In vitro fertilisation - AbsoluteAstronomy.com

In vitro fertilisation (IVF) is a process by which egg cells

Ovum

An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...

are fertilised

Fertilisation

Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...

by sperm

Spermatocyte

A spermatocyte is a male gametocyte, derived from a spermatogonium, which is in the developmental stage of spermatogenesis during which meiosis occurs. It is located in the seminiferous tubules of the testis.-Spermatogenesis:...

outside the body: in vitro

In vitro

In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

. IVF is a major treatment in infertility

Infertility

Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...

when other methods of assisted reproductive technology

Assisted reproductive technology

Assisted reproductive technology is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments. Some forms of ART are also used in fertile couples for genetic reasons...

have failed. The process involves hormonally controlling the ovulatory process, removing ova

Ovum

(eggs) from the woman's ovaries

Ovary

The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...

and letting sperm

Spermatozoon

A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...

fertilise them in a fluid medium. The fertilised egg (zygote

Zygote

A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...

) is then transferred to the patient's uterus

Uterus

The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...

with the intent to establish a successful pregnancy. The first successful birth of a "test tube baby", Louise Brown

Louise Brown

Louise Joy Brown is the first person to be conceived by in vitro fertilization, or IVF.-Birth:...

, occurred in 1978. Robert G. Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in Physiology or Medicine

Nobel Prize in Physiology or Medicine

The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

in 2010.

The term in vitro

In vitro

, from the Latin

Latin

Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...

root

Root (linguistics)

The root word is the primary lexical unit of a word, and of a word family , which carries the most significant aspects of semantic content and cannot be reduced into smaller constituents....

meaning in glass, is used, because early biological experiments involving cultivation of tissues outside the living organism from which they came, were carried out in glass containers such as beaker

Beaker (glassware)

A beaker is a simple container for stirring, mixing and heating liquids commonly used in many laboratories. Beakers are generally cylindrical in shape, with a flat bottom. Most also have a small spout to aid pouring as shown in the picture...

s, test tube

Test tube

A test tube, also known as a culture tube or sample tube, is a common piece of laboratory glassware consisting of a finger-like length of glass or clear plastic tubing, open at the top, usually with a rounded U-shaped bottom....

s, or petri dish

Petri dish

A Petri dish is a shallow glass or plastic cylindrical lidded dish that biologists use to culture cells or small moss plants. It was named after German bacteriologist Julius Richard Petri, who invented it when working as an assistant to Robert Koch...

es. Today, the term in vitro is used to refer to any biological procedure that is performed outside the organism it would normally be occurring in, to distinguish it from an in vivo

In vivo

In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

procedure, where the tissue remains inside the living organism within which it is normally found. A colloquial term for babies conceived as the result of IVF, "test tube babies", refers to the tube-shaped containers of glass or plastic resin, called test tubes, that are commonly used in chemistry labs and biology labs. However, in vitro fertilisation is usually performed in the shallower containers called Petri dish

Petri dish

es. One IVF method, Autologous Endometrial Coculture

Autologous endometrial coculture

Autologous Endometrial Coculture is a technique of assisted reproductive technology. It involves placing a patient’s fertilized eggs on top of a layer of cells from her own uterine lining, creating a more natural environment for embryo development and maximizing the chance for an in vitro...

, is actually performed on organic material, but is still considered in vitro.

Indications

IVF may be used to overcome female infertility

Female infertility

-Causes and factors:Causes or factors of female infertility can basically be classified regarding whether they are acquired or genetic, or strictly by location.-Acquired versus genetic:...

in the woman due to problems of the fallopian tube

Fallopian tube

The Fallopian tubes, also known as oviducts, uterine tubes, and salpinges are two very fine tubes lined with ciliated epithelia, leading from the ovaries of female mammals into the uterus, via the utero-tubal junction...

, making fertilisation in vivo difficult. It may also assist in male infertility

Male infertility

Male infertility refers to the inability of a male to achieve a pregnancy in a fertile female. In humans it accounts for 40-50% of infertility. Male infertility is commonly due to deficiencies in the semen, and semen quality is used as a surrogate measure of male fecundity.-Pre-testicular...

, where there is defect sperm quality, and in such cases intracytoplasmic sperm injection

Intracytoplasmic sperm injection

Intracytoplasmic sperm injection is an in vitro fertilization procedure in which a single sperm is injected directly into an egg.-Indications:...

(ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm have difficulty penetrating the egg, and in these cases the partner's or a donor's sperm may be used. ICSI is also used when sperm numbers are very low. ICSI results in success rates equal to those of IVF.

For IVF to be successful it typically requires healthy ova, sperm that can fertilise, and a uterus

Uterus

that can maintain a pregnancy

Pregnancy

Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

. Due to the costs of the procedure, IVF is generally attempted only after less expensive options have failed.

IVF can also be used with egg donation or surrogacy

Surrogacy

Surrogacy is an arrangement in which a woman carries and delivers a child for another couple or person. This woman may be the child's genetic mother , or she may carry the pregnancy to delivery after having an embryo, to which she has no genetic relationship whatsoever, transferred to her uterus...

where the woman providing the egg isn't the same who will carry the pregnancy

Pregnancy

to term. This means that IVF can be used for females who have already gone through menopause

Menopause

Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...

. The donated oocyte

Oocyte

An oocyte, ovocyte, or rarely ocyte, is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in the ovary during female gametogenesis. The female germ cells produce a primordial germ cell which undergoes a mitotic...

can be fertilised in a crucible

Crucible

A crucible is a container used for metal, glass, and pigment production as well as a number of modern laboratory processes, which can withstand temperatures high enough to melt or otherwise alter its contents...

. If the fertilisation is successful, the embryo will be transferred into the uterus, within which it may implant.

IVF can also be combined with preimplantation genetic diagnosis

Preimplantation genetic diagnosis

In medicine and genetics pre-implantation genetic diagnosis refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered another way to prenatal diagnosis...

(PGD) to rule out presence of genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

s. A similar but more general test has been developed called Preimplantation Genetic Haplotyping

Preimplantation Genetic Haplotyping

Preimplantation Genetic Haplotyping is a clinical method of preimplantation genetic diagnosis . PGH was first developed in 2006 at London's Guy's Hospital and greatly advances PGD by using DNA fingerprinting rather than identifying the actual genetic signature .- Scope :Compared with previous PGD...

Method

Theoretically, in vitro fertilisation could be performed by collecting the contents from a woman's fallopian tubes or uterus after natural ovulation, mixing it with semen, and reinserting into the uterus. However, without additional techniques, the chances of pregnancy would be extremely small. Such additional techniques that are routinely used in IVF include ovarian hyperstimulation to retrieve multiple eggs, ultrasound-guided transvaginal oocyte retrieval

Transvaginal oocyte retrieval

Transvaginal oocyte retrieval , also referred to as oocyte retrieval or even simply egg collection, is a technique used in in vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body...

directly from the ovaries, egg and sperm preparation, as well as culture and selection of resultant embryos before embryo transfer

Embryo transfer

Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy...

back into the uterus.

Ovarian hyperstimulation

There are two main protocols for stimulating the ovaries for IVF treatment. The long protocol involves downregulation (suppression or exhaustion) of the pituitary ovarian axis by the prolonged use of a GnRH agonist. Subsequent ovarian hyperstimulation, typically using follicle stimulating hormone (FSH), starts once the process of downregulation is complete, generally after 10 to 14 days.

