Invitro Fertilisation (IVF)

In vitro fertilisation (IVF) is the process by which oocytes (eggs) are taken from the woman’s body, fertilised in a laboratory with the sperm and incubated, then replaced into the woman’s body a few days later for development. The basic stages involved in the IVF procedure are detailed below but may vary for different patients and different fertility clinics.  This is designed to be an overview and lists the options available. Patients should discuss their treatment with their specialist doctor and the nurses at the fertility clinic.

The IVF treatment involves seven main stages:

1. Growth and maturation of oocytes;
2. Monitoring oocyte development for exact timing of retrieval of these oocytes;
3. The retrieval of the oocytes and collection of the semen sample;
4. Fertilisation of the oocytes that may become embryos;
5. Transfer of the embryo/s back into the uterus;
6. Freezing of excess suitable embryos;
7. Follow up tests.

1.  Growth and maturation of oocytes

• Medications used in Ovarian Stimulation

The normal cycle usually produces one oocyte but fertility drugs are used to hyperstimulate the ovaries to aim to develop between 6 and 10 oocytes in the IVF cycle. Pregnancy rates in IVF are improved if a number of oocytes can be collected. Follicle stimulating hormone is the most common method of stimulating follicular development.

• Ovarian Stimulation Protocols

There are almost as many stimulation protocols in use in the world as there are IVF clinics. A common protocol used by most IVF units in Australia is the down regulation protocol. Another protocol is the flare protocol using GnRH (Synarel/Lucrin), flare protocol using Cetrotide, and combination protocols. The specialist doctor will advise which protocol will provide the optimum result.

2.  Monitoring Oocyte Development

The oocytes (ova) develop inside the ovaries in follicles, which are like little cysts or fluid filled sacs. These follicles produce increasing amounts of oestradiol (an oestrogen hormone) as they grow. The size can be measured by ultrasound, although the oocytes themselves are much too small to see. A blood test and ultrasound scan will be done on about the seventh day after commencing FSH.  After the doctor has reviewed the results of each test, the fertility clinic will inform patients when another ultrasound scan or a blood test is required. 

• Timing of oocyte retrieval

The oestradiol levels (from the blood tests) and the number and the size of the follicles (from the ultrasound) are together used to assess the maturity of the oocytes and the right time for oocyte retrieval. There is no correct oestradiol level to reach and there is enormous variation between patients. It is the whole pattern of blood and ultrasound results which determine whether the response to treatment is optimum.

3.  Oocyte Retrieval and Collection of Semen Sample

Admission will be arranged to the hospital or clinic where the oocyte retrieval is to take place.  Patients will remain in recovery for about 2–4 hours after oocyte retrieval until recovery from the anaesthetic/sedation used during surgery.

• hCG injections

hCG (human chorionic gonadotropin) is a hormone that performs the function of LH, triggering the final maturation of the oocytes and ovulation. In an IVF cycle a single injection of hCG medication (Pregnyl or Profasi) is given usually 37 hours before the operation is planned. Most patients give themselves this injection at home at the specified time, and will receive instruction from a nurse at the fertility clinic. After this trigger injection the other two medications (Lucrin / Synarel / Cetrotide and Puregon / Gonal-F) are normally stopped.

• Oocyte retrieval

  This will be undertaken using laparoscopy or an ultrasound guided retrieval and the specialist will decide which method is best for individual patients. The oocyte retrieval is usually done under sedation in a day surgery hospital.

  The follicles are visualised using trans-vaginal ultrasound, and the fluid inside them is sucked through a needle and tubing into a test tube. The tube is passed immediately to the embryologist who looks for the oocyte under the microscope. The oocytes are then put in the incubator. Most patients are sleepy, and some are nauseated for a few hours after the operation. Patients can be discharged 2–4 hours after the operation. Patients may be visited by a nurse from the fertility clinic and given further instructions before discharge.

  No oocytes collected:  This occasionally happens, and can occur where there is no access to the ovary (very rare) or ovulation has unexpectedly occurred prior to the oocyte retrieval procedure or there are no oocytes obtained from the follicles.

  The latter is called empty follicle syndrome (EFS) and is a frustrating condition in which no oocytes are retrieved at IVF, even though ultrasound and oestradiol measurements showed the presence of potential follicles.  The mechanism responsible for Empty Follicle Syndrome remains obscure. Many hypotheses have been put forward, but none truly explain this syndrome. The most likely cause of EFS is ovarian ageing, as many patients who suffer from EFS are also poor responders, meaning that they do not produce many follicles even after taking medications to stimulate follicles in that cycle.  If an EFS cycle does occur during treatment, patients should discuss it thoroughly with their gynaecologist and the clinic counsellor.

