In Vitro Fertilization – Everything You Need to Know

In vitro fertilization (IVF) has a literal meaning of fertilization carried outside a living organism, in an artificial laboratory setup. It is more commonly known as the process of a test-tube baby. IVF is an assisted reproductive technology in which an egg is retrieved from a woman’s ovaries and combined with a male’s sperm (fertilized) in vitro or outside the body.

Before 1978, many women with damaged fallopian tubes or ovulation disorders were largely considered to be sterile. But things changed after 1978 when Louise Brown, the first child in the world to be known as in vitro or test-tube baby was born in Oldham, England after her mother received IVF treatment. The procedure was co-developed by physiologist Robert G. Edwards, obstetrician and gynecologist Patrick Steptoe and embryologist Jean Purdy at Dr. Kershaw’s Hospital in Royton, England.

Before this success, there were heated debates about the ethics and safety of IVF, remarkably similar to the ethical debates about the production and use of human embryonic stem cells. IVF is now a routine procedure and has produced more than eight million children worldwide, today.

IVF has revolutionized the treatment of human infertility. About 10% of human couples in the world have problems relating to infertility, and the male-female infertility ratio accounts somewhat 50:50. IVF is a suitable treatment for a majority of reduced fertility cases. In a woman, it includes blocked or damaged fallopian tubes, ovulation disorders– infrequent or absent ovulation, premature ovarian failure, endometriosis– the growth of uterine tissue outside of the uterus, uterine fibroids– benign tumors in the uterine wall, and removal of fallopian tubes in some women. In man, IVF can be useful for cases of oligospermia (low sperm count), poor sperm motility, impaired sperm size and shape, anti-sperm antibody problems, and the inability of sperm to penetrate or survive in the cervical mucus. Apart from these, there may be some unexplained infertility factors in both male and female or some kind of genetic disorder.

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Process of IVF

The process of IVF starts with controlled ovarian hyperstimulation, in which the woman is treated hormonally with gonadotropins (Follicle Stimulating Hormone or Luteinizing hormone). This stimulates the development of multiple follicles of the ovaries in one single cycle, resulting in super-ovulation. Human chorionic gonadotropin (HCG) is injected extensively for final maturation induction of oocytes (eggs). Then eggs are retrieved from the follicles by means of laparoscopy or ultrasonography under anesthesia. Sperm cells are extracted directly from the man’s testes with a special syringe. Other medications that might be required for the woman are those to prevent premature ovulation and progesterone supplements to prepare the lining of the uterus for implantation.

In the laboratory, the identified eggs are stripped of surrounding cells and prepared for fertilization while the semen is prepared by sperm washing (removing inactive cells). The sperm and the egg are co-incubated in a ratio of about 75000:1 in a culture medium for 4-16 hours. In most cases, the eggs will be fertilized by that time and bear two pronuclei. However, in certain situations, such as low sperm count or motility, an egg is fertilized by injecting a single sperm into it in a process called Intracytoplasmic Sperm Injection (ICSI).

The zygote is incubated until it becomes an embryo of 6-8 cell stage (2-3 days after co-incubation) or, blastocyst stage (5-6 days after co-incubation). Then 2-3 best-looking embryos are transferred through the cervix into the uterine cavity of the woman with a catheter under ultrasound guidance, while the remaining embryos are usually cryopreserved for further implantations, if necessary.

Pre-implantation Genetic Screening and Diagnosis

In addition to revolutionizing the treatment of infertility, IVF has opened up many new possibilities for manipulating the reproductive process. It has, for example, made it possible for parents carrying a defective gene to avoid passing the gene on to their children, by screening IVF embryos for the gene before implanting them into the uterus.

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Pre-implantation Genetic Diagnosis is a procedure used before embryo transfer to determine a specific genetic defect. A Day 3 embryo usually has 8 cells and one of these cells is extracted and examined for the specific defect. For instance, if both the parents are carriers for Cystic Fibrosis, then the child is at high risk for passing CF to their child. Through this diagnosis, it is possible to detect the embryo having the defect and thus only the embryos having normal cells can be transferred into the woman’s uterus.

Pre-implantation Genetic Screening is used to ensure that the embryos are chromosomally normal. The biopsy can either be performed on Day 3 or Day 5 blastocysts and screening methods such as Fluorescent In-Situ Hybridization (FISH) or Comparative Genetic Hybridization (CGH) is done to analyze all 46 (including sex) chromosomes. This is suitable to check for aneuploidy (abnormal number of a chromosome) which may lead to genetic disorders such as Down syndrome.

Risks Involving IVF

  • The transfer of several embryos increases the probability of success. Multiple embryo transfers also increase the risk of multiple pregnancies. This carries a risk to both mother and baby.
  • Ovarian Hyper-stimulation Syndrome: Gonadotropins given to mature multiple follicles may show symptoms of the ovarian hyperstimulation syndrome, which includes increased ovarian size, nausea, and vomiting, accumulation of fluid in the abdomen, breathing difficulties, increased concentration of RBCs, kidney and liver problems.
  • Many have worried that the use of fertility drugs could lead to an increased risk of cancer—in particular, breast, ovarian, and uterine (including endometrial) cancers. Studies and researches are being carried out regarding this.
  • Pregnancies that occur with IVF are associated with increased risks of certain conditions: pre-eclampsia, placenta previa, placental abruption, and gestational diabetes.
  • In about 2 to 5 percent of the cases of IVF treatment, ectopic (tubal, cervical and abdominal) pregnancies have occurred.
  • Many believe that IVF babies seem to be at a slightly increased risk for birth defects. This is, however, due to delayed conception and the underlying infertility issues, and sometimes due to multiple pregnancies.
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IVF, despite all its benefits and risks, is financially draining as it is an expensive procedure. In the US, an average cycle, from egg retrieval to embryo transplant, costs from $10,000 to $15,000. The average cost is around $8000 in the U.K. and in Australia, $3000 – $6000 in Europe, $3000 in India, $7000 in Thailand and Malaysia, and about $4000 in South Africa.