Ovulation Induction


Instructions for Ovulation Induction or Controlled Ovarian Hyperstimulation with Gonadotropins

Introduction: Induction of ovulation with gonadotropins requires advanced training of the physician and a great deal of patient and physician commitment. All of RMA's physicians are highly qualified to provide this treatment. Our offices are open 7-days a week to provide the access necessary for optimal treatment. These therapies are not without risk and should be used only as directed and with close monitoring and follow-up.

The Drugs: Each of these drugs is a protein hormone. Gonal F and Follistim Pen are made by recombinant DNA technology, while Menopur and Bravelle are isolated from the urine of menopausal women and freeze-dried into a powder. All of them have been specially processed to ensure maximum safety and potency. Because they are in powder form, they must be reconstituted with sterile water or saline before injection. The hormones that these drugs provide are Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH), which are hormones that your pituitary gland normally produces. Although FSH is the hormone primarily responsible for follicular development, both FSH and LH play a role in the normal development and ovulation of ovarian follicles. LH is normally responsible for triggering ovulation when a mature follicle is present. Each of these drugs acts directly on the ovaries and do not have activities elsewhere in the body.

Gonal F / Follistim Pen: (75 IU FSH, no LH) are pure FSH made by recombinant DNA technology and are given subcutaneously. Gonal F is made by Serono Inc. and comes in ampules (75 IU) and multi-dose (1200 IU) vials and pens. Follistim is made by Organon, Inc. and comes in vials and pens (75 IU).

Menopur: (75 IU FSH, < 0.1 IU LH): is almost pure FSH and is given subcutaneously. Menopur is a more purified form of Bravelle and is made by Ferring, Inc.

Bravelle: (75IU FSH, 1.0 IU LH) highly purified FSH and is given subcutaneously. Is similar (but more highly purified to the old drug Metrodin. Bravelle is made by Ferring, Inc.

HCG (Human chorionic gonadotropin, the "pregnancy hormone"): Its actions are identical to LH, but it lasts longer. It is used to simulate the normal mid-cycle LH surge, which causes the final maturation of the egg and ovulation. It is used because the FSH-containing drugs have altered the normal feedback mechanisms and the LH surge may not occur on its own. Pregnyl and Novarelare isolated from the urine of pregnant women and given intramuscularly. Pregnyl is made by Organon, Inc. and Novarel is made by Ferring. Ovridel is HCG that is made by recombinant DNA technology by Serono and is given subcutaneously.

Indications for Treatment: In women who do not ovulate on their own, these drugs induce ovulation, thus the term Ovulation Induction. In women who do ovulate on their own, these drugs are used to produce more follicles from the ovaries in a controlled fashion, thus the expression Controlled Ovarian Hyperstimulation (COH). Gonadotropins are a first line drug for anovulatory women with normal to low FSH and LH levels. They are a second line drug for women who fail to ovulate or conceive after optimal clomiphene citrate (and/or metformin) therapy. They may also be a first or second line drug for ovulatory women with unexplained infertility and endometriosis. In most women, any of the six FSH-containing gonadotropins may be appropriate to use. However, in certain situations, one drug may be more advantageous to you. The choice of medicines will be discussed at your counseling session prior to initiating therapy.