  EFS is an infrequent event and has been estimated to occur in between 2% to 7% of IVF cycles. However, if an EFS cycle has occurred then the overall risk of recurrence in later IVF cycles is 20%.  The risk of recurrence is higher as the age of the patient increases, with a risk of recurrence of 10% in patients less than 35 years, and  24% for those between 35 and 39 years, and 57% for those over 40 years of age.

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It is important to understand that not every follicle seen on ultrasound yields an oocyte, and that not every oocyte collected is likely to become an embryo. However most patients will have more oocytes retrieved than are needed for the current cycle. Usually patients will fertilise all oocytes and freeze any surplus embryos for later use in frozen embryo transfer (FET) cycles.  Before the cycle commences patients will be asked what they would prefer done with any excess oocytes and will indicate this on their signed consent form.

• Sperm sample for IVF

Patients can expect to be informed of the approximate sperm retrieval time once the oocyte retrieval time has been arranged. It is usually 1–3 hours after the operation. Two to three days abstinence from ejaculation is preferred prior to oocyte retrieval. The sperm sample is produced by masturbation at the fertility clinic or by other means by arrangement.

4.  Fertilisation and Events in the Laboratory

The sperm sample is prepared and put with the oocytes (fertilisation), 3–6 hours after retrieval. The oocytes and sperm are kept in an incubator until next inspected 15–20 hours later. At this time they are checked under the microscope to determine whether fertilisation has occurred. Patients should be in contact with the nurses at the fertility clinic during these interim days to be informed of the fertilisation results and embryo progress results. At about 60–70 hours after fertilisation, the embryos will be transferred to the uterus.

• Fertilisation

‘I have had IVF and when I phoned the clinic they told me that I had 6 out of 10 fertilised, but there might be more the next day, and I am confused.’

The process of fertilisation is a complex process, which commences with attachment of a sperm to the egg, and finishes with cell division to form a 2-cell embryo. The embryologist checks the eggs for fertilisation, first at an intermediary stage called the pronuclear stage (see Embryo at 2 pronuclear stage image), and then later at the cell division stage when the embryo is at 4 cell stage.  The 8 cell embryo shown would be expected at the third check approximately 3 days after fertilisation.

Blastocyst culture of embryos is now widely used, please see Treatment Options>Blastocyst Culture for further information and diagrams of embryo development to blastocyst stage.

5.  Embryo Transfer

Embryo transfer usually takes place between 2 and 6 days after oocyte retrieval.  At 2 to 3 days the embryo is called an embryo and at 5 to 6 days is called a blastocyst.  At 4 days the embryo is at an intermediary stage and is called a morula. Patients usually elect to transfer at blastocyst stage and must nominate this on their signed consent form.  The embryo or blastocyst transfer is usually carried out in the fertility clinic. Under normal circumstances no more than 2 embryos/blastocysts will be replaced because of the risk of multiple pregnancies. (See Treatments>IVF>How Many Embryos Should Be Transferred?)

6.  Freezing of Excess Embryos

If extra embryos result from an IVF cycle above the one or two required for embryo transfer, then these embryos can be frozen (cryopreserved) for later use in a Frozen Embryo Transfer (FET) cycle.  Please see the section Treatments>Frozen Embryo Transfer (FET) for further information.  Note that the fees for this freezing are not included in the IVF cycle fees.

7.  Follow-up Tests

Blood tests may be done at frequent intervals to monitor progesterone levels and pregnancy hormone, hCG (often at 7, 10, and 12 days after oocyte retrieval). To maintain progesterone levels after IVF progesterone support is often prescribed and is routinely given as a vaginal pessary.

Pregnancy

The blood tests taken two weeks after the oocyte retrieval will detect whether the pregnancy hormone (hCG) is present: however it is too early to know whether there is a healthy continuing pregnancy.

Repeat In-Vitro Fertilisation attempts

No pregnancy resulting after an embryo transfer is still the most common outcome of IVF and reflects our current state of knowledge and the limitations of ART.  Often, specialists will be unable to give a reason why the embryo transfer has failed.If pregnancy does not occur, a cycle to transfer frozen embryos or a repeat attempt of IVF can usually be made approximately 3 months later, depending on the diagnostic findings of the most recent treatment cycle.

Cancellation of Cycles

Cycle cancellation occurs in about one in seven cycles. In the majority of cases, this is just a reflection of the variation in the biological system and a more satisfactory response is obtained in the next cycle attempt, possibly using a different drug dose or protocol.