effect of tnf-α blocker (infliximab) on blastocyst development rate
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Conclusion: Patients with HOMP face difficult clinical decisions that mayaffect subsequent obstetrical outcome. In our program, approximately equalproportions of HOMP patients chose to undergo SLRE or deliver all babies.The age of the patient and the occurrence of a previous pregnancy lossappeared to be important factors in determining if a patient chose to undergoSLRE or to deliver all babies.
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Prolongued coasting duration affects implantation rates. Juan A. Gar-cia-Velasco, Luis Moreno, Andres Zuniga, Amparo Villasante, AntonioRequena, Antonio Pellicer. IVI-Madrid, Madrid, Spain.
Objective: Ovarian hyperstimulation syndrome (OHSS) is one of themajor complications from ovarian hypestimulation. Withholding gonado-tropins (“coasting”) has been described as an effective way of avoidingcycle cancellation, while decreasing the risk of severe OHSS. However, thelength of the coasting duration has not been precisely studied, and it seemsthat a prolongued coasting may affect oocyte and embryo quality, thus,reducing implantation rates.
Design: Retrospective, case-series.Materials and Methods: From November 1999 to January 2003, 132
patients with high response to ovarian hypestimulation (E2 �4000 pg/mLand/or more then 20 follicles �17mm) were coasted due to an extremelyhigh risk for the developement of OHSS. Daily measurements of serum E2were evaluated while FSH/hMG administration was withheld and GnRHanalogue was maintained. Once E2 levels decreased to �3500 pg/mL, 5000IU hCG were administered and ovarian punctured performed 36h after-wards.
Results: IVF cycle outcome according to the duration of the coastingprocedure are presented in the following table
Conclusion: There was a clear trend to an extended duration of coastingwith higher E2 levels at the beginning of the coasting procedure. Althoughfertilization rates were similar regardless how many days were required todiminish E2 levels, there was a significant decrease in implantation ratewhen coasting was required for more than 4 days together with a trendtowards a higher cancellation rate.
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High Order Multiple (HOM) pregnancies and IVF cycle number: Isthere an association? Sigal Klipstein, Aimee Eyvazzadeh, Kim L. Thorn-ton, Lorna S. Timmreck, David A. Ryley, Richard H. Reindollar. BethIsrael Deaconess Medical Ctr and Boston IVF, Boston, MA; Beth IsraelDeaconess Medical Ctr, Boston, MA; Boston IVF, Waltham, MA.
Objective: The avoidance of high order multiple (HOM) pregnancies is asignificant concern in IVF cycles. This analysis was undertaken to deter-mine factors placing women at risk for conceiving HOMs. We hypothesizedthat triplets may result from more aggressive treatment in couples who failto conceive in early cycles, perhaps resulting from the transfer of moreembryos.
Design: Retrospective analysis of IVF cycles in which HOMs wereconceived.
Materials and Methdos: Our database identified 237 IVF cycles initiatedin nulliparous women �41 years old between January 1995 and June 2002,resulting in �3 sacs on initial ultrasound. This group was contrasted with acomparison group of 8389 IVF cycles in nulliparas �41 who had 0-2 sacson initial ultrasound, but were similar for all other parameters. Only non-donor oocytes cycles were included in the analysis.
Results: The 237 HOM pregnancies identified included 215 triplet, 19
quadruplet and 3 quintuplet gestations. The largest group of HOMs (40.9%)were conceived in the first IVF cycle. Additionally, while a decrease innumber of HOMs occurred with subsequent cycles, nearly 1/3 occurred inthe 3rd and 4th cycles, and 21.3% of all HOMs occurred beyond the 3rd cyclein the face of an increasing number of embryos transferred and a normalfollicular response. There was a slight increase in the number of embryostransferred with increasing cycle numbers. When compared to cycles thatdid not result in HOMs, there were a greater number of embryos transferredfor each cycle number in the context of good ovarian response. The meanages in the HOM and comparison groups were not significantly different(34.4 vs. 34.6).
Previous cycle data was available for 122/140 patients who conceivedHOMs in cycles 2-10 .In these women, there was an average increase of 1.3embryos transferred in the cycle resulting in HOM as compared to theprevious failed cycle. 9% of women were cancelled in the previous cycle,and 87% were not pregnant in the previous cycle. Of the 13% who had apregnancy in the previous cycle, 7/16 (44%) transferred at least one addi-tional embryo in the cycle resulting in a HOM.
