Assisted Reproductive Technology
|Embryology - 31 Jul 2015 Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Trends in ART procedures
- 4 18 Ways to Make a Baby
- 5 In Vitro Fertilization
- 6 Blastocyst Formation (in vitro)
- 7 Embryo Culture Milestones
- 8 Oldest IVF Mother
- 9 IVF Sex Ratios
- 10 Oocyte and Embryo Quality
- 11 In Vitro Maturation
- 12 Assisted Reproductive Technology (Australia and New Zealand)
- 13 Assisted Reproductive Technology (USA)
- 14 European Society of Human Reproduction and Embryology
- 15 Human Fertilisation and Embryology Authority UK (HFEA)
- 16 Canada
- 17 Sweden
- 18 Controlled Ovarian Stimulation
- 19 Gamete Banking
- 20 Ovarian Reserve
- 21 Ovarian Follicle Growth in vitro
- 22 References
- 23 External Links
- 24 Terms
- 25 Glossary Links
In vitro fertilization is one of now many different reproductive options know collectively as Assisted Reproductive Technologies (ART). These techniques continue to grow worldwide with development of new medical technologies. In vitro fertilization covers the aided fertilization process, in contrast with in vivo fertilization which is the normal uterine occuring fertilization process.
The earliest experiments 1945-48, involved fertilising oocytes that had been collected from women with spermatozoa in a petri dish. 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 Latin, In vitro = "in glass" meaning in essence a test tube as apposed to in vivo (in life or a living body), fertilisation (Aus spelling) and fertilisation (US spelling). Even in vivo fertilization can also now be considered "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)
- ART Links: Assisted Reproductive Technology | In Vitro Fertilization | Oocyte | Spermatozoa | Fertilization | Lecture - Fertilization | Lecture - Week 1 and 2 | Lecture - Genital Development | Robert Edwards | ART Glossary
Some Recent Findings
|More recent papers|
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Shigang Zhao, Ye Tian, Xuan Gao, Xiuqing Zhang, Hongbin Liu, Li You, Yongzhi Cao, Shizhen Su, Wai-Yee Chan, Yun Sun, Han Zhao, Zi-Jiang Chen Family-based analysis of eight susceptibility loci in polycystic ovary syndrome. Sci Rep: 2015, 5;12619 PMID: 26220222 Nikoletta Panagiotopoulou, Stamatios Karavolos, Meenakshi Choudhary Endometrial injury prior to assisted reproductive techniques for recurrent implantation failure: a systematic literature review. Eur. J. Obstet. Gynecol. Reprod. Biol.: 2015, 193;27-33 PMID: 26218557 Yingying Qin, Ting Guo, Guangyu Li, Tie-Shan Tang, Shidou Zhao, Xue Jiao, Juanjuan Gong, Fei Gao, Caixia Guo, Joe Leigh Simpson, Zi-Jiang Chen CSB-PGBD3 Mutations Cause Premature Ovarian Failure. PLoS Genet.: 2015, 11(7);e1005419 PMID: 26218421 Andreas Lammerich, Peter Bias, Beate Gertz Phase 1 safety, tolerability, and pharmacokinetic study of single ascending doses of XM17 (recombinant human follicle-stimulating hormone) in downregulated healthy women. Int J Womens Health: 2015, 7;707-16 PMID: 26213478 Akane Kitamura, Naoko Miyauchi, Hirotaka Hamada, Hitoshi Hiura, Hatsune Chiba, Hiroaki Okae, Akiko Sato, Rosalind M John, Takahiro Arima Epigenetic alterations in sperm associated with male infertility. Congenit Anom (Kyoto): 2015, 55(3);133-44 PMID: 26212350
Trends in ART procedures
- In the last 5 years there has been a shift from day 2-3 embryo (cleavage stage) transfers to day 5-6 embryo (blastocyst) transfers.
- The proportion of blastocyst transfers has increased from 27.1% in 2006 to 52.1% in 2010.
- Increase in the transfer of vitrified (ultra-rapid frozen) embryos. Compared with 2009, the proportion has more than doubled from 18.3% to 38.2%.
- reduction in the rate of multiple birth deliveries, with a decrease from 12% in 2006 to 7.9% in 2010.
- shifting to single embryo transfer, the proportion of which increased from 56.9% in 2006 to almost 70% in 2009 and 2010.
