IVF (In-Vitro Fertilisation) This is the most used assisted conception technique worldwide. IVF literally means fertilisation "in-glass", hence the origin of the name "test tube baby". For IVF, eggs are collected from the ovaries and then put together with sperm to fertilise in a laboratory dish before being transferred into the uterus (womb).
Ovarian stimulation protocol IVF involves taking daily fertility drugs (hMG or recombinant FSH or recombinant FSH/LH with or without GnRH agonist or antagonist) to stimulate the ovaries to produce a high number of oocytes (eggs). The recruitment and development of follicles, which contain the eggs, is tracked by regular transvaginal ultrasound scans and sometimes blood tests. When at least three follicles are mature (greater than 17mm in diameter) a hormone injection (hCG) is given to ripen the eggs. Egg collection is performed generally under ultrasound guidance, and very seldom using laparoscopy 34-36 hours later. The egg collection procedure takes about 20 minutes. The ovarian stimulation protocol is individualised to maximise the chances of success while reducing the risks, complications and possibly the costs of treatment.
Natural cycle Sometimes it is possible to proceed to IVF without using any drugs for ovarian stimulation. In most cases only one or two eggs are collected but immature eggs can be matured in vitro before being fertilised. In most cases only one healthy embryo is available for transfer. Usually there are not enough embryos to be stored. Some people argue that using "natural cycle IVF" the endometrium (lining of the womb) may be more receptive to the implanting embryos.
What is IVF? Once collected the eggs are placed in a laboratory dish, mixed with the sperm, which in most cases has been produced on the same day, and left overnight to fertilise. Following fertilisation, one or two embryos are transferred into the uterus through the cervix using a fine and thin tube called catheter. The healthy embryos can be transferred two to five days after fertilisation. Embryo transfer may be done under ultrasound guidance. Any good quality suitable remaining embryos may be frozen for future use.
Who are the candidates for IVF? a) women whose fallopian tubes are blocked, damaged or absent b) men whose sperm is moderately abnormal (count and/or motility) c) couples in which previous IUI treatment cycles have failed d) couples who are known to be at risk of genetic disease or who have already had a child with a serious genetic disease and require preimplantation genetic diagnosis (PGD) e) women with a history of severe pelvic endometriosis with altered pelvic anatomy because of scarring and adhesions f) women who have hormone imbalance and require high doses of fertility drugs The success rate of IVF measured as live birth rate can be as high as 40% per cycle with fresh embryos and up to 25% with frozen embryos.
Risks and complications of IVF
Failure of treatment -- this can result from cycle cancellation because of no response or over-response to stimulation drugs, failure to collect eggs, failure to fertilize eggs, failure of the embryos to develop normally and failure of implantation. Failure of treatment can result in emotional strain, psychological stress and depression, and some couples may require psychological counseling. Risks associated with egg collection -- discomfort, bleeding, infection and injury to organs (bladder and bowel). Multiple pregnancy -- more than one fetus grows at any one time in the uterus (womb) after the transfer of two or more embryos. This is the single greatest complication of IVF treatment. Although the prospect of twin or triplets may seem attractive to some couples, high order of multiple pregnancies are associated with increased risks of maternal and fetal complications throughout pregnancy. In addition, multiple pregnancies place enormous strains for the parents including financial difficulties, emotional distress and physical exhaustion. Ovarian hyperstimulation syndrome (OHSS) -- potentially a very serious condition which result from over-stimulation of the ovaries following treatment with fertility drugs. Several follicles develop in each of the ovaries and fluid collects in the abdomen. In severe cases (1-2%) fluid may fill the entire abdominal cavity and the chest. Admission to the hospital may be required and IVF treatment abandoned in that cycle. Ectopic pregnancy -- when an embryo develops and implants outside the womb, generally into the fallopian tube. Women undergoing IVF treatment because of problems with their tubes have a greater risk of having an ectopic pregnancy. This can be a serious condition and admission to the hospital may be required.
GLOSSARY -- Hum Reprod 2009, 24:2683-87
Assisted hatching: an in vitro procedure in which the zona pellucida of an embryo is either thinned or perforated by chemical, mechanical or laser methods to assist separation of the blastocyst.