Monitoring

  1. It is essential that close monitoring with ultrasound and blood tests (estrogen and progesterone) be done to reduce the chances of adverse consequences and to increase the chances of success.
  2. Please call the office when your period starts (day 1 of your cycle). If your period starts after 9:00 pm, day 1 is the next day. Medicines are usually started on day 3 of the cycle. A baseline ultrasound and blood work are required before starting the medicine. You should call to arrange testing as soon as your period starts. If your period starts on a weekend, please leave a message at 248-619-3100. We can start the medicine between days 3-5 of the cycle; your doctor will determine the start after review of the baseline studies.
  3. The tests that will be done initially and at most visits will be an ultrasound and two blood tests: estrogen and progesterone. The ultrasound determines how many follicles are developing and how mature they are, based on their size. The estrogen level is a reflection of the follicle's activity. The progesterone level also reflects follicular activity and is a tip-off of ovulation starting to occur spontaneously.
  4. After the baseline tests, you will take the medicine 4-6 days then return for an ultrasound and blood tests. Lab results are reported late in the afternoon after the physicians have reviewed them. You will be called at your home number by a nurse or physician and informed of (a) adjustments in medicine dosage, or (b) when to return for repeat testing. Most cycles will have 3-6 rounds of tests. Thus, you should expect to be seen every 1-3 days until the follicles are mature.
  5. If you have not been called with your results and plans by 5:00 pm, please call our emergency number at (248) 619-3100. Our answering service will contact a nurse or a physician for you.
  6. Once we have reached our goals for follicle development and the estrogen is in a safe level HCG will be give to induce the final maturation of the egg and ovulation. Do not take the HCG until you are told to. HCG is given because spontaneous ovulation will occur in only a small number of women treated with these medicines.
  7. We generally do two inseminations (IUI's) because we feel that it increases the chances of conception. The inseminations will be about 12 and 36 hours after the HCG injection. If inseminations are not used, timing of intercourse will be discussed with you.
  8. About 5 days after the HCG, a progesterone level will be drawn to confirm that ovulation did occur.
  9. The earliest a pregnancy test may be done is 16 days after the HCG was given. Please call if you get your period sooner.

Adverse Reactions and Risks to Gonadotropin Therapy

  • Local irritation at injection site
  • Symptoms of estrogen excess (dizziness, nausea, headaches, mood swings irritability, hot flashes, breast fullness or tenderness)
  • Ovarian enlargement
  • Ovarian\ Torsion (twisting of an ovary, usually because it is enlarged)
  • Ovarian Hyperstimulation Syndrome
  • Multiple pregnancy
  • Miscarriage
  • Ectopic (tubal) pregnancy
  • Cycle cancellation

Multiple Pregnancies - Multiple pregnancies are more common with gonadotropins than with clomiphene citrate (Clomid, Serophene). The risk is directly proportional to the number of mature follicles. Overall, multiple pregnancies represent 15-20 % of the gonadotropin induced pregnancies with 2-5 % of all pregnancies being high order multiple pregnancies (e.g. Triplets or more)

Ovarian Hyperstimulation Syndrome (OHSS) is a sudden enlargement of the ovaries and accumulation of fluid in the abdomen. It can be a rapidly progressive medical emergency, which may require hospitalization and even intensive care services in its worst form. The cause is unknown, but it is associated with high estrogen levels. Many of the women who develop it are pregnant. The monitoring is designed to attempt prevent OHSS from occurring. Still, it happens in milder forms in 5-10% of gonadotropin cycles. Severe forms are less common. Early symptoms may include weight gain (over 5 pounds), bloating, nausea vomiting, diarrhea and shortness of breath. If you think you have these symptoms, please notify us immediately.

Cancellation of the Cycle - Canceling the cycle (not giving the hCG or doing the IUI) can prevent OHSS and multiple pregnancies. At times, this may be the safest way to proceed. Cycles may also be canceled for inadequate response.


Results of Ovulation Induction / Controlled Ovarian Hyperstimulation with Gonadotropins

This is listed to provide you with an overall perspective regarding the general effectiveness of this therapy. The results that you obtain are dependant upon many factors including the woman's age, quality of sperm and quality of pelvic anatomy, as well as other diagnoses that may be present.

Indication for Ovulation Induction or COH % Ovulating (per cycle) % Pregnant (per cycle) Total % Pregnant after 3 cycles
Anovulation (e.g. PCOS) 75 - 90% 14 - 17% 37 - 42%
Unexplained infertility / Endometriosis (no IUI) 100% 8.7% 23.8%
Unexplained Infertility / Endometriosis (with IUI) 100% 17 - 25% 42 - 56%

Additional Risks

  • Congenital anomalies: risk equal to the general population
  • Miscarriage Rate: 20-25 %, about equal to the general population. Is age dependent
  • Ectopic Pregnancy Rate: 2-5%, equal to or slightly higher than the general population
  • Duration of Therapy: 3-6 cycles. 
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