant on stimulation day six (S6), as in the fixed protocol. Our aim was to determine the proportion of patients stimulated on a flexible GnRH-ant regimen who met the criteria for antagonist administration after S6, and to compare their clinical characteristics and cycle outcome to patients who started the antagonist on S6 or earlier. Retrospective study. Charts of 442 patients undergoing their first IVF cycle using a flexible GnRH-ant protocol were reviewed. Group A patients met the criteria for antagonist administration on S6 or earlier (follicle size>12 mm, E2>300 pg/mL). Group B patients started GnRH-ant later. Demographic, clinical and laboratory outcome parameters were compared. Overall, 119 patients (27%) began GnRH-ant after S6. Similar implantation (30.4 vs 33.7%), clinical (47.4 vs 52.9%) and ongoing pregnancy (41.2 vs 47.9%) rates were observed in groups A and B respectively. Group B patients had a significantly higher BMI (26.0±5.2 vs 23.9±4.7;P<0.001), longer stimulation (12.2±2.5 vs 9.3±1.6 days;P<0.001), increased FSH dosage (2670±1388 vs 1779±725 IU;P<0.001), a lower number of zygotes (4.50±3 vs 5.6±3.4;P=0.002) and less cycles with embryo freezing (31.1 vs 43.7%;P=0.023). PCOS patients were more likely to be in group B (OR 4.54, CI 1.97-10.56, P<0.0001). In logistic regression every 1kg/m2 increase in BMI was associated with a 7.3% increase in likelihood of being in group B (OR 1.073, CI 1.007-1.143, P=0.029). A considerable proportion of patients on a flexible regimen begin antagonist administration later than S6. Despite different stimulation and laboratory characteristics, their reproductive outcome is not compromised as compared to patients with an earlier GnRH-ant start.

Ultrasound guided embryo transfer (UGET) is now widely accepted as the preferred method for embryo transfer (ET). However, we still do not know which parameters may be related to success rate when performing UGET. Our study is aimed to examine whether parameters such as uterine position, bladder fullness, quality of imaging and level of difficulty in performing ET are related to pregnancy rates. Retrospective, observational study. In 873 UGET of fresh (785 ET) or frozen (88 ET) embryos performed only by highly experienced IVF physicians we collected data regarding the ET process. The performing physician summarized the data regarding: uterine position (anterior, middle or posterior), bladder fullness (full, empty or partially full), imaging quality (good, moderate or bad), difficulty during embryo transfer (easy, moderate, difficult), blood on catheter (yes or no). We evaluated the correlation between these parameters and pregnancy rates. Pregnancy rates did not differ when comparing uterine position, (33.6%, 38.2% and 30.9% for anterior, middle and posterior positions respectively) bladder fullness (32.8%, 34.6% and 33.1% for full, empty and partially full bladder respectively), imaging quality (33.2%, 34% and 32.3% for good, moderate and bad imaging quality respectively) and difficulty performing ET (33.3%, 36% and 30.4% for easy, moderate and difficult transfer respectively). The only parameter showing a tendency to affect pregnancy rates was the finding of blood on the transfer catheter (26.1% vs. 34.5% for presence or absence of blood on catheter respectively). We did not find a significant correlation between the parameters of bladder fullness, uterine position, quality of imaging and level of difficulty and pregnancy rates. The only parameter that had a tendency to lower pregnancy rates was the finding of blood on the transfer catheter.

OBJECTIVE:To describe a successful in vitro fertilization (IVF) twin pregnancy in a patient with complete uterine septum who underwent partial correction during cesarean section.DESIGN:Case report.SETTING:An IVF unit at a university hospital.PATIENT(S):A 29-year-old female patient with complete uterine septum undergoing IVF-intracytoplasmic sperm injection.INTERVENTION(S):In vitro fertilization-intracytoplasmic sperm injection with single embryo transfer to each uterine cavity.MAIN OUTCOME MEASURE(S):Pregnancy course and outcome.RESULT(S):Both transferred embryos underwent implantation, resulting in twin pregnancy with a single embryo in each hemi-uterus. Cesarean section was performed at 34 weeks' gestation. Two healthy neonates were born. Resection of the uterine septum by electrocauterization was attempted during cesarean section. Diagnostic hysteroscopy performed 6 months later demonstrated the presence of the uterine septum reaching approximately 40% of the cavity.CONCLUSION(S):Whether prophylactic metroplasty should be performed in patients with uterine septae without prior history of miscarriage or pregnancy complications is still under debate. Successful implantation and fetal development might occur without prior metroplasty, as described in our case report. Metroplasty during cesarean section might be only partly successful because part of the septum might be confined in the stretched gravid uterus.

Hyaluronan is a major glycosaminoglycan in uterine fluid that has been shown to increase cell-cell and cell-matrix adhesion, and may therefore improve embryo apposition and attachment. Previous studies in mice and humans have revealed that high hyaluronan concentration in embryo transfer medium increases implantation and pregnancy rates. Our study is aimed to evaluate whether the use of embryo transfer medium enriched with hyaluronan (EmbryoGlue - Vitrolife, Gothenburg, Sweden) improves implantation and pregnancy rate in fresh embryo transfers. Prospective randomized study. Fresh embryo transfers in the period between July 2004 and November 2004 were randomly allocated on the day of embryo transfer into two groups: In the EmbryoGlue group (79 patients), embryos were transferred in EmbryoGlue medium that contains 0.5 mg/ml hyaluronan (Vitrolife, Gothenburg, Sweden). In the control group (69 patients) embryos were transferred in medium G-1 that contains 0.125 mg/ml hyaluronan (Vitrolife, Gothenburg, Sweden). Fertilization and embryo culture conditions were similar in both groups. Fertilization was performed in G-Fert medium (Vitrolife, Gothenburg, Sweden) and the embryos were transferred into culture medium G-1. The Chi square test was used for comparison of proportions and the Mann-Whitney U test was used to compare the differences between the groups. The EmbryoGlue group and the control group were similar with respect to age (34.8±5.8 and 34.3±5.9 respectively), infertility duration (3.9±3.2 and 3.6±2.8 years), previous IVF cycles (4.5±4.1 and 5.4±4.9), total gonadotropin dose (37.6±17.3 and 40.5±20.1 amps), oocyte number (7.6±4.1 and 7.4±4.9), embryo quality and number of transferred embryos (2.3±0.8 and 2.2±0.8). The implantation rate in the EmbryoGlue group was 11.5% compared with 15.5% in the control group. The pregnancy rates were 26.6% and 30.4% respectively. Both differences were not statistically significant. The use of hyaluronan enriched medium (EmbryoGlue) for transfer of fresh embryos does not improve implantation and pregnancy rate as compared with the G-1 medium.

