To determine if measuring the estrogen flare effect after two days of MCD Lupron in fresh IVF cycles is predictive of cycle outcome. Retrospective study in an academic institution. A retrospective analysis of fresh MCD flare cycles (n=326) performed during the years 2006 through 2013 was undertaken. Subgroup analyses were performed on a cohort of patients who did not receive oral contraceptives (OCPs) prior to initiation of the cycle (n=89) versus those who did receive OCPs (n=237). MCD was usually initiated day 1 of the patient's menstrual cycle with baseline estradiol levels obtained. Estradiol levels were then repeated 48 hours later before the initiation of gonadotropins. The percent change in estradiol between these two time points was calculated. Main outcome measures included live birth, number of mature oocytes, number of grade 2 or better blasts and cycle cancellation. Receiver operator characteristic (ROC) curves were used to determine the predictive value of each measure. Of the 326 patients, 72(22%) were cancelled and did not undergo retrieval. Patients were usually cancelled for poor response, defined as 3 or fewer follicles greater than 10mm. The subgroup of patients without OCP priming had 20 cancellations (22%) vs. 51 cancellations (22%) in OCP primed cycles. The area under the curve (AUC) for all patients for cycle cancellation was 0.67. For live birth, number of mature eggs greater than 6, and greater than two blastocysts grade 2 or better, the AUCs were 0.55, 0.56, and 0.58 respectively. Subgroup analysis in patients with no OCP priming showed AUCs for cycle cancellation, live birth, number of mature eggs >6, 2 or blastocysts grade 2 or better were 0.75, 0.59, 0.59, 0.54 respectively. Patients with OCP priming showed AUCs for cycle cancellation, live birth, number of mature eggs > 6, 2 or blastocysts grade 2 or better of 0.68, 0.59, 0.52, and 0.55 respectively. Measuring the estradiol flare during MCD cycles can help to predict cancellation but is not predictive of live births, number of mature eggs > 6 and (2 or more) blastocysts grade 2 or better. Either the test can be abandoned in MCD cycles, or caution must be exercised when interpreting the test for cycle cancellation as the AUC values indicates poor performance of this measure.

Carrier screening for recessive genetic diseases is offered to patients at fertility centers. Couples carrying the same genetic disease have a 25% chance of having an affected child. Such couples have several reproductive options available, including PGD. Our goal was to determine how many such couples pursue PGD. Retrospective. The Illumina Infinium HD Custom Genotyping platform was used to identify 1578 mutations associated with 190 high impact recessive genetic diseases. This analysis includes data obtained from 762 couples referred by fertility centers. Informed consent to utilize data in a de-identified manner was obtained. Carrier couples were identified. Couples that then pursued PGD through our partner laboratory were identified, and their PGD testing outcomes were reviewed. Of the 762 couples, 18 (2.4%) were identified as carriers of the same genetic disease as shown. Of these, 7 couples pursued single gene PGD through our partner laboratory.Table 1Disease# Carrier Samples# PGD SamplesPGD Status/ResultsSickle Cell Disease30Cystic Fibrosis42Preparation Complete, Preparation CompleteNonsyndromic Hearing Loss & Deafness: DFNB1 Related31InitiatedCarnitine Palmitoyltransferase II Deficiency10Familial Dysautonomia11Unaffected Embryos TransferredNiemann-Pick Disease: Type A10Hurler Syndrome11Unaffected/Non-Carrier Polar Bodies SelectedSpinal Muscular Atrophy: SMN1 Linked21InitiatedFamilial Mediterranean Fever10Tay-Sachs Disease11No Unaffected/Chromosomally Normal Embryos AvailableTotal187 Open table in a new tab Results show that 11/18 carrier couples referred by fertility centers chose not to pursue PGD. There are several explanations for this. PGD may not be consistent with a couple's personal beliefs or may not have the financial resources to pursue PGD. Additionally, it is possible that some couples pursued PGD through another laboratory, became pregnant without fertility treatment, or chose not to pursue fertility treatment in general. In this study, at least one affected embryo was detected for each couple that pursued and completed PGD testing, demonstrating the importance of performing PGD testing in these cases.

