Talk:In Vitro Fertilization

Introduction

Louise Brown, the first IVF baby as an adult.

In vitro fertilization covers the aided fertilization process, in contrast with in vivo fertilization which is the normal uterine occuring fertilization process. The first successful IVF was carried out in the UK in 1978 by Edwards RG, et al., receiver of the 2010 Nobel Prize in Medicine. The now many different reproductive options are know as Assisted Reproductive Technologies (ART) and this technique continues to grow worldwide with development of new medical technologies.

The Latin, In vitro = "in glass" meaning in essence a test tube as apposed to in vivo (in life or a living body). Note that even in vivo fertilization can also now be assisted through some fertility drug treatments. Both processes have the same biological outcome, fusion of male and female gametes to form a diploid zygote.

In Australia, the first successful IVF occurred in 1980. and during 2005 1,596 IVF babies were born. In the same year in Australia and New Zealand 51,017 treatment cycles were reported, an increase of 13.7% of ART treatment cycles from 2004. In all countries using Assisted Reproductive Technologies (ART), pregnancy rates vary for the different methods of treatment and also between individual IVF or GIFT units. In Australia best clinical pregnancy rate (per 100 oocyte retrieval cycles) by most successful 25% of all clinics increased from 24.9% (1998) to 34.4% (2001) (NPSU data - ART 2002 report)

Author Comments
	Please not this is an Embryology educational site and does not provide any specific clinical or therapeutic information.

Some Recent Findings

Intracytoplasmic sperm insemination

The Nobel Prize in Physiology or Medicine 2010 was awarded to Robert G. Edwards "for the development of in vitro fertilization". Nobel Prize 2010 Use of zona pellucida-bound sperm for intracytoplasmic sperm injection produces higher embryo quality and implantation than conventional intracytoplasmic sperm injection "The proportion of high-quality embryos (grades 1 and 2) and implantation rate were significantly higher in the test group than in the control group, but the difference in fetal heart pregnancy rate was not significant despite seven more pregnancies being obtained in the test group (26 pregnancies) versus the control group (19 pregnancies) following fresh embryo transfers." Assisted Reproductive Technologies (ART) With Baboons A Nonhuman Primate Model for ART and Reproductive Sciences "The first ART baboons produced by ICSI, a pair of male twins, were delivered naturally at 165 days postgestation. Genetic testing of these twins confirmed their ART parental origins and demonstrated that they are unrelated fraternal twins not identicals." Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: data for 25 years. "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."

18 Ways to Make a Baby

1. Natural sex
2. Artificial insemination - of mother with father's sperm
3. Artificial insemination - of mother with donor sperm
4. Artificial insemination - with egg and sperm donors, using surrogate mother
5. In vitro fertilization (IVF) - using egg and sperm of parents
6. IVF - with Intra-Cytoplasmic Sperm Injection (ICSI)
7. IVF - with frozen embryos
8. IVF - with Preimplantation Genetic Diagnosis (PGD)
9. IVF - with egg donor
10. IVF - with sperm donor
11. IVF - with egg and sperm donor
12. IVF - with surrogate using parents' egg and sperm
13. IVF - with surrogate and egg donor
14. IVF - with surrogate and sperm donor
15. IVF - with surrogate using her egg, sperm from baby's father
16. IVF - with surrogate using egg and sperm donors*
17. Cytoplasmic transfer**
18. Nuclear transfer and cloning

First IVF Baby

Louise Brown was born at 1147 BST on 25 July, 1978, in Oldham, United Kingdom.

Blastocyst Formation (in vitro)

The table below shows human blastocyst in vitro changes during week 1 development.

