Influence of race and ethnicity on in vitro fertilization outcomes: systematic review

Accepted Manuscript Influence of race and ethnicity on in vitro fertilization outcomes: systematic review Leigh A. Humphries, Olivia Chang, MD, Kathryn Humm, MD, Denny Sakkas, PhD, Michele R. Hacker, ScD PII:

S0002-9378(15)01026-1

DOI:

10.1016/j.ajog.2015.09.002

Reference:

YMOB 10642

To appear in:

American Journal of Obstetrics and Gynecology

Received Date: 10 June 2015 Revised Date:

19 August 2015

Accepted Date: 1 September 2015

Please cite this article as: Humphries LA, Chang O, Humm K, Sakkas D, Hacker MR, Influence of race and ethnicity on in vitro fertilization outcomes: systematic review, American Journal of Obstetrics and Gynecology (2015), doi: 10.1016/j.ajog.2015.09.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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TITLE Influence of race and ethnicity on in vitro fertilization outcomes: systematic review

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AUTHORS Leigh A. Humphriesa,b; Olivia Chang, MDa,b; Kathryn Humm, MDa,b,c; Denny Sakkas, PhDc; Michele R. Hacker, ScDa,b

a

Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, 330 Brookline

Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, 25

Shattuck Street, Boston, MA, 02115, USA

Boston IVF, 130 Second Avenue, Waltham, MA, 02451, USA

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c

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Avenue, Kirstein 3, Boston, MA, 02215, USA b

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AFFILIATIONS AND ADDRESSES

CONFLICT OF INTEREST/DISCLOSURE STATEMENT The authors report no conflict of interest.

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CORRESPONDING AUTHOR

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Michele R. Hacker, ScD, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Kirstein 3, Boston, MA 02215 (Phone: 617.667.2933; FAX: 617.667.5011; email: [email protected]) LOCATION OF STUDY

Department of Obstetrics and Gynecology, Beth Israel Deconess Medical Center, Boston, MA WORD COUNT Abstract: 181 Main Text: 4,071

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CONDENSATION Although current evidence points to race and ethnicity as predictors of pregnancy and live birth

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Race/ethnicity and in vitro fertilization

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outcomes after IVF, better data and analytic methods are needed to fully address the question.

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ABSTRACT Objective: We conducted a systematic review to evaluate the influence of race and ethnicity on

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clinical pregnancy and live birth outcomes after in vitro fertilization. Data Sources: We searched PubMed, EMBASE, Web of Science, CINAHL, POPLINE, and Cochrane Central, and hand-searched relevant articles published through July 22, 2015.

Study Appraisal and Synthesis Methods: Two reviewers independently evaluated abstracts to

and/or ethnic groups after non-donor IVF cycles.

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identify studies that compared clinical pregnancy rates and live birth rates for two or more racial

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Results: Twenty-four studies were included. All five U.S. registry-based studies showed that black, Hispanic, and Asian women had lower clinical pregnancy rates and/or live birth rates after IVF, compared with white women. Similarly, most clinic-specific studies reported significant disparities in these primary outcomes, potentially attributable to differences in infertility

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diagnosis, spontaneous abortion, and obesity. Studies varied with respect to definitions of race/ethnicity, inclusion of first cycles vs. multiple cycles for individual women, and collected covariates. Most studies were limited by sample size, inadequate adjustment for confounding,

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selection bias, and extensive missing data.

Conclusions: Although current evidence points to race and ethnicity, especially black race, as

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strong predictors of poorer outcomes after in vitro fertilization, the utility of results is constrained by the limitations described.

KEYWORDS

in vitro fertilization; racial disparities

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INTRODUCTION

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Infertility is a global, multiethnic problem that affects 50 to 70 million couples worldwide (1). Infertile women of many races and ethnicities benefit from assisted reproductive

technologies (ART), particularly in vitro fertilization (IVF), now offered at clinics in over 162 countries (2). However, women who have a live birth using IVF are disproportionately white or

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Caucasian and are highly educated with middle-to-high income (3, 4). Several factors may

influence this trend. First, non-white women are less likely to utilize IVF services, despite higher

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infertility rates among black (7.2%) and Hispanic women (6.1%), compared with white women (5.5%) (5). IVF is a costly, complex treatment and may be prone to disparities caused by gaps in coverage or differences in cultural beliefs and educational level. Also, race and ethnicity may serve as a surrogate for known risk factors of IVF failure, such as age, obesity, smoking, or

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uterine abnormalities (6, 7). Finally, women of racial and ethnic minority groups may be genetically or environmentally predisposed to worse outcomes, independent of other clinical risk factors.

