Objective: To study the value of E-2 production during controlled ovarian hyperstimulation (COH) in predicting IVF-ET outcome.Design: Historical cohort.Setting: Academic infertility center.Patient(s): A cohort of 270 patients who completed 324 consecutive IVF-ET treatment cycles.Intervention(s): None.Main Outcome Measure(s): Area under the curve for E-2 levels (AUC-E-2) from the first day of COH until the day of hCG administration was calculated and cycles grouped into low, average, and high AUC-E-2 groups. Clinical pregnancy rates per cycle were compared among the three groups, and correlation with AUC-E-2 values were calculated for all patients and after sub-grouping according to age, COH protocol and infertility diagnosis.Result(s): Cycles with low and high AUC-E-2 values had significantly lower pregnancy rates particularly in patients 35 years or older. There was a positive correlation between AUC-E-2 and pregnancy rates up to a certain AUC-E-2 level above with a negative correlation was found. The turning point between positive and negative correlation occurred at a significantly lower AUC-E-2 level in patients 35 years or older.Conclusions: Estradiol production during OCH correlates with IVF-ET outcome. Women > 35 years of age seem more vulnerable to high E-2 levels.

PURPOSE:Most studies reported estradiol (E2) levels attained on day of hCG administration when investigating effect of E2 on IVF outcome. We studied whether a relationship exists between the area under the curve for E2 levels (AUC-E2) and E2 levels on hCG day during IVF-ET.METHODS:Retrospectively, we analyzed data for 313 patients who completed one IVF-ET cycle each. Patients were sorted according to AUC-E2 levels. Then we compared between each patient's own AUC-E2 and the corresponding E2 level on hCG day for the same patient.RESULTS:Although overall AUC-E2 correlated positively with E2 levels on hCG day, there was no consistent correlation between individual patients.CONCLUSIONS:AUC-E2 reflects more accurately the amount of E2 produced by the follicles during controlled ovarian hyperstimulation. The absence of a uniform correlation between AUC-E2 and E2 on hCG day may result in different conclusions when studying outcomes of IVF treatment.

Objective: To report a live birth after transfer of cryopreserved blastocysts derived from testicular sperm that were cryopreserved 15 hours after biopsy due to inclement weather.Design: Case report.Setting: University-affiliated private clinic.Patient(s): Couple undergoing lVF with intracytoplasmic sperm injection (ICSI) using testicular extracted sperm for male factor infertility due to unexplained obstructive azoospermia.Intervention(s): An IVF,case involving testicular biopsy, cryopreservation, and thawing of testicular tissue, ICSI, embryo freezing, and transfer of cyropreserved blastocysts.Main Outcome Measure(s): The ability to use cryopreserved testicular tissue in which optimal time from biopsy to freezing had been delayed because the weather was inclement.Result(s): In spite of a 15-hour delay in processing and cryopreservation of the testicular biopsy, subsequent thawing yielded viable sperm that resulted in viable embryos after ICSI. Transfer of fresh embryos was unsuccessful. However, subsequent use of supernumerary viable blastocysts that were frozen resulted in the live birth of a baby.Conclusion(S): A 15-hour delay in processing and cryopreservation of a testicular biopsy did not affect the viability of the extracted sperm after thawing. Although it is desirable to freeze the testicular specimen as soon as possible, the delay in processing in this case due to inclement weather did not affect the potential for fertilization and implantation of a viable cryopreserved blastocyst. (C)2005 by American Society for Reproductive Medicine.

There is evidence that infertility treatment, including in vitro fertilization and embryo transfer (IVF-ET), is associated with less favorable obstetric outcome, specifically, higher pregnancy loss, preterm labor and low birth weight (BW). Vanishing-twin is a phenomenon in which one or more of implanted embryos fail to continue. We studied outcome of singleton pregnancies after vanishing-twin compared to pregnancies that started as singletons. Retrospective analysis of 61 consecutive live-births from singleton pregnancies in women undergoing IVF-ET. Five pregnancies started as twins and ended as singletons due to vanishing-twin; 56 pregnancies started as singletons. Vanishing-twin was diagnosed by ultrasound at 6-wks (2 gestational sacs with 2 heartbeats) followed by another ultrasound showing loss of one of the twins at 8 to 12 wks. Gestational age (GA) was calculated from ET day until delivery. BW was calculated as percentage from BW expected according to GA (expected BW was calculated from control population similar to Western New York region matching patients who underwent IVF-ET). Vanishing-twin pregnancies were associated with significantly lower BW and shorter GA. There was no significant difference regarding age, gravity, infertility factor and duration, ovarian stimulation protocol, or in vitro conditions (oocyte insemination, day and number of embryos transferred, fertilization or implantation rate). Pregnancies associated with vanishing-twin after IVF-ET are associated with higher risk for low BW and short GA.Tabled 1P value < .05 considered significantVanishing twin pregnanciesSingleton pregnanciesP valueAge(y)34 ± 233 ± 3.4Gravity.8 ± .8.7 ± .8.4Infertility duration (mo)31 ± 1731 ± 17.5GA(wk)32 ± 536 ± 2.001%BW88 ± 1299 ± 11.03Data presented as mean ± SD Open table in a new tab

