New Hope for Hyperstim...Curing the OHSS Woes (Part 1: Lupron Trigger).

I have been writing this blog for a couple of years now. Year in and year out the most popular post has been my discussion of OHSS (see the OHSS Woes). Hundreds of comments have been posted with some pretty scary stories of OHSS. Well, there will always be some risk of OHSS in patients who take fertility drugs but some recent advances may markedly reduce the risk. So here are some details about some new ways to manage OHSS that you may want to discuss with your RE....

#1. Lupron trigger
All egg collections must be timed so that the egg within the follicle is ready to ovulate but the procedure is scheduled before that occurs. Traditional timing of egg collection is 34-36 hours after an HCG injection. HCG is very similar to the LH hormone produced by the pituitary (master gland in the brain) and fools the follicle into thinking (if follicles could think) that it is time for the egg to pack its bags and get ready to pop out. The problem is that HCG hangs around for over a week whereas the LH that the brain releases is gone within hours. It is this prolonged HCG exposure that drives the OHSS bus. Similarly this explains why pregnancy makes OHSS so much worse...the developing placenta makes HCG constantly increasing the production from the ovary of the proteins that lead to OHSS symptoms.

So we need HCG in order to do the egg collection and actually get eggs out of the follicles but we really want the HCG to go away quicker to prevent OHSS. Some of us use 5000 IU of HCG to try and avoid OHSS, but the truth of the matter is that all my severe OHSS patients have gotten 5000 IU instead of 10,000 IU so clearly this is not all that effective...

However, some fertility clinics (including ours) are now using Lupron to trigger patients for egg collection. Lupron will cause the patient's pituitary glad to release the LH that is in storage and that LH is usually sufficient to get the eggs ready to be retrieved. The LH then drops precipitously and the risk of OHSS is very close to zero! Wow! What a great option....BUT...

Unfortunately, there is always a "but."

First of all, you can't use Lupron trigger in patients who have been on Lupron for their stim...no MDL flare patient, no Luteal Lupron protocol patients.

Secondly, the estrogen levels with Lupron trigger fall FAST. I mean really fast. This rapid drop in estrogen levels is good for OHSS prevention. It is not so good for implantation. DrD attended the Santa Barbara IVF meeting this summer and came back enthusiastic about Lupron trigger but he noted that although the rate of OHSS is nearly zero, the present recommendation is to freeze all the embryos and save them for an FET cycle because most REs believe that the implantation rate in a Lupron trigger fresh cycle is much lower than expected.

Thirdly, in patients with insurance coverage for IVF this may be problematic as the insurance could count this as 2 separate IVF attempts (one fresh and one FET...even though no fresh ET was ever planned)....Ugh. Nothing is ever simple.

So how do we like Lupron trigger? Well, I have had some very nice success rates with FET cycles with Lupron trigger but our experience seemed consistent with that of other clinics when it came to fresh ET with Lupron trigger. Some patients with really difficult stims (PCOS, AMH level off the wall, history of canceled cycles with estrogen levels >10,000 pg/mL) have made it through egg collection without an issue and their estrogen levels fall really fast and they have very little symptoms of OHSS. I believe this represents the future of IVF stimulations but there remain some unanswered questions....

Next post: New Hope for Hyperstim...Curing the OHSS Woes (Part 2: GnRH-antagonist Rescue).

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Goodbye Summer...Hello Autumn!

Goodbye Summer…

Growing up in New England you get used to summer lasting only a few weeks. Of course, here in DC it seems like summer lasts a lot longer as temperatures can be in the 90s in April…. However, in Boston the weather in Spring may not be very Spring-like as I remember a snowstorm one year in June!

The end of summer is always sad to me. In June it seemed like there were an almost infinite number of possibilities for the coming season….then by September you are faced with all the fantastic activities that you failed to pursue. This summer was pretty good. There was the obligatory "honey-do" list which including clearing out closets of junk ("What do you mean I should throw out my high school soccer jacket?!?) but I did learn to wakeboard ("Wow Dad you look pretty good for a fat, hairy, balding, old guy!")…

The Bob Seger song "Night Moves" sums up my view of the end of summer:

I woke last night to the sound of thunder
How far off I sat and wondered
Started humming a song from 1962
Ain't it funny how the night moves
When you just don't seem to have as much to lose
Strange how the night moves
With autumn closing in

But as we say goodbye to the heat and humidity I guess that Fall has some positive aspects to it as well. Just gotta get over the things that we didn't get to this summer and move on.

