In vitro fertilization, fertilization
In vitro fertilization (IVF) is a process by which an egg is fertilised by sperm outside the body: in vitro . The process involves monitoring and stimulating a woman's ovulatory process, removing an ovum or ova (egg or eggs) from the woman's ovaries and letting sperm fertilise them in a liquid in a laboratory. The fertilised egg (zygote) is cultured for 2–6 days in a growth medium and is then implanted in the same or another woman's uterus, with the intention of establishing a successful pregnancy.
IVF techniques can be used in different types of situations. It is a technique of assisted reproductive technology for treatment of infertility. IVF techniques are also employed in gestational surrogacy, in which case the fertilised egg is implanted into a surrogate's uterus, and the resulting child is genetically unrelated to the surrogate. In some situations, donated eggs or sperms may be used. Some countries ban or otherwise regulate the availability of IVF treatment, giving raise to fertility tourism. Restrictions on availability of IVF include to single females, to lesbians and to surrogacy arrangements. Due to the costs of the procedure, IVF is mostly attempted only after less expensive options have failed.
The first successful birth of a "test tube baby", Louise Brown, occurred in 1978. Louise Brown was born as a result of natural cycle IVF where no stimulation was made. Robert G. Edwards, the physiologist who developed the treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. With egg donation and IVF, women who are past their reproductive years or menopause can still become pregnant. Adriana Iliescu held the record as the oldest woman to give birth using IVF and donated egg, when she gave birth in 2004 at the age of 66, a record passed in 2006.
IVF may be used to overcome female infertility where it is due to problems with the fallopian tubes, making fertilisation in vivo difficult. It can also assist in male infertility, in those cases where there is a defect in sperm quality; in such situations intracytoplasmic sperm injection (ICSI) may be used, where a sperm cell is injected directly into the egg cell. This is used when sperm has 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. When indicated, the use of ICSI has been found to increase the success rates of IVF.
According to the British NICE guidelines, IVF treatment is appropriate in cases of unexplained infertility for women that have not conceived after 2 years of regular unprotected sexual intercourse. This rule does not apply to all countries. (See infertility.)
IVF is also considered suitable in cases where any of its expansions is of interest, that is, a procedure that is usually not necessary for the IVF procedure itself, but would be virtually impossible or technically difficult to perform without concomitantly performing methods of IVF. Such expansions include preimplantation genetic diagnosis (PGD) to rule out presence ofgenetic disorders, as well as egg donation or surrogacy where the woman providing the egg isn't the same who will carry the pregnancy to term.
The major complication of IVF is the risk of multiple births. 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 < 2,500 grams (5.5 lb).
Recent evidence also suggest that singleton offspring after IVF is at higher risk for lower birth weight for unknown reasons.
Spread of infectious disease By sperm washing, the risk that a chronic disease in the male providing the sperm would infect the female or offspring can be brought to negligible levels. In males with hepatitis B, The Practice Committee of the American Society for Reproductive Medicine advises that sperm washing is not necessary in IVF to prevent transmission, unless the female partner has not been effectively vaccinated. In females with hepatitis B, the risk of vertical transmission during IVF is no different from the risk in spontaneous conception. However, there is not enough evidence to say that ICSI procedures are safe in females with hepatitis B in regard to vertical transmission to the offspring. Regarding potential spread of HIV/AIDS, Japan's government prohibited the use of in vitro fertilisation procedures for couples in which both partners are infected with HIV. Despite the fact that the ethics committees previously allowed the Ogikubo, Tokyo Hospital, located in Tokyo, to use in vitro fertilisation for couples with HIV, the Ministry of Health, Labour and Welfare of Japan 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 to the egg provider/retriever A risk of ovarian stimulation is the development of ovarian hyperstimulation syndrome, particularly if hCG is used for inducing final oocyte maturation. This results in swollen, painful ovaries. It 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 in breathing, chest infection, allergic reactions to medication, or nerve damage (laproscopy). Ectopic pregnancy may also occur if a fertilised egg develops outside the uterus, usually in the fallopian tubes and requires immediate destruction of the foetus. IVF does not seem to be associated with an elevated risk of cervical cancer, nor with ovarian cancer or endometrial cancer when neutralising the confounder of infertility itself. Nor does it seem to impart any increased risk for breast cancer. Regardless of pregnancy result, IVF treatment is usually stressful for patients. Neuroticism and the use of escapist coping strategies are associated with a higher degree of distress, while the presence social support has a relieving effect. A negative pregnancy test after IVF is associated with an increased risk for depression 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.