Objective: To study the value of E2 concentrations attained during COH (controlled ovarian hyperstimulation) in predicting the outcome of treatment in women undergoing IVF-ET. Design: Retrospective study. Materials and Methods: We analyzed data of 270 infertile women who completed 324 cycles of IVF-ET during the period of January 2001 and July 2002 at a tertiary referral academic IVF center. The AUC for E2 concentrations was calculated from the available daily E2 concentrations along the follicular phase starting on the first day of COH until the day of hCG administration. We studied the value of AUC in predicting treatment outcome by comparing clinical pregnancy rates among three patient groups defined according to mean AUC. Group 1 (low responders) included patients with AUC Mean + 1SD and group 3 (average responders) included patients with AUC between Mean minus 1SD to Mean plus 1SD. We also compared pregnancy rates among groups of patients divided according to AUC at increments of (3000 pg/ml/stimulation). Correlation between AUC and clinical pregnancy rates was calculated using linear regression analysis. The analysis was done for all patients and for patients <35 and >35 years separately. Results: Both low and high AUC (low and high responders groups were associated with significantly lower pregnancy rates than average responders (P <.05). The difference was more significant in patients > 35 years (P <.01). There was a positive correlation between AUC and pregnancy rates until a certain AUC value above which, a negative correlation was noticed. The turning AUC level between positive and negative correlation occurred at a significantly lower level in patients >35 years. Conclusions: AUC for E2 levels attained during COH are better predictors of treatment outcome after IVF-ET. There might be an optimum range of AUC for E2 that is associated with the best outcome. Levels below (low responders) and above (high responders) the optimum range are associated with poor treatment outcome. In women > 35 years, the negative correlation occurred at a lower AUC level when compared to women < 35 years indicating a higher vulnerability for the possible deleterious effects of high estrogen levels in this age group. Optimizing AUC for E2 levels during COH may help in improving the treatment outcome after IVF-ET by using less aggressive stimulation protocols as well as other possible agents such as aromatase inhibitors that might lower E2 levels without affecting the number of mature follicles. Clinical Pregnancy Rates Among Three Study Groups Tabled 1∗ = P value was < .05 when compared with the corresponding low and high responders separately View Large Image Figure ViewerDownload (PPT) ∗ = P value was < .05 when compared with the corresponding low and high responders separately

Objective: To study the effect of age on the pattern of estrogen production per mature ovarian follicle and in response to FSH stimulation during different ovarian stimulation protocols Design: Retrospective. Materials and Methods: Patients undergoing ovarian stimulation in conjunction with intrauterine insemination or for IVF-ET (in vitro fertilization and embryo transfer) have been included from two tertiary referral academic infertility centers in the period from January 2000 and July 2002. Patients were divided into two groups, first group included patients who underwent COH (controlled ovarian hyperstimulation) for IVF-ET (226 patients had 254 cycles). Both standard and microdose flare protocol were applied for COH. The second group included 357 patients who received different ovarian stimulation protocols in conjunction with IUI (intrauterine insemination) in 493 cycles. Clomiphene citrate was used alone in 176 cycles and in conjunction with FSH in 28 cycles, FSH injection alone in 87 cycles, letrozole (an aromatase inhibitor) was used alone in 84 cycles and in conjunction with FSH in 118 cycles). The AUC for E2 production was calculated from available daily E2 levels along the follicular phase starting on the first day of ovarian stimulation until the day of hCG administration (or endogenous LH surge in IUI cycles). AUC for E2 production per FSH unit administered (AUC/FSH) as well as the AUC for E2 produced per mature follicle (AUC/follicle) were calculated. Patients were sub-grouped according to the age in ascending matter. Each patient group was analyzed separately and after subdividing them according to the protocol of ovarian stimulation. Results: Group 1 (IVF) patients had a positive correlation between AUC/follicle and advancing age (P<0.05) and a negative correlation between AUC/FSH and advancing age (P<0.05). This was true when all patients were analyzed together and after subgrouping according to the stimulation protocol (long standard and microdsoe flare up protocol). The same findings were found in the second patient group when all patients were analyzed together and when subdivided into different ovarian stimulation protocol. Pregnancy rates negatively correlated well with advancing age as expected and was also negatively correlating with increasing AUC/follicle and decreasing AUC/FSH. The effect of age on AUC/follicle, AUC/FSH and Pregnancy Rate in IVF-ET cycles Tabled 1 View Large Image Figure ViewerDownload (PPT) Conclusions: High AUC/follicle and low AUC/FSH seem to be features of advancing age irrespective of type of ovarian stimulation. Both parameters also might serve as predictors for poor treatment outcome.