I have spent a lot of time going through the 35 mm slides that I rescued from my parents' home following my Mom's death in May. My Dad really had no place to store them and I was appointed keeper of the family memorabilia. The amazing thing about those images is that there are slides of me and my brothers and parents that I have never seen before….In today's digital world where we have instant access to thousands of photos on our iPhones, it is hard to remember what it was like to have a box of slides that contained unknown images from the past. Opening each box of slides is like an archeological expedition. Some trigger sharp memories and other register complete blanks with me.

I love this photo of me and my best friend Karma. She was an excellent dog. Rescued by my Dad (after a lot of pleading) from Camp Cody in New Hampshire she was my buddy. This photo reminds me that Fall isn't so bad after all...


What does any of this have to do with IVF and infertility? Well, not a lot I guess except that for many of our patients their view of their fertile years may be initially like my view of summer from the perspective of June. Then suddenly the years flash by and autumn seems to be closing in. But there can be good days in autumn….with or without your canine companion.

This past week I met up with a couple that had been through a lot including a tough mid trimester loss. We discussed issues of diminished ovarian reserve, and age-related aneuploidy (chromosome abnormalities). I spent some time discussing Natural Cycle IVF. Ultimately, they politely stopped me and told me that they were really more interested in hearing about donor egg IVF. They had moved beyond Summer and were prepared to embrace and love Fall. Patients are always a doctor's best teachers…

P.S. My Brother Steve is still kicking my butt in terms of Mom's Scholarship Fund.....

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Free Advice is Worth What You Pay for It....

Recently my older brother Steven and I were having a discussion about the Internet and this Blog in particular. He wondered why I spent so much time and effort responding to posts from patients all over the country and the world whom I would never meet face to face. In addition, we discussed the fact that I often referenced Mom and Dad in my posts and shared my grief over her final illness and passing at the end of May.

Honestly, the whole blog thing is out of character for me. In fact, I am a rather introverted person. I do not do well at cocktail parties and have a real problem putting names and faces together...although I pretty much have my kids down pat at this point...more or less. Yet my profession requires me to delve into the most intimate of details when working with a couple. Few issues are as difficult to discuss as those concerning reproduction and family building. Money is another one and as many of our treatments are not covered by insurance, money enters into the decision making as well!

As a 3rd generation physician I have an old-fashioned view of the doctor-patient relationship. I remember asking my Dad one time, as we drove past the Hollow restaurant on Adams Street in Quincy, MA, why we never ate there. He said that it was hard to go there because so many of his patients worked there, ate there or hung out there. I persisted and finally he agreed to take my Mom and me to dinner at the Hollow. It was like seeing the paparazzi descend on Leonardo DiCaprio! I think that he ate only about half of his meal because so many people came over to say "hi" and thank him for being such a great surgeon. That dinner made a real impression on me at the time. To this day my Dad views his identity as physician first and everything else second. Although I have attempted to develop a more balanced identity, I will admit that being a physician is very important as part of my worldview.

So why do I persist in answering post after post on this blog. And why do I drag myself over to Fairfax Hospital early in the morning to lecture to the students and residents. Well, I have always viewed teaching as being a big component of my job as a physician. As DrD states "I teach because someone taught me." As above, I lecture every week to the medical students and residents. I have served as a preceptor for Princeton pre-med students and every summer I have been a speaker at the National Youth Leadership Forum on Medicine (an organization that encourages high achieving high school students to explore medicine as a career). So I use this blog as means to teach and to educate the 12 people who read this blog regularly. Along the way I try to give some insight into how I think and practice. Sometimes I share some personal history as part of a quid pro quo...."Hi I am Dr. Gordon. How often do you two have sex?" Yikes. What a crazy way to make a living...

So back to my brother Steve. We are very competitive. So competitive that we rarely play one on one games anymore. Plus I hate to beat an old guy. In any case, he was very proud of all the contributions that had been made to the Tufts Medical School Scholarship Fund in memory of my Mom by his professional associates. In particular he said "so where are your internet buddies now?"

Dear Readers, I have never asked for anything from you...until now. If you have found any part of the hundreds of posts on this blog and my answers to questions helpful then please consider a nominal $5 gift to the Tufts Medical School Scholarship Fund in honor of my Mom (Claire Braverman Gordon). Contributions are totally voluntary and I will continue to answer all questions to the best of my ability..but I really hate to lose to my big brother...

Claire Braverman Gordon Memorial Scholarship Fund
Tufts University School of Medicine
Office of Development & Alumni Relations
136 Harrison Ave.
Boston, MA 02111

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It only takes one...

