Ovarian Hyperstimulation

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Hello Again to Everyone,

Today I am bringing to you the topic of Ovarian Hyperstimulation Syndrome (OHSS). Here you will read about the definition of OHSS, the causes and risks. You will see why OHS is what every good doctor strives to avoid, and of course, what every patient would like to avoid as well.

I would like to start by saying that you will read some things that may be frightening, because the most severe forms of OHSS can lead to significant medical problems. However, OHSS does not occur with great frequency and the severe forms are very rare. The next blog will review ways to lower the risks. In many cases it is preventable, although even when your doctor is very careful, OHSS can still occur.

OHSS occurs as a result of taking fertility drugs. These cause the ovaries to become larger than normal and to leak fluid. The more eggs that are produced in the cycle, the higher the risk of OHSS. The leaking fluid can cause significant abdominal swelling, and some of the fluid could make its way to the lungs. We will get back to these and other problems with OHSS in a bit.

OHSS, except for some very rare instances, can only be caused by fertility drugs. When we use infertility drugs, clomid or the injectables, we are hyperstimulating the ovaries. The goal of fertility treatment is to get the ovaries to make more eggs per month than usual. Sometimes we use the drugs to try to just make one egg, but usually we are going for more. In fact,therapy with any of these drugs is called Controlled Ovarian Hyperstimulation. Controlled is the key word. Therefore we expect all women receiving fertility drugs to have enlarged ovaries with the possibility of a small amount of fluid leaving the ovaries, and some cramping. When Controlled Ovarian Hyperstimulation becomes less controlled, OHSS can result.

The development of OHSS through the use of clomid is quite rare, but it has been known to occur. However,the injectables (examples are Follistim, Gonal-F, Menopur, Bravelle) pose much more of a threat. Clomid is a very different drug than the injectables. Clomid nudges along the normal ovulation process by getting the brain (actually the pituitary gland) to put out a little extra FSH. Because there is only so much FSH stored in the pituitary, usually 1-3 eggs will ovulate, as opposed to the one egg that ovulates when no drugs are used. For almost all women, this is not enough stimulation to cause OHSS. The injectables, on the other hand, are more powerful. They are FSH (sometimes with a bit of LH), and more FSH is delivered to the ovaries than in a natural cycle or with Clomid. The injections directly stimulate the ovaries to develop a larger number of eggs for ovulation. Because more eggs are produced, the injectables carry a higher risk of OHSS.

Who is at risk for OHSS? Women who are most likely to make a high number of eggs. The first and obvious group is younger women. For better or for worse, young women have more eggs, and develop more eggs for ovulation when given the injectables. Women with polycystic ovaries (PCO) are at higher risk for OHSS. This is because women with PCO have a very large number of eggs. These eggs are in follicles that have reached the stage just prior to entering the ovulation process. The fertility drugs can get many of these “almost ready” eggs to come up at once. And there are the exceptions, women who do not have risk factors, yet hyperstimulate when exposed to drug.

The severity of OHSS varies widely. Most textbooks divide the various degrees into mild, moderate and severe. Mild does not cause medical problems but may cause a woman to take notice of the changes in her body. In the mild form, the ovaries produce a few eggs and as a result have enlarged slightly. The ovaries have released some fluid, which the patient perceives as bloating. Cramping is mild. Many women have mild hyperstimulation, however they are not at all bothered by the symptoms and they go about business feeling no need to contact a physician for evaluation. The majority of women who take the injectable medications fall into this category. Some women with the same degree of mild hyperstimulation, are more bothered and concerned and may let us know that they do not feel well. Like many things in medicine, we can’t explain why 2 women with the same number of eggs and the same amount of fluid around the ovaries feel differently.

The two worse forms of OHSS are moderate and severe. In these cases, the problems are more complex than just large ovaries and a bit of fluid in the pelvis. In these cases, the OHSS can affect other areas of the body. Dehydration comes into play, and can be very problematic. This occurs as the ovaries leak larger amounts of fluid. The abdomen becomes noticeably distended. Women gain weight as the tummy accumulates more and more fluid. This probably doesn’t sound like dehydration to you, but it is. What’s happening is the leaking fluid comes from the blood which is circulating through the ovaries. As more fluid leaks out, less is fluid is in the blood and the blood becomes thicker, thus the dehydration. Not only does the blood lose water, but with the water flows sodium, so in the blood, sodium levels are low. Proper levels of sodium are necessary for normal function of the brain.

