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Tuesday, September 9, 2014

Goodbye Summer...You'll be missed. Goodbye OHSS....You will not be missed!

I am always sad to say goodbye to summer. It is my favorite season....probably the result of spending so many happy summers on Cape Cod or at Storer Scout Reservation in New Hampshire or swimming in our little backyard pool under the watchful eye of my Mom (see photo). Along with my kids I get a feeling of dread as school begins and those carefree days fade into memory.

My feelings about Ovarian Hyperstimulation Syndrome (OHSS) are completely different. I hate OHSS. I hate how bad our patients feel when suffering with OHSS and I hate worrying about the rare complications that can occur with OHSS.

However, there has been a revolution in terms of stimulated IVF and the key to that revolution has been the use of leuprolide (Lupron) to trigger for egg collection instead of previous standard of hCG (Pregnyl, Profasi, etc). Lupron causes the pituitary gland to release its store of luteinizing hormone (LH). LH is the signal from the brain to the follicle that tells the egg to "pack its bags and get out of Dodge." Or more specifically it is the signal that tells the follicle to release the egg within the next 42 hours (give or take a few hours).

But the amazing thing about using Lupron to trigger in IVF is that LH is gone within a day. In comparison, HCG can linger for 7-9 days. It is the prolonged stimulation from HCG that leads to OHSS. The ovaries stay enlarged. These enlarges ovaries produce other proteins that increase capillary permeability leading to extreme bloating and swelling.  The fluid leak leads to dehydration and hemoconcentration and things start to go downhill real fast. There is no real treatment for OHSS except tincture of time and avoiding ongoing HCG exposure by freezing all embryos and canceling any planned embryo transfer. Pregnancy makes everything worse and pregnant patients often get the sickest and take longer to recover. Not fun.

However, there are limitations to the use of Lupron to trigger. Not all patients are good candidates for such a protocol.

First of all, Lupron cannot be used to trigger in patients who have already been taking Lupron as part of a microdose Lupron flare (MDL) protocol or as a luteal or long Lupron (LTL) protocol.

Secondly, patients with irregular/absent periods who suffer from hypothalamic amenorrhea (if you are underweight and ran in the Nation's Triathlon last week then you know who you are) may not be able to release enough LH to mature the follicles and get eggs at egg collection. Some clinics hedge their bets by triggering with both Lupron and a reduced dose of HCG. We have elected to stick with either/or and not mix the two. Patients can still get pretty bad OHSS even from as little as 1500 IU of HCG. 

Thirdly, patients who have been on oral contraceptives for many months may act like hypothalamic amenorrhea patients and not respond to Lupron trigger.

Finally, patients who trigger with Lupron should probably not have a fresh ET but rather may be best served by freezing all embryos. The estrogen and progesterone levels plummet so rapidly after egg collection in these patients that the lining falls apart and implantation rates suffer. So patients using Lupron trigger must trust that their clinic has a very good FET program and they themselves must be OK with waiting until a later cycle to undergo ET.

How amazing is the Lupron trigger? Well recently I had a patient who underwent stimulated IVF with a GnRH-antagonist  protocol with planned Lupron trigger. She had an excellent stimulation and responded very well to relatively low doses of stimulation medications. At egg collection after Lupron trigger she had over 35 eggs and 90% were mature. I was taken aback by the total egg count and was a bit worried about how she would feel following retrieval. In the past, such a patient would often need to followed on a daily basis and not infrequently they would have to undergo paracentesis to drain off excess abdominal fluid. Rarely, such patients would be hospitalized. But not after Lupron trigger. In this case the patient felt very well and within 5 days of egg collection her ovaries were nearly back to normal size. Just amazing.

So goodbye OHSS....we're happy to see you go!


Monday, August 18, 2014

Where Miracles Happen Every Day.....Dominion Fertility

I have been practicing Reproductive Endocrinology for 18 years. Although I have some understanding of the emotions involved in patients suffering from infertility, it wasn't until this past week that I gained a fuller insight of how it feels to achieve success after so much disappointment. Interestingly enough, the insight didn't come during a patient consult or sonogram or any type of medical procedure at all...it came on horseback in Colorado.

Over six separate week-long ranch vacations spanning 8 years I have desperately tried to learn how to lope (canter). According to Wikipedia the definition of a canter/lope is as follows:

"The canter is a controlled, three-beat gait performed by a horse. It is a natural gait possessed by all horses, faster than most horses' trot but slower than the gallop, and is used by all riders. The speed of the canter varies between 16–27 km/h (10–17 mph), depending on the length of the stride of the horse. A variation of the canter, seen in western riding, is called a lope, and generally is quite slow, no more than 13–19 km/h (8–12 mph)."

The best part of that definition is "used by all riders." I guess it should say "used by all riders except balding reproductive endocrinologists with no sense of rhythm who should know better than to learn how to ride a horse after the age of 40." 

My previous attempts to learn how to lope had been met with failure and ridicule (not necessarily in that order). Every year I was encouraged to keep trying by well-meaning wranglers but by the end of my week of vacation I was usually suffering from back spasms and a very poor attitude which made my kids question why we kept taking these vacations year after year... But the sad truth was that I really love it out West.  I appreciate the natural beauty, the kindness of the people  and the power of the horses. Plus, everyone else was loping and having a great time so I hated to be a stick in the mud.