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There is relatively low minority representation in IVF clinics, and as a result, literature on ART predominantly reflects the experiences of white women. This is problematic because racial

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and ethnic groups differ in fertility characteristics and incidence of adverse perinatal outcomes. Disparities found in the outcomes of spontaneously conceived pregnancies are known to persist after adjustment for socioeconomic status and demographic characteristics, suggesting that other biological, environmental, or behavioral factors are at play (8, 9). These same factors may affect IVF outcomes as well. In fact, black and Hispanic women are more likely to have preterm birth after IVF, compared with white women, and infants born to black, Hispanic, and Asian women

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after IVF are more likely to have moderate and severe growth restriction (10, 11). A recent study of ART in the U.S. reported that, of all the patient characteristics thought to influence ART success, non-Hispanic black race had the strongest negative association with a good perinatal

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outcome after ART (12).

Knowledge of disparities in IVF could inform clinical decision-making and other

treatment modifications to improve the potential for success in certain populations. Previous

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reviews examining race/ethnicity and IVF outcomes have lacked systematic methodology (1315) or included only data collected at the national level (16). We therefore conducted a

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systematic review in order to report the clinical pregnancy rates (CPRs) and live birth rates (LBRs) among different racial and ethnic groups, using national and clinic-specific data for nondonor IVF. By tabulating success rates for each race/ethnicity group and framing them in a broader context, this review may help clinicians counsel and treat individual patients seeking

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infertility treatment.

OBJECTIVE: •

The aim of this study is to perform a systematic review of the literature to identify studies

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that compare pregnancy and live birth outcomes for women of different racial and/or

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ethnic groups.

MATERIALS AND METHODS We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses

guidelines and performed a search of PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central, and POPLINE on July 22, 2015 using terms for race and ethnicity, IVF treatment, and pregnancy and live birth outcomes (Suppl. A1) (17). Our ability to capture race/ethnicity as a variable is inevitably imperfect since no consensus exists on the definitions of race and ethnicity

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or on how such data should be collected.There are fifteen race categories defined by the U.S. Census Bureau (White; Black or African American; American Indian or Alaska Native; Asian Indian; Chinese; Filipino; Japanese; Korean; Vietnamese; Native Hawaiian; Guamanian or

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Chamorro; Samoan; Other Pacific Islander; Other Asian; and Some Other Race), as well as two ethnicity categories (Hispanic or Latino, and not Hispanic or Latino). These, according to the Bureau, reflect the social definition of race and ethnicity recognized in the U.S. We augmented

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this list with PubMed MeSH headings and other terms, such as native, aboriginal, and of color. We used the broad categories of white, black, Asian, and Hispanic to simplify presentation of

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data. If studies used more specific terms, including Caucasian, African American, South Asian, and Indian, we referred to these terms when reporting their findings. We reviewed all abstracts that compared CPRs and/or LBRs after IVF for at least two racial and/or ethnic groups. All study designs and languages were eligible for inclusion. We also

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searched the reference lists of included manuscripts to identify additional relevant manuscripts. Two investigators (L.A.H. and O.C.) independently reviewed all abstracts and excluded animal studies, reviews/meta-analyses, or case reports, as well as studies that did not evaluate IVF,

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included oocyte donation, did not report pregnancy or live birth rate, or did not include race/ethnicity. Studies that compared outcomes for one race to those of all other races (e.g. white

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vs. non-white) were also excluded. Disagreement about abstract classification was adjudicated. Outcome data were extracted independently by two investigators from full-text articles. Details of each included study also were extracted, and we identified whether there was adjustment for potential confounding, and, if so, which variables were adjusted for. Where “not significant” is reported in the tables, it is because the actual p values were unavailable in the full-text articles.

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No identifiable data was utilized in the course of this project; thus, institutional review board approval was not required.

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RESULTS Of the 47 abstracts that initially met inclusion criteria, we identified 24 full-text

publications that compared CPRs and/or LBRs after IVF for two or more racial and/or ethnic groups (Figure 1). Five national studies reported data from the SART Clinic Outcome Reporting

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System (SART CORS), and 19 site-specific studies reported data from individual IVF clinics (Tables 1 and 2). All studies used white (or Caucasian) women as the referent group, and all

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included more than twice as many white women as those of other racial or ethnic minority groups. When a study compared multiple minority groups with white women, we presented the results in respective tables for black, Asian, and Hispanic women separately. We identified 15 studies that met inclusion criteria, but were published as meeting abstracts only with no

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corresponding full-text publication (Suppl. A2). Tabulated results of these studies are in Suppl.

