Women age <25 have been reported to have less favorable IVF treatment outcomes compared to women age 25-35 (1). A bimodal distribution of aneuploidy rates has also been described in the general IVF population, with most women ≤25 in that study having higher aneuploidy rates than women age 35-37 (2). A difference in euploidy rates among young oocyte donors could change the way donors are selected, provide evidence of benefit for preimplantation genetic testing for aneuploidy (PGT-A) in some of these cycles, as well as increase our overall understanding of euploidy according to age. Therefore, our objective was to examine euploidy rates among age sub-groups of young oocyte donors. Retrospective cohort. All donor oocyte IVF cycles with trophectoderm biopsy for PGT-A using either aCGH or NGS between January 2015 and December 2016 at a single fertility clinic were screened for inclusion. Only cycles from donors age 21-30 were included for analysis. Cycles were then divided by donor age in two groups: Group 1: 21-25, Group 2: 26-30. The main outcome measure was blastocyst euploidy rate. Statistical analysis were performed with a t-test; percentage data were transformed using arcsine transformation and then compared with the t-test. Differences with p<0.05 were considered significant in all comparisons. A total of 132 donor cycles with 1123 biopsied blastocysts were included. There were 64 cycles done with donors age 21-25 and 68 cycles with donors age 26-30; mean donor age was 23.2 and 27.8 years respectively. The total number of blastocysts formed were 865 and 760, whereas the total number of blastocysts biopsied were 546 and 577 for group 1 and 2 respectively. There were no statistical differences in the average amount of gonadotropins administered, average peak estradiol, or blastocyst formation rate. The average number of oocytes retrieved (33.4 ± 13.3 (SD) vs. 28.1 ± 11.2 (SD), p=0.015) and the euploidy rate (81.4% ± 16.10% (SD) vs. 75.7% ± 18.20% (SD), p=0.037) in group 1 were significantly higher than in group 2.Tabled 1Age group 1Age group 221-25 (yo)26-30 (yo)P valueGonadotropin administered (IU)32703070NSAverage peak E2 (pg/ml)45824215NSAverage number of eggs retrieved33.428.10.015Blastocyst rate62.10%62.90%NSEuploidy rate81.40%75.70%0.037 Open table in a new tab In contrast to prior studies, these data demonstrate that oocyte donors age 21-25 have higher euploidy rates compared to donors age 26-30. In addition, they have a higher average number of retrieved oocytes. These differences, although statistically significant, may not be clinically relevant. This continues to support the practice of not favoring a specific age sub-group of young oocyte donors.

Purpose This study investigates a case series of eight couples who underwent trophectoderm (TE) biopsy and comprehensive chromosomal screening (CCS) for routine aneuploidy screening and were found to have CCS results concerning for previously undetected parental balanced reciprocal translocations. Methods In each case, controlled ovarian hyperstimulation and in vitro fertilization (IVF) yielded multiple blastocysts that each underwent CCS with high-density oligonucleotide microarray comparative genomic hybridization (aCGH). Results Parental translocations were suspected based on the finding of identical break point mutations in multiple embryos from each couple. Confirmation of these suspected translocations within blastocysts was performed with next-generation sequencing (NGS). Subsequent parental karyotypic evaluation resulted in a diagnosis of parental balanced reciprocal translocation in each case. Conclusions We demonstrated that high-resolution aCGH and NGS on TE biopsies can accurately detect parental reciprocal translocations when previously unrecognized.

Individuals with infertility or recurrent pregnancy loss are at higher risk for having a balanced translocation compared to the general population (1). Array comparative genomic hybridization (aCGH) was the first technology to become widely available for comprehensive chromosomal screening (CCS) for in vitro fertilization (IVF) patients (2). Next generation sequencing (NGS) is a newer technology that has also been applied to CCS (3). Preimplantation genetic screening, with both aCGH and NGS, is performed with the purpose of improving implantation rate, but the technologies to date have not been fully evaluated in their ability to detect balanced translocations (3, 4). To demonstrate that previously unknown or undetected parental balanced reciprocal translocations can be detected by trophectoderm biopsy and CCS using both high-density oligonucleotide aCGH and NGS in IVF-derived blastocysts. A case series of four cases in which CCS using both aCGH and NGS detected unbalanced reciprocal translocations in multiple embryos. These findings ultimately led to a diagnosis of a parental translocation, which was previously undetected using a conventional karyotype. In each case, standard IVF stimulation yielded multiple blastocysts that underwent trophectoderm biopsy for CCS with oligonucleotide aCGH. Previously unidentified translocations were identified in multiple embryos and repeat CCS using NGS confirmed these translocations. A translocation was suspected when a segmental abnormality was detected with the identical break point in more than one embryo. Re-evaluation of the parent couples revealed the presence of a balanced reciprocal translocation in each case. Unknown or previously undetected translocations can be identified when unbalanced translocations are found in multiple embryos from the same cohort using both high-density oligonucleotide aCGH and NGS. Use of CCS with these latest technologies can detect reciprocal translocations even with previously errantly normal parental karyotypes.

To evaluate the percentage of euploid embryo development in patients with obstructive and non-obstructive azoospermia. Retrospective data analysis. From March 2013 to April 2016, 36 azoospermic men underwent 45 cycles of ICSI-PGS cycles with blastocyst trophoectoderm biopsy for comprehensive chromosomal screening using high density oligonucleotide microarray comparative genomic hybridization. 30 cycles used testicular sperm from obstructive azoospermia men with prior vasectomy, 9 cycles were non-obstructive, and 6 cycles were from azoospermic men with unknown causes. The results were compared with 621 In-Vitro Fertilization (IVF) patients that used ejaculated sperm during the same time period. 3,475 blastocysts were generated and underwent trophoectoderm biopsy and PGS. Tabled 1Age group# ICSI Cycle# MII eggs ICSI’d#2PN(Fert rate)Blastocyst # (rate)Euploid #(rate)P value<37TESE38446341 (76.5%)206 (60.4%)133/163 (81.6%)P=0.6<37EJ40143723096 (70.8%)3271/5361 (61.0%)1911/2491 (76.7%)38-42TESE75448 (88.5%)19 (39.6%)10/19 (52.5%)P=0.438-42EJ2201044885/1044 (84.8%)771/1537 (50.2%)306/802 (38.2%) Open table in a new tab Our data demonstrate that testicular sperm from azoospermic patients have comparable fertilization, blastocyst formation and euploid rates compared to cycles using ejaculated sperm. These comparable rates of fertilization, blastocyst formation and rates of euploid embryos with the use of testicular sperm requires further study but may be due in part to female partners with more favorable fertility potential.

