- Email: [email protected]
Evaluation and treatment of patients with recurrent implantation failure
Abstracts - WARM: Beyond infertility: breakthroughs in reproductive medicine and technology
Laboratory aspects A single medium for culture of the human embryo from zygote to blastocyst
in sequential media systems. Global has significant other practical advantages. For instance, only one medium needs to be tested and mix-up of media is not likely to occur.
Cohen J1,2,3, Rieger D4, Wiemer K4,5 Research Laboratories, Livingston, New Jersey 07039, USA; 2Reprogenetics, Livingston, New Jersey 07039, USA; 3IVF online, Guelph, Ontario N1H2G6, Canada; 4LifeGlobal, Guelph, Ontario N1H2G6, Canada; 5Northwest Center for Reproductive Sciences, Washington 98101, USA
Evaluation and treatment of patients with recurrent implantation failure Zorina IV1,3, Yakovenko SA1,2 1AltraVita IVF Clinic, 4A Nagornaya St., Moscow 117186, Russia; 2Biophysics Dept, Moscow State University, Vorobievy Gory, Moscow 117234, Russia; 3e-mail: [email protected]
Introduction: The assumptions used to justify sequential media systems for human IVF are questionable, and the need for sequential media is not supported by direct experimental evidence. In fact, many clinical studies have shown that a single medium, such as Global®, can support the development of human embryos at least as well as sequential media systems. The objective of this paper is to present a brief summary of the history of the development of Global and the results of some of the clinical studies in which Global was directly compared with sequential media systems for culture of the human embryo to the blastocyst stage. Materials and methods: Global was made using two manufacturing laboratories aimed at providing optimal product quality and quality control. Each step of manufacturing and quality control was witnessed by a second observer. Results: In the mid-1980s, the US National Institutes of Health funded a multicentre project dedicated to the development of better embryo culture media. John Biggers was part of this ‘Culture Club’, and he and Joel Lawitts applied the engineering principles of simplex optimization to develop simplex optimization medium (SOM). They showed that SOM was capable of supporting the development of the mouse embryo through its 2-cell block and onward to the blastocyst stage. SOM was subsequently modified with additional potassium (KSOM) and then with amino acids (KSOMaa). KSOM and KSOMaa were shown to support the development of embryos of a variety of species including cattle, rabbit, monkey, pig and rat. Most notably, in 2002, Biggers and Racowsky showed that KSOMaa could support the development of the human embryo from the zygote to the blastocyst stage. At about the same time, Wiemer and his colleagues modified KSOMaa for the culture of human embryos and this became Global. Among other differences, Global contained alanyl-glutamine as a replacement for glutamine in the KSOMaa formulation. Based on recent observations by John Biggers, and after clinical testing, the alanyl-glutamine in Global was replaced with glycyl-glutamine. There are at least 17 published studies of Global for the culture of human embryos. Of those, four were direct comparisons with other media for culture from day 1 to day 3, and eight were direct comparisons with sequential media systems for culture from day 1 to the blastocyst stage. In all of the eight published studies comparing Global with sequential media systems, in-vitro development to the blastocyst stage and subsequent pregnancy and implantation rates were as good or better for Global than for sequential media. There appear to be no published studies showing any sequential media system to be superior to Global for the culture of human embryos to the blastocyst stage. Conclusions: The in-vitro development and subsequent pregnancy and implantation rates are as good or better for embryos cultured in Global compared with embryos cultured
Introduction: In the last few years of IVF practice, the problem of recurrent implantation failure (RIF) remains the most important and is still unsettled. RIF is defined as three or more failed IVF cycles with the presence of good-quality embryos for transfer in an IVF centre with overall pregnancy rate of no less than 30%. Materials and methods: A protocol of diagnostics and treatment was designed for patients with two previous negative IVF cycles carried out in the clinic. The main inclusion criterion for the patients to undergo this protocol was the presence of high-quality embryos for transfer. In 2007, 120 patients with RIF were evaluated and treated. Results: Diagnostic procedures included hysteroscopy and immunogenetic analysis – human leukocyte antigen typing of the couple, thrombophilic gene mutations, antiphospholipid or other autoantibodies. Treatment included hysteroscopic correction of uterine cavity pathology, laparoscopy for salpingectomy in case of hydrosalpinges, myomectomy, treatment of endometrium pathology, immunotherapy (intravenous immunoglobulin, steroids, aspirin and heparin), preimplantation genetic screening, assisted hatching, twostep embryo transfer and tailoring the stimulation protocols. Application of this protocol allowed an increase of the pregnancy rate for patients with RIF up to 42%. Conclusions: Because of the absence of evidence-based data about investigation and treatment of patients with RIF, additional diagnostic procedures and treatment for this group of patients are considered necessary.
