Compare morphometric timing of a fresh oocyte cohort used in IVF compared to the same patients Vitrified Oocytes cohort, cultured simultaneously in the Embryoscope® Fertilitech. Patient who had previously vitrified oocytes due to no sperm available at time of IVF. Patient subsequently presented for a fresh IVF/ICSI cycle using Fresh partners sperm. This unique situation provided the opportunity to culture both cohorts simultaneously to ascertain a comparison of developmental milestones. The Oocyte vit cycle yielded 19 oocytes of which 17 were MII. The fresh cycle yielded 8 oocytes all of which all were MII. The same ejaculate was used for ICSI for both. The vit group with 14 fertilized normally. The fresh group had 5 fertilized normally. All embryos were placed into the Embryoscope after fertilization assessment. Embryo Transfer occurred on Day 3 of embryo development exclusively from the Vitrified/Warmed cohort.. Two embryos were transferred (8 cell and 9 cell both (A quality). This resulted in a singleton live birth. We compared the key Mean developmental indicators looking at Time of 2PN fade and fist cleavage between the two groupsTable 1Vitrified GroupFresh Group2PN fade (syngamy)24.3 hrs21.3 hrs1st cleavage27.6 hrs27.4 hrs2 cell32.3 hrs27.4 hrs4 cell40.1 hrs39.0 hrs6 cell53.2 hrs51.6 hrs8 cell62.1 hrs52.4 hrsMorula91.5 hrs91.7 hrsBlast112.0 hrs108.4 hrsWe next compared cleavage times at key times: 2 cell, 4 cell, 6 cell, 8 cell, Morula and finally Blastulation time. Open table in a new tab We next compared cleavage times at key times: 2 cell, 4 cell, 6 cell, 8 cell, Morula and finally Blastulation time. Many of the time points evaluated demonstrated very similar developmental rates. The ones that seem to have a difference are the time to 2PN fade (prior to first Cleavage) as well as time to 8 cell. These differences may be due to post vitrification recovery. Based on these results one should expect a vitrified and warmed oocyte to develop at a very similar rate to a fresh cohort.
Morphometrics has been the main tool in IVF laboratories to grade and choose embryos for transfer. The Alpha/ESHRE Consensus meeting in 2010 outlined key time points at which to grade embryos, but currently there is limited data to support how long an embryo should stay at certain developmental stages before engaging in cytokinesis relative to embryo quality. Wong et. al described cytokinesis intervals of day 2 embryos to predict blastocyst formation. The focus of this study is to determine key indicators of embryo development which indicate a successful clinical outcome. The Embryoscope® Fertilitech allows IVF labs to leave embryos undisturbed in culture while scoring, which it theorized to benefit embryo development. Dynamics of embryo cleavage and development are paramount to patient success. Retrospective analyses of patients (n=69) having IVF and cultured in the Embryoscope® Fertilitech at the Fertility Centers of New England from April 2012 through October 2012. Embryos with 100 % implantation rate (IR) vs. embryos with 0 % IR were included in this study. 69 patients: 57 had 0 % IR and 12 had 100 %. Patients with 100 % IR had an mean age of 31years while patients with 0% had a mean of 37 years. Average BMI for both groups is 24. Looking at rates of cleavage as it related to implantation we identified three key points of development: 3 cell embryos with an increased lag to the 4 cell stage similar to Wong et.al., cleavage from 4 to 5 cell showed a difference, but less important. The time lag between the morula and blastocyst stage seems to be an important indicator of implantation potential. Due to the small N, additional data collection is warranted. Further data is currently being collected to analyze and validate these findings. If an embryo has already cleaved by the recomended time scoring, the embryoscope allows us to determine the exact time of cytokinesis.
