In vitro fertilisation involves fertilising an egg with sperm in a lab, then injecting the resulting embryo into the uterus. There are many steps along the way, and it is a complicated and expensive process. As a result, funding criteria are very strict and vary between areas. Couples are limited to a set number of cycles funded by the NHS.
Each attempt has a roughly 25 – 30% success rate at producing a live birth.
Intrauterine insemination (IUI) is different from IVF. It is a more straightforward process, and involves injecting sperm into the uterus, avoiding intercourse. IUI is used in cases such as donor sperm for same-sex couples, HIV (avoiding unprotected sex) and practical issues with vaginal sex.
Criteria for Funding
A cycle of IVF involves a single episode of ovarian stimulation and collection of oocytes (eggs). A single cycle may produce several embryos. Each of these embryos can be transferred separately in multiple attempts at pregnancy, all during one “cycle” of IVF. Embryos that are not used immediately may be frozen to be used at a later date. Frozen embryos can potentially be used years later, even after a successful pregnancy.
Process
There are a number of steps involved in the process of IVF:
- Suppressing the natural menstrual cycle
- Ovarian stimulation
- Oocyte collection
- Insemination / intracytoplasmic sperm injection (ICSI)
- Embryo culture
- Embryo transfer
Suppression of the Natural Menstrual Cycle
There are two protocols for the suppression of the natural menstrual cycle, preventing ovulation and ensuring the ovaries respond correctly to the gonadotropins (i.e. FSH). Suppression of the natural cycle involves either the use of GnRH agonists or GnRH antagonists. The choice between the GnRH agonist and GnRH antagonist protocol depends on individual factors.
For the GnRH agonist protocol, an injection of a GnRH agonist (e.g. goserelin) is given in the luteal phase of the menstrual cycle, around 7 days before the expected onset of the menstrual period (usually day 21 of the cycle). This initially stimulates the pituitary gland to secrete a large amount of FSH and LH. However, after this initial surge in FSH and LH, there is negative feedback to the hypothalamus, and the natural production of GnRH is suppressed. This causes suppression of the menstrual cycle.
For the GnRH antagonist protocol, daily subcutaneous injections of a GnRH antagonist (e.g. cetrorelix) are given, starting from day 5 – 6 of ovarian stimulation. This suppresses the body releasing LH and causing ovulation to occur.
Without suppression of the natural gonadotropins (LH and FSH) using one of the above protocols, ovulation would occur and the follicles that are developing would be released before it is possible to collect them.
Ovarian Stimulation
Ovarian stimulation involves using medications to promote the development of multiple follicles in the ovaries. This starts at the beginning of the menstrual cycle (usually day 2), with subcutaneous injections of follicle-stimulating hormone (FSH) over 10 to 14 days. The FSH stimulates the development of follicles, and this is closely monitored with regular transvaginal ultrasound scans.
When enough follicles have developed to an adequate size (usually around 18 millimetres), the FSH is stopped, and an injection of human chorionic gonadotropin (hCG) is given. This injection of HCG is given 36 hours before collection of the eggs. The hCG works similarly to LH does naturally, and stimulates the final maturation of the follicles, ready for collection. This is referred to as a “trigger injection”.
Oocyte Collection
The oocytes (eggs) are collected from the ovaries under the guidance of a transvaginal ultrasound scan. A needle is inserted through the vaginal wall into each ovary to aspirate the fluid from each follicle. This fluid contains the mature oocytes from the follicles. The procedure is usually performed under sedation (not a general anaesthetic). The fluid from the follicles is examined under the microscope for oocytes.
Oocyte Insemination
The male produces a semen sample around the time of oocyte collection. Frozen sperm from earlier samples may be used. The sperm and egg are mixed in a culture medium. Thousands of sperm need to be combined with each oocyte to produce enough enzymes (e.g. hyaluronic acid) for one sperm to penetrate the corona radiata and zona pellucida and fertilise the egg.
Intracytoplasmic Sperm Injection
Intracytoplasmic sperm injection (ICSI) is a treatment used mainly for male factor infertility, where there are a reduced number or quality of sperm. It is an addition to the IVF process. After the eggs are harvested, and a semen sample is produced, the highest quality sperm are isolated and injected directly into the cytoplasm of the egg.
Embryo Culture
Dishes containing the fertilised eggs are left in an incubator and observed over 2 – 5 days to see which will develop and grow. They are monitored until they reach the blastocyst stage of development (around day 5).
Embryo Transfer
After 2 – 5 days, the highest quality embryos are selected for transfer. A catheter is inserted under ultrasound guidance through the cervix into the uterus. A single embryo is injected through the catheter into the uterus, and the catheter is removed. Generally, only a single embryo is transferred. Two embryos may be transferred in older women (i.e. over 35 years). Any remaining embryos can be frozen for future attempts at transfer.
Pregnancy
A pregnancy test is performed around day 16 after egg collection. When this is positive, implantation has occurred. Even after a positive test, there is still the possibility of miscarriage or ectopic pregnancy.
When the pregnancy test is negative, implantation has failed. At this point, hormonal treatment is stopped. The woman will go on to have a menstrual period. The bleeding may be more substantial than usual given the additional hormones used during ovarian stimulation.
Progesterone is used from the time of oocyte collection until 8 – 10 weeks gestation, usually in the form of vaginal suppositories. This is to mimic the progesterone that would be released by the corpus luteum during a typical pregnancy. From 8 – 10 weeks the placenta takes over production of progesterone, and the suppositories are stopped.
An ultrasound scan is performed early in the pregnancy (around 7 weeks) to check for a fetal heartbeat, and rule out miscarriage or ectopic pregnancy. When the ultrasound scan confirms a health pregnancy, the remainder of the pregnancy can proceed with standard care, as with any other pregnancy.
Complications
The main complications relating to the overall process are:
- Failure
- Multiple pregnancy
- Ectopic pregnancy
- Ovarian hyperstimulation syndrome
There is a small risk of complications relating to the egg collection procedure:
- Pain
- Bleeding
- Pelvic infection
- Damage to the bladder or bowel
Last updated August 2020