To evaluate if day of blastocyst biopsy is associated with embryo chromosomal status as determined by high density oligonucleotide microarray comparative genomic hybridization (aCGH). Retrospective cohort analysis at a private fertility center. In-vitro fertilization (IVF) cycles from January 2014 - December 2014 with blastocysts that underwent trophectoderm biopsy for comprehensive chromosomal screening (CCS) with aCGH were included. Both donor and autologous cycles were included. Repeat cycles from the same patient were excluded. Cycles were evaluated for oocyte age, blastocyst number, day of blastocyst biopsy (day 5, day 6 or day 7), and euploidy rate. Cycles were stratified by SART age group (donor, <35, 35-37, 38-40, 41-42, >42) and analyzed to determine whether day of trophectoderm biopsy is associated with euploidy rate. Statistical analysis was performed with a mixed model test of fixed effects. A total of 388 IVF cycles and 2,132 biopsied blastocysts were evaluated (Table 1). Average patient age was 35. The percent of blastocysts biopsied on day 5, day 6, and day 7 were 62.5%, 35.8% and 1.7%, respectively. Average blastocyst euploidy rate on day 5, day 6, and day 7 were 49.5%, 36.5% and 32.9%, respectively. Earlier day of blastocyst biopsy was significantly associated with increased euploidy rate (p<0.0001). Younger maternal age (p<0.0001) and higher number of blastocysts biopsied per patient (p=0.0063) were both independently associated with greater euploidy. Donor status, infertility diagnosis, partner age and stimulation protocol were not significantly associated with euploidy after controlling for covariates. Faster progression to the blastocyst stage, allowing for earlier trophectoderm biopsy, is independently associated with a higher percentage of euploid embryos. This relationship was shown for both autologous and donor embryos. For patients who choose not to biopsy, these data support selection of a day 5 blastocyst for transfer over a later-developing embryo. Additionally, these results can assist in counseling of patients undergoing IVF with CCS regarding expectations by utilizing not only maternal age and number of total blastocysts, but also day of biopsy to best predict likelihood of a euploid embryo for transfer. To our knowledge, this is the first study to examine day of blastocyst biopsy and euploidy rate presented by SART category.Tabled 1Embryo characteristics by SART age groupdonor<3535-3738-4041-42>43Avg # oocytes retrieved33.2718.5615.3113.697.558.03Ave # matureoocytes21.813.239.959.355.646.23Fertilization rate (%)66.466.862.965.171.476.9Blast rate (%)62.864.263.260.352.645.0Ave # D5 blasts8.324.573.122.971.281.13Ave # D6 blasts5.262.942.411.961.151.42Ave # D7 blasts0.230.130.030.090.060.03Ave D5 euploid rate (%)78.371.757.946.234.28.8Ave D6 euploid rate (%)63.858.141.533.021.11.4Ave D7 euploid rate (%)63.950.050.033.300Total Euploid rate (%)76.165.749.742.828.210.0 Open table in a new tab

ObjectiveTo analyze the implantation rates (IR) of previously vitrified euploid blastocysts after comprehensive chromosomal screening (CCS) as a function of female age.DesignRetrospective data analysis.Materials and MethodsFrom Jan 2014 through March 2015, 322 patients underwent 349 vitrified blastocyst embryo transfer cycles (FET). On day 5 or 6 of embryo culture, trophectoderm samples were obtained using a Lykos ZTK laser (Hamilton Thorne) immediately prior to vitrification. Samples were sent to PacGenomics for 24 chromosome microarray testing [1]. A total of 490 blastocysts were warmed, and 349 blastocyst FET cycles were performed. One way ANOVA was used to calculate p values.ResultsThere were no differences observed in the implantation rates of previously vitrified euploid blastocysts across all patient age groups (p>0.05). The number of FET cycles, the total and mean number of blastocysts transferred, clinical pregnancy rates and the implantation rates stratified by female partner age are shown in the table below. Clinical pregnancies and IP were defined as deliveries or ongoing pregnancies after the documentation of fetal cardiac activity.ConclusionsTabled 1Implantation rates in each age group after vitrified euploid blastocysts ET.FET cycles (n)Total number of blastocysts transferred(n)Mean number of blastocysts transferred(n)Heart Beat# (n)Implantation rates (%)Donor1262021.611155%<35y941281.46954%35-37y48591.23559%38-40y49641.33961%41-42y18201.11470%>42y14171.21165% Open table in a new tab ObjectiveTo analyze the implantation rates (IR) of previously vitrified euploid blastocysts after comprehensive chromosomal screening (CCS) as a function of female age. To analyze the implantation rates (IR) of previously vitrified euploid blastocysts after comprehensive chromosomal screening (CCS) as a function of female age. DesignRetrospective data analysis. Retrospective data analysis. Materials and MethodsFrom Jan 2014 through March 2015, 322 patients underwent 349 vitrified blastocyst embryo transfer cycles (FET). On day 5 or 6 of embryo culture, trophectoderm samples were obtained using a Lykos ZTK laser (Hamilton Thorne) immediately prior to vitrification. Samples were sent to PacGenomics for 24 chromosome microarray testing [1]. A total of 490 blastocysts were warmed, and 349 blastocyst FET cycles were performed. One way ANOVA was used to calculate p values. From Jan 2014 through March 2015, 322 patients underwent 349 vitrified blastocyst embryo transfer cycles (FET). On day 5 or 6 of embryo culture, trophectoderm samples were obtained using a Lykos ZTK laser (Hamilton Thorne) immediately prior to vitrification. Samples were sent to PacGenomics for 24 chromosome microarray testing [1]. A total of 490 blastocysts were warmed, and 349 blastocyst FET cycles were performed. One way ANOVA was used to calculate p values. ResultsThere were no differences observed in the implantation rates of previously vitrified euploid blastocysts across all patient age groups (p>0.05). The number of FET cycles, the total and mean number of blastocysts transferred, clinical pregnancy rates and the implantation rates stratified by female partner age are shown in the table below. Clinical pregnancies and IP were defined as deliveries or ongoing pregnancies after the documentation of fetal cardiac activity. There were no differences observed in the implantation rates of previously vitrified euploid blastocysts across all patient age groups (p>0.05). The number of FET cycles, the total and mean number of blastocysts transferred, clinical pregnancy rates and the implantation rates stratified by female partner age are shown in the table below. Clinical pregnancies and IP were defined as deliveries or ongoing pregnancies after the documentation of fetal cardiac activity. ConclusionsTabled 1Implantation rates in each age group after vitrified euploid blastocysts ET.FET cycles (n)Total number of blastocysts transferred(n)Mean number of blastocysts transferred(n)Heart Beat# (n)Implantation rates (%)Donor1262021.611155%<35y941281.46954%35-37y48591.23559%38-40y49641.33961%41-42y18201.11470%>42y14171.21165% Open table in a new tab

