Assisted Reproductive Technology

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Introduction

Louise Brown, the first IVF baby as an adult
Louise Brown, the first IVF baby as an adult.
ART Preimplantation blastomere biopsy
ART Preimplantation blastomere biopsy[1]

In vitro fertilization is one of now many different reproductive options know collectively as Assisted Reproductive Technology (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.


More than 5 million babies have been born worldwide through IVF (2015)


The earliest experiments 1945-48, involved fertilising oocytes that had been collected from women with spermatozoa in a petri dish.[2] The first successful IVF was carried out in the UK in 1978 by Edwards RG, et al.[3], 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.[4] 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 | Oncofertility | In Vitro Oogenesis | NIPT | oocyte | spermatozoa | fertilization | Lecture - Fertilization | Lecture - Week 1 and 2 | Lecture - Genital Development | Robert Edwards | IVF Questions | ART Report 2013 | ART USA | ART Glossary | Category:ART


Robert Edwards.jpg

Robert Edwards

The Nobel Prize in Physiology or Medicine 2010 - Awarded to Robert G. Edwards "for the development of in vitro fertilization" who battled societal and establishment resistance to his development of the in vitro fertilization procedure, which has so far led to the birth of around 4 million people. (More? Assisted Reproductive Technology | Nobel Prize 2010)


10 April 2013 - Sir Robert Edwards has died aged 87. BBC News

Some Recent Findings

Swapping mitochondrial DNA mammalian oocytes
Intracytoplasmic sperm insemination
  • Follicle size indicates oocyte maturity and blastocyst formation but not blastocyst euploidy following controlled ovarian hyperstimulation of oocyte donors[5] "Is there is an association between follicle size and the quality of oocytes retrieved from them as judged by ability to achieve the blastocyst stage, blastocyst grades and blastocyst ploidy? SUMMARY ANSWER: Although follicle size is a valuable predictor of oocyte maturity and is a significant predictor of the ability of a fertilized oocyte to become a quality blastocyst, the ploidy of each quality blastocyst is not related to the size of the follicle from which its oocyte was retrieved."
  • Associations of Assisted Reproductive Technology and Twin Pregnancy With Risk of Congenital Heart Defects[6] "The extent to which assisted reproductive technology is associated with increased risk of congenital heart defects independent of its known association with twinning remains uncertain. To assess the extent to which assisted pregnancy is associated with increased risk of congenital heart defects independent of its known association with twinning. This retrospective cohort study linked records of congenital heart defect diagnoses with assisted reproductive technology cycles in 507 390 singleton or twin pregnancies (10 149 assisted pregnancies and 497 241 nonassisted pregnancies), including singleton and twin early pregnancy losses, stillbirths, and live births (follow-up to 1 year of age) in Ontario, Canada, between April 1, 2012, and October 31, 2015. Statistical analysis was performed from January 1, 2017, to September 9, 2019. Assisted reproductive technology and its 2 subtypes: intracytoplasmic sperm injection and in vitro fertilization without intracytoplasmic sperm injection. The main outcome was congenital heart defects (prevalence and relative risk measured as odds ratios [ORs]). Mediation analysis was performed to assess the extent to which the association between assisted reproductive technology and congenital heart defects was mediated by twinning. CONCLUSIONS AND RELEVANCE: Our study results suggest that the association between assisted reproductive technology and congenital heart defects may be mediated by twinning." cardiovascular abnormalities
  • The cytokine profile of follicular fluid changes during ovarian ageing[7] "Ovarian ageing is one of the commonest causes of infertility in patients consulting for assisted reproductive technology. The composition of the follicular fluid (FF), which reflects the exchanges between the oocyte and its microenvironment, has been extensively investigated to determine the metabolic pathways involved in various ovarian disorders. Considering the importance of cytokines in folliculogenesis, we focused on the cytokine profile of the FF during ovarian ageing. Our cross-sectional study assesses the levels of 27 cytokines and growth factors in the FF of two groups of women undergoing in vitro fertilization. One group included 28 patients with ovarian ageing clinically characterized by a diminished ovarian reserve (DOR), and the other group included 29 patients with a normal ovarian reserve (NOR), serving as controls. ...Thus, PDGF-BB would seem to be implicated in the physiopathology of DOR, potentially in relation to its role in folliculogenesis or in the protection against oxidative stress." OMIM - PDGF-BB
More recent papers 
Mark Hill.jpg
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More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Assisted Reproductive Technology

Older papers 
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.