The short protocol skips the downregulation part, and consists of a regimen of fertility

Fertility

Fertility is the natural capability of producing offsprings. As a measure, "fertility rate" is the number of children born per couple, person or population. Fertility differs from fecundity, which is defined as the potential for reproduction...

medications to stimulate the development of multiple follicles

Ovarian follicle

Ovarian follicles are the basic units of female reproductive biology, each of which is composed of roughly spherical aggregations of cells found in the ovary. They contain a single oocyte . These structures are periodically initiated to grow and develop, culminating in ovulation of usually a single...

of the ovaries. In most patients, injectable gonadotropin

Gonadotropin

Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...

s (usually FSH analogues) are used under close monitoring. Such monitoring frequently checks the estradiol

Estradiol

Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...

level and, by means of gynecologic ultrasonography

Gynecologic ultrasonography

Gynecologic ultrasonography or Gynecologic sonography refers to the application of medical ultrasonography to the female pelvic organs, specifically the uterus, the ovaries, the Fallopian tubes, as well as the bladder, the adnexa, the Pouch of Douglas, and any findings in the pelvis of relevance...

, follicular growth. Typically approximately 10 days of injections will be necessary. Spontaneous ovulation during the cycle is typically prevented by the use of GnRH antagonists that are used just during the last days of stimulation to block the natural surge of luteinising hormone (LH) and allow the physician to start the ovulation process by using medication, usually injectable human chorionic gonadotropin

Human chorionic gonadotropin

Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...

s.

Ovarian stimulation carries the risk of excessive stimulation. This complication is life-threatening and ovarian stimulation using gonadotropins must only be carried out under strict medical supervision.

Egg retrieval

When the ovarian follicles have reached a certain degree of development, final maturation is induced, generally by an injection of human chorionic gonadotropin

Human chorionic gonadotropin

(hCG). Commonly, this is known as the "trigger shot." hCG acts as an analogue of luteinising hormone, and ovulation would occur between 38 and 40 hours after a single HCG injection, but the egg retrieval is performed at a time usually between 34 and 36 hours after hCG injection, that is, just prior to when the follicles would rupture. This avails for scheduling the egg retrieval procedure at a time where the eggs are fully mature. HCG injection confers a risk of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe.-Causative medications:...

. Using a GnRH agonist instead of hCG eliminates the risk of ovarian hyperstimulation syndrome, but with a delivery rate of approximately 6% less than with hCG.

The eggs are retrieved from the patient using a transvaginal technique called transvaginal oocyte retrieval

Transvaginal oocyte retrieval

, involving an ultrasound-guided needle piercing the vaginal wall to reach the ovaries. Through this needle follicles can be aspirated, and the follicular fluid is handed to the IVF laboratory to identify ova. It is common to remove between ten and thirty eggs. The retrieval procedure takes about 20 minutes and is usually done under conscious sedation or general anaesthesia

General anaesthesia

General anaesthesia is a state of unconsciousness and loss of protective reflexes resulting from the administration of one or more general anaesthetic agents...

Egg and sperm preparation

In the laboratory, the identified eggs are stripped of surrounding cells and prepared for fertilisation

Fertilisation

Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...

. An oocyte selection

Oocyte selection

Oocyte selection is a procedure that is performed prior to in vitro fertilization, in order to use oocytes with maximal chances of resulting in pregnancy. In contrast, embryo selection takes place after fertilization.-Techniques:...

may be performed prior to fertilisation to select eggs with optimal chances of successful pregnancy. In the meantime, semen

Semen

Semen is an organic fluid, also known as seminal fluid, that may contain spermatozoa. It is secreted by the gonads and other sexual organs of male or hermaphroditic animals and can fertilize female ova...

is prepared for fertilisation by removing inactive cells and seminal fluid in a process called sperm washing

Sperm washing

Sperm washing is a term used to describe the process in which individual sperms are separated from the seminal fluid. The sperms are then used in intrauterine insemination or in vitro fertilization ....

. If semen is being provided by a sperm donor, it will usually have been prepared for treatment before being frozen and quarantined, and it will be thawed ready for use.

Fertilisation

The sperm and the egg are incubated together at a ratio of about 75,000:1 in the culture media for about 18 hours. In most cases, the egg will be fertilised by that time and the fertilised egg will show two pronuclei. In certain situations, such as low sperm count or motility, a single sperm may be injected directly into the egg using intracytoplasmic sperm injection

Intracytoplasmic sperm injection

Intracytoplasmic sperm injection is an in vitro fertilization procedure in which a single sperm is injected directly into an egg.-Indications:...

(ICSI). The fertilised egg is passed to a special growth medium and left for about 48 hours until the egg consists of six to eight cells.

In gamete intrafallopian transfer

Gamete intrafallopian transfer

Gamete intrafallopian transfer is a tool of assisted reproductive technology against infertility. Eggs are removed from a woman's ovaries, and placed in one of the Fallopian tubes, along with the man's sperm...

, eggs are removed from the woman and placed in one of the fallopian tubes, along with the man's sperm. This allows fertilisation to take place inside the woman's body. Therefore, this variation is actually an in vivo

In vivo

fertilisation, not an in vitro

In vitro

fertilisation.

Embryo culture

Typically, embryos are cultured until having reached the 6–8 cell stage three days after retrieval. In many Canadian, American and Australian programmes, however, embryos are placed into an extended culture system with a transfer done at the blastocyst

Blastocyst

The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...

stage at around five days after retrieval, especially if many good-quality embryos are still available on day 3. Blastocyst stage transfers have been shown to result in higher pregnancy rates. In Europe, transfers after 2 days are common.

Culture of embryos can either be performed in an artificial culture medium or in an autologous endometrial coculture

Autologous endometrial coculture

(on top of a layer of cells from the woman's own uterine lining). With artificial culture medium, there can either be the same culture medium throughout the period, or a sequential system can be used, in which the embryo is sequentially placed in different media. For example, when culturing to the blastocyst stage, one medium may be used for culture to day 3, and a second medium is used for culture thereafter. Single or sequential medium are equally effective for the culture of human embryos to the blastocyst stage. Artificial embryo culture media basically contain glucose, pyruvate, and energy-providing components, but addition of amino acids, nucleotides, vitamins, and cholesterol improve the performance of embryonic growth and development. Methods to permit dynamic embryo culture with fluid flow and embryo movement are also available. A new method in development uses the uterus as an incubator and the naturally occurring intrauterine fluids as culture medium by encapsulating the embryos in permeable intrauterine vessel.

Embryo selection

Laboratories have developed grading methods to judge oocyte and embryo

Embryo

An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...

quality. In order to optimise pregnancy rate

Pregnancy rate

Pregnancy rate in infertility treatment is the success rate for pregnancy. It is the percentage of all attempts that leads to pregnancy, with attempts generally referring to menstrual cycles where insemination or any artificial equivalent is used, which may be simple artificial insemination or AI...

s, there is significant evidence that a morphological scoring system is the best strategy for the selection of embryos. However, presence of soluble HLA-G

HLA-G

HLA-G histocompatibility antigen, class I, G, also known as human leukocyte antigen G , is a protein that in humans is encoded by the HLA-G gene....

might be considered as a second parameter if a choice has to be made between embryos of morphologically equal quality. Also, two-pronuclear zygotes (2PN) transitioning through 1PN or 3PN states tend to develop into poorer-quality embryos than those that constantly remain 2PN.

More advanced methods of embryo profiling may also be performed in order to optimise embryo selection, as further described in the "expansions"-section below.

Embryo transfer

Embryos are failed by the embryologist based on the amount of cells, evenness of growth and degree of fragmentation. The number to be transferred depends on the number available, the age of the woman and other health and diagnostic factors. In countries such as Canada, the UK, Australia and New Zealand, a maximum of two embryos are transferred except in unusual circumstances. In the UK and according to HFEA regulations, a woman over 40 may have up to three embryos transferred, whereas in the USA, younger women may have many embryos transferred based on individual fertility diagnosis. Most clinics and country regulatory bodies seek to minimise the risk of pregnancies carrying multiples. As it is not uncommon for more implantations to take than desired, the next step faced by the expectant mother is that of selective abortion. The embryos judged to be the "best" are transferred to the patient's uterus through a thin, plastic catheter

Catheter

In medicine, a catheter is a tube that can be inserted into a body cavity, duct, or vessel. Catheters thereby allow drainage, administration of fluids or gases, or access by surgical instruments. The process of inserting a catheter is catheterization...