Mitochondria are key to cellular energy generation, homeostasis and cell life; function actively during oocyte maturation, fertilization and embryo development through ATP production. Measuring ATP content necessitates oocyte destruction, but measuring activity through oxygen consumption is non-invasive. Retrospective. Respiration rates (RR; nL/H) of single oocytes from ICSI (D 0; GV and M I) and insemination cycles (D1; GV, M I, M II) were measured non-invasively (EmbryoScope-Unisense, Aarhus, Denmark) at 15–60 minutes over 3–5 hours, for base respiration rate (BRR). Oocytes were cultured overnight (18 hours) to assess developmental and maturational competence (maturation, arrest, attresia) which was correlated with BRR. BRR was correlated with infertility diagnosis, days of FSH administration, total number of oocytes retrieved and fertilization rates in non-ICSI cycles. BRR significantly correlated with oocyte developmental and cellular competence, reduced rates in those that became attretic (0.0019) and high in oocytes that were abnormal (1.24). Intermediate rates were obtained for arrested or matured oocytes. BRR of oocytes derived from failed fertilization with no male factor had significantly decreased rates. BRR of oocytes from patients with decreased ovarian reserve, PCOS and repeat pregnancy loss was significantly reduced. Oocytes derived from patients with <8 days of FSH and with >25 oocytes retrieved had reduced BRR. BRR correlated with fertilization rates, developmental competence, infertility etiology and factors affecting ovarian stimulation. Since our technique is non-invasive and BRR can be obtained expeditiously, respiration rates of oocytes may provide a feasible selection technique for enhanced development and clinical outcome.
ObjectiveDuring ICSI, the presence of a first polar body is used to determine if an oocyte is mature and competent for fertilization. Human oocytes also require additional time post PB extrusion to acquire developmental competency (1). The timing of polar body extrusion within a cohort of retrieved oocytes may not be uniform, meaning the duration of MII arrest prior to ICSI may also be variable. This study's objective was to test the hypothesis that the duration of time between the extrusion of the first polar body and sperm injection will influence the developmental competence of the resulting embryo.DesignProspective data collection.Materials and methodsOocytes for ICSI were stripped of cumulus cells at 38 h post hCG (ER at 36 h) and sorted by maturation stage. M11 Oocytes were injected with sperm at 40 h post hCG followed by any M1 oocytes that had matured in the intervening 2 to 2.5 hrs. Fertilization of the different oocytes, their PN score (16–18 h post hCG), their Day 2 scores (41–42 h post hCG) and their developmental potential for ET was recorded as these parameters have been previously shown to impact implantation and delivery potential. Fertilization and development of oocytes/embryos from ICSI cases where early stripping and scoring for maturity was not done were used as the control group (the previous 3 months).ResultsTableMorphology ParametersFertilization %Z1/Z2 PN %Day 2, 4-cellDay 2, 1n/b %Day 2, MN %Day 2, Even Cells %D3, 8-cellM1-M241∗∗49∗∗36∗27∗∗56∗∗5012∗∗M284785761136167Control68594855215849∗P<0.05; ∗∗ P<0.01. Open table in a new tab ConclusionsOocytes recently matured prior to ICSI were not fully competent for fertilization. Those that did fertilize exhibited signs of nuclear (highly significant multinucleation on day 2) and cytoplasmic (retarded cellular division on day 3) deficiencies in the resulting embryos. The data would suggest that early scoring of oocyte maturity for ICSI may aide in selecting those that have completed both cytoplasmic and nuclear maturation on time relevant to hCG administration. ObjectiveDuring ICSI, the presence of a first polar body is used to determine if an oocyte is mature and competent for fertilization. Human oocytes also require additional time post PB extrusion to acquire developmental competency (1). The timing of polar body extrusion within a cohort of retrieved oocytes may not be uniform, meaning the duration of MII arrest prior to ICSI may also be variable. This study's objective was to test the hypothesis that the duration of time between the extrusion of the first