IVF

What is IVF or the test-tube baby technique?

Test-tube baby treatment is the popular name for in vitro fertilization, usually shortened to IVF. It is the process by which egg and sperm are mixed outside the body and then returned to the uterus after fertilization. It involves the removal of an egg from the woman’s ovary, the collection and purification of sperm from her partner, the mixing of sperm and egg in laboratory and, if fertilization occurs, the insertion of the developing fertilised egg – the embryo – into the uterus. The embryo, still quite invisible to the naked eye, is placed in its mother’s uterus usually two days after fertilisation, while it still consists of only a few cells and long before any organs have formed.

When should IVF be considered?

The main situations when IVF may be worth considering are:

• When the tubes are badly damaged and tubal surgery has less chance of success than IVF or in most cases where tubal surgery has already been unsuccessful. IVF should be considered because it bypasses the tubes.
• When the man’s sperm count is on the low side or abnormal, yet potentially capable of fertilizing an egg. Here IVF may be useful because fertilization can possible be manipulated and observed by the scientific team. This does not necessarily require sperm injection, or zona drilling, but simply very careful preparation of the sperm in suitable laboratory solutions.
• For certain women who have problems with the cervix perhaps ‘hostile’ mucus, IVF bypasses the cervix and its mucus.
• For women who are not ovulating spontaneously, but who produce eggs on fertility drugs without conceiving. In this situation, the ability to force the ovary to produce many eggs and then select the best ones for fertilization and transfer means that IVF may be suitable option.
• For some women with endometriosis or with very carefully investigated infertility which remains unexplained. We think that endometriosis is an excellent indication for IVF and have had particular success.
• For couples who have several factors together which are causing infertility; commonly a combination of poor male fertility and tubal disease are the most usual indications.
• Most recently, for certain couples who are at high risk of having genetically abnormal babies.

1. Testing a couple’s suitability before treatment

Preliminary preparation for an ART procedure may be as important as the procedure itself.

• Testing for ovarian reserve may be recommended in order to predict how the ovaries will respond to fertility medication.
• Blood tests to assess the general health of the couple (ask the clinic for a complete list).
• Hysteroscopy to assess the inside of the uterus to look for problems like fibroids, polyps, or a septum may need to be corrected before IVF.
• Laparoscopy may be required to assess problems like endometriosis and to treat problems like hydrosalpinx; a fluid-filled, blocked fallopian tube which reduces IVF success should be removed prior to IVF.
• Semen analysis and culture.
• Lifestyle issues should be addressed before ART. Smoking, for example, may lower a woman’s chance of success by as much as 50%. All medications, including over-the-counter supplements, should be reviewed since some may have detrimental effects. Alcohol and drugs may be harmful, and excessive caffeine consumption should be avoided. Some vitamins especially folic acid is started.

2. Choosing the correct method of down regulation

Long protocol:

For this purpose an injection is started usually in the previous cycle (d21) or sometimes even in the same cycle. At a particular time, (usually d2) blood levels of estradiol (e2) and lh are tested to confirm the down regulation before starting stimulation. Mainly used for patients with endometriosis. It causes greater suppression of own hormones requiring higher dose of injections to be given from outside. greater chances of OHSS.

Antagonist protocol:

In this protocol, used for most patients nowadays (in our clinic more than 90% patients are on this protocol), the body's own hormones are not suppressed in the beginning of the cycle. This leads to lower amount of drugs needed and thus lower costs. This is good for patients who have low ovarian reserve and for those having PCOS. Later during the cycle, antagonist injections are used to lower the body's internal hormones.

3. Ovarian stimulation

The best chance of successful pregnancy is obtained when more than one embryo is placed in the uterus at the same time. This is because so many early human embryos, normally fertilised, are lost or do not develop into babies. Consequently, one way of overcoming this natural loss is to put back several embryos simultaneously during IVF. During ovarian stimulation, also known as ovulation induction, ovulation drugs, or "fertility drugs", are used to stimulate the ovaries to produce multiple eggs rather than the single egg that normally develops each month. Multiple eggs are needed because some eggs will not fertilize or develop normally after egg retrieval. Drug type and dosage vary depending on the program and the patient. Most often, ovulation drugs are given over a period of 9 to 11 days. Ovulation drugs include human menopausal gonadotrophins (hmg), follicle stimulating hormone (fsh), recombinant fsh and lh, and human chorionic gonadotrophin (HCG). Gonadotropin releasing hormone (gnrh) agonists or gnrh antagonists are used in conjunction with these medications to prevent premature ovulation.

4. Assessing the development of the eggs

Egg collection is generally timed to within a few hours of when the woman is expected to ovulate. If eggs are not collected very close to this time, they may not fertilise properly. This is the main reason why so many tests are often done to confirm the status of the woman’s hormones and, thus, development of her eggs.

• Hormone tests:

  As the follicle swells, the hormone oestrogen (estradiol or e2) is produced in increasing amount. Regular blood test can detect this increase.

• Ultrasound:

  The swelling follicle can be directly measures using transvaginal ultrasound. This is usually done daily. We know from experience that, when the follicle is about 20 mm across, ovulation is imminent.

• Ultrasound:

  The swelling follicle can be directly measures using transvaginal ultrasound. This is usually done daily. We know from experience that, when the follicle is about 20 mm across, ovulation is imminent.

5. Egg retrieval

When the ovaries are ready, HCG or other medications are given. The HCG replaces the woman’s natural lh surge and helps the eggs to mature so they may be capable of being fertilized. The eggs are retrieved before ovulation occurs, usually 34 to 36 hours after the HCG injection is given. However, 10% to 20% of cycles are cancelled prior to the HCG injection.