Early prediction of pregnancy outcome is of major importance for both patients and the medical team in ART. It may reduce patients' stress and anxiety when favorable outcome is expected and on the other hand to alert the physician when the risk of unfavorable outcome like abortion or ectopic pregnancy is increased. Our study is aimed at examining the value of early consecutive beta HCG, progesterone and estradiol measurements in predicting pregnancy outcome. Retrospective chart review. 198 women with positive beta HCG 12 days after transfer of fresh embryos (ET) had three consecutive measurements of serum beta HCG, progesterone and estradiol on days 12, 14 and 16 after ET. The outcome of these pregnancies were recorded and classified as normal (delivery) or abnormal (biochemical pregnancy, miscarriage or ectopic pregnancy). Ovarian stimulation and luteal support protocols were similar in both groups. The implications of hormonal levels, their alteration pattern and their combination in predicting pregnancy outcome were evaluated. The T-test was used for comparison of means and the Pearson product correlation coefficient was used for correlation test. 110 women (56%) had a normal pregnancy outcome and 88 (44%) had an abnormal pregnancy outcome. A significant correlation was found between pregnancy outcome and the following hormone levels: progesterone and estradiol levels on days 12, 14 and 16 and HCG levels on days 14 and 16 (P<0.05). The mean levels of those hormones were higher in the normal pregnancy group.Mean progesterone levels in the normal pregnancy group on days 12, 14 and 16 were 49.8±16.7, 50.7±15.9 and 51.2±15.1 ng/ml as compared with 42.7±19.4, 43.6±17.6 and 42.2±19.6 ng/ml in the abnormal pregnancy group respectively (P<0.01). Mean estradiol levels in the normal pregnancy group on days 12, 14 and 16 were 1600±2094, 1543±1058 and 1738±1203 pg/ml as compared with 1053±896, 1160±919 and 1249±1026 pg/ml in the abnormal pregnancy group respectively (P<0.05). Mean HCG levels in the normal pregnancy group on days 14 and 16 were 276±130 and 621±337 units/ml as compared with 227±204 and 485±379 units/ml in the abnormal pregnancy group respectively (P<0.05). The HCG rise pattern between day 12 and day 16 (expressed by the ratio 'day 12 / day16 level') levels of HCG (0.27 and 0.43 in the normal and abnormal group respectively, P=0.03) and progesterone (0.99 and 1.54 in the normal and abnormal group respectively, P=0.04) also differed significantly between normal and abnormal pregnancy groups. Combining the three hormones by using principal component analysis method revealed a significant difference between the normal and abnormal pregnancy group. In normal pregnancies early beta HCG, progesterone and estradiol levels were higher as compared with pregnancies with early adverse outcome. The increase in HCG level was steeper in normal pregnancies. Early measurements of beta HCG, progesterone and estradiol could serve as indicators of pregnancy outcome.

ObjectiveSystematic reviews comparing GnRH antagonist with long agonist protocols have found significantly lower clinical pregnancy rates in antagonist cycles. It can be argued that fundamental differences in cycle dynamics between long agonist and the antagonist protocols, rather than the antagonist molecule itself, are adversely affecting cycle outcome. An elegant way to explore this issue would be to compare conventional antagonist use with an "artificial" long antagonist protocol, in which the antagonist is used first to induce pituitary suppression and ovarian stimulation begins once ovarian quiescence has been achieved. Our aim was to compare follicular and hormone dynamics in conventional versus "long" antagonist cycles.DesignProspective randomized study.Materials and methodsThirty IVF patients <35 years old, with <2 failed attempts, regular cycles, basal FSH levels < 12 IU/L and BMI ≤29 were included. Patients were randomized to either: Conventional Cetrotide Protocol (group S): Ovarian stimulation from cycle day 3 consisting of 225IU of FSH daily for 5 days. Thereafter, stimulation with a combination of FSH/hMG and gonadotropin doses individually adjusted. Cetrotide 0.25 mg was given daily once follicles ≥ 13 mm were present, until (including) hCG day. 'Long' Cetrotide Protocol (group L): Cetrotide 0.25 mg daily from cycle day 2 until hCG day. After 7 days of Cetrotide treatment patients were evaluated for pituitary suppression and once it was confirmed, ovarian stimulation was commenced as descibed above. hCG was administered when ≥2 follicles have reached ≥20 mm. Clinical and laboratory outcome parameters were compared for both groups.ResultsTwo group L patients failed to suppress under Cetrotide treatment and were exluded. One group S patient conceived spontaneouly after receruitment and another had FSH level of 25.1on treatment cycle day 3 and both were excluded. Overall, 12 group L and 14 group S patients completed the study. Patients characteristics were comparable in terms of age (29.8±3.1 vs 30.9±3 yrs), infertility duration (3.2±2.4 vs 2.1±0.6 yrs), basal FSH (5.6±1.7 vs 6.2±1.6 IU/L) and number of pervious IVF cycles (0.4±0.6 vs 0.3±0.4), for groups S and L, respectively. Pituitary suppression was effectively achieved within 7 days in 12 group L patients. The duration of gonadotropin stimulation (S: 9.9±1.75 vs L: 9.17±1.5 days), gonadotropin consumption (S: 26.9±5.2 vs L: 23.8±4.3 amps.) and E2/oocyte ratio (L: 225±55 vs S: 213±87) were comparable. Significanly more Cetrotide doses were given in group L (16.5±1.5 vs 5.1±1.6; p<0.0001). A trend towards higher E2 levels on hCG day (2371±727 vs 1806±890 pg/mL and higher number of oocytes retrived (10.6±3.0 vs 9.0±3.8) was observed in group L. Comparable results were obtained for: P, FSH and LH level on hCG day, no. of medium-sized and large follicls, fertilization rate, no. of embryos transferred and no. of cycles with embryo freezing. Eleven pregnancies (44%) were achieved, consisting of 7 in the S group and 4 in the L group (NS).ConclusionThe results of our study confirm the feasibilty of a "long antagonist" protocol. Ovarian quiescence can be quickly achieved with GnRH antagonists without the typical drawbacks associated with the long agonist protocol (cyst formation and hypoestrogenic side effects). The size of the study groups was too small to detect fundamental differences in cycle dynamics, but the "long antagonist" protocol is feasible and can be further explored. ObjectiveSystematic reviews comparing GnRH antagonist with long agonist protocols have found significantly lower clinical pregnancy rates in antagonist cycles. It can be argued that fundamental differences in cycle dynamics between long agonist and the antagonist protocols, rather than the antagonist molecule itself, are adversely affecting cycle outcome. An elegant way to explore this issue would be to compare conventional antagonist use with an "artificial" long antagonist protocol, in which the antagonist is used first to induce pituitary suppression and ovarian stimulation begins once ovarian quiescence has been achieved. Our aim was to compare follicular and hormone dynamics in conventional versus "long" antagonist cycles. Systematic reviews comparing GnRH antagonist with long agonist protocols have found significantly lower clinical pregnancy rates in antagonist cycles. It can be argued that fundamental differences in cycle dynamics between long agonist and the antagonist protocols, rather than the antagonist molecule itself, are adversely affecting cycle outcome. An elegant way to explore this issue would be to compare conventional antagonist use with an "artificial" long antagonist protocol, in which the antagonist is used first to induce pituitary suppression and ovarian stimulation begins once ovarian quiescence has been achieved. Our aim was to compare follicular and hormone dynamics in conventional versus "long" antagonist cycles. DesignProspective randomized study. Prospective randomized study. Materials and methodsThirty IVF patients <35 years old, with <2 failed attempts, regular cycles, basal FSH levels < 12 IU/L and BMI ≤29 were included. Patients were randomized to either: Conventional Cetrotide Protocol (group S): Ovarian stimulation from cycle day 3 consisting of 225IU of FSH daily for 5 days. Thereafter, stimulation with a combination of FSH/hMG and gonadotropin doses individually adjusted. Cetrotide 0.25 mg was given daily once follicles ≥ 13 mm were present, until (including) hCG day. 'Long' Cetrotide Protocol (group L): Cetrotide 0.25 mg daily from cycle day 2 until hCG day. After 7 days of Cetrotide treatment patients were evaluated for pituitary suppression and once it was confirmed, ovarian stimulation was commenced as descibed above. hCG was administered when ≥2 follicles have reached ≥20 mm. Clinical and laboratory outcome parameters were compared for both groups. Thirty IVF patients <35 years old, with <2 failed attempts, regular cycles, basal FSH levels < 12 IU/L and BMI ≤29 were included. Patients were randomized to either: Conventional Cetrotide Protocol (group S): Ovarian stimulation from cycle day 3 consisting of 225IU of FSH daily for 5 days. Thereafter, stimulation with a combination of FSH/hMG and gonadotropin doses individually adjusted. Cetrotide 0.25 mg was given daily once follicles ≥ 13 mm were present, until (including) hCG day. 'Long' Cetrotide Protocol (group L): Cetrotide 0.25 mg daily from cycle day 2 until hCG day. After 7 days of Cetrotide treatment patients were evaluated for pituitary suppression and once it was confirmed, ovarian stimulation was commenced as descibed above. hCG was administered when ≥2 follicles have reached ≥20 mm. Clinical and laboratory outcome parameters were compared for both groups. ResultsTwo group L patients failed to suppress under Cetrotide treatment and were exluded. One group S patient conceived spontaneouly after receruitment and another had FSH level of 25.1on treatment cycle day 3 and both were excluded. Overall, 12 group L and 14 group S patients completed the study. Patients characteristics were comparable in terms of age (29.8±3.1 vs 30.9±3 yrs), infertility duration (3.2±2.4 vs 2.1±0.6 yrs), basal FSH (5.6±1.7 vs 6.2±1.6 IU/L) and number of pervious IVF cycles (0.4±0.6 vs 0.3±0.4), for groups S and L, respectively. Pituitary suppression was effectively achieved within 7 days in 12 group L patients. The duration of gonadotropin stimulation (S: 9.9±1.75 vs L: 9.17±1.5 days), gonadotropin consumption (S: 26.9±5.2 vs L: 23.8±4.3 amps.) and E2/oocyte ratio (L: 225±55 vs S: 213±87) were comparable. Significanly more Cetrotide doses were given in group L (16.5±1.5 vs 5.1±1.6; p<0.0001). A trend towards higher E2 levels on hCG day (2371±727 vs 1806±890 pg/mL and higher number of oocytes retrived (10.6±3.0 vs 9.0±3.8) was observed in group L. Comparable results were obtained for: P, FSH and LH level on hCG day, no. of medium-sized and large follicls, fertilization rate, no. of embryos transferred and no. of cycles with embryo freezing. Eleven pregnancies (44%) were achieved, consisting of 7 in the S group and 4 in the L group (NS). Two group L patients failed to suppress under Cetrotide treatment and were exluded. One group S patient conceived spontaneouly after receruitment and another had FSH level of 25.1on treatment cycle day 3 and both were excluded. Overall, 12 group L and 14 group S patients completed the study. Patients characteristics were comparable in terms of age (29.8±3.1 vs 30.9±3 yrs), infertility duration (3.2±2.4 vs 2.1±0.6 yrs), basal FSH (5.6±1.7 vs 6.2±1.6 IU/L) and number of pervious IVF cycles (0.4±0.6 vs 0.3±0.4), for groups S and L, respectively. Pituitary suppression was effectively achieved within 7 days in 12 group L patients. The duration of gonadotropin stimulation (S: 9.9±1.75 vs L: 9.17±1.5 days), gonadotropin consumption (S: 26.9±5.2 vs L: 23.8±4.3 amps.) and E2/oocyte ratio (L: 225±55 vs S: 213±87) were comparable. Significanly more Cetrotide doses were given in group L (16.5±1.5 vs 5.1±1.6; p<0.0001). A trend towards higher E2 levels on hCG day (2371±727 vs 1806±890 pg/mL and higher number of oocytes retrived (10.6±3.0 vs 9.0±3.8) was observed in group L. Comparable results were obtained for: P, FSH and LH level on hCG day, no. of medium-sized and large follicls, fertilization rate, no. of embryos transferred and no. of cycles with embryo freezing. Eleven pregnancies (44%) were achieved, consisting of 7 in the S group and 4 in the L group (NS). ConclusionThe results of our study confirm the feasibilty of a "long antagonist" protocol. Ovarian quiescence can be quickly achieved with GnRH antagonists without the typical drawbacks associated with the long agonist protocol (cyst formation and hypoestrogenic side effects). The size of the study groups was too small to detect fundamental differences in cycle dynamics, but the "long antagonist" protocol is feasible and can be further explored. The results of our study confirm the feasibilty of a "long antagonist" protocol. Ovarian quiescence can be quickly achieved with GnRH antagonists without the typical drawbacks associated with the long agonist protocol (cyst formation and hypoestrogenic side effects). The size of the study groups was too small to detect fundamental differences in cycle dynamics, but the "long antagonist" protocol is feasible and can be further explored.