  • Association of In Vitro Fertilization With Childhood Cancer in the United States[8] "This study found a small association of IVF with overall cancers of early childhood, but it did observe an increased rate of embryonal cancers, particularly hepatic tumors, that could not be attributed to IVF rather than to underlying infertility. Continued follow-up for cancer occurrence among children conceived via IVF is warranted." See also earlier 2016 paper.[9]
  • Review - Mitochondrial replacement therapy and assisted reproductive technology[10] "Emerging techniques, involving maternal spindle transfer (MST) and pronuclear transfer (PNT), have demonstrated in preventing carryover of the unbidden (mutated) mtDNA in egg or in early embryos. The House of Parliament in the United Kingdom passed regulations permitting the use of MST and PNT in 2015. Furthermore, the Human Fertilization and Embryology Authority (HFEA) to granted licenses world first use of those techniques in March 2017. However, recent evidence demonstrated gradual loss of donor mtDNA and reversal to the nuclear DNA-matched haplotype in MRT derivatives. CONCLUSION: While further studies are needed to clarify mitochondrial biogenesis responsible for reversion, ruling in United Kingdom may shift the current worldwide consensus that prohibits gene modification in human gametes or embryos, toward allowing the correction of altered genes in germline."
  • New national outcome data on fresh versus cryopreserved donor oocytes[11] "A retrospective analysis of 2013 through 2015 aggregate U.S. national data reported by the Society for Assisted Reproductive Technology which included 30,160 IVF cycles with either fresh or cryopreserved donor oocytes was performed. During the study period utilization of fresh oocyte donations rapidly declined by 32.9%, while cryopreserved oocyte donation increased by 44.4%. Fresh donor oocytes produced significantly higher live birth rates per recipient cycle start than cryopreserved donor oocytes (51.1% vs. 39.7%). Over the three-year study period fresh donor oocytes produced stable live birth rates per recipient cycle start while those with cryopreserved oocytes significantly declined year-by-year."
  • Severity of congenital heart defects associated with assisted reproductive technologies[12]"In this study, the rate of CHD in pregnancies resulting from ART at a single high-risk pregnancy referral center are compared to the published literature. METHODS: Pregnancies were screened by fetal echocardiography for the indication of ART over a 2-year period. CHD were classified as either mild or severe based on the need for postnatal surgical intervention. Results were compared to findings from a literature review of studies examining CHD in pregnancies resulting from ART since 1980. RESULTS: Over the course of two years, 363 fetuses in 264 pregnancies from our cohort were screened for CHD. The incidence of mild CHD in fetuses from ART pregnancies was 2.75% (10 out of 363 fetuses). None of the affected fetuses had severe CHD. Review of the literature yielded 20 studies since 1980 that examined CHD in pregnancies resulting from ART. Composite data from the studies was described based on characterization of severity of the CHD anomalies. The incidence of mild CHD in ART pregnancies was 2.2%, compared to 1% in non-ART pregnancies (out of 332,157 infants). The incidence of severe CHD in ART pregnancies and naturally conceived pregnancies was 1.4% and 1.2%, respectively (out of 661,455 infants). The incidence of unspecified CHD in ART pregnancies was 1.8%, compared to 1% in naturally conceived pregnancies (out of 1,593,277 infants)."
  • Inter-laboratory agreement on embryo classification and clinical decision: Conventional morphological assessment vs. time lapse[13] "This study compares the data obtained from a pilot study of external quality control (EQC) of time lapse, performed in 2014, with the classical EQC of the Spanish Society for the Study of Reproductive Biology (ASEBIR) performed in 2013 and 2014. In total, 24 laboratories (8 using EmbryoScope™, 15 using Primo Vision™ and one with both platforms) took part in the pilot study. The clinics that used EmbryoScope™ analysed 31 embryos and those using Primo Vision™ analysed 35. ...In conclusion, time-lapse technology does not improve inter-laboratory agreement on embryo classification or the analysis of each morphological variable. Moreover, depending on the time-lapse platform used, inter-laboratory agreement may be lower than that obtained by CMA. However, inter-laboratory agreement on clinical decisions is improved with the use of time lapse, regardless of the platform used."
  • Does Embryo Culture Medium Influence the Health and Development of Children Born after In Vitro Fertilisation?[14] "In animal studies, extensive data revealed the influence of culture medium on embryonic development, foetal growth and the behaviour of offspring. However, this impact has never been investigated in humans. For the first time, we investigated in depth the effects of embryo culture media on health, growth and development of infants conceived by In Vitro Fertilization until the age of 5 years old. ...The culture medium had no significant effect on birthweight, risk of malformation (minor and major), growth and the frequency of medical concerns. However, the children of the Global medium (Global group) were less likely than those of the Single Step Medium (SSM group) to show developmental problems (p = 0.002), irrespective of the different domains. In conclusion, our findings showed that the embryo culture medium may have an impact on further development."
