The Alternative-Natural Cycle IVF

April 2, 2007

Resolve

“The Alternative – Natural Cycle IVF”

Michael DiMattina, M.D. and John David Gordon, M.D.

Dominion Fertility
Arlington, Va

Imagine undergoing in vitro fertilization (IVF) with no ovarian stimulation drugs. You may think that this is not possible, but actually the world’s first IVF baby, Louise Brown, was born in 1978 after Doctors Steptoe and Edwards treated her mother, Leslie Brown, with Natural Cycle IVF (NC-IVF) using no ovarian stimulation drugs.

Initially, the IVF pregnancy rates were very low, so ovarian stimulation drugs were routinely used to obtain multiple eggs and embryos for better pregnancy rates. Over 3 million IVF babies have been produced world wide using modern conventional IVF. However, after many years of embryo research together with major advances in technology, IVF pregnancy rates have greatly improved, obviating the need to transfer many embryos. What is unique about NC-IVF is that it uses no ovarian stimulation drugs, so only one egg and one embryo is produced. And this results in a far more patient friendly, less stressful, less expensive IVF treatment.

How Does NC-IVF Work?

In a woman’s natural menstrual cycle, her body self selects the one best egg for that cycle. The development and maturation of the egg can be monitored using ultrasound measurements of the follicle that contains the egg and by measuring the blood levels of estradiol produced from the maturing follicle and egg. Because no ovarian stimulation drugs are used, fewer office visits (usually 3 or 4) are necessary to monitor the developing egg. Once the egg is mature, it is retrieved by placing a needle into the follicle in a simple in-office procedure with minimal sedation. The patient may even return to work the same day that the egg is retrieved. The egg is then fertilized in the IVF laboratory and 3 days later the single embryo so produced is transferred back into the women’s uterus, again in a simple in-office procedure. And again, she may return to work that day. Two weeks later a pregnancy test is obtained. The whole process takes about 4 weeks or the length of a typical menstrual cycle.

The advantages of NC-IVF are many compared with conventional IVF, which usually takes 6 weeks or more to perform and requires many more office visits. Because NC-IVF avoids the use of ovarian stimulation drugs, a treatment cycle is a lot less expensive than conventional IVF, which can cost $12,000 to $20,000. Fertility drugs cost about four thousand dollars per treatment cycle. The total cost for NC-IVF is about 25% of the total cost of a conventional stimulated cycle of IVF. In our program, a rebate is provided if the egg is not retrieved or if the patient experiences premature ovulation. To date, however, we have successfully collected the egg in all patients who have undergone egg retrieval.

With conventional IVF, the fertility drugs require multiple daily injections over several weeks. The drugs produce several eggs and embryos leading to ovarian enlargement, pelvic pressure and pain, sometimes ovarian hyperstimulation sydrome, and often multiple pregnancy. With NC-IVF, all these risks are avoided and since only one embryo is transferred, the chances for twins are almost zero. Legal, moral and ethical issues concerning cryopreservation, storage and later disposition of extra embryos are also avoided with NC-IVF.

Advantages of NC-IVF

• Simple, in-office procedure
• Less stressful and costly
• Monthly treatments
• No missed work
• No ovarian hyperstimulation
• No ovarian stimulation drugs
• Near zero multiple pregnancy rate
• Cumulative pregnancy rates may be similar to one stimulated IVF

NC-IVF has its own set of disadvantages. For example, by not using fertility drugs, unexpected premature changes in hormones (“LH surging”) or ovulation can occur leading to cycle cancellation of the planned egg retrieval. This occurs in about one third to one half of menstrual cycles. In such cases, if the fallopian tubes are open, the doctor may recommend converting the treatment cycle to an intrauterine insemination(IUI) to try to produce a pregnancy in that cycle. Indeed, in our first patient for NC-IVF, premature LH surging occurred but she underwent IUI and became pregnant.

Another disadvantage with NC-IVF is that the pregnancy rates per treatment are lower than with conventional IVF because only one embryo is replaced. With conventional IVF, several embryos are produced and typically more than one embryo transferred. But because NC-IVF is so simple, it can be performed consecutively month after month with “cumulative” pregnancy rates similar to conventional IVF within 1 to 4 treatments. A study in 2001, at King’s CollegeHospital in London, England showed a cumulative pregnancy rate of about 50% per embryo transfer within l to 4 treatments of NC-IVF. A recent study from Canada, showed a 27% pregnancy rate per embryo transfer for patients under 35 years old treated with NC-IVF. The authors believed that after 3 cycles of NC-IVF, the pregnancy rates would be similar to conventional IVF.

Who Should Consider NC-IVF?

We believe that any patient with regular menstrual cycles who is a good candidate for IVF should first consider NC-IVF before undergoing conventional IVF. Such patients are less than 36 years old with a normal day 3 FSH and estradiol level and have a “most favorable” prognosis for pregnancy with IVF. Patients over 35 or who have a poor prognosis for success may do better with conventional IVF with multiple embryos for transfer. Patients with male factor infertility should especially consider NC-IVF rather than simple IUI which has a very low probability for success. Others with tubal factor infertility, endometriosis or unexplained infertility may also be treated with NC-IVF. Unfortunately, however, most studies show NC-IVF is not a good option for patients with abnormal day 3 hormones or diminished ovarian reserve.

Patient Acceptance of NC-IVF

Studies show that one in three patients in the United States who undergo their first treatment with conventional IVF will refrain from undergoing a second treatment of IVF not only because of the costs or poor prognosis but because of the stress and side effects associated with the treatment itself. Studies show that NC-IVF is more patient friendly and that patients are more willing to undergo more treatment cycles than with stimulated or conventional IVF.

Hojgaard, in 2001, reported on patient satisfaction after treatment with NC-IVF, minimal stimulation IVF or conventional IVF, and found that “the patients seemed to prefer the simplicity and short duration of a low stimulation regimen in spite of the drawbacks such as a high risk of cycle cancellations and accordingly the necessity for more cycles.” Furthermore, stress due to cycle cancellation was perceived as mild or not perceptible in significantly more patients who had NC-IVF or low stimulation IVF compared with patients having conventional IVF.

The World of IVF is Changing

For many years, European fertility centers have been using NC-IVF with success. In December, 2006, the “World’s First International Congress on NC-IVF” was held in London. Over 300 fertility doctors from over 55 countries attended. Sadly, only 3 American physicians attended (Dr. DiMattina was one of these). For many reasons, the availability of NC-IVF has been limited in the United States. We believe, however, that NC-IVF will soon become increasingly available as patients will demand less stressful and less costly fertility treatments that result in good pregnancy rates and outcomes without fertility drugs.

Furthermore, we believe that the success of IVF should be judged not by a single treatment of IVF to get the highest pregnancy rate at any cost. Rather, the success of IVF should be considered in the overall context of the entire IVF process to obtain a term, healthy, singleton pregnancy, with the least amount of patient discomfort, complications, and costs.

References:

• Phillips, SJ, et al, 2007, “Controlled natural cycle IVF: experience in a world of stimulation”, Repro Biol on line, 14, 356-359
• Nargund, et al, 2001, “Cumulative conception and live birth rates in natural (unstimulated) IVF cycles.” Human Repro, Jul; 17(7):1926
• Heijnen, et al, 2004, “What is the most relevant standard of success in assisted reproduction?” Human Repro, June; 19(9):1936
• Hojgaard, et al, 2001, “Friendly IVF: Patient Opinions.” Human Repro, Vol 16, No.7, 1396