Ovulation Induction and Intrauterine Insemination

Ovulation Induction (OI) uses fertility medications to cause or regulate ovulation, or increase the number of eggs produced during a cycle. Because these powerful hormones produce significant changes in your system, their effects are tracked by blood tests and ultrasound. These same tests are used to determine a baseline – indicating your natural hormone levels – and your medication start date. For this reason, OI cycles also may be called "monitored" cycles.

These medications include clomiphene citrate. This oral drug promotes growth of the fluid-filled sacks (follicles) containing the eggs. If you do not ovulate, or you ovulate and do not become pregnant after clomiphene therapy, other medications may be prescribed either alone or in combination. These drugs, called gonadotropins, are taken by injection under the skin. They replace natural follicle stimulating hormone (FSH) and, if they are successful, the ovaries produce multiple follicles and high quality, mature eggs.

Your hormone levels and follicular development are tracked throughout a stimulation cycle. If required, your medication protocol (the type and dose) may be altered for optimum results. When the follicles are mature, usually between 16 and 20 millimeters in diameter depending on your stimulation medication, you will take an intramuscular injection of hCG, in preparation for intercourse or intrauterine insemination (IUI).

A variety of medications are available and your physician will choose the drug or combination of stimulation drugs that are best in each case. They include:

Clomipene Citrate (Clomid or Seraphene) – prescribed to women with infrequent periods and long cycles, it blocks the effects of estrogen and causes the body to produce more follicle stimulating hormone.

Human Menopausal Gonadotropin (hMG: Perganol, Humegon and Repronex) – stimulates the development of multiple follicles and eggs during a cycle, hMG is derived from the urine of post-menopausal women.

Follicle Stimulating Hormone (FSH: Gonal F and Follistim) – stimulates development of the fluid-filled sacks containing the eggs, this drug is available in a natural form, derived from the urine of postmenopausal women, or as a "recombinant" or manufactured drug.

Human Chorionic Gonadotropin (hCG: Pregnyl, Profasi and Ovidrel) – produced by the placenta during pregnancy and extracted from the urine of pregnant women, hCG triggers ovulation, releasing the eggs.

 

Getting Started With An OI Cycle

Day 1 of an OI cycle is the first day of full menstrual flow prior to midnight. You should call and let us know that your cycle has started, and ask to speak to a nurse if you need more information. Next, you will visit our office between 7 a.m. and 9 a.m. on Day 3 of your cycle, unless instructed otherwise.

Cycle Monitoring
Day 3 is the first day of monitoring and we will take a blood sample to determine your baseline levels of estrogen and other hormones. This test, along with an ultrasound examination, will indicate your level of ovarian function and help us to determine the appropriate type and level of medication for your cycle. You will receive a call from a nurse in the afternoon with your medication instructions, which may require you to start that evening.

OI With Clomiphene Citrate
Clomiphene citrate, in 50 milligram tablets, increases the production of FSH and LH, hormones produced by the pituitary gland to promote follicular development. This drug also helps to support the luteal phase of the cycle, between ovulation and the start of your next period.

In many cases, clomiphene is effective in increasing FSH for patients who lack this hormone in sufficient levels. The result is the development of follicles and ovulation in about 80% of women who use the drug because they don’t ovulate. About 50% of women requiring this medication become pregnant during the first three clomiphene cycles; however, the rate is less for those who ovulate on their own but cannot achieve pregnancy for other reasons. Also, the chance of pregnancy diminishes with each subsequent clomiphene cycle and it is rare after 6 cycles.

The most common dose of clomiphene is one or two tablets daily for 5 consecutive days, beginning on the third or fifth day of your cycle. As many as 5 pills may be prescribed at a different time in your cycle, depending on individual factors.

An ovulation predictor kit, such as Clear Plan Easy or Ovu Quick, will help you determine the best time to have intercourse or IUI. You will use the kit to test your urine, beginning as early as Day 10 of your cycle, or as otherwise instructed, based on the length of your cycle. When a color change indicates a surge of luteinizing hormone (LH), have intercourse that evening and the following day.

If insemination is required, you will call the office on the day of the LH surge to schedule the procedure the following day. If ovulation is likely to occur on a Saturday, Sunday or Monday, call ahead to schedule a tentative appointment.

OI With Injectable Hormones
If you have been diagnosed as having anovulatory cycles or polycystic ovaries, your doctor may recommend stimulation by small amounts of injectable hormones over a period of approximately 14 days. Your individualized medication protocol will be determined by your physician. These medications, called gonadotropins, are administered by subcutaneous injection and consistency is important. Therefore, choose a time between 5 p.m. and 11:00 p.m. that will be convenient for the duration of your cycle.

To ensure that the medications are working as intended, you will visit our office for blood tests to determine your hormone levels and ultrasounds to track follicle development. Because monitoring varies, a nurse will instruct you when to come in. Depending on how you respond to stimulation, you may require adjustments to your medication and monitoring up to 10 times during your cycle. You will receive a call from a nurse in the afternoon after each monitoring session, with instructions to proceed with your medication as prescribed or to adjust your dosage. It is critical that you do not make any changes to your medication protocol or injection schedule without specific instructions from a nurse.

Once the follicles have matured, you may be instructed to take an injection of either 5,000 or 10,000 units of human chorionic gonadotropin (hCG), a hormone to trigger ovulation. HCG mimics the surge of luteinizing hormone during a natural menstrual cycle and helps the eggs prepare for release.