Assisted reproductive technology (ART): all treatments or procedures that include the in vitro handling of both human oocytes and sperm, or embryos, for the purpose of establishing a pregnancy. This includes, but is not limited to, in vitro fertilisation and embryo transfer, gamete intrafallopian transfer, zygote intrafallopian transfer, tubal embryo transfer, gamete and embryo cryopreservation, oocytes and embryo donation, and gestational surrogacy. ART does not include assisted insemination (artificial insemination) using sperm from either a woman's partner or a sperm donor.
Biochemical pregnancy (preclinical spontaneous abortion/miscarriage): a pregnancy diagnosed only by the detection of hCG in serum or urine and does not develop into a clinical pregnancy.
Blastocyst: an embryo, five or six days after fertilisation with inner cell mass, outer layer of trophoectoderm and a fluid-filled blastocoele cavity.
Cancelled cycle: an ART cycle in which ovarian stimulation or monitoring has been carried out with the intention to treat, but did not proceed to follicular aspiration or, in the case of a thawed embryo, to embryo transfer.
Clinical pregnancy: a pregnancy diagnosed by ultrasonographic visualisation of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy. Multiple gestational sacs are counted as one clinical pregnancy.
Clinical pregnancy rate: the number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles or embryo transfer cycles. When clinical pregnancy rates are given, the denominator (initiated, aspirated or embryo transfer cycles) must be specified.
Clinical pregnancy with fetal heart beat: the pregnancy diagnosed by ultrasonographic or clinical documentation of at least one fetus with heart beat. It includes ectopic pregnancy.
Congenital anomalies: all structural, functional and genetic anomalies diagnosed in aborted fetuses, at birth or in the neonatal period.
Controlled ovarian stimulation (COS) for ART: pharmacological treatment in which women are stimulated to induce the development of multiple ovarian follicles to obtain multiple oocytes at follicular aspiration.
Controlled ovarian stimulation (COS) for non-ART cycles: pharmacological treatment for women in which the ovaries are stimulated to ovulate more than one oocyte.
Cryopreservation: the freezing or vitrification and storage of gametes, zygotes, embryos or gonadal tissue.
Cumulative delivery rate with at least one live born baby: the estimated number of deliveries with at least one live born baby resulting from one initiated or aspirated ART cycle including the cycle when fresh embryos are transferred, and subsequent frozen/thawed ART cycles. This rate is used when less than the total number of embryos fresh and/or frozen/ thawed have been utilised from one ART cycles. The delivery of a singleton, twin or other multiple pregnancy is registered as one delivery.
Delivery: the expulsion or extraction of one or more fetuses from the mother after 20 completed weeks of gestational age.
Delivery rate after ART treatment per patient: the number of deliveries with at least one live born baby per patient following a specified number of ART treatments.
Delivery rate: the number of deliveries expressed per 100 initiated cycles, aspiration cycles or embryo transfer cycles. When delivery rates are given, the denominator (initiated, aspirated or embryo transfer cycles) must be specified. It includes deliveries that resulted in the birth of one or more live babies and/or stillborn babies. The delivery of a singleton, twin or other multiple pregnancy is registered as one delivery.
Early neonatal death: death of a live born baby within 7 days of birth.
Ectopic pregnancy: a pregnancy in which implantation takes place outside the uterine cavity (womb).
Elective embryo transfer: the transfer of one or more embryos, selected from a larger cohort of available embryos.
Embryo: the product of the division of the zygote to the end of the embryonic stage, eight weeks after fertilisation.
Embryo donation: the transfer of an embryo resulting from gametes (sperm and oocytes) that did not originate from the recipient and her partner.
Embryo recipient cycle: an ART cycle in which a woman receives zygote(s) or embryo(s) form donor(s)
Embryo/fetus reduction: a procedure to reduce the number of viable embryos or fetuses in a multiple pregnancy.
Embryo transfer (ET): the procedure in which one or more embryos are placed in the uterus or Fallopian tube.
Embryo transfer cycle: an ART cycle in which one or more embryos are transferred into the uterus (womb) or Fallopian tube.
Extremely low birth weight: birth weight less than 1,000 grams.
Extremely preterm birth: a live birth or stillbirth that takes place after at least 20 but less than 28 completed weeks of gestational age.
Fertilisation: the penetration of the ovum by the sperm and combination of their genetic material resulting in the formation of a zygote.
