Ovulation Induction

secretion of hypothalamic and pituitary hormones such as FSH, and can normalize the pattern of follicle development in order to produce ovulation. CC is usually taken orally for 5 days early in the menstrual cycle. Approximately 80% of women will ovulate when treated with the proper dose of CC. The starting dose is usually 50 mg which may be increased by 50mg steps if ovulation is not produced at the first dose. Most physicians will use a dose of up to 150 mg, though some will consider doses of up to 250 mg. The best dose of CC is the lowest dose which produces predictable and regular ovulation. The side effects of CC are usually minor and include hot flushes, headaches, upset stomach, breast tenderness, and irritability. Excessive stimulation of the ovaries (ovarian hyperstimulation syndrome) in response to CC is rare. There is an increased risk of twins in women who are taking CC, estimated to be 5 to 8% of pregnancies. However, CC is rarely associated with high order multiple gestation (triplets or more), and is not known to increase the risk of birth defects.

It is important to monitor women on CC to find out if the treatment is working. Most women taking CC ovulate sometime between 4 and 10 days after the last pill, with most common days being days 6 and 7. Sometimes women taking CC choose to monitor their cycles by taking their temperature every morning (basal body temperature). After ovulation, progesterone secretion increases and causes a temperature raise of approximately 0.5 degrees F. This rise will not occur in women who do not ovulate. While this technique is helpful in confirming ovulation, it is not very useful in determining exactly when ovulation occurred since the day of the temperature rise may be as much as 2 days before or 2 days after the actual day of ovulation. For this reason, trying to conceive by having intercourse on the day of the temperature rise may prove to be inefficient.

A more reliable way to predict ovulation is by using an over the counter ovulation predictor kit (OPK). These kits test for a surge in the pituitary hormone LH which begins approximately 36 hours before ovulation occurs. LH appears in the urine in increasing amounts after the surge, and can usually be detected by a commercially available OPK beginning approximately 18-24 hours prior to ovulation. Women trying to become pregnant are usually advised to have intercourse the day of the surge and the day following the surge to optimize the chance of conception. Women who decide to use an OPK should begin testing 2 or 3 days after the last CC dose because the medication itself con produce a false positive LH test. Testing should continue until the LH surge is detected or 14 days has since the last pill.

Sometimes women are uncertain if they have ovulated in response to CC, or they have not become pregnant even though their OPK testing suggests that they hove ovulated. In these cases, ultrasound evaluation of the ovarian follicles and the uterine lining (endometrium) can be very helpful to monitor response to the medication. The ultrasound is usually performed 4 to 5 days after the last CC pill. If the doctor sees an enlarged follicle with well-prepared endometrium, the woman can be confident that ovulation is likely to occur. Furthermore, the doctor may be able to give the patient a good idea about when ovulation will take place based on the size of the follicle. Ovulation can be confirmed by drawing a blood progesterone level about 7 days after the expected day of ovulation. A progesterone value greater than 5ng/ml confirms ovulation.

group of medications called gonadotropins. Gonadotropin medications contain either FSH alone or FSH plus LH and are given by injection. Gonadotropins allow the physician to directly stimulate the ovary with the pituitary hormones necessary to induce ovulation. Thus, they are different from clomiphene citrate which acts indirectly on the hypothalamus and pituitary to increase FSH. Because all gonadotropin medications directly stimulate the ovaries, they overcome the normal mechanism by which women limit ovulation to one egg. For this reason physicians will always closely monitor women receiving gonadotropins in order to avoid over stimulating the ovary and producing high order multiples {triplets or more} or ovarian hyperstimulation syndrome. Monitoring consists of frequent evaluation of ovarian follicle development by ultrasound and measurement of blood estrogen {estradiol) levels, both of which help the physician understand how the ovary is responding. The dose of gonadotropins is often adjusted up or down based on the monitoring results. When the developing follicle(s) reaches a mature size {usually 16 to 20 mm), human chronic gonadotropin (hCG) is administered by injection to stimulate the release of the egg(s). Ovulation is expected to occur 36 to 46 hours later.

Sometimes monitoring shows that too many follicles are developing, and the risk of a multiple pregnancy is too high. When this occurs, treatment is usually stopped, hCG is withheld, and ovulation induction in that cycle is cancelled.

Women with PCOS are particularly at risk for this problem as well as ovarian hyperstimulation (OHSS). OHSS occurs when hCG is given after a large number of follicles develops, even if many of the follicles are small. In this condition, the ovaries enlarge and leak fluid into the abdomen which can lead to discomfort, weight gain, nausea, and vomiting. In very severe cases, there may be accumulation of a large amount of fluid in the abdomen and around the lungs which can lead to breathing difficulties, dehydration, decreased kidney function and development of blood clots in the legs or in the lungs (deep venous thrombosis, pulmonary embolism).

Severe OHSS is a very serious medical problem and usually requires hospitalization and intravenous fluids. Inserting a needle into the abdomen to drain fluid (paracentesis) is sometimes required. OHSS usually starts to develop within 5 to 10 days of the hCG injection, and will get better on its own over the course of 5 to 10 days if the woman does not experience complications as described.

A multiple pregnancy is the most common problem seen with the use of gonadotropins. As many as 25% of pregnancies that occur with gonadotropin stimulation will be multiples. The vast majority of these are twins, but these medications can be associated with triplets as well as the much publicized cases of quadruplets, quintuplets and even more.

While these outcomes are rare, it is always wise for a woman to discuss the risks and benefits of gonadotropin treatment with physician before deciding on this course of therapy.