Selecting embryos with the highest implantation potential is the most important challenges in the field of Assisted Reproduction. Previously, morphologic criteria were the most commonly used standards for embryo selection. The introduction of preimplantation genetic screen (PGS-24) provides a novel method to determinate embryo competence. Our goal was to evaluate the clinical outcomes in patients with and without PGS-24 testing. Retrospective study. 532 patients who underwent FET using vitrified-thawed blastocysts at our fertility center from Jan 2013 to Dec 2013 were included. 253 received PGS-24 testing and 279 patient did not. Patients were divided into 5 age groups (<35, 35-37, 38-40, >40 and donor). Clinical pregnancy rate and implantation rate were compared. Clinical pregnancy rate and implantation rate for each age group were generally higher in the PGS compared to the non-PGS group (Table 1). The mean number of embryos transferred was significantly lower in PGS group vs non-PGS. These data demonstrate significant improvements in clinical outcomes in patients with PGS-24 testing, suggesting that PGS-24 is an effective method to determine blastocyst competence. Furthermore, PGS-24 screening facilitates elective single embryo transfer while reducing the probability of ovarian hyperstimulation syndrome and avoiding multiple gestation.Tabled 1COMPARISONS OF CLINICAL OUTCOMES BETWEEN PATIENTS WITH AND WITHOUT PGS-24 SCREENINGTable 1 (A) Sample SizeAge GroupsSample SizePGS-24NO PGS-24DONORN=82N=103<35N=67N=8835-37N=42N=4238-40N=39N=25>40N=23N=21Table 1 (B) Comparisons of Clinical Pregnancy Rate and On Going Clinical Pregnancy RateAge GroupClinical Pregnancy Rate (%)On Going Pregnancy Rate (%)PGS-24NO PGS-24p valuePGS-24No PGS-24p valuedonor66440.00*54380.04*<3569630.4260510.2935-3771520.0767450.04*38-4067600.5956480.51>4052190.04*43100.02*Table 1 (C) Comparisons of Implantation Rate and Implantation Leading to Ongoing PregnancyAge GroupsImplantation Rate (%)Implantation Leading to Ongoing PregnancyPGS-24No PGS-24P valuePGS-24No PGS-24p valuedonor55280.00*47230.00*<3558460.1150380.1135-3761270.00*58210.00*38-4052380.2046350.29>405340.00*4440.00*Table 1 D. Number of Transferred EmbryosAge GroupsNumber of Transferred EmbryosPGS-24No PGS-24p valuedonor1.7±0.542.1±0.900.00*<351.4±0.521.8±0.530.00*35-371.4±0.671.9±0.660.00*38-401.5±0.552.0±1.070.01*>401.5±0.592.0±0.760.02** P<0.05 Significant difference Open table in a new tab

To evaluate the correlation between blastocyst grade, time of blastocyst formation, maternal age and chromosomal aneuploidy. Retrospective analysis. 377 patients who underwent IVF at our center from Jan 2013 to Dec 2013 were included. A total of 1403 blastocysts underwent trophectoderm biopsy and comparative genomic hybridization (CGH). The association of morphologic score, time of blastocyst formation, maternal age and the rate of aneuploidy were analyzed. Embryos that progressed to blastocysts on day5 were less likely to be aneuploid than day6 blastocysts (Table1 A). A surprisingly high percentage of grade AA blastocysts were aneuploid. More than half of the grade AB and BB blastocysts were aneuploid (Table 1B). The aneuploidy rate increased significantly with maternal age (Table 1C). Our data suggest a correlation between aneuploidy and the time of blastocyst formation, blastocyst quality and maternal age. A significant proportion of grade AA blastocysts were aneuploid suggesting morphologic analysis alone is insufficient to ensure transfer of normal embryos. Younger age groups had a high percentage of aneuploidy suggesting that PGS testing may be considered even in younger patients. Very few D6 blastocysts from patients >40 years were euploid. PGS-testing should be strongly considered in D6 embryos in this age group.Tabled 1THE ASSOCIATION BETWEEN TIME OF BLASTOCYST FORMATION, EMBRYO GRADE, MATERNAL AGE AND RATE OF ANEUPLOIDYTable1 (A) Association between time of blastocyst formation and aneuploidyAneuploidy Rate (%)Age GroupsD5 BlastocystD6 Blastocystp valuedonor29 (n=217)38 (n=88)0.17<3524 (n=229)46 (n=128)0.00*35-3737 (n=139)53 (n=100)0.02*38-4055 (n=160)68 (n=124)0.04*41-4276 (n=80)84 (n=45)0.36>4276 (n=42)93 (n=51)0.04*Table1 (B) Association between embryo grade and aneuploidyAneuploidy Rate (%)p valueAAAB/BABBAA vs AB/BAAA vs BBAB/BA vs BBD5 Blastocyst31 (n=527)55 (n=197)58 (n=118)0.00*0.00*0.64D6 Blatocyst42 (n=177)58 (n=118)69 (n=224)0.120.00*0.04*Table1 (C) Association between maternal age and aneuploidyAge Groupsdonor<3535-3738-4041-42>42Aneuploidy Rate (%)323344617985p valuedonor vs <35 p=0.87; donor vs 35-37 p=0.00*; donor vs 38-40 p=0.00*; donor vs 41-42 p=0.00*; donor vs >42 p=0.00*; <35 vs 35-37 p=0.00*, <35 vs 38-40 p=0.00*; <35 vs 41-42 p=0.00*; <35 vs >42 p=0.00*; 35-37 vs 38-40 p=0.00*; 35-37 vs 41-42 p=0.00*; 35-37 vs >42 p=0.00*; 38-40 vs 41-42 p=0.00*; 38-40 vs >42 p=0.00*; 41-42 vs >42 p=0.29* p<0.05 statistical significant difference Open table in a new tab

