More IVF questions

Q: How many eggs do you retrieve in an IVF cycle?

A: As many as develop. We're happy if we get a dozen. We won't do the egg retrieval if we think we'll get only one or two.

The maximum number of eggs in the human ovaries is found at 20 weeks of intrauterine life. For reasons that remain unclear, some of the eggs atrophy, so that by birth only 1 to 2 million eggs remain. These primordial follicles (remember that a follicle is a cyst with an egg inside) remain in a state of suspended animation, but every day some of the follicles begin to develop, or mature. This maturation process is thought to take as long as one year, and once it begins, there is no going back – the follicle either winds up releasing the egg at the time of ovulation, or it stops developing and atrophies along the way. The mechanism regulating this process of follicular recruitment from the pool of primordial follicles is the “terra incognita” of reproductive physiology – if you figure it out, please let me know. We will quit our jobs and make some big money! Think of the possibilities if we could develop a pill that could stop this recruitment process. Not only would it be a very effective contraceptive, but we could postpone menopause indefinitely!

But I digress. At the very end of this maturation process, the developing follicles must see follicle stimulating hormone (FSH) for maturation to continue. At the start of the spontaneous menstrual cycle, one of the developing follicles gets ahead of the others and does something very sneaky – it revs up its cellular machinery to become more sensitive to FSH while sending a hormonal signal to the pituitary gland to decrease FSH production. (There are actually two hormonal signals that do this: estradiol and inhibin.) Thus, the dominant follicle continues to develop while its siblings starve from lack of FSH, and out of the many follicles that began to develop, only one completely matures to ovulate.

So, what can you do if you want more eggs to complete this maturation process? Simple, just give the woman FSH at the start of her menstrual cycle, subverting this process of follicle selection and dominance. This is why IVF patients take FSH injections (many IVF programs give luteinizing hormone (LH) as well, since LH also plays a role in follicle maturation). We typically retrieve about a dozen eggs in an IVF cycle, and sometimes many more (I think my personal record is 80 or so, but this isn't a record to be proud of, as women with too many eggs developing can get sick from ovarian hyperstimulation, and sometimes the quality of the eggs obtained isn't so good). If we see only one or two mature follicles, we will cancel the IVF cycle and treat the woman with a higher FSH dose in a subsequent cycle.

But sometimes even higher FSH doses don't result in more follicles developing. After all, FSH only rescues eggs that would have been lost before ovulation, and if only a few follicles are developing, there aren't many to rescue. As women get older, the number of follicles maturing at any one time declines until no follicles are left, and this process of follicle depletion occurs at different rates among women. Sometimes the reason for running out of eggs prematurely is obvious. Cancer chemotherapy, radiation treatment, and cigarette smoking can do it, as can ovarian surgery (like removing an ovarian cyst). Many times, though, there is no clear reason. I think some cases of unexplained infertility are due to accelerated follicular atresia, as the last eggs to mature seem to work the worst (although this concept is much debated among fertility specialists).

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