  • Assisted reproductive technology and the risk of preterm birth among primiparas[15] "Among (USA) singleton births to primiparas, those conceived with ART had an increased risk for preterm birth, even when only the male partner had been diagnosed with infertility. The risk of preterm birth for ART-conceived infants whose mothers were diagnosed with infertility included the earliest deliveries. " Preterm
  • Surveillance of congenital malformations in infants conceived through assisted reproductive technology or other fertility treatments[16] "Outcomes were assessed from the New York State Congenital Malformations Registry. Specific malformations were examined to determine if there is elevated risk for exposed singleton infants compared with infants conceived naturally. RESULTS: The study included 7120 in the ART group, 11,890 in the other fertility treatments group and 1,118,162 in the comparison group. The relative risk for a congenital malformation was 1.43 (95% CI 1.19-1.72) for singleton infants conceived through ART compared with singleton infants conceived naturally. The specific defects associated with ART were patent ductus arteriosus, hypospadias, and obstructive defect in the renal pelvis and ureter, while spina bifida, other specific anomalies of the spinal cord, atresia or stenosis of the pulmonary valve, hypospadias, and obstructive defects of the renal pelvis and ureter were associated with other fertility treatment. Assisted reproductive technology is associated with a slight excess risk of birth defects. The specific congenital malformations with elevated risks for singleton infants vary depending on the exposure. Further research is necessary to understand the mechanism related to the increase in risk."
  • Births Resulting From Assisted Reproductive Technology: Comparing Birth Certificate and National ART Surveillance System Data, 2011.[17] "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) among the subset of jurisdictions that adopted the 2003 revised birth certificate as of January 1, 2011, with information on ART. 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." USA Statistics
  • Congenital anomalies identified at birth among infants born following assisted reproductive technology in ColoradoPubmedParser error: Invalid PMID, please check. (PMID: < 24532453<) "This study suggests that conception by means of ART is not associated with an increased risk of congenital abnormalities identified by birth certificate data in Colorado when compared with births following natural conception."
  • Assisted reproductive technology in Europe, 2007[18] "This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007. 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, this represents a 7.6% increase since 2006."
  • Retransplantation of cryopreserved ovarian tissue: the first live birth in Germany[19] "Cryopreserved ovarian tissue can be retransplanted to restore fertility after radiation or chemotherapy. To date, 15 live births after retransplantation have been reported worldwide. We report the first pregnancy and the first live birth after retransplantation in Germany. This was the first live birth after retransplantation of cryopreserved ovarian tissue in Germany and also the first case with histological confirmation that the oocyte from which the patient conceived could only have come from the retransplanted tissue."
  • Assisted reproductive technology in Australia and New Zealand 2009[20] "In 2009, there were 70,541 assisted reproductive technology (ART) treatment cycles undertaken in Australian and New Zealand. Of these cycles, 17.2% resulted in a live delivery (the birth of at least one liveborn baby). In total, 13,114 liveborn babies were born following ART treatment in 2009. The most important trend in ART treatment has been the increase of single embryo transfer, from 48.3% in 2005 to 69.7% in 2009. This trend has resulted in significant reduction of multiple delivery rate from 14.1% in 2005 to 8.2% in 2009." (More? Reports)
  • Sperm storage for cancer patients in the UK: a review of current practice[21] "An increasing number of cancer patients can now hope to have a full and normal life due to significant improvements in treatment outcomes and survival rates. The application of cryobiology to store fertile gametes before sterilizing treatments has been a natural progression. Greater awareness has markedly increased the worldwide demand for long-term storage of sperm, and has prompted the UK Human Fertilization and Embryology Authority to extend the period of storage permitted by their regulations to 55 years. Other patients undergoing sterilizing chemotherapy and/or radiotherapy such as haemoglobinopathies requiring bone marrow transplantation and autoimmune disorders such as rheumatoid arthritis may further increase the indications for sperm storage. Most adult and adolescent patients and their relatives/spouses/parents/guardians value this service even though very few eventually use the sperm. There is an urgent need to develop national and international guidelines for the provision, organization, maintenance and management of the cryopreservation services."