Predictors of success
The main potential factors that influence pregnancy (and live birth) rates in IVF have been suggested to be maternal age, sperm quality, 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.
Antral follicle count, with higher count giving higher success rates.Biomarkers that affect the pregnancy chances of IVF include:
Other determinants of outcome of IVF include:
Aspirin is sometimes prescribed to women for the purpose of increasing the chances of conception by IVF, but there is insufficient evidence to show that it actually works.A 2013 review and metaanalysis of randomised controlled trials of acupuncture as an adjuvant therapy in IVF found no overall benefit, and concluded that an apparent benefit detected in a subset of published trials where the control group (those not using acupuncture) experienced a lower than average rate of pregnancy requires further study, due to the possibility ofpublication bias and other factors.
A Cochrane review came to the result that endometrial injury performed in the month prior to ovarian hyperstimulation appeared to increase both the live birth rate and clinical pregnancy rate in IVF compared with no endometrial injury. However, there was a lack of data reported on the rates of adverse outcomes such as miscarriage, multiple pregnancy, pain and/or bleeding.
For females, intake of antioxidants (such as N-acetyl-cysteine, melatonin, vitamin A, vitamin C, vitamin E, folic acid, myo-inositol, zinc or selenium have not been associated with a significantly increased live birth rate or clinical pregnancy rate in IVF according to Cochrane reviews.On the other hand, oral antioxidants given to the men in couples with male factor or unexplained subfertility resulted in significantly higher live birth rate in IVF.
A Cochrane review in 2013 came to the result that there is no evidence identified regarding the effect of pre-conception lifestyle advice on the chance of a live birth outcome.
A semen pH value outside of the normal range which is harmful to sperm and can cause infertility.
Female disorder in reproductive system at which a woman miss the uterus and thus she is not able to get pregnant and carry a child.
A type of cancerous tumor that develops in the gland cells.
A tumor-forming variant of adenomyosis (endometriosis in the myometrium of the uterus).
Medical condition characterized by the presence of ectopic endometrial tissue within the myometrium.
Failure of the adrenal glands to produce sufficient amounts of hormones.
The absence of a menstrual period in women of reproductive age.
The pathological inability to ejaculate in males, with (orgasmic) or without (anorgasmic) orgasm.
A neurodevelopmental disorder with intellectual and developmental disability, sleep disturbance, seizures, jerky movements and frequent laughter.
A disorder of sex development in which individuals have both testes absent at birth.
An eating disorder characterized by the maintenance of a body weight below average, fear of gaining weight, and a distorted body image.
Failure of the ovaries to release an oocyte over a period of time generally exceeding 3 months.
A condition when immune system mistakenly attacks some of the standard proteins in blood.
An inflammation of the appendix that may be associated with female infertility.
A medical condition, where the walls of the uterus stick to one another due to bands of scar tissue.
Male diagnosis connected with male infertility characterised by the complete absence of semen.
The thickening, hardening and loss of elasticity of the walls of arteries.
A condition arising from an abnormal immune response to a normal body part.
A disease in which antibodies against the thyroid gland and its hormone products are produced and destroy the thyroid’s cells and the entire gland.
Complete absence of sperm in the ejaculate of a man.
A noncancerous increase in size of the prostate.