Two large studies allowed us to characterize national IVF success rates for the four main

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racial/ethnic groups of white, black, Asian, and Hispanic (10, 18). Both studies used SART data for 2004-2006 yet differed slightly in inclusion criteria and covariates. Baker et al. incorporated

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other/mixed and unknown categories but neglected to specify the overall race/ethnicity distribution. They reported lower CPRs for black, Asian, and Hispanic women (32.2%, 31.2%, and 37.5%, respectively), compared with white women (40.5%), as well as lower LBRs per pregnancy for black, Asian, and Hispanic women (75.1%, 81.5%, and 82.1%), compared with white women (83.7%). As expected, Fujimoto et al. reported essentially the same rates, but adjusted for fewer covariates and found that only Asian ethnicity was significantly predictive of

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a lower CPR. Both studies attributed the lower likelihood of live birth to the increased risk of pregnancy loss in black, Asian, and Hispanic women.

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Black / African American

Similar to the studies by Baker et al. and Fujimoto et al., two studies by Seifer et al.

confirmed lower CPR and LBR among black women, regardless of prior ART treatment (Table

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3). In the study with the most extensively adjusted model, the significant effect of race persisted after adjusting for treatment and patient factors, as well as clinic-level variables such as clinic

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volume and overall clinic pregnancy rate (19).

The smaller site-specific studies had some conflicting results. Sharara and McClamrock published the first evidence in 2000 that black women had lower CPR and lower LBR per cycle, as well as lower implantation rate than white women. The patients were matched based on age,

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diagnosis, and other factors; however, black women had higher BMI, longer duration of infertility, higher tubal factor infertility, and higher peak estradiol (E2) levels, potentially contributing to poorer outcomes. Three other studies conducted at military ART centers found

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disparities even in these “equal-access-to-care” settings. The study by McCarthy-Keith et al. examined 2,050 cycles from three IVF centers and found significantly lower CPR and LBR for

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black women, compared with white women. A smaller study by Csokmay et al. also found that black race was significantly predictive of lower LBR. The third military study by Feinberg et al. (2006) reported a “clinically significant” difference with lower LBR for black women, but this did not reach statistical significance. Of note, these studies did not adjust for observed differences in infertility diagnoses known to influence IVF success. Feinberg et al. (2006) stratified by uterine leiomyoma, but this did not affect the results. In contrast, Gleicher et al.

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controlled for fragile X mental retardation genotypes, as well as age, BMI, and AMH level, and found that decreased rates of pregnancy in black women persisted. A recent large study conducted by McQueen et al. found significantly lower CPR and LBR after adjustment for age,

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BMI, FSH, smoking status, and infertility diagnosis, demonstrating a live birth rate among black women that was almost half that of white women (16.9% vs. 30.7%) (20).

Nichols et al. was the only study reporting a higher CPR in African American women by

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comparing 24 African Americans to 273 whites. Almost all black women in this study were undergoing their first IVF cycle compared with 72% of whites. Dayal et al. found no significant

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differences in CPR, LBR, or implantation rate after controlling for tubal or uterine factors, BMI, and gonadotropin dose, but their study was underpowered and could detect only a 27% difference in pregnancy rates. Similarly, a study by Bendikson et al. had small numbers of minority patients and found no differences in unadjusted LBRs or miscarriage rates.

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For women who used cryopreserved embryos, SART data showed that black women had lower LBRs after transfer of frozen-thawed embryos than white women, although CPRs were not different (21). Analysis of a military center’s data by Csokmay et al. revealed no differences in

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CPR, LBR, or the spontaneous abortion rate for frozen-thawed cycles only. Of note, this study did find significant differences in the LBR after the completion of a fresh embryo transfer and a

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subsequent frozen-thawed transfer, with an overall LBR for whites of 62.2% compared with only 37.5% for African American women.

Asian / Indian

The three SART studies of Asian race reported worse CPR and LBR for this subgroup, independent of other patient- and treatment-related factors. Purcell et al., which used a 1999-

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2000 SART dataset, found lower CPR and LBR per cycle for Asian women than white women, after controlling for gravidity, parity, day 3 FSH and E2 levels, as well as the variables used in Baker et al. and Fujimoto et al.. The same study evaluated cycles from a California IVF clinic

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with a relatively large Asian patient population and confirmed that Asian race was associated with lower CPR than that of white women. Access to individual clinic data allowed them to include additional variables in their model, such as primary vs. secondary infertility, endometrial

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thickness, and difficulty of transfer.

