Talk:In Vitro Fertilization

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2010

Relationship of Follicular Size to the Development of Intracytoplasmic Sperm Injection-derived Human Embryos

Taiwan J Obstet Gynecol. 2010 Sep;49(3):302-5.

Lee TF, Lee RK, Hwu YM, Chih YF, Tsai YC, Su JT.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taitung, Taiwan. Abstract OBJECTIVE: To compare the embryonic development of oocytes obtained from follicles of different sizes.

MATERIALS AND METHODS: Oocytes (n = 819) were retrieved from women at 40 years of age or younger during 86 in vitro fertilization cycles and categorized as small, medium, or large based on the estimated volume of follicular fluid at the time of retrieval.

RESULTS: The rates of good quality embryos from the large, medium, and small groups on days 2 and 3 were 76.85% and 66.20%, 74.00% and 61.33%, and 69.81% and 58.49%, respectively. There were no significant differences in the rates of good quality embryos between the three follicular volume groups.

CONCLUSION: Even though fewer oocytes completed maturation in the small follicle group than in the other two groups, the quality of the embryos in all three groups was the same on days 2 and 3. These findings suggest that follicles of all sizes should be aspirated during the intracytoplasmic sperm injection cycle as follicles of every size were a good source of embryos.

PMID: 21056315


Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage

Nat Biotechnol. 2010 Oct 3. [Epub ahead of print]

Wong CC, Loewke KE, Bossert NL, Behr B, De Jonge CJ, Baer TM, Pera RA.

[1] Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, California, USA. [2] Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, California, USA. [3] These authors contributed equally to this work. Abstract We report studies of preimplantation human embryo development that correlate time-lapse image analysis and gene expression profiling. By examining a large set of zygotes from in vitro fertilization (IVF), we find that success in progression to the blastocyst stage can be predicted with >93% sensitivity and specificity by measuring three dynamic, noninvasive imaging parameters by day 2 after fertilization, before embryonic genome activation (EGA). These parameters can be reliably monitored by automated image analysis, confirming that successful development follows a set of carefully orchestrated and predictable events. Moreover, we show that imaging phenotypes reflect molecular programs of the embryo and of individual blastomeres. Single-cell gene expression analysis reveals that blastomeres develop cell autonomously, with some cells advancing to EGA and others arresting. These studies indicate that success and failure in human embryo development is largely determined before EGA. Our methods and algorithms may provide an approach for early diagnosis of embryo potential in assisted reproduction.

PMID: 20890283

http://www.ncbi.nlm.nih.gov/pubmed/20890283?dopt=Abstract

http://www.nature.com/nbt/journal/vaop/ncurrent/full/nbt.1686.html

Biomarkers of human oocyte developmental competence expressed in cumulus cells before ICSI: a preliminary study

Assidi M, Montag M, Van Der Ven K, Sirard MA.

J Assist Reprod Genet. 2010 Oct 16.

Centre de recherche en biologie de la reproduction, Département des Sciences Animales, Laval University, Ste-Foy, Québec, Canada, G1K 7P4. Abstract PURPOSE: To identify reliable genomic biomarkers expressed in cumulus cells that accurately and non-invasively predict the oocyte developmental competence and reinforce the already used morphological criteria.

METHODS: Eight consenting patients were selected for ovarian stimulation and ICSI procedures. Cumulus-oocyte complexes were transvaginally punctured and individually selected based on both good morphological criteria and high zona pellucida birefringence. Following ICSI, two 3-day embryos per patient were transferred. Pregnancy outcome was recorded and proven implantation was thereafter confirmed. Differential gene expression was assessed using two microarray platforms. Further real-time PCR validation, Ingenuity pathways analysis and intra-patient analysis were performed on 17 selected candidates.

RESULTS: Seven genes were differentially (p ≤ 0.05) associated to successful pregnancy and implantation. These biomarkers could be used to predict the oocyte developmental competence.

CONCLUSIONS: These genomic markers are a powerful reinforcement of morphological approaches of oocyte selection. Their large-scale validation could increase pregnancy outcome and single embryo transfer efficiency.

PMID: 20953827

http://www.springerlink.com/content/0jv15jr4k35r64p5/fulltext.html

Timeline

  • 1959 Min Chueh Chang, working in the United States, had managed to carry out IVF in rabbits.
  • 1960s, and now based at Cambridge University, that he read of Patrick Steptoe’s experience in using the then novel technique of laparoscopy.