Inborn morphological deviation of the uterus - one of the Müllerian duct anomalies where the uterine cavity is divided in the upper part.
A blockage of both fallopian tubes.
A cancer that develops from breast tissue.
Condition causing cervical mucus too thick and hostile to allow the sperm to penetrate the cervix.
Narrowing of cervix - the opening to the uterus.
A common sexually transmitted disease (STD) caused by the Chlamydia trachomatis bacteria that can lead to serious reproductive morbidity.
A condition in which the vasa deferentia reproductive organs, fail to form properly prior to birth.
Fallopian tube(s) blocked from birth unabling to let the ovum and the sperm converge, thus making fertilization impossible.
Male infertility diagnosis characterized by extremely low concentration of sperm in semen.
A man's inability for or persistent difficulty in achieving orgasm, despite typical sexual desire and sexual stimulation.
A class of sexual disorders defined as the subjective lack of normal ejaculation.
Cancer that arises from the endometrium, the lining of the uterus.
Thickening of the lining of the uterus.
The finger like overgrowths attached to the inner wall of the uterus that extend into the uterine cavity which are made of endometrial tissue
Benign ovarian cysts containing thick, old blood that appears as a brown fluid.
A state in which pieces of the tissue alike to the lining of the uterus (endometrium) grow in other parts of the body.
An inflammation of the inner uterine lining that could interfere with conception and pregnancy outcomes.
An inflammation of epididymis.
The inability (that lasts more than 6 months) to develop or maintain an erection of the penis during sexual activity.
An obstruction prevents the egg or sperm from traveling down the tube, thus making fertilization impossible.
An abnormal growth of fallopian tube tissue.
Persistent, recurrent problems with sexual response, desire, orgasm or pain which may cause fertility problems.
Genetic condition that is the most common inherited cause of intellectual disability, as well as the most frequent cause of autism spectrum disorder.
A sexually transmitted infection which is the most common cause of diseases accompanied by genital ulceration.
Fleshy growths or lumps found around the genitals and anus transmitted through sexual intercourse or during labor.
A group of rare diseases in which abnormal trophoblast cells grow inside the uterus after conception.
A rare abnormality of sperm morphology, with the majority of sperm cells being round-headed, which leads to male infertility.
Any congenital developmental disorder of the reproductive system characterized by a progressive loss of germ cells on the developing gonads.
A sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae.
The tumor that arises from the granulosa cells (normally surrounding the oocytes and line the developing follicle) and could impair menstrual periods.
Occlusion of some part of the female genital tract, especially occlusion of the vagina by a thick membrane.
Various types of conditions that can affect the function of the heart or blood vessels, which may have the negative effect also to the infertility
A collection or retention of blood in the uterus, affecting the patient´s fertility.
Hematosalpinx is a medical condition involving bleeding into the fallopian tube.
An infection caused by the hepatitis B virus which inflames the liver and which could also impair sperm motility.
An infection caused by the hepatitis C virus (HCV) that affects the liver and could be transmitted through sexual intercourse by blood or from infecte
A viral infection that progressively destroys certain white blood cells and can cause acquired immunodeficiency syndrome (AIDS).
A common virus that affects both males and females that could result in genital warts or cancer.
An accumulation of clear fluid in the tunica vaginalis, the most internal of membranes containing a testicle.
A hydrosalpinx is an abnormal pouch containing liquid in a fallopian tube.
A medical condition characterized by excessive levels of androgens in the body.
An excessive amount of estrogenic activity in the body.
Decreased functional activity of the gonads, with retardation sexual development, associated with high levels of hormones that stimulate the gonads.
The condition of elevated concentrations of gonadotropins within the blood.
Excess levels of insulin circulating in the blood relative to the level of glucose and impairing the hormonal levels, even those involved in reproduct
Abnormally elevated levels of any or all lipids in the blood.
The presence of abnormally high levels of prolactin in the blood.
Condition that occurs due to excessive production of thyroid hormone by the thyroid gland.
