University of California San Francisco
Saint Barnabas Medical Center
In this lesson, we’ll showcase a number of studies that incorporate data (often from the U.K. and the U.S.) comparing Caucasian and “Asian” populations.
We should point out that the approach is inherently challenged for a few reasons.
First, by and large, most studies only categorize groups according to female heritage, race or ethnicity. This approach may ignore any impact of the man providing sperm.
Next, within such racial and ethnic groupings, definitions vary. Many studies leave it unclear which countries of ethnic origin constitute each group. For instance, some studies include women of Indian heritage in their “Asian” population grouping, while others don’t. When possible, we'll clarify which groups are likely being included in the population being studied.
Next, even when there is clarity and consistency, these populations in-and-of themselves are typically inherently different, and an over-representation of some groups may mask, overstate, or understate observations as they apply to other groups.
To illustrate the point, let's look at a study on a different topic: breast cancer. In 1997, researchers compared breast cancer rates in the United States between Caucasian women and women of “Asian and Pacific Island” heritage. The results are below and seem simple enough.
However, when the investigators looked at sub-segment groups, they noticed an enormous degree of heterogeneity. Breast cancer seemed to occur in Japanese populations at double the rate for Chinese or Korean populations. As a result, one could argue the above statistic for “Asian” populations don’t really seem to reflect any of the Asian populations included.
The same concepts and challenges likely apply here as well. Classification of, and representation in, “Asian”or "East Asian" groups may lead us to some overly-broad, or off-base, observations.
Finally, some of the data provided here comes from patient populations studied in the United States or Europe and published in respected, but uniformly, English-language journals. The degree to which the findings here are generalizable in other countries may remain an open question. In addition, there may be high quality studies or findings not published in peer-reviewed English language journals that our rundown does not include.
Investigators in California and Oregon compared the "time to pregnancy" between patients of Caucasian and (mostly East) Asian heritage who were pregnant having conceived
"naturally." They observed no "statistically significance" between the two groups once they accounted for age, but once they corrected for additional variables, they came to the conclusion, "Asian women had higher fecundability and shorter time to pregnancy."
If natural conception isn't possible, the age at which a woman begins treatment can impact the odds that treatment will work. You may recall this from our last lesson. You can see this in the data below on IUI and IVF from the U.S., China, and Japan. Again, these charts are only meant to express the univeral age-related decline in treatment success and are not meant to elicit comparisons of outcomes between regions. Here is the data on IUI.
Here is the data on IVF, which we’ve had to manipulate somewhat to account for the fact these studies measure success at differing age cutoffs.
While it’s not been widely studied, in the United States one well-regarded clinic in California noted that when looking at success rates with IUI, Asian patients (most of whom were of East Asian heritage) were far more likely to start treatment after a two-year (or longer) duration of infertility.
If patients of Asian heritage are indeed delayed in accessing treatment, there may be multiple plausible explanations.
Within the United States, there is a broad body of literature that indicates patients of Asian and Pacific Island heritage are more likely to feel the forces of discrimination and are less likely to positively perceive the care they receive. In the minds of many experts like Trinh-Shevrin, Islam, and Rey, this creates a substantial barrier to receiving medical care in any form.
With regard to infetility specifically, referring doctors may be less likely to perceive “Asian-American” women to be in need of treatment. In a small survey of 155 general practitioners in a region with relatively few Asian-American patients, less than 1% identified “Asian-American” women to be the ethnic group most in need of care. Rather, 82% (incorrectly) cited women of European ancestry. In regions with larger Asian-American populations, this study's findings may not apply.
Finally, women and couples may delay treatment for personal reasons. They may remain optimistic about their ability to conceive naturally or find their current challenges difficult to acknowledge.
We’ve yet to see hard data that indicates Asian patients are any more likely to harbor these feelings than non-Asian groups. However, when we speak with patients and doctors of East Asian heritage, many share with us a feeling that prospective patients in East Asian cultures may be more likely to ascribe self-blame for their challenges or grow up in environments where topics like intercourse, reproduction, and fertility were less likely to be broached. In "Asian American Communities and Health" Trinh-Shevrin arrives at a similar conclusion and considers this to be a major disintermediator between patients and doctors.
In a following lesson, we'll cover the emotional impact infertility can have on patients globally and on patients in Japan, China and other regions.
As we'll cover in the next few sessions, treatment success rates tend to look different for fertility patients of Asian heritage and for fertility patients of Caucasian heritage.
Some believe this is not a reflection of how well certain patients respond to treatment, but rather is a function of the observation that Asian patients may be delayed in accessing treatment longer than Caucasian patients. The implication is that those patients who ultimately end up presenting at a clinic (and being studied) have been trying to conceive "naturally" for longer, are thus less fertile, and thus will require more treatment to have a child. With that important caveat, let's start looking at some data.
As you’ll recall, in many ways IUI is “frontline treatment” for fertility patients because it’s often the least expensive and least invasive procedure that can be done at a clinic.
According to the study we referenced above, investigators at UCSF noticed that after one IUI, (mostly East) “Asian” patients were less likely than Caucasian patients to conceive. While the relative difference (33%) appears large, the absolute difference (9.3% vs 7.1%) might be considered small.