polar body and sperm injection will influence the developmental competence of the resulting embryo. During ICSI, the presence of a first polar body is used to determine if an oocyte is mature and competent for fertilization. Human oocytes also require additional time post PB extrusion to acquire developmental competency (1). The timing of polar body extrusion within a cohort of retrieved oocytes may not be uniform, meaning the duration of MII arrest prior to ICSI may also be variable. This study's objective was to test the hypothesis that the duration of time between the extrusion of the first polar body and sperm injection will influence the developmental competence of the resulting embryo. DesignProspective data collection. Prospective data collection. Materials and methodsOocytes for ICSI were stripped of cumulus cells at 38 h post hCG (ER at 36 h) and sorted by maturation stage. M11 Oocytes were injected with sperm at 40 h post hCG followed by any M1 oocytes that had matured in the intervening 2 to 2.5 hrs. Fertilization of the different oocytes, their PN score (16–18 h post hCG), their Day 2 scores (41–42 h post hCG) and their developmental potential for ET was recorded as these parameters have been previously shown to impact implantation and delivery potential. Fertilization and development of oocytes/embryos from ICSI cases where early stripping and scoring for maturity was not done were used as the control group (the previous 3 months). Oocytes for ICSI were stripped of cumulus cells at 38 h post hCG (ER at 36 h) and sorted by maturation stage. M11 Oocytes were injected with sperm at 40 h post hCG followed by any M1 oocytes that had matured in the intervening 2 to 2.5 hrs. Fertilization of the different oocytes, their PN score (16–18 h post hCG), their Day 2 scores (41–42 h post hCG) and their developmental potential for ET was recorded as these parameters have been previously shown to impact implantation and delivery potential. Fertilization and development of oocytes/embryos from ICSI cases where early stripping and scoring for maturity was not done were used as the control group (the previous 3 months). ResultsTableMorphology ParametersFertilization %Z1/Z2 PN %Day 2, 4-cellDay 2, 1n/b %Day 2, MN %Day 2, Even Cells %D3, 8-cellM1-M241∗∗49∗∗36∗27∗∗56∗∗5012∗∗M284785761136167Control68594855215849∗P<0.05; ∗∗ P<0.01. Open table in a new tab ∗P<0.05; ∗∗ P<0.01. ConclusionsOocytes recently matured prior to ICSI were not fully competent for fertilization. Those that did fertilize exhibited signs of nuclear (highly significant multinucleation on day 2) and cytoplasmic (retarded cellular division on day 3) deficiencies in the resulting embryos. The data would suggest that early scoring of oocyte maturity for ICSI may aide in selecting those that have completed both cytoplasmic and nuclear maturation on time relevant to hCG administration. Oocytes recently matured prior to ICSI were not fully competent for fertilization. Those that did fertilize exhibited signs of nuclear (highly significant multinucleation on day 2) and cytoplasmic (retarded cellular division on day 3) deficiencies in the resulting embryos. The data would suggest that early scoring of oocyte maturity for ICSI may aide in selecting those that have completed both cytoplasmic and nuclear maturation on time relevant to hCG administration.
ObjectivePublished studies in 1991 reported gonadotropin IUI and IVF live birth rates to be similar. Insurance companies in mandated states have used these prior studies to design criteria for IVF approval; today this often requires the patient complete at least three FSH/IUI cycles before IVF approval. Calculations of IUI versus IVF outcome and cost-effectiveness must incorporate timely pregnancy rates. SART reported an IVF pregnancy rate/retrieval of 15.2% in 1991 vs. 32.6% in 2002. This doubling of IVF pregnancy rates prompts re-evaluation of prior comparisons. This study reviews pregnancy rates in high-responding gonadotropin IUI cycles emergently converted to IVF. These converted cycles provide an initial comparison for fast track versus systematic treatment of patients, where cost and pregnancy outcome are to be considered.DesignA retrospective analysis of IVF and FSH/IUI data in 2004 in a private clinic in an insurance mandated state.Materials and methodsFour patient