- decrease in the multiple delivery rate was achieved while clinical pregnancy rates remained stable at about 23% per cycle.
Data: Assisted reproductive technology in Australia and New Zealand 2010
18 Ways to Make a Baby
- Natural sex
- Artificial insemination - of mother with father's sperm
- Artificial insemination - of mother with donor sperm
- Artificial insemination - with egg and sperm donors, using surrogate mother
- In vitro fertilization (IVF) - using egg and sperm of parents
- IVF - with Intra-Cytoplasmic Sperm Injection (ICSI)
- IVF - with frozen embryos
- IVF - with Preimplantation Genetic Diagnosis (PGD)
- IVF - with egg donor
- IVF - with sperm donor
- IVF - with egg and sperm donor
- IVF - with surrogate using parents' egg and sperm
- IVF - with surrogate and egg donor
- IVF - with surrogate and sperm donor
- IVF - with surrogate using her egg, sperm from baby's father
- IVF - with surrogate using egg and sperm donors*
- Cytoplasmic transfer**
- Nuclear transfer and cloning
In Vitro Fertilization
First IVF Baby
Louise Brown was born at 1147 BST on 25 July, 1978, in Oldham, United Kingdom.
- Links: BBC Profile Louise Brown
Blastocyst Formation (in vitro)
The table below shows human blastocyst in vitro changes during week 1 development.
Embryo Culture Milestones
- 1944-48 human oocytes fertilised by spermatozoa in vitro
- 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."
Oocyte and Embryo Quality
There have been many attempts to establish morphological, biochemical or molecular markers of oocyte quality with variable results by different groups. Recently studies have also looked at the molecular quality of cumulus and granulosa cells. Earlier studies of this support cell population have looked at markers of mitosis and apoptosis, with positive and negative correlation respectively. Following removal of these support cells, oocyte features such as; nuclear maturation status, meiotic spindle presence, cytoplasm morphology, zona pellucida structure, and polar body presence and structure have all been investigated.
Several different microscopic techniques have also been used to visually analyse oocyte appearance:
- normal light microscopy
- phase contrast microscopy
- differential interference microscopy
- polarized light microscopy - A study has used polarization microscope to identify the spindle in rescue ICSI of unfertilized oocytes appears to result in better normal fertilization rate and less 3PN rate compared to the control group.
- confocal microscopy (not for clinical use)
A 2010 meeting of the Alpha Executive, and ESHRE Special Interest Group of Embryology, held in Istanbul, led to the "Istanbul consensus" established a consensus criteria and terminology for grading oocytes, zygotes and embryos that would be amenable to routine application in any IVF laboratory. The following sub-heading are brief summary points of the complete consensus.
Optimal oocyte morphology is that of a spherical structure enclosed by a uniform zona pellucida, with a uniform translucent cytoplasm free of inclusions and a size-appropriate polar body. Oocytes undergo both nuclear and cytoplasmic maturation, and that these processes are neither the same nor necessarily even synchronous.
- Cumulus-oocyte complex (COC) scoring - provides a tool for troubleshooting not a correlation with embryo developmental competence. This should be a binary score (0 or 1), with a ‘good' COC (score of 1) defined as having expanded cumulus and a radiating corona.
- Zona pellucida scoring- no specific benefit to measuring zona thickness, as evidence for any effect on outcome. However, it was noted that there could be patient-specific effects, and so a note should be made of exceptional observations regarding the colour or thickness of the zona pellucida.
- Perivitelline space - presence of inclusions in the perivitelline space is anomalous. However, there was insufficient evidence to support any specific prognosis associated with this observation. Therefore, the observation of inclusions should be noted, there is no requirement to count or measure them, only noted if it is exceptionally large.
- Polar body scoring - presence or absence of the first polar body should be noted in the uninseminated oocyte, where possible. Exceptionally large polar body should be noted and should not be inseminated, due to the risk of oocyte aneuploidy.
- Cytoplasm scoring - homogeneous cytoplasm is expected, and that non-homogeneous cytoplasm is of unknown biological significance.
- ‘Granularity' of the cytoplasm is ill-defined, and distinctly different from clustering of organelles.
- Organelle clustering is associated with lower implantation potential.
- smooth endoplasmic reticulum (sER) disks are associated with the risk of a serious, significantly abnormal outcome.