Two studies published in 2015, including McQueen et al. conducted in Chicago and Kan

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et al. conducted in Sydney, Australia, evaluated the outcomes of more than 500 Asian women (Table 4). McQueen et al. found lower CPR and LBR for Asian women compared with white women, after adjustment for key factors such as age, BMI, and infertility diagnosis, although the analysis did not account for observed differences in stimulation time and peak E2 levels. Kan et

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al. identified differences in CPR and LBR that were no longer significant after controlling for age and duration of infertility, as Asian women tended to be older and waited longer to pursue IVF.

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Other clinic-specific studies focusing on Asian race were generally limited by small sample size or lacked statistical analysis. However, the three additional studies that did perform

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statistical analysis with adjustment for covariates concluded that disparities were present. Langen et al. used multivariate analysis to compare blastocyst transfer cycles in white women with cycles in Japanese, Chinese, and Filipino women and found significantly lower CPR and LBR for the Asian subgroup. In the study by Shahine et al., a lower LBR for Asian (Indian) women persisted after adjusting for age, stimulation protocol, and polycystic ovarian syndrome (PCOS) prevalence. Palep-Singh et al. examined cycles stratified by diagnosis of PCOS or tubal factor

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infertility, and found that Indian women with PCOS had lower CPR and LBR compared with white women. Asian women with tubal factor infertility, however, had similar outcomes as white women.

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The other studies showed no differences in CPR and/or LBR. Mahmud et al. noted that the CPR and LBR per cycle were influenced by greater abandonment of IVF cycles among

Indian women. Lashen et al. reported no difference in CPR between Indian or Pakistani women

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and matched white women, with no adjustment for variation in infertility duration and diagnosis. Neither Bendikson et al. nor Sharara et al. adjusted for significant differences in age, FSH level,

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and incidence of PCOS among Asian and white women. Gleicher et al. and Rudick et al. reported CPR values for Asians vs. Caucasians but conducted no statistical comparison.

Hispanic

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Baker et al. reported that Hispanic women had lower CPR and lower LBR per pregnancy compared with white women, corresponding to increased rates of stillbirth and fetal loss. Of the clinic-specific studies, McQueen et al. had the largest sample size comprising 288 Hispanic

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women and 3,003 white women. Although the CPR and LBR were both lower in absolute terms for Hispanic women compared with white women, there was no significant difference after

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controlling for age, BMI, day 3 FSH, smoking status, and infertility diagnosis. Three other studies that reported outcomes of Hispanic women undergoing IVF likewise found no significant differences in CPR or LBR between Hispanic and white women (22-24). These studies did not adjust for observed differences in infertility diagnosis. Inadequate power likely also impacted results, given that the numbers of Hispanic women in these studies ranged from just 18 to 134.

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Both McCarthy-Keith et al. and Rudick et al. found lower CPR and LBR for Hispanics, yet no

Potential for Bias and Unmeasured Confounding Race/Ethnicity

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statistical comparison was reported (25).

Race/ethnicity was not a required field for SART CORS until 2005, and therefore these

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data were missing in at least one-third of cycles in national studies (18). Three studies used data only from clinics that reported race in >95% of cycles (19, 21, 26). Seifer et al. (2010) also

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analyzed SART cycles with and without race/ethnicity data and found similar CPRs and LBRs, suggesting that the distribution of missing race/ethnicity data may be unrelated to outcomes. No other studies reported the proportion of women at their clinics for which race/ethnicity designation was complete. The probability for such data to be missing may be associated with

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race/ethnicity and with the treatment outcome, introducing selection bias. Even when race/ethnicity is documented, the method for doing so varies, leading to potential misclassification. Use of self-identification, assignment by provider, or other methods

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to determine race/ethnicity is unknown in the SART database. Of the clinic-specific studies, ten used self-reporting, two used both self-reporting and independent verification by a provider, and

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seven did not specify. It is also important to note that the broad categories of white, black, Hispanic, and Asian groups may ignore important differences in reproductive outcomes based on genetic make-up and country of origin. Socioeconomic Factors and Lack of Access None of the studies controlled for socioeconomic status, insurance, or other social or cultural factors that could contribute to lower success rates in minority individuals. Women who

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might otherwise benefit from IVF may not undergo it due to expense, language/cultural barriers, and limited access to care. In the U.S., the average cost for one IVF cycle is $12,400, and many couples undergo multiple cycles before achieving a live birth, such that total treatment and

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medication costs can reach $85,000 (27-29). Currently, 15 states mandate that insurers cover ART, however not all specifically cover IVF treatment (30). Even in cases of IVF coverage, there is no evidence that these mandates increase access among racial and ethnic minorities or

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persons of lower socioeconomic status (31). In fact, mandates have primarily increased IVF utilization among highly educated white women age 30 and older. Disparities in access have not

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disappeared at military IVF centers, which are considered “equal-access-to-care” settings with low-cost treatment. A higher proportion of African Americans seek infertility services at military centers than at other centers, but the patient populations at military centers and in states with comprehensive insurance coverage still do not reflect national demographics (32).

