Assisted Reproductive Technology

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Introduction

Louise Brown, the first IVF baby as an adult.

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.[1][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 | Oocyte | Spermatozoa | Fertilization | Lecture - Fertilization | Lecture - Week 1 and 2 | Lecture - Genital Development | Robert Edwards | ART Glossary


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
  • Congenital anomalies identified at birth among infants born following assisted reproductive technology in Colorado[5] "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."
  • Sep 2012 UK - Human Fertilisation and Embryology Authority (HFEA) launches a public consultation on the ethical and social implications of new in vitro fertilisation (IVF) techniques designed to avoid the maternal transmission of mitochondrial disease. Technique The oocyte normally provides the mitochondria to the embryo (maternally-derived), therefore a different oocyte cytoplasm with an affected mother's nucleus would prevent transmission of mitochondrial disease. Report - Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review Reports
  • Assisted reproductive technology in Europe, 2007[6] "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[7] "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[8] "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[9] "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."
  • The Nobel Prize in Physiology or Medicine 2010 was awarded to Robert G. Edwards "for the development of in vitro fertilization". [3] Nobel Prize 2010
More recent papers
Mark Hill.jpg
This table shows an automated computer PubMed search using the listed sub-heading term.
  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

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.

Links: References | Discussion Page | Pubmed Most Recent


Search term: Assisted Reproductive Technology

Satoshi Kamimura, Yuki Hatanaka, Ryutaro Hirasawa, Kazuya Matsumoto, Mami Oikawa, Jiyoung Lee, Shogo Matoba, Eiji Mizutani, Narumi Ogonuki, Kimiko Inoue, Takashi Kohda, Fumitoshi Ishino, Atsuo Ogura Establishment of Paternal Genomic Imprinting in Mouse Prospermatogonia Analyzed by Nuclear Transfer. Biol. Reprod.: 2014; PMID:25232016 Ab Levine, Md Lockshin Assisted reproductive technology in SLE and APS. Lupus: 2014, 23(12);1239-41 PMID:25228714 Min Wang, Jian Sun, Li Wang, Xiaohong Gao, Xiang Lu, Zhengmu Wu, Yongwei Wang, Kai Liu, Jiewei Tao, Yu Wu Assessment of density gradient centrifugation (DGC) and sperm chromatin dispersion (SCD) measurements in couples with male factor infertility undergoing ICSI. J. Assist. Reprod. Genet.: 2014; PMID:25227693 Mina Alikani, Kathryn J Go, Caroline McCaffrey, David H McCulloh A comprehensive evaluation of contemporary assisted reproduction technology laboratory operations to determine staffing levels that promote patient safety and quality care. Fertil. Steril.: 2014; PMID:25226853 Georgina M Chambers, Van Phuong Hoang, Evelyn Lee, Michele Hansen, Elizabeth A Sullivan, Carol Bower, Michael Chapman Hospital Costs of Multiple-Birth and Singleton-Birth Children During the First 5 Years of Life and the Role of Assisted Reproductive Technology. JAMA Pediatr: 2014; PMID:25222633

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[10]

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.[11] 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[1][2]
  • 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[12]

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 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.[13] 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.[14]

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
  • confocal microscopy (not for clinical use)


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.[15]

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)

  • 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.

2014

Birthweight percentiles by gestational age for births following assisted reproductive technology in Australia and New Zealand, 2002-2010[16]

"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

2010

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[10]
  • 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[17] 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.[18]
   

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.[18]

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.