groups (divided into > and < 38 y.o.) were analyzed for delivery rates: 1) first time IUI cycles 2) total (1-3) IUI cycles; 3) IUI cycles emergently converted to IVF due to ≥ 5 mature follicles present after stimulation; and 4) first time IVF cycles. The delivery/ongoing pregnancy rates were computed. Chi-square statistical comparisons were made.ResultsTabled 1* P<0.01, ** P<0.001ConclusionHigh-responding gonadotropin IUI cycles should be converted to IVF. The increased pregnancy rate in this converted group as compared to first time IVF patients also suggests possible effects of patient selection, down-regulation or FSH acclimatization. The favorable pregnancy rates in the converted cycles also prompts re-evaluation of required FSH/IUI treatment prior to IVF approval in insurance mandated states. ObjectivePublished studies in 1991 reported gonadotropin IUI and IVF live birth rates to be similar. Insurance companies in mandated states have used these prior studies to design criteria for IVF approval; today this often requires the patient complete at least three FSH/IUI cycles before IVF approval. Calculations of IUI versus IVF outcome and cost-effectiveness must incorporate timely pregnancy rates. SART reported an IVF pregnancy rate/retrieval of 15.2% in 1991 vs. 32.6% in 2002. This doubling of IVF pregnancy rates prompts re-evaluation of prior comparisons. This study reviews pregnancy rates in high-responding gonadotropin IUI cycles emergently converted to IVF. These converted cycles provide an initial comparison for fast track versus systematic treatment of patients, where cost and pregnancy outcome are to be considered. Published studies in 1991 reported gonadotropin IUI and IVF live birth rates to be similar. Insurance companies in mandated states have used these prior studies to design criteria for IVF approval; today this often requires the patient complete at least three FSH/IUI cycles before IVF approval. Calculations of IUI versus IVF outcome and cost-effectiveness must incorporate timely pregnancy rates. SART reported an IVF pregnancy rate/retrieval of 15.2% in 1991 vs. 32.6% in 2002. This doubling of IVF pregnancy rates prompts re-evaluation of prior comparisons. This study reviews pregnancy rates in high-responding gonadotropin IUI cycles emergently converted to IVF. These converted cycles provide an initial comparison for fast track versus systematic treatment of patients, where cost and pregnancy outcome are to be considered. DesignA retrospective analysis of IVF and FSH/IUI data in 2004 in a private clinic in an insurance mandated state. A retrospective analysis of IVF and FSH/IUI data in 2004 in a private clinic in an insurance mandated state. Materials and methodsFour patient groups (divided into > and < 38 y.o.) were analyzed for delivery rates: 1) first time IUI cycles 2) total (1-3) IUI cycles; 3) IUI cycles emergently converted to IVF due to ≥ 5 mature follicles present after stimulation; and 4) first time IVF cycles. The delivery/ongoing pregnancy rates were computed. Chi-square statistical comparisons were made. Four patient groups (divided into > and < 38 y.o.) were analyzed for delivery rates: 1) first time IUI cycles 2) total (1-3) IUI cycles; 3) IUI cycles emergently converted to IVF due to ≥ 5 mature follicles present after stimulation; and 4) first time IVF cycles. The delivery/ongoing pregnancy rates were computed. Chi-square statistical comparisons were made. ResultsTabled 1* P<0.01, ** P<0.001 * P<0.01, ** P<0.001 ConclusionHigh-responding gonadotropin IUI cycles should be converted to IVF. The increased pregnancy rate in this converted group as compared to first time IVF patients also suggests possible effects of patient selection, down-regulation or FSH acclimatization. The favorable pregnancy rates in the converted cycles also prompts re-evaluation of required FSH/IUI treatment prior to IVF approval in insurance mandated states. High-responding gonadotropin IUI cycles should be converted to IVF. The increased pregnancy rate in this converted group as compared to first time IVF patients also suggests possible effects of patient selection, down-regulation or FSH acclimatization. The favorable pregnancy rates in the converted cycles also prompts re-evaluation of required FSH/IUI treatment prior to IVF approval in insurance mandated states.