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Amid the substantial socioeconomic and educational barriers to IVF, there is evidence that minority women, particularly black women, generally wait longer before seeking care, resulting in longer duration of infertility (33). Cultural variation may play a role, given that

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African American and Asian women express more concerns than do white women about the social stigma of infertility, disappointing spouse or family, and using science or technology to

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conceive (34). When women of racial/ethnic minorities do seek care, they may be older with greater risk of diminished ovarian reserve and worse prognosis. Additionally, Seifer et al. (2010) found that black women were significantly more likely than white women to seek care and receive IVF treatment at lower-volume centers with overall lower pregnancy rates. Of note, controlling for clinic volume, age and duration of infertility did not eliminate the disparities identified in several studies in this review.

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One study by Smith et al., which did not meet our inclusion criteria, nevertheless did evaluate the effects of household income, education, and race on the use of infertility services and on pregnancy rates (35). White race was associated with higher odds of pregnancy after IVF

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in bivariate analyses; however, multivariable regression revealed differences in outcome only based on whether women held a college degree. Further research is needed to delineate the influence of socioeconomics, education, and race on IVF outcomes.

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Pregnancy Loss / Miscarriage

Several studies in this review suggested that early and/or late pregnancy loss may be a

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mediator explaining the lower CPR and LBR among minority women (18-21, 36, 37). For example, Baker et al. found that compared with white women, Hispanics and Asians had a significantly greater risk of pregnancy loss in the second and third trimesters, and blacks had a greater risk in all trimesters. Black and Hispanic women may disproportionately exhibit risk

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factors for miscarriage after IVF, such as older age, elevated BMI, reduced ovarian reserve, and other comorbidities, thus leading to confounding. Interestingly, though, studies of SART data in this review report differences in spontaneous abortion rates independent of age, BMI, previous

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spontaneous abortions, gonadotropin dose, and other factors (18, 19, 21). In studies for which such data were available, minority women and white women generally showed similar embryo

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quality and number of embryos retrieved, as well as no clinically significant differences in endometrial thickness. It is also worth noting that increased pregnancy loss among minority women is not necessarily unique to IVF. It may be difficult to determine if lower pregnancy and LBR after IVF are the result of IVF-specific factors or if they primarily reflect the greater risk of miscarriage already known to exist in black and Hispanic women (38). Infertility Diagnosis

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Tubal factors, such as hydrosalpinx, and uterine factors, such as leiomyoma, are common causes of infertility and are associated with significantly reduced implantation rates, CPRs, and LBRs after IVF as well as increased risk of spontaneous abortion (39-41). Conversely, surgical

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treatment of hydrosalpinges prior to IVF can result in the doubling of clinical and ongoing

pregnancy rates (42). It has been hypothesized that differences in chlamydia infection may

influence infertility diagnosis in some racial and ethnic groups given chlamydia infection is an

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important risk factor for tubal factor infertility and is six times more common in black women and two times more common in Hispanic women than in white women in the U.S. (43).

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Additionally, black women are known to develop leiomyoma at two to three times the rate of white women, and they have increased tumor size and severity of symptoms, despite diagnosis at a younger age (44, 45). Based on findings of higher tubal factor and uterine factor infertility among black patients, multiple studies proposed that differences in infertility diagnosis might

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drive worse IVF outcomes (19-21, 37, 46-48).

Other infertility diagnoses may also contribute to variation in IVF success. Compared to minority women, white women have a higher incidence of male factor infertility (19, 21, 37, 49).

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White women may be more likely to have PCOS, endometriosis, and/or other ovulation disorders compared with black or Hispanic women, and there is conflicting evidence on whether PCOS is

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more common in Asians than whites undergoing IVF (19, 21, 24, 37, 49-52). Though unlikely to fully explain disparities, ethnic differences in the prevalence and metabolic/reproductive consequences of PCOS have been previously identified (14). Palep-Singh et al. (2007) found that among women with PCOS Caucasian women had 2.5 times higher chance of clinical pregnancy than Indian women.