- Vacuolization - observation of large vacuoles in the oocyte should be noted.
- small vacuoles (5–10 µm in diameter) few small fluid filled and transparent are unlikely to be of biological consequence.
- large vacuoles (>14 µm in diameter) are associated with fertilization failure.
Pronuclear scoring - three categories can provide additional information to the fertilization check, and that both should be performed at the same time.
- abnormal - pronuclei with no NPBs (‘ghost pronuclei’), single nucleolar precursor body (‘bulls-eye pronuclei”).
- Assessment of cell number - 4 cells on Day 2 and 8 cells on Day 3 and related to embryo cell cleavage rates.
- more slowly than the expected rate have a reduced implantation potential
- faster than the expected rate are likely to be abnormal and have a reduced implantation potential.
- Fragmentation - an extracellular membrane-bound cytoplasmic structure that is <45 µm diameter in a Day-2 embryo and <40 µm diameter in a Day-3 embryo. Relative degrees of fragmentation were defined as:
- mild (<10%)
- moderate (10–25%)
- severe (>25%).
- Multi nucleation - the presence of more than one nucleus in a blastomere, and includes micronuclei, and is associated with a decreased implantation potential, increased level of chromosome abnormality and increased risk of spontaneous abortion.
- Cell size - embryos at the 2-, 4- and 8-cell stages, blastomeres should be even sized. For all other cell stages, one would expect a size difference in the cells, as the cleavage phase has not been completed.
Day 4 Assessment (Morula stage)
- optimal embryo at this stage (92 ± 2 h) would be compacted or compacting, and have entered into a fourth round of cleavage. T the consensus system uses three grades, the reason for a fair or poor grade should also be included.
Day 5 Assessment (Blastocyst stage)
- optimal embryo at this stage (116 ± 2 h) would be a fully expanded through to hatched blastocyst with an ICM that is prominent, easily discernible and consisting of many cells, with the cells compacted and tightly adhered together, and with a TE that comprises many cells forming a cohesive epithelium. It was agreed that while the ICM has a high prognostic value for implantation and fetal development, a functional TE is also essential. The consensus for a blastocyst scoring system was that there should be a combination of stage and score. It was agreed that ‘hatching' is defined as the obvious emergence of the TE with enclosed blastocoel through a thinning zona pellucida. It was also agreed that hatching cannot be reliably assessed in embryos with an artificially breached zona pellucida (with the exception of the breach made during ICSI). The ICM and TE should be graded relative to the Gardner A–C scale, but that a grade of 1–3 (rather than A–C) should be given—with Grade 1 equivalent to Gardner A.
- a non-viable embryo is an embryo in which development has been arrested for at least 24 h, or in which all the cells have degenerated or lysed.
In Vitro Maturation
In Vitro Maturation (IVM) is a term used to describe a range of techniques for developing ovarian follicles and oocytes outside of the body. These oocytes are generally retrieved from the antral follicles of either unstimulated or minimally stimulated ovaries. The technique has been suggested for polycystic ovary syndrome and other ovarian pathologies for fertility preservation. This is a relatively new approach to human fertility.
Assisted Reproductive Technology (Australia and New Zealand)
- Over 100,000 ART babies born over the last three decades in Australia and New Zealand.
- ART children estimated as 3.3% and 2.0% of all children currently born in Australia and New Zealand respectively.
Birthweight percentiles by gestational age for births following assisted reproductive technology in Australia and New Zealand, 2002-2010
- "What is the standard of birthweight for gestational age for babies following assisted reproductive technology (ART) treatment? A total of 69 315 births (35 580 males and 33 735 females) following ART treatment were analysed for the birthweight percentile. Preterm births (birth before 37 completed weeks of gestation) and low birthweight (<2500 g) were reported for 9.7 and 7.0% of live born singletons following ART treatment. The mean birthweight was 3280 g for live born singletons following fresh cycles (3338 g for male infants and 3217 for female infants) and 3413 g for live born singletons following thaw cycles (3475 g for male infants and 3349 for female infants). The comparison of birthweight percentile charts for ART births and general population births provide evidence that the proportion of SGA births following ART treatment was comparable to the general population for SET fresh cycles and significantly lower for thaw cycles. Both fresh and thaw cycles showed better outcomes for singleton births following SET compared with DET. Policies to promote single embryo transfer should be considered in order to minimize the adverse perinatal outcomes associated with ART treatment."
|ART in Australia and New Zealand 2010
||ART in Australia and New Zealand 2009 9 Nov 2011
|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."