(The first 100 or so attempts ended in failure, with the embryo dying early on in the pregnancy.)

http://www.bmj.com/content/341/bmj.c5533.full


Other Species

SMH 2004 article - http://www.smh.com.au/articles/2004/09/13/1094927508626.html

Preimplantation mouse embryo selection guided by light-induced dielectrophoresis

PLoS One. 2010 Apr 13;5(4):e10160.

Valley JK, Swinton P, Boscardin WJ, Lue TF, Rinaudo PF, Wu MC, Garcia MM.

Berkeley Sensor & Actuator Center, Electrical Engineering and Computer Sciences, University of California, Berkeley, California, United States of America. Abstract Selection of optimal quality embryos for in vitro fertilization (IVF) transfer is critical to successful live birth outcomes. Currently, embryos are chosen based on subjective assessment of morphologic developmental maturity. A non-invasive means to quantitatively measure an embryo's developmental maturity would reduce the variability introduced by the current standard. We present a method that exploits the scaling electrical properties of pre-transfer embryos to quantitatively discern embryo developmental maturity using light-induced dielectrophoresis (DEP). We show that an embryo's DEP response is highly correlated with its developmental stage. Uniquely, this technique allows one to select, in sequence and under blinded conditions, the most developmentally mature embryos among a mixed cohort of morphologically indistinguishable embryos cultured in optimized and sub-optimal culture media. Following assay, embryos continue to develop normally in vitro. Light-induced dielectrophoresis provides a non-invasive, quantitative, and reproducible means to select embryos for applications including IVF transfer and embryonic stem cell harvest.

PMID: 20405021

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010160

Blastocyst versus cleavage stage transfer in in vitro fertilization: differences in neonatal outcome?

Fertil Steril. 2010 Oct;94(5):1680-3. Epub 2010 Feb 4.

Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Olausson PO.

Tornblad Institute, University of Lund, Lund, Sweden. Bengt.Kallen@med.lu.se Abstract OBJECTIVE: To compare neonatal outcome of blastocyst and cleavage stage embryo transfers after IVF.

DESIGN: Register study.

SETTING: Births recorded in the Swedish Medical Birth Register after IVF performed, 2002-2006.

PATIENT(S): Treatments reported from all Swedish IVF clinics.

INTERVENTION(S): None.

MAIN OUTCOME MEASURE(S): Some neonatal characteristics were compared in 1,311 infants born after blastocyst-stage transfer and 12,562 infants born after cleavage-stage transfer. Comparisons were also made with all births, 2002-2007 (n = 598,687).

RESULT(S): After adjusting for year of birth, maternal age, parity, smoking habits, and body mass index, the risk of preterm birth among singletons was significantly greater after blastocyst-stage transfer than after cleavage-stage transfer. The risk of congenital malformations was also significantly higher. When the analysis was restricted to clinics where blastocyst transfers were made, the risk estimates increased for preterm birth, low birth weight, low APGAR score, and respiratory diagnoses, but did not change for congenital malformations.

CONCLUSION(S): The results indicate a small increase in risk associated with blastocyst transfer, perhaps owing to the longer period of in vitro culture. There is a possibility that this effect is due, at least in part, to a selection of women for blastocyst transfers. Further studies are needed either to verify or to refute the found associations.

PMID: 20137785


Comparison of the major malformation rate of children conceived from cryopreserved embryos and fresh embryos

Chin Med J (Engl). 2010 Jul;123(14):1893-7.

Li HZ, Qiao J, Chi HB, Chen XN, Liu P, Ma CH.

Medical Center for Human Reproduction, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China. Abstract BACKGROUND: Cryopreserved embryo transfer has become indispensable in reproductive technology. More and more children are conceived from frozen-thawed embryo transfer (FET). The risk of birth defects associated with frozen-thawed embryo transfer has been evaluated and conflict results are obtained. The aim of this study was to compare the rate of major malformations in children conceived from cryopreserved embryos with that of children from fresh embryos.

METHODS: A retrospective analysis was performed on children conceived from frozen-thawed embryos and fresh embryos between January 2005 and December 2008 at the Reproduction Center of the Third Hospital, Peking University. The major malformation rates were compared between two groups for all children, as well as singletons or twins, separately. The frequencies of different subtypes of malformations classified according to different organ system were also compared.