Links: Week 1 | Blastocyst

Embryo Culture Milestones

• 1949 8 cell mouse embryo -> blastocyst (in saline and egg yolk)
• 1956 8 cell mouse embryo -> blastocyst (first embryo culture medium)
• 1957 2 cell mouse embryo -> blastocyst
• 1958 8 cell mouse embryo -> blastocyst, then transferred to pregnant recipient
• 1960's development of culture requirements for mouse mebryos
• 1965 2 cell mouse embryo -> blastocyst, then transferred into pseudopregnant recipient
• 1968 zygotes from mouse -> blastocysts
• 1968,70 2 & 4 cell rabbit embryos -> blastocyst in serum supplemented medium
• 1970,71 1 & 2 cell rabbit embryos -> blastocyst in defined medium
• 1970,81 Culture of in vitro fertilized human embryo -> 16 cells -> blastula
• 1998 Cloning of adult sheep "dolly"
• 2004 Cloning of human blastocysts

Data modified from

Oldest IVF Mother

There is still risk, ethical and genetic debate about very old women becoming pregnant by IVF.

• 2003 India - A 65-year old Indian woman was the oldest in the world to give birth by IVF.
• 2006 United Kingdom - A 62-year old woman has become the UK's oldest woman to give birth to a child.
• 2008 Australia - A 54-year old woman was Australia's oldest woman pregnant by IVF (most Australian IVF clinics do not treat women over 50)
• 2010 Australia - A 57-year old woman is now the oldest mother to give birth in Australia, has delivered IVF twins in Western Australia.

IVF Sex Ratios

A recent paper looked at Australian assisted reproductive technology (ART) data (2002-2006) studied the effect on human sex ratio at birth by different procedures. PMID:20875033

"More males were born following in vitro fertilisation single embryo transfer (IVF SET) (53.0%) than intracytoplasmic sperm insemination (ICSI) SET (50.0%), and following blastocyst SET (54.1%) than cleavage-stage SET (49.9%). For a specific ART regimen, IVF blastocyst SET produced more males (56.1%) and ICSI cleavage-stage SET produced fewer males (48.7%). The change in the sex ratio at birth of SET babies is associated with the ART regimen. The mechanism of these effects remains unclear. Fertility clinics and patients should be aware of the bias in the sex ratio at birth when using ART procedures."

Assisted Reproductive Technology (Australia and New Zealand)

	2005 - 51,017 treatment cycles reported to ANZARD in Australia and New Zealand in 2005. Of these cycles, 91.1% were from Australian fertility centres and 8.9% from New Zealand's centres. There is an increase of 13.7% of ART treatment cycles from 2004.

Average age of women was 35.5 years (35.2 years in 2002). Women aged older than 40 years has increased from 14.3% in 2002 to 15.3% in 2005.

Since ANZARD was established in 2002 there has been a significant increase in the number of embryos transfer cycles where women received single-embryo transfers (SET). SET cycles accounted for 48.3% of embryos transfer cycles in 2005, compared to 28.4% in 2002. The increase of SET cycles resulted more singleton deliveries. The proportion of singleton deliveries was 85.9% in 2005, the highest proportion ever reported.

Babies born to women who had a single-embryo transfer had better outcomes compared to babies born to women who had a double-embryo transfer (DET). In 2005, there were 3,681 SET babies and 5,589 DET babies. In SET babies, 96.1% were singletons, compared to 61.6% singletons in DET babies. SET babies had a lower proportion of preterm babies (11.7%), compared to 30.6% in DET babies. Similarly, 8.0% of SET liveborn babies were low birthweight, compared to 25.0% in DET liveborn babies.

Perinatal mortality rate is a measure of perinatal outcomes. In 2005, for all babies born following ART treatment, the perinatal mortality rate was 14.7 deaths per 1,000 births, a 23.8% decrease from 19.3 deaths per 1,000 births in 2004. The perinatal mortality rate was the lowest among singletons born following SET (7.3 deaths per 1,000 births) in 2005.