ObjectiveTo evaluate the utility and efficiency of freezing M1 oocytes as measured by post-thaw fertilization, blastulation and implantation rates. Outcomes are compared to metaphase 2 (M2) oocytes.DesignRetrospective Cohort.Materials and MethodsAutologous oocyte thaw cycles at NYU medical center between 2008 and 2013 were reviewed. 99 patients thawed a total of 144 (MI) and 1008 (M2). Survival, fertilization, cleavage stage and blastocyst formation rate and live birth rates were analyzed and compared to M2 outcomes. Subgroup analysis was completed comparing patients under age 37 to age 37 and older. T-tests of means, were employed.ResultsTabled 1Autologous oocyte thaw outcomes 2008-2013All Patients:FrozenThawedSurvivedFertilizationCleavageBlastocystsTransferredM119914450(35%)25(17%)19(13%)2(1%)3(2%)M210201008805(80%)643(64%)557(55%)197(20%)111(11%)Patients by Age*Survived2PNCleavageBlastocystAge less than 37 M120%5.5%5.5%0%Age 37 and older M124%13%11%2%p-value**0.620.190.290.38Age less than 37 M278%64%53%22%Age 37 and older M283%69%60%19%p-value**0.280.230.180.55*results in percentages **T-test of means. Open table in a new tab ConclusionCryopreservation of MI oocytes has yet to show benefit (no confirmed clinical pregnancy). In our center approx. 23,000 oocytes have been frozen, 14.3% of which are M1. M1 oocytes are therefore responsible for a significant proportion of the work and materials associated with egg freeze/thaw laboratory services, including added storage burden. In addition, patients with stored M1s become hopeful that those eggs will contribute to their success. M2 oocytes, however, continue to show excellent survival, blastocyst formation and clinical pregnancy rates. As more clinical data materializes, the utility of preserving M1 oocytes should be regularly assessed. ObjectiveTo evaluate the utility and efficiency of freezing M1 oocytes as measured by post-thaw fertilization, blastulation and implantation rates. Outcomes are compared to metaphase 2 (M2) oocytes. To evaluate the utility and efficiency of freezing M1 oocytes as measured by post-thaw fertilization, blastulation and implantation rates. Outcomes are compared to metaphase 2 (M2) oocytes. DesignRetrospective Cohort. Retrospective Cohort. Materials and MethodsAutologous oocyte thaw cycles at NYU medical center between 2008 and 2013 were reviewed. 99 patients thawed a total of 144 (MI) and 1008 (M2). Survival, fertilization, cleavage stage and blastocyst formation rate and live birth rates were analyzed and compared to M2 outcomes. Subgroup analysis was completed comparing patients under age 37 to age 37 and older. T-tests of means, were employed. Autologous oocyte thaw cycles at NYU medical center between 2008 and 2013 were reviewed. 99 patients thawed a total of 144 (MI) and 1008 (M2). Survival, fertilization, cleavage stage and blastocyst formation rate and live birth rates were analyzed and compared to M2 outcomes. Subgroup analysis was completed comparing patients under age 37 to age 37 and older. T-tests of means, were employed. ResultsTabled 1Autologous oocyte thaw outcomes 2008-2013All Patients:FrozenThawedSurvivedFertilizationCleavageBlastocystsTransferredM119914450(35%)25(17%)19(13%)2(1%)3(2%)M210201008805(80%)643(64%)557(55%)197(20%)111(11%)Patients by Age*Survived2PNCleavageBlastocystAge less than 37 M120%5.5%5.5%0%Age 37 and older M124%13%11%2%p-value**0.620.190.290.38Age less than 37 M278%64%53%22%Age 37 and older M283%69%60%19%p-value**0.280.230.180.55*results in percentages **T-test of means. Open table in a new tab *results in percentages **T-test of means. ConclusionCryopreservation of MI oocytes has yet to show benefit (no confirmed clinical pregnancy). In our center approx. 23,000 oocytes have been frozen, 14.3% of which are M1. M1 oocytes are therefore responsible for a significant proportion of the work and materials associated with egg freeze/thaw laboratory services, including added storage burden. In addition, patients with stored M1s become hopeful that those eggs will contribute to their success. M2 oocytes, however, continue to show excellent survival, blastocyst formation and clinical pregnancy rates. As more clinical data materializes, the utility of preserving M1 oocytes should be regularly assessed. Cryopreservation of MI oocytes has yet to show benefit (no confirmed clinical pregnancy). In our center approx. 23,000 oocytes have been frozen, 14.3% of which are M1. M1 oocytes are therefore responsible for a significant proportion of the work and materials associated with egg freeze/thaw laboratory services, including added storage burden. In addition, patients with stored M1s become hopeful that those eggs will contribute to their success. M2 oocytes, however, continue to show excellent survival, blastocyst formation and clinical pregnancy rates. As more clinical data materializes, the utility of preserving M1 oocytes should be regularly assessed.