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)

2010

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

2009

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

2006

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

  • Assisted reproductive technology in Europe, 2007[6] "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)

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.[19]

"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[20])

  • 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.[21]

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.[22]

Male

A recent paper[9] 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

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.[23]

Ovarian Follicle Growth in vitro

Ovarian follicle growth in vitro.jpg

2D and 3D methods of ovarian follicle growth in vitro.[24]

References

  1. 1.0 1.1 J Rock, M F Menkin IN VITRO FERTILIZATION AND CLEAVAGE OF HUMAN OVARIAN EGGS. Science: 1944, 100(2588);105-7 PMID:17788930 | Science
  2. 2.0 2.1 M F MENKIN, J ROCK In vitro fertilization and cleavage of human ovarian eggs. Am. J. Obstet. Gynecol.: 1948, 55(3);440-52 PMID:18903892
  3. 3.0 3.1 R G Edwards, P C Steptoe, J M Purdy Establishing full-term human pregnancies using cleaving embryos grown in vitro. Br J Obstet Gynaecol: 1980, 87(9);737-56 PMID:6775685
  4. A Lopata, I W Johnston, I J Hoult, A I Speirs Pregnancy following intrauterine implantation of an embryo obtained by in vitro fertilization of a preovulatory egg. Fertil. Steril.: 1980, 33(2);117-20 PMID:7353686
  5. 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; PMID:24532453
  6. 6.0 6.1 J de Mouzon, V Goossens, S Bhattacharya, J A Castilla, A P Ferraretti, V Korsak, M Kupka, K G Nygren, A Nyboe Andersen, The 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);954-966 PMID:22343707
  7. 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
  8. 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
  9. 9.0 9.1 Vinay Sharma Sperm storage for cancer patients in the UK: a review of current practice. Hum. Reprod.: 2011, 26(11);2935-43 PMID:21873609
  10. 10.0 10.1 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
  11. 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
  12. B D Bavister Culture of preimplantation embryos: facts and artifacts. Hum. Reprod. Update: 1995, 1(2);91-148 PMID:15726768
  13. 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
  14. Laura Rienzi, Basak Balaban, Thomas Ebner, Jacqueline Mandelbaum The oocyte. Hum. Reprod.: 2012, 27 Suppl 1;i2-21 PMID:22811312 | Hum Reprod.
  15. 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: 2012; PMID:23352100
  16. 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; PMID:24908671
  17. 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
  18. 18.0 18.1 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
  19. Bengt Källén, Orvar Finnström, Karl Gösta Nygren, Petra Otterblad Olausson Temporal trends in multiple births after in vitro fertilisation in Sweden, 1982-2001: a register study. BMJ: 2005, 331(7513);382-3 PMID:15894553 | BMJ
  20. Mourad Assidi, Markus Montag, Katrin Van der Ven, Marc-André Sirard Biomarkers of human oocyte developmental competence expressed in cumulus cells before ICSI: a preliminary study. J. Assist. Reprod. Genet.: 2011, 28(2);173-88 PMID:20953827
  21. B Lawrenz, E Neunhoeffer, M Henes, S Lessmann-Bechle, B Krämer, Tanja Fehm Management of fertility preservation in young breast cancer patients in a large breast cancer centre. Arch. Gynecol. Obstet.: 2010, 282(5);547-51 PMID:20499073
  22. Jacques Donnez, Jean Squifflet, Céline Pirard, Pascale Jadoul, Marie-Madeleine Dolmans Restoration of ovarian function after allografting of ovarian cortex between genetically non-identical sisters. Hum. Reprod.: 2010, 25(10);2489-95 PMID:20663793
  23. S Lie Fong, J S E Laven, F G A J Hakvoort-Cammel, I Schipper, J A Visser, A P N Themmen, F H de Jong, M M van den Heuvel-Eibrink Assessment of ovarian reserve in adult childhood cancer survivors using anti-Müllerian hormone. Hum. Reprod.: 2009, 24(4);982-90 PMID:19153092
  24. Nina Desai, Anastasia Alex, Faten AbdelHafez, Anthony Calabro, James Goldfarb, Aaron Fleischman, Tommaso Falcone Three-dimensional in vitro follicle growth: overview of culture models, biomaterials, design parameters and future directions. Reprod. Biol. Endocrinol.: 2010, 8;119 PMID:20946661 | Reprod Biol Endocrinol.


Reviews

Articles

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


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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)


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Cite this page: Hill, M.A. (2014) Embryology Assisted Reproductive Technology. Retrieved September 22, 2014, from https://php.med.unsw.edu.au/embryology/index.php?title=Assisted_Reproductive_Technology

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© Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G