6. Insemination, fertilization, and embryo culture

After the eggs are retrieved, they are examined in the laboratory. The best quality, mature eggs are placed in IVF culture medium and transferred to an incubator to await fertilization by the sperm. Sperm, obtained by ejaculation or a special condom used during intercourse, are separated from the semen in a process known as sperm preparation. Motile sperm are then placed together with the eggs, in a process called insemination, and stored in an incubator. Fertilization occurs in the laboratory when the sperm cell penetrates the egg, usually within hours after insemination.

What happens during an IVF cycle?

A typical IVF self stimulation cycle (involving wife’s eggs) at Care IVF starts at day 2 of menstrual cycle. It follows the 4 basic stages:

What happens during stimulations?

The day two of menstrual cycle is usually the day 1 of stimulation. This is when we start giving the stimulation injections.

The typical IVF stimulation protocol follows the following steps:

Period day 2 = injections day 1:

Period	Injection
d2 - d5	d1 – d4	A baseline scan is done. The ovaries are assessed for cysts abd antral follicle count. Stimulation injections are started form d1 and continues till d4
d6	d5	The patients e2 and progesterone levels are tested, and follicular scan is done. Based on the result the injection dosage may remain same or may be revised. This injection protocol continues till trigger. The husband’s semen sample is taken for freezing. This acts as a backup sample.
d7 - d8	d6 - d9	Stimulation inj + antagonist inj on day 6, if the follicle size is more than 13mm, antagonist protocol is started.
d10 - d11	d9/10	Once the desired size of follicles are achieved (17-18 mm), trigger is induced by administering trigger injections. The opu should occur 36 hours from trigger.
d12 - d13	d11/12	36 hours post trigger the eggs are retrieved by oocyte retrieval. Husband is asked to deposit fresh sample on this day. IVF/ICSI is done on the same day within hours of pick up.

The husband needs to submit a fresh semen sample on the day of the pick up. The oocytes are retrieved by ovum pick up procedure (opu). The eggs are fertilized by IVF or ICSI within a few hours. Effectively the fertilization is done on the same day of the opu and this is considered day 0 of embryos.

The embryos may be grown till day three and transferred or grown till day 5 and transferred. Day 5 embryos transfer, also called a blastocyst transfer and has better rate of implantation.

Tthe pregnancy card test is done 9 days after (day 5) transfer and two weeks following this a usg tvs scan is done to confirm the positive cardiac activity.

IVF treatment cycle typically should not take more than 15 to 20 days. If you are wondering about how many days you may need to stay and how many times your husband has to visit the clinic please take a look at the IVF calendar below.

What does a typical IVF cycle looks like?

This is what a typical IVF calendar of a woman undergoing IVF self-treatment would look like.

Risks of ART

• Small risk of hyperstimulation. The stimulated cycle is very carefully monitored. However in any cycle there is a small risk of hyperstimulation which may result in enlargement of the ovaries. Most cases resolve with very simple treatment.
• Pregnancies involving assisted reproduction have slightly higher miscarriage rates than normal.
• Removing eggs through an aspirating needle entails a slight risk of bleeding, infection, and damage to the bowel, bladder, or a blood vessel.
• The chance of multiple pregnancies is increased in all assisted reproductive technologies (about 20%) when more than one embryo is transferred. Some couples may consider multifetal pregnancy reduction to decrease the risks due to multiple pregnancies.
• First trimester bleeding may signal a possible miscarriage or ectopic pregnancy. Some evidence suggests that early bleeding is more common in women who undergo IVF and gift and is not associated with the same poor prognosis as it is in women who conceive spontaneously. Miscarriage occurs after ultrasound in nearly 15% of women younger than age 35, in 25% at age 40, and in 35% at age 42 after ART procedures. In addition, there is approximately a 5% chance of ectopic pregnancy with ART.

Assisted Reproductive Technologies involve a significant physical, financial, and emotional commitment on the part of the couple. Psychological stress is common, and some couples describe the experience as an emotional roller coaster. The treatments are involved and costly. Patients have high expectations, yet failure is common in any given cycle. Couples may feel frustrated, angry, isolated, and resentful. At times, this feeling of frustration leads to depression and feelings of low self-esteem, especially in the immediate period following a failed ART attempt. The support of friends and family members is very important at this time. Couples are encouraged to consider psychological counselling as an additional means of support and stress management. We have a mental health professional on staff to help couples deal with the grief, tension, or anxieties associated with infertility and its treatment.

Reasons For Cancellation

The IVF cycle will be cancelled if specific criteria occur:

• Abnormal screening hormonal levels.
• Lack of proper stimulation.
• Failure of estradiol to increase by 20% daily or less than four adequate sized follicles (>20 mm) on ultrasound before retrieval day.
• Decline in estradiol level the morning after hCG administration (by 20% from the maximum).
• LH surge prior to HCG administration plus a drop in estradiol.
• No eggs retrieved on day of oocyte pickup.
• Lost follicles the day of retrieval. Ovulation occurs spontaneously in a small percentage of ART stimulation cycles, despite the use of preventive drugs. When this occurs, the eggs may be lost in the pelvic cavity, and the cycle is usually cancelled.

When To End Treatment ?

Studies indicate that the chance for pregnancy in consecutive IVF cycles remains similar in up to four cycles. However, many other factors should be considered when determining the appropriate endpoint in therapy, including financial and psychological reserves. Members of the IVF team can help couples decide when to stop treatment and discuss other options such as egg and/or sperm donation or adoption, if appropriate. The physician, support groups, and other couples undergoing infertility treatment can provide valuable support and guidance.

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