However, the difference in cumulative success rates after six IUIs begins to look more meaningful (26% vs. 20%). Once investigators corrected for a few factors, this difference met statistical significance. All this despite the fact that a greater percentage of (mostly East) “Asian” patients were prescribed aggressive drugs (gonadotropin) that often drive higher live birth rates with IUI.
All the same, this study likely needs greater context that can help us calibrate how to interpret the results.
For one, this study was conducted at a single clinic and idiosyncrasies of the clinic itself may explain some of the results. The degree to which the findings are generalizable across clinics and regions can be hard to say.
Additionally, while these results may warrant patients to recalibrate their quoted odds of success with IUI, the distinction may not be big enough to meaningfully alter expectations in timelines, costs, or the most common decision: when to switch to, or from, IUI.
A registry of patients in the United States revealed that “Asian” patients (countries of heritage and origin were not defined) undergoing IVF record dramatically lower IVF success rates than their Caucasian peers.
When investigators at UCSF conducted a similar analysis on their own patients, they noticed a similar phenomenon. Even after accounting for differences in the two groups (Asian women were likely to be older and more likely to have challenging diagnosis like “Diminished Ovarian Reserve”), the difference remained statistically significant and consistent both nationally and at the clinic level.
Another possible explanation for any disparity in outcome may relate to differing rates of success using "fresh" versus "frozen" embryos.
Let's look at a smaller study out of Stanford that compared IVF success rates amongst patients undergoing IVF with a “fresh embryo transfer".
In the Stanford study, the "Asian" group excluded women who identified as being of Indian heritage or mixed heritage. As you can see, this group produced roughly the same number of eggs, that lead to a similar number of high quality, blastocyst embryos.
However, challenges began when those high-quality embryos were transferred back into a woman’s uterus. As you can see, the odds the embryo “implanted” were dramatically lower in the “Asian” cohort. This drove lower pregnancy rates, and since miscarriage rates were similar between the two groups, ultimately lower live birth rates.
One observation, that may be related, is investigators have noticed across multiple studies that Asian women record higher estrogen levels in response to the fertility drugs given.
This may be a useful observation because if estrogen levels remain elevated during the time of embryo transfer, the uterus may be less “receptive” to the embryo’s efforts to implant.
During a “fresh embryo" transfer, a woman’s body has only 3-7 days to recover from the injectable hormones given leading up to the egg retrieval, and so estrogen levels may remain high and the uterus may be less "receptive".
However, when embryos are frozen before a transfer, a woman’s body is typically given a month or more to recover, estrogen levels tend to drop, the uterus may become more "receptive," and implantation rates tend to rise.
To illustrate how this may be a clue, let’s look at a continuation of the Stanford study. You’ll see that when the women who had an unsuccessful fresh transfer are given time to recover, and then undergo a frozen embryo transfer, the discrepancy in implantation rates dissipates. In turn, pregnancy and live birth rates pull even with what Caucasian patients record.
While interesting, we need to be somewhat cautious in interpreting the results.
First, few studies like this exist, and far more are needed to make any broader inference.
Second, this is a smaller study conducted at a single clinic and may reflect idiosyncracies of the clinic's population, or its approach, rather than a more generalizable phenomenon.
As an example, not all clinics available to a patient may be equally as skilled at growing embryos to "blastocyst" stage, freezing them and then thawing them. When patients weigh their options, it can be important to calibrate the abilities and track record of the clinic's laboratory (see our lesson here).
There can be compelling reasons for a patient to have a "fresh" embryo transfer, and a nuanced discussion with your doctor will be needed.
There's reason to believe fertility patients of certain East Asian heritages (e.g. Filipino, Korean) are far more likely to suffer from endometriosis than fertility patients of other ethnicities and heritages.
For this reason, and because endometriosis is an immensely complex diagnosis that's often overlooked, we suggest you consult our full course here.
As to whether a higher prevalence of endometriosis explains the possible lower rates of IVF success, one study's investigators concluded the answer was likely not and other factors (a few of which we've covered) were likely at play.
For any patient living in a country where smoking is more common (e.g. China, Mongolia, Indonesia, South Korea, and Japan are in the top 20%), it’s important to keep in mind the negative ways male and female smoking (and secondhand smoke) can impact the ability to conceive naturally or through treatment.
Smoking dramatically lowers the likelihood a woman will manage to conceive naturally. In each of 12 separate studies, investigators concluded women who smoked were far more likely to be unable to conceive, and when the 12 studies were merged together, investigators determined women who smoke were 60% less likely to conceive than those who avoid smoking.
While many of us believe IVF solves the issue of infertility, the reality is most IVF cycles don’t work and when women smoke, their cycles are nearly twice as likely to fail according to a dataset from over 20 studies.
That nearly 2x drop in success for female smokers shows up for male smokers, too. A German team looked just at this issue in 2003 and showed that amongst over 700 couples, IVF cycles had far lower pregnancy rates when the man smoked (even if the woman didn’t). As you can see from the data below, even when couples resorted to using ICSI to fertilize their eggs during IVF, it didn’t close the gap in success rates between male smokers and non-smokers.