, which goes through her vagina

Vagina

The vagina is a fibromuscular tubular tract leading from the uterus to the exterior of the body in female placental mammals and marsupials, or to the cloaca in female birds, monotremes, and some reptiles. Female insects and other invertebrates also have a vagina, which is the terminal part of the...

and cervix. Several embryos may be passed into the uterus to improve chances of implantation and pregnancy

Pregnancy

Success rates

IVF success rates are the percentage of all IVF procedures which result in a favorable outcome. Depending on the type of calculation used, this outcome may represent the number of confirmed pregnancies, called the pregnancy rate

Pregnancy rate

or number of live births, called the live birth rate.

Due to advancement in reproductive technology, the IVF success rates are substantially better today than they were just a few years ago. The most current data available in the United States a 2009 summary complied by the Society for Reproductive Medicine (SART) which reports the average national IVF success rates per age group using non-donor eggs (see table below).

	<35	35-37	38-40	41-42
Pregnancy Rate	47.6	38.9	30.1	20.5
Live Birth Rate	41.4	31.7	22.3	12.6

The live birth rates using donor eggs are also given by the SART and include all age groups using either fresh or thawed eggs.

	Fresh Donor Egg Embryos	Thawed Donor Egg Embryos
Live Birth Rate	55.1	33.8

In 2006, Canadian clinics reported an average pregnancy rate of 35%. A French study estimated that 66% of patients starting IVF treatment finally succeed in having a child (40% during the IVF treatment at the center and 26% after IVF discontinuation). Achievement of having a child after IVF discontinuation was mainly due to adoption

Adoption

Adoption is a process whereby a person assumes the parenting for another and, in so doing, permanently transfers all rights and responsibilities from the original parent or parents...

(46%) or spontaneous pregnancy (42%).

Live birth rate

The live birth rate is the percentage of all IVF cycles that lead to a live birth. This rate does not include miscarriage

Miscarriage

Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...

or stillbirth

Stillbirth

A stillbirth occurs when a fetus has died in the uterus. The Australian definition specifies that fetal death is termed a stillbirth after 20 weeks gestation or the fetus weighs more than . Once the fetus has died the mother still has contractions and remains undelivered. The term is often used in...

and multiple-order births such as twins and triplets are counted as one pregnancy. The live birth rate is calculated as follows:

Number of live births ÷ Number of procedures performed (cycle start, egg retrieval or embryo transfer)

In 2006, Canadian clinics reported a live birth rate of 27%. Birth rates in younger patients were slightly higher, with a success rate of 35.3% for those 21 and younger, the youngest group evaluated. Success rates for older patients were also lower and decrease with age, with 37-year-olds at 27.4% and no live births for those older than 48, the oldest group evaluated. Some clinics exceeded these rates, but it is impossible to determine if that is due to superior technique or patient selection, because it is possible to artificially increase success rates by refusing to accept the most difficult patients or by steering them into oocyte donation cycles (which are compiled separately). Further, pregnancy rates can be increased by the placement of several embryos at the risk of increasing the chance for multiples.

Because not each IVF cycle that is started will lead to oocyte retrieval or embryo transfer, reports of live birth rates need to specify the denominator, namely IVF cycles started, IVF retrievals, or embryo transfers. The Society for Assisted Reproductive Technology (SART) summarised 2008-9 success rates for US clinics for fresh embryo cycles that did not involve donor eggs and gave live birth rates by the age of the prospective mother, with a peak at 41.3% per cycle started and 47.3% per embryo transfer for patients under 35 years of age.

IVF attempts in multiple cycles result in increased cumulative live birth rates. Depending on the demographic group, one study reported 45% to 53% for three attempts, and 51% to 71% to 80% for six attempts.

Pregnancy rate

Pregnancy rate may be defined in various ways. In the United States, the pregnancy rate used by the Society for Assisted Reproductive Technology and the Centers for Disease Control (and appearing in the table in the Success Rates section above) are based on fetal heart motion observed in ultrasound examinations. However, some clinics may advertise pregnancy rates based on pregnancy tests which are less definitive, such as urine or blood tests for hCG. This is the rate most often published by fertility clinics because often at the time of publishing not all IVF patients have given birth. The pregnancy rate is calculated as follows:

Number pregnancies / Number of procedures performed (cycle start, egg retrieval or embryo transfer)

Success or failure factors

The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be maternal age, duration of infertility or subfertility, bFSH and number of oocytes, all reflecting ovarian function. Optimal woman’s age is 23–39 years at time of treatment.

Stress

In a 2005 Swedish study, 166 women were monitored starting one month before their IVF cycles, and the results showed no significant correlation between psychological stress and IVF outcome. The study concluded with the recommendation to clinics that it might be possible to reduce the stress experienced by IVF patients during the treatment procedure by informing them of those findings. While psychological stress experienced during a cycle might not influence an IVF outcome, it is possible that the experience of IVF can result in stress that leads to depression. The financial consequences alone of IVF can influence anxiety and become overwhelming. However, for many couples, the alternative is infertility, and the experience of infertility itself can also cause extreme stress and depression.

Acupuncture

An increasing number of fertility specialists and centers offer acupuncture

Acupuncture

Acupuncture is a type of alternative medicine that treats patients by insertion and manipulation of solid, generally thin needles in the body....

as a part of their IVF protocol. Limited but supportive evidence from clinical trials and case series suggests that acupuncture may improve the success rate of IVF and the quality of life of patients undergoing IVF and that it is a safe adjunct therapy. A systematic review and meta-analysis published in the British Medical Journal found that complementing the embryo transfer process with acupuncture was associated with significant and clinically relevant improvements in clinical pregnancy (where the expected number of patients needed to be treated

Number needed to treat

The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...

to produce 1 additional pregnancy was 10), ongoing pregnancy (NNT

Number needed to treat

9), and live birth (NNT

Number needed to treat

9).

Acupuncture mechanisms

Four mechanisms by which it has been suggested that acupuncture may improve IVF outcomes are

Neuroendocrinological modulations
Increased blood flow to uterus and ovaries
Modulation in cytokines
Reduction of stress, anxiety, and depression

Electro-acupuncture in oocyte retrieval for IVF

Electro-acupuncture has been found to be a good alternative to conventional medical analgesia, it results in shorter hospitalisation times and lower costs.

Other factors

Other determinant

Risk factor

In epidemiology, a risk factor is a variable associated with an increased risk of disease or infection. Sometimes, determinant is also used, being a variable associated with either increased or decreased risk.-Correlation vs causation:...

s of outcome of IVF include:

Tobacco smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...

reduces the chances of IVF producing a live birth by 34% and increases the risk of an IVF pregnancy miscarrying by 30%.
A body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...

(BMI) over 27 causes a 33% decrease in likelihood to have a live birth after the first cycle of IVF, compared to those with a BMI between 20 and 27. Also, pregnant women who are obese have higher rates of congenital abnormality
Congenital abnormality
A congenital anomaly is a condition which is present at the time of birth which varies from the standard presentation....

, miscarriage
Miscarriage
Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...

, gestational diabetes
Gestational diabetes
Gestational diabetes is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy . It is widely accepted as a disease only in the United States, there is some question whether the condition is natural during pregnancy...

, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, thromboembolism and problems during delivery
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

. Ideal body mass index is 19–30.
Salpingectomy
Salpingectomy
Salpingectomy refers to the surgical removal of a Fallopian tube.-Indications:The procedure was first performed by Lawson Tait in patients with a bleeding ectopic pregnancy; this procedure has since saved the lives of countless women...

before IVF treatment increases chances for women with hydrosalpinges
Success with previous pregnancy and/or live birth increases chances
Low alcohol/caffeine intake increases success rate
Level of DNA fragmentation
DNA fragmentation
DNA fragmentation is the separation or breaking of DNA strands into pieces. It can be intentional by laboratory personnel or the cells, or it can be spontaneous.-Intentional:Restriction digest is the intentional laboratory breaking of DNA strands....

as measured e.g. by Comet assay
Comet assay
The Single Cell Gel Electrophoresis assay is an uncomplicated and sensitive technique for the detection of DNA damage at the level of the individual eukaryotic cell. It was first described by Singh et al. in 1988...

, advanced maternal age
Advanced maternal age
Advanced maternal age is defined as an increase in the age at which women give birth to their first child, is now a widespread, and indeed near universal, phenomenon across the OECD countries....

and semen quality
Semen quality
Semen quality is a measure of the ability of semen to accomplish fertilization. Thus, it is a measure of fertility in a man. It is the sperm in the semen that are of importance, and therefore semen quality involves both sperm quantity and quality...

.
The number of embryos transferred in the treatment cycle.
Other factors of semen quality
Semen quality
Semen quality is a measure of the ability of semen to accomplish fertilization. Thus, it is a measure of fertility in a man. It is the sperm in the semen that are of importance, and therefore semen quality involves both sperm quantity and quality...

for the sperm provider.
Women with ovary-specific FMR1
FMR1
FMR1 is a human gene that codes for a protein called fragile X mental retardation protein, or FMRP. This protein, most commonly found in the brain, is essential for normal cognitive development and female reproductive function...

genotypes including het-norm/low have significantly decreased pregnancy chances in IVF.
Some studies also suggest the autoimmune disease
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

may also play a role in decreasing IVF success rates by interfering with proper implantation of the embryo after transfer.

Aspirin, however, was shown by a meta-analysis to not improve pregnancy rates after IVF.

Risks

Possible risks may occur throughout the procedure, but the risk you may encounter depend on the specific step of the procedure. During ovarian stimulation, hyperstimulation syndrome may occur. This results in swollen, painful ovaries and some form of it (mild, moderate or severe) occurs in 30% of patients. Mild cases can be treated with over the counter medications and cases can be resolved in the absence of pregnancy. In moderate cases, ovaries swell and fluid accumulated in the abdominal cavities and may have symptoms of heartburn, gas, nausea or loss of appetite. In severe cases patients have sudden excess abdominal pain, nausea, vomiting and will result in hospitalisation. During egg retrieval, there’s a small chance of bleeding, infection, and damage to surrounding structures like bowel and bladder (transvaginal ultrasound aspiration) as well as difficulty breathing, chest infection, allergic reactions to meds, or nerve damage (laproscopy). During embryo transfer, if more than one embryo is transferred there’s always a risk of multiple pregnancy, infertile couples may see this is good news but there may be risk to the embryos and to the mother such as premature delivery. Ectopic pregnancy

Ectopic pregnancy

An ectopic pregnancy, or eccysis , is a complication of pregnancy in which the embryo implants outside the uterine cavity. With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the parent, since internal haemorrhage is a life threatening complication...

may also occur if a fertilised egg develops outside the uterus, usually in the fallopian tubes and requires immediate destruction of the fetus.

Multiple Births

The major complication of IVF is the risk of multiple birth

Multiple birth

A multiple birth occurs when more than one fetus is carried to term in a single pregnancy. Different names for multiple births are used, depending on the number of offspring. Common multiples are two and three, known as twins and triplets...

s. This is directly related to the practice of transferring multiple embryos at embryo transfer. Multiple births are related to increased risk of pregnancy loss, obstetrical complications, prematurity, and neonatal morbidity with the potential for long term damage. Strict limits on the number of embryos that may be transferred have been enacted in some countries (e.g. Britain, Belgium) to reduce the risk of high-order multiples (triplets or more), but are not universally followed or accepted. Spontaneous splitting of embryos in the womb after transfer can occur, but this is rare and would lead to identical twins. A double blind, randomised study followed IVF pregnancies that resulted in 73 infants (33 boys and 40 girls) and reported that 8.7% of singleton infants and 54.2% of twins had a birth weight of < 2500 grams (5.5 lb).

However, despite the risks, some recent evidence suggests that twins conceived by IVF actually have a 40% decreased outcome risk for complications than spontaneous twin conceptions. Experts believe that this could be due to high level of prenatal monitoring received from the moment of conception.

Recent evidence also suggest that singleton offspring after IVF is at higher risk for lower birth weight for unknown reasons.

Birth defects

The issue of birth defects has been a controversial topic in IVF. Many studies do not show a significant increase after use of IVF, and some studies suggest higher rates for ICSI, whereas others do not support this finding. In 2008, an analysis of the data of the National Birth Defects Study in the US found that certain birth defects were significantly more common in infants conceived through IVF, notably septal heart defects, cleft lip with or without cleft palate, esophageal atresia

Esophageal atresia

Esophageal atresia is a congenital medical condition which affects the alimentary tract. It causes the esophagus to end in a blind-ended pouch rather than connecting normally to the stomach. It comprises a variety of congenital anatomic defects that are caused by an abnormal embryological...

, and anorectal atresia; the mechanism of causality is unclear.

A 2002 study, reviewing the birth records of all the IVF babies in Western Australia

Western Australia

Western Australia is a state of Australia, occupying the entire western third of the Australian continent. It is bounded by the Indian Ocean to the north and west, the Great Australian Bight and Indian Ocean to the south, the Northern Territory to the north-east and South Australia to the south-east...

"has found IVF kids are twice as likely to have birth defects as normal births". The study allowed for the effects of multiple births and the mother's age. The higher incidence of birth defects "up to one year of age" included: heart defects, "chromosomal abnormalities like Down syndrome, spina bifida, gastro-intestinal abnormalities, musculo-skeletal, dislocated hips," and club feet. The IVF children also were found to have a higher incidence of lower birth weights, pre-term births, and cerebral palsy.

Japan's government prohibited the use of in vitro fertilisation procedures for couples in which both partners are infected with HIV

HIV

Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

. Despite the fact that the ethics committees previously allowed the Ogikubo, Tokyo Hospital, located in Tokyo

Tokyo

, ; officially , is one of the 47 prefectures of Japan. Tokyo is the capital of Japan, the center of the Greater Tokyo Area, and the largest metropolitan area of Japan. It is the seat of the Japanese government and the Imperial Palace, and the home of the Japanese Imperial Family...

, to use in vitro fertilisation for couples with HIV, the Ministry of Health, Labour and Welfare

Ministry of Health, Labour and Welfare (Japan)

The ' is a cabinet level ministry of the Japanese government. It is commonly known as Kōrō-shō in Japan. This ministry provides regulations on maximum residue limits for agricultural chemicals in foods, basic food and drug regulations, standards for foods, food additives, etc.It was formed with...

of Japan

Japan

Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...

decided to block the practice. Hideji Hanabusa, the vice president of the Ogikubo Hospital, states that together with his colleagues, he managed to develop a method through which scientists are able to remove HIV from sperm.

Other Risks

Another risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome

Ovarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe.-Causative medications:...

, particularly if hCG is used to "trigger ovulation".

If the underlying infertility is related to abnormalities in spermatogenesis, it is plausible, but too early to examine that male offspring is at higher risk for sperm abnormalities.

Behavior and socioemotional functioning of children conceived by IVF is normal overall, according to studies on 9–18-year-old IVF children.

A negative pregnancy test after IVF is associated with an increased risk for depression

Depression (mood)

Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...

in women, but not with any increased risk of developing anxiety disorders. Pregnancy test results do not seem to be a risk factor for depression or anxiety among men.

Expansions

There are various expansions or additional techniques that can be applied in IVF, which are usually not necessary for the IVF procedure itself, but would be virtually impossible or technically difficult to perform without concomitantly performing methods of IVF.

