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Fertility, IVF and Egg Donation
Ideal treatment of the poor responder for in vitro fertilization is problematic. Over time, I see more and more patients that have failed multiple IVF attempts at other clinics. The majority of these patients fit into the poor responder category.
Generally, the poor responders should be identified by the fertility doctors before starting an IVF cycle. At our fertility clinic we use ovarian reserve testing to evaluate a woman’s expected response to the stimulating medications. As our basic ovarian reserve screening, we do:
- Antral follicle counts by ultrasound
- Anti-mullerian hormone (AMH) blood tests
- Day 3 FSH, LH and estradiol blood tests
These tests will identify the vast majority of poor responders before they get to an IVF attempt. Identifying the problem in advance allows us an opportunity to do something to improve the response (and the outcome) with the first IVF attempt.
The definition of a poor responder is variable. Regardless of the definition one uses, the basic idea is that poor responders do not respond well to the IVF ovarian stimulation protocol by making a good number of mature follicles. Less mature follicles means less eggs retrieved which results in lower numbers of embryos and less chance to have one that is a “marathon runner” (baby).
For example, women under 35 years old give an average of 12 eggs with IVF. However, poor responders would only produce about 1 to 6 eggs. The chances for success with IVF are very much dependent on two variables – the quantity and the quality of the eggs.
Therefore, if we could come up with a treatment that would help the poor responders to give either more eggs or better quality eggs or both, we would be able to positively impact the chance of having a baby.
Various types of supplementation protocols have been used to try to improve outcomes for IVF poor responders. In this article I want to discuss the use of growth hormone for this purpose.
Growth hormone has been used for poor responders for many years. However due to the very high cost of growth hormone in the past it was rarely utilized. However, over the years with more competition in the pharmaceutical marketplace the cost of growth hormone has come down. During this same time frame, more studies have been published showing benefit from treatment with growth hormone for IVF low responders.
20 years ago, growth hormone treatment added about $5000 to the cost of IVF. That was too high. With the drop in the market price for growth hormone the cost has come down to about $1000 currently. This price change has made it more feasible and potentially a cost-effective addition to the IVF stimulation protocol.
Although all of the studies that have investigated this had small sample sizes, several of them showed significantly improved IVF success rates in poor responders that supplement their stimulation with growth hormone. For the most part, the studies all showed the same thing. Adding growth hormone to the ovarian stimulation protocol for poor responders significantly increases the chances for a pregnancy and a live birth.
The mechanism by which growth hormone would improve IVF success rates is not clear. However, based on animal and human studies it has been shown that growth hormone is involved in production of steroid hormones in the ovary and in development of ovarian follicles. Studies have shown that if mice are lacking the growth hormone receptor and growth hormone binding protein there is a significant reduction in the development of ovarian follicles.
It is also thought the growth hormone could increase the production of insulin-like growth factor 1 (IGF-1) in the ovaries. IGF-I is thought to be involved in regulating follicle development, estrogen hormone production and maturation of eggs.
Several studies have shown improved IVF live birth success rates after supplementation of growth hormone in poor responders. Although the success rates are still not as high as seen in normal responders to stimulation, they are significantly improved over the baseline success rates expected in poor responders.
For this reason, I have been using growth hormone supplementation for many of my poor responding IVF patients. Whether the additional cost of the growth hormone supplementation is worth it is a more difficult question.
Of course, if we knew that the growth hormone would get the patient to a successful pregnancy and a live birth – it would be a no-brainer. However, this is not magic and many women who use growth hormone supplementation will still have unsuccessful IVF attempts.
Some couples will move on to egg donation because of the high success rates with donor eggs instead of continuing to attempt low-yield IVF with their own eggs.
The most effective dosage and duration of growth hormone has not been clarified yet. The published studies have used:
- Doses between 4mg – 24mg, given daily or every other day
- Used it for the first several days of stimulation, or for the entire stimulation phase
Poor ovarian response to stimulation is a difficult problem without a perfect solution at this time. Supplementation with growth hormone is one way we can try to improve the odds for poor responders.
Larger randomized controlled trials are needed to figure out how much improvement in outcome we can expect by using growth hormone as well as which subgroups of patients could benefit the most.
Welcome to the
Richard Sherbahn, MD is a Board Certified Reproductive Endocrinology and Infertility specialist.
Dr. Sherbahn founded the Advanced Fertility Center of Chicago in 1997.
He will post regularly about fertility issues.
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- Advanced Fertility Center of Chicago
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