RESULTS: Thirty-four of 3125 children from cryopreserved embryos had a major malformation. The malformation rate was 1.09%, which was comparable to that for children after fresh embryos transfer (1.53% (55/3604), OR: 0.71, 95%CI; 0.46-1.09). The malformation rate was also similar when the analysis was limited to children from cryopreserved embryos resulted from in vitro fertilization (IVF) (1.39%) and fresh IVF (1.3%). However, children from cryopreserved embryos resulted from intracytoplasmic sperm injections (ICSI) had much lower malformation rate than from fresh ICSI (0.63% vs.1.83%, OR: 0.34, 95%CI: 0.16-0.75). No difference was found in the incidence of major malformations in singletons from cryo ICSI (0.73%) and fresh ICSI (1.9%), or from cryo IVF (1.49%) and fresh IVF (1.67%). Similar malformation rate was found in multiples from cryo ICSI (0.52%) and fresh ICSI (1.76%), or cryo IVF (1.30%) and fresh IVF (0.90%). The distribution and risk of the subtype of malformations, such as cardiovascular, gastrointestinal, neural tube, urogenital, musculoskeletal and facial abnormalities was not different between the cryo group and fresh group.

CONCLUSIONS: The major malformation rate is similar between fetuses/children conceived from cryopreserved embryos and those from fresh embryos. Large prospective and long-term follow-up studies are needed to get exact results concerning the birth defects of the children born after cryopreserved embryos.

PMID: 20819574


http://www.ncbi.nlm.nih.gov/pubmed/20819574

Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years.

Hum Reprod. 2010 Apr;25(4):1026-34. Epub 2010 Feb 5.

Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Otterblad Olausson P.

Tornblad Institute, University of Lund, Biskopsgatan 7, SE-223 62 Lund, Sweden. bengt.kallen@med.lu.se Abstract

BACKGROUND: Marked changes have occurred in in vitro fertilization (IVF) methodology during the past 25 years but also in characteristics of couples undergoing treatment.

METHODS: This study was based on 27 386 women undergoing IVF treatment from 1982 to 2006 and giving birth to 31 850 infants. Outcomes of deliveries were studied using Swedish health registers. Comparisons were made with all deliveries in the population (n = 2 603 601). Adjusted odds ratios were calculated when important changes in background rates had occurred.

RESULTS: There was a substantial increase in the use of intracytoplasmatic sperm injection (ICSI) and the transfer of cryopreserved embryos. Among all ICSI cases, the proportion using epididymal or testicular sperm varied between 5 and 10%. Maternal characteristics changed during the observation period but the median age remained relatively constant in spite of the increasing maternal age in the population. There was a decline in the rate of some maternal pregnancy diagnoses (notably pre-eclampsia, premature rupture of membranes) and some neonatal diagnoses (notably preterm births, low birthweight, cerebral hemorrhage, respiratory diagnoses, use of continuous positive airway pressure and mechanical ventilation, sepsis/pneumonia). Up till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% towards the end of the period whereas higher order multiples nearly disappeared. The total rate of infants with congenital malformations changed only little.

CONCLUSIONS: The decrease in unwanted outcomes can, to a large extent, be explained by the reduced rate of multiple births but was seen also among singletons. Other explanations can be sought in changes in the characteristics of patients undergoing IVF.

PMID: 20139431 [PubMed - indexed for MEDLINE]

Effects

  • Reorganization of the Endoplasmic Reticulum and Development of Ca2+ Release Mechanisms During Meiotic Maturation of Human Oocytes. http://www.ncbi.nlm.nih.gov/pubmed/20610804
    • "Oocyte maturation in rodents is characterized by a dramatic reorganization of the endoplasmic reticulum (ER) and an increase in the ability of an oocyte to release Ca(2+) in response to fertilization or inositol 1,4,5-trisphosphate (IP(3)). We examined if human oocytes undergo similar changes during cytoplasmic meiotic maturation both in vivo and in vitro. Immature, germinal vesicle (GV)-stage oocytes had a fine network of ER throughout the cortex and interior, whereas the ER in in vivo-matured metaphase II (MII)-stage oocytes was organized in large (~2-3 microm) accumulations throughout the cortex and interior. Likewise, oocytes matured in vitro exhibited cortical and interior clusters with no apparent polarity with regard to the meiotic spindle. In vivo-matured oocytes contained approximately 1.5X the amount of IP3 receptor protein and released significantly more Ca(2+) in response to IP(3) than GV-stage oocytes; however, oocytes matured in vitro did not contain more IP(3) receptor protein or release more Ca(2+) in response to IP(3) than GV-stage oocytes. These results show that at least one cytoplasmic change occurs during in vitro maturation of human oocytes that might be important for fertilization and subsequent embryonic development but suggest that a low developmental competence of in vitro matured oocytes could be due to deficiencies in the ability to release Ca(2+) at fertilization."