1Tyho-Galileo
Improving micromanipulation Barak Y Dr Yona Barak Laboratories Ltd, 13 Ilanot st, Rosh HaAyin, Israel, 48570; e-mail: [email protected] The usage of micromanipulation techniques has led to a huge progress in the field of assisted reproductive technologies. The introduction of intracytoplasmic sperm injection (ICSI) resulted in consistent, relatively high pregnancy rates. The technique of injecting a whole, single spermatozoon directly into the oocyte cytoplasm by means of micromanipulation was found to be the superior solution for couples who due to male infertility could not conceive. ICSI became the main tool in IVF units worldwide for treating couples of male factor infertility with ejaculated or testicular spermatozoa. Additionally, ICSI enabled the enhancement of fertilization in oocytes that underwent maturation in vitro. Micromanipulation has also opened a window for technologies such as assisted zona hatching and preimplantation genetic diagnosis (PGD). PGD enables detection of various genetic abnormalities in the developing embryo in vitro, prior to embryo transfer. Major factors affecting the improvement of micromanipulation
S-19 Reproductive BioMedicine Online, Vol. 17, Suppl. 2, September 2008
Laboratory aspects A single medium for culture of the human embryo from zygote to blastocyst
in sequential media systems. Global has significant other practical advantages. For instance, only one medium needs to be tested and mix-up of media is not likely to occur.
Cohen J1,2,3, Rieger D4, Wiemer K4,5 Research Laboratories, Livingston, New Jersey 07039, USA; 2Reprogenetics, Livingston, New Jersey 07039, USA; 3IVF online, Guelph, Ontario N1H2G6, Canada; 4LifeGlobal, Guelph, Ontario N1H2G6, Canada; 5Northwest Center for Reproductive Sciences, Washington 98101, USA
Evaluation and treatment of patients with recurrent implantation failure Zorina IV1,3, Yakovenko SA1,2 1AltraVita IVF Clinic, 4A Nagornaya St., Moscow 117186, Russia; 2Biophysics Dept, Moscow State University, Vorobievy Gory, Moscow 117234, Russia; 3e-mail: [email protected]
Introduction: The assumptions used to justify sequential media systems for human IVF are questionable, and the need for sequential media is not supported by direct experimental evidence. In fact, many clinical studies have shown that a single medium, such as Global®, can support the development of human embryos at least as well as sequential media systems. The objective of this paper is to present a brief summary of the history of the development of Global and the results of some of the clinical studies in which Global was directly compared with sequential media systems for culture of the human embryo to the blastocyst stage. Materials and methods: Global was made using two manufacturing laboratories aimed at providing optimal product quality and quality control. Each step of manufacturing and quality control was witnessed by a second observer. Results: In the mid-1980s, the US National Institutes of Health funded a multicentre project dedicated to the development of better embryo culture media. John Biggers was part of this ‘Culture Club’, and he and Joel Lawitts applied the engineering principles of simplex optimization to develop simplex optimization medium (SOM). They showed that SOM was capable of supporting the development of the mouse embryo through its 2-cell block and onward to the blastocyst stage. SOM was subsequently modified with additional potassium (KSOM) and then with amino acids (KSOMaa). KSOM and KSOMaa were shown to support the development of embryos of a variety of species including cattle, rabbit, monkey, pig and rat. Most notably, in 2002, Biggers and Racowsky showed that KSOMaa could support the development of the human embryo from the zygote to the blastocyst stage. At about the same time, Wiemer and his colleagues modified KSOMaa for the culture of human embryos and this became