As the blood becomes more concentrated, levels of clotting factors increase. Clotting factors are proteins that are necessary for us to prevent excessive bleeding when injured; they make the blood clot. If the levels of these proteins get too high, the blood will be more likely to clot without any injury. For instance, clots can occur spontaneously in the legs, arms,neck and lungs. The worse the OHSS, the greater the risk if blood clotting.

OHSS can have a big effect on the kidneys. As the dehydration progresses, the overall volume of the blood decreases. Good blood volume is necessary for the normal kidney function of cleaning the blood. Decreased blood volume means that less blood is getting to the kidneys, and therefore the kidneys have trouble doing their job. The blood cannot be cleared of its waste, which is bad for the body.

OHSS has an effect on the lungs. The sheer volume of fluid in the abdomen can make breathing a problem for a couple of reasons. The first has to do with the pressure that builds in the chest as the abdomen fills. We’ve all heard that we breathe with our diaphragm, which is true statement. The abdominal fluid pushes up putting pressure on the diaphragm, making it harder to freely breathe in and out. The second problem has to do with fluid getting into the lungs. When the abdomen gets packed with fluid, it can squeeze through the diaphragm, into the spaces around the lungs. A small amount of fluid around the lungs is tolerable, but larger amounts make it harder to breathe and can cause chest pain.

If you have never taken these drugs, I do not want this blog to discourage you from taking the medicine you may need. If you have any concerns, talk to your doctor about the possible side effects and complications of these medications.
Next time we will discuss ways to prevent and treat OHSS.

Thanks for reading and don’t forget disclaimer 5.17.06.

Dr. Licciardi

References:

  • Ovarian hyperstimulation syndrome. Practice Committee of American Society for Reproductive Medicine. Fertil Steril. 2008 Nov;90(5 Suppl):S188-93.
  • Grossman LC, Michalakis KG, Browne H, Payson MD, Segars JH. The pathophysiology of ovarian hyperstimulation syndrome: an unrecognized compartment syndrome. Fertil Steril. 2010 Sep;94(4):1392-8.
  • Mullin CM, Fino ME, Reh A, Grifo JA, Licciardi F. Symptomatic isolated pleural effusion as an atypical presentation of ovarian hyperstimulation syndrome. Case Rep Obstet Gynecol. 2011; 2011:967849.

17 responses to “Ovarian Hyperstimulation”

  1. Interesting article. I had moderate OHSS after producing 28 eggs. My clinic has a policy of freezing if more than 20 eggs are retrieved. I had a major craving for salty food while suffering from OHSS (maybe due to lack of sodium??) I couldn’t get any water into me as I felt sick all the time – ended up on a drip due to dehydration.

  2. Cherbear says:

    This is a great post. I enjoy ALL your posts but this one is definitely something to keep in mind, with IVF #2 coming up.

  3. wheelchairs says:

    Superb blog post, I have book marked this internet site so ideally I’ll see much more on this subject in the foreseeable future!
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  4. Anonymous says:

    Dr. L, I was wondering if you can comment on DHEA for poor ovarian response candidates. I’m currently 35 and have normal FSH of 5.5 but a low antral follie count on day 3 of only 6 AFC total last cycle. Do you think DHEA can help me increase the antral follicle count number and egg quality?

  5. Mummy says:

    Thanks for a very interesting blog entry.

    I (age 39, 1 child from previous relationship) have been through 2 rounds of hormonal stimulation.

    On both counts, follicle count were about 5-7 in each ovary but at retrieval, I ended up with 23 and 29 eggs respectively (making the last egg count at retrieval a record at the clinic treating us). Of the last batch, 13 were successfully fertilised. I had one fresh egg transferred while OHSS but unsuccessfully. 14 days ago, 2 eggs were transferred in own menstrual cycle without any hormonal stimulation. (I’m waiting to take the pregnancy test in 2 days time).