ObjectiveThe application of ZIFT in the general IVF population has gradually declined worldwide over the years. A meta-analysis of randomized, controlled trials found no difference in pregnancy and implantation rates between women undergoing ZIFT and IVF-ET {Habana and Palter; Fertil Steril 2001}. For the last ten years, the therapeutic approach at our institution has been to offer IVF with ZIFT to patients with repeated implantation failure (RIF), whenever permitted by tubal status. In previous publications, we have clearly demonstrated the superiority of ZIFT over conventional embryo transfer (ET) {Levran et al. Fertil Steril, 1998} and over blastocyst stage transfer {Weissman et al. Fertil. Steril. 2002} in patients with RIF . Our aim was to summarize our ten years experience with ZIFT performed exclusively in patients with RIF.DesignRetrospective study.Materials and methodsBetween the years 1995 and 2004, 176 patients underwent 280 ZIFT cycles at the IVF Unit of the Wolfson Medical Center. Patients were eligible for ZIFT whenever all of the following 4 criteria were fulfilled: (1) >3 previous failed IVF-ET attempts, excluding frozen-thawed ET (2) a normal uterine cavity, as evidenced by hysteroscopy (3) presence of at least one patent tube (3) normal response to controlled ovarian stimulation (COH) in previous attempts (4) patients <43 years of age. COH consisted of standard IVF protocols using gonadotropin stimulation combined with either agonists or antagonists of GnRH. Laparoscopic ZIFT was performed 24 hours (ZIFT; n=205) or 48 hours (embryo intrafallopian transfer - EIFT; n=75) following egg retrieval.ResultsThe mean age of the patients was 34.2±5.3 years, basal FSH 7.14±3.0 IU/L, mean gravidity 0.97±1.76, parity 0.32±0.56, and they had a mean of 8.15±3.9 previous failed cycles. There were 274 fresh and 6 frozen ZIFT cycles. A mean of 11.2±6.08 oocytes were retrieved. ICSI was applied in 76.7% of the cycles, and the overall fertilization rate was 72.2±17.9%. A mean of 5.24±1.2 zygotes/embryos were replaced, resulting in 96 pregnancies (34.3%). There were 72 live birth (75%), 19 miscarriages (19.8%) and 5 ectopic pregnancies (5.2%). Out of 72 live births, 38 were singletons (52.8%), 31 twins (44.4%) and 2 triplets (2.8%). Out of 32 twin births, 5 were reduced from triplets, 5 reduced from quadruplets, one reduced from quintuplets. The high-order multiple pregnancy rate was therefore 18% (13/72). Seventy of 176 treated patients had a live birth (39.8%).ConclusionThe results of our study clearly demonstrate the efficacy of ZIFT as a powerful clinical tool in the management of patients with RIF. The favorable pregnancy and birth rates were consistent throughout the ten years study period. Our research is currently focused on better selection of patients who may benefit from ZIFT, as well as better selection of zygotes for transfer so that the number of zygotes transferred can safely reduced, without compromising the favorable results. ObjectiveThe application of ZIFT in the general IVF population has gradually declined worldwide over the years. A meta-analysis of randomized, controlled trials found no difference in pregnancy and implantation rates between women undergoing ZIFT and IVF-ET {Habana and Palter; Fertil Steril 2001}. For the last ten years, the therapeutic approach at our institution has been to offer IVF with ZIFT to patients with repeated implantation failure (RIF), whenever permitted by tubal status. In previous publications, we have clearly demonstrated the superiority of ZIFT over conventional embryo transfer (ET) {Levran et al. Fertil Steril, 1998} and over blastocyst stage transfer {Weissman et al. Fertil. Steril. 2002} in patients with RIF . Our aim was to summarize our ten years experience with ZIFT performed exclusively in patients with RIF. The application of ZIFT in the general IVF population has gradually declined worldwide over the years. A meta-analysis of randomized, controlled trials found no difference in pregnancy and implantation rates between women undergoing ZIFT and IVF-ET {Habana and Palter; Fertil Steril 2001}. For the last ten years, the therapeutic approach at our institution has been to offer IVF with ZIFT to patients with repeated implantation failure (RIF), whenever permitted by tubal status. In previous publications, we have clearly demonstrated the superiority of ZIFT over conventional embryo transfer (ET) {Levran et al. Fertil Steril, 1998} and over blastocyst stage transfer {Weissman et al. Fertil. Steril. 2002} in patients with RIF . Our aim was to summarize our ten years experience with ZIFT performed exclusively in patients with RIF. DesignRetrospective study. Retrospective study. Materials and methodsBetween the years 1995 and 2004, 176 patients underwent 280 ZIFT cycles at the IVF Unit of the Wolfson Medical Center. Patients were eligible for ZIFT whenever all of the following 4 criteria were fulfilled: (1) >3 previous failed IVF-ET attempts, excluding frozen-thawed ET (2) a normal uterine cavity, as evidenced by hysteroscopy (3) presence of at least one patent tube (3) normal response to controlled ovarian stimulation (COH) in previous attempts (4) patients <43 years of age. COH consisted of standard IVF protocols using gonadotropin stimulation combined with either agonists or antagonists of GnRH. Laparoscopic ZIFT was performed 24 hours (ZIFT; n=205) or 48 hours (embryo intrafallopian transfer - EIFT; n=75) following egg retrieval. Between the years 1995 and 2004, 176 patients underwent 280 ZIFT cycles at the IVF Unit of the Wolfson Medical Center. Patients were eligible for ZIFT whenever all of the following 4 criteria were fulfilled: (1) >3 previous failed IVF-ET attempts, excluding frozen-thawed ET (2) a normal uterine cavity, as evidenced by hysteroscopy (3) presence of at least one patent tube (3) normal response to controlled ovarian stimulation (COH) in previous attempts (4) patients <43 years of age. COH consisted of standard IVF protocols using gonadotropin stimulation combined with either agonists or antagonists of GnRH. Laparoscopic ZIFT was performed 24 hours (ZIFT; n=205) or 48 hours (embryo intrafallopian transfer - EIFT; n=75) following egg retrieval. ResultsThe mean age of the patients was 34.2±5.3 years, basal FSH 7.14±3.0 IU/L, mean gravidity 0.97±1.76, parity 0.32±0.56, and they had a mean of 8.15±3.9 previous failed cycles. There were 274 fresh and 6 frozen ZIFT cycles. A mean of 11.2±6.08 oocytes were retrieved. ICSI was applied in 76.7% of the cycles, and the overall fertilization rate was 72.2±17.9%. A mean of 5.24±1.2 zygotes/embryos were replaced, resulting in 96 pregnancies (34.3%). There were 72 live birth (75%), 19 miscarriages (19.8%) and 5 ectopic pregnancies (5.2%). Out of 72 live births, 38 were singletons (52.8%), 31 twins (44.4%) and 2 triplets (2.8%). Out of 32 twin births, 5 were reduced from triplets, 5 reduced from quadruplets, one reduced from quintuplets. The high-order multiple pregnancy rate was therefore 18% (13/72). Seventy of 176 treated patients had a live birth (39.8%). The mean age of the patients was 34.2±5.3 years, basal FSH 7.14±3.0 IU/L, mean gravidity 0.97±1.76, parity 0.32±0.56, and they had a mean of 8.15±3.9 previous failed cycles. There were 274 fresh and 6 frozen ZIFT cycles. A mean of 11.2±6.08 oocytes were retrieved. ICSI was applied in 76.7% of the cycles, and the overall fertilization rate was 72.2±17.9%. A mean of 5.24±1.2 zygotes/embryos were replaced, resulting in 96 pregnancies (34.3%). There were 72 live birth (75%), 19 miscarriages (19.8%) and 5 ectopic pregnancies (5.2%). Out of 72 live births, 38 were singletons (52.8%), 31 twins (44.4%) and 2 triplets (2.8%). Out of 32 twin births, 5 were reduced from triplets, 5 reduced from quadruplets, one reduced from quintuplets. The high-order multiple pregnancy rate was therefore 18% (13/72). Seventy of 176 treated patients had a live birth (39.8%). ConclusionThe results of our study clearly demonstrate the efficacy of ZIFT as a powerful clinical tool in the management of patients with RIF. The favorable pregnancy and birth rates were consistent throughout the ten years study period. Our research is currently focused on better selection of patients who may benefit from ZIFT, as well as better selection of zygotes for transfer so that the number of zygotes transferred can safely reduced, without compromising the favorable results. The results of our study clearly demonstrate the efficacy of ZIFT as a powerful clinical tool in the management of patients with RIF. The favorable pregnancy and birth rates were consistent throughout the ten years study period. Our research is currently focused on better selection of patients who may benefit from ZIFT, as well as better selection of zygotes for transfer so that the number of zygotes transferred can safely reduced, without compromising the favorable results.