ObjectiveTo compare the clinical outcomes for TE biopsy vs. day 3 embryo biopsy (EB) for preimplantation genetic diagnosis (PGD) of single gene mutations or preimplantation genetic screening (PGS) of all 24 chromosomes including translocations.DesignRetrospective cohort study.Materials and MethodsA total of 185 patients underwent an IVF cycle with PGD or PGS. Group A (n=96; mean maternal age 36.5) underwent EB on day 3 and only euploid or embryos not affected with genetic disease had embryo transfer (ET) on day 5. Group B (n=89; mean maternal age 35) underwent TE biopsy on days 5 and/or 6. Biopsied blastocysts were vitrified shortly after biopsy and only euploid or unaffected blastocysts were transferred in a subsequent FET.ResultsIn Group A, 164 embryos were found to be euploid or unaffected by genetic disease and suitable for fresh ET on day 5 (mean=1.7 embryos/ET). In Group B, 153 vitrified embryos were warmed and transferred (mean=1.4 embryos per FET). There was a significantly higher IR of 48% (74/153) following TE biopsy and vitrification as compared to day 3 EB 36% (59/164) (P=0.0232). Also a significantly higher CPR expressed per retrieval cycle was achieved following warming and FET of TE biopsy with 65% (58/89) pregnancy rate with fetal hearts as compared to 43% (41/96) for the day 3 EB (P=0.0031).ConclusionPGD/PGS analysis of multiple cells biopsied from the TE of blastocysts on days 5 or 6 displayed significantly higher IR and CPR when compared to day 3 EB. Despite vitrification and warming in subsequent cycle, the euploid/unaffected blastocysts transferred following TE biopsy appear to be more viable than those that have day 3 EB with fresh ET. These results validate TE biopsy being a more efficient tool to identify euploid embryos and achieve viable pregnancies. ObjectiveTo compare the clinical outcomes for TE biopsy vs. day 3 embryo biopsy (EB) for preimplantation genetic diagnosis (PGD) of single gene mutations or preimplantation genetic screening (PGS) of all 24 chromosomes including translocations. To compare the clinical outcomes for TE biopsy vs. day 3 embryo biopsy (EB) for preimplantation genetic diagnosis (PGD) of single gene mutations or preimplantation genetic screening (PGS) of all 24 chromosomes including translocations. DesignRetrospective cohort study. Retrospective cohort study. Materials and MethodsA total of 185 patients underwent an IVF cycle with PGD or PGS. Group A (n=96; mean maternal age 36.5) underwent EB on day 3 and only euploid or embryos not affected with genetic disease had embryo transfer (ET) on day 5. Group B (n=89; mean maternal age 35) underwent TE biopsy on days 5 and/or 6. Biopsied blastocysts were vitrified shortly after biopsy and only euploid or unaffected blastocysts were transferred in a subsequent FET. A total of 185 patients underwent an IVF cycle with PGD or PGS. Group A (n=96; mean maternal age 36.5) underwent EB on day 3 and only euploid or embryos not affected with genetic disease had embryo transfer (ET) on day 5. Group B (n=89; mean maternal age 35) underwent TE biopsy on days 5 and/or 6. Biopsied blastocysts were vitrified shortly after biopsy and only euploid or unaffected blastocysts were transferred in a subsequent FET. ResultsIn Group A, 164 embryos were found to be euploid or unaffected by genetic disease and suitable for fresh ET on day 5 (mean=1.7 embryos/ET). In Group B, 153 vitrified embryos were warmed and transferred (mean=1.4 embryos per FET). There was a significantly higher IR of 48% (74/153) following TE biopsy and vitrification as compared to day 3 EB 36% (59/164) (P=0.0232). Also a significantly higher CPR expressed per retrieval cycle was achieved following warming and FET of TE biopsy with 65% (58/89) pregnancy rate with fetal hearts as compared to 43% (41/96) for the day 3 EB (P=0.0031). In Group A, 164 embryos were found to be euploid or unaffected by genetic disease and suitable for fresh ET on day 5 (mean=1.7 embryos/ET). In Group B, 153 vitrified embryos were warmed and transferred (mean=1.4 embryos per FET). There was a significantly higher IR of 48% (74/153) following TE biopsy and vitrification as compared to day 3 EB 36% (59/164) (P=0.0232). Also a significantly higher CPR expressed per retrieval cycle was achieved following warming and FET of TE biopsy with 65% (58/89) pregnancy rate with fetal hearts as compared to 43% (41/96) for the day 3 EB (P=0.0031). ConclusionPGD/PGS analysis of multiple cells biopsied from the TE of blastocysts on days 5 or 6 displayed significantly higher IR and CPR when compared to day 3 EB. Despite vitrification and warming in subsequent cycle, the euploid/unaffected blastocysts transferred following TE biopsy appear to be more viable than those that have day 3 EB with fresh ET. These results validate TE biopsy being a more efficient tool to identify euploid embryos and achieve viable pregnancies. PGD/PGS analysis of multiple cells biopsied from the TE of blastocysts on days 5 or 6 displayed significantly higher IR and CPR when compared to day 3 EB. Despite vitrification and warming in subsequent cycle, the euploid/unaffected blastocysts transferred following TE biopsy appear to be more viable than those that have day 3 EB with fresh ET. These results validate TE biopsy being a more efficient tool to identify euploid embryos and achieve viable pregnancies.

