Older women seeking motherhood, but who face 'ovarian aging', defined as poor ovarian reserve, high follicle stimulating hormone (FSH) and estrogen levels, and low levels of inhibin B (a hormone that suppresses FSH production) may be able to undergo a type of in vitro fertilization (IVF) approach that incorporates the use of seminatural cycles. So says a new study published this month in the journal Fertility and Sterility.1
Natural-Cycle IVF is Not a New Concept
When IVF was first used in the late 1970s, it was not uncommon to perform the method using natural cycles, wrote Rene Frydman, MD, in the department of Obstetrics and Gynecology and Reproductive Medicine at Hopital Antoine Beclere in Clarmart, France, and her associates.
This method was later replaced with controlled ovarian hyperstimulation (COH), in which fertility medications are used to induce ovulation. This not only allows for more control over ovulation, but allows your doctor to collect more eggs by "rescuing" follicles (fluid-filled sacs inside the ovaries that contain the eggs) that would otherwise degenerate. Prior to ovulation, only one of several follicles in the ovaries actually grows to a mature level in which it can release an egg. The rest, while growing together initially, eventually stop.
Controlled Stimulation Outcomes Vary
COH is successful with some women undergoing fertility treatment, but not with others, however. "Unfortunately, poor response to COH due to ovarian status defects is not rare," wrote the researchers. "It represents from 9% to 24% cancellation rate in IVF-ET [embryo transfer] cycles."
Thus, to increase the odds of success for these women, some medical experts have suggested reverting back to the use of natural cycles in IVF. Nonetheless, to maintain some control over the timing of ovulation, Frydman and her team have proposed using semi-natural cycles in IVF. This involves the use of natural cycles combined with fertility drugs.
Do Seminatural Cycles Improve the Odds?
This study, therefore, was an attempt to determine whether patients who undergo this approach because of poor ovarian response have better success than they would otherwise.
Frydman's group studied the outcomes of 75 women at their hospital who underwent IVF between 2001 and 2004. These women had either low ovarian reserve or poor ovarian response to COH.
Each patient underwent semi-natural ovulation induction by allowing follicular growth to occur naturally. When the dominant follicle reached a certain size, doctors had given each of the patients a gonadotropin-releasing hormone (GnRH) antagonist, a medication that prevents the premature hormone surges that trigger ovulation, in order to allow for a more controlled environment.2
Women also received doses of human menopausal gonadotropin (hMG), a hormone that induces the ovulation of more than one egg.3 This was followed by the use of human chorionic gonadotropins (hCG), hormonal drugs that also trigger ovulation.3
In all, more than 150 cycles were performed involving these patients. About 20 percent of those classified as having low ovarian reserve had cancelled cycles compared to about 14 percent of those with poor ovarian response, the study team found. In all, 28 cycles had to be cancelled, either because of a luteinizing hormone (LH) surge or because of inadequate follicle growth.
A total of 94 eggs were collected for in vitro fertilization, though intracytoplasmic sperm injection (ICSI) was performed in 50 instances, according to Frydman and her colleagues. About 80% of the eggs that underwent either IVF or ICSI were successfully fertilized. Sixty-seven resulting embryos were transferred for pregnancy, and 28% of the cases resulted in a healthy pregnancy. However, among those who underwent all three cycles offered by the hospital, the pregnancy rate jumped to approximately 35%. Five of those patients had miscarriages.
'Reasonable' Option
In conclusion, Frydman and her colleagues believe that the use of semi-natural cycles in IVF approaches are "reasonable" for those with low ovarian reserve or poor ovarian response. While other treatment alternatives have been advocated for these women—for example, the use of very high-dose gonadotropins, or combining standard ovulation induction with growth hormone, low-dose dexamethasone, aromatase inhibitors, or low-dose aspirin—they all have their shortcomings, the authors explained.
Still, Frydman's group says the higher number of cycle cancellations seen in this study was "unexpected", and attributes it to inadequate ovulatory function. As such, semi-natural cycle success is highly dependent on the development of a mature follicle that can properly release an egg, they write.
On the upside, however, the researchers stress that the use of semi-natural cycles offer several advantages, including the ability to execute the approach in consecutive cycles, its lower cost, simpler approach for both clinicians and patients, and reduced stress for patients.
"The use of IVF with a seminatural cycle protocol is a valuable alternative to controlled ovarian hyperstimulation in poor responders," they wrote. "This alternative should be considered in patients who require IVF and demonstrate endocrinologic evidence of ovarian aging, and those who have had one or two cancelled COH cycles."
1. Castelo Branco A, Achour-Frydman N, Kadoch J, Fanchin R, Tachdjian G, Frydman R. In vitro fertilization and embryo transfer in seminatural cycles for patients with ovarian aging. Fertil Steril 2005 Oct;84(4):875-80.
2. The Merck Manual. Endometriosis. Available at: http://www.merck.com/mmhe/sec22/ch245/ch245a.html?qt=gnrh%20antagonists&alt=sh. Accessed October 20, 2005.
3. Sher Institutes For Reproductive Medicine. Glossary. Available at: http://www.haveababy.com/learn/glossary.asp?glossary=h&site=. Accessed October 20, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