A medical condition characterized by not enough androgenic activity in the body.
A lower than normal level of estrogen which is the primary sex hormone in women.
A medical term which describes a diminished functional activity of the gonads – the testes and ovaries.
Partial or complete loss of production of one or more of the pituitary gland hormones.
A deficiency in the serum levels of the prolactin hormone.
An anomaly of the penis, with the opening of the urethra located on the underside of the penis, which may lead to infertility.
A condition in which a man has an unusually low ejaculate (or semen) volume.
Group of diseases, which have impact on function of hypothalamus.
A surgery performed to remove a woman's uterus.
A condition in which fertility impairment occurs spontaneously or due to an unknown cause.
A genetic condition where the primary symptom is a failure to start puberty or a failure to fully complete puberty.
The set of symptoms that result from two or more X chromosome in males.
Laurence-Moon syndrome (LMS) is a genetically predisposed disorder affecting both genders.
A presence of more than one million of white blood cells in 1 millimeter (mL) of ejaculate.
Mutation causing impaired Leydig cell differentiation and testosterone production.
Patients with a low number of retrieved oocytes despite adequate ovarian stimulation during fertility treatment.
Collection of autoimmune diseases in which the human immune system becomes hyperactive and attacks normal, healthy tissues.
The luteinisation of ovulatory follicle without a release of an oocyte.
The time in most women's lives when menstrual periods stop permanently, and the woman is no longer able to have children.
An abnormal condition in a woman's menstrual cycle.
The condition of only one testicle present in the scrotum.
Mumps was a common childhood viral disease caused by the mumps virus. Mumps frequently causes orchitis and impairs male fertility.
Necrospermia is a condition in which spermatozoa in semen are either immobile or dead
Type of cancer arising from the lymphoid tissue.
Complete absence of sperm in the ejaculate due to testicular failure.
A frequent autosomal dominant developmental disorder primarily characterized by short stature, typical facial features and heart defects.
A manifest variant of nutcracker phenomenon, renal vein entrapment syndrome, or mesoaortic compression of the left renal vein.
A disease of excess body fat that can have a negative effect on health, leading to reduced life expectancy and other health problems.
Absence of sperm in the ejaculate despite normal spermatogenesis, caused by an obstruction of the genital tract.
Repetitive nocturnal complete collapses (apneas) or partial collapses (hypopneas) of the upper airway during sleep.
Male fertility diagnosis defined as a combination of low sperm concentration, reduced motility and abnormal sperm morphology in the ejaculate.
Light or infrequent menstrual ﬂow at intervals of 39 days to 6 months or 5–7 cycles in a year.
Semen with a low concentration of sperm and is a common finding in male infertility.
Defect during oocyte maturation.
An inflammation of the testes, involving swelling and heavy pains.
A type of cancer in which abnormal cells begin to grow in one or both of a woman's ovaries.
Abnormal sacs filled with liquid or semi-solid matter found in the ovary, which can have negative impact on female fertility.
A clinical symptom complex that can occur in some women undergoing assisted reproductive technologies and that could result in pregnancy complications
Surgical removal of one or both ovaries.
A physical syndrome described by pain or burning sensation of the urethra or perineum during or following ejaculation.
The rare chronic disease typically features a number of small, interlinked abscesses within the pelvis.
A form of abdominal adhesions in the pelvis.
Infection of the upper part of the female reproductive system and a common complication of some sexually transmitted diseases.
An infectious disease caused by the bacterium Mycobacterium tuberculosis and one of cause female infertility.
A pituitary malfunction is a disorder affecting the pituitary gland, either by overproduction or underproduction any of pituitary gland hormones.
An abnormal growth that develops in the pituitary gland that could impair the hormonal balance needed for fertility function.
A condition in which a woman has an imbalance of female sex hormones. This may lead to changes in the menstrual cycle, cysts in the ovaries, trouble g
A condition of abnormally high concentration (more than 250 million / ml ) of sperm in the semen.