OBJECTIVE: Our goal is to determine the effects of elevated serum progesterone (P4) at the day of human chorionic gonadotropin (hCG) trigger on the clinical outcomes following in vitro fertilization-embryo transfer (IVFET). DESIGN: Retrospective case control study. MATERIALS AND METHODS: We reviewed 655 IVF-ET cycles in which ovulation were performed using antagonist protocol. The thresholds of serum P4 were set at 1.4, 2.0 and 2.5 ng/ml. Patients with a level of P4 less than the threshold were subjected to control group, and those with a level higher than threshold were subjected to elevated p4 group. The clinical outcomes between two groups were compared. RESULTS: The total number of retrieved oocytes was significantly higher in elevated P4 group (18.8 10.8, 22.2 10.8 and 25.2 10.8) than in control(12.2 7.7, 14.0 9.1 and 14.8 9.5) at all three P4 thresholds(p1⁄40.000). The number of blastocysts was also significantly higher in elevated P4 group (4.5 4.5, 5.6+5.5 and 6.2 5.9) than in control (2.7 3.1, 3.2 3.5 and 3.2 3.6) at all thresholds (p1⁄40.000). However, when the thresholds were set to 2.0 and 2.5ng/ml, the clinical pregnancy rate was lower in the elevated P4 group (41.6% and 37.3%) than in control (46.3% and 46.0%), but the difference were not statistically significant (p1⁄40.197, p1⁄40.144 respectively). The fertilization rate was not different.

Our goal is to determine the effects of elevated serum progesterone (P4) at the day of human chorionic gonadotropin (hCG) trigger on the clinical outcomes following in vitro fertilization-embryo transfer (IVF-ET). Retrospective case control study. We reviewed 655 IVF-ET cycles in which ovulation were performed using antagonist protocol. The thresholds of serum P4 were set at 1.4, 2.0 and 2.5 ng/ml. Patients with a level of P4 less than the threshold were subjected to control group, and those with a level higher than threshold were subjected to elevated p4 group. The clinical outcomes between two groups were compared. The total number of retrieved oocytes was significantly higher in elevated P4 group (18.8±10.8, 22.2±10.8 and 25.2±10.8) than in control(12.2±7.7, 14.0±9.1 and 14.8±9.5) at all three P4 thresholds(p=0.000). The number of blastocysts was also significantly higher in elevated P4 group (4.5±4.5, 5.6+5.5 and 6.2±5.9) than in control (2.7±3.1, 3.2±3.5 and 3.2±3.6) at all thresholds (p=0.000). However, when the thresholds were set to 2.0 and 2.5ng/ml, the clinical pregnancy rate was lower in the elevated P4 group (41.6% and 37.3%) than in control (46.3% and 46.0%), but the difference were not statistically significant (p=0.197, p=0.144 respectively). The fertilization rate was not different.Tabled 1HSVHomemadeCryotoptotal% Survived81.484.671.482.6Fertilization Rate88.678.26081.1Transferred2222Blastocyst Rate19.434.910031.2% Positive HCG10062.510077Implantation Rate62.554.557.9 Open table in a new tab Our data demonstrated that higher serum progesterone reflects good follicular recruitment and better chance of obtaining blastocysts for transfer or cryopreservation.Our data suggested that elevated P4 levels may adversely affect clinical pregnancy rate in IVF-ET patients. However, the difference was not sufficient to warrant a clinical intervention such as deferring fresh embryo transfer and freezing all embryos for future transfer.To elucidate the mechanisms underlying the increased probability of pregnancy in FET than ET, additionalfactors should be analyzed.

ObjectiveIt has long been thought that fresh embryo transfer (ET) is a better way to achieve higher pregnancy rates when compared to frozen embryo transfer (FET). With the advance of embryo cryopreservation technique, especially the development of vitrification, several reports demonstrated higher pregnancy rates in FET cycles than in ET cycles. Our goal is to discern the potential effects of ovarian stimulation on implantation potential by comparing the clinical outcomes between ET and FET.DesignRetrospective case control study.Materials and Methods1263 patients 40 years of age or less who underwent ET or FET in our center from Jan 2010 to March 30, 2013 were included. Of the 1263 patients, 682 received ET and 581 received FET. Embryos were slow frozen or vitrified using the Cryotop method (Cryotop, HSV, homemade straws etc). Patients were divided into three age groups (35, 35-37 and 38-40 years of age). Clinical pregnancy rates were compared between the ET and FET groups that were matched for age.ResultsTabled 1Comparisons of clinical outcomes between ET and FET patientsAge (year)TansferNo. of cyclesNo. of transferred embryosClinical pregnancy rate (%)<35ET2872.0±0.653.3FET3042.1±0.963.2P valueP=0.099P=0.01735-37ET1822.3±0.848.4FET1482.0±0.850.7p valueP=0.001P=0.37938-40ET2132.9±1.238.0FET1292.5±1.248.8p valueP=0.001P=0.032 Open table in a new tab ConclusionOur data demonstrated a significantly greater chance of clinical pregnancy in patients who underwent a FET than with ET. This suggests that endometrial receptivity may be impaired in ET patients after ovarian stimulation. To maximize the probability of pregnancy, postponing fresh transfer and freezing all embryos for future transfer should be considered. ObjectiveIt has long been thought that fresh embryo transfer (ET) is a better way to achieve higher pregnancy rates when compared to frozen embryo transfer (FET). With the advance of embryo cryopreservation technique, especially the development of vitrification, several reports demonstrated higher pregnancy rates in FET cycles than in ET cycles. Our goal is to discern the potential effects of ovarian stimulation on implantation potential by comparing the clinical outcomes between ET and FET. It has long been thought that fresh embryo transfer (ET) is a better way to achieve higher pregnancy rates when compared to frozen embryo transfer (FET). With the advance of embryo cryopreservation technique, especially the development of vitrification, several reports demonstrated higher pregnancy rates in FET cycles than in ET cycles. Our goal is to discern the potential effects of ovarian stimulation on implantation potential by comparing the clinical outcomes between ET and FET. DesignRetrospective case control study. Retrospective case control study. Materials and Methods1263 patients 40 years of age or less who underwent ET or FET in our center from Jan 2010 to March 30, 2013 were included. Of the 1263 patients, 682 received ET and 581 received FET. Embryos were slow frozen or vitrified using the Cryotop method (Cryotop, HSV, homemade straws etc). Patients were divided into three age groups (35, 35-37 and 38-40 years of age). Clinical pregnancy rates were compared between the ET and FET groups that were matched for age. 1263 patients 40 years of age or less who underwent ET or FET in our center from Jan 2010 to March 30, 2013 were included. Of the 1263 patients, 682 received ET and 581 received FET. Embryos were slow frozen or vitrified using the Cryotop method (Cryotop, HSV, homemade straws etc). Patients were divided into three age groups (35, 35-37 and 38-40 years of age). Clinical pregnancy rates were compared between the ET and FET groups that were matched for age. ResultsTabled 1Comparisons of clinical outcomes between ET and FET patientsAge (year)TansferNo. of cyclesNo. of transferred embryosClinical pregnancy rate (%)<35ET2872.0±0.653.3FET3042.1±0.963.2P valueP=0.099P=0.01735-37ET1822.3±0.848.4FET1482.0±0.850.7p valueP=0.001P=0.37938-40ET2132.9±1.238.0FET1292.5±1.248.8p valueP=0.001P=0.032 Open table in a new tab ConclusionOur data demonstrated a significantly greater chance of clinical pregnancy in patients who underwent a FET than with ET. This suggests that endometrial receptivity may be impaired in ET patients after ovarian stimulation. To maximize the probability of pregnancy, postponing fresh transfer and freezing all embryos for future transfer should be considered. Our data demonstrated a significantly greater chance of clinical pregnancy in patients who underwent a FET than with ET. This suggests that endometrial receptivity may be impaired in ET patients after ovarian stimulation. To maximize the probability of pregnancy, postponing fresh transfer and freezing all embryos for future transfer should be considered.

