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Tuesday, November 11, 2014

Wishing all those who serve a safe journey home....

In 1951 my parents returned from Trieste, Italy where my Dad had served as Chief of Surgery at the Army hospital located far from Charlestown, MA where he was born and raised.

Their time in Europe was a defining part of their lives and I still have literally hundreds of 35 mm slides and many notebooks filled with my Mom's beautiful handwriting as she dutifully studied Italian.

When they finally began their journey back to the United States they were not returning empty handed as can be seen in this photo. They were bringing back their infant son who had been born at the Italian hospital in Trieste. Mom went into preterm labor and was unable to be airlifted to the American hospital in Rome before my brother Michael was born.

Their journey to parenthood was not easy as my Mom had been informed by one of the leading fertility specialists in the country (Dr. Rubin in NYC) that she would never have any children. Dad, always the General Surgeon, told me that he never liked that doctor and thought that he was an ass. Well, Dad proved correct in the end as my brother Steve and I followed over the next 12 years. Every time I perform an HSG using a Rubin-type cannula, I think about how wrong Dr. Rubin was about my Mom. Although my parents had headed off to Europe completely prepared to adopt a war orphan, they were not yet ready to give up all hope of biologically becoming parents. Obviously, I am glad that they kept trying...although my Dad did diagnose my Mom as being in menopause when she became pregnant with me (hey, you can't be right all of the time...). 

So on this Veteran's Day 2014, I salute all those who serve in our military and wish them Godspeed and safe passage home from wherever they are currently stationed. God bless all of you who serve or have served our great country both in peacetime and in war.

Wednesday, November 5, 2014

Tell me a story.....about Dominion Fertility.

I love audiobooks. I have been known to sit in my car in the driveway or in the garage at work just waiting for the end of a chapter. I know I am really engaged in a great listen when I see the beltway looking like a parking lot and silently rejoice that I will have the chance to listen to even more of my book. I have a pretty wide range of taste in terms of audiobooks: from science fiction to non-fiction and everything in between. However, one book that really grabbed hold of me since I first listened to it over 3 years ago was "The Thirteenth Tale" by Diane Setterfield. This Gothic tale is all about telling stories and telling the truth, although sometimes it is unclear what is the truth and what is fiction. Plus, it's a story about twins...so its clearly right up the alley of a Reproductive Endocrinologist.

Relating stories is an important part of being a physician. I believe that patients often feel so alone in thinking that their problems are so unusual that we physicians have no idea of what to make of the situation. Of course, that is usually not the case. In a recent, NY Times blog, this issue of using clinical vignettes to enlighten both colleagues and patients alike was thoughtfully presented. When patients hear stories that resonate with their own situation, I think that it provides more reassurance than reviewing a multitude of randomized controlled trials...although some of our patients do love to share their latest internet research....

So since we are talking about telling stories, let me share a story (with her permission) about a patient that just gave me some very happy news.....

I first met VW and her husband back in 2010.  She was almost 35 years old and they had been trying for over a year to conceive. At first we thought that their biggest issue was one of timing since as busy Washington DC professionals they were like ships passing in the night for months at a time. Her ovarian reserve was concerning with an AMH of 0.3 ng/ml (normal is 1.5-2.5 ng/ml) and we talked about stimulated IVF as an aggressive first step. They elected to go with a very low tech approach and pursued Natural Cycle IUI. Happily, they conceived on the second IUI and delivered a healthy full term daughter 9 months later. As a wise man once said, if all else fails listen to the patient. Perhaps this really was just a timing issue.

They returned a year later to try for baby #2. However, her ovarian reserve was much lower now with an AMH of <0 .16="" 14="" 30="" 3="" a="" additional="" after="" again="" an="" and="" antral="" be="" chance="" chose="" conceived="" could="" count="" cycle="" cycles.="" cycles="" diminished="" dinner="" discuss="" do="" egg="" elected="" estrogen="" failed="" fertility="" follicle="" fsh="" gal="" given="" going="" had="" her="" however="" i="" if="" iu="" iui="" ivf.="" latter.="" level="" low="" medications="" met="" ml.="" ml="" month="" movie="" natural="" ng="" of="" on="" one="" options.="" or="" our="" ovarian="" p="" pg="" pretty="" previously="" reserve="" responding="" results.="" she="" since="" so="" sonogram.="" that="" the="" then="" they="" thought="" to="" type="" undergo="" was="" we="" well="" with="">
NC IVF cycle #1 went to retrieval but no egg. NC IVF #2 went to retrieval and ET but negative beta. NC IVF #3 went to retrieval and she got an egg but no fertilization. NC IVF #4 went to retrieval and ET and resulted in a positive beta but it ended up as a biochemical pregnancy. They were encouraged and went for NC IVF #5. We got an egg, an embryo and a positive beta. She was sent off to her Ob Gyn with a normal looking pregnancy and in spite of some scary first trimester bleeding she went full term and delivered another healthy baby girl weighing over 8 and a half pounds!