A condition of low fertility characterized by low numbers of remaining oocytes in the ovaries or possibly impaired oocyte development or recruitment.
A genetic disorder due to loss of function of specific genes on chromosome 15.
A man experiences orgasm and expels semen soon after sexual activity and with minimal penile stimulation.
The loss of function of the ovaries before age 40.
An inflammation of the prostate gland.
A distally blocked Fallopian tube filled with pus.
Three or more consecutive pregnancy losses prior to 20 weeks gestational age from the last menstrual period.
Three or more consecutive pregnancy losses before 20-24 weeks of gestation or below a fetal weight of 500 g.
A kidney cancer that originates in a part of the very small tubes in the kidney that transport waste molecules from the blood to the urine.
The absence of implantation after three or more transfers of high quality embryos or after placement of 10 or more embryos in multiple transfers.
The semen, which would normally be ejaculated via the urethra, is redirected to the urinary bladder.
A long-term autoimmune disorder that primarily affects joints.
Surgical removal of one (unilateral) or both (bilateral) fallopian tube(s).
An acute inflammation of the fallopian tubes.
The absence of any developmental stage of sperm cell in the testes.
An infection of the paranasal sinuses and/or the lungs, associated with several conditions of impaired fertility.
Antibodies that bind to sperm, inhibiting their movement, stopping recognition and entry into the egg.
High level of DNA damage in sperm cells that may lead to male infertility.
A rare disorder characterized by a phenotypic female with an XY karyotype.
A sexually transmitted infection caused by the bacterium Treponema pallidum subspecies pallidum.
Teratospermia is a condition characterized by the presence of sperm with abnormal morphology that affects fertility in males.
A medical condition in which the testes diminish in size and may be accompanied by loss of function (production of sperm and testosterone).
Cancer that develops in the testicles.
The inability of the testicles to produce sperm or testosterone.
Emergency medical condition occurring when the spermatic cord twists and cuts off the testicle's blood supply.
Cancers that develop within the thyroid gland.
A medical condition impairing the function of the thyroid.
Medical emergency that afflicts the human penis.
A permanent form of female sterilization, in which the fallopian tubes are severed and sealed or "pinched shut", in order to prevent fertilization.
The type of blockage that affects the part of the fallopian tube end towards the ovary.
Turner syndrome is a genetic disorder in which a female is partly or completely missing one X chromosome that results in ovarian dysgenesis.
In the case of cryptorchidism one or both testes are absent from the scrotum. It is is the most common etiologic factor of azoospermy in the adult.
Congenital uterine anomaly (one of the Müllerian duct anomalies) usually associated with communicating or non-communicating rudimentary horn.
A condition of blocked passage through one of the Fallopian tubes.
The most common benign smooth muscle tumors of the uterus encountered in women of reproductive age.
Rare uterine malignant tumour that arises from the smooth muscular part of the uterine wall.
A type of female genital malformation resulting from an abnormal development of the Müllerian duct(s) during embryogenesis.
Congenital uterine malformation where both Müllerian ducts develop but fail to fuse, thus the woman has a "double uterus".
A form of a congenital malformation where the uterine cavity is partitioned by a longitudinal septum. It is one of Müllerian duct anomalies.
A form of a congenital malformation where the uterus is partially divided by a longitudinal septum. It is one of Müllerian duct anomalies.
A physical or psychological condition in which woman cannot engage in any form of vaginal penetration.
A disease of the vagina caused by excessive growth of bacteria, with possible detrimental effect on female fertility.
An abnormal enlargement of the pampiniform venous plexus in the scrotum.
The male sex chromosomal disorder characterized by a spectrum of clinical presentations, ranging from ambiguous to normal male genitalia.
A rare condition causing chronic lung disease, rhinosinusitis and azoospermia.
A surgery used to remove part of one ovary or part of both ovaries.