To determine the effects of elevated serum progesterone (P4) at the day of hCG trigger on the clinical outcomes following IVF-ET. Retrospective case control study. We reviewed 655 IVF-ET cycles. The thresholds of serum P4 were set at 1.4, 2.0 and 2.5 ng/ml. Patients with a level of P4 less than the threshold were subjected to control group, and those higher than threshold were subjected to elevated p4 group. The clinical outcomes between two groups were compared. The total number of retrieved oocytes was significantly higher in elevated P4 group (18.8±10.8, 22.2±10.8 and 25.2±10.8) than in control(12.2±7.7, 14.0±9.1 and 14.8±9.5) (p=0.000). The number of blastocysts was significantly higher in elevated P4 group (4.5±4.5, 5.6+5.5 and 6.2±5.9) than in control (2.7±3.1, 3.2±3.5 and 3.2±3.6) (p=0.000). However, when the thresholds were set to 2.0 and 2.5ng/ml, the clinical pregnancy rate was lower in the elevated P4 group (41.6% and 37.3%) than in control (46.3% and 46.0%), but the difference were not statistically significant (p=0.197and p=0.144).Tabled 1Outcome of ET cycles in women with different P4 levels on the hCG dayNumber of cyclesClinical pregnancy rate (%)Total blastocyst numberNumber of retrieved oocytesFertilization rate (%)P4≤1.4321 (49%)44.52.7±3.112.2±7.777.8±22P4>1.4334 (51%)46.14.5±4.518.8±10.878.8±20P valueP=0.374P=0.000P=0.000P=0.054P4≤2.0523 (79.8%)46.33.2±3.514.0±9.179.4±21.2P4>2.0132 (20.2%)41.75.6±5.522.2±10.874.2±19.5P valueP=0.197P=0.000P=0.000P=0.195P4≤2.5604 (92.2%)46.03.2±3.614.8±9.578.6±21.1P4>2.551 (7.8%)37.36.2±5.925.2±10.876.1±19.6P valueP=0.144P=0.000P=0.000P=0.491 Open table in a new tab Our data demonstrated that higher serum P4 reflects good follicular recruitment and better chance of obtaining blastocysts. It also suggested that elevated P4 may adversely affect pregnancy rate. However, the difference was not sufficient to warrant a intervention such as deferring fresh embryo transfer and freezing embryos for future transfer.

OBJECTIVE(S): To compare the implantation rate as function of patient age between cleavage stage and blastocyst stage embryo transfer (ET). DESIGN: Retrospective chart review study of 969 consecutive fresh IVF/ICSI cycles. SETTING: Private IVF clinic. PATIENT(S): Patients underwent 969 fresh IVF/ICSI cycles in a private fertility clinic between 2007 and 2008. INTERVENTION(S): Embryo culture and ET at cleavage stage versus blastocyst stage in a triple gas system. MAIN OUTCOME MEASURE(S): Implantation rate (IR) (defined as fetal cardiac activity 5 to 6 weeks post ET) as a function of maternal chronological age. RESULT(S): Tabled 1Age groupCleavage Stage or Blastocyst ETCyclesTotal # of embryos transferred# of Clinical pregnancies# of heart beatsAverage # of embryos transferredImplantation RateP valueDonor groupD3/D4 ET205712/20132.913/57 (22.8%)(P=0.02)D5 ET162362121/1621792.2179/362 (49.4%)<35y groupD2/D3/D4 ET9228341/92583.158/283 (20.5%)(P=0.008)D5 ET183433105/1831422.4142/433 (32.8%)35-37yD2/D3/D4 ET8828035/88453.245/280 (16.1%)(P=0.02)D5 ET7017336/70482.548/173 (27.7%)38-40yD2/D3/D4 ET11342739/113535.153/427 (12.4%)(P=0.36)D5 ET4816023/48263.326/160 (16.3%)>40yD2/D3/D4 ET16062130/160283.928/621 (4.5%)(P=0.15)D5 ET3314916/33124.512/149 (8%) Open table in a new tab The implantation rate was significantly higher for day 5 blastocyst versus day 3 ET in donor ova cycles and in patient 37 years old and younger. Despite a favorable trend, the implantation rate was not improved in day 5 blastocyst versus day 3 ET cycles for patients 38 years of age and older. CONCLUSION(S):(1)In patients 37 years of age or younger and patients using donor ova, blastocyst transfer was associated with higher implantation rates when compared to cleavage stage ET.(2)Lower numbers of embryo were transferred in the blastocyst stage ET group compared with the cleavage stage ET groups, with the exception of patients over 40 year old.(3)Efficiency, in terms of embryo utilization, is improved by day 5 blastocyst transfer. This may be attributed to a) better selection of viable embryo(s) for ET, and (b) better synchronization of embryo placement and endometrial receptivity.