2004 - 41,904 IVF treatment cycles were started in Australia 92.6% (38,823) and New Zealand 7.4% (3,081). (More? NPSU Assisted Reproduction Technology Reports)

In Vitro Fertilization - ABC News Baby born from frozen embryo

"In what's thought to be a world first, a baby has been born in Melbourne using a woman's frozen egg and a donor's frozen sperm which created an embryo that was also frozen, then thawed and implanted into the mother"

"JOHN MCBAIN: Oh egg freezing is very difficult. Embryo freezing itself is very well established. We would probably have about 55 per cent of all the babies born from our program, and that's about 1,400 a year, come from frozen embryos. So, that's very well established technology. But even with these embryos, only 70 per cent of the embryos survive the freezing and thawing. With eggs, it's closer to 40 to 50 per cent, and then you have to have the number which don't fertilise following that, and then you have to have those which end up being frozen, possibly not surviving the embryo freezing stage too, and that's a reason we don't promote it."

Assisted Reproductive Technology (USA)

• Centre for Disease Control (USA) 1999 Survey of Assisted Reproductive Technology: Embryo Laboratory procedures and Practices (January 29, 1999) USA statistics including the survey document.

1996 Assisted Reproductive Technology Success Rates National Summary and Fertility Clinic Reports

• The 1996 report of pregnancy success rates is the second to be issued. The report includes a national report that uses information from 300 U.S. fertility clinics to provide an indepth national picture of ART; fertility clinic tables that provide ART success rates for each clinic that submitted and verified its1996 data; and an appendix containing a glossary of terms and lists of reporting and nonreporting clinics in the United States. (See Pie Graph)

1995 Assisted Reproductive Technology Success Rates National Summary and Fertility Clinic Report.]

• This report gives consumers and potential assisted reproductive technology (ART) users an idea of a woman's average chances of having a pregnancy and a live birth by using ART. The report includes a national summary that uses the information from all reporting fertility clinics to provide an indepth national picture of ART; fertility clinic reports that provide ART success rates for 259 clinics in the United States; and an appendix containing a glossary of terms used in the national and clinic reports.

European Society of Human Reproduction and Embryology

Reports annually (in the journal Human Reproduction) on the European results of assisted reproductive techniques. Listed below are some statistical information gathered from reporting clinics for the current 2001 report. ESHRE Report 2001

Highlights from the 2001 Report

• From 23 countries, 579 clinics reported 289,690 cycles
• IVF 120,946, ICSI 114,378, frozen embryo transfer (FER) 47,195 and egg donation (ED) 7,171 (4% increase since the year 2000)
• European data on intra-uterine inseminations (IUIs) were reported from 15 countries. A total of 67 124 cycles [IUI husband'sperm (IUI-H) 52 949 and IUI donor sperm (IUI-D) 14 185] were included.
• In 12 countries where all clinics reported to the register, a total of 108 910 cycles were performed in a population of 131.4 million (829 cycles/million inhabitants).
• IVF- clinical pregnancy rate per aspiration and per transfer was 25.1 and 29.0%, respectively.
• ICSI- clinical pregnancy rate per aspiration and per transfer was 26.2 and 28.3% (similar to the results from 2000).
• IUI-H- clinical pregnancy rate was 12.8% in women less than 40 and 9.7% in women 40 years of age.
• After IVF and ICSI, the distribution of transfer of one, two, three and 4 embryos was 12.0, 51.7, 30.8 and 5.5%, respectively.
• Distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 74.5, 24.0 and 1.5%, respectively.
• Range of triplet deliveries after IVF and ICSI differed from 0.0 to 8.2% between countries.
• After IUI-H in women less than 40 years of age, 10.2% were twin and 1.1% were triplet gestations.

Human Fertilisation and Embryology Authority UK (HFEA)

The UK Human Fertilisation and Embryology Authority (HFEA) was established in August 1991 following the passing of the Human Fertilisation and Embryology Act 1990 (HFE Act).

The HFEA's principal  tasks are to:

• License and monitor clinics that carry out in vitro fertilisation (IVF) and donor insemination
• License and monitor research centres undertaking human embryo research
• Regulate the storage of gametes and embryos

HFEA also provide a downloadable patient booklet: Your Guide to Infertility and website information on Patients' Guide to Donor Insemination (DI)

Links: Human Fertilisation and Embryology Authority, UK)

Sweden

Sweden had its first child born after in vitro fertilisation 20 years ago. A recent paper in BMJ looks at the change in multiple birthrates since a change in the early 1990s, to reduce the number of embryos transferred in the clinic from three to two.

