Question 60. My reproductive endocrinologist has recommended a protocol that uses birth control pills. Why would birth control pills be used in IVF?

Last night I was speaking to a group of high school students that are interested in medicine as a career. I have spoken to such groups many times over the past 5 years and sometimes I feel like I am on the TV show "Kids Say the Darndest Things." Sometimes they get hung up on asking about transgendered individuals. Sometimes they ask about multiples like John and Kate plus Eight or the Octomom. Last night we got sidetracked into a discussion of the NuvaRing and oral contraceptives. These are high school kids I remind you....When I was in high school I spent most Saturday nights watching the Love Boat....I certainly was not wondering which girls were on forms of oral contraception. But amazingly enough I was able to eventually date, marry and reproduce...it gives me hope that geeks everywhere will be able to overcome social adversity...just look at Leonard on the Big Bang Theory as another success story!

Ok. So it's Friday afternoon and I am off this weekend so I am a bit punchy....What does all this have to do with IVF? Well some IVF protocols actually use oral contraceptives as part of the medication recipe. Personally, we don't use a lot of OCPs except in high responders. Recently I had a patient that came in for a second opinion prior to stimulated IVF. Her planned protocol was OCPs plus luteal Lupron and then stimulation drugs. She was 38 years old with an AMH of 0.5 and I recommended against that approach because I thought she would be over suppressed. Ultimately she went back to the original clinic, followed that recipe and never came close to egg collection as her stimulation was a total bust. She called me up and we discussed the plan over the phone and she was very upset....why did that clinic use OCPs on everyone? I told her that I couldn't answer that question and she should ask her RE at that clinic. She said that she was calling me since they never return her calls! Oh well. Hopefully next time she will have a better response...

So here is today's Question of the Day from 100 Questions and Answers about Infertility, Second Edition...

60. My reproductive endocrinologist has recommended a protocol that uses birth control pills. Why would birth control pills be used in IVF?

Birth control pills or, more correctly, oral contraceptive pills (OCPs) can be used as a part of the IVF stimulation protocol in several different settings.

First, in patients who are known or suspected to be high responders, OCPs may help mitigate the risk of ovarian hyperstimulation syndrome (OHSS). Second, in patients without predictable regular menstrual cycles, OCPs can be used in combination with Lupron to initiate an IVF cycle. In our practice, we usually start OCPs in such cases after confirming with a blood test that the woman has not recently ovulated. Then, after 1 week on OCPs, we add Lupron. After 1 more week, we stop the OCPs and continue the Lupron and wait for withdrawal bleeding. Once a patient has bled, we begin the gonadotropin stimulation.

Some clinics use OCPs as part of the protocol for microdose Lupron (MDL) flare, traditional flare, or GnRH-antagonist (Antagon, Centrotide) cycles in the hope that pretreatment with OCPs will prevent one follicle from growing faster than the other follicles once the stimulation has begun. We have not routinely used OCPs with our MDL flare patients, as we have rarely had problems with the emergence of a single dominant follicle compared with the more common problem of oversuppression and a cancelled cycle. Given that prolonged OCP use can lead to oversuppression in low responders, we use these medications very carefully.

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Question 59. What is natural cycle IVF? And why does my fertility clinic not offer this treatment?

As readers of this blog are well aware, we have a particular interest in Natural Cycle (unstimulated IVF). All I can say is that the past 4 years have been filled with outcomes that I would never have believed if these were not my own patients. Although it is not surprising that young healthy women with tubal factor infertility can conceive with Natural Cycle IVF, it is the patients that we thought were clearly long-shots that stick in your memory.

Once recent patient was B.W. (not her initials) who was a 41 year old whose husband had a vasectomy reversal 3 years earlier but had failed to conceive. Her evaluation revealed an FSH of 23 and an AMH that was < 0.16 (essentially zero!). We discussed donor egg and donor embryo and adoption. She was really not interested at this time in pursuing those options even though the success rates were clearly markedly superior to those with her own eggs.

So we elected to attempt NC IVF and during the treatment cycle her day 3 FSH came back at 40! I wasn't even sure if she would have normal follicle development but she did and we were able to get a mature egg. It fertilized with ICSI. It grew into a perfect looking blastocyst. She had an easy ET and her first beta was very positive. She currently has a normal ongoing pregnancy. I actually just called her this morning and she had her 20 week anatomy scan and all looks well!

If you made up cases like this, then no one would even believe it because it seems to fly in the face of conventional wisdom. So here is a bit of conventional wisdom from 100 Questions and Answers about Infertility, 2nd Edition...

59. What is natural cycle IVF? And why does my fertility clinic not offer this treatment?

Natural-cycle IVF (NC-IVF) has been proposed as a means of reducing the risk of multiple pregnancies, eliminating the costs and risks associated with fertility drugs, and reducing the stress and time commitment needed for traditional stimulated IVF. This approach has been espoused by a number of leaders in the field of IVF, including Dr. Robert Edwards, whose pioneering work along with Dr. Patrick Steptoe’s led to the birth of the world’s first IVF baby, Louise Brown, using NC IVF in 1978.

NC-IVF avoids the use of expensive ovarian stimulation drugs and their associated cost of about $4000 per treatment cycle. With NC-IVF the risks of ovarian hyperstimulation, multiple pregnancy, and the issues of cryopreserved extra embryos are avoided as only one embryo is produced. Total cost of Natural Cycle IVF is about 20% to 25% of the total cost of a conventional IVF cycle.

However, NC-IVF has its own set of disadvantages. For example, by not using fertility drugs, unexpected premature “LH surging” or ovulation can occur, leading to cancellation of the planned egg retrieval. This occurs in about 10% to 15% of treatment cycles. In such cases, if the fallopian tubes are open, the doctor may recommend converting the treatment to an intrauterine insemination (IUI) and possible a successful pregnacy. Furthermore, because only one egg and one embryo are produced, the chances for pregnancy are less than with conventional IVF when two or more embryos are transferred. Proponents of NC-IVF expect the “cumulative” pregnancy rate for NC-IVF to be similar to a single cycle of conventional IVF within one to three treatment cycles of NC-IVF.

The best candidates for NC-IVF are patients with regular menstrual cycles who are less than 36 years old and have normal ovarian reserve. Patients with tubal-factor infertility or male factor infertility may be good candidates for NC-IVF before resorting to conventional IVF. Older patients, patients with previous stimulated cycle IVF failures, patients with poor ovarian reserve or unexplained infertility all can be considered for NC-IVF but may experience lower pregnancy rates compared with younger patients with well defined fertility issues and no previous fertility treatments.

Many European fertility centers routinely use NC-IVF with good success rates. For a variety of reasons, the availability of NC-IVF in the United States has been limited. We believe that NC-IVF will soon become increasingly available as patients demand less stressful and less costly fertility treatments that utilize little to no fertility drugs with good pregnancy rates. In our clinic we have routinely demonstrated pregnancy rates of 25% per successful egg collection and 30-40% pregnancy rate per embryo transfer with NC-IVF. We have seen success in patients who had previously failed stimulated IVF and were told that donor egg IVF was their only option so NC IVF may represent a viable treatment option for many infertile couples even those with a poor prognosis with stimulated cycle IVF.

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