BACKGROUND: Current techniques that analyze all chromosomal abnormalities in blastocyst biopsies still can only achieve an implantation success rate of approximately 80%. It is possible that this is in part due to array CGH, CGH, SNP arrays, and qPCR not being sensitive enough to detect potential abnormalities associated with implantation failure. The higher resolution of whole genome sequencing could help improve the implantation success rate, as well as provide much more detailed analysis of potential genetic abnormalities. OBJECTIVE(S): To show in a proof-of-principle manner that a complete whole genome sequence can be obtained from a blastocyst and that a known genetic mutation within some of the blastocysts can be identified. MATERIAL AND METHODS: Two DNA amplification METHODS were compared to see which one generates sufficient quality template DNA for whole genome sequence analysis using Complete Genomics' DNA nanoarray sequencing platform (1). The METHODS were SurePlex, which is commonly used for array CGH, and a modified multiple displacement amplification (MDA) (2). 10-20 cells were biopsied from embryos affected with the R-1MT mutation of Myotonic Dystrophy. The samples were lysed and the DNA denatured in a single tube. Approximately 2 ug of DNA were generated by both amplification METHODS. Prior to whole genome sequence analysis, amplified samples were screened with 96 independent qPCR markers spread across the genome to select samples with the lowest amount of bias. Briefly, we determined the average cycle number across the entire plate and subtracted that from each individual marker to compute a “delta cycle” number. The delta cycle was plotted against the GC content of the 1000 base pairs surrounding each marker. This gave us a sense of the relative GC bias of each sample. To get a sense of the overall “noise” of the samples, the absolute value of each delta cycle was summed to create the “sum of deltas” measurement. From our experience, a low sum of deltas and a relatively flat plotting of the data against GC content yields a well-represented whole genome sequence. The best amplified samples were processed by Complete Genomics at their Mountain View, CA sequencing facility as previously described (1). RESULT(S): The sum of deltas was 61 for the MDA method and 287 for the SurePlex. As such, the MDA method was used to amplify the rest of the samples and process them for complete genome sequencing. The results of the sequencing process are expected by the end of December 2010. CONCLUSION(S): Although PGD with whole genome sequencing is currently cost prohibitive, one could amplify DNA, separate an aliquot for analysis by current METHODS, and then sequence the remaining few normal embryos, in order to lower the cost of the procedure. SUPPORT: Departmental funds1.Drmanac et al. (2010) Science 327, 78-81.2.Dean et al. (2002) Proc Natl Acad Sci U S A 99, 5261-5266.

OBJECTIVE: The 24C PGS panel (array CGH and microarray with parental analysis) provides considerably more information about the genetic make-up of an embryo than the 5, 9 or 12C panel. However, what impact the additional abnormalities detected have on IVF outcome is unknown. We analyzed association of 24C on % normal embryos, number of embryos transferred (#ET), IR and CPR in patients undergoing PGS to detect aneuploidy. DESIGN: Retrospective. MATERIALS AND METHODS: Data from all PGS IVF cycles from Jan 2009-Apr 2010 (n=142) were collected and grouped by assay (5, 9, 12, or 24C). Embryo biopsies were performed on day 3 and fresh ET on day 4 or 5. PGS results, #ET, IR, and CPR were analyzed. Cycles with incomplete data or PGD for single gene disorders, translocations, or Fragile X were excluded, yielding 99 cycles for analysis. Chi2 or students' ttest were performed as appropriate. RESULTS: There were no differences noted in the baseline characteristics of age (mean 38.1y) or # of embryos analyzed (mean 10.2 per cycle) among groups. Overall IR and CPR were 40 and 36% respectively (49 and 45% excluding cycles resulting in no ET), compared with 65 and 57% for all non-PGS IVF cycles over the same time period. Average #ET per cycle was 1.5. No significant difference was observed in these endpoints associated with # of chromosomes evaluated by PGS.Tabled 1PGS results and ET by Assay24C (n=20)12C (n=42)9C (n=28)5C (n=9)% Normal embryos per cycle16 (p=.01)233159 (p<.001)% Cycles where an embryo w/abnl or incomplete results was transferred25 (p<.01)700p values are given only where statistical significance was attained. Open table in a new tab p values are given only where statistical significance was attained. CONCLUSION: 24C yielded fewer "normal" embryos, and ET of embryos with incomplete or abnormal results were increased by use of these assays; however, #ET, IR, and CP were unaffected. These preliminary results are reassuring. Our ongoing analysis of 24C PGS cycles, incorporating live birth and miscarriage rates, will further evaluate clinical utility of this novel diagnostic tool.

OBJECTIVE: To report on our results using enhanced oocyte screening methods and to assess the value of such measures in a large oocyte donation program. DESIGN: Retrospective analysis at a university-based IVF center from 1997-2006. MATERIALS AND METHODS: After passing initial questionnaire screening, donor candidates were examined in accordance with ASRM guidelines, which included a health status questionnaire, on-site consultation and examination with a physician and psychologist, and the mandatory tests for infectious disease, drug use, and cystic fibrosis. Enhanced screening included: face to face consultations with a genetic counselor, the Minnesota Multiphasic Personality Inventory (MMPI), universal screening for Tay Sachs, Fragile X (as of 2005), and karyotypic abnormalities. Recipient husbands were tested in the case of Ashkanazi matches. RESULTS: Of 1,071 candidates presenting for on-site evaluation, 511 (48%) passed the screening process, of whom 474 (93%) donated. Twenty percent (n=212) of candidates withdrew their applications, and 560 (32%) failed screening. Candidates failed due to genetic factors (11%), psychological factors (10%), medical conditions (6%), infectious diseases (3%), and positive drug screens (2%). Of the 121 candidates rejected for genetic factors, 68 were for abnormal genetic testing and 53 for a personal/family history suggestive of a transmissible genetic trait, such as dyslexia, early cardiac disease, and aggressive cancers. There were 29 cystic fibrosis mutation carriers, and 12 abnormal hemoglobin electrophoresis patterns. Enhanced screening accounted for 21% of the genetic exclusions, with 9 Tay Sachs carriers, 6 inconclusive Tay Sachs results, 8 abnormal karyotypes, and 2 Fragile X carriers (intermediate range). Of the 112 candidates excluded for psychological factors, 24 had a personal history of a psychological disorder, 28 with unacceptable behavioral traits, and 44 with a family history of psychological disorders. Enhanced screening accounted for 14% of the psychological exclusions, as 16 had an elevated MMPI score. CONCLUSIONS: While enhanced oocyte donor screening uncovers a significant number of donors with potential problems, it also reduces the numbers of available donors. Programs may want to use the information presented here to determine if some or all of the elements of enhanced donor screening should be incorporated into their protocols.