Although we strive for multiple embryos in stimulated IVF, sometimes we loose track of the concept that it really takes just a single embryo to make a baby. I have a current patient who went through IVF with PGS (preimplantation genetic screening) and had multiple grade AAA blastocysts for embryo biopsy on day 5. Interestingly, only a single embryo of all these normal looking blasts was genetically normal. We transferred that single embryo and now she has an ongoing pregnancy. Would we have found that single normal embryo eventually? Yes. Would the patient have become emotionally drained, frustrated and financially strapped by the repeated transfers... Possibly...

So as we revise our approach to stimulated IVF, PGS may become more and more common. In the end, it still just takes a single good embryo to make a baby. Does Natural Cycle IVF create a higher percentage of normal embryos compared with stimulated IVF? We don't really know but this could explain the higher implantation rate that we see in NC IVF....

Last weekend I was in Boston cleaning out my parent's home as my Dad prepared to move into an apartment. I ended up with a minivan full of thousands and thousands of slides. Many of these were photos of yours truly that I had never seen. (These photos would serve to undercut my brother Steve's assertion that I was found in the gutter one night and raised in my parents' home under the mistaken impression that I was actually a Gordon born and bred....).

The photo on the right is me with my dog Karma. Although not evident in the photo, Karma was actually missing her right front leg which was amputated after she was struck by a car early in her life. She lived to be about 13 years old and it never slowed her down. In her case it took only 3 legs to live a full and happy life and in your case remember it only takes a single good embryo!

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Crazy Twin Stories #2

Here is another one that leaves you scratching your head....

RL is a 32 year old fertility patient who had failed to conceive with less invasive therapies and elected to pursue stimulated IVF. At the time of egg collection we anticipated around 12 eggs but only got 4 eggs plus a couple of empty zona (egg shell only with no egg inside). From those 4 eggs we ended up with only a single embryo. However, it was a beautiful blastocyst and we had high hopes for success in spite of the relative inefficiency of the cycle...In fact, she did conceive and her betas were very high....really high.

At the first ultrasound visit I saw two sacs. At the next visit both sacs had embryos with heartbeats. I was very concerned about her ability to carry twins but she and her husband were ecstatic. She had an uneventful pregnancy and delivered at 38 weeks. Both babies were healthy and went home with Mom after delivery. So what, the informed reader may declare...another case of identical twins...ho hum. Yes indeed....except that the babies were a boy and a girl...clearly not identical.

So the explanation is that her fallopian tubes did catch at least one egg that we failed to retrieve and they had sex prior to retrieval and voila....bonus baby. This happened to me previously in a case where I froze all embryos because of OHSS and then the patient failed to get a period and was actually pregnant. She had been intimate with her husband 5 days prior to retrieval and I got 28 eggs in that case...but apparently I left one behind. That was a tough case to enter into our statistics....retrieval, no transfer but pregnancy and delivery...go figure.

Mark Hughes (smartest doctor I know) reported a case where he was comparing the results of PGD/PGS with pregnancy outcomes once the babies were delivered. In one patient, the baby was definitely the genetic child of the couple but did not match any of the embryos that were transferred. Another case of slipping one past the goalie I guess...

So the take home message is that if you have sex during stimulation then once in a great while you may see outcomes that defy the odds....

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Crazy Twin Stories #1

Here at Dominion Fertility we are really doing our best to reduce the number of twin pregnancies. Seriously. No, I really mean it. Recently we were commended by the CDC for our exceptionally high rate of single embryos transfers.

Usually we urge patients to pursue elective single embryo transfer (eSET) if it is their first cycle of stimulated IVF and they are < 35 years old and embryo quality is very good to excellent. However, as many patients/couples view twins as an acceptable and even desirable outcome it is hard to sell eSET to many of them.

In this case, the couple had been through a lot but was open to eSET. I was very happy when I saw the first beta level but figured it was just a really healthy singleton. Then came the first pregnancy sonogram and I saw a single gestational sac with two yolk sacs. Oh well. Follow-up sonograms demonstrated that the twins were not in a single sac which would have made the pregnancy a much higher risk endeavor. Still identical twins were not on our radar screen as the rate of identical twinning is usually only 1-2%.

So in spite of eSET, not all pregnancies will be singletons but as I really can't transfer less than one embryo we are stuck with a small risk of twins no matter what....

Still, as I tell my patients at the time of ET, I don't babysit and I don't change diapers anymore..

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Thanks from Dr G

I really want to thank all of my patients, friends and associates who have extended their heartfelt condolences on my loss. Your kindness is much appreciated. I apologize to any of my patients who were inconvenienced in my absence and also to those who have been trying to schedule appointments and have been unable to get in as quickly as usual to see me. Please understand that I am doing my best to accommodate everyone's schedule.

Thanks again,

DrG

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