Thursday, January 20, 2011

Bicornuate or septate uterus? (part 1)

This question frequently comes up, and physicians (ob/gyns, radiologists, even fertility specialists) often get tripped up by it. I saw two patients this week who came in with the wrong diagnosis, even though it's pretty straightforward to distinguish the two conditions, and it doesn't require any fancy imaging. One of the patients had been told to give up and use a surrogate! (She now has two healthy children that she carried herself.) What follows is the conversation that I have with patients who present with this question.

The fallopian tubes, uterus, cervix, and upper vagina begin development as two parallel tubular structures - these are the mullerian ducts. During embryonic development, the lower part of these structures grow together - this process is called fusion. Then the parts that are fused together disappear to form a single (larger) tubular structure - this process is called resorption. The fused (and partially resorbed) part of the mullerian ducts becomes the uterus, cervix, and upper vagina. The (unfused) upper part becomes the fallopian tubes. The diagram at left shows a cross-section of a normal uterus.

When this embryonic process goes awry, a number of different genital birth defects can occur. If there is no fusion, two separate uteri result (this is called uterus didelphys). The will be two separate cervices, and sometimes two vaginas. If fusion occurs only at the very bottom of the ducts, you get a bicornuate ("two horned") uterus. The diagram at left is a cross-section of a bicornuate uterus. Note that the upper part of the uterus consists of two distinct structures separated by a cleft. Women with a bicornuate uterus are at an increased of (late) miscarriage, preterm birth, and abnormal fetal lie (usually breech). Although there is a surgical procedure described to fix a bicornuate uterus, it is no longer recommended by experts in the field, because: (1) the pregnancy outcomes are quite good if you just stitch up the cervix in the next pregnancy, and (2) it's a fairly drastic operation, involving cutting the uterus open and sewing it back together.

If fusion occurs but resorption is incomplete, you get a septate uterus. Here is the diagram of a septate uterus. In the middle of the uterine cavity is a fibrous, avascular partition (the septum). Note that from the outside, the top of the uterus appears normal. (It's generally a bit wider than normal, but the top has no cleft just like a normal uterus.) Women with a uterine septum have twice the risk of miscarriage as other women, and they are more likely to have problems with preterm delivery and breech birth, too. The treatment for a uterine septum is to just cut the septum with scissors, and this can be done as an outpatient.

Generally, a woman finds out she has a bicornuate or septate uterus when she gets a hysterosalpingogram for infertility or recurrent miscarriages.

Here are some normal uterine cavities on HSG:

Note that the uterus in the lower photo has a bit of a curve in the top of the cavity. This is a normal variant.

Now take a look at these HSGs:

There is an obvious cleft in the uterine cavity. This HSGs are commonly read as "bicornuate uterus" by some physicians, but in reality it could be a septate uterus or a bicornuate uterus. Let me state this again: YOU CANNOT DISTINGUISH A SEPTATE UTERUS FROM A BICORNUATE UTERUS WITH A HYSTEROSALPINGOGRAM. Yes, I know there was a paper published years ago which said you could distinguish them by measuring the angle between the cavities, but it just ain't so. The two tests which can best distinguish a septate from a bicornuate uterus are a transvaginal ultrasound and a pelvic MRI.

Now, the sad thing is that one of my recent patients actually had an MRI, and the diagnosis was still missed. It turns out that not all radiologists understand the difference between a septate and a bicornuate uterus. They often just put "uterine duplication" in the MRI report, and that's what probably happened with my patient.

The next post will show how to distinguish a septate uterus from a bicornuate uterus using transvaginal sonography.

Tuesday, January 4, 2011

Unexplained infertility

Another reader asks: "1. What would be your recommendation for a couple with unexplained infertility? On paper the couple is perfect but even with IUI cycles and injectibles cannot seem to conceive. Especially if Insurance says no to any procedures for infertility treatment, ie IVF or the IUI's. 2. Is there a point when a couple with unexplained infertility and no disposable income for IVF procedures should just give up on having a baby?"


Depending on how you define unexplained infertility, the prevalence of this diagnosis in a fertility clinic varies from zero to 20% of the patient population. How can there be such a range? A famous professor/fertility expert once said "a cause for infertility can be found in all couples if enough tests are obtained." I am afraid this reveals a rather unsophisticated understanding of medical testing, as if you do enough tests on normal healthy couples, something will eventually turn up positive. The trick in medicine is to do the right tests on the right patients (this maximizes the "predictive value" of the test). But what are the right tests? One way to approach this would be to do fertility tests on fertile and infertile couples. If the test under study is abnormal more frequently in the infertile group, the test probably has some value in a fertility evaluation. This approach has been performed in a meaningful way for only a few fertility tests: semen analysis (some value) and endometrial biopsy (worthless). I was involved in both these studies, and believe me, they were challenging to do, involving millions of your tax dollars. A friend and mentor once tried to do all the standard fertility tests on both fertile and infertile couples and couldn't collect enough data to make meaningful conclusions. It's an interesting report to read though, as he often found fertile couples with abnormal fertility test results (see here to read it:

Here is what I recommend for a basic infertility evaluation: semen analysis, hysterosalpingrogram, post-coital test (PCT), and midluteal progesterone level. Yes, I know the PCT is controversial and many fertility clinics don't bother with it, but I still think it's a meaningful (and fairly inexpensive) test. And the progesterone level is an easy way to confirm that ovulation is occurring. If all these tests are normal, I encourage infertile women to have a laparoscopy, unless your insurance won't cover it. In my view, you can't give a diagnosis of "unexplained infertility" without a laparoscopy to confirm it.