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All analyses of national data adjusted extensively for infertility diagnosis and reported differences in pregnancy-related outcomes independent of these factors. However, statistical adjustment was inconsistently applied in clinic-specific studies; in fact, eight studies found

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racial/ethnic differences in infertility diagnosis, but did not adjust for these differences (22, 24, 36, 48-50, 53, 54). Obesity and Other Comorbidities

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In this review, six studies noted significantly higher BMI among black women, one noted higher BMI in Hispanic women, and several also found lower BMI among Asian women. This is

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consistent with age-adjusted obesity prevalence in the U.S., which was significantly higher among black women (56.6%) and Hispanic women (44.4%), compared with white women (32.8%), and Asian women (11.4%) (55). A recent SART study by Luke et al. that did not meet our inclusion criteria found that more than one-third of black women undergoing donor and non-

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donor IVF were obese, compared with only 16% of white women and 7% of Asian women (56). All obese women were less likely to have a clinical pregnancy. Of note, significant racial and ethnic differences in outcomes persisted even within BMI categories and after adjustment for

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BMI, with both obese and non-obese minority women more likely to fail to achieve pregnancy and live birth after IVF. Potential explanations for worse prognosis in obese women include

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insulin resistance, abnormal secretion of hormones, such as leptin, and direct effects on oocyte and embryo quality, although the mechanisms are largely unknown (57-60). It is notable that no studies in this review assessed the influence of comorbidities, with

the exception of obesity, that vary in prevalence according to race/ethnicity and may affect IVF prognosis, such as diabetes, coronary artery disease, and chronic hypertension, likely due to unavailability of the data. To determine the etiology of disparities, it may be important to

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examine differences in chronic diseases and overall health status. Ovarian Function and Hormone Levels

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No studies in this review directly reported rates of premature ovarian insufficiency (POI) by race/ethnicity; however, Gleicher et al. found racial/ethnic differences in genotypes predictive of pregnancy and associated with increased POI, as well as PCO-like phenotype and risk of

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autoimmunity (61, 62). In line with these findings, race/ethnicity is known to be predictive of menopausal onset, as well as hormone levels and other markers of ovarian aging (13, 63, 64).

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AMH levels for black and Hispanic women are reportedly about 25% lower than that for white women (65), although with significant variation according to age (66). Genetic variants in Caucasian and African American women have also been predictive of AMH and FSH levels, with important implications on FSH serum levels, receptor sensitivity to FSH, and response to stimulation (64, 67, 68). Finally, three studies in this review also found significantly higher peak

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E2 levels, which may affect implantation, in black women compared with white women, and two

COMMENT

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reported this finding in Asian women (20, 22, 26, 36, 48).

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Large, controlled studies that assess the effects of race/ethnicity on IVF outcomes are relatively sparse. The SART data from 2004-2006 provide the strongest evidence of disparities for black, Asian, and Hispanic women, and these data are bolstered by similar findings in 19992000 for black and Asian women. By also accounting for clinic-specific studies, this review suggests a relationship between black race and worse outcomes after IVF, since 8 out of 12 studies have shown significant differences in CPR and/or LBR for black vs. white women. There are important limitations in these studies, however, and the results for Asian and Hispanic

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women are largely inconsistent. Overlapping datasets, variability in the use of multiple cycles per woman, and differences in inclusion criteria and adjustment for covariates thwart the use of meta-analysis. In addition, study findings may have limited generalizability given that the

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population of couples who undergo IVF does not reflect the population suffering from infertility. Not only are there disparities in access to infertility treatment, but there is also evidence that the time to initiate care and the case volume of the treatment center vary with race/ethnicity.

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Lack of complete race/ethnicity data and other key variables caused many studies to be susceptible to selection bias, misclassification, and confounding. Although clinic-specific studies

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provide additional demographic and treatment variables not captured by SART, they often have inadequate statistical power to detect differences that may be clinically meaningful. Of note, it is important to consider whether the variable of interest, such as obesity, is acting as a mediator along the casual pathway between the exposure and IVF outcome or as a confounder that

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requires adjustment to avoid spurious associations.

Additionally, most published studies use IVF cycles, rather than women, as the unit of analysis. Women may be represented multiple times in these datasets, but statistical methods

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employed typically do not account for the repeated measures. Outcomes per cycle are less useful in a clinical setting, given a patient is generally interested in knowing her chances of having a

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baby over the entire treatment course, or the cumulative rate. Most studies in this review attempted to overcome the limitations of per-cycle estimates by including only first IVF cycles. This approach only conveys IVF success rates on the first try, whereas most women will undergo multiple cycles before achieving a live birth or terminating treatment. Racial and ethnic disparities in IVF outcomes are highly relevant to clinical practice. As racial and ethnic populations expand and IVF improves as a successful, accessible, and

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affordable infertility treatment, we will require better understanding of disparities in IVF outcomes. For decades, clinical research in IVF has been performed in the context of white or Caucasian populations, and adjustments may be necessary to personalize protocols for expanding

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and increasingly heterogeneous patient populations. Evidence of disparities may motivate such innovation, and at the very least, it would improve patient counseling and inform accurate

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projections of IVF success.