Global. Among other differences, Global contained alanyl-glutamine as a replacement for glutamine in the KSOMaa formulation. Based on recent observations by John Biggers, and after clinical testing, the alanyl-glutamine in Global was replaced with glycyl-glutamine. There are at least 17 published studies of Global for the culture of human embryos. Of those, four were direct comparisons with other media for culture from day 1 to day 3, and eight were direct comparisons with sequential media systems for culture from day 1 to the blastocyst stage. In all of the eight published studies comparing Global with sequential media systems, in-vitro development to the blastocyst stage and subsequent pregnancy and implantation rates were as good or better for Global than for sequential media. There appear to be no published studies showing any sequential media system to be superior to Global for the culture of human embryos to the blastocyst stage. Conclusions: The in-vitro development and subsequent pregnancy and implantation rates are as good or better for embryos cultured in Global compared with embryos cultured
Introduction: In the last few years of IVF practice, the problem of recurrent implantation failure (RIF) remains the most important and is still unsettled. RIF is defined as three or more failed IVF cycles with the presence of good-quality embryos for transfer in an IVF centre with overall pregnancy rate of no less than 30%. Materials and methods: A protocol of diagnostics and treatment was designed for patients with two previous negative IVF cycles carried out in the clinic. The main inclusion criterion for the patients to undergo this protocol was the presence of high-quality embryos for transfer. In 2007, 120 patients with RIF were evaluated and treated. Results: Diagnostic procedures included hysteroscopy and immunogenetic analysis – human leukocyte antigen typing of the couple, thrombophilic gene mutations, antiphospholipid or other autoantibodies. Treatment included hysteroscopic correction of uterine cavity pathology, laparoscopy for salpingectomy in case of hydrosalpinges, myomectomy, treatment of endometrium pathology, immunotherapy (intravenous immunoglobulin, steroids, aspirin and heparin), preimplantation genetic screening, assisted hatching, twostep embryo transfer and tailoring the stimulation protocols. Application of this protocol allowed an increase of the pregnancy rate for patients with RIF up to 42%. Conclusions: Because of the absence of evidence-based data about investigation and treatment of patients with RIF, additional diagnostic procedures and treatment for this group of patients are considered necessary.
1Tyho-Galileo
Improving micromanipulation Barak Y Dr Yona Barak Laboratories Ltd, 13 Ilanot st, Rosh HaAyin, Israel, 48570; e-mail: [email protected] The usage of micromanipulation techniques has led to a huge progress in the field of assisted reproductive technologies. The introduction of intracytoplasmic sperm injection (ICSI) resulted in consistent, relatively high pregnancy rates. The technique of injecting a whole, single spermatozoon directly into the oocyte cytoplasm by means of micromanipulation was found to be the superior solution for couples who due to male infertility could not conceive. ICSI became the main tool in IVF units worldwide for treating couples of male factor infertility with ejaculated or testicular spermatozoa. Additionally, ICSI enabled the enhancement of fertilization in oocytes that underwent maturation in vitro. Micromanipulation has also opened a window for technologies such as assisted zona hatching and preimplantation genetic diagnosis (PGD). PGD enables detection of various genetic abnormalities in the developing embryo in vitro, prior to embryo transfer. Major factors affecting the improvement of micromanipulation
S-19 Reproductive BioMedicine Online, Vol. 17, Suppl. 2, September 2008