2004 Newsletter - Page Four Of Four
Mark P. Trolice, M.D., FACOG, FACS
Milton McNichol, M.D, FACOG
Board Certified in Reproductive Endocrinology and Infertility
The Case for Classical Ovulation Induction
Before assisted reproduction technology became widely used, standard treatment of normogonadotrophic anovulatory women consisted of inducing ovulation with clomiphene citrate followed by injection of follicle-stimulating hormone (FSH). Because this is a time-consuming approach and associated with a high rate of complications, first-line treatment for infertile women, regardless of the cause, has increasingly become "controlled" ovulation combined with intrauterine insemination (IUI) or in vitro fertilization (IVF).
van Santbrink and Fauser from Erasmus Medical Center, the Netherlands, argue that there is no sound scientific basis for this change in treatment strategy, which will likely lead to higher rates of multiple pregnancy and higher costs.
A prospective study of 240 patients who were treated by the classic approach (initial treatment with clomiphene citrate followed by FSH for those who failed to conceive) showed a cumulative singleton live birth rate of 71%. Such results can be improved by use of new gonadotrophin preparations, alternative dose regimens, more individualized treatment approaches and prediction models (i.e., identification of patient characteristics that may be able to predict the outcome of treatment).
"Step-up" treatment regimens that start with low doses of FSH and increase the dosage in small increments are now commonly used and are associated with fewer complications. More recently, a "step-down" strategy, reducing the dose of FSH administered during follicular development, has also proved reliable. Ovarian hyperstimulation syndrome (OHSS) is a particular danger for women treated with FSH, particularly when the initial dose is high. Because OHSS is associated with multiple follicle growth and multiple pregnancy, a model has been developed that includes measuring serum androstenedione, the ovarian response to clomiphene citrate and the number of antral follicles on initial screening.
Studies of this model have confirmed that women who are good responders to the initial FSH dose do not require any increased dosage for follicular development. On the other hand, for women who are not good responders, a higher initial dose might be given, avoiding the time-consuming step-up regimen.
Conclusions and Clinical Implications
The classical treatment strategy of ovulation induction with clomiphene citrate followed by FSH is highly effective, although there is room for improvement. New drugs and prediction models should lead to a more individually tailored approach in the future. More research to this end is needed before patients are referred prematurely for IVF; it is questionable if the latter, with or without in vitro maturation of oocytes, is any safer or more effective than ovulation induction strategies.
van Santbrink EJP, Fauser BCJM. Is there a future for ovulation induction in the current era of assisted reproduction? Human Reprod 2003;18:2499-2502.
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