ObjectivePreimplantation genetic diagnosis (PGD) for aneuploidy allows chromosomally normal embryos for the 9 chromosomes analyzed to be selected and transferred in order to minimize the rates of pregnancy loss and implantation failure in certain populations of patients. These include patients of advanced maternal age, recurrent pregnancy loss, repeat IVF failure and repeat biochemical loss after IVF. Not all "normal" embryos transferred implant and many of those that do, result in an early SAB. The objective of this study was to analyze pregnancy loss after the transfer of "normal" embryos in relation to morphometric parameters that have been correlated with pregnancy, in order to understand the lack of implantation after PGD.DesignRetrospective Data Analysis of 14 months of data of FISH for aneuploidy. Ecluded are single gene and translocation cases. All cases of aneuploidy were included, regardless of diagnosis or age.Materials and methodsAll euploid embryos that were used in embryo transfer were included. The day 1, day 2 and day 3 scores for PN morphology, day 2 cell number, state of multinucleation and evenness of cell division and day 3 morphology were compared with implantation and ongoing pregnancy.ResultsTabled 1Tabled 1ConclusionAlthough patients undergoing IVF with PGD for aneuploidy have embryos transferred that are chromosomally normal for the chromosomes analyzed, transferred embryos with poor pronuclear and day two morphology may negatively impact their overall success. This data suggests that while transferiing a chromosomally normal embryo is important, acheiving a successful pregnancy also depends on the biology and quality of the embryo transferrred. Poor pronuclear morphology and the presence of uneven cell sizes or multinucleation on day two may represent aneuploidy of the nine chromosomes tested with PGD, but also aneuploidy of other less commonly tested chromosomes, or the quality of metabolic function in the embryo itself. Embryos with normal PGD result as well as those with normal morphology scores should be preferentially selected for transfer when available. ObjectivePreimplantation genetic diagnosis (PGD) for aneuploidy allows chromosomally normal embryos for the 9 chromosomes analyzed to be selected and transferred in order to minimize the rates of pregnancy loss and implantation failure in certain populations of patients. These include patients of advanced maternal age, recurrent pregnancy loss, repeat IVF failure and repeat biochemical loss after IVF. Not all "normal" embryos transferred implant and many of those that do, result in an early SAB. The objective of this study was to analyze pregnancy loss after the transfer of "normal" embryos in relation to morphometric parameters that have been correlated with pregnancy, in order to understand the lack of implantation after PGD. Preimplantation genetic diagnosis (PGD) for aneuploidy allows chromosomally normal embryos for the 9 chromosomes analyzed to be selected and transferred in order to minimize the rates of pregnancy loss and implantation failure in certain populations of patients. These include patients of advanced maternal age, recurrent pregnancy loss, repeat IVF failure and repeat biochemical loss after IVF. Not all "normal" embryos transferred implant and many of those that do, result in an early SAB. The objective of this study was to analyze pregnancy loss after the transfer of "normal" embryos in relation to morphometric parameters that have been correlated with pregnancy, in order to understand the lack of implantation after PGD. DesignRetrospective Data Analysis of 14 months of data of FISH for aneuploidy. Ecluded are single gene and translocation cases. All cases of aneuploidy were included, regardless of diagnosis or age. Retrospective Data Analysis of 14 months of data of FISH for aneuploidy. Ecluded are single gene and translocation cases. All cases of aneuploidy were included, regardless of diagnosis or age. Materials and methodsAll euploid embryos that were used in embryo transfer were included. The day 1, day 2 and day 3 scores for PN morphology, day 2 cell number, state of multinucleation and evenness of cell division and day 3 morphology were compared with implantation and ongoing pregnancy. All euploid embryos that were used in embryo transfer were included. The day 1, day 2 and day 3 scores for PN morphology, day 2 cell number, state of multinucleation and evenness of cell division and day 3 morphology were compared with implantation and ongoing pregnancy. ResultsTabled 1Tabled 1 ConclusionAlthough patients undergoing IVF with PGD for aneuploidy have embryos transferred that are chromosomally normal for the chromosomes analyzed, transferred embryos with poor pronuclear and day two morphology may negatively impact their overall success. This data suggests that while transferiing a chromosomally normal embryo is important, acheiving a successful pregnancy also depends on the biology and quality of the embryo transferrred. Poor pronuclear morphology and the presence of uneven cell sizes or multinucleation on day two may represent aneuploidy of the nine chromosomes tested with PGD, but also aneuploidy of other less commonly tested chromosomes, or the quality of metabolic function in the embryo itself. Embryos with normal PGD result as well as those with normal morphology scores should be preferentially selected for transfer when available. Although patients undergoing IVF with PGD for aneuploidy have embryos transferred that are chromosomally normal for the chromosomes analyzed, transferred embryos with poor pronuclear and day two morphology may negatively impact their overall success. This data suggests that while transferiing a chromosomally normal embryo is important, acheiving a successful pregnancy also depends on the biology and quality of the embryo transferrred. Poor pronuclear morphology and the presence of uneven cell sizes or multinucleation on day two may represent aneuploidy of the nine chromosomes tested with PGD, but also aneuploidy of other less commonly tested chromosomes, or the quality of metabolic function in the embryo itself. Embryos with normal PGD result as well as those with normal morphology scores should be preferentially selected for transfer when available.
