If the primary goal of treatment is pregnancy with PCOS, the primary effort is to induce ovulation. Because PCOS is characterized by arrest of follicle maturation at preantral follicle stages, treatment has to push the eggs past this block. Two classes of oral fertility medications can induce ovulation: clomiphene citrate (Clomid), and aromatase inhibitors (Letrozole, with brand name Femara being the most widely used). Whether either of these drugs is preferable as first-line medication has remained controversial, and is currently under investigation in a number of multicenter clinical trials.
When these oral medications don’t work, ovulation needs to be induced with a class of injectable fertility drugs called gonadotropins. Gonadotropins are more potent, produce larger numbers of follicles and, therefore, pose higher risk of ovarian hyperstimulation syndrome (OHSS) and high-order multiple births.
Oral fertility medications can be used to induce ovulation in PCOS patients.
OHSS is the most serious maternal complication of ovarian stimulation, and the risk is especially high in PCOS patients. While a milder form of OHSS involving some minor discomfort from fluid collecting in the abdomen is much more common than a more severe form that involves severe abdominal pain and sometimes difficulty breathing, OHSS must be avoided at all cost.
When it comes to the complications in the offspring, high-order multiples is the most feared complication due to the associated risk of severe prematurity, which, in turn, is associated with severe neurological and other defects in newborns. High-order multiples should also be avoided in fertility treatments, not only for PCOS patients but for fertility patients in general.
CHR, therefore, rarely uses gonadotropins in PCOS patients who are undergoing intrauterine inseminations (IUI) or other forms of infertility treatments that do not allow physicians careful control. In contrast, in PCOS patients undergoing IVF, both complications can be greatly reduced by stimulating the ovaries carefully, puncturing all follicles including even very small ones at egg retrieval, aspirating their fluid, and controlling the number of embryos transferred. We have cautioned against using gonadotropins in established PCOS patients, and reported over 10 years ago in the journal New England Journal of Medicine that even with most careful medical supervision, high-order multiples are almost impossible to avoid in association with spontaneous intercourse and/or intrauterine inseminations (Gleicher et al., N Engl J Med 2000;343:2-7).
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Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned specialist in reproductive endocrinology, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.