So what if all these tests are normal? If the woman is young (less than 30), and the duration of infertility is brief (less than 2 years), I encourage a few months of watchful waiting to see if pregnancy occurs spontaneously. If these criteria are not met, than the next step is to take clomiphene and do intrauterine inseminations. I usually recommend 3 cycles of this. If the woman is older (over 35) or if she has already taken clomiphene, I encourage women to go straight to gonadotropins and IUI. What about doing IVF? Great idea, but it's more expensive than the other two options. It does have a lower risk of triplets or higher, though, as long as you don't get carried away by putting in too many embryos. I occasionally have patients who don't get pregnant with clomiphene/IUI go straight to IVF for this reason. One fertility clinic recently tried to determine whether it was more cost-effective to do the gonadotropin/IUI first or go straight to IVF; the results didn't particularly favor either approach.

Our reader with unexplained inferility asks what to do if IVF is not an option, but gonadotropin/IUI hasn't worked. Well, in general you have reached the end of your fertility treatment. The only thing beyond IVF is IVF with donor eggs, which is even more expensive. When to quit? Other than when your money or insurance coverage runs out, or the fertility treatment is driving you crazy, I would recommend quitting when you get to the point of taking gonadotropins and you only make a couple of mature follicles, despite high doses of medicine (300 units or above). This is an ominous sign that you are running out of eggs faster than other women your age, and the success of IVF under these circumstances is low. For those women, egg donor IVF is the best approach.I think women with such diminished ovarian reserve as their only fertility problem are just as likely to conceive on their own as with IVF, and occasionally former patients will call me to confirm that very event (they like to rub it in a bit, but I am happy for them nonetheless).

Saturday, January 1, 2011

Acupuncture and Infertility

A reader asks, "What are your thoughts on acupuncture and infertility treatment?"

Short answer: Go get a massage instead.

Long answer: Let's start at Wikipedia (one of my favorite Web sites): "Acupuncture is a practice in which needles are inserted into various traditionally determined points of the body ("acupuncture points") and then manipulated ... Acupuncture is based on tradition and authority, not on the scientific method, and is not based in, and does not relate to, other interrelated fields of science such as human anatomy, human physiology, cellular biology, neuroscience, biochemistry, or physics."

Here is my basic philosophy of treating patients: I don't recommend treatments that are not based on a scientific rationale and supported by at least some reasonable medical/scientific evidence. If you abandon this philosophy and say "let's try treatment X; after all, it can't hurt", you enter the Neverland of medicine, with no rules, boundaries, or logic. And as to the concept "it can't hurt", sometimes it does hurt. Ephedra, an herbal preparation used in traditional Chinese medicine for thousands of years, was pulled off the US market in 2004 after about 100 people died from taking it. And this problem isn't restricted to herbal medicines; there are many cases where well-meaning physicians tried a treatment based on very limited data that turned out to hurt, not help (DES is a classic example).

The problem with my philosophy is that medical evidence is not absolute, it can ebb and flow, and what is "some reasonable evidence" to one person may be insufficient to another. You can find one study in the medical literature that proves just about anything (my favorite example is a paper that claimed preeclampsia was caused by worms. It was published in a fairly respectable obstetric journal!). And although I am pretty conservative about what treatments to recommend, there are physicians more conservative than me on some things.

OK, back to acupuncture. There were a few small studies published that claimed acupuncture improved IVF success. Most of these studies compared acupuncture to nothing. More recently, larger studies which compared Chinese acupuncture to "sham" acupuncture, in which a needle was poked into the patient randomly, showed no influence on IVF outcomes. One study (So EW et al., Hum Reprod. 2009 Feb;24(2):341-8; the study was done in Hong Kong, where they should know something about acupuncture) showed the sham acupuncture group to have a slightly higher success rate (it was just a fluke, but the authors claimed sham acupuncture might have some benefit - arrgh!). Several other large, well-designed clinical trials also have shown no benefit to IVF patients getting acupuncture. Here is what the authors of a recent compilation of acupuncture studies concluded: "New emerging evidence from clinical trials demonstrates that acupuncture performed at the time of embryo transfer does not improve the pregnancy or live birth outcome after treatment. This evidence raises questions regarding the futility of conducting further research in this area and the quality of evidence needed before any specific intervention is incorporated into routine clinical practice, particularly when a scientific rationale is lacking." (El-Toukhy T, Khalaf Y. Reprod Biomed Online. 2010 Sep;21(3):278-9)).

I hope you enjoy your massage.