Ovulation Induction

Fertility medications are commonly used to stimulate the follicles in the ovaries resulting in the production of multiple eggs in one cycle. Fertility medications also control the time that you release the eggs, or ovulate, so sexual intercourse, intrauterine inseminations, and In Vitro Fertilization procedures can be scheduled at the most optimal time to achieve pregnancy.

As with most medications, there are a few risks associated with the use of ovulation induction medications including an increase in the chance for high order multiple births and the development of ovarian cysts. Please take time to read about the fertility medications below and note the side effects associated with each medication.

The medications most commonly used in fertility treatment are clomiphene citrate, gonadotropins, Metformin and Parlodel. 

Clomiphene citrate (Clomid, Serophene) is an oral tablet taken to induce ovulation in some women and to stimulate multiple follicle development in others. Clomid induces ovulation by increasing the output of certain hormones from the pituitary gland, which stimulate follicular growth in the ovary and subsequent ovulation. The usual dosage is 50-150 milligrams (one to three 50 mg tablets) taken days 3 through 7 or days 5 to 9 of the menstrual cycle. Most pregnancies occur within the first 3 – 4 ovulatory cycles. The pregnancy rate with additional cycles is low, even though the patient may be ovulatory.

Multiple birth pregnancy occurs in approximately 8% of patients using clomiphene citrate (almost entirely twins). The risk of a triplet pregnancy with clomiphene is less than 1%. Other side effects include: hot flashes, ovarian cyst formation (which generally resolves spontaneously), abdominal discomfort, nausea and vomiting, headache, breast tenderness, and moodiness. Rarely, visual disturbances are noted which would contraindicate further use.

Gonadotropins (Repronex, Follistim, Bravelle, Pergonal and GonalF) - These are injectable medications containing FSH or FSH & LH. They are utilized to stimulate multiple ovarian follicular development and egg maturation. These gonadotropins may be used in women who don’t produce their own FSH, in women who have failed clomiphene citrate, or to increase the chance of pregnancy in ovulatory women. This treatment requires careful monitoring. Side effects may include abdominal distention/discomfort, bloating sensation, mood swings, fatigue or restlessness.  Other risks include ovarian hyperstimulation syndrome and multiple pregnancy. The risk of multiple pregnancy with gonadotropins is about 20 – 30 percent. The data regarding ovarian cancer risk is conflicting. Pregnancy and breast feeding reduce ovarian cancer risk. Overall it is recommended to minimize the total number of cycles to those necessary. Most pregnancies occur within three treatment cycles.

Gonadotropins (Profasi, Pregnyl, Ovidrel) – This is an injectable medication containing hCG (human chorionic gonadotropin). hCG is used to induce the release of the egg once the follicles are developed and the eggs are mature. Ovulation will occur 36 to 72 hours after hCG injection. hCG is commonly added to clomiphene or FSH, FSH/LH cycles. The use of hCG helps time intercourse or inseminations.

Glucophage (Metformin) - Metformin is an oral pill given to patients as an insulin lowering medication. Most commonly used in PCOS patients, the medication has been shown to improve the endocrine abnormalities seen with polycystic ovary syndrome within two or three months. The use of Metformin can result in decreased hair loss, diminished facial and body hair growth, regulation of menses, weight loss and normal fertility. Side effects include nausea and vomiting, diarrhea, and stomach intolerance.

Parlodel - Parlodel is a medication used to lower prolactin levels. It will also reduce pituitary tumor size (pituitary adenoma’s), should one be present. An oral medication taken with meals, Parlodel has few side effects and is relatively inexpensive. Side Effects include nausea, dizziness and headaches.

There are different levels of ovulation induction commonly used to treat infertility related to ovulation disorders, male factor or unknown causes. One method of treatment involves clomiphene citrate (Clomid or Serophene) taken in pill form for 5 days at the beginning of a cycle. For women whose only infertility problem is an ovulation, up to 80% of patients will ovulate using this medication and 40% of those will conceive. Clomiphene may be combined with intrauterine insemination to boost the success of the medication by placing the sperm and egg in closer proximity to each other.