"The rate of multiple births after in vitro fertilisation increased to a maximum of 29% in 1991 but fell to 18.5% by 2001, resulting in a 70% reduction of preterm births"

Temporal trends in multiple births after in vitro fertilisation in Sweden, 1982-2001: a register study Bengt Kallen, Orvar Finnstrom, Karl Gosta Nygren, Petra Otterblad Olausson

Spermatozoa Production

Human spermatozoa

• Fertile Male - Spermatozoa are generally collected from the male by ejaculation. These sperm can be used fresh or stored frozen for later use (spermatozoa banking).
• Infertile Male - Spermatozoa can also be collected from men who have had a vasectomy or with obstructive azoospermia (OA), by a testicular biopsy. A study has shown that both spermatozoa yield and rate of clinical pregnancy were lower in these male populations.

Ovarian Stimulation

A variety of drug based techniques are used to stimulate maternal oocyte development, called ovarian stimulation, for any in vitro fertilization procedure. The recommended for technique will vary for some procedures and also from clinic to clinic and between countries.

An example of ovarian stimulation (based on PMID20953827)

• Gonadotrophin releasing hormone agonist (GnRHa) triptorelin acetate (0.1 mg/day) treatment started on the 22nd day of the preceding menstrual cycle.
• Human menopausal gonadotrophin (HMG) and/or follicular stimulating hormone (FSH) was carried out daily 12 to 15 days later.
  • Dosage may vary dependent upon patient response and can be monitored by hourmone levels (oestradiol) and transvaginal ultrasound (follicular size).
• The resulting ovulatory wave generates large follicles (greater than 18 mm in diameter).
• Human chorionic gonadotrophin (HCG) is then administered (36 to 38 h later)
• Clinical transvaginal puncture is used to collect from these follicles cumulus-oocyte complexes.
• Oocytes are then isolated from these cumulus-oocyte complexes.

Links: Menstrual Cycle | Ovary Development | Oocyte Development | Pituitary

Gamete Banking

Women undergoing clinical procedures of chemotherapy and/or radiotherapy (ionizing radiation) can have induced premature ovarian failure. Therefore a growing reproductive option has been the collecting of oocytes or ovarian tissue before commencing these procedures and storing ("banking") by cryopreservation for later use. One major issue is coordination of the two procedures, as most cancer therapies commence immediately, and most reproductive procedures require substantial preparation time. Currently the cryopreservation techniques required for ovarian tissue preservation are also improving all the time. In a number of clinics women with breast cancer and of reproductive age are being counselled about their reproductive options.

Chemotherapy, alkylating and alkylating-like agents attach to the guanine base of DNA, cross-linking the DNA, preventing replication and cell division. Some examples include: busulfan, carboplatin, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, thiotepa

A third potential option that may also in future be available is the transplanting (allografting) of ovarian cortex between individuals, this has recently been carried out between genetically non-identical sisters.

Links: Abnormal Development - Environmental | Abnormal Development - Drugs | Abnormal Development - Radiation

Ovarian Reserve

Ovarian reserve is a term referring to the evaluation of ovary oocyte (egg) number and quality. A negative finding has been described as Diminished Ovarian Reserve, or an ovarian insufficiency or premature ovarian failure and may be seen in adult childhood cancer survivors and adult patients undergoing a number of therapies.

The anti-Müllerian hormone (AMH) level is currently the most sensitive marker of ovarian reserve.