OBJECTIVE: To compare the pregnancy rates of 990 fresh IVF/ICSI with 212 FET blastocyst transfers as a function of patient age. DESIGN: Ongoing longitudinal review. MATERIALS AND METHODS: From Jan. 2007 to Dec. 2008, an extended culture with triple gas system was used for 990 fresh IVF/ICSI cycles. After transfer the left blastocysts were cryopreserved by slow rate method. At the same time, 212 blastocyst FET cycles were completed. Main outcome measures: clinical pregnancy rate (CPR) (defined as viable delivery and/or ongoing pregnancy). RESULTS: The pregnancy rates of different patient age groups are shown in table 1 for donor and non-donor cycles. Table 1: Pregnancy results by age group in 990 fresh IVF/ICSI cycles and 212 blastocyst FET cycles.Table 1Pregnancy results by age group in 990 fresh IVF/ICSI cycles and 212 blastocyst FET cycles.Donor<35 yrs35-37 yrs38-40yrs≥41 yrsTotalFresh Cycle #187273164162204990Fresh Cycle Pregnancy rate142 (76%)178 (65.2%)89 (54.3%)76 (46.9%)58 (28.4%)543 (54.8%)Fresh Cycle CPR129 (69%)148 (54.2%)66 (40.2%)58 (35.8%)40 (19.6%)441 (44.5%)FET Cycle #5289271810212Blastocysts thawed147267734737571Survived # (rate)137 (93.2%)242(90.6%)67(91.8%)38(80.9%)36(97.3%)520(91.1%)Average ET#2.52.62.523.62.4FET Pregnancy rate34 (65.4%)64 (71.9%)18 (66.7%)10 (55.6%)3 (30%)129 (60.8%)FET CPR31 (59.6%)55 (61.8%)14 (51.9%)9 (50%)2 (20%)111 (52.4%) Open table in a new tab CONCLUSIONS: Fresh CPR was similar to FET CPR in the Donor group (69% vs. 59.6%, P =0.6536). No significant differences in CPR were found in all age groups between fresh and cryopreserved embryo transfer cycles. Effective blastocyst cryopreservation is a highly effective method to increase the cumulative clinical pregnancy rate per ova retrieval.

OBJECTIVE: This is a case report of a frozen-thawed day 7 blastocyst transfer resulting in an ongoing twin pregnancy. DESIGN: Private IVF clinic. MATERIALS AND METHODS: The patient is a 30 year old nulligravida female with two years of primary infertility whose husband has male factor infertility. Semen parameters on the day of ova retrieval revealed a sperm density of 2 million per ml with 20% progressive motility. In January 2008, she received a total of 2025 IU of gonadotropins using a GnRH antagonist protocol, 18 oocytes were retrieved. 12 metaphase-II oocytes were injected via intracytoplasmic injection (ICSI) using her husband's sperm. After ICSI, oocytes were cultured in Life Global (LG) medium supplemented with Serum Substitute Supplement (SSS, Irvine Scientific, Cat #99193) and 3% Human Serum Albumin (HSA, Irvine Scientific, Cat#9988). Eleven two-pronuclear stage embryos were observed 18h after ICSI. On day 3, embryos were transferred into fresh LG medium for continuous culture. On day 5, one early blastocyst and two morula stage embryos were selected for embryo transfer (ET). On day 6 of culture, the leading embryos had reached the early blastocyst stage and were not deemed suitable for cryopreservation. Therefore, the remaining embryos were cultured until Day 7. On Day 7, three expanded blastocysts were cryopreserved using blastocyst freezing media F1 and F2 (Irvine Scientific, Cat#90108) and a slow freezing protocol. RESULTS: The patient did not conceive in the fresh cycle. Forty one days later she completed a frozen embryo transfer cycle following endometrial priming with I.M. estradiol valerate and I.M. progesterone. Three, day 7 blastocysts were thawed on the morning of transfer using blastocyst thawing solution T1 and T2 (Irvine Scientific, Cat#90110). All three blastocysts survived and re-expanded prior to ET. Assisted hatching was performed one hour prior to ET on all embryos using acid Tyrode's solution. 12 days after ET, the patient's serum hCG level was 772 mIU/ml. Thirty-four days after ET, two gestational sacs with fetal cardiac activity were observed via transvaginal ultrasound. Forty-five days after ET, at 10 and 4/7 weeks gestation, a viable diamniotic dizygotic twin gestation was confirmed. The patient was then referred for obstetrical care. CONCLUSIONS: An ongoing clinical diamniotic dizygotic twin gestation was established using cryopreserved-thawed day 7 blastocysts. Day 7 blastocysts may be considered for cryopreservation, especially from patients of young reproductive age.

Objective: To optimize ongoing clinical pregnancy rates in an unselected IVF population, we retrospectively compared two different media formulations (P1/G1/G2 sequential and LifeGlobal medium), contrasted a 6% CO2 in air with a 6% CO2/5% O2/89% N2 gas incubator environment, and finally evaluated the effectiveness of two different types of incubators (Sanyo MCO-5M vs. Hearus 240). Over a 1-year period between April 2006 and March 2007, treatments were applied in quarterly increments. Methods: All patients experienced controlled ovarian hyperstimulation, followed by egg retrieval 35 h after hCG. Eggs were recovered and placed in P1 medium + 5% HSA until insemination. Eggs were moved to a more complex medium containing 5% HSA/5% SS after ICSI or after IVF fertilization check. Embryos were evaluated on day 3 and transfered on day 3 to 5 depending on the number/quality of embryos available and the IVF history of the patient. Transfers were performed under ultrasound guidance, primarily using a Wallace catheter. Results: Tabled 1Age <35 yr + donor cyclesAge <38 yr + donorsCategorynn (%) + b-hCGn (%) OngPregnn (%) + b-hCGn (%) OngPreg6% CO2/air incubation[2ndQrt06]P1/G1/G2 media4940 (82)aSignificant difference (P<.05) within column subsection.31 (63)aSignificant difference (P<.05) within column subsection.7554 (72)42 (56)[4thQrt06]Global medium4929 (59)24 (49)6542 (65)33 (51)6% CO2/5% O2/90% N2 incubation[1stQrt07]Sanyo Mini2922 (76)21 (72)aSignificant difference (P<.05) within column subsection.3825 (66)24 (63)[LG media]Heraeus 2402115 (71)13 (62)3224 (75)aSignificant difference (P<.05) within column subsection.20 (63)Combined TG5037 (74)34 (68)7049 (70)44 (63a Significant difference (P<.05) within column subsection. Open table in a new tab Conclusions: Overall, both the P1/G1/G2 sequential system and the LG all-in-one medium produced good pregnancy rates under standard 6% CO2 in air conditions. In contrast, the LG system with tri-gas incubation significantly improved pregnancy outcomes by reducing SABs and biochemical pregnancies (50% decrease), resulting in higher ongoing clinical pregnancy rates. No difference was observed in the type of incubator used; however, this is one of the first reports validating the clinical effectiveness of the new Sanyo mini-incubators.