Embryo profiling

In addition to the methods already mentioned in the embryo selection above, there are more advanced techniques of embryo profiling that give more information to aid in the selection of the optimal embryo.

Also, methods are emerging in making comprehensive analyses of up to entire genome

Genome

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

s, transcriptome

Transcriptome

The transcriptome is the set of all RNA molecules, including mRNA, rRNA, tRNA, and other non-coding RNA produced in one or a population of cells.-Scope:...

s, proteome

Proteome

The proteome is the entire set of proteins expressed by a genome, cell, tissue or organism. More specifically, it is the set of expressed proteins in a given type of cells or an organism at a given time under defined conditions. The term is a portmanteau of proteins and genome.The term has been...

s and metabolome

Metabolome

Metabolome refers to the complete set of small-molecule metabolites to be found within a biological sample, such as a single organism...

s which may be used to score embryos by comparing the patterns with ones that have previously been found among embryos in successful versus unsuccessful pregnancies:

In transcriptome evaluation, however, gene expression profiling studies of human embryos are limited due to legal and ethical issues. An alternative or complement is gene expression profiling of cumulus cells surrounding the oocyte and early embryo, or on granulosa cell
Granulosa cell
A granulosa cell or follicular cell is a somatic cell of the sex cord that is closely associated with the developing female gamete in the ovary of mammals.-Anatomy and function:...

s. Profiling of cumulus cells can give valuable information regarding the efficiency of an ovarian hyperstimulation protocol, and may indirectly predict oocyte aneuploidy, embryo development and pregnancy outcomes, without having to perform any invasive procedure directly in the embryo.
Proteome profiling of embryos can indirectly be evaluated by sampling of proteins found in the vicinity of embryos, thereby providing a non-invasive method of embryo profiling. Examples of protein markers evaluated in such profiling include CXCL13
CXCL13
C-X-C motif chemokine 13 also known as B lymphocyte chemoattractant is a protein that in humans is encoded by the CXCL13 gene.- Function :CXCL13 is a small cytokine belonging to the CXC chemokine family...

and granulocyte-macrophage colony-stimulating factor, where lower protein amounts are associated with higher implantation rates.

Another level of opportunity can be achieved by having the evaluation of the embryo profile tailored to the maternal status in regard to, for example health or immune status, potentially further detailed by similar profiling of the maternal genome, transcriptome, proteome and metabolome. Two examples of proteins that may be included in maternal profiling are endometrium

Endometrium

-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...

-derived stathmin 1 and annexin A2

Annexin A2

Annexin A2 also known as annexin II is a protein that in humans is encoded by the ANXA2 gene.Annexin 2 is involved in diverse cellular processes such as cell motility , linkage of membrane-associated protein complexes to the actin cytoskeleton, endocytosis, fibrinolysis, ion channel formation, and...

, whose down- and up-regulation, respectively, are associated with higher rates of successful implantation.

The end-point of interest in the evaluation of an embryo profile is not necessarily the success rate of the pregnancy at hand, but may also be the health of the potential person

Potential person

A potential person has been defined as an entity which is not currently a person but which is capable of developing into a person, given certain biologically and/or technically possible conditions...

as a child and adult in the future, such as in detection of inheritable diseases by preimplantation genetic diagnosis

Preimplantation genetic diagnosis

(PGD) or screening (PGS):

Preimplantation genetic screening or diagnosis (PGS or PGD)

Preimplantation genetic screening (PGS) or preimplantation genetic diagnosis (PGD) has been suggested to be able to be used in IVF to select an embryo that appears to have the greatest chances for successful pregnancy. However, a systematic review and meta-analysis of existing randomised controlled trials came to the result that there is no evidence of a beneficial effect of PGS as measured by live birth rate. On the contrary, for women of advanced maternal age

Advanced maternal age

Advanced maternal age is defined as an increase in the age at which women give birth to their first child, is now a widespread, and indeed near universal, phenomenon across the OECD countries....

, PGS significantly lowers the live birth rate. Technical drawbacks, such as the invasiveness of the biopsy, and non-representative samples because of mosaicism

Mosaic (genetics)

In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...

are the major underlying factors for inefficacy of PGS.

Still, as an expansion of IVF, patients who can benefit from PGS/PGD include:

Couples who have a family history of inherited disease
Couples who want to use gender selection to prevent a gender-linked disease
Couples who already have a child with an incurable disease and need compatible cells from a second healthy child to cure the first, resulting in a "saviour sibling" that matches the sick child in HLA type.

PGS screens for numeral chromosomal abnormalities while PGD diagnosis the specific molecular defect of the inherited disease. In both PGS and PGD, individual cells from a pre-embryo are analysed during the IVF process. Before the transfer of a pre-embryo back to a woman's uterus, one or two cells are removed from the pre-embryos (8-cell stage). These cells are then evaluated for normality. Typically within one to two days, following completion of the evaluation, only the normal pre-embryos are transferred back to the woman's uterus. In addition, PGS can reduce the risk of multiple pregnancies because fewer embryos are needed for implantation.

Cryopreservation

Cryopreservation is a process where cells or whole tissues are preserved by cooling to low sub-zero temperatures, such as 77 K or −196 °C . At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, is effectively stopped...

can be performed as oocyte cryopreservation

Oocyte cryopreservation

Human oocyte cryopreservation is a novel technology in which a woman’s eggs are extracted, frozen and stored. Later, when she is ready to become pregnant, the eggs can be thawed, fertilized, and transferred to the uterus as embryos.-History:Cryopreservation itself has always played a central role...

before fertilisation, or as embryo cryopreservation

Embryo cryopreservation

Cryopreservation of embryos is the process of preserving an embryo at sub-zero temperatures, generally at an embryogenesis stage corresponding to pre-implantation, that is, from fertilisation to the blastocyst stage.-Indications:...

after fertilisation.

The Rand Consulting Group has estimated there to be 400,000 frozen embryos in the United States. The advantage is that patients who fail to conceive may become pregnant using such embryos without having to go through a full IVF cycle. Or, if pregnancy occurred, they could return later for another pregnancy. Spare oocytes or embryos resulting from fertility treatments may be used for oocyte donation or embryo donation to another woman or couple, and embryos may be created, frozen and stored specifically for transfer and donation by using donor eggs and sperm. Also, oocyte cryopreservation can be used for women who are likely to lose their ovarian reserve due to undergoing chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

.

The outcome from using cryopreserved embryos has uniformly been positive with no increase in birth defects or development abnormalities.

Other expansions

Intracytoplasmic sperm injection
Intracytoplasmic sperm injection
Intracytoplasmic sperm injection is an in vitro fertilization procedure in which a single sperm is injected directly into an egg.-Indications:...

(ICSI) is where a single sperm
Spermatozoon
A spermatozoon is a motile sperm cell, or moving form of the haploid cell that is the male gamete. A spermatozoon joins an ovum to form a zygote...

is injected directly into an egg
Ovum
An ovum is a haploid female reproductive cell or gamete. Both animals and embryophytes have ova. The term ovule is used for the young ovum of an animal, as well as the plant structure that carries the female gametophyte and egg cell and develops into a seed after fertilization...

. Its main usage as an expansion of IVF is to overcome male infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...

problems, although it may also be used where eggs cannot easily be penetrated by sperm, and occasionally in conjunction with sperm donation
Sperm donation
Sperm donation is the provision by a man, , of his sperm, with the intention that it be used to impregnate a woman who is not usually the man's sexual partner, in order to produce a child....

