How to Make a Family: The Blog

Passin On The Good Stuff Again

Okay, off my high horse, back to more compassionate reality again... The organization I mentioned long ago, Fertile Dreams, is hosting another conference and they've asked me to mention it.

Fertility conferences come and go, all over the place -- but this one is not only free, the keynote speaker is none other than Ali Domar, herself.

Alice Domar, PhD, is the woman who's taken mind-body concepts (pioneered and shown the public light of day by her Harvard mentor, Herbert Benson) into the realm of women's health and fertility and never looked back. You may see "mind-body" stuff touted everywhere you go, but Dr Domar is the It Woman who started the concepts on the path to infertility clinics.

You can see her speak for no charge at the Fertile Dreams 4th Annual Pathways to Parenthood Conference. Registration in advance is required.

Nothing New, But Stay Tuned

A New York Times piece, Racing to Beat the Maternal Clock, was published on December 12, under the section head Frontline Report.

With my own daily existence being rather mired in the topic, I can no longer provide the perspective of a newcomer to the infertility world. But really -- a NYT article on how reproductive biology is still trumping science? This is still news?

Right. Lots of people are buying into the heavy-duty marketing by the industry that nearly claims the ability to get anyone pregnant at any time. At least, that's how desperate minds can translate what they read. The relationship between provider and receiver of family-building help is a two-way street.

The instinctual drive to have a baby can be for some a cause of near insanity. Otherwise reasonable people will literally hear and read what they long for the most -- that their dilemma can be resolved by the experts. Fertility experts are often happy to oblige.

My face is overtaken by a grin when I read (in Leslie Berger's NYT article) how Dr Bradley Van Voorhis of the University of Iowa School of Medicine referred to the older patients crowding fertility clinics' doors as "otherwise highly educated..."

One quote in the same article did catch my eye, with the same sort of zing that I recall when finding out about PGD back in the mid-90's. Sherman Silber, a doc in St Louis who's made history in the field a few times, announced his opinion that egg-freezing "will emancipate women as much as the birth control pill did in 1960." That's a keeper for posterity.

Not all fertility docs are as quotable as Zev Rosenwaks. Berger's interview of him, Turning Points on the Road to Conception, is more informative than the 'maternal clock' piece. Still, even he, the Director of The Center for Reproductive Medicine and Infertility at New York-Presbyterian Hospital, says "Today, we help most of our patients depending on their age. Depending on how far couples are willing to go, we can treat them pretty successfully 90 percent of the time." This near the end of the interview in which he started by saying that the sometimes-reported "higher" rates of infertility are really just a product, especially in the U.S., of people trying to conceive later in life.

While he 'hopes' that people will take what we know about the biological clock into consideration when they're planning families, Rosenwaks and others stand by, waiting to offer the best they can to those of us who pursue life as if our unborn children are angels in the wings who will enter on cue. 

Ambience is Everything

It's nice to see studies that confirm my own unfounded opinions, even if there's a slight 'duh' factor involved.

Turns out that little in vitro embies don't like nasty lighting. Neither do I. My colleagues and I at AIDS Foundation Houston, back in the day, were affectionately referred to as "the lamp people" -- we refused to use our office hovel's fluorescents overhead, favoring the soft warm glow of incandescent lamps on our desks. Life was tough enough doing social work with sick people at their homes; when we had to be desk-bound, we wanted as much soothing as could be mustered in that moldy building. But I digress...

So, me and the embies have it right. Fluorescent (and even sunlight for the little ones) is out. Warm-white is in.

Link: IVF News - Lights in fertility clinics may damage embryos.

Too Much of a Good Thing?

Coming up from the 'Better Late Than Never' Dept:

Recent articles sprouted from published research that implies there's a bit too much ICSI going 'round. So, I asked both the researcher and one of the pioneers of the technology to comment on the media hullabaloo that ensued.

ICSI, for the uninitiated, is the acronym for intracytoplasmic sperm injection, arguably one of the most diety-like assisted reproductive technologies available. Just like it's name says, ICSI is performed by an embryologist who uses tiny tools to pick up a single sperm cell and injects it into the cytoplasm of an egg cell. In "ordinary" IVF, a batch of egg and sperm cells are tossed together in a dish to see who the winner is -- with ICSI, only two specially chosen cells get the honor of trying to make a baby.

Dr. Tarun Jain in Chicago is the lead author of the study, published in the July 19 New England Journal of Medicine. The study concludes with a question mark as to why so much ICSI is being performed.

ICSI's primary benefit is the treatment of male-factor infertility, that is, problematic sperm. Combined with pretty darned invasive sperm gathering techniques for some men, even those whose semen analyses render no visible sperm cells have been able to become biological dads. In lay person's terms, guys who are shooting blanks can still get a woman pregnant. That's no small science.