Trends in ART procedures

Assisted reproductive technology in Australia and New Zealand 2010
  • 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[22]

18 Ways to Make a Baby

USA-ART2009-types-of-ART.jpg
  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

In Vitro Fertilization

First IVF Baby

Louise Brown, the first IVF baby as an adult.

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.[23] Human blastocyst formation-in vitro.jpg


Human-blastocyst-day-3-6-icon.jpg
 ‎‎Day 3 to 6
Page | Play
Human blastocyst day 5-6.jpg
 ‎‎Contractions
Page | Play
Human blastocyst hatching movie icon.jpg
 ‎‎Hatching
Page | Play
Links: Week 1 | Blastocyst

Embryo Culture Milestones

  • 1944-48 human oocytes fertilised by spermatozoa in vitro[2][24]
  • 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[25]

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.[26] 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.[27]

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.[28]
  • 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"[29][30] 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.

Oocyte Scoring

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.

Zygote Scoring

Pronuclear scoring - three categories can provide additional information to the fertilization check, and that both should be performed at the same time.

  1. symmetrical
  2. non-symmetrical
  3. abnormal - pronuclei with no NPBs (‘ghost pronuclei’), single nucleolar precursor body (‘bulls-eye pronuclei”).

Cleavage-stage Scoring

  • 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.

Non-viable Embryo

  • 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.


Links: Ovary_Development | Polycystic Ovary Syndrome

Assisted Reproductive Technology (Australia and New Zealand)


  • There were 88,929 ART treatment cycles reported from Australian and New Zealand fertility clinics in 2019 (81,049 and 7,880 respectively), representing an increase of 6.2% in Australia and 2% in New Zealand from 2018. This equates to 15.6 cycles per 1,000 women of reproductive age (15–44 years) in Australia, compared with 7.9 cycles per 1,000 women of reproductive age in New Zealand. Women used their own oocytes or embryos (autologous cycles) in 95% of treatments. Embryos and oocytes that had been frozen and thawed were used in 36.7% of autologous cycles.
  • Overall, live birth rates per embryo transfer have risen from 25.3% in 2015 to 28% in 2019.


