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IVF Stimulation Cycles

 

  IVF Stimulation Cycles 

Unlike IUI cycles, which take place over the course of one month using gonadotropins to stimulate the ovaries to produce one to three eggs, many IVF cycles take place over a two month time span. Additional medications may precede ovarian stimulation with higher doses of gonadotropins for a longer period of time in order to obtain a greater number of eggs to be retrieved and exposed to sperm in the ART laboratory to create embryos for transfer to the uterus. 

Each fertility center has its own protocols for IVF stimulation and physicians choose the protocol that they believe will optimize ovarian response for each patient based on her individual clinical situation. Patient age, diagnosis and previous response to stimulation are all considered. The following is a general description of a typical ART stimulation protocol. Your doctor or nurse will discuss your protocol with you and give you specific instructions regarding medication dose and schedule.  IVF stimulation protocols start with your period. You will need to contact your physician or nurse on the first day of your period for specific instructions. These protocols are used for women doing IVF with their own eggs and for women who are Egg Donors. 

Birth Control Pills      OCPs

Many physicians will use the first month of the IVF cycle to quiet the ovaries in order to have control during the second month of stimulation. This may involve taking birth control pills starting cycle day 3 for 12 to 28 days. 

GnRH Agonists

The GnRH agonist, leuprolide acetate or Lupron, is used to suppress the ability of the pituitary gland to release follicle stimulating hormone FSH and leutinizing hormone LH. This means that the ovaries will not be able to make an egg or ovulate without taking gonadotropins. This works well for IVF cycles so that gonadotropins can be given to recruit a good number of follicles containing eggs without the risk that a spontaneous LH surge would cause ovulation before egg retrieval. There are several ways to use leuprolide acetate/Lupron in IVF stimulation protocols. Your physician will choose the protocol that will optimize your response. Protocols include: 

            Lupron Down Regulation or Luteal Phase Protocol

This is one of the most commonly used IVF stimulation protocols. Leuprolide acetate/Lupron is generally started somewhere between cycle day 17 and 22 (the luteal phase) of the cycle before your stimulation. This may or may not be used in addition to birth control pills. Subcutaneous injections of 10 to 20 units are usually taken in the evening for 10 to 14 days. An ultrasound and bloodwork are done to confirm that the ovaries are quiet and the estrogen level is low before stimulation is started. Injections continue at a lower dose, 5 to 10 units, along with gonadotropin injections in the stimulation phase. Once there are enough mature follicles and a high enough estradiol level, both leuprolide acetate/Lupron and gonadotropins are discontinued and a single injection of hCG is taken on a particular day at a specific time that is determined by the scheduled egg retrieval day and time. HCG injections are generally given 32 to 34 hours before scheduled egg retrieval.  

Mini Dose Protocol

This protocol can be used if there is concern about ovarian response. Leuprolide acetate/Lupron is started in the cycle before stimulation as above at a dose of 5 to 10 units for 10 to 14 days with or without birth control pills. Once an ultrasound and bloodwork confirms quiet ovaries stimulation with gonadotropins begins and the leuprolide is discontinued. 

Flare Protocol

This is another protocol that can be used when there is concern about ovarian response. Leuprolide acetate/Lupron is started on day 2 of the cycle and gonadotropins may be started at the same time or a day or two later. The dose is usually 10 units each day until the time of the hCG injection. 

Lupron Microdose Protocol

Some physicians prefer this protocol for women who do not respond well to other protocols. Birth control pills are usually taken for 21 days in the cycle before stimulation. An ultrasound and blood test are done to confirm quiet ovaries. Full strength leuprolide acetate/Lupron is diluted at the pharmacy so that 10 units now contain 40 mcg of the drug rather than the usual dose. 10 units of this dilute preparation are taken each morning and evening as directed and gonadotropins are taken each morning and evening starting the morning of the third or fourth day until it is time for hCG and egg retrieval. 

GnRH Antagonists

GnRH antagonists can also be used in IVF stimulation protocols to prevent an LH surge. These drugs, Ganirelix Acetate and Cetrotide, work immediately to suppress the pituitary from releasing LH and FSH. They are started during the stimulation phase of the IVF cycle, during gonadotropin stimulation and before there is a risk of an LH surge. Some physicians start these on a particular day in the stimulation phase and others wait until the biggest follicle is a specific size or there is a specific estradiol level. The first subcutaneous injection is usually taken in the evening and then it may be given morning or evening every day until HCG for egg retrieval. Both Ganirelix acetate and Cetrotide come in 0.25 mg taken every 24 hours and Cetrotide also comes as a 3 mg long acting dose that is taken once and supplemented with the daily dose if longer stimulation is needed. 

Gonadotropin Stimulation

The ovaries are stimulated with either an FSH product (Gonal-F, Follistim, Bravelle) or an FSH product in combination with a product that also contains LH (Luveris, Repronex, Menopur) to develop many follicles containing eggs which will be retrieved and exposed to sperm in the ART laboratory. The gonadotropin and the dosage are determined by a many factors including physician preference, insurance guidelines, patient age, diagnosis and previous response patterns. Some women take their gonadotropins once a day, others twice a day. Most are given subcutaneously (SC) but in some cases they are given intramuscularly(IM).

 Most women take gonadotropins for 3 to 5 days and then have an ultrasound and blood test to evaluate their response. At this point the dosage may stay the same, increase or decrease and another ultrasound and blood test will be scheduled within 1 to 3 days. Stimulation often takes 10 to 13 days. This process continues until there are enough follicles of a good size and a high enough estradiol level to proceed to egg retrieval. At that time all stimulation protocol medications are discontinued and a single injection of an hCG product (Ovidrel, Novarel, Pregnyl, generic HCG) is given 32 to 34 hours prior to egg retrieval. This injection causes the eggs to mature and be retrieved from the ovaries. 

Egg Donors should not require any medications after egg retrieval. 

Progesterone

Most physicians will prescribe a Progesterone product starting the day of or day after egg retrieval each evening until the pregnancy test. Progesterone may be given orally, vaginally or as an IM injection. Progesterone stimulates the uterine lining (endometrium) to continue to develop so that an embryo that implants will have a thick, supportive environment to nourish it.

 

Gina Paoletti-Falcone, RN, BSN is the Clinical Services Manager at Freedom Fertility Pharmacy, the leading fertility specialty pharmacy in the US (www.freedomfertility.com). Prior to joining Freedom, Gina worked as a fertility nurse and as a Clinical Services Manager at one of the largest fertility practices in the Boston area for 16 years. Gina developed the Freedom MedTEACH website, an on-line patient educational resource with video instruction for all the injectable fertility medications, because she believes that patients’ anxiety over injectable medication administration can be addressed by giving them control over when and how often they  have the opportunity to review the information, including when they are ready to administer their medication.

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