Historically Day 2 ET was performed but this practice has become less popular with advances in culture media. Currently ET is preferentially performed on Day 3 or Day 5. For some patients, embryonic development in vitro is compromised, regardless of culture system, or patients fail to conceive after multiple IVF attempts with either Day 3 or Day 5 ET. Day 2 ET has been considered in these patients as a way of reducing detrimental in vitro effects. Private practice in an insurance mandated state. Retrospective analysis of 14 months of IVF data where repeat failure patients or patients with lack of embryo development had ET on Day 2. Three groups were studied: 1) elective day 2 ET with >3 embryos available for selection; 2) non-elective Day 2 ET due to only 1 or 2 embryos being available (lack of choice); 3) Routine day 3 patients <43 years in age; no donor, surrogate or PGD. No Day 5 data was considered. FHB rates in the control group were also computed for cycle number and total embryos available for ET. Data presented in the tables below. Of the 110 Day 2 ET, 8 were from cancelled PGD cycles, due to too few embryos; 1 pregnant with a singleton ongoing (included in the data below). In the elective Day 2 ET, the mean age was 34.5, mean cycle number was 3.5 (2-5), and mean number of 2PN was 7.4 +/- 2.8. Tabled 1*previously zero, P<0.01 Tabled 1 Tabled 1 *previously zero, P<0.01 Day 2 elective ET is a viable option and can be considered when there is repeat IVF failure, regardless of number of available embryos. In this group, elective day 2 ET resulted in an ongoing pregnancy rate equivalent to day 3 ET on 1st and 2nd cycle patients.
OBJECTIVE: Preimplantation genetic diagnosis (PGD) for aneuploidy allows chromosomally normal embryos for the 9 chromosomes analyzed to be selected and transferred in order to minimize the rates of pregnancy loss and implantation failure in certain populations of patients. These include patients of advanced maternal age, recurrent pregnancy loss, repeat IVF failure and repeat biochemical loss after IVF. Not all “normal” embryos transferred implant and many of those that do, result in an early SAB. The objective of this study was to analyze pregnancy loss after the transfer of “normal” embryos in relation to morphometric parameters that have been correlated with pregnancy, in order to understand the lack of implantation after PGD. DESIGN: Retrospective Data Analysis of 14 months of data of FISH for aneuploidy. Ecluded are single gene and translocation cases. All cases of aneuploidy were included, regardless of diagnosis or age. MATERIALS AND METHODS: All euploid embryos that were used in embryo transfer were included. The day 1, day 2 and day 3 scores for PN morphology, day 2 cell number, state of multinucleation and evenness of cell division and day 3 morphology were compared with implantation and ongoing pregnancy. RESULTS: Although not statistically significant, there is an apparent trend towards a higher miscarriage rate in PGD/aneuploidy patients with poor pronuclear and day two morphology embryos transferred. The data is shown in the tables. There was no difference with day 3 cell number (not shown).