Australia Birthweight Data 2002-2010

Birthweight percentiles by gestational age for births following assisted reproductive technology in Australia and New Zealand, 2002-2010[31]

"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."
Links: Australian Statistics | Birth Weight
Australia 2010 Data  
Assisted reproductive technology in Australia and New Zealand 2010. Assisted reproductive technology in Australia and New Zealand 2009.
ART in Australia and New Zealand 2010[22]
  • In 2010, there were 61,774 assisted reproductive technology (ART) treatment cycles performed in Australia and New Zealand.
  • Of these, 23.9% resulted in a clinical pregnancy and 18.1% in a live delivery (the birth of at least one liveborn baby).
  • There were 12,056 liveborn babies following ART treatments in 2010.
ART in Australia and New Zealand 2009[32] 9 Nov 2011
  • In 2009, there were 70,541 assisted reproductive technology (ART) treatment cycles undertaken in Australian and New Zealand.
  • Of these cycles, 17.2% resulted in a live delivery (the birth of at least one liveborn baby).
  • In total, 13,114 liveborn babies were born following ART treatment in 2009.
  • The most important trend in ART treatment has been the increase of single embryo transfer, from 48.3% in 2005 to 69.7% in 2009.
  • This trend has resulted in significant reduction of multiple delivery rate from 14.1% in 2005 to 8.2% in 2009.
IVF cycles ANZ 1999-2004.jpg 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.[33]
   

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.[33]

ART 2004

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.

Current legislation

  • 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)


Links: NHMRC information | RTAC

Assisted Reproductive Technology (USA)

USA 2016 Data

Based on CDC’s 2016 Fertility Clinic Success Rates Report, there were 263,577* ART cycles performed at 463 reporting clinics in the United States during 2016, resulting in 65,996 live births (deliveries of one or more living infants) and 76,930 live born infants. Of the 263,577 ART cycles performed in 2016, 65,840 were banking cycles in which the intent of the ART cycle was to freeze all resulting eggs or embryos for future ART cycles and for which we would not expect a resulting pregnancy or birth. Although the use of ART is still relatively rare as compared to the potential demand, its use has doubled over the past decade. Today, approximately 1.7% of all infants born in the United States every year are conceived using ART.

Assisted Reproductive Technology (ART)

"Fertility clinics in the U.S. report and verify data on the assisted reproductive technology (ART) cycles started and carried out in their clinics, and the outcomes of these cycles, during each calendar year. ART includes all fertility treatments in which either eggs or embryos are handled. The main type of ART is in vitro fertilization (IVF). IVF involves extracting a woman’s eggs, fertilizing the eggs in the laboratory, and then transferring the resulting embryos into the woman’s uterus through the cervix."

USA 2013 Data

ART USA (2013)
  • 6.9 million (11%) of the 61 million women aged 15–44 years had received infertility services at some time in their lives.
  • 93,787 fresh nondonor ART cycles were started in 2013.
  • 33,425 (36%) led to a pregnancy, but only 27,406 (29%) resulted in a live birth.
  • 6,019 (almost 1 in 5) of ART pregnancies did not result in a live birth.

USA 2012 Data

ART USA 2012 Data
USA ART Report 2012 cover

2012 Assisted Reproductive Technology National Summary Report[34]

  • 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).
Links: 2012 Assisted Reproductive Technology National Summary Report

Multiple births resulting from assisted reproductive technology (2012)[35]

  • 134,381 ART transfer cycles performed in 2012
  • 51,262 resulted in live births
  • 13,563 (26.5%) were multiple births
    • 3,123 twin and 440 triplet and higher order births.
  • 46.1%) of these multiple births resulted from 4 cycle types:
  1. two fresh blastocyst transfers among favorable prognosis patients less than 35 years (1,931 multiple births)
  2. two fresh blastocyst transfers among average prognosis patients less than 35 years (1,341 multiple births)
  3. two fresh blastocyst transfers among donor-oocyte recipients (1,532 multiple births)
  4. two frozen/thawed ETs among patients less than 35 years (1,452 multiple births).
  • More than half of triplet or higher order births resulted from the transfer of two embryos
    • 52.5% of births among fresh autologous transfers
    • 67.2% of births among donor-oocyte recipient transfers
    • 42.9% among frozen/thawed autologous transfers

ART USA Archive

ART USA 2011 - 2009Data
ART 20011

Births Resulting From Assisted Reproductive Technology: Comparing Birth Certificate and National ART Surveillance System Data, 2011[17]

  • 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.
Links: CDC - National ART Surveillance System Data 2011 Report
ART USA 2010 Data

2010 Assisted Reproductive Technology National Summary Report | 2010 Assisted Reproductive Technology Report

  • 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
ART USA 2009 Data
USA ART Report 2009 cover


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
ART USA 2006 Data
USA- ART clinics (2006)
USA assisted reproductive technology 1996.jpg

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.