Regulation of Assisted Reproductive Technology
Assisted Reproductive Technology (ART) , including IVF (or in vitro fertilisation) is regulated in Australia through both legislative and voluntary compliance frameworks. Legislation in three states is underpinned by a national system of accreditation by the Reproductive Technology Accreditation Committee (RTAC) of the Fertility Society of Australia, which is in turn is underpinned by guidelines produced by the NHMRC. This is outlined in more detail below.
- ART is regulated by specific legislation in three States, the Victorian Infertility Treatment Act (1995) , the South Australian Reproductive Technology Act (1988) and the Western Australian Human Reproductive Technology Act (1991) . Each of these pieces of legislation establishes a State regulatory body which issues Licences to clinics that provide ART services.
- There is no Commonwealth legislation covering the regulation of ART clinical practice.
- The Research Involving Human Embryos Act 2002 includes a requirement that use of non-excess ART embryos occurs in an RTAC-accredited ART clinic.
Reproductive Technology Accreditation Committee (RTAC). RTAC, under the Fertility Society of Australia, administers a national Code of Practice and a system for the accreditation of ART clinics in Australia. Through its Code of Practice, RTAC sets professional and laboratory standards for ART clinical practice.
(Information from the NHMRC)
Assisted Reproductive Technology (USA)
2012 Assisted Reproductive Technology National Summary Report
- ART procedures reported with the intention to transfer at least one embryo (157,662 cycles of the 176,247 total ART cycles performed in 2012).
- ART cycles started with the intention of freezing and banking all resulting eggs or embryos (18,585 cycles of the 176,247 total).
- ART additional cycles in which a new treatment procedure was being evaluated (27 total new treatment procedures in 2012 that are not counted as part of the 176,247 total ART cycles performed in 2012).
- ART cycles that used only fresh nondonor eggs or embryos from nondonor eggs or, in a few cases, a mixture of fresh and frozen embryos from nondonor eggs (99,665 cycles resulting in 80,783 transfers).
- ART cycles that used only frozen embryos from nondonor eggs (38,150 cycles resulting in 35,508 transfers).
- ART cycles that used only donated eggs or embryos (19,847 cycles resulting in 18,154 transfers).
Births Resulting From Assisted Reproductive Technology: Comparing Birth Certificate and National ART Surveillance System Data, 2011
- This report compares data on births resulting from assisted reproductive technology (ART) procedures from 2011 birth certificates with data from the 2011 National ART Surveillance System (NASS)
- Birth certificate data are based on 100% of births registered in 27 states and the District of Columbia. NASS data included all ART cycles initiated in 2010 or 2011 for which a live birth in 2011 was reported.
- Overall, the percentage of births resulting from ART procedures was 2.06 times higher for NASS data (1.44%) compared with birth certificate data (0.70%). The ratio for each jurisdiction varied from 1.04 for Utah and Wisconsin to 7.50 for Florida. Higher-risk groups had more consistent reporting between data sources [e.g., triplet or higher-order multiples (1.36) compared with singletons (2.11)].
- Births resulting from ART procedures appear to be underreported on the birth certificate; however, the magnitude of underreporting varied by jurisdiction and maternal-infant health characteristics.
- Number of ART clinics in the United States - 474
- Number of ART clinics that submitted data - 443
- Number of ART cycles reported - 147,260 (Excludes banking cycles and cycles in which a new treatment procedure was being evaluated)
- Number of live-birth deliveries resulting from ART cycles started - 47,090
- Number of infants born as a result of ART cycles performed - 61,564
- Graph Links: Report cover | clinics | types of ART | outcomes | donor-vs-own-eggs | donor fresh outcomes | maternal age | nondonor embryos transferred | nondonor frozen fresh outcomes | nondonor low birthweight | nondonor maternal age | nondonor miscarriage | nondonor outcomes 1 | nondonor outcomes 2 | nondonor outcomes 3 | nondonor outcomes 4 | nondonor outcomes 5 | nondonor preterm | nondonor procedure | nondonor results | ART USA | Assisted Reproductive Technology
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.