The chance for conception with IVF is improved by transferring more than one embryo to the uterus but this practice carries the risk of high order multiple gestation (HOMG). Effective 2000, we decided to transfer one fewer embryo on day 5, post-oocyte retrieval (D5ET) than the traditional number on day 3. From 1999 to 2003, this resulted in a 58% decline in HOMG, while maintaining the overall clinical pregnancy (CP, +fetal heartbeat) rate at 47%. The current data extends our results through 2006. Retrospective analysis of 2958 fresh D5ETs at a University-based IVF program. Ovarian stimulation, egg retrieval and insemination were performed using standard IVF protocols. Embryo culture was in Quinn's cleavage media from days 1–3 post-egg retrieval and, if performed, in Quinn's blastocyst media on days 4–6. Culture to blastocyst was extended when there were more embryos than we were willing to transfer on D3; patients with fewer embryos had D3ET (n = 1041). On D5 blastocysts were graded on size and trophectoderm+inner cell mass status. In 96 cycles, ET was delayed to D6 for better embryo selection. The # embryos transferred were:1–2 for ≤37 yrs and donor egg recipients (OR); 2–3 for 38–40 yrs and 3 + for ≤41 yrs. CP, implantation (sac/embryo transferred) and twin and triplet CP rates were calculated. D5ET rate was highest in young patients <40 yrs and OR, groups known to have the greatest pregnancy potential but with a significant risk for HOMG. The % D5/6ET for all patient groups has increased by ∼10% since 2003 when we lowered our criteria for culture extension. Triplet CP rates for each group were dramatically reduced when compared to the mean 1999 rate of 14%; significantly, 24/67 (36%) triplet CPs resulted from a 2 ET on D5. Patients ≤42 yrs with supernumerary cryopreserved embryos had a CP rate >70%. Extended embryo culture generates high pregnancy and implantation rates even when few embryos are transferred to reduce the risk of HOMG. However, twin pregnancy rates were high in OR and patients up to 42 yrs and this observation suggests that, in the future, a single embryo transfer may be a more suitable option for these patient groups.

We describe our experience of over 300 cycles of preimplantation genetic diagnosis (PGD) and report clinical pregnancy rates (35%-67%) that support using this technology to screen for genetic disorders and chromosomal abnormalities. In clinical practice for over ten years, PGD offers couples the earliest form of genetic screening and may help improve ongoing pregnancy rates in poor-prognosis patients.

Objective: An association between the rate of embryo development in vitro and gender has been suggested by observations in domestic animals that male embryos develop faster than female siblings. In our IVF program, embryos selected for transfer on Day 3 are chosen on the basis of quality; blastomere number routinely ranges between 5 and 9 cells and embryos with larger cell numbers are rarely transferred. However, on Day 5 embryo selection is primarily based on developmental stage and the most advanced stage blastocysts are preferentially transferred. This study assesses whether these different embryo selection strategies impact on the gender ratio observed at birth. Design: Retrospective analysis of live birth outcomes of IVF and donor oocyte (OD) cycles conducted at a large university-based IVF program in 2000–2001. Materials and Methods: At cycle onset, all IVF patients and OD recipients are eligible for a Day 5 embryo transfer (ET); however, depending on oocyte number, fertilization rate and subsequent embryonic development, the transfer may be converted to Day 3. As a general policy, patients with 3 or more 6–8 cell embryos (grade 2.5 or better) on Day 3 continue to a Day 5 ET, otherwise their best quality embryos are hatched and transferred that day. On Day 5, the most advanced blastocysts are selected for ET since implantation and pregnancy rates are highest when advanced stage blastocysts (Stage 3–5) are transferred. This analysis includes all Day 3 and Day 5 ETs which resulted in the live birth of an offspring of known gender. Data were analyzed by X2 test. Results: Day 3 ETs resulted in gender ratios of 243:234 and 43:34 for IVF patients and OD recipients. In contrast, the respective ratios for Day 5 ETs, 278:203 and 113:70, reflected significantly greater tendencies for male offspring. Similar ratios were noted when Day 5 ET cycles were separately analyzed as ICSI and non-ICSI cycles. Stage 3–5 blastocysts were transferred in ∼70% of the Day 5 ETs, but statistically significant relationships did not exist between blastocyst stage and gender. Tabled 1 Conclusion: Our data indicates that, for Day 5 ET, selecting embryos according to developmental status only skews the sex ratio of the offspring to favor males. The observation that this pattern persists in ICSI and non-ICSI cases suggests that in humans, the rate of development through early embryogenesis varies between male and female embryos.