    My symptoms were as you described, swollen abdomen (ironically making me look 4 months pregnant – my consultant said my ovaries were the size of oranges), with fluid pressing against my lungs making me short of breath and giving me sharp chest pains. Some nights I could hardly sleep due to chest pain. The symptoms disappeared after 7-8 days.

  6. endogirl says:

    Interesting information on OHSS, thanks for sharing. I just had my first IVF cycle canceled for the opposite reason. I was told by my RE that he was worried I would be more at risk for OHSS and so I was put on the long Lupron protocol and started on low doses of Bravelle and Menopur at 150 each. After CD 4 E2 of 75 I was upped to 225 each. My antral follicle count was 7-8. IVF cycle was canceled CD 7 when only two good follicles were shown. I am 30. My FSH six months ago was 11 and E2 was 52. Last month my FSH was 7 with E2 of 96. Is it worth me trying another IVF cycle? Or am I already screwed with the high FSH? (My RE never said anything about the level other than it was a little bit high and did not explain what that meant) I have mild endometriosis. I did five medicated cycles prior, 3 with Clomid 50mg and 2 with Femara (lowest dose). Each of those cycles I had 3-5 good follicles. Guess I’m still confused as to what happened with my IVF cycle?! Was my RE right in being concerned about OHSS?

  7. ERINToBe says:

    Can you talk about the difference between Natural Frozen Embryo Transfer and Medicated Frozen Embryo Transfer. Is one success rate better than another? My cycle has been regular for 3 years execpt for one month before starting my second fresh IVF when I ovulated 10 days late. I am 34 and have unexplained infertility as all tests are normal.

  8. Anonymous says:

    Thank you so much, Dr. Licciardi, you are doing a great service to the public. Your explanations are crystal clear, yet you never patronise us or make us feel stupid. I wish all doctors could read your blog and learn what a good answer is to a patient’s questions. Thank you so much.

  9. Anonymous says:

    I have done three fresh ivf’s and 5 fets all three times I produced over 24 eggs. I have reg cycles so apparently don’t have pcos. I usually produce high quality blasts and have frozens. I have transferred 20 blasts now and I have one pregnancy and one son. I have six left to transfer. If these fail should I give up on trying for a sibling, I am almost 41 . I feel like this is abnormal and there must be something wrong genetically with the embryos…your opinion? Is it possible the high numbers yield poor quality despite looking good? Is there anything more my clinic could do, I have never changed and wonder now if there is any point.

  10. Francisca says:

    This is a great blog. I am seeing answers for many of my questions. I am 35 and suffering from secondary infertility (timed intercourse for 15 cycles). My first pregnancy was conceived in only 3 months, 3 years ago. The doctors are making me wait and keep trying on my own, because they think secondary infertility is very rare. The thing is since birth my cycles were never the same as before. They became irregular (24-34 days, always 30 days before), I stopped feeling ovulation pain, and I have mid-cycle spotting (can last several days) and pre-menstrual spotting (never had those before), and my luteal phase went from 14 to 12 days. Besides, my libido became very low, I have mood swings and sometimes night sweats. I was convinced I was menopausal, but my FSH levels came back 7 and 9. My husband’s sperm are perfect. My question is, should I stop trying to find out what is wrong and go for an IVF, or are there any more tests or treatments I could do (besides day 3 hormones and hsg)?

  11. Samual says:

    This comment has been removed by the author.

  12. Laura says:

    Thanks for this wonderful blog post. I just started clomid and was terribly worried about OHSS, but now after reading this I feel much better about taking it as I know the risk is low.

  13. Anonymous says:

    I am 37 and was just hospitalized after my egg retrieval. I have had most of the symptoms of moderate OHSS but the consultant said it couldnt be OHSS because I only had 9 eggs removed. Could you please confirm whether OHSS is possible? I had a CT scan which showed significant build up of blood and fluid in abdomen, vomiting, distended abdomen, pain, dehydration, sodium and potassium deficiency, low WBC count…

  14. Philip says:

    Its really a good one.thanks for sharing.
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  17. binksmommy says:

    If I got OHSS once while on clomid will I definitely get it the next time??

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