Objective: Ovarian follicle and cyst formation have been recognized as an advance phenomenon associated with GnRH agonist administration. With the use of GnRH antagonists, pituitary suppression is immediate and no flare effect and follicle growth are expected. We describe two patients who developed a dominant follicle and presumably ovulated in response to hCG triggering under continuous sole administration of a GnRH antagonist.Design: Case report.Setting: An IVF unit at a university hospital.Patient(s): Two young healthy female patients undergoing IVF because of male-factor infertility.Intervention(s): Continuous daily administration of a GnRH antagonist from menstruation with the aim of achieving ovarian suppression.Main Outcome Measure(s): Endocrine and ultrasound characteristics of follicular growth.Result(s): Both patients developed a dominant follicle under sole administration of a GnRH antagonist, accompanied by a gradual rise in serum estradiol and endometrial thickness which culminated in a spontaneous LH surge. Ovulation was triggered by hCG and mid-luteal progesterone levels were suggestive of ovulation.Conclusion(s): We describe for the first time the development of a dominant follicle and presumable ovulation under continuous administration of a GnRH antagonist. Serum gonadotropin concentrations indicate that the pituitary failed to suppress in both patients. The exact mechanism of this phenomenon remains to be elucidated. (Fertil Steril (R) 2007;88:1677.e15-7. (C) 2007 by American Society for Reproductive Medicine.)