“Superovulation” is a bit more aggressive level of ovulation induction. This treatment uses gonadotropins or sometimes a combination of clomiphene and gonadotropins to stimulate the production of multiple eggs. Patients undergoing superovulation must be closely monitored by blood tests and ultrasounds. Monitoring ensures that the patient does not hyperstimulate and also helps the physician administer the correct dosage of medication so that only a few follicles develop. This is a critical step to keeping the multiple pregnancy rates low. At the end of the superovulation treatment process, human chorionic gonadotropin (hCG) may be prescribed to stimulate ovulation. Ovulation will occur between 36-72 hours after hCG. The patient is instructed to either have intercourse during this time or to come in for an intrauterine insemination. Depending on the cause of infertility, the success rate per superovulation treatment cycle is approximately 10-20% based on the woman's age.

Ovarian Hyperstimulation Syndrome (OHSS)  

The ability to induce and control ovarian stimulation has greatly enhanced the treatment of infertility. The use of fertility drugs for ovulation induction is however not without risk. The ovarian hyperstimulation syndrome (OHSS) is a rare but serious side effect of ovulation induction therapy. The reported incidence is 20%, with 1-2% of cases being severe. The syndrome is rare unless human chorionic gonadotropin (hCG) is administered to trigger ovulation. Symptoms commonly develop three to ten days after hCG administration.

The diagnosis of OHSS is made and the severity of the syndrome is determined by a combination of the history, physical examination, ultrasound and laboratory findings. This syndrome is characterized by significant enlargement of the ovaries, abdominal pain, bloating, nausea, and possible fluid retention in the abdomen.

Classifications

Ovarian hyperstimulation syndrome (OHSS) is classified as mild, moderate, or severe based upon ovarian size as determined by ultrasound and laboratory tests.

• Mild hyperstimulation is defined as ovarian enlargement less than 6cm. In the absence of gastrointestinal symptoms or other problems, the treatment is outpatient management. Therapy consists of bed rest at home, pelvic rest, limited activities, and monitoring of daily weights, urine output, and abdominal girth.
• Moderate hyperstimulation is frequently associated with increased abdominal discomfort and other problems requiring hospitalization. In selected cases, patients may be cautiously managed at home with pain medication, rest and monitoring (as with mild hyperstimulation) and close contact with the fertility clinic.
• Severe hyperstimulation is characterized by severe abdominal pain, nausea and vomiting, very low urine output, shortness of breath, and fluid in the abdomen. Hospitalization is usually required.

Management

The most common scenario of hyperstimulation is spontaneous resolution. Clinical resolution usually occurs within 7 to 14 days in nonpregnant women, and may require 30 days when pregnancy occurs, as the hormones of the pregnancy may provide additional ovarian stimulation.

General Instructions

If you experience symptoms such as abdominal pain, bloating, dizziness, nausea, and vomiting, you are to contact LifeStart Fertility Center at (818) 889-4532. Limit your activities and obtain bed rest and pelvic rest (no intercourse, nothing per vagina).

If excessive amounts of pain or nausea and vomiting ensue, you need to be evaluated at the LifeStart Fertility Center, or if after hours, report to the Hospital Emergency Room. Please tell the ER staff that you are a fertility patient who is currently undergoing an ovulation induction regimen, and that you are NOT TO HAVE A PELVIC EXAMINATION. All assessments of your ovaries will be done by ultrasound.

In Summary

1. If abdominal pain, nausea, vomiting or dizziness occur, call LifeStart Fertility Center at (818) 889-4532.
2. Strict bed rest, limit activities (up to the bathroom only)
3. No intercourse or pelvic exams

Please contact LifeStart Fertility Center serving greater Los Angeles for more information on Ovulation Induction and to schedule a consultation appointment.

Infertility Medication Instructions

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