. It can be used in teratozoospermia, since once the egg is fertilised abnormal sperm morphology does not appear to influence blastocyst
Blastocyst
The blastocyst is a structure formed in the early embryogenesis of mammals, after the formation of the morula. It is a specifically mammalian example of a blastula. It possesses an inner cell mass , or embryoblast, which subsequently forms the embryo, and an outer layer of cells, or trophoblast,...

development or blastocyst morphology.
Assisted zona hatching
Assisted zona hatching
Assisted zona hatching is a procedure of assisted reproductive technology in which a small hole is made in the zona pellucida, using a micromanipulation, thereby facilitating for zona hatching to occur.....

(AZH) can be performed shortly before the embryo is transferred to the uterus. A small opening is made in the outer layer surrounding the egg in order to help the embryo hatch out and aid in the implantation process of the growing embryo.
In egg donation and embryo donation, the resultant embryo after fertilisation is inserted in another woman than the one providing the eggs. These are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age
Advanced maternal age
Advanced maternal age is defined as an increase in the age at which women give birth to their first child, is now a widespread, and indeed near universal, phenomenon across the OECD countries....

. In the egg donor process, eggs are retrieved from a donor's ovaries, fertilised in the laboratory with the sperm from the recipient's partner, and the resulting healthy embryos are returned to the recipient's uterus.
Embryo splitting can be used for twinning to increase the number of available embryos.

Leftover embryos or eggs

There may be leftover embryos or eggs from IVF procedures if the woman for whom they were originally created has successfully carried one or more pregnancies to term. With the woman's or couple's permission, these may be donated to help other women or couples as a means of third party reproduction

Third party reproduction

Third party reproduction refers to a process where another person provides sperm or eggs or where another woman provides her uterus so that a woman can have a child. Thus the reproductive process goes beyond the traditional father-mother model. However, the third party's involvement is limited to...

.

In embryo donation, these extra embryos are given to other couples or women for transfer

Embryo transfer

Embryo transfer refers to a step in the process of assisted reproduction in which embryos are placed into the uterus of a female with the intent to establish a pregnancy...

with the goal of producing a successful pregnancy. The resulting child is considered the child of the woman who carries it and gives birth, and not the child of the donor, the same as occurs with egg donation

Egg donor

Egg donation is the process by which a woman provides one or several eggs for purposes of assisted reproduction or biomedical research. For assisted reproduction purposes, egg donation involves the process of in vitro fertilization as the eggs are fertilized in the laboratory. After the eggs...

or sperm donation

Sperm donation

Sperm donation is the provision by a man, , of his sperm, with the intention that it be used to impregnate a woman who is not usually the man's sexual partner, in order to produce a child....

.

Typically, genetic parents donate the eggs to a fertility clinic

Fertility clinic

Fertility clinics are staffed medical clinics that assist couples, and sometimes individuals, who want to become parents but for medical reasons have been unable to achieve this goal via the natural course...

or embryo bank where they are preserved by oocyte cryopreservation

Oocyte cryopreservation

or embryo cryopreservation

Embryo cryopreservation

until a carrier is found for them. Typically the process of matching the embryo(s) with the prospective parents is conducted by the agency itself, at which time the clinic transfers ownership of the embryos to the prospective parents.

In the United States, women seeking to be an embryo recipient undergo infectious disease screening required by the U.S. Food and Drug Administration (FDA), and reproductive tests to determine the best placement location and cycle timing before the actual Embryo Transfer occurs. The amount of screening the embryo has already undergone is largely dependent on the genetic parents' own IVF clinic and process. The embryo recipient may elect to have her own embryologist conduct further testing.

Alternatives to donating unused embryos are destroying them (or having them implanted at a time where pregnancy is very unlikely), keeping them frozen indefinitely, or donating them for use in research (with results in their unviability). Individual moral views on disposing leftover embryos may depend on personal views on the beginning of human personhood

Beginning of human personhood

The beginning of human personhood is the period in an individual's life when he or she is recognized, or begins to be recognized, as a person. The precise timing and nature of this occurrence is not universally agreed upon, and has been the subject of discussion and debate in science, religion and...

and definition and/or value of potential future persons

Potential person

A potential person has been defined as an entity which is not currently a person but which is capable of developing into a person, given certain biologically and/or technically possible conditions...

and on the value that is given to fundamental research questions. Some people believe donation of leftover embryos for research is a good alternative to discarding the embryos when patients receive proper, honest and clear information about the research project, the procedures and the scientific values).

History

There was a transient biochemical pregnancy reported by Australian Foxton School researchers in 1953. John Rock

John Rock (American scientist)

John Rock was an American obstetrician and gynecologist. He is best known for the major role he played in the development of the first hormonal contraceptive, colloquially called "the pill".-Early life and career:...

was the first to extract an intact fertilised egg. The first pregnancy achieved through in vitro human fertilisation of a human oocyte was reported in The Lancet from the Monash University

Monash University

Monash University is a public university based in Melbourne, Victoria. It was founded in 1958 and is the second oldest university in the state. Monash is a member of Australia's Group of Eight and the ASAIHL....

team in 1973, although it lasted only a few days and would today be called a biochemical pregnancy. There was also an ectopic pregnancy reported by Patrick Steptoe

Patrick Steptoe

Patrick Christopher Steptoe FRS was a British obstetrician and gynaecologist and a pioneer of fertility treatment. Steptoe was responsible with biologist and physiologist Robert Edwards for developing in vitro fertilization...

and Robert Edwards in 1976. In 1977, Steptoe and Edwards successfully carried out a pioneering conception which resulted in the birth of the world's first baby to be conceived by IVF, Louise Brown

Louise Brown

Louise Joy Brown is the first person to be conceived by in vitro fertilization, or IVF.-Birth:...

on 25 July 1978, in Oldham General Hospital, Greater Manchester

Greater Manchester

Greater Manchester is a metropolitan county in North West England, with a population of 2.6 million. It encompasses one of the largest metropolitan areas in the United Kingdom and comprises ten metropolitan boroughs: Bolton, Bury, Oldham, Rochdale, Stockport, Tameside, Trafford, Wigan, and the...

, UK.

In October 1978, it was reported that Subash Mukhopadyay

Subhash Mukhopadhyay (physician)

Subhash Mukhopadhyay was a physician from Kolkata, India.-Early life:He was born on January 16, 1931 in Hazaribag, Bihar , India. He studied and graduated with an honours degree in physiology from the Calcutta National Medical College, which was then affiliated with the prestigious University...

, a relatively unknown physician from Kolkata

Kolkata

Kolkata , formerly known as Calcutta, is the capital of the Indian state of West Bengal. Located on the east bank of the Hooghly River, it was the commercial capital of East India...

, India

India

India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...

was performing experiments on his own with primitive instruments and a household refrigerator and this resulted in a test tube baby, later named as "Durga" (alias Kanupriya Agarwal) who was born on October 3, 1978. However, state authorities prevented him from presenting his work at scientific conferences and, in the absence of scientific evidence, his work is not recognised by the international scientific community.

Steptoe and Edwards were responsible for the world’s second (confirmed) baby conceived by IVF, Alastair MacDonald born on 14 January 1979 in Glasgow. A team led by Ian Johnston and Alex Lopata were responsible for Australia’s first baby conceived by IVF, Candice Reed born on 23 June 1980 in Melbourne. It was the subsequent use of stimulated cycles with clomiphene citrate and the use of human chorionic gonadotrophin (hCG) to control and time oocyte maturation, thus controlling the time of collection, that converted IVF from a research tool to a clinical treatment.

This was followed by a total of 14 pregnancies resulting in nine births in 1981 with the Monash University team. The Jones team at the Eastern Virginia Medical School

Eastern Virginia Medical School

Eastern Virginia Medical School commonly referred to as EVMS, in Norfolk, Virginia is a public-private medical school founded by the citizens of Hampton Roads, Virginia...

in Norfolk, Virginia

Norfolk, Virginia

Norfolk is an independent city in the Commonwealth of Virginia in the United States. With a population of 242,803 as of the 2010 Census, it is Virginia's second-largest city behind neighboring Virginia Beach....