Use of intracytoplasmic sperm injection (ICSI) in couples with mild oligoteratoasthenozoospermia decreases the complete fertilization failure rate and may also reduce the embryo cleavage rate. ICSI does not benefit couples with normal sperm.

ObjectivePatients with repeated implantation failure (RIF) are common in Israeli IVF clinics and present a frustrating challenge to the caring physician. Culture and transfer of human embryos at the blastocyst stage has gained widespread popularity and has also been advocated as an effective therapeutic modality for treatment of patients with RIF (Cruz et al. 1999). Our group, however, has found this treatment approach ineffective in patients with RIF (Levran et al. 2002 ). One of the advantages of blastocyst culture and transfer is the selection of embryos with increased implantation potential after the initiation of embryonic genome activation (Braudeet al 1988). It may therefore be of particular interest to explore and document whether this genomic shift ever occurs in patients with RIF. Hence, culture and transfer at the blastocyst stage in RIF patients can be also regarded as a diagnostic step with potential prognostic implications. These considerations have led us to introduce blastocyst cultures in the management of RIF. The prospect of patients who failed to produce a blastocyst in their treatment cycles became a major point of interest and the focus of the following research. Our aim was to study the effect of failure to produce a blastocyst on the long term reproductive outcome of patients with RIF.DesignProspective, longitudinal observational study.Materials and methodsTwenty-five IVF patients with >4 failed IVF-ET attempts who failed to produce a blastocyst in a cycle in which all embryos were subjected to extended culture comprised our study group. Study cycles took place between 1997–2002 and the mean follow up period was 4.3±1.35 years. Their mean age was 35.3±4.8 years (range 26–44), with a mean duration of infertility of 8.5±6.6 years (range 2–22). The mean basal FSH level was 8.24±3.5 (range 3.1–16.4) and mean number of previous failed IVF attempts was (8.7±5.4; range 4–28). The major etiology for infertility was: male factor (n=8), tubal (n=9), endometriosis (n=1), unexplained (n=3). Four patients had more than one fertility factor involved. Twelve patients were nulligravida (overall mean gravidity 1.32±1.52) and 5 patients had a live birth in the past (mean parity 0.26±0.52). Five patients in the study group had two treatment cycles without blastocyst formation. Overall, 30 treatment cycles were analyzed. The long GnRH-a protocol was most commonly used (n=23), whereas in 4 cycles the short, and in 3 cycles a GnRH antagonist was used. The mean number of oocytes retrieved was 9.73±4.35, and in 22 cycles (73.3%) ICSI was used. The overall fertilization rate was 60.1±24%, and the mean number of generated embryos per patient was 5.5±3.5. In 26 cycles there were 6–8 cell embryos present on day 3 post insemination, and in 17 cycles there were top quality (Grade I) embryos available on day 3. Yet, none of these embryos turned into blastocysts.ResultsSixteen of the patients (64%) conceived in future treatment cycles and 11 (44%) had a live birth. Two patients had subsequent biochemical pregnancies, which also confirm blastocyst formation.ConclusionFailure to produce a blastocyst in a given IVF treatment cycle has no prognostic significance for the reproductive outcome of patients with RIF. Thus, blastocyst culture and transfer should not be regarded or offered as a diagnostic tool in counseling patients with RIF. ObjectivePatients with repeated implantation failure (RIF) are common in Israeli IVF clinics and present a frustrating challenge to the caring physician. Culture and transfer of human embryos at the blastocyst stage has gained widespread popularity and has also been advocated as an effective therapeutic modality for treatment of patients with RIF (Cruz et al. 1999). Our group, however, has found this treatment approach ineffective in patients with RIF (Levran et al. 2002 ). One of the advantages of blastocyst culture and transfer is the selection of embryos with increased implantation potential after the initiation of embryonic genome activation (Braudeet al 1988). It may therefore be of particular interest to explore and document whether this genomic shift ever occurs in patients with RIF. Hence, culture and transfer at the blastocyst stage in RIF patients can be also regarded as a diagnostic step with potential prognostic implications. These considerations have led us to introduce blastocyst cultures in the management of RIF. The prospect of patients who failed to produce a blastocyst in their treatment cycles became a major point of interest and the focus of the following research. Our aim was to study the effect of failure to produce a blastocyst on the long term reproductive outcome of patients with RIF. Patients with repeated implantation failure (RIF) are common in Israeli IVF clinics and present a frustrating challenge to the caring physician. Culture and transfer of human embryos at the blastocyst stage has gained widespread popularity and has also been advocated as an effective therapeutic modality for treatment of patients with RIF (Cruz et al. 1999). Our group, however, has found this treatment approach ineffective in patients with RIF (Levran et al. 2002 ). One of the advantages of blastocyst culture and transfer is the selection of embryos with increased implantation potential after the initiation of embryonic genome activation (Braudeet al 1988). It may therefore be of particular interest to explore and document whether this genomic shift ever occurs in patients with RIF. Hence, culture and transfer at the blastocyst stage in RIF patients can be also regarded as a diagnostic step with potential prognostic implications. These considerations have led us to introduce blastocyst cultures in the management of RIF. The prospect of patients who failed to produce a blastocyst in their treatment cycles became a major point of interest and the focus of the following research. Our aim was to study the effect of failure to produce a blastocyst on the long term reproductive outcome of patients with RIF. DesignProspective, longitudinal observational study. Prospective, longitudinal observational study. Materials and methodsTwenty-five IVF patients with >4 failed IVF-ET attempts who failed to produce a blastocyst in a cycle in which all embryos were subjected to extended culture comprised our study group. Study cycles took place between 1997–2002 and the mean follow up period was 4.3±1.35 years. Their mean age was 35.3±4.8 years (range 26–44), with a mean duration of infertility of 8.5±6.6 years (range 2–22). The mean basal FSH level was 8.24±3.5 (range 3.1–16.4) and mean number of previous failed IVF attempts was (8.7±5.4; range 4–28). The major etiology for infertility was: male factor (n=8), tubal (n=9), endometriosis (n=1), unexplained (n=3). Four patients had more than one fertility factor involved. Twelve patients were nulligravida (overall mean gravidity 1.32±1.52) and 5 patients had a live birth in the past (mean parity 0.26±0.52). Five patients in the study group had two treatment cycles without blastocyst formation. Overall, 30 treatment cycles were analyzed. The long GnRH-a protocol was most commonly used (n=23), whereas in 4 cycles the short, and in 3 cycles a GnRH antagonist was used. The mean number of oocytes retrieved was 9.73±4.35, and in 22 cycles (73.3%) ICSI was used. The overall fertilization rate was 60.1±24%, and the mean number of generated embryos per patient was 5.5±3.5. In 26 cycles there were 6–8 cell embryos present on day 3 post insemination, and in 17 cycles there were top quality (Grade I) embryos available on day 3. Yet, none of these embryos turned into blastocysts. Twenty-five IVF patients with >4 failed IVF-ET attempts who failed to produce a blastocyst in a cycle in which all embryos were subjected to extended culture comprised our study group. Study cycles took place between 1997–2002 and the mean follow up period was 4.3±1.35 years. Their mean age was 35.3±4.8 years (range 26–44), with a mean duration of infertility of 8.5±6.6 years (range 2–22). The mean basal FSH level was 8.24±3.5 (range 3.1–16.4) and mean number of previous failed IVF attempts was (8.7±5.4; range 4–28). The major etiology for infertility was: male factor (n=8), tubal (n=9), endometriosis (n=1), unexplained (n=3). Four patients had more than one fertility factor involved. Twelve patients were nulligravida (overall mean gravidity 1.32±1.52) and 5 patients had a live birth in the past (mean parity 0.26±0.52). Five patients in the study group had two treatment cycles without blastocyst formation. Overall, 30 treatment cycles were analyzed. The long GnRH-a protocol was most commonly used (n=23), whereas in 4 cycles the short, and in 3 cycles a GnRH antagonist was used. The mean number of oocytes retrieved was 9.73±4.35, and in 22 cycles (73.3%) ICSI was used. The overall fertilization rate was 60.1±24%, and the mean number of generated embryos per patient was 5.5±3.5. In 26 cycles there were 6–8 cell embryos present on day 3 post insemination, and in 17 cycles there were top quality (Grade I) embryos available on day 3. Yet, none of these embryos turned into blastocysts. ResultsSixteen of the patients (64%) conceived in future treatment cycles and 11 (44%) had a live birth. Two patients had subsequent biochemical pregnancies, which also confirm blastocyst formation. Sixteen of the patients (64%) conceived in future treatment cycles and 11 (44%) had a live birth. Two patients had subsequent biochemical pregnancies, which also confirm blastocyst formation. ConclusionFailure to produce a blastocyst in a given IVF treatment cycle has no prognostic significance for the reproductive outcome of patients with RIF. Thus, blastocyst culture and transfer should not be regarded or offered as a diagnostic tool in counseling patients with RIF. Failure to produce a blastocyst in a given IVF treatment cycle has no prognostic significance for the reproductive outcome of patients with RIF. Thus, blastocyst culture and transfer should not be regarded or offered as a diagnostic tool in counseling patients with RIF.