OBJECTIVE: To present the first known case of a viable triamniotic/monochorionic triplet pregnancy case after single embryo transfer.DESIGN: Case Report.MATERIALS AND METHODS: A 35-year-old Gravida 1 Para 1 with approximately one year of secondary infertility. Her husband has a history of mild male factor. Her first baby was conceived on the fifth cycle of controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI). She generally had generated one to three mature follicles at the time of HCG trigger with aggressive doses of gonadotropins (300 to 450 IU daily). The patient breastfed for one year and then began to pursue fertility in 2004. She had an elevated day 3 FSH (12 mIu/mL) in September, 2006. She completed two additional cycles of COH/IUI cycles prior to proceeding to IVF/ Intracytoplasmic Sperm Injection (ICSI) treatment. She received 7195 IU of gonadotropins with a GnRH antagonist protocol. On October 12, 2006 three ova were retrieved. Post wash semen sample revealed 14 million spermatozoa/mL, with 35% progressive motility, with < 5% normal morphology. ICSI was performed on two metaphase-2 oocytes (the third oocyte was atretic). One two-pronuclear embryo was observed 18hrs post-ICSI. The embryo was cultured in Life Global medium with 5% Serum Substitute Supplement (SSS, Irvine Scientific, Cat #99193) and 3% Human Serum Albumin (HSA, Irvine Scientific, Cat#9988). One four-cell good quality embryo was transferred following assisted hatching (with acid Tyrode's solution) 47 hours post ova retrieval.RESULTS: The patient's serum hCG level was 120 mIU/ml on 10/26/2006, twelve days after embryo transfer. On 12/04/2006, at 9 weeks 3 days gestation, a transvaginal ultrasound confirmed a triamniotic/monochorionic triplet pregnancy, each with fetal cardiac activity. The patient subsequently delivered monozygotic female triplets on May 20, 2007 at 33 weeks and 3 days gestation via cesarean section. All three infants were eventually discharged in good condition and have had no identifiable neurological or physical abnormalities.CONCLUSIONS: To our knowledge, this is the first known case of viable triamniotic/monochorionic triplet pregnancy following a single embryo transfer in IVF-ET. OBJECTIVE: To present the first known case of a viable triamniotic/monochorionic triplet pregnancy case after single embryo transfer. DESIGN: Case Report. MATERIALS AND METHODS: A 35-year-old Gravida 1 Para 1 with approximately one year of secondary infertility. Her husband has a history of mild male factor. Her first baby was conceived on the fifth cycle of controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI). She generally had generated one to three mature follicles at the time of HCG trigger with aggressive doses of gonadotropins (300 to 450 IU daily). The patient breastfed for one year and then began to pursue fertility in 2004. She had an elevated day 3 FSH (12 mIu/mL) in September, 2006. She completed two additional cycles of COH/IUI cycles prior to proceeding to IVF/ Intracytoplasmic Sperm Injection (ICSI) treatment. She received 7195 IU of gonadotropins with a GnRH antagonist protocol. On October 12, 2006 three ova were retrieved. Post wash semen sample revealed 14 million spermatozoa/mL, with 35% progressive motility, with < 5% normal morphology. ICSI was performed on two metaphase-2 oocytes (the third oocyte was atretic). One two-pronuclear embryo was observed 18hrs post-ICSI. The embryo was cultured in Life Global medium with 5% Serum Substitute Supplement (SSS, Irvine Scientific, Cat #99193) and 3% Human Serum Albumin (HSA, Irvine Scientific, Cat#9988). One four-cell good quality embryo was transferred following assisted hatching (with acid Tyrode's solution) 47 hours post ova retrieval. RESULTS: The patient's serum hCG level was 120 mIU/ml on 10/26/2006, twelve days after embryo transfer. On 12/04/2006, at 9 weeks 3 days gestation, a transvaginal ultrasound confirmed a triamniotic/monochorionic triplet pregnancy, each with fetal cardiac activity. The patient subsequently delivered monozygotic female triplets on May 20, 2007 at 33 weeks and 3 days gestation via cesarean section. All three infants were eventually discharged in good condition and have had no identifiable neurological or physical abnormalities. CONCLUSIONS: To our knowledge, this is the first known case of viable triamniotic/monochorionic triplet pregnancy following a single embryo transfer in IVF-ET.