USA ART live birth rates 1996.jpg

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

ESHRE Atlas2012.jpg Citation: ESHRE Atlas of Human Embryology: from Oocytes to Preimplantation Embryo (2012)

This online textbook edition is designed mainly for ART clinicians covering only the developmental period between oocytes to the preimplantation embryo.


Links: Online Textbook | ESHRE | Assisted Reproductive Technology

  • Assisted reproductive technology in Europe, 2007[18] "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

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)

Canada

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[36]


Links: Canada ART | [[Canada Statistics

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.[37]

"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[38])

  • 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

Both men and women undergoing clinical procedures of chemotherapy and/or radiotherapy (ionizing radiation) can have induced gametogenic failure.

Female

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.[39]

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.[40]

Male

A recent paper[21] 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."


Links: Environmental | Drugs | Radiation

Ovarian Reserve

See ovarian reserve section on ovary page.

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.[41]


Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells[42]

"The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been postulated that putative oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Here, we report single-cell transcriptomes and cell surface antigen profiles of over 24,000 cells from high quality ovarian cortex samples from 21 patients. Our data identify transcriptional profiles of six main cell types; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Cells captured by DDX4 antibody are perivascular cells, not oogonial stem cells. Our data do not support the existence of germline stem cells in adult human ovaries, thereby reinforcing the dogma of a limited ovarian reserve."

Ovarian Follicle Growth in vitro

Ovarian follicle growth in vitro.jpg

2D and 3D methods of ovarian follicle growth in vitro.[43]


Germline Gene Editing

The European Society of Human Genetics and the European Society for Human Reproduction and Embryology have developed a consensus statement covering germline gene editing and the following ART-related topics.[44]

"expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF"


Technology development in germline gene editing has allowed the development of many animal models of human congenital defects. More recently there has been debate around the ethics of using similar methods in "correcting" these abnormalities using similar techniques in humans. In 2018 the European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a background document and recommendations to inform and stimulate ongoing societal debates.[45][46]


Historic Embryology

John Charles Rock (1890-1984) was a Boston gynaecologist and human fertility researcher. In 1938 he began a collaboration with pathologist Arthur Hertig and the researcher Miriam Menkin (1901 – 1992; née Miriam Friedman). Rock and Menkin were the earliest clinical researchers in the USA looking at human in vitro fertilisation techniques[2] for treatment of infertility. John Rock was also the main subject of a recent book on changes in reproduction.[47]
John Charles Rock
John Charles Rock (1890-1984)

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Reviews

Articles

Smitz J, Dolmans MM, Donnez J, Fortune JE, Hovatta O, Jewgenow K, Picton HM, Plancha C, Shea LD, Stouffer RL, Telfer EE, Woodruff TK & Zelinski MB. (2010). Current achievements and future research directions in ovarian tissue culture, in vitro follicle development and transplantation: implications for fertility preservation. Hum. Reprod. Update , 16, 395-414. PMID: 20124287 DOI.

Meintjes M, Chantilis SJ, Ward DC, Douglas JD, Rodriguez AJ, Guerami AR, Bookout DM, Barnett BD & Madden JD. (2009). 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. , 24, 782-9. PMID: 19147504 DOI.

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External Links

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Terms

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)
  • Luteal-phase insufficiency - stimulated IVF cycles can disrupt the maternal pituitary gland pulsatile release of luteinizing hormone (LH) during the menstrual cycle luteal phase. Clinically, progesterone supplementation (support) is given during the luteal-phase of stimulated IVF cycles.


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Cite this page: Hill, M.A. (2024, March 19) Embryology Assisted Reproductive Technology. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Assisted_Reproductive_Technology

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© Dr Mark Hill 2024, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G