Objective: There is a controversy regarding the effect of supraphysiologic estradiol (E2) levels attained during controlled ovarian hyperstimulation (COH) in patients undergoing assisted reproductive technology (ART) cycles on the outcome of treatment. Some investigators suggested unfavorable outcome associated with high responders who attained significantly high E2 levels while others failed to find such an effect. Most of the studies observed E2 concentrations attained on the day of hCG administration rather than the area under the curve for E2 concentrations which is expected to reflect more accurately the amount of E2 produced during COH. In this report we studied the relationship between AUC for E2 and E2 concentration on the day of hCG administration for E2 concentrations attained during COH in patients undergoing IVF-ET. Design: Retrospective study. Materials and Methods: Retrospectively we analyzed data from 313 patients who completed one IVF-ET cycle each. We sorted the patients according to the AUC for E2 levels comparing each patient's own AUC with the corresponding E2 concentration on the day of hCG administration. Results: Although the overall AUC for E2 concentrations positively correlated with the E2 concentrations attained on the day of hCG administration, there was no uniform correlation between successive individual patients. Figures 1 and 2 show representative E2 concentrations in two samples (pregnant and non-pregnant cycles), each consisted of 21 patients selected around the mean levels of AUC. View Large Image Figure ViewerDownload (PPT) Conclusions: In calculating AUC, the duration of ovarian stimulation as well as several E2 measurements are taken into consideration, which is expected to reflect, more accurately, the amount of E2 attained during ART cycles. The absence of a uniform correlation between AUC and E2 on hCG day among individual patients suggests that AUC rather than E2 concentration on the day of hCG administration should be used when studying the effect of E2 on the outcome of ART treatment.

During the follicular phase of the menstrual cycle, FSH stimulates follicular growth, granulosa cell aromatase activity, induction of LH receptors on the granulosa cell membrane, and estradiol secretion. As a result of negative feedback of estradiol on the pituitary, serum FSH concentrations decline. Despite the fall in FSH concentrations, the maturing follicle continues to develop to the preovulatory stage. In a prospective randomized trial, we tested the hypothesis that a key mechanism by which the dominant follicle continues to develop in the face of decreasing concentration of FSH is by acquiring LH responsiveness. In 24 women, pituitary gonadotropin secretion was down-regulated with a GnRH agonist. Follicular growth was then stimulated with recombinant human FSH (r-hFSH) until a 14-mm follicle was identified by ultrasound. The women were then randomized to 1 of 4 groups for a 2-day period: continued r-hFSH treatment, substitution of r-hFSH with saline, low dose r-hLH (150 IU, twice daily), or high dose r-hLH (375 IU, twice daily). Serum estradiol concentrations in the women receiving saline declined by the end of the 2-day randomization period. In contrast, serum estradiol concentrations continued to rise in women receiving either r-hFSH or r-hLH compared with those in the saline-treated group (P < 0.05). Pregnancies occurred in each of the gonadotropin treatment groups. These findings indicate that once FSH initiates follicular growth, either FSH or LH is capable of sustaining follicular estradiol production. Extrapolating these findings to the normal menstrual cycle suggests that the maturing follicle may continue to develop in the presence of diminishing FSH concentrations by acquiring the capacity to respond to LH.