ObjectiveChronic endometritis is a poorly defined entity in terms of the diagnostic criteria, clinical manifestations, and its effect on embryo implantation. Most authors agree that the diagnostic hallmark is plasma cell infiltration. Additional characteristics include: stromal edema and lymphocytic infiltration. It has been suggested that chronic endometritis may interfere with implantation. We therefore postulated that it may be more prevalent in patients with repeated implantation failure (RIF). Our study was designed in order to assess the prevalence of chronic endometritis among RIF patients and to evaluate the association between currently accepted histopathological criteria and embryo implantation.DesignCase-controlMaterials and methodsThirty-two patients with >4 failed IVF-ET cycles comprised the study group and 21 egg recipients who conceived in their first IVF attempt served as controls. Study group patients had an endometrial biopsy in the midluteal phase of the preceding cycle, whereas egg recipients had the biopsy in the "midluteal phase" of a mock cycle with artificially prepared endometrium. Biopsy slides were evaluated and graded by a single pathologist blinded to their source. The following parameters were recorded and compared for both groups: 1. Stromal edema 2. lymphocytic infiltration. 3. Surface and glandular epithelial infiltration. 4. Plasma cell infiltration. Among study group patients, 14 were diagnosed with chronic endometritis and had a second biopsy. Eight of them received broad-spectrum antibiotics. Histopathologic findings were also compared between first and second biopsies.ResultsMean patients' age in study and control groups was 34.9±6.3 and 39.9±6.7 years, respectively. Comparison of histopathological findings revealed that stromal edema was significantly more common and profound in controls. Moderate to severe stromal lymphocytic infiltration was more common in the study group (20%) than in controls (9%) (p=0.007). T cell lymphocytes were significantly more prevalent in the study group with no difference found for B cell lymphocytic infiltration. Focal surface epithelial infiltration was noted in 100% of control biopsies compared to 6.3% in the study group (p<.001). A similar finding was found for glandular epithelial infiltration. No plasma cell infiltration was detected in 46.9% of biopsies from RIF patients and in 31.8% of the biopsies from the control group (NS). Mild to moderate degree of plasma cell infiltration was noted in 15% of control biopsies and in none of the study group patients (p=.052). Chronic endometritis was diagnosed in 45.5% and 35% of biopsies in the study group and controls, respectively (NS). The severity grading for chronic endometritis was comparable in both groups. Plasma cell infiltration was significantly decreased in second biopsies of RIF patients with chronic endometritis following antibiotic treatment but not in affected patients who did not get antibiotics.ConclusionBased on our findings chronic endometritis is unlikely to represent a significant causative factor for RIF. Stromal edema, that was found to be more common in the control group, does not necessarily represent endometritis and is not a bad prognostic sign. Surprisingly, plasma cell infiltration was more common in the control group (NS). This finding raises the question of whether plasma cell infiltration in ART patients is indeed a marker for chronic endometritis as was previously suggested. ObjectiveChronic endometritis is a poorly defined entity in terms of the diagnostic criteria, clinical manifestations, and its effect on embryo implantation. Most authors agree that the diagnostic hallmark is plasma cell infiltration. Additional characteristics include: stromal edema and lymphocytic infiltration. It has been suggested that chronic endometritis may interfere with implantation. We therefore postulated that it may be more prevalent in patients with repeated implantation failure (RIF). Our study was designed in order to assess the prevalence of chronic endometritis among RIF patients and to evaluate the association between currently accepted histopathological criteria and embryo implantation. Chronic endometritis is a poorly defined entity in terms of the diagnostic criteria, clinical manifestations, and its effect on embryo implantation. Most authors agree that the diagnostic hallmark is plasma cell infiltration. Additional characteristics include: stromal edema and lymphocytic infiltration. It has been suggested that chronic endometritis may interfere with implantation. We therefore postulated that it may be more prevalent in patients with repeated implantation failure (RIF). Our study was designed in order to assess the prevalence of chronic endometritis among RIF patients and to evaluate the association between currently accepted histopathological criteria and embryo implantation. DesignCase-control Case-control Materials and methodsThirty-two patients with >4 failed IVF-ET cycles comprised the study group and 21 egg recipients who conceived in their first IVF attempt served as controls. Study group patients had an endometrial biopsy in the midluteal phase of the preceding cycle, whereas egg recipients had the biopsy in the "midluteal phase" of a mock cycle with artificially prepared endometrium. Biopsy slides were evaluated and graded by a single pathologist blinded to their source. The following parameters were recorded and compared for both groups: 1. Stromal edema 2. lymphocytic infiltration. 3. Surface and glandular epithelial infiltration. 4. Plasma cell infiltration. Among study group patients, 14 were diagnosed with chronic endometritis and had a second biopsy. Eight of them received broad-spectrum antibiotics. Histopathologic findings were also compared between first and second biopsies. Thirty-two patients with >4 failed IVF-ET cycles comprised the study group and 21 egg recipients who conceived in their first IVF attempt served as controls. Study group patients had an endometrial biopsy in the midluteal phase of the preceding cycle, whereas egg recipients had the biopsy in the "midluteal phase" of a mock cycle with artificially prepared endometrium. Biopsy slides were evaluated and graded by a single pathologist blinded to their source. The following parameters were recorded and compared for both groups: 1. Stromal edema 2. lymphocytic infiltration. 3. Surface and glandular epithelial infiltration. 4. Plasma cell infiltration. Among study group patients, 14 were diagnosed with chronic endometritis and had a second biopsy. Eight of them received broad-spectrum antibiotics. Histopathologic findings were also compared between first and second biopsies. ResultsMean patients' age in study and control groups was 34.9±6.3 and 39.9±6.7 years, respectively. Comparison of histopathological findings revealed that stromal edema was significantly more common and profound in controls. Moderate to severe stromal lymphocytic infiltration was more common in the study group (20%) than in controls (9%) (p=0.007). T cell lymphocytes were significantly more prevalent in the study group with no difference found for B cell lymphocytic infiltration. Focal surface epithelial infiltration was noted in 100% of control biopsies compared to 6.3% in the study group (p<.001). A similar finding was found for glandular epithelial infiltration. No plasma cell infiltration was detected in 46.9% of biopsies from RIF patients and in 31.8% of the biopsies from the control group (NS). Mild to moderate degree of plasma cell infiltration was noted in 15% of control biopsies and in none of the study group patients (p=.052). Chronic endometritis was diagnosed in 45.5% and 35% of biopsies in the study group and controls, respectively (NS). The severity grading for chronic endometritis was comparable in both groups. Plasma cell infiltration was significantly decreased in second biopsies of RIF patients with chronic endometritis following antibiotic treatment but not in affected patients who did not get antibiotics. Mean patients' age in study and control groups was 34.9±6.3 and 39.9±6.7 years, respectively. Comparison of histopathological findings revealed that stromal edema was significantly more common and profound in controls. Moderate to severe stromal lymphocytic infiltration was more common in the study group (20%) than in controls (9%) (p=0.007). T cell lymphocytes were significantly more prevalent in the study group with no difference found for B cell lymphocytic infiltration. Focal surface epithelial infiltration was noted in 100% of control biopsies compared to 6.3% in the study group (p<.001). A similar finding was found for glandular epithelial infiltration. No plasma cell infiltration was detected in 46.9% of biopsies from RIF patients and in 31.8% of the biopsies from the control group (NS). Mild to moderate degree of plasma cell infiltration was noted in 15% of control biopsies and in none of the study group patients (p=.052). Chronic endometritis was diagnosed in 45.5% and 35% of biopsies in the study group and controls, respectively (NS). The severity grading for chronic endometritis was comparable in both groups. Plasma cell infiltration was significantly decreased in second biopsies of RIF patients with chronic endometritis following antibiotic treatment but not in affected patients who did not get antibiotics. ConclusionBased on our findings chronic endometritis is unlikely to represent a significant causative factor for RIF. Stromal edema, that was found to be more common in the control group, does not necessarily represent endometritis and is not a bad prognostic sign. Surprisingly, plasma cell infiltration was more common in the control group (NS). This finding raises the question of whether plasma cell infiltration in ART patients is indeed a marker for chronic endometritis as was previously suggested. Based on our findings chronic endometritis is unlikely to represent a significant causative factor for RIF. Stromal edema, that was found to be more common in the control group, does not necessarily represent endometritis and is not a bad prognostic sign. Surprisingly, plasma cell infiltration was more common in the control group (NS). This finding raises the question of whether plasma cell infiltration in ART patients is indeed a marker for chronic endometritis as was previously suggested.