, further improved stimulated cycles by incorporating the use of a follicle-stimulating hormone (uHMG). This then became known as controlled ovarian hyperstimulation (COH). Another step forward was the use of gonadotrophin-releasing hormone agonists (GnRHA), thus decreasing the need for monitoring by preventing premature ovulation, and more recently gonadotrophin-releasing hormone antagonists (GnRH Ant), which have a similar function. The additional use of the oral contraceptive pill has allowed the scheduling of IVF cycles, which has made the treatment far more convenient for both staff and patients.

The ability to freeze and subsequently thaw and transfer embryos has significantly improved the feasibility of IVF use. The other very significant milestone in IVF was the development of the intracytoplasmic sperm injection (ICSI) of single sperms by André van Steirteghem in Brussels, 1992. This has enabled men with minimal sperm production to achieve pregnancies. ICSI is sometimes used in conjunction with sperm recovery, using a testicular fine needle or open testicular biopsy. Using this method, some men with Klinefelter's syndrome

Klinefelter's syndrome

Klinefelter syndrome, 46/47, XXY, or XXY syndrome is a condition in which human males have an extra X chromosome. While females have an XX chromosomal makeup, and males an XY, affected individuals have at least two X chromosomes and at least one Y chromosome...

, and so would be otherwise infertile, have occasionally been able to achieve pregnancy. Thus, IVF has become the final solution for most fertility problems, moving from tubal disease to male factor, idiopathic subfertility, endometriosis, advanced maternal age

Advanced maternal age

Advanced maternal age is defined as an increase in the age at which women give birth to their first child, is now a widespread, and indeed near universal, phenomenon across the OECD countries....

, and anovulation not responding to ovulation induction.

Robert Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine

Nobel Prize in Physiology or Medicine

"for the development of in vitro fertilization". Carl Wood

Carl Wood

Edwin Carlyle "Carl" Wood, AC, CBE, FRCS, FRANZCOG was a prominent Australian gynaecologist, best known for his pioneering work developing and commercialising the technique of in-vitro fertilisation...

was dubbed "the father of IVF (in vitro fertilisation)" for having pioneered the use of frozen embryos.

In the US, ART cycles started in 2006 resulted in 41,343 births (54,656 infants), which is slightly more than 1% of total US births.

Issues

In a few cases, laboratory mix-ups (misidentified gametes, transfer of wrong embryos) have occurred, leading to legal action against the IVF provider and complex paternity suits. An example is the case of a woman in California who received the embryo of another couple and was notified of this mistake after the birth of her son. This has led to many authorities and individual clinics implementing procedures to minimise the risk of such mix-ups. The HFEA, for example, requires clinics to use a double witnessing system, where the identity of specimens is checked by two people at each point at which specimens are transferred. Alternatively, technological solutions are gaining favour, to reduce the manpower cost of manual double witnessing, and to further reduce the risk of human error. Technological solutions typically involve tagging individual specimen containers with uniquely numbered RFID tags which can be identified by readers connected to a computer. The computer tracks specimens throughout the process and alerts the embryologist if non-matching specimens are identified.

Another concern is that people will screen in or out for particular traits, using preimplantation genetic diagnosis

Preimplantation genetic diagnosis

. For example, a deaf British couple, Tom and Paula Lichy, have petitioned to create a deaf baby using IVF. Some medical ethicists

Bioethics

Bioethics is the study of controversial ethics brought about by advances in biology and medicine. Bioethicists are concerned with the ethical questions that arise in the relationships among life sciences, biotechnology, medicine, politics, law, and philosophy....

have been very critical of this approach. Jacob Appel

Jacob M. Appel

Jacob M. Appel is an American author, bioethicist and social critic. He is best known for his short stories, his work as a playwright, and his writing in the fields of reproductive ethics, organ donation, neuroethics and euthanasia....

wrote that "intentionally culling out blind or deaf embryos might prevent considerable future suffering, while a policy that allowed deaf or blind parents to select for such traits intentionally would be far more troublesome."

Pregnancy past menopause

Although menopause is a natural barrier to further conception, IVF has allowed women to be pregnant in their fifties and sixties. Women whose uterus has been appropriately prepared receive embryos that originated from an egg of an egg donor. Therefore, although these women do not have a genetic link with the child, they have an emotional link through pregnancy and childbirth. In many cases the genetic father of the child is the woman's partner. Even after menopause the uterus is fully capable of carrying out a pregnancy.

Same-sex couples, single and unmarried parents

A 2009 statement from the ASRM found no persuasive evidence that children are harmed or disadvantaged solely by being raised by single parents, unmarried parents, or homosexual parents. It did not support restricting access to assisted reproductive technologies on the basis of a prospective parent's marital status or sexual orientation.

Ethical concerns include reproductive rights, the welfare of offspring, nondiscrimination against unmarried individuals, homosexual, and professional autonomy.

A recent controversy in California focused on the question of whether physicians opposed to same-sex relationships should be required to perform IVF for a lesbian couple. Guadalupe T. Benitez, a medical assistant from San Diego, sued doctors Christine Brody and Douglas Fenton of the North Coast Women's Care Medical Group after Brody told her that she had "religious-based objections to treating homosexuals to help them conceive children by artificial insemination," and Fenton refused to authorise a refill of her prescription for the fertility drug Clomid on the same grounds. The California Medical Association had initially sided with Brody and Fenton, but the case, North Coast Women's Care Medical Group v. Superior Court

North Coast Women's Care Medical Group v. Superior Court

North Coast Women's Care Medical Group vs. Superior Court is a case decided before the California Supreme Court on August 19, 2008, ruling that physicians must offer IVF services to gays and lesbians despite religious objections or find a colleague in their office who will do so.The suit was...

, was decided unanimously by the California State Supreme Court in favor of Benitez on August 19, 2008.

Nadya Suleman

Nadya Suleman

Nadya Denise Doud-Suleman , known as Octomom in the media, is an American woman who came to international attention when she gave birth to octuplets in January 2009. The Suleman octuplets are only the second full set of octuplets to be born alive in the United States...

came to international attention after having twelve embryos implanted, eight of which survived, resulting in eight newborns being added to her existing six-child family. The Medical Board of California sought to have fertility doctor Michael Kamrava, who treated Suleman, stripped of his license. State officials allege that performing Suleman's procedure is evidence of unreasonable judgment, substandard care, and a lack of concern for the eight children she would conceive and the six she was already struggling to raise. On June 1, 2011 the Medical Board issued a ruling that Kamrava's medical license be revoked effective July 1, 2011.
http://documents.latimes.com/michael-kamrava-disciplinary-decision/

Catholic objections

The Catholic Church opposes all kinds of in vitro fertilisation because, as with contraception

Contraception

Contraception is the prevention of the fusion of gametes during or after sexual activity. The term contraception is a contraction of contra, which means against, and the word conception, meaning fertilization...

, it separates the procreative purpose of the marriage act from its unitive purpose:

This particular doctrine, often expounded by the magisterium of the Church
Magisterium
In the Catholic Church the Magisterium is the teaching authority of the Church. This authority is understood to be embodied in the episcopacy, which is the aggregation of the current bishops of the Church in union with the Pope, led by the Bishop of Rome , who has authority over the bishops,...

, is based on the inseparable connection, established by God, which man on his own initiative may not break, between the unitive significance and the procreative significance which are both inherent to the marriage act.

The reason is that the fundamental nature of the marriage act, while uniting husband and wife in the closest intimacy, also renders them capable of generating new life—and this as a result of laws written into the actual nature of man and of woman. And if each of these essential qualities, the unitive and the procreative, is preserved, the use of marriage fully retains its sense of true mutual love and its ordination to the supreme responsibility of parenthood to which man is called. We believe that our contemporaries are particularly capable of seeing that this teaching is in harmony with human reason.