Conclusions: In conclusion, the largest group of patients with HOMsconceived from their first IVF cycle. Additionally, over 20% of HOMsoccurred beyond the 3rd cycle and up to the 10th cycle. Most of theseoccurred in the setting of increasing numbers of embryos transferred and anormal follicular response following previously failed cycles. Strategies toprevent HOMs include: limiting the total number of ET for all patients andavoiding the temptation to increase the # of ET in subsequent cycles in theabsence of a pregnancy. Additionally, our data also suggest that no numberof prior failed IVF cycles guarantees immunity to HOMs.
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Effect of TNF-� blocker (Infliximab) on blastocyst development rate.Javier Noriega, Mohamed A. Bedaiwy, Rakesh K. Sharma, Ashok Agarwal,Tommaso Falcone. Cleveland Clin Fdn, Cleveland, OH.
Objectives: TNF-� has gained recent attention in the pathophysiology ofautoimmune disease. Numerous studies have demonstrated that TNF-�levels are elevated in serum and peritoneal fluid of patient with endometrio-sis.The use of immunomodulators have proven to be effective means in themanagement for many autoimmune diseases. Perhaps a similar therapy mayprove useful in treating endometriosis. As such, targeting TNF-� would bea logical starting point in the development of novel treatments for theendometriosis. Infliximab (Remicade) is currently approved for the treat-ment of rheumatoid arthritis and Chron’s disease. It is a chimeric mono-clonal antibody that binds both soluble and membrane forms of TNF-� andneutralizes its biological effects. There is no data available on its effects onearly embryonic development. During controlled clinical trials, maximumiflximab plasma levels do not exceed 10 �g/ml, even at maximum doses.The objective of this study was to evaluate the effects of variable doses ofinflximab on early embryo development using two-cell stage mouse embryomodel.
Design: Experimental study in a research laboratory in a tertiary carefacility.
Materials and methods: Thawed mouse embryos were pooledand ran-domly distributed between 7 groups: (A) composed of HTF supplementedwith inflximab 1 �g/ml, (B) HTF supplemented with inflximab 10 �g /ml,(C)HTF supplemented with inflximab 50 �g /ml, (D) HTF supplementedwith inflximab 100 �g /ml, (E) HTF supplemented with inflximab 200 �g/ml, (F) HTF supplemented with inflximab 400 �g /ml and a control groupcomposed of plain HTF media (G). The numbers of embryos were from 30
S176 Abstracts Vol. 80, Suppl. 3, September 2003
to 50 embryos per group. Blastocyst development rates (BDR) werechecked after 72 hours of incubation.
Results: Blastocyst development rates were 96.3%, 86.7%, 77.3%,86.7%, 80%, 10% and 96% for the 7 groups respectively (Figure). BDRrates of all groups but F were comparable with the control group. On theother hand, Group F had significantly lower BDR compared to the controlgroup (P�0.0001).
Conclusions: At concentrations similar to the maximum in vivo levels,inflximab does not affect BDR. Embryotoxic effects of inflximab appearonly at a concentration 40 fold its maximum in vivo level. Inflximab doesnot have any toxic effects on early cleaving embryos. Inflximab can be usedsafely either before or during ovulation induction for patients with endo-metriosis.
Figure: Effect of different concentrations of infliximab on the blastocystdevelopment rate of mouse embryos.
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Elective fresh transfer of one or two embryos. Del E. Marek, Martin T.Langley, Joey R. Howell, Anna C. Nackley, Kathleen M. Doody, Kevin J.Doody. Ctr for Assisted Reproduction, Bedford, TX.
Objective: Reports of high incidence of multiple gestations associatedwith in-vitro fertilization (IVF) procedures have led many clinics to limit thenumber of embryos transferred. These data will evaluate pregnancy andimplantation rates resulting from elective transfer of one or two blastocystembryos derived from extended embryo culture.
Design: A retrospective analysis of elective single and double embryotransfer results from January 1, 1998 through March 31, 2003.