Background: Ectopic pregnancy occurs in approximately 4–11% of pregnancies after IVF. Risk factors for EP after IVF have been studied in several case series and include history of tubal factor infertility, increased age, decreased parity, history of myomectomy, and the use of assisted hatching. Studies of subsequent pregnancies after an EP have suggested that factors predicting unfavorable pregnancy outcomes include increased age, history of pelvic inflammatory disease, history of infertility, and tubal damage.Objective: To study the risk factors for EP in patients undergoing IVF in one center and to evaluate their subsequent pregnancy outcomes.Materials and Methods: After reviewing data from 855 cycles in one center from October, 2004 through September, 2006, 13 consecutive cases of EP were reviewed. Data collected from charts included age; infertility diagnoses; duration of infertility; pregnancy history; in utero DES exposure; tobacco use; history of intrauterine device and oral contraceptive use; history of and current tubal pathology; history of genital infection; surgical history; IVF parameters; location, diagnosis, and treatment of EP; and subsequent pregnancies.Results: The most common risk factors for EP were tubal factor infertility (54%), prior tubal surgery (38%), and tubal pathology at the time of IVF (54%). A previous EP had occurred in 23% of cases. Assisted hatching was used in 23% of all EP cases. Ninety-two percent of EPs were treated with methotrexate, while the remainder was treated by laparoscopy. Of those treated with methotrexate, 33% then required laparoscopy and salpingostomy. Tubal rupture occurred in 8% of cases. Subsequent pregnancy outcomes included spontaneous viable intrauterine pregnancy in 15%, viable pregnancy following IVF in 15%, missed abortions following IVF in 31%, and no further pregnancies in 39%.Conclusion: Pre-existing tubal disease was an important risk factor for the development of an EP following IVF pregnancies. EP rarely recurred, and approximately one-third of patients subsequently had viable pregnancies, either spontaneously or following IVF. This information should facilitate the counseling of patients undergoing IVF regarding their risk of EP and guide their expectations for future fertility when an EP does occur. Background: Ectopic pregnancy occurs in approximately 4–11% of pregnancies after IVF. Risk factors for EP after IVF have been studied in several case series and include history of tubal factor infertility, increased age, decreased parity, history of myomectomy, and the use of assisted hatching. Studies of subsequent pregnancies after an EP have suggested that factors predicting unfavorable pregnancy outcomes include increased age, history of pelvic inflammatory disease, history of infertility, and tubal damage. Objective: To study the risk factors for EP in patients undergoing IVF in one center and to evaluate their subsequent pregnancy outcomes. Materials and Methods: After reviewing data from 855 cycles in one center from October, 2004 through September, 2006, 13 consecutive cases of EP were reviewed. Data collected from charts included age; infertility diagnoses; duration of infertility; pregnancy history; in utero DES exposure; tobacco use; history of intrauterine device and oral contraceptive use; history of and current tubal pathology; history of genital infection; surgical history; IVF parameters; location, diagnosis, and treatment of EP; and subsequent pregnancies. Results: The most common risk factors for EP were tubal factor infertility (54%), prior tubal surgery (38%), and tubal pathology at the time of IVF (54%). A previous EP had occurred in 23% of cases. Assisted hatching was used in 23% of all EP cases. Ninety-two percent of EPs were treated with methotrexate, while the remainder was treated by laparoscopy. Of those treated with methotrexate, 33% then required laparoscopy and salpingostomy. Tubal rupture occurred in 8% of cases. Subsequent pregnancy outcomes included spontaneous viable intrauterine pregnancy in 15%, viable pregnancy following IVF in 15%, missed abortions following IVF in 31%, and no further pregnancies in 39%. Conclusion: Pre-existing tubal disease was an important risk factor for the development of an EP following IVF pregnancies. EP rarely recurred, and approximately one-third of patients subsequently had viable pregnancies, either spontaneously or following IVF. This information should facilitate the counseling of patients undergoing IVF regarding their risk of EP and guide their expectations for future fertility when an EP does occur.

Background: Although controversial, the guidelines from the American Association of Clinical Endocrinologists (AACE) have suggested lowering the upper reference range of TSH to 3.0 uIU/mL for the diagnosis of hypothyroidism. In reproductive-age women, hypothyroidism has a prevalence that ranges between 7.5–8.5 percent. Hypothyroidism has many sequelae, including infertility and asymptomatic hypothyroidism, that can have adverse effects on the offspring of pregnant women, such as diminished cognitive function.

Background: In an attempt to correct for the iatrogenic luteal phase defect induced by IVF, a multitude of studies have been conducted to assess the use of progesterone for luteal supplementation. The preponderance of these studies has shown a significant improvement in implantation and pregnancy rates with luteal progesterone supplementation compared to no supplementation (Pritts and Atwood, 2002). The addition of estradiol (E2) for luteal supplementation is more controversial. Studies investigating the addition of E2 (oral or transdermal) to standard progesterone luteal supplementation have been limited, and the results have been conflicting. Several randomized controlled studies have shown significantly higher implantation and pregnancy rates with addition of oral E2 in the luteal phase vs. placebo (Farhi et al., 2000; Lukaszuk et al., 2005) and that increasing the dose of E2 may further improve the outcomes (Lukaszuk et al., 2005). Recently, a large retrospective study by Leondires et al. (2006) showed that E2 supplementation (vs. no supplementation), regardless of ovarian stimulation protocol, increased pregnancy rates. However, a recent prospective study using transdermal E2 showed no benefit vs. placebo (Serna et al., 2006). The inconsistency between the studies showing improved outcome vs. no improvement with luteal phase E2 supplementation appears to be the route of administration (oral vs. transdermal). Objective: To compare the implantation and pregnancy rates of patients who received a combined regimen of oral and transdermal E2 compared with transdermal only E2 regimen. Materials and Methods: A retrospective chart review was performed. Women (40 years or younger with a minimum of 6 oocytes aspirated) who underwent IVF cycles with luteal oral and transdermal estradiol supplementation were identified during the period of August 2006 – November 2006 (Group 1). Group 1 received intramuscular P in oil, 2-mg E2 tablets orally three times a day, and two 0.1-mg transdermal E2 patches every 48 hours until negative pregnancy test or 10 week gestational age (n = 18). Age-matched women undergoing IVF during the same time period were chosen for controls (Group 2). Group 2 received intramuscular P in oil and two 0.1-mg transdermal E2 (n = 19). Patient characteristics, including, age, parity, number of failed ovulation induction cycles, characteristics of the IVF cycle including number of oocytes retrieved and fertilized, number of embryos implanted, and ongoing pregnancy, were recorded. Results: The demographic data between the two groups were similar. The results expressed as mean ± SD or percentages, as appropriate, are summarized below. Group 1 had significantly higher implantation and multiple pregnancy rates. However, the ongoing pregnancy rate was similar between the two groups.Tabled 1Group 1Transdermal/oral E2/PGroup 2Transdermal E2/PNumber of patients1819Age (years)33.2 ± 4.834.2 ± 4.3Peak E2 (pg/mL)3113.6 ± 1607.42364.6 ± 829.5Number of embryos transferred2.7 ± 1.002.7 ± 0.9Implantation rate∗42 (21/50)23 (12/52)Pregnancy rate55 (10/18)47 (9/19)Multiple pregnancy rate∗38 (7/18)10 (2/19) Open table in a new tab ∗ denotes significant P value (<.05). Conclusions: This preliminary data suggests that for luteal phase E2 supplementation combined regimen of luteal phase transdermal and oral E2 improves implantation rates compared to a transdermal E2 regimen. Although the pregnancy rate between the two groups is comparable, the women treated with the combined regimen of transdermal/oral E2 have a higher rate of implantation and multiple gestation.