Ovulation Induction (OI)

There are some patients who have inadequate egg production (ovulation) as the cause of infertility. Common categories are patients with Polycystic ovaries, Hypogonadotropic hypogonadism and others. The clinic would diagnose the problem with a simple Transvaginal ultrasound scan and some hormone estimations such as serum FSH, LH, Testosterone, Prolactin, Thyroid stimulating hormone, DHEA-S and more recently Anti Mullerian Hormone (AMH).

The first line of treatment for these patients is ovulation induction using one or more of several drugs that are available for this purpose.

Clomiphene citrate (often called fertomid / fertyl / clomid / clome) is the commonest and most prescribed drug for ovulation induction. The starting dose is 50 mg given once daily from the 2nd or 3rd day of menstruation. The clinic might like to do a ultrasound on that day to ensure that you have had a proper period (menstrual blood flow and complete shedding of the endometrium). Subsequently, you have to undergo serial ultrasounds for a follicle study to assess the response of the ovaries to this drug and to time the exact date of ovulation. When the lead follicle reaches a diameter of 18-20mm, you would be given an injection of human chorionic gonadotropin (HCG) 10,000 IU so that the eggs are released after 40 hours. The doctor would also give you the dates and time for sexual intercourse to optimize the chances of pregnancy.

Letrozole is now extremely popular for ovulation induction in polycystic ovarian syndrome and patients with anovulation. The starting dose is usually 2.5 to 5 mg per day. Ultrasound monitoring is important for optimal results.

Sometimes, if the above two fail, the clinic might decide to try injections of Follicle stimulating hormone (FSH) or hMG (human menopausal gonadotropin) for inducing multiple eggs to grow. We might also add a GnRH agonist such as leuprolide or busarlin OR a GnRH antagonist such as cetrorelix or ganirelix to the FSH injections. This helps prevent premature release of the eggs and also helps in timing the procedure (if you are going for an Intrauterine insemination).

Aims of Ovulation Induction

The aim is to stimulate preferably one or two and a maximum of three ripe follicles. When the size of the follicle suggests that the follicle is ripe, another hormone, Human Chorionic Gonadotrophin (HCG) is administered which releases the egg. The couple is then advised to have intercourse around the time of ovulation.

The chance of a pregnancy with simple ovulation induction is about 20% per cycle, with a small risk of multiple pregnancies (usually only twins) of about 20%.

The risks are that too many follicles may be produced (ovarian hyperstimulation), in which case the cycle is cancelled (the HCG hormone is not administered) and intercourse is avoided. It is very rare for the symptoms of sore swollen ovaries with abdominal fluid (ascites) to develop after OI. You may also be given an option of converting to IVF whereby the clinic can remove the eggs, fertilize them with your husband's sperm and freeze the embryos. These can then be transferred in the next cycle. This is a very good option as you would have spent a lot of money on the injections and it would nice if we could save the cycle for you and still give you the best chance.

After the first cycle if there was ovulation but no conception, the cycle is repeated. If too many follicles were produced, the dose of FSH is kept lower for longer.

Normally, pregnancy occurs in the first 3-4 months of ovulation induction. If not, you would need a re-evauation and might have to progress to more advanced techniques such as IVF or ICSI.

Key Points

Hyperprolactinemia (high prolactin levels) need to be corrected before beginning with ovulation induction. MRI of the pituitary might be needed in case of very high prolactin levels to rule out any tumors in the brain.

Hypothyroidism (low thyroid function) also needs to be corrected before OI. You may consult an endocrinologist for this purpose. If uncorrected, if might lead to failure of treatment and early pregnancy losses and miscarriage.

Serum FSH levels on the 2nd day of periods (spontaneous cycle and with no hormone tablets having being taken in the previous month) are good indicators for egg reserve. Levels of < 8 mIU/ml indicate a good egg reserve and optimal chances of pregnancy. Levels of > 8 miu/ml indicate a low egg reserve and the doctor might suggest medication such as Coenzyme Q, L-Arginine, etc for 60-90 days before treatment. Also, these patients need aggressive treatment with high dose FSH injections to hasten the pregnancy process.

• Serum AMH levels done at any time of the menstrual cycle accurately reflect egg reserve. If the level is between 2 – 6, it suggests an excellent egg reserve. For levels less than 2, again pre-treatment as above for 2-3 months before treatment is advisable.