Question 58. Which types of drug protocols are used in IVF, and how is the most appropriate protocol selected?

So last August I developed a wicked (note Bostonian roots given use of this adjective) toothache while on vacation at the Outer Banks. Naturally, I did what most physicians do...I started myself on antibiotics and ibuprofen and didn't call a dentist. By the next Monday I was not a happy camper and went to my general dentist only to be told I needed a root canal. Ugh. What a way to return from vacation. I took the recommendation of a local specialist and he did a fantastic job. Took 40 minutes and the next day I felt great! Last week it all started again and I went to my general dentist who said that I may need another root canal (different tooth). He proposed doing it himself without a referral to the specialist. I was in the chair already and it was 4:45 PM so I agreed to let him try. In retrospect, this was not a good decision. He found 2 of the 3 roots but ultimately quit the procedure at 6 PM and told me that I needed to see the specialist the next day anyway. I should have gone there first and next time I will. Dr. DiMattina scolded me for not knowing better....

REs are the specialists in this story. Many generalists are truly excellent physicians but infertility work represents only a small percetage of most general Ob/Gyn practices. Your RE only treats infertility and as a result I think that the advice and approach is superior. Of course, I have a jaded view being a specialist but I should have gotten out of that chair and high-tailed it back to the root canal specialist...Think about this carefully before taking 6 months of clomid with your Ob/Gyn!

Not all patients are created equal. Some patients are destined to be high-responders and some are low responders. This past year I had a patient who had PCOS and I was planning on using a lower dose stimulation. She went to another clinic because of insurance and was hit very hard with stimulation meds and ultimately the cycle was a bust. When we tried stimulation again I had her on one of the lowest doses that I had ever used for IVF but it was successful and we were all much relieved that the OHSS did not materialize. More recently we have been using the GnRH-antagonist protocol with Lupron instead of HCG to trigger for retrieval. This approach is very reasonable in the PCOS patient at risk for OHSS but care must be taken to support the endometrium following retrieval as the estrogen levels tend to drop like a rock and that may affect inplantation.....yup, no such thing as a free lunch.

So here is today's Question of the Day...

58. Which types of drug protocols are used in IVF, and how is the most appropriate protocol selected?

Although several drugs and protocols are available to stimulate the ovaries to produce extra eggs for IVF, most clinics utilize only a few of these stimulation protocols.

One of the more common IVF protocols is called luteal suppression (or long luteal or simply just long) and involves suppression of the ovaries using a GnRH-analog (Lupron) during the luteal phase of the menstrual cycle preceding the planned IVF treatment cycle. Once the ovaries are suppressed, ovarian stimulation is accomplished with daily injections of gonadotropins (e.g., Gonal-F, Follistim). Lupron is usually continued until the day of the hCG trigger shot. A common variation of this protocol is to stop Lupron at the time of starting stimulation. Not surprisingly, this protocol is called “stop Lupron.”

Another common protocol is called flare stimulation. In this case, the woman does not take any medications until the second day of her menstrual cycle. At that time, a microdose (most commonly) of Lupron is used to “flare” the pituitary gland and induce it to release its store of FSH and LH. Simultaneously, gonadotropins are started, producing a “one–two punch” in terms of ovarian stimulation. Premature ovulation of the eggs rarely occurs despite the low dose of GnRH agonist utilized in this protocol.

A third, more recent option is GnRH-antagonist stimulation, in which GnRH antagonists are added later in the stimulation to prevent premature ovulation. In this method, the gonadotropins are started on cycle day 2 of a normal menstrual period. Once the follicles have reached a specific size (usually 12 to 14 mm), the woman begins the GnRH-antagonist medication, which almost instantaneously prevents the pituitary gland from generating an LH surge.

Some reproductive endocrinologists prescribe oral contraceptive pills to their female patients prior to beginning the actual ovarian stimulation drugs, but this practice varies between patients and fertility clinics. We have found that the use of birth control pills often results in oversuppression of the ovaries and cycle cancellation except in those patients known to be high responders (women with PCOS, in particular).

The type of protocol selected for any patient (i.e., luteal suppression, flare stimulation or GnRH antagonist) depends on the individual patient and the philosophy of the fertility clinic. Factors that may influence the type of stimulation protocol selected include the patient’s age, her day 3 hormone levels, her follicle antral count as determined by ultrasound, and her previous responses to any other attempts at ovarian stimulation.