Fetal death (stillbirth): death prior to the complete expulsion or extraction from its mother of a product of fertilisation, at or after 20 completed weeks of gestational age. The death is indicated by the fact that after such separation, the fetus does not breathe or show any other evidence of life such as heart beat, umbilical cord pulsation, or definite movement of voluntary muscles.
Fetus: the product of fertilisation from completion of embryonic development, at eight completed weeks after fertilisation, until abortion or birth.
Frozen/thawed embryo transfer cycle (FET): an ART procedure in which cycle monitoring is carried out with the intention of transferring a frozen/thawed embryo or frozen/thawed embryos. A FET cycle is initiated when specific medication is provided or cycle monitoring is started with the intention to treat.
Frozen/thawed oocytes cycle: an ART procedure in which cycle monitoring is carried out with the intention of fertilising thawed oocytes and performing embryo transfer.
Full-term birth: a live birth or stillbirth that takes place between 37 competed and 42 completed weeks of gestational age.
Gamete intrafallopian transfer (GIFT): an ART procedure in which gametes (oocytes and spermatozoa) are transferred in to the Fallopian tubes.
Gestational age: age of an embryo or fetus calculated by adding 2 weeks (14 days) to the number of completed weeks since fertilisation. For frozen/thawed embryo transfers, an estimated date of fertilisation is computed by subtracting the embryo age at freezing from the transfer date of the FET cycle.
Gestational carrier (surrogate): a woman who carries a pregnancy with an agreement that she will give the offspring to the intended parent(s). Gametes can originate from the intended parent(s) and /or a third party (or parties).
Gestational sac: a fluid-filled structure associated with early pregnancy, which may be located inside or outside the uterus (in case of an ectopic pregnancy).
Hatching: the process by which an embryo at the blastocyst stage (day 5) separates from the zona pellucida.
High-order multiple: a pregnancy or delivery with three or more fetuses or neonates.
Implantation: the attachment and subsequent penetration by the zona-free blastocysts (usually in the endometrium) that starts five to seven days after fertilization.
Implantation rate: the number of gestational sacs observed, divided by the number of embryos transferred.
In vitro fertilization (IVF): an ART procedure that involves extra-corporeal fertilization.
Induced abortion: the termination of a clinical pregnancy, by deliberate interference that takes place before 20 completed weeks of gestational age (18 weeks post fertilization) or, if gestational age is unknown, of an embryo/fetus less than 400 grams.
Infertility (clinical definition): a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse.
Initiated cycle: an ART cycle in which the woman receives specific medication for ovarian stimulation, or monitoring in the case of natural cycles, with the intention to treat, irrespective of whether or not follicular aspiration is attempted.
IntraCytoplasmic Sperm Injection (ICSI): a procedure in which a single sperm is injected into the oocyte cytoplasm.
Live birth: the complete expulsion or extraction from its mother of a product of fertilization, irrespective of the duration of the pregnancy, which, after such separation, breathes or shows any other evidence of life such as heart beat, umbilical cord pulsation, or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached.
Live birth delivery rate: the number of deliveries that resulted in at least one live born baby expressed per 100 initiated cycles, aspiration cycles or embryo transfer cycles. When delivery rates are given, the denominator (initiated, aspirated, or embryo transfer cycles) must be specified.
Low birth weight: Birth weight less than 2,500 grams.
Medically Assisted Reproduction (MAR): reproduction brought about through ovulation induction, controlled ovarian stimulation, ovulation triggering, ART procedures, and intrauterine, intracervical, and intravaginal insemination with semen of husband/partner or donor.
MESA: Microsurgical Epididymal Sperm Aspiration.
MESE: Microsurgical Epididymal Sperm Extraction.
Micromanipulation: a technology that allows micro-operative procedures to be performed on the sperm, oocyte, zygote or embryo.
MicroTESE: Microsurgical Testicular Sperm Extraction.
Mild ovarian stimulation for IVF: a procedure in which the ovaries are stimulated with either gonadotrophins and/or other compounds, with the intent to limit the number of oocytes obtained for IVF to fewer than seven.
Missed abortion (miscarriage): a clinical abortion (miscarriage) where the embryo(s) or fetus(es) is/are non-viable and is/are not expelled spontaneously from the uterus.