Objective: To determine whether there was a difference in IVF outcome with transfer of embryos on day 3 (D3) vs. day 5 (D5) in patients who had a borderline quality and/or number of embryos on D3.Design: Retrospective analysis of data on IVF cycles during 2001 at a large University-based IVF program. Cycles in which embryo quality and/or number was borderline were studied in detail.Materials/Methods: In January, 2001, specific prospective criteria were put in place concerning IVF cycles in which embryo culture extended to D5 for the purpose of blastocyst (BL) transfer. These criteria were: patients up to age 42 were eligible for BL transfer providing they had 5 or more 6–8 cell embryos (grades:1- 3) on D3 of which 3 or more 6–8 cell embryos (grades: 1–2.5). Day 3 embryos in thirty five patients only partially met the criteria to go on to day 5, either due to sub adequate embryo quality but adequate number, or adequate quality but too few in number. The decision to proceed to day 5 was made by the clinical judgement of the physician on day 3. Nineteen patients had embryos transferred on D3 (group I) and 16 on D5 (group II). Parameters examined included patient age, prior IVF history, baseline FSH, baseline and peak serum estradiol levels, number of eggs retrieved, use of ICSI, fertilization rate, number of embryos transferred, pregnancy rate (defined by documentation of fetal cardiac activity), number of multiple gestations, availability of embryos for cryopreservation, and the degree of difficulty at the time of transfer. Chi-square and t-tests were used; P <0.05 was considered significant.Results: The pregnancy rate did not differ between Group II (D5, 63%) and Group I (D3, 47%) embryo transfers even though Group II patients had significantly fewer number of embryos transferred (3 ± 1 vs. 4 ± 1). There were no triplet gestations and the twinning rate was the same in both groups (3/9 in Group I and 4 /10 in Group II). In addition, there was no significant group I vs group II difference with respect to patient age (37 ± 3 vs. 35 ± 4 years), prior history of an IVF cycle (14 /19 vs. 7/16 patients ), base line FSH (7 ± 2 vs. 5 ± 2 mIU/mL), peak serum estradiol (1480 ± 680 vs. 1490 ± 622 pg/ml), number of eggs retrieved (11 ± 4 vs. 10 ± 5 ), incidence of ICSI (5/19 vs. 6/16 cycles), the availability of embryos for cryopreservation (1/19 patients vs, 1/16 cycles ), and the degree of difficulty at embryo transfer. However, baseline estradiol levels were significantly greater in group I (34 ± 13 vs. 25 ± 6 pg/ml) and fertilization rate was greater in group II (63 ± 19 % vs. 78 ± 12% ).Conclusions: In a program utilizing blastocyst transfer, extending embryo culture in patients with borderline embryo quality and or number does not adversely affect IVF outcome. In fact, with time the pregnancy rate may ultimately prove to be higher with D5 embryo transfer in these patients. D5 transfers limit the number of embryos transferred, thereby minimizing the risk of a high order pregnancy.Supported by: None. Objective: To determine whether there was a difference in IVF outcome with transfer of embryos on day 3 (D3) vs. day 5 (D5) in patients who had a borderline quality and/or number of embryos on D3. Design: Retrospective analysis of data on IVF cycles during 2001 at a large University-based IVF program. Cycles in which embryo quality and/or number was borderline were studied in detail. Materials/Methods: In January, 2001, specific prospective criteria were put in place concerning IVF cycles in which embryo culture extended to D5 for the purpose of blastocyst (BL) transfer. These criteria were: patients up to age 42 were eligible for BL transfer providing they had 5 or more 6–8 cell embryos (grades:1- 3) on D3 of which 3 or more 6–8 cell embryos (grades: 1–2.5). Day 3 embryos in thirty five patients only partially met the criteria to go on to day 5, either due to sub adequate embryo quality but adequate number, or adequate quality but too few in number. The decision to proceed to day 5 was made by the clinical judgement of the physician on day 3. Nineteen patients had embryos transferred on D3 (group I) and 16 on D5 (group II). Parameters examined included patient age, prior IVF history, baseline FSH, baseline and peak serum estradiol levels, number of eggs retrieved, use of ICSI, fertilization rate, number of embryos transferred, pregnancy rate (defined by documentation of fetal cardiac activity), number of multiple gestations, availability of embryos for cryopreservation, and the degree of difficulty at the time of transfer. Chi-square and t-tests were used; P <0.05 was considered significant. Results: The pregnancy rate did not differ between Group II (D5, 63%) and Group I (D3, 47%) embryo transfers even though Group II patients had significantly fewer number of embryos transferred (3 ± 1 vs. 4 ± 1). There were no triplet gestations and the twinning rate was the same in both groups (3/9 in Group I and 4 /10 in Group II). In addition, there was no significant group I vs group II difference with respect to patient age (37 ± 3 vs. 35 ± 4 years), prior history of an IVF cycle (14 /19 vs. 7/16 patients ), base line FSH (7 ± 2 vs. 5 ± 2 mIU/mL), peak serum estradiol (1480 ± 680 vs. 1490 ± 622 pg/ml), number of eggs retrieved (11 ± 4 vs. 10 ± 5 ), incidence of ICSI (5/19 vs. 6/16 cycles), the availability of embryos for cryopreservation (1/19 patients vs, 1/16 cycles ), and the degree of difficulty at embryo transfer. However, baseline estradiol levels were significantly greater in group I (34 ± 13 vs. 25 ± 6 pg/ml) and fertilization rate was greater in group II (63 ± 19 % vs. 78 ± 12% ). Conclusions: In a program utilizing blastocyst transfer, extending embryo culture in patients with borderline embryo quality and or number does not adversely affect IVF outcome. In fact, with time the pregnancy rate may ultimately prove to be higher with D5 embryo transfer in these patients. D5 transfers limit the number of embryos transferred, thereby minimizing the risk of a high order pregnancy. Supported by: None.