- Report Links: USA Statistics | 2009 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | [ http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5209a1.htm 2000]
European Society of Human Reproduction and Embryology
- Assisted reproductive technology in Europe, 2007 "This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007.
Highlights from the 2007 Report
- From 33 countries, 1029 clinics reported 493 184 treatment cycles
- IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731)
- preimplantation genetic diagnosis/preimplantation genetic screening (4638)
- in vitro maturation (660) and frozen oocytes replacements (3607)
- overall a 7.6% increase since 2006.
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
Society of Obstetricians and Gynaecologists of Canada summary statements (for January 2005 to December 2012) lists 15 key statements for pregnancy outcomes after assisted human reproduction
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"
Controlled Ovarian Stimulation
A variety of drug based techniques are used to stimulate maternal oocyte development, called controlled ovarian stimulation (COS), 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)
- 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.
Both men and women undergoing clinical procedures of chemotherapy and/or radiotherapy (ionizing radiation) can have induced gametogenic failure.
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.
A recent paper described the current practice of spermatozoa banking in the United Kingdom in relation to cancer patients. The UK Human Fertilization and Embryology Authority have now extended the period of storage permitted by their regulations to 55 years. They point to a lack of "national and international guidelines for the provision, organization, maintenance and management of the cryopreservation services."
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.
Ovarian Follicle Growth in vitro
2D and 3D methods of ovarian follicle growth in vitro.
- Tanya Milachich New advances of preimplantation and prenatal genetic screening and noninvasive testing as a potential predictor of health status of babies. Biomed Res Int: 2014, 2014;306505 PMID: 24783200 | PMC3982254 | Biomed Res Int.
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- Angela S Heisey, Erin M Bell, Michele L Herdt-Losavio, Charlotte Druschel Surveillance of congenital malformations in infants conceived through assisted reproductive technology or other fertility treatments. Birth Defects Res. Part A Clin. Mol. Teratol.: 2015; PMID: 25684703
- Marie E Thoma, Sheree Boulet, Joyce A Martin, Dmitry Kissin Births Resulting From Assisted Reproductive Technology: Comparing Birth Certificate and National ART Surveillance System Data, 2011. Natl Vital Stat Rep: 2014, 63(8);1-12 PMID: 25493705
- X J Ethan Moses, Tirsa Torres, Anna Rasmussen, Christopher George Congenital anomalies identified at birth among infants born following assisted reproductive technology in Colorado. Birth Defects Res. Part A Clin. Mol. Teratol.: 2014, 100(2);92-9 PMID: 24532453
- J de Mouzon, V Goossens, S Bhattacharya, J A Castilla, A P Ferraretti, V Korsak, M Kupka, K G Nygren, A Nyboe Andersen, European IVF-Monitoring (EIM), Consortium for the European Society on Human Reproduction and Embryology (ESHRE) Assisted reproductive technology in Europe, 2007: results generated from European registers by ESHRE. Hum. Reprod.: 2012, 27(4);954-66 PMID: 22343707
- Andreas Müller, Katja Keller, Jennifer Wacker, Ralf Dittrich, Gudrun Keck, Markus Montag, Hans Van der Ven, David Wachter, Matthias W Beckmann, Wolfgang Distler Retransplantation of cryopreserved ovarian tissue: the first live birth in Germany. Dtsch Arztebl Int: 2012, 109(1-2);8-13 PMID: 22282711
- Wang YA, Macaldowie A, Hayward I, Chambers GM, & Sullivan EA 2011. Assisted reproductive technology in Australia and New Zealand 2009. Assisted reproduction technology series no. 15. Cat. no. PER 51. Canberra: AIHW. Online Summary | PDF
- Vinay Sharma Sperm storage for cancer patients in the UK: a review of current practice. Hum. Reprod.: 2011, 26(11);2935-43 PMID: 21873609
- AIHW, Macaldowie A, Wang YA, Chambers GM & Sullivan EA 2012. Assisted reproductive technology in Australia and New Zealand 2010. Assisted reproduction technology series. Cat. no. PER 55. Canberra: AIHW. Online Summary | PDF | 26 Oct 2012
- C Y Fong, A Bongso Comparison of human blastulation rates and total cell number in sequential culture media with and without co-culture. Hum. Reprod.: 1999, 14(3);774-81 PMID: 10221713
- B D Bavister Culture of preimplantation embryos: facts and artifacts. Hum. Reprod. Update: 1995, 1(2);91-148 PMID: 15726768
- Asli Uyar, Saioa Torrealday, Emre Seli Cumulus and granulosa cell markers of oocyte and embryo quality. Fertil. Steril.: 2013, 99(4);979-97 PMID: 23498999
- Laura Rienzi, Basak Balaban, Thomas Ebner, Jacqueline Mandelbaum The oocyte. Hum. Reprod.: 2012, 27 Suppl 1;i2-21 PMID: 22811312 | Hum Reprod.
