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Hello Again,

 

Today we will continue our discussion of ovarian hyperstimulation syndrome (OHSS). We will review ways to minimize its occurrence and eventually get to the best ways to treat the symptoms. As we said last time, OHSS can occur in women undergoing fertility drug use for IUI or IVF.

I will start by saying that OHSS is not preventable in every case. Even with the best intentions of proper medical care and a focus on patient safety, OHSS can occur. Some of you reading this may have had OHSS and are concerned that your difficulties may have been preventable. While this may be true for some, for others the outcome was unexpected.

I am providing general information about this topic; therefore my experiences and protocols cannot take the place of the medical advice provided by your personal physician.

The first step in preventing OHSS is to use the lowest dose of medication that is expected to give a reasonable response.

The good news is that I believe that the incidence of OHSS has been decreasing. One reason is that doctors understand the value of using lower doses of medication. We are more aware of the problems associated with multiple gestations, and try to reduce follicle number to reduce multiples. We are also more cognizant of the problems and risks of OHSS, and are working harder to avoid it.

My goal in an iui cycle using FSH is to stimulate the ovaries to produce about 3-5 follicles. Other physicians have similar goals, but others may give higher doses of drugs to obtain more eggs. I typically use doses of 75, 100 or 150 units for my iui cycles, meaning I am not afraid to start a suspected good responder on a very low dose of drug. Worst case scenario, the response is lower than expected and we need to perform another cycle with a higher dose.

The same principals apply on the IVF side. Women do not need 25 eggs to become pregnant with IVF. Poor responders or women near and over 40 may need more drug, but in this group, even more drug is less likely to cause OHSS. Women in their mid 30’s or younger, with normal FSH levels and good antral follicle counts, should be given lower doses of medication. In this group, and again, these are my personal protocols, 225 units is the highest amount of drug I use, unless there is a history of a poor response. In women with a large amount of resting follicles, the starting dose may be 150-200 units. Body size also comes into play, with small women getting lower doses. I do give 225 usually to donors, because it’s hard to take a chance on low egg production, and donors will not get pregnant from the cycle, and not being pregnant diminishes the symptoms of OHSS.

All of this being said, there are women who escape the vigilance, and over-respond to low doses of medication. This brings us to the next step in preventing OHSS. When a woman has more eggs than desired for an iui cycle, the number one option is stopping or cancelling the cycle. Cancelling and withholding the hCG injection prevents OHSS from even starting. hCG stimulates ovulation, but it has a long life in the body and the prolonged exposure to hCG causes the follicles to continue to grow and make the hormones that contribute to OHSS.

A second option, used less frequently, is to continue with the meds, and hCG, but converting the iui cycle to an IVF cycle. This is sometimes difficult because a patient may not be mentally prepared to jump from iui to IVF. Additionally, IVF is a much more costly option, and even if insurance will cover IVF, the last minute change may by problematic for pre-approvals etc. I typically do not like converting, because while the number of eggs present may be too many for an iui cycle, there may be fewer than desired for an IVF cycle.

Why would converting from an IUI cycle to an IVF cycle reduce the risk of OHSS? Certainly many women hyperstimulate with IVF, but the risks are greater with iui for a couple of reasons. First, during IVF, a needle is placed into each follicle, removing the egg and some granulosa cells, which are the estrogen producing cells of the ovary. So disturbing the follicle lowers its estrogen-producing capabilities thus lowering the risk of OHSS. In addition, with IVF we can control the number of embryos reaching the uterus. Pregnancy makes OHSS worse, and the more fetuses, the more risk. If there are too many follicles in an iui cycle, the odds of twins or more increases, increasing the OHSS risk.

How do we reduce the OHSS risk in an IVF cycle? Choosing the correct dose of drug is the first step. Not giving hCG could be an option, but again this cancels the cycle. Another option is to give hCG a little early, by 1-2 days. When taking fertility injections a woman’s estrogen level rises every day until she gets hCG. So if she gets her hCG a little early, there is less time for the estrogen levels to become higher than desired. This may translate into more immature eggs, but usually women who hyperstimulate have >15-20 eggs, leaving room for some of them to be immature.

Lowering the dose of hCG is commonly done for women at risk. However, the literature does not convincingly support this strategy as effective.

Having the retrieval, but cancelling the transfer is another way to lower the risk of OHSS. Here the embryos are frozen, and thawed 1-2 months later, after the ovaries are no longer over stimulated. This works well, and pregnancy rates are very good in these cases. One potential problem here is that OHSS can still be moderate to severe even in the case of no immediate pregnancy, however in almost all cases, the symptoms are less than if pregnancy had been initiated. For instance, egg donors who do not become pregnant during their ivf cycle, sometimes develop significant hyperstimulation, however their condition resolves in a predictable way.

Transferring fewer embryos and reducing multiples is thought to reduce the risk of OHSS. Since most women who are at risk are younger, an acceptable pregnancy rate can still be achieved by transferring only one embryo.

Next time we will discuss a new alternative method to prevent OHSS, and talk a little about treatment.

Thanks for reading and please read disclaimer 5/17/06.

Dr. Licciardi

References:

  • Humaidan P, Quartarolo J, Papanikolaou EG. Preventing ovarian hyperstimulation syndrome: guidance for the clinician. Fertil Steril. 2010 Jul;94(2):389-400.
  • Nastri CO, Ferriani RA, Rocha IA, Martins WP. Ovarian hyperstimulation syndrome: pathophysiology and prevention. J Assist Reprod Genet. 2010 Feb;27(2-3):121-8.
  • Tang H, Hunter T, Hu Y, Zhai SD, Sheng X, Hart RJ. Cabergoline for preventing ovarian hyperstimulation syndrome. Cochrane Database Syst Rev. 2012 Feb 15; 2:CD008605.
  • Aboulghar M. Symposium: Update on prediction and management of OHSS. Prevention of OHSS. Reprod Biomed Online. 2009 Jul;19(1):33-42.