Materials and Methods: Patients underwent Antagon(r) (Organon) orCetrotide(r) (Serono) antagonist protocols, Lupron(r) (TAP) agonist proto-cols, or flare protocols prior to controlled ovarian hyper-stimulation withFollistim(r) (Organon) or Gonal-F(r) (Serono). Oocyte retrieval occurred36-39 hours post Human Chorionic Gonadotropin (hCG) administration.Insemination was performed 38-42 hours post hCG using a two hourco-incubation of sperm with oocytes or sperm injection. Oocytes wereindividually placed in 50-100�l micro-drops of sequential media (S1, G1.2,G1.3, IVF Science, Vitrolife) under oil (Squibb, Sigma) and culturedovernight. Fertilization was evaluated 18-20 hours after insemination. Fer-tilized oocytes were placed into fresh 50-100�l micro-drops of sequentialmedia (G1.2, G1.3) and cultured in groups of two under oil to Day 3.Multi-cell embryos were moved to new 50-100�l micro-drops of sequentialmedia (S2, CCM, G2.2, G2.3, IVF Science, Vitrolife) under oil for cultureto Day 5 or Day 6 and subsequent blastocyst embryo transfer. Patients werecounseled and given the option to transfer one or two embryos irrespectiveof embryo grading/scoring and have their additional embryos cryopre-served. To assist intrauterine placement of the embryo transfer catheter(Wallace, Cook), an abdominal ultrasound (5 MHz) was utilized. A sono-gram to determine total gestational sacs and fetal hearts was performed at4-6 weeks post positive hCG.
Results:
Conclusion: Upon review of results a large number of patients (95.3%)elected to transfer two embryos rather than one. It is remarkable that nosignificant difference was noted for overall (P�1.002), clinical (P�.1717)and ongoing (P�.4512) pregnancy rates between transfer of one or twoembryos. In addition, no significant difference was recorded for implanta-tion rate between the two groups (P�.6523). Similar pregnancy and im-plantation rates between elective fresh one and two embryo transfer groupswarrant serious consideration for single blastocyst transfer in select patientpopulations and/or when supernumerary embryos are present. Single blas-tocyst transfer does show a dramatic reduction in multiple gestations.
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Cytogenetic analysis in fetuses from spontaneous abortions after InVitro Fertilization (IVF) by comparative genomic hybridization. Yue-qiu Tan. Institute of Reproduction and Stem Cell Engineering, South UnivXiang-Ya Sch of Medicine, Changsha, China.
Objective: To detect the chromosome anomalies in fetuses from sponta-neous abortions after in vitro fertilization (IVF), thus provide useful infor-mation to decrease the spontaneous abortion rate in IVF treatment.
Design: Retrospective analysis.Materials and Methods: A total of 41 fetal specimens were derived from
early spontaneous abortions after in vitro fertilization (IVF). Cytogeneticanalysis was performed by comparative genomic hybridization.
Results: Abnormal chromosomes were identified by CGH in 63.4% ofspontaneous abortion samples, including chromosome gains and partialgains (41.5%), monosomy X (14.6%), and other anomalies involved twochromosomes in the same time (7.3%). Most frequently involved in tri-somies were chromosomes 22 (9.8%), 21(7.3%) and 4,13 (4.9% each).
Conclusion: Our data suggest that the chromosome abnormalities inspontaneous abortions after IVF are not whole consistent with other spon-taneously aborted samples. Chromosome X, Y, 21, 22 and 13 are the mostfrequently abnormal chromosomes, while abnormal incidence rate of chro-mosome 16 is relative low. Thus, exclusion of abnormalities of chromosomeX, Y, 21, 22 and 13 in preimplantation embryo might significantly decreasethe possibility of spontaneous abortion in IVF.
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Ectopic pregnancy in IVF with own versus donated oocytes. Nancy M.Molina, Ernesto Bosch, Carlos Troncoso, Carlos Simon, Antonio Pellicer,Jose Remohı. Inst Valenciano de Infertilidad, Valencia, Spain.
Objective: The objective of the present study was to analyze the incidenceof ectopic pregnancy (EP) in IVF/ICSI with own oocytes vs donatedoocytes.
Design: Retrospective, analytic and comparative study.Materials and Methods: Retrospective, analytic and comparative study in
which 1,694 IVF/ICSI procedures and 1,416 oocyte donation procedureswith positive pregnancy test performed in our Institution between January1st, 1998 and October 31st, 2002 were included. The incidence of EPbetween both kind of procedures was compared.
We evaluated the age of patients, donors and recipient, background oftubal pathology, EP (surgically treated), miscarriage with curettage, numberand quality of the embryos transferred (number of blastomeres and frag-mentation rate) and embryo stage (day 2, 3 or blastocyst).
Results: The incidence of EP was 2.9% (50/1694) in patients with ownoocytes and 1.1% (16/1416) in donated oocytes (P�0.001).
The Table N° 1 summarizes the characteristics of each group based in theembryo stage at the moment of the transfer.
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