- Jeong Hee Moon, Weon-Young Son, Sara Henderson, Alina Mahfoudh, Michael Dahan, Hananel Holzer Spindle examination in unfertilized eggs using the polarization microscope can assist rescue ICSI. Reprod. Biomed. Online: 2013, 26(3);280-5 PMID: 23352100
- Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum. Reprod.: 2011, 26(6);1270-83 PMID: 21502182 | Hum Reprod.
- ALPHA Scientists In Reproductive Medicine, ESHRE Special Interest Group Embryology Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Reprod. Biomed. Online: 2011, 22(6);632-46 PMID: 21481639
- Zhuoyang Li, Yueping A Wang, William Ledger, Elizabeth A Sullivan Birthweight percentiles by gestational age for births following assisted reproductive technology in Australia and New Zealand, 2002-2010. Hum. Reprod.: 2014, 29(8);1787-800 PMID: 24908671
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- Wang YA, Dean JH & Sullivan EA. Assisted Reproduction Technology in Australia and New Zealand 2005 National Perinatal Statistics Unit (2007) AIHW Assisted reproduction technology series no. 11
- Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2012 Assisted Reproductive Technology National Summary Report. Atlanta (GA): US Dept of Health and Human Services; 2014. http://www.cdc.gov/art/ART2012
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J Smitz, M M Dolmans, J Donnez, J E Fortune, O Hovatta, K Jewgenow, H M Picton, C Plancha, L D Shea, R L Stouffer, E E Telfer, T K Woodruff, M B Zelinski Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation. Hum. Reprod. Update: 2010, 16(4);395-414 PMID: 20124287
Marius Meintjes, Samuel J Chantilis, David C Ward, James D Douglas, Alfred J Rodriguez, Ali R Guerami, David M Bookout, Brian D Barnett, James D Madden A randomized controlled study of human serum albumin and serum substitute supplement as protein supplements for IVF culture and the effect on live birth rates. Hum. Reprod.: 2009, 24(4);782-9 PMID: 19147504
July 2010 "Assisted Reproductive Technology" All (45041) Review (5016) Free Full Text (8551)
"in vitro fertilization" All (29785) Review (3172) Free Full Text (6189)
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.
- 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
- Victorian Assisted Reproductive Treatment Authority (VARTA) This group provides public education and resources for professionals and the community on fertility and issues related to assisted reproductive treatment, including IVF, surrogacy and donor-conception.
- USA CDC - Assisted Reproductive Technology
- 2012 Assisted Reproductive Technology National Summary Report
- Society for Assisted Reproductive Technology The Society for Assisted Reproductive Technology (SART) promotes and advances the standards for the practice of assisted reproductive technology to the benefit of patients, members and society at large.
- The American Society for Reproductive Medicine (ASRM) is a multidisciplinary organization for the advancement of information, education, advocacy and standards in the field of reproductive medicine.
- American Fertility Association (AFA) is a national consumer organization that offers support for men and women dealing with infertility. Their purpose is to educate the public about reproductive disease and support families during struggles with infertility and adoption.
- RESOLVE: The National Infertility Association is a national consumer organization that offers support for men and women dealing with infertility. Their purpose is to provide timely, compassionate support and information to people who are experiencing infertility and to increase awareness of infertility issues through public education and advocacy.
- 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
- National Conference of State Legislatures (USA) Embryo and Gamete Disposition Laws Updated July 2007
For a full list of terms see ART Glossary
- 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)
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Cite this page: Hill, M.A. (2015) Embryology Assisted Reproductive Technology. Retrieved July 31, 2015, from https://embryology.med.unsw.edu.au/embryology/index.php/Assisted_Reproductive_Technology
- © Dr Mark Hill 2015, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G