 

Insemination

Following stimulation during an OI cycle, some couples will be instructed to have intercourse at the optimal time for pregnancy. In other cases, "artificial insemination" may be required if the male partner is impotent, has excessively low sperm count or other problems such as decreased sperm mobility. Insemination also may be required if healthy, plentiful sperm are prevented from entering the uterus because of problems with the women’s cervix or a negative interaction between the sperm and her cervical mucous. Donor sperm is required in the absence of a male partner or in cases of severe male infertility that cannot be overcome with intracytoplasmic sperm injection (ICSI), a procedure that has revolutionized the treatment of male factor infertility.

Because fertilization is most likely to occur closest to the time of ovulation, intercourse and/or an insemination procedure must be timed accordingly. An ovulation predictor kit can be used to test your urine, beginning as early as Day 10 - or according to instructions by a nurse – depending on the length of your cycle. When a color change indicates a surge of luteinizing hormone (LH), have intercourse that evening and the following day. If hCG is prescribed to trigger ovulation, the optimal time for insemination is within 24-to-36 hours after the injection.

Intrauterine Insemination (IUI)
In an artificial insemination, sperm is collected from the male partner or secured from a donor. It is "washed," or removed from the seminal fluid, to remove impurities. The sample is processed to select out the motile (moving) specimens, which are concentrated into a small amount of sterile medium. Sperm preparation takes about an hour, so the male should plan accordingly and arrive in time to provide a sample.

The insemination procedure, best tolerated with an empty bladder, takes only 5 to 10 minutes. A speculum is inserted into the vaginal opening. The prepared sperm and medium are placed in a small catheter, which is passed directly into the woman’s uterine cavity (intrauterine insemination – IUI). You may experience mild cramping during the procedure, but it will subside when it is completed.

Post-Procedure Care for IUI
You will need to rest for 5 to 10 minutes following the procedure and you may be instructed to return the following day for a second insemination. In the meantime, you may resume normal activities but avoid exposure to extreme temperatures. You also will be told when to return to the office for blood work. Progesterone may be prescribed, in oral or suppository form, to provide luteal support if indicated by your blood work. This medication helps prepare the lining of the uterus to accept and support the embryo during pregnancy.

You will be scheduled to return to our office for a pregnancy test 13-25 days after the procedure. Progesterone, if prescribed, will be taken for 6 or 7 weeks if the test is positive. If you are pregnant, we will continue to monitor you for 4 to 5 weeks (or until you are approximately 8 to 9 weeks pregnant). If the procedure is not successful, a nurse will call to discuss the next steps.

 

Risks and Side Effects of OI and Insemination

The risks and side effects linked to fertility drugs and ovulation induction will be discussed with you before you receive this treatment. It is important that you ask questions and follow all instructions carefully to minimize adverse affects.

For some patients, clomiphene citrate can cause hot flashes and mood swings while the drug is being taken; and depression, nausea and breast tenderness later in the cycle. Severe headaches or visual problems are extremely rare, but they will prompt your physician to stop treatment immediately. Clomiphene also can negatively affect the uterine lining to a point where it cannot accept the fertilized egg (embryo) or cause changes in cervical mucous that are hostile to sperm.

Most patients taking gonadotropins by injection do not have problems with blood sampling and hormone injections; however, some experience local discomfort, redness or bruising at the injection sites. Injections can be painful and the side effects of the drugs may include hot flashes, breast tenderness, fluid retention, a bloated feeling, moodiness, depression and/or tenderness in the ovaries.

Monitoring during your stimulation cycle is extremely important, as it allows our physicians and nurses to closely regulate medications to minimize your discomfort and side effects. However, in a relatively small number of cases, they cannot be avoided.

Other complications are rare and occur in less than 1% of cases. They can include infection, cervical bleeding, abdominal pain and cramping and fever.

Ovarian Hyperstimulation (OHSS)
In fewer than 1% of all OI cases, a patient may form ovarian cysts that could rupture, a twisting of the ovaries that may require surgery, or experience ovarian hyperstimulation syndrome (OHSS). The latter, associated with enlarged ovaries and fluid in the abdomen, can lead to dehydration, large amounts of fluid accumulation in the abdominal and lung cavities, blood clotting disorders and kidney damage.

Any possible links between stimulation drugs and ovarian cancer continue to be a subject of extensive researched; however, a positive causal effect has not been established.

Ectopic Pregnancy
Ectopic pregnancies, also called tubal pregnancies because they occur in the fallopian tubes, are reported in 1 to 3% of cases involving fertility medications. This risk is only slightly higher than the 1-to-2% reported for the general population. Ectopic pregnancy can often be treated with medication. However some, including those that occur along with intrauterine (heterotropic) pregnancies, require surgery.

Multiple Births
The chance of multiple births is higher in OI cycles because the fertility drugs stimulate the ovaries to produce multiple follicles and eggs. Unlike in vitro fertilization (IVF), where we can control the number of embryos transferred back into the uterus, OI does not provide the same control. Women taking clomiphene have about a 10% chance of having twins; and less than a 1% chance of triplets or higher order multiples. When FSH is used, multiples occur in 15 to 25% of cycles. Of these, about two-thirds are twins and one-third are triplets or more.

Multiple gestations can pose serious risks to both the mother and developing fetuses, including pregnancy loss, premature delivery, abnormalities and handicaps related to premature deliveries, pregnancy-induced hypertension and hemorrhage. Even in the event of successful deliveries, multiple births can be associated with a host of medical, financial and emotional issues affecting both parents and children. Therefore, if multiple eggs are fertilized as a result of OI, you may have to choose between having more than one child and undergoing multifetal reduction to reduce the number of embryos carried to term.

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