Objective: To evaluate whether there are any benefits to distributing the oocytes retrieved during an anonymous oocyte donation cycle to a single recipient rather than sharing among two recipients. Design: Retrospective review of oocyte donation cycles conducted at a large, university- based oocyte donation program. Materials/Methods: All anonymous oocyte donation cycles (n = 221) during 2000 and 2001 were evaluated. There were 100 exclusive (1 recipient) and 121 shared (2 recipients) cycles; of these 2 exclusive and 1 shared donation were used for embryo banking purposes. Data were analyzed by χ2 or the Mann-Whitney Rank-Sum test. Results: Despite differences in egg and embryo number, the clinical pregnancy rate per transfer and the embryo implantation rate were not different between the two groups. While the exclusive group had more cycles with cryopreservation, the absolute difference was only 18%. Shared cycles were significantly more efficient than exclusive, as demonstrated by the doubled pregnancy and implantation rate per retrieval. Conclusions: Sharing oocyte donors is vastly more efficient than using donors for just one recipient. When instituting a shared cycle system, a donor egg program can service considerably more recipients, while offering virtually identical implantation and pregnancy rates. The small loss of opportunity for cryopreservation is more than offset by the large reduction of the cost for a shared donor. The shared oocyte system allows for the study of the implantation potential of embryos that would not otherwise be transferred. This study demonstrates that the quality of all embryos transferred to 2 recipients is equal to the quality of the 'best' embryos used in an exclusive recipient cycle. Tabled 1Exclusive (n = 100)Shared (n = 121)p valueMean # eggs/recipient19.4 ± 1.111.7 ± 0.3p# 2 pn/recipient11.6 ± 0.77.2 ± 0.2p# ET/recipient2.26 ± 0.72.33 ± 0.06nscryopreservation rate50% (50/100)31.8% (77/242)ns# embryos per freeze5.6 ± 0.64.2 ± 0.5nsclin preg rate (+ FH)56% (55/98)56% (135/241)nsimplantation rate40% (86/221)41% (225/543)nspregnancies/retrieval0.561.11pimplantations/retrieval0.861.86p Open table in a new tab Supported by: none.

Objective: To compare the incidence of ectopic pregnancy between patients receiving embryos at cleavage stage (day 3) or at morula/blastocyst stage (day 5) and to examine factors that may contribute to the ectopic pregnancy rate. Design: Retrospective analysis of data collected from all IVF/ET cycles at a large University-based IVF center of all IVF/ET cycles from 1996 to 2002. Materials/Methods: The protocol for extending embryo culture to day 5 (D5) for blastocyt transfer was initiated in September 1999. Only those patients with an appropriate number of good quality embryos were considered to be candidates for blastocyst transfer (Group A); otherwise embryos were transferred on day 3 (D3, Group B). Variables examined included patient age and diagnosis, baseline and peak serum estradiol (E2) levels, number of eggs retrieved, number of embryos transferred, the type of catheter used for embryo transfer, the degree of difficulty of the transfer, and the physician and embryologist handling the embryos. Pregnancy was defined by the presence of a fetal heartbeat. Chi-square and t-tests were used for statistical analysis; p <0.05 was considered significant Results: The rate of clinical pregnancy rate per transfer and the ectopic pregnancy rate per clinical pregnancy remained unchanged for patients who had D3 embryo transfers prior to (44% and 1.2%) and following (41% and 1.4%) the adoption of blastocyst protocol. Although a significantly greater proportion of ectopic pregnancies occurred after D5 transfers (Group A: 11/ 719 transfers) compared to D3 transfers (Group B: 9/ 1570 transfers, p <0.05), the incidence of ectopic pregnancy as a function of clinical pregnancies observed did not differ (Group A:11/ 426 or 2.6%; Group B: 9/ 659 or 1.4%). There was no difference between groups A and B with respect to patient age (35 ± 3 vs. 37 ± 4 yrs), baseline E2 (31 ± 17 vs. 35 ± 11 pg/ml), peak E2 (2052 ± 878 vs. 1719 ± 1136 pg/ml), number of eggs retrieved (19 ± 9 vs. 12 ± 10) and the number of embryos transferred (3 ± 1 vs. 4 ± 1). Furthermore, there was no difference between Groups A and B with respect to the physician and embryologist handling the transfer, the frequency of various diagnoses as indication for IVF including the diagnosis of pelvic factor (pelvic adhesions, endometriosis and tubal disease), the degree of difficulty of the transfer and the type of catheter used for embryo transfer. Conclusions: Although a higher rate of ectopic pregnancy per transfer was experienced with D5 compared to the conventional D3 embryo transfers, this higher ectopic rate is most likely related to the higher implantation and pregnancy rates that result from the transfer of morulae or blastocysts. Previous studies by other investigators have linked ectopic pregnancy to an aberrant uterine contractility pattern; our data suggest that IVF patients are as likely to develop such anomalous patterns on D3 as on D5. Supported by: None.