ACKNOWLEDGMENTS

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None.

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REFERENCES

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1. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod 2007;22(6):1506-12. 2. Jones HW, Jr., Cooke I, Kempers R, Brinsden P, Saunders D. International Federation of Fertility Societies Surveillance 2010: preface. Fertil Steril 2011;95(2):491. 3. Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J. Fertility, family planning, and reproductive health of U.S. women: data from the 2002 National Survey of Family Growth. Vital Health Stat 23 2005(25):1-160. 4. Katz P, Nachtigall R, Showstack J. The economic impact of the assisted reproductive technologies. Nat Cell Biol 2002;4 Suppl:s29-32. 5. Chandra A, Copen CE, Stephen EH. Infertility and Impaired Fecundity in the United States, 19822010: Data From the National Survey of Family Growth. National Health Statistics Reports 2013. 6. Lintsen AM, Pasker-de Jong PC, de Boer EJ, Burger CW, Jansen CA, Braat DD, et al. Effects of subfertility cause, smoking and body weight on the success rate of IVF. Hum Reprod 2005;20(7):186775. 7. Penzias AS. Recurrent IVF failure: other factors. Fertil Steril 2012;97(5):1033-8. 8. Berg CJ, Wilcox LS, d'Almada PJ. The prevalence of socioeconomic and behavioral characteristics and their impact on very low birth weight in black and white infants in Georgia. Matern Child Health J 2001;5(2):75-84. 9. Giscombe CL, Lobel M. Explaining disproportionately high rates of adverse birth outcomes among African Americans: the impact of stress, racism, and related factors in pregnancy. Psychol Bull 2005;131(5):662-83. 10. Fujimoto VY, Luke B, Brown MB, Jain T, Armstrong A, Grainger DA, et al. Racial and ethnic disparities in assisted reproductive technology outcomes in the United States. Fertil Steril 2010;93(2):382-90. 11. Xiong X, Pridjian G, Dickey RP. Racial and ethnic disparities in preterm births in infants conceived by in vitro fertilization in the United States. Am J Obstet Gynecol 2013;209(2):128 e1-6. 12. Joshi N, Kissin D, Anderson JE, Session D, Macaluso M, Jamieson DJ. Trends and correlates of good perinatal outcomes in assisted reproductive technology. Obstet Gynecol 2012;120(4):843-51. 13. Butts SF, Seifer DB. Racial and ethnic differences in reproductive potential across the life cycle. Fertil Steril 2010;93(3):681-90. 14. Huddleston HG, Cedars MI, Sohn SH, Giudice LC, Fujimoto VY. Racial and ethnic disparities in reproductive endocrinology and infertility. Am J Obstet Gynecol 2010;202(5):413-9. 15. Spitzer T, Fujimoto VY. Ethnic differences in assisted reproductive technologies outcomes. Semin Reprod Med 2013;31(5):360-4. 16. Wellons MF, Fujimoto VY, Baker VL, Barrington DS, Broomfield D, Catherino WH, et al. Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes. Fertil Steril 2012;98(2):406-9. 17. Moher D, Liberati A, Tetzlaff J, Altman D. Preferred reporting items forsystematic reviews and meta-analyses: the PRISMA statement. Annals of Internal Medicine 2009;153(4):264-269. 18. Baker VL, Luke B, Brown MB, Alvero R, Frattarelli JL, Usadi R, et al. Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Fertil Steril 2010;94(4):1410-6. 19. Seifer DB, Frazier LM, Grainger DA. Disparity in assisted reproductive technologies outcomes in black women compared with white women. Fertil Steril 2008;90(5):1701-10.