The science and related micro-technology have been around for awhile. One of the first in the arena was embryologist Michael Tucker, PhD, who works in Atlanta and Baltimore and Chicago. Since ICSI's early days (way back in the late 80's, early 90's, a long time for this fast-moving field), technicians have become more adept at using the tiny tools, and labs have learned more about things like fluids that promote viability of cells. The result is quite a big change in the consistency of infertility treatment outcomes, for the better. In short, ICSI not only helps men with sperm cell problems, it takes a lot of guess-work and chance out of IVF for people with non-male-factor issues.

So Jain, who has gained a reputation as a reproductive doctor whose research studies advocate for the little guy (e.g. patients who cannot afford treatment or who are discriminated against), wondered on paper why there was so much ICSI being done when male-factor infertility rates seem to be static.

I've interviewed both Jain and Tucker over the years and assert that they're both good guys and not necessarily diametrically opposed. So I'll just quote them, from emailed responses to my query for their comments.

To Tarun Jain, from me: Could you comment on what spurred you and the co-researchers toward examining the use of ICSI?

From Jain:
Thanks for your interest.

ICSI is an important and useful technique that is used frequently as part of IVF treatment for male factor infertility.  We had anecdotally been seeing a greater use of ICSI for other indications.  There has also been a lot of recent debate in the literature about the indications for ICSI use.  We therefore set out to objectively look at the true utilization of ICSI in the US over a 10 year period.  Our study was the result of that impetus.

Best regards,
Tarun Jain

To Michael Tucker, from me: I would love to know both your quotable and off-the-record comments on the NEJM pub'd study by Tarun Jain et al from U of Illinois to Chicago.

From Tucker (only the quotables...):

I remember getting fired up about this back in the day (for example, Tucker et al. Lancet 2001 in a back-and-forth on when to use IXI), and I hav always been very aggressive with it's use simply because over the years I have seen (my own "evidenced based" assessments!), the ability of IXI to overcome complete failure of fertilization following conventional insemination, even when no male factor is involved.  And these cases are due simply (for example) to issues with the receptors on the oocytes, possibly due to the unphysiological nature of the ovarian hyperstimulation or inherent bad oocyte quality, and in some cases you can take these unfertilised eggs, fertilize them with "rescue IXI", make embryos (rescue IXI = FIXI...), and transfer them even though developmentally they are 12-18 hrs delayed, and generate healthy babies (see for example, Morton et al Fert Steril 1997).

Heck, this can go either way. Do I think IXI is sometimes needlessly utilised? Yes, maybe just occasionally, but on balance, it can be argued that it is the way to go for all cases. I have been offsite director in Chicago (www.fcionline.com) for about 3-4 yrs, and they do 100% ICSI - why? Because they have an all inclusive deal with the insurance companies that makes IXI dirt cheap; it allows optimal examination of oocyte quality and maturity on all patients the day they are retrieved; avoids the 5-10% unexpected failed or reduced fertililzation cases that compromise about 10-20% of all conventional insemination cases; and further it may improve on nature... This last statement is based on a newer emphasis in the last few years where we get much more particular about which sperm we actually inject.  We utilize higher magnification than we used to, to scrutinise the precise morphology of the sperm that we immobilise for IXI, and this appears to be linked significantly with improved clinical outcomes, making the not unreasonable leap that good morphology correlates with better overall DNA packaging - see for example,  Bartoov et al, J Androl 2002.

The enthusiastic and motivated Tucker continues, expressing frustration at "studies like this" because... they are so missing alot of the multifactorial stuff that goes into the making of decisions in our business - not to mention a 31 to 33% outcome comparison is no way significant in such a mess of patients. Steve Ory mentioned the "art" of what we do; and by and large we are one of the most "policed" areas of medicine (cue Michael Moore?), and while there may be a little "abuse"/overuse of IXI, I think it is utilised principally in a totally appropriate and well-intentioned way. If done properly in the lab, it kicks arse, and that's the only way we use it under my guidance (usually about 55-65% of cases in most labs other than Chicago), and the patients get a good deal, believe me. That there are extra chromosomal / genetic disorder issues with IXI is (IMHO) entirely due to the nature of the gametes that are achieving fertilization and oftimes pregnancy, that would not have a donkey's chance on the horse stud farm to achieve success (healthy pregnancy) otherwise.

It's good to know that professionals like both Jain and Tucker are on the job. To me, they represent two essential components to problem resolution -- inspired, enlightened momentum and compassionate, educated caution.

Evidence-based Science Versus The Desperate Wanna-be Mom

Back when it seemed like I was miscarrying pregnancies left and right (approximately every 6 months, to be accurate), scouring the Internet for answers developed from a hobby into an obsession and, finally, a career. If there was something out there that my MFM or RE hadn't suggested yet, by gosh, I was going to find it and lay it out for them.

That's how I wound up begging to use prednisone, a glucocorticoid aka steroid hormone.

Link: Steroid use fails to boost pregnancy rates in infertility treatments.