Two weeks ago we headed to Rainbow Trout Ranch in southern Colorado and I adopted the mantra of "lope or die." This year would be different. This year I would finally make that breakthrough. This year I would be able to go on longer rides and see what everyone was talking about in regards to loping. At first, my hopes seemed to be misplaced. Same old instructions. Same old difficulties. But then I ended up with a wrangler named Eva who was an expert equestrian instructor. With the supportive presence of my wife, Eva broke down every part of my positioning and carefully explained her theory on why I was having such a tough time getting my horse to lope. Finally, she told me her piece of magical advice....I needed to sing.

Let me assure you all that I am a far cry from Bucky Goldstein, the singing cowboy. However, as an Eagle Scout and former Boy Scout Camp counselor (Wild Goose Camp, Storer Scout Reservation, Center Barnstead, NH; 1977-1981) I do have a pretty good repertory of campfire songs.  These are best sung in the shower or in the presence of a roaring campfire especially given the fact that I am tone deaf.

So following Eva's advice I selected a song that I had sung literally thousands of times over my Boy Scout career. I tightened up my reins. I grabbed the mane of my horse to keep my hand low and my weight lined up...and I began to sing. We trotted and then my horse Dunbar (see photo above) kicked into another gear and we were loping.

I was totally unprepared for the rush of emotions that flooded me. Eight years of trying. Hours upon hours in the saddle. The embarrassment of being the only non-lope capable guest fell away as we were flying up the logging road.  At the half-way break in our ride we dismounted and I gave my wife and Eva a hug. Words failed me as I tried to express how grateful I was for Eva's assistance.

I know that riding a horse is not an essential life experience. I know that being able to take a ranch vacation is a privilege. I know that finally learning to lope is nothing in comparison to overcoming a life altering medical condition such as cancer or infertility. But as I was loping along up that road with Dunbar, I think I finally got a taste for how some of our patients feel when they get that first positive beta, or hear that tiny flickering heartbeat or hold their baby in their arms following delivery.

So thank you Eva, it was a lesson well learned. Hey howdy hey.




Wednesday, July 2, 2014

Stim...retrieve...transfer....fail....repeat. NOT the Dominion Fertility approach to IVF.

Readers of this blog know that I have wide ranging taste in movies. On the one hand I loved Frozen and have been known to sing along with Broadway show tunes (much to the chagrin of my wife and kids). On the other hand, I am a lover of Sci Fi and zombie movies who surfs through the movie channels every night looking for giant monsters or giant robots or giant monsters fighting giant robots (Pacific Rim anyone?). In particular, I love movies that feature time travel such as Star Trek: First Contact, Looper, Source Code, X-Men: Days of Future Past, and now my current favorite chronologically confused film: Edge of Tomorrow.

What a great movie! What a great movie concept! Who would have ever thought of combining Groundhog Day (Bill Murray's best movie IMHO) with Starship Troopers (one of my all time favorite films but one with no redeeming social value)...what an inspired concept. In this movie, Tom Cruise actually does some excellent acting and Emily Blunt plays a hardened super-soldier which is playing against type to say the least. As you can probably guess from my description and the movie poster Tom Cruise ends up with the ability to relive his last 24 hours over and over again after being splattered with alien blood and gore on the battlefield. Like the Bill Murray character in Groundhog Day he grows as a person while becoming the soldier that he never thought he would nor wanted to be (he starts the movie and an unapologetic coward who is happy being a "talking head" for the military but completely uninterested in seeing war up close and personal). Tom Cruise doesn't draw the fans in as much as he once did so I convinced my daughters to accompany me to the multiplex last Sunday to catch the film before it was too late. My older daughter loves intense, kick-ass movies that feature the military fighting zombies, giant monsters, bad guys etc. She is seriously considering attending a service academy and her favorite new TV show is The Last Ship on TNT. However, after watching Edge of Tomorrow she definitely is leaning towards Navy and not West Point based upon how J Platoon fared in their hand to hand combat with the alien horde. My younger daughter took some convincing to see the movie and I kept an eye out for agents from Child Protective Services when purchasing our tickets (the movie is PG-13 but the Family Filmgoer described it as loud and intense but without blood and gore). They both loved the movie as did I so you need to go see this movie before it gets bumped out of the multiplex for Transformers.....Tell them DrG sent you.

So what does a 5'7" actor killing disgusting inter-galactic squid-like creatures have to do with infertility and IVF? I guess the point I want to make is regarding adapting and thinking outside of the box. To illustrate, let me share the stories of two patients pursuing fertility treatments.