Modified natural cycle: and IVF procedure in which one or more oocytes are collected from the ovaries during a spontaneous menstrual cycle. Drugs are administered with the sole purpose of blocking the spontaneous LH surge and/or inducing final oocyte maturation.
Multiple gestation/birth: a pregnancy/delivery with more than one fetus/neonate.
Natural IVF cycle: an IVF procedure in which one or more oocytes are collected from the ovaries during a spontaneous menstrual cycle without any drug use.
Neonatal death: death of a live born baby within 28 days of birth.
Neonatal period: the time interval that commences at birth and ends 28 completed days after birth.
Oocyte donation cycle: a cycle in which oocytes are collected from a donor for clinical application or research.
Oocyte recipient cycle: an ART cycle in which a woman receives oocytes from a donor.
Ovarian Hyper Stimulation Syndrome (OHSS): an exaggerated systemic response to ovarian stimulation characterised by a wide spectrum of clinical and laboratory manifestations. It is classified as mild, moderate or severe according to the degree of abdominal distension, ovarian enlargement and respiratory, haemodynamic and metabolic complications.
Ovarian torsion: the partial or complete rotation of the ovarian vascular pedicle that causes obstruction to ovarian blood flow, potentially leading to necrosis of ovarian tissue.
Ovulation induction (OI): pharmacological treatment of women with anovulation or oligo-ovulation with the intention of inducing normal ovulatory cycles.
Perinatal mortality: fetal or neonatal death incurring during late pregnancy (at 20 completed weeks of gestational age and later), during childbirth and up to 7 completed days after birth.
PESA: Percutaneous Epididymal Sperm Aspiration.
Post-term birth: a live birth or stillbirth that takes place after 42 completed weeks of gestational age
Preimplantation Genetic Diagnosis (PGD): analysis of polar bodies, blastomeres or trophectoderm from oocytes, zygotes or embryos for the detection of specific genetic, structural and/or chromosomal alterations.
Prelimplantation Genetic Screening (PGS): analysis of polar bodies, blastomeres or trophectoderm from oocytes, zygotes or embryos for the detection of aneuploidy, mutation and/or DNA rearrangement.
Preterm birth: a live birth or stillbirth that takes place after at least 20 but before 37 completed weeks of gestational age.
Recurrent spontaneous abortion/miscarriage: the spontaneous loss of two or more clinical pregnancies.
Reproductive surgery: surgical procedures performed to diagnose, conserve, correct and/or improve reproductive function.
Severe Ovarian Hyper Stimulation Syndrome: severe OHSS is defined to occur when hospitalisation is indicated (see definition of Ovarian Hyper Stimulation Syndrome).
Small for gestational age: birth weight less than 2 standard deviations below the mean or less than the 10th centile according to local intrauterine growth charts.
Sperm recipient cycle: an ART cycle in which a woman receives sperm from a donor who is someone other than her partner.
Spontaneous abortion/miscarriage: the spontaneous loss of a clinical pregnancy that occurs before 20 completed weeks of gestational age (18 weeks post fertilization) or, if gestational age is unknown, the loss of an embryo/fetus of less than 400 grams.
TESA: Testicular Sperm Aspiration.
TESE: Testicular Sperm Extraction.
Total delivery rate with at least one live birth: the estimated total number of deliveries with at least one live born baby resulting from one initiated or aspirated ART cycle including all fresh cycles and all frozen/thawed ART cycles. This rate is used when all of the embryos fresh and/or frozen/thawed have been utilised from one ART cycle. The delivery of a singleton, twin or other multiple pregnancies is registered as one delivery.
Vanishing Sac(s) or embryo(s): spontaneous disappearance of one or more gestational sacs or embryos in an ongoing pregnancy, documented by ultrasound.
Very low birth weight: birth weight less than 1,500 grams.
Very preterm birth: a live birth or stillbirth that takes place after at least 20 but less than 32 completed weeks of gestational age.
Vitrification: an ultra-rapid cryopreservation method that prevents ice formation within the suspension which is converted to a glass-like solid.
Zygote: a diploid cell resulting from the fertilization of an oocyte by a sperm, which subsequently divides to form an embryo.
Zygote Intra-Fallopian Transfer (ZIFT): a procedure in which zygote(s) is/are transferred into the fallopian tube.