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20. McQueen DB, Schufreider A, Lee SM, Feinberg EC, Uhler ML. Racial disparities in in vitro fertilization outcomes. Fertil Steril 2015;104(2):398-402 e1. 21. Seifer DB, Zackula R, Grainger DA, Society for Assisted Reproductive Technology Writing Group R. Trends of racial disparities in assisted reproductive technology outcomes in black women compared with white women: Society for Assisted Reproductive Technology 1999 and 2000 vs. 2004-2006. Fertil Steril 2010;93(2):626-35. 22. Bendikson K, Cramer DW, Vitonis A, Hornstein MD. Ethnic background and in vitro fertilization outcomes. Int J Gynaecol Obstet 2005;88(3):342-6. 23. Feinberg EC, Larsen FW, Wah RM, Alvero RJ, Armstrong AY. Economics may not explain Hispanic underutilization of assisted reproductive technology services. Fertil Steril 2007;88(5):1439-41. 24. Shuler A, Rodgers AK, Budrys NM, Holden A, Schenken RS, Brzyski RG. In vitro fertilization outcomes in Hispanics versus non-Hispanic whites. Fertil Steril 2011;95(8):2735-7. 25. Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod 2012;27(11):3321-7. 26. Purcell K, Schembri M, Frazier LM, Rall MJ, Shen S, Croughan M, et al. Asian ethnicity is associated with reduced pregnancy outcomes after assisted reproductive technology. Fertil Steril 2007;87(2):297-302. 27. Collins J. Cost-effectiveness of in vitro fertilization. Semin Reprod Med 2001;19(3):279-89. 28. Martin JR, Bromer JG, Sakkas D, Patrizio P. Insurance coverage and in vitro fertilization outcomes: a U.S. perspective. Fertil Steril 2011;95(3):964-9. 29. Neumann PJ, Gharib SD, Weinstein MC. The cost of a successful delivery with in vitro fertilization. N Engl J Med 1994;331(4):239-43. 30. Technologies SfAR. State Infertility Insurance Laws. In. 31. Bitler M, Schmidt L. Health disparities and infertility: impacts of state-level insurance mandates. Fertil Steril 2006;85(4):858-65. 32. Jain T, Hornstein MD. Disparities in access to infertility services in a state with mandated insurance coverage. Fertil Steril 2005;84(1):221-3. 33. Jain T. Socioeconomic and racial disparities among infertility patients seeking care. Fertil Steril 2006;85(4):876-81. 34. Missmer SA, Seifer DB, Jain T. Cultural factors contributing to health care disparities among patients with infertility in Midwestern United States. Fertil Steril 2011;95(6):1943-9. 35. Smith JF, Eisenberg ML, Glidden D, Millstein SG, Cedars M, Walsh TJ, et al. Socioeconomic disparities in the use and success of fertility treatments: analysis of data from a prospective cohort in the United States. Fertil Steril 2011;96(1):95-101. 36. Csokmay JM, Hill MJ, Maguire M, Payson MD, Fujimoto VY, Armstrong AY. Are there ethnic differences in pregnancy rates in African-American versus white women undergoing frozen blastocyst transfers? Fertil Steril 2011;95(1):89-93. 37. Feinberg EC, Larsen FW, Catherino WH, Zhang J, Armstrong AY. Comparison of assisted reproductive technology utilization and outcomes between Caucasian and African American patients in an equal-access-to-care setting. Fertil Steril 2006;85(4):888-94. 38. Mukherjee S, Velez Edwards DR, Baird DD, Savitz DA, Hartmann KE. Risk of miscarriage among black women and white women in a U.S. Prospective Cohort Study. Am J Epidemiol 2013;177(11):12718. 39. Sunkara SK, Khairy M, El-Toukhy T, Khalaf Y, Coomarasamy A. The effect of intramural fibroids without uterine cavity involvement on the outcome of IVF treatment: a systematic review and metaanalysis. Hum Reprod 2010;25(2):418-29.

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40. Camus E, Poncelet C, Goffinet F, Wainer B, Merlet F, Nisand I, et al. Pregnancy rates after in-vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a meta-analysis of published comparative studies. Hum Reprod 1999;14(5):1243-9. 41. Zeyneloglu HB, Arici A, Olive DL. Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization-embryo transfer. Fertil Steril 1998;70(3):492-9. 42. Johnson N, van Voorst S, Sowter MC, Strandell A, Mol BW. Surgical treatment for tubal disease in women due to undergo in vitro fertilisation. Cochrane Database Syst Rev 2010(1):CD002125. 43. CDC. Sexually Transmitted Disease Surveillance 2012. U.S. Department of Health and Human Services 2014. 44. Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol 1997;90(6):967-73. 45. Kjerulff KH, Langenberg P, Seidman JD, Stolley PD, Guzinski GM. Uterine leiomyomas. Racial differences in severity, symptoms and age at diagnosis. J Reprod Med 1996;41(7):483-90. 46. Dayal MB, Gindoff P, Dubey A, Spitzer TL, Bergin A, Peak D, et al. Does ethnicity influence in vitro fertilization (IVF) birth outcomes? Fertil Steril 2009;91(6):2414-8. 47. Nichols JE, Jr., Higdon HL, 3rd, Crane MMt, Boone WR. Comparison of implantation and pregnancy rates in African American and white women in an assisted reproductive technology practice. Fertil Steril 2001;76(1):80-4. 48. Sharara FI, McClamrock HD. Differences in in vitro fertilization (IVF) outcome between white and black women in an inner-city, university-based IVF program. Fertil Steril 2000;73(6):1170-3. 