To study Junctional Zone Contractions (JZC) frequency patterns throughout entire IVF-ET cycles, in order to detect the earliest point during the cycle at which JZC frequency is significantly increased and to assess whether successful and unsuccessful treatment cycles are characterized by different JZC patterns. We studied 41 infertile women who underwent controlled ovarian hyperstimulation (COH) and IVF-ET. The mean age of the patients was 29.6 ± 3.8 years, they had 2.8 ± 2.5 previous failed IVF cycles and 3.0 ± 1.2 embryos transferred. Ultrasound scans were performed at the early follicular phase, mid follicular phase, hCG day, ET day (before ET), and one week after ET. The endometrium was visualized in a sagittal plane and observed over 5 minutes. Signals were videotaped and JZC frequency was subsequently analyzed at fast-forward replay. During the early follicular phase the uterus is in a nearly quiescent state. Contractility progressively increases and becomes significantly increased on hCG day. Thereafter, JZC frequency decreases during the luteal phase and the uterus returns to a nearly quiescent state. Sub-group analysis reveals a similar pattern in pregnant and non pregnant patients. A significantly lower JZC frequency was measured as early as the hCG day in patients who subsequently conceived. JZC frequency increases during the follicular phase of COH cycles, reaching a peak on hCG day. On hCG day patients with failed cycles have significantly higher JZC frequencies. Once therapeutic modulation of JZC becomes available it should be instituted on the hCG day or even earlier. Alternatively, in patients with high frequency JZC elective cryopreservation of all embryos may be considered.

Objective: Junctional zone contractions (JZC) frequency has been reported to be directly correlated with plasma estrogen concentrations (Oike et al., 1990). A progressive increase in JZC frequency has been described throughout the follicular phase of the menstrual cycle (Lyons et al.,1991; Ijland et al., 1996). In contrast, Fanchin et al. (1988) found no association between plasma estrogen concentration in stimulated cycles and JZC frequency. This conflict prompted us to investigate JZC patterns in natural cycles and to compare them to IVF cycles, where controlled ovarian hyper stimulation (COH) leads to supra-physiological estrogen concentrations. Design: Prospective study. Materials and Methods: We compared group A (4 women) undergoing frozen embryo transfer in natural cycles to group B (37 women) undergoing COH prior to IVF. Transvaginal sonography was performed at 4 points during the cycle (early follicular phase, late follicular phase, ET day and one week after ET). A sagittal view of the uterine cavity was obtained and the ultrasound probe was held steady for 5 min. The video-recorded image was analyzed at fast forward replay. Results: Despite lower estradiol concentrations during the follicular phase in natural cycles as compared to COH (285±218 vs. 827±862 pg/mL, respectively; p<0.05) similar JZC frequencies were recorded in both the early (1.9±0.1 vs. 2.6±1.12, respectively; NS) and late follicular phase (2.1±0.95 versus 2.5±0.75 respectively; NS). Similarly, luteal phase JZC frequencies were similar in both groups: at the time of ET (2.4±1.1 vs. 2.3±0.9 for natural and COH cycles, respectively; NS) and one week after transfer (1.3±0.30 versus 1.1±0.99, respectively; NS). Conclusion: Our study suggests that JZC pattern is similar in natural and stimulated cycles, despite a significant increase in plasma estradiol concentrations during COH. Both natural and COH cycles were supported with progesterone during the luteal phase, a fact that may be responsible for the similarities observed in JZC frequencies after ovulation in both groups. While the size of the group of patients observed during natural cycles certainly has to be increased, our preliminary findings suggest that, beyond a certain threshold, factors other than estradiol concentration are responsible for JZC frequency. As JZC frequency may affect the chance for implantation and pregnancy, further investigation should be directed at the physiology and pathophysiology of JZC.

