In-vitro fertilization and embryo transfer (IVF), also known as ‘test-tube baby’, is an effective treatment for infertility. It involves collecting eggs from the woman’s ovaries, fertilizing the eggs with the man’s sperms in the laboratory, culturing these fertilized eggs to become embryos and returning them into the woman’s womb. It was originally developed to help women with blocked fallopian tubes to conceive, but has since been expanded to treat couples with various causes of infertility.
Women with blocked or damaged fallopian tubes;
Men with poor semen quality;
Women with severe endometriosis;
Women in their advanced reproductive age or low ovarian reserve, as time to conception is critical;
All other causes of infertility including unexplained infertility, especially if treatment with other methods has failed;
Couples with an inherited genetic disease that they wish to avoid passing on to their child, and in this case, IVF is combined with pre-implantation genetic testing (PGT) to select embryos without the disease for transfer.
(I) Ovarian Stimulation
(II) Egg Collection
(IV) Embryo Culture
(V) Embryo Transfer
(VI) Embryo Freezing
In order to collect more eggs, fertility drugs are used to stimulate the ovaries. There are different stimulation protocols. The most commonly used one is the antagonist protocol.
Antagonist protocol: The woman takes daily ovarian stimulation drug injections in the beginning of her cycle to boost the growth of follicles (or eggs). Another injection drug, known as an antagonist, is added in the latter part of the stimulation period to prevent the eggs from being released too soon. The woman needs ultrasound scans and blood tests to monitor the growth of the follicles. When the eggs are ready, an ovulation trigger injection is given to complete the final maturation of the eggs and egg collection can be arranged.
Other less commonly used protocols include:
The egg collection procedure is performed under ultrasound guidance. An ultrasound probe is inserted into the vagina to identify the follicles. A thin needle is then inserted into an ultrasound guide to go through the vagina and into the follicle (Egg collection YouTube Link). The follicular fluid is aspirated and collected into a test tube. An embryologist then looks at the follicular fluid under a stereomicroscope to collect the eggs.
An embryologist is looking down a stereomicroscope, checking follicular fluid to see if an egg can be found.
The egg collection procedure takes around 30–45 minutes. It is a painful procedure, and therefore anaesthesia is given. The woman can go home after resting in the IVF centre for a few hours, and return to work the next day.
The man has to produce a semen sample on the day of the egg collection. The semen sample is processed, and the sperms are used for insemination with one of the following methods:
Intracytoplasmic sperm injection (ICSI) is a procedure involving the direct injection of a single sperm into an egg to assist fertilization (ICSI YouTube Link). ICSI is usually performed in couples with specific indications:
The day of the egg collection is called Day 0 in the timeline of embryo development. On Day 1, embryologists check the eggs to see if fertilization is successful. On Day 2, the fertilized eggs undergo cell division and become embryos. The embryos can be cultured for up to 5 days when they are called blastocysts. They can be transferred back into the uterus on either Day 2, Day 3 or Day 5.
A cleavage stage embryo is assessed by the number of cells in the embryo, whether the cells are even in size, and the degree of fragmentation.
A blastocyst is assessed by the development of cavity, inner cell mass (ICM) and trophoectoderm:
Degree of expansion of the cavity. This is graded on a scale of 1-6:
1 = the cavity is beginning to form
2 = the cavity fills 1/3 of the embryo
3 = partial expansion, the cavity fills 70% of the embryo
4 = fully expanded cavity
5 = the embryo has expanded and the zona pellucida splits open
6 = the embryo has completely hatched from the zona pellucida
Appearance of the inner cell mass (ICM) (the cells that will grow to become the baby). This is graded into either A, B, or C:
A = well-defined clump of cells
B = less well defined; may be grainy in appearance
C = a few dark cells , appear degenerative
Appearance of the trophoectoderm (the cells that will form the placenta). This is also graded into either A, B or C:
A = many smooth cells, equal in size, forming a neat layer
B = irregular cell layer, some grainy cells
C = very irregular cell layer, cells may be dark and / or grainy
During embryo transfer, a small tube (catheter) is inserted through the cervix (the neck of the womb) and the embryo(s) is/are put into the womb cavity. The procedure is similar to taking a Pap smear. Anaesthesia or analgesia is usually not required. The woman can go home after embryo transfer and resume work the next day. She has to insert hormone pessaries into the vagina to help the lining of the uterus. A pregnancy test can be done usually around 2 weeks later.
After embryo transfer, any remaining good quality embryos are frozen for use in the future, in case treatment does not work or to try for a sibling.
In HKARC, the embryos are frozen by vitrification (rapid freezing)
and stored in liquid nitrogen tanks. The vitrification method has
a higher embryo survival rate on thawing as compared to the
old-fashioned slow freezing method, and has therefore become
the preferred method of freezing embryos nowadays
Embryos can be stored for up to a maximum of 10 years. Patients in certain circumstances, such as cancer patients, can store their embryos for up to 10 years or when they are 55 years old, whichever is later.
Reason for embryo storage
Maximum storage period
Patients in certain circumstances
10 years, or up to 55 years old, whichever is later
All other patients