An individual patient's success in in-vitro fertilization (IVF) is tightly intertwined with her response to ovulation induction stimulation, say doctors at Cornell University in new research.1
What Predicts Patient Prognosis?
While age is a definite indicator of whether a woman will have better success with IVF or not, "patients who have a good response to controlled ovarian hyperstimulation (COH) have been found to have a better prognosis for IVF treatment," wrote lead investigator Melissa Yih, MD, in the Center for Reproductive Medicine and Infertility at Cornell, and her fellow researchers. "In this study, we attempted to define how ovarian response coupled with ovarian reserve can predict age-independent IVF outcome."
Unlike men, who are able to produce fresh, healthy sperm well into their later years, experts say women are born with all the eggs that they will ever have. In addition, some women carry poorer quality eggs. Thus, ovarian reserve screening is one way in which fertility specialists can predict the reproductive potential of a particular patient, as well as the potential of her eggs to result in a healthy pregnancy.2
Evaluating the Impact of COH Response
To assess whether the response to ovarian stimulation is a predictor of IVF success, independent of a woman's age, Yih's team retrospectively evaluated IVF outcomes performed in their fertility clinic between 1996 and 2000.
Patients were classified in the study as either having normal or poor ovarian reserve. The researchers defined abnormal ovarian reserve as those patients who had abnormally high follicle stimulating hormone (FSH) levels, which previous studies have suggested can be used as an indicator of such a condition.3
Women found to have normal ovarian reserve underwent standard IVF with a gonadotropin-releasing hormone (GnRH) agonist (Lupron/TAP Pharmaceuticals) until natural hormonal suppression was achieved. By contrast, those classified as having poor ovarian reserve began ovarian stimulation on the second day of their treatment cycle, and were placed on a flare-based, clomiphene citrate (Clomid, Aventis Pharmaceuticals) or no Lupron protocol.
A flare protocol involves the use of Lupron on day 2 of the cycle to stimulate release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), followed by FSH and LH suppression several days later as Lupron continues to be given. This allows doctors to take advantage of the initial "flare-up" response of these two hormones whose production prompts the release of eggs from the ovary. The idea is that Lupron will jump-start the follicles to producing more eggs to use in IVF.4
For all patients, ovarian stimulation involved the use of human menopausal gonadotropins (hMG) and/or FSH. When mature follicles were observed ultrasonographically, human chorionic gonadotropin (hCG) was given to prompt egg release. Later, eggs were retrieved for IVF.
After IVF, embryos deemed to be normal were transferred to each patient. The number of embryos transferred for pregnancy varied, depending on the woman's age.
Another Way to Predict IVF Success
Throughout the 4-year period analyzed, 4,862 cycles were performed, Yih and her group reported. While the age of a patient and her ovarian reserve significantly predicted whether she would be successful in IVF (younger patients and those deemed to have normal ovarian reserve had better success), the researchers also learned that a woman's response to ovarian stimulation was also a significant indicator of whether she would have a subsequently successful IVF-based pregnancy.
"A significantly higher number of embryos were transferred for patients with a higher ovarian response," the physicians wrote. "Additionally, ovarian response was associated with clinical pregnancy rate. This was more dramatically seen in patients with normal ovarian reserve."
Yih's team also found that those women who had a better response to ovarian stimulation also tended to have more successful embryo implantations after IVF transfer. "A significantly higher implantation rate was seen in women between 34-41 years of age who had a better ovarian response," they wrote. "Interestingly, younger patients with normal ovarian reserve still maintained very high implantation rates despite a poor ovarian response."
'Valuable Information' for Patients
In conclusion, Yih's group said their study shows that women who have more eggs retrieved after ovulation induction, indicating a more favorable response to the treatment, will more likely be more successful in IVF. And that's regardless of age and a woman's ovarian reserve, they noted.
For example, among women older than age 42 in their study, those who had at least 8 eggs retrieved versus those who produced no more than four had double the odds of a successful pregnancy, Yih and her colleagues pointed out.
"One way to explain our findings is that despite the fact that ovarian reserve and embryo quality decrease with advancing maternal age, if enough oocytes [eggs] are produced and hence embryos, the selection of embryos for transfer is improved, and allows for transfer of the best embryos back to the patient," they wrote. "This study provides valuable information when counseling patients regarding cycle response and expected pregnancy rates for future cycles."
Armed with that information, patients who have a poor response to controlled ovarian hyperstimulation can decide whether or not it is worthwhile to continue with their treatment cycle, they stated.
1. Yih MC, Spandorfer SD, Rosenwaks Z. Egg production predicts a doubling of in vitro fertilization pregnancy rates even within defined age and ovarian reserve categories. Fertil Steril 2005 Jan;83(1):24-29.
2. Institute for Reproductive Health. Cincinnati, OH. Ovarian Reserve Testing. Available at: http://www.cincinnatifertility.com/In_Vitro/Ovarian_Reserve.htm. Accessed January 18, 2005.
3. Toner JP, Philput CB, Jones GS, Muasher SJ. Basal follicle-stimulating hormone level is a better predictor of in vitro fertilization performance than age. Fertil Steril 1991;55:784-91.
4. Advanced Fertility Center of Chicago. Ovarian Stimulation for IVF. Available at: http://www.advancedfertility.com/ivfstim.htm. Accessed January 18, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