According to the Catechism of the Catholic Church

Catechism of the Catholic Church

The Catechism of the Catholic Church is the official text of the teachings of the Catholic Church. A provisional, "reference text" was issued by Pope John Paul II on October 11, 1992 — "the thirtieth anniversary of the opening of the Second Vatican Ecumenical Council" — with his apostolic...

Techniques involving only the married couple (homologous artificial insemination and fertilization) are perhaps less reprehensible, yet remain morally unacceptable. They dissociate the sexual act from the procreative act. The act which brings the child into existence is no longer an act by which two persons give themselves to one another, but one that "entrusts the life and identity of the embryo into the power of doctors and biologists and establishes the domination of technology over the origin and destiny of the human person. Such a relationship of domination is in itself contrary to the dignity and equality that must be common to parents and children."

The Catholic Church maintains that it is not objectively evil to be infertile, and advocates adoption as an option for such couples who still wish to have children:

The Gospel
Gospel
A gospel is an account, often written, that describes the life of Jesus of Nazareth. In a more general sense the term "gospel" may refer to the good news message of the New Testament. It is primarily used in reference to the four canonical gospels of Matthew, Mark, Luke, and John...

shows that physical sterility is not an absolute evil. Spouses who still suffer from infertility after exhausting legitimate medical procedures should unite themselves with the Lord's Cross
Christian cross
The Christian cross, seen as a representation of the instrument of the crucifixion of Jesus Christ, is the best-known religious symbol of Christianity...

, the source of all spiritual fecundity. They can give expression to their generosity by adopting abandoned children or performing demanding services for others.

Gamete Intrafallopian Transfer (GIFT) is not technically in vitro fertilisation because with GIFT, fertilisation takes place inside the body, not on a Petri dish. The Catholic Church nevertheless is concerned with it because "Some theologians consider this to be a replacement of the marital act, and therefore immoral."

Availability and utilisation

In the USA, overall availability of IVF in 2005 was 2.5 IVF physicians per 100,000 population, and utilisation was 236 IVF cycles per 100,000. Utilisation highly increases with availability and IVF insurance coverage, and to a significant extent also with percentage of single persons and median income.

The cost of IVF rather reflects the costliness of the underlying healthcare system than the regulatory or funding environment, and ranges, on average for a standard IVF cycle and in 2006 United States dollars, between $12,500 in the United States to $4,000 in Japan. In Ireland, IVF costs around €4,000, with fertility drugs, if required, costing up to €3,000. The cost per live birth is highest in the United States ($41,000) and United Kingdom ($40,000) and lowest in Scandinavia and Japan (both around $24,500).

Many fertility clinics in the United States limit the upper age at which women are eligible for IVF to 50 or 55 years. These cut-offs make it difficult for women older than fifty-five to utilise the procedure.

In Australia, the average age of women undergoing ART treatment is 35.5 years among those using their own eggs (one in four being 40 or older) and 40.5 years among those using donated eggs.

Legal status

Government agencies in China

China

Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

passed bans on the use of IVF in 2003 by unmarried women or by couples with certain infectious diseases. Sunni Muslim nations generally allow IVF between married couples when conducted with their own respective sperm and eggs, but not with donor eggs from other couples. But Iran, which is Shi'a Muslim, has a more complex scheme. Iran bars sperm donation but allows donation of both fertilised and unfertilised eggs. Fertilised eggs are donated from married couples to other married couples, while unfertilised eggs are donated in the context of mut'ah or temporary marriage to the father. The nation of Costa Rica

Costa Rica

Costa Rica , officially the Republic of Costa Rica is a multilingual, multiethnic and multicultural country in Central America, bordered by Nicaragua to the north, Panama to the southeast, the Pacific Ocean to the west and the Caribbean Sea to the east....

has a complete ban on all IVF technology, it having been ruled unconstitutional by the nation's Supreme Court because it "violated life." Costa Rica is the only country in the western hemisphere that forbids this technique. The Inter-American Court on Human Rights ruled out that the Costa Rican government has violated the human rights of infertile couples when it banned the use of this technique. According to the rule, Costa Rica had to enact legislation allowing the use of this type of procedure. The Court set a first dateline on February 2011 for a report on the question by the Costa Rican government. The latter missed the dateline and new datelines were set. All of them have been missed by the Costa Rican government. A law project sent reluctantly by the government of Pres. Laura Chinchilla was rejected at the Costa Rican parliament. Consequently, observers expect that Costa Rica will not abide to the request of the Inter-American Court on Human Rights. President Chinchilla, whose strong Catholic views have won her to be named officially as Preferred Daughter of the Virgin Mary has not publicly stated her position on the question of in vitro fertilisation. However, given the massive influence of the Catholic Church in her government any change in the status quo seems very unlikely La Costa Rica católica se atasca con la fertilización in vitro CIDH Extends Deadline For Approval Of Law For In-Vitro Fertilization In Costa Rica. Federal regulations in the United States include screening requirements and restrictions

Current Good Tissue Practices

Current Good Tissue Practice , also known as Good Tissue Practice , is a term that is one of the "GxP" requirements derived from cGMP. The rule was written and is enforced by the U.S. Food and Drug Administration , specifically the Center for Biologics Evaluation and Research...

on donations, but generally do not affect sexually intimate partners. However, doctors may be required to provide treatments due to nondiscrimination laws, as for example in California.

All major restrictions on single but infertile women using IVF were lifted in Australia in 2002 after a final appeal to the Australian High Court was rejected on procedural grounds in the Leesa Meldrum case. A Victorian

Victoria (Australia)

Victoria is the second most populous state in Australia. Geographically the smallest mainland state, Victoria is bordered by New South Wales, South Australia, and Tasmania on Boundary Islet to the north, west and south respectively....

federal court had ruled in 2000 that the existing ban on all single women and lesbians using IVF constituted sex discrimination. Victoria's government announced changes to its IVF law in 2007 eliminating remaining restrictions on fertile single women and lesbians, leaving South Australia

South Australia

South Australia is a state of Australia in the southern central part of the country. It covers some of the most arid parts of the continent; with a total land area of , it is the fourth largest of Australia's six states and two territories.South Australia shares borders with all of the mainland...

as the only state maintaining them. The US state of Tennessee

Tennessee

Tennessee is a U.S. state located in the Southeastern United States. It has a population of 6,346,105, making it the nation's 17th-largest state by population, and covers , making it the 36th-largest by total land area...

proposed a bill in 2009 that would have defined donor IVF as adoption. During the same session another bill proposed barring adoption from any unmarried and cohabitating couple, and activist groups stated that passing the first bill would effectively stop unmarried people from using IVF. Neither of these bills passed.

External links

UK IVF clinics and statistics (HFEA
Human Fertilisation and Embryology Authority
The Human Fertilisation and Embryology Authority is a statutory body in the United Kingdom that regulates and inspects all UK clinics providing in vitro fertilisation, artificial insemination and the storage of human eggs, sperm or embryos. It also regulates Human Embryo research...

)
US information, statistics, and lists on assisted reproductive technology (CDC
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

)
Test Tube Babies on PBS
BBC profile of Louise Brown (July, 2003)
Make Room for Multiples | Couples experience with IVF

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.

Indications

Method

Ovarian hyperstimulation

Egg retrieval

Egg and sperm preparation

Fertilisation

Embryo culture

Embryo selection

Embryo transfer

Success rates

Live birth rate

Pregnancy rate

Success or failure factors

Stress

Acupuncture

Other factors

Risks

Multiple Births

Birth defects

Other Risks

Expansions

Embryo profiling

Preimplantation genetic screening or diagnosis (PGS or PGD)

Cryopreservation

Other expansions

Leftover embryos or eggs

History

Issues

Pregnancy past menopause

Same-sex couples, single and unmarried parents

Catholic objections

Availability and utilisation

Legal status

See also

External links