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Improving the ovarian response in IVF

The poor responder to stimulation of the ovary, the aim of which is to produce a reasonable number of eggs for in-vitro fertilization (IVF), is one of the most frustrating problems in assisted reproductive technology. These ‘poor responders’ are mostly comprised of women at the older end of the fertile age group. They are often more than 40 years old and have examinations which reflect a low ovarian reserve of available eggs.

In general, for clinical problems, the greater the number of solutions that have been proposed to solve the problem, the less likely that a solution has been found. Such is the case for attempting to improve ovarian response. These include the use of very high doses of gonadotrophins and flare-up, stop and ultra-short protocols of GnRH agonists, the addition to the stimulation protocol of DHEA (dihydroepiandrosterone), growth hormone, LH, testosterone, letrozole and aspirin among others. None of these has been conclusively shown to help which is hardly surprising as it is impossible to stimulate eggs that are not there and female age cannot be lowered at this stage of our knowledge.

Although DHEA has been claimed to “make you younger”, evidence that it can improve ovarian response is still not convincing. A little more promising is the use of testosterone patches or letrozole tablets, both of which, at least, have some physiological basis in that they help the progression of development of egg-containing follicles. Growth hormone, LH or aspirin addition to stimulation protocols for poor responders have been uniformly unimpressive. The use of GnRH agonist or antagonist similarly make little difference in these patients although a ‘flare-up’ protocol using GnRH agonist is generally favoured.

In summary, this is a difficult area for reproductive practitioners. As poor response generally indicates a poor prognosis for pregnancy, tough decisions of when to stop treatment and offer egg donation have to be made. The fact that eggs donated from young women make an enormous difference in pregnancy rates to poor responders once again emphasises the importance of egg quality and female age to the infertile woman.

Amit Shah, Anil Gudi, Prof Homburg

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