Follicle Growth in vitro

References

Articles

<pubmed>20124287</pubmed> <pubmed>19147504</pubmed>

Search Pubmed

July 2010 "in vitro fertilization" All (29785) Review (3172) Free Full Text (6189)

Search Pubmed Now: in vitro fertilization | assisted reproduction technology

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

• Australia Assisted reproductive technology in Australia and New Zealand 2002 Report - Highlights Has links to the full report online. | (Australian) National Perinatal Statistics Unit | (Australian) National Perinatal Statistics Unit Assisted Reproduction Technology Reports | The Australian Infertility Support Group
• USA CDC - Assisted Reproductive Technology
• UK | Human Fertilisation and Embryology Authority (UK) | Your Guide to Infertility | Patients' Guide to Donor Insemination (DI) | Patients FAQs | Patients Guide to IVF Clinics (UK)
• IVF Directory
• The Merck Manual | The Merck Manual- Infertility | The Merck Manual- Pregnancy | Search The Merck Manual "Infertility" | Search The Merck Manual "Pregnancy"
• Sydney Commercial IVF Sites Sydney IVF | Citywest IVF | IVF South | North Shore Fertility Pty Ltd

Terms

• empty follicle syndrome - (EFS) Term used to describe a condition in which no oocytes are recovered/obtained after an apparently successful ovarian stimulation.

• follicle stimulating hormone - (FSH, gonadotropin) A glycoprotein hormone secreted by anterior pituitary (adenohypophysis gonadotrophs, a subgroup of basophilic cells) and acts on gametogenesis and other systems in both males and females. In females, FSH acts on the ovary to stimulate follicle development. Negative feedback by inhibin from the developing follicle decreases FSH secretion. In males, acts on the testis Sertoli cells to increase androgen-binding protein (ABP) that binds androgens and has a role in spermatogenesis. FSH-defficiency in females results in infertile (block in folliculogenesis prior to antral follicle formation) and in males does not affect fertility (have small testes but are fertile). FSH protein has a molecular weight 30 kDa and a 3-4 hour half-life in circulation. Gonadotrophins have been used clinically in humans for the treatment of infertility.
• human chorionic gonadotropin - (hCG, human chorionic gonadotrophin) Placental hormone initially secreted by cells (syncitiotrophoblasts) from the implanting conceptus during week two, supporting the ovarian corpus luteum, which in turn supports the endometrial lining and therefore maintains pregnancy. Hormone can be detected in maternal blood and urine and is the basis of many pregnancy tests. Hormone also stimulates the onset of fetal gonadal steroidogenesis, high levels are teratogenic to fetal gonadal tissues.

• human menopausal gonadotropin - (HMG) A clinical hormone preparation used in assisted reproductive technologies (ART). This hormone is collected from the urine of menopausal women and has similar biological activity to that of follicle stimulating hormone (FSH). This is used in an injectable form along with human chorionic gonadotropin (hCG) to induce ovulation. Some commercial product names include Menogon or Organon.
• triptorelin acetate - A gonadotropin-releasing hormone (GnRH) agonist used clinically in an acetate or pamoate form inreproduction for assisted reproductive technologies (ART, in vitro fertilization, IVF). This decapeptide (pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2) agonist stimulates the pituitary to decrease secretion of gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH). Also used for other clinical conditions.

• zona pellucida birefringence - (ZPB) Optical property of the zona pellucida using polarization imaging when viewed microscopically. Used to qualitatively predict the developmental potential of a in vitro matured metaphase-II (MII) oocytes. High birefringence has been associated with oocytes contributing to conception cycles when compared with those of nonconception cycles and higher implantation, pregnancy, and live birth rates from transferred oocytes. (More? PMID18284880 | PMID20079896)

Glossary Links

Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link

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Cite this page: Hill, M.A. (2026, September 19) Embryology In Vitro Fertilization. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:In_Vitro_Fertilization

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© Dr Mark Hill 2026, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G

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

• Sheep (ovine) http://www.ncbi.nlm.nih.gov/pubmed/20615540
• Horse (equine) http://www.ncbi.nlm.nih.gov/pubmed/20591059

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

• Effects of In Vitro Maturation on Histone Acetylation in Metaphase II Oocytes and Early Cleavage Embryos. http://www.ncbi.nlm.nih.gov/pubmed/20613962
  • free article http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2896857/?tool=pubmed

• 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."