L.P. is a 37 year old who came to see me after 3 failed stimulated IVF attempts at another IVF clinic. Her FSH was 14 IU/liter with an AMH < 0.16 ng/mL. Each of her 3 stimulated IVF cycles with had ended poorly without a single attempt at egg collection. In each case she had failed to meet the other clinic's minimal requirement of 3 large follicles needed to permit a patient to go to retrieval. Each stimulation essentially utilized the same protocol without much variation. Their recommendation was donor egg or adoption. When I met with L.P. she was uninterested in donor egg or adoption and thus only wanted to try Natural Cycle IVF. On the second attempt she was successful and delivered a full term healthy baby. She returned several years later and at the age of 41 was interested in another attempt at NC IVF. Amazingly enough, she was again successful on the second cycle and again delivered a healthy baby. Stim...fail to respond....repeat. Not a recipe for success. Kudos to her for hanging in there and believing that something so simple could be successful...twice!

The second patient had traveled a different path to Dominion. K.F. is a 35 year old who had also undergone 3 cycles of stimulated IVF at another clinic. However, she had been an excellent responder to medication so she represented the opposite end of the spectrum from L.P. Each of her stimulated IVF cycles resulted in over 20 follicles and she had over 15 eggs retrieved each time. However, her embryo growth was disappointing with most embryos failing to develop well and no pregnancies and nothing to freeze in any cycle. We discussed the situation and I explained that we were dealing with one of three issues: 1) an intrinsic egg issue that we could not fix; 2) an intrinsic sperm issue that we could not fix or 3) a stimulation issue. The only way to prove that the issue is an intrinsic one with the egg and sperm would be to a) use donor egg/donor sperm, b) do PGS to see if they could produce any normal embryos or c) get pregnant. Option (a) was not acceptable and option (c) would have been nice but seemed unlikely without assistance leaving us with option (b). Although we could do PGS, we needed to consider changing her stimulation in order to get adequate embryos to blastocyst. I recommended reducing her stim dose aiming to get 8-12 eggs hoping that the concept of quality over quantity would hold true for her. Fortunately, her stimulation went very well and several embryos made it to blastocyst and were biopsied for PGS. Two genetically normal embryos were transferred but she failed to conceive. So we had demonstrated that as a couple they could generate genetically normal embryos but these had failed to implant. At this point we discussed performing an endometrial biopsy prior to additional IVF attempts, gestational carrier IVF or repeating an IVF cycle now that we seemed to have a better protocol for her and skipping the PGS since we had proved that they were able to produce genetically normal embryos. This time we hit the jackpot and they conceived with IVF.

I hope that these stories indicate the benefit of modifying future IVF based on past IVF cycles. Sometimes these changes are significant such as changing to Natural Cycle IVF whereas other times the changes can be subtle such as adjusting stimulation meds or doing an endometrial biopsy or convincing a bad-ass like Emily Blunt that you need to call off the planned battle with the Mimics and look for the Omega (which is hiding under the Louvre in Paris) in order to save the Earth...oops, wait that was a movie....I think.


Thursday, June 5, 2014

Avoid getting stung...advice from Dr G at Dominion Fertility

No good deed goes unpunished. I spend a fair amount of time traveling between our Fair Oaks and Arlington offices in order to do my best to do all the egg collections and embryo transfers on my own patients. So when my wife called to say that there was a lot of unanticipated activity in our neighbors backyard that seemed to involve significant tree work I thought that it would be helpful for me to pop in on my way back to Arlington for a quick look. Once at home I assured myself that the neighbor was not decimating trees on my side of the fence and thought that I could quickly knock some items off my project list and clear out a cedar dog house that our dog refuses to use. Bad idea. Did you know that bumblebees have small nests that usually are in the ground? I didn't. Did you know that bumblebees can make a nest in an old dog mat instead of in a hole in the ground? I didn't. Did you know that bumblebees are usually pretty docile and slow to anger and slow to sting a human....unless their nest is disturbed? I didn't. Did you know that angry bumblebees go for the eyes of any intruder who disturbs their nest? Well, I do now...

So as I ran screaming like a little girl away from the dog house, the angry bees followed and one of them managed to sting me on my eyelid. In short order my face started to swell on that side in spite of ice and benadryl. For some reason, this series of events elicits laughter from everyone who hears the story...my wife, the nurses, DrD.... I returned in time to see my afternoon patients. I wore my biggest set of glasses but did warn patients that indeed my face was swollen on one side. Of course, they could no longer look anywhere else and spent the consultations fascinated by my facial asymmetry.

So what does this have to do with Reproductive Medicine? Well, I guess the point I am trying to make is that you never know when you are going to get stung....in the eyelid. When counseling patients about a course of treatment one of my biggest concerns is that of multiple pregnancy. With twins (and worse) you just never know when you are going to end up in a tough situation. Twins have a markedly increased risk of preterm delivery compared with singletons and all the problems that go along with prematurity. Time Magazine recently had a cover story about preemies and how far we have come in handling our smallest patients. But the best treatment for prematurity is prevention. Electing to pursue IVF instead of superovulation and IUI will help. Preimpantation genetic screening to identify the normal embryos will help since if we transfer a single genetically proven normal embryo then the risk of twins will be incredibly low (although not zero because of the chance of identical twins). I spend a lot of my day trying to convince patients that twins are not a "buy-one get one free" type of deal. There is a cost involved....to the family, the children and to society. So try your best not to get stung....go with elective single euploid (genetically normal) embryo transfer and watch out for those damn bumblebees.