Using Stem Cells to Create Sperm

Far from being a done deal, there is at least the possibility of more hope on the horizon for men with cellular level infertility. Research published in the American Journal of Pathology reports that infertile mice recognized promising results when bone marrow stem cells were transplanted into the testis to see if they would replace nonfunctioning cells.

While no full sperm cells were created, the stem cells did indeed differentiate into either germ cells or supporting cells. Also, the different types of "new" cells were found among similar types, indicating influence on the stem cells by their immediate environment.

This is one of those very precursory studies in a long line of future explorations, but hopefully it's one that we'll all look back on one day and say "Remember when we'd just started to figure out how to use stem cells to create sperm?"

Link: Treating Male Infertility With Stem Cells.

Letting Fertility Docs Off the Hook

For years, the rates of multiple and other high-risk pregnancies have been on the rise. For the same amount of time, reproductive specialists have taken a beating for at least having the appearance of being the primary sources for the increase.

But in this AP article by Marilynn Marchione on the Monterey Herald website, comments by maternal-fetal medicine (MFM) experts call attention to the other players in the high-risk baby story.

Link: Monterey County Herald | 02/13/2007 | Risky pregnancies increase.

IVM: Good Stuff, But Not Really New

When the worlds of marketing and medicine collided a few years back, a lot of popular media and their readers got lost in the fray. A recent example: Polly Curtis' article in the Dec 30 '06 edition of The Guardian tries to make IVM look shiny and brand spanking new.

IVM (for in vitro maturation), a technique that pulls immature follicles from the ovary and facilitates their ripening in vitro before utilizing ICSI or luck to fertilize them, has been used to successfully make babies for awhile now. Of course, "successfully" is a relative term, and IVM is still a work in progress in many ways.

But IVM's not really the news that Curtis purports. Her story, highlighting good results from a notably large Danish study of the technique, misleads from the first sentence: "Scientists have unveiled a new form of IVF..." Even the article's "Backstory" section fails to mention any precursors to the Danish trial.

Okay, just as "successful" is in the eye of the beholder, so, too, may be "new" -- but in a fast-developing arena like reproductive medicine, it seems like techniques that have been used for nearly a decade or so no longer qualify as being "unveiled."

Dr. Seang Lin Tan and fellow researchers of McGill Reproductive Centre in Canada have patented their particular IVM process, having made babies with it since April 2005. As a brief history in this article on the McGill team (from McGill Headway, Fall 2005) lists, the first baby in the world resulting from IVM (using donated eggs) was born in South Korea in 1991. The first from a mom's own eggs, born 1994 in Australia. There have even been two IVM World Congresses, gatherings of researchers and interested practitioners, held thus far, with a third coming up later in 2007 in conjunction with the International Society for IVF's meeting. The Danish study about which Curtis reports was presented at an alternate gathering of interest, titled "The First World Congress on Natural Cycle/Minimal Stimulation IVF" and organized by The International Society of Natural Cycle Assisted Reproduction.

The Danish researchers may not be to blame for declaring their findings as the Latest & Greatest, exactly. Admittedly, I'm not privy to whatever press release went across Polly Curtis' desk before she wrote her piece. From my own experience, I surmise that any missives going out from the researchers' communications team may have sounded similar to this science-oriented blog post dated June 2004, in which McGill University's own marketing folks describe IVM as "a new way to preserve the fertility of women who must undergo chemotherapy."

The real news that could've been reported might have had more to do with the fine details of technique from the laboratory, details that certainly a lot of baby-hungry patients don't care much about, as long as there is success in the end.

So, how should such news be reported? At last year's meeting of the European Society for Human Reproduction & Embryology, University of Adelaide researcher Dr. Robert Gilchrist received a prestigious award for his contribution to the egg maturation process. In this University press release from last August, the writers avoid the use of attention-getting hyperbole, stating even "IVM is not a new concept" while also remarking on Dr. Gilchrist's particular innovation, which stems from studies on growth factors.

Semantic details probably slide right by most readers, especially those who aren't personally struggling with the topic at hand. And yes, IVM is gaining clinical respect as scientists fine-tune the lab technique, at least in countries where reproductive medicine isn't quite the several billion dollar industry that it is in the United States. Perhaps the news lies somewhere in between.

Male IF Tx: Varicocele Embolization

More fodder for the straight-to-ICSI-or-not debate.

From the source:

Minimally invasive treatment helps infertile couples conceive from PhysOrg.com
Couples struggling with infertility face uncertain odds when considering various treatment options. But a new study reveals that embolization, a minimally invasive treatment for arguably the most common cause of infertility in men, can significantly improve a couple's chances for pregnancy. The findings were presented today at the annual meeting of the Radiological Society of North America. http://www.physorg.com/news83942028.html

Egg Quality-Control of the Cellular Kind

Harvard researchers have found that a protein, p63, may be the deciding factor in nature's genetic screening process for egg cells.

Link: BBC NEWS | Health | How damaged eggs are weeded out.