Objective: It has been demonstrated that pregnancy rates do not change over the first three IVF-ET cycles but decrease by 40% for four or more prior failed attempts (Templeton et al., 1998). Thus, failure in more than four cycles is commonly defined as repeated implantation failure (RIF). Our objective was to search for clinical and laboratory characteristics that would help predict RIF as early as the time of the first or second IVF attempt.Design: Retrospective data analysis.Materials and methods: Between 1995 and 2002 3,659 IVF cycles were conducted in 1171 patients. We collected the data for patients who had their first IVF cycle in our center and either conceived within two cycles (n= 202) or failed to conceive after four consecutive fresh cycles (n=32) in our center. Every possible clinical and laboratory outcome variable was used for analysis and comparison between the groups. Variables which were found most contributory and significant for prediction of RIF were combined in an algorithm that gives an estimation for failure in subsequent cycles for a given patient.Results: The following variables were not significantly different between patients who conceived within 2 cycles and those who had RIF: Basal hormone testing (excluding FSH), infertility etiology and duration, sperm concentration and motility, presence of azoospermia, COH protocol, the use of IVF or ICSI, transfer day and technique. The following were significantly different between the groups:Patient age (years), total gonadotropin ampoules used and number of embryos transferred were found most powerful in prediction of failure in a given cycle. The following function represents the probability of NOT getting pregnant: Tabled 1−7.2676+ (0.1579∗B)+(0.0628∗C)−(0.5471∗D)[B=age; C=gonadotropin amps; C=No. of embryos transferred]A live demonstration of the algorithm will be included in the presentation.Conclusions: Better understanding of the factors leading to RIF may: 1. Lead to the introduction of treatment modalities that increase the efficiency of IVF-ET in RIF at an earlier stage. 2. Allow better counseling to our patients. Our current work is one small step toward this goal. Objective: It has been demonstrated that pregnancy rates do not change over the first three IVF-ET cycles but decrease by 40% for four or more prior failed attempts (Templeton et al., 1998). Thus, failure in more than four cycles is commonly defined as repeated implantation failure (RIF). Our objective was to search for clinical and laboratory characteristics that would help predict RIF as early as the time of the first or second IVF attempt. Design: Retrospective data analysis. Materials and methods: Between 1995 and 2002 3,659 IVF cycles were conducted in 1171 patients. We collected the data for patients who had their first IVF cycle in our center and either conceived within two cycles (n= 202) or failed to conceive after four consecutive fresh cycles (n=32) in our center. Every possible clinical and laboratory outcome variable was used for analysis and comparison between the groups. Variables which were found most contributory and significant for prediction of RIF were combined in an algorithm that gives an estimation for failure in subsequent cycles for a given patient. Results: The following variables were not significantly different between patients who conceived within 2 cycles and those who had RIF: Basal hormone testing (excluding FSH), infertility etiology and duration, sperm concentration and motility, presence of azoospermia, COH protocol, the use of IVF or ICSI, transfer day and technique. The following were significantly different between the groups: Patient age (years), total gonadotropin ampoules used and number of embryos transferred were found most powerful in prediction of failure in a given cycle. The following function represents the probability of NOT getting pregnant: Tabled 1−7.2676+ (0.1579∗B)+(0.0628∗C)−(0.5471∗D)[B=age; C=gonadotropin amps; C=No. of embryos transferred]A live demonstration of the algorithm will be included in the presentation. −7.2676+ (0.1579∗B)+(0.0628∗C)−(0.5471∗D) [B=age; C=gonadotropin amps; C=No. of embryos transferred] A live demonstration of the algorithm will be included in the presentation. Conclusions: Better understanding of the factors leading to RIF may: 1. Lead to the introduction of treatment modalities that increase the efficiency of IVF-ET in RIF at an earlier stage. 2. Allow better counseling to our patients. Our current work is one small step toward this goal.

Objective: Several studies have focused on junctional zone contractions (JZC) frequency and the outcome of IVF-ET. Fanchin et al. (1988) have noticed a stepwise decrease in pregnancy and implantation rates with increasing JZC frequency before ET. One possible mechanism for repeated implantation failure (RIF) in IVF-ET could be an abnormal pattern of JZC during the periovulatory period and at the time of ET, causing the expulsion of embryos from the uterine cavity. ZIFT has been suggested as a powerful clinical tool for the treatment of patients with RIF (Levran et al., 1998). Our objective was to evaluate and characterize the pattern of JZC in patients with RIF undergoing ZIFT. Design: Prospective observational study. Materials and Methods: Twenty-three women with a history of > 3 failed IVF cycles and presence of a patent tube underwent ZIFT. Transvaginal ultrasound was performed for 5 minutes immediately before and right after general anesthesia and during the actual tubal transfer procedure and five minutes later. The scan was centered on a sagittal plane of the uterus. The signals were recorded and analyzed during fast-forward replay. The frequency and direction of contractions were evaluated for each examination and compared. Results: The mean age of the patients was 34±5.1 years, they had 7.3±3.3 previous IVF cycles and 5.05±0.85 zygotes were transferred. Six (26.1 %) of the patients conceived. JZC were observed in all cases. A high JZC frequency was observed just before anesthesia (4.5±2.4 /min), which decreased significantly after anesthesia (2.1±1.6; p = 0.001). Contractions frequency was significantly increased again during ZIFT (5.5±2.6 /min) as compared to the frequency after anesthesia (p = 0.001), and decreased again after completing the procedure (4.0±1.4; p = 0.002). Interestingly, JZC frequency before anesthesia was significantly lower in patients who conceived as compared to those who did not (2.04±0.6 vs.5.4±226; p = 0.004). No correlation was found between the direction of JZC and conception. Conclusion: This is the first report on JZC during ZIFT. Our study clearly demonstrates that general anesthesia reduces JZC frequency and tubal manipulation induces JZC. As with conventional ET, a correlation between increased JZC frequency before ZIFT and cycle failure has been established. Measurement of JZC frequency may aid in better selection of patients who may benefit from ZIFT. The quest for the mechanism responsible for the high efficiency of ZIFT in patients with RIF remains ongoing.

Objective: To compare two stimulation protocols designed for low responders undergoing IVF.Design: Randomized, prospective study.Setting: University hospital IVF unit.Patient(s): Sixty low responders who were recruited on the basis of results in previous cycles.Intervention(s): Modified 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.Main Outcome Measure(s): Number of oocytes retrieved.Result(s): Twenty-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.Conclusion(s): These 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. (C) 2003 by American Society for Reproductive Medicine.

Objective: High-frequency junctional zone contractions (JZC) on the day of ET adversely affect cycle outcome (Fanchin et al., 1998), possibly by expelling embryos from the uterine cavity. Our objective was to study JZC frequency patterns throughout the entire IVF-ET cycle, in order to detect the earliest point during the cycle at which JZC frequency is significantly increased. Design: Prospective, observational study. Materials and Methods: We studied 41 infertile women who underwent controlled ovarian hyperstimulation (COH) and IVF-ET. The mean age of the patients was 29.6±3.8 years, they had 2.8±2.5 previous failed IVF cycles and 3.0±1.2 embryos transferred. Ultrasound scans were performed at the early follicular phase, mid-follicular phase, hCG day, ET day (before ET), and one week after ET. The endometrium was visualized in a sagittal plane and observed over a 5 min period. Signals were videotaped and JZC frequency was subsequently analyzed at fast-forward replay. Subgroup analysis was performed for pregnant vs. non-pregnant patients. Results: During the early follicular phase the uterus is in a nearly quiescent status. Contractility progressively increases and becomes significantly increased on hCG day. Thereafter, JZC frequency decreases during the luteal phase and the uterus returns to a nearly quiescent state in the mid-luteal phase. Sub-group analysis reveals a similar pattern in pregnant and non-pregnant patients. A significantly lower JZC frequency was measured in patients who subsequently conceived as early as the hCG day. Tabled 1 Conclusion: JZC frequency increases during the follicular phase of COH cycles, reaching a peak on hCG day. On hCG day patients with failed cycles have significantly higher JZC frequencies. Once therapeutic modulation of JZC becomes available it should be instituted on the hCG day or even earlier. Alternatively, in patients with high-frequency JZC elective cryopreservation of all embryos should be considered.