Objective: To establish prognostic relevance of parameters assessed in oocyte donation cycles.Design: Retrospective analysis.Setting: Large university-based donor oocyte program.Patient(s): All oocyte recipient cycles achieving embryo transfer from September 1995 to October 1998.Intervention(s): None.Main Outcome Measure(s): Pregnancy.Result(s): Recipient age and reproductive status, day 9 and 12 serum estradiol (E-2) levels and a progesterone (P) level obtained 2 days after initiation of hormonal therapy did not correlate with pregnancy. Endometrial thickness, but not endometrial pattern, was useful in predicting pregnancy outcome. The clinical pregnancy and live-birth rate in cycles where the endometrial thickness was less than s mm was significantly lower when compared to cycles with an endometrial thickness greater than or equal to9 mm. Cycles where optimal quality embryos were transferred had the highest implantation (36%), clinical pregnancy (63%) and live birth (54%) rates and these rates were significantly higher than those of cycles where only poor quality embryos were available for transfer (10% implantation, 17% clinical pregnancy, and 8% Live birth rates, respectively; P < .05).Conclusion(s): The most reliable predictive factors for pregnancy in oocyte donation cycles are the quality of the embryos transferred and the recipient's mid-cycle endometrial thickness. Recipient monitoring should minimally include ultrasound assessment of endometrial thickness. (C) 2001 by American Society for Reproductive Medicine.

Objective: To assess the impact of ET difficulty on IVF outcome and to optimize the ET procedure.Design: Retrospective analysis of IVF outcome by ET catheter type and ET difficulty. Prospective treatment and follow-up of patients with a history of extremely difficult cervical passage.Setting: Large university-based IVF program.Patient(s): All patients <40 years of age undergoing IVF-ET from September 1995 to May 1998.Intervention(s): Surgical correction of cervical stenosis.Main Outcome Measure(s): Pregnancy and embryo implantation rates.Result(s): Only 0.6% of ETs were "extremely difficult." Pregnancy rates were not statistically significantly different among ETs graded easy, moderate, and difficult. In contrast, no pregnancies occurred in the rare "extremely difficult" ET group. Eight patients with a history of extremely difficult cervical passage underwent surgical correction of their cervical stenosis. Twelve postoperative IVF-ET in these women resulted in eight clinical pregnancies, six of which were multiple gestations. The embryo implantation rate of these cycles was 42.2%.Conclusion(s): Patients with a history of extremely difficult ET may benefit from hysteroscopic evaluation and possible modification of their cervical canal before a future IVF attempt. (C) 1999 by American Society for Reproductive Medicine.

Objective: To determine if laparoscopic ovarian follicle puncture and GIFT induces pelvic adhesions.

OBJECTIVE:Since the corpus luteum (CL) is known to play an important role in early pregnancy, its activity could possibly be a marker for pregnancy outcome.DESIGN:The late estradiol (E2) concentration in 48 viable pregnancies and 39 pregnancies which resulted in spontaneous abortions after in vitro fertilization and embryo transfer were used to evaluate such predictability.SETTING:All patients studied were of the Center for Reproductive Medicine at Cornell University Medical College.PATIENTS, PARTICIPANTS:Eighty-seven patients.INTERVENTIONS:None.MAIN OUTCOME MEASURE:Serum E2 and human chorionic gonadotropin (hCG) concentrations on day +11, +13, +15 (day +1 = day of ovum pick-up) were measured and studied.RESULTS:The late luteal CL activity after rescue had a positive correlation with the number and quality of the implanted embryos. Reduced CL activity was indicative of abortion. The late luteal E2 pattern when compared with hCG doubling time had a better abortion predictability (37.8% versus 63.9%, respectively).CONCLUSION:Corpus luteum activity demonstrated to be a better prognosticator of abortion than serial beta-hCG titers.