In "The Thirteenth Tale" the reclusive author Vida Winter is exhorted by another character to "tell me the truth." So here is the truth about NC IVF. It really does work. It really can result in good outcomes for patients with diminished ovarian reserve, and persistence can be rewarded with eventual success. But even if you have no interest in NC IVF, do yourself a favor the next time you are stuck in beltway traffic and listen to a ripping good audiobook like the Thirteenth Tale.

Tuesday, September 23, 2014

8 years, 3 successful pregnancies, 4 babies (3 is for quitters)....at Dominion Fertility.

This is my 16th year at Dominion Fertility and for 8 of those years SH (not her initials) and her husband have been my patients. Although I cannot remember what I bought my wife for Christmas last year, I still remember speaking with her parents following a laparoscopy back in 2006....

Could I guarantee that she would be successful with IVF?

Would I swear to do my best to help her become pregnant?

I told them that although I could not guarantee success, I believed that she had an excellent probability of success and I would absolutely do my best to help their daughter. In looking at the options for IVF they elected to enroll in our Financial Guarantee Program and on her first IVF attempt she conceived following a fresh ET and had an uneventful pregnancy.

When they returned for follow-up their son was almost a year old. No problem we all thought...this should be easy. But after another stimulated IVF followed by 2 FETs they had come up empty. We moved onto another stimulated IVF but that fresh transfer and one additional FET also failed. An endometrial biopsy had been normal and for the final FET cycle I decided to take a dramatically different approach by using low dose stimulation to prepare the lining for the final FET from her stimulated/freeze all cycle. Not a typical approach but we were all getting a bit frustrated (complete understatement) and her only pregnancy to date had been on a fresh ET. Shazzaam! Pregnant on the FET and after an uneventful pregnancy their second son joined their family.

But they were not sure that their family was complete so when son#2 was almost 18 months old they returned to discuss options. Stimulated IVF was not an option that they wanted to pursue so they opted for NC IVF.

NC IVF #1 resulted in no fertilization. Needless to say they were very surprised since in their stimulated cycles they had always had excellent fertilization.

NC IVF #2 resulted in a transfer and a pregnancy...but then a miscarriage after 10 weeks. Pregnancy loss is so devastating and in this situation it was totally unexpected given how good things had looked early in the pregnancy.

18 months passed and they finally decided that one more try was in order. Sink or swim....this would be the final hurrah. No pressure, Dr. G....

NC IVF #3 went perfectly and she underwent ET of a nice looking early blastocyst. Success! Her betas rose appropriately and we all very excited when she came in for her Ob sonogram. At first I wasn't sure if I could trust my eyes, but I was pretty sure that I was seeing 2 fetal poles and 2 yolk sacs and 2 heartbeats! Although I can certainly understand how an expanded blastocyst can split like a soap bubble into identical twins, I must admit that I was not expecting this turn of fate since we had transferred an early blastocyst.

Well, last week I received an email with the happy news that Mom and their 2 new DAUGHTERS were doing just great. Talk about instant family balancing....

SH agreed to let me share her story and all the ups and downs that these 8 years have represented. The joys and the sorrows. the good times and the bad.... After 19 total years in practice she has claimed my top spot with delivery of babies #3 and #4. I have several couple who have had 3 babies from our efforts but I think that this is a first for me.

On the Disney Channel Show "Good Luck Charlie" Teddy (the oldest daughter) asked the Mom (Amy) why on Earth they had decided to have a 4th child.....Amy's reply: "Because 3 was too easy. 3 is for quitters!"

Congrats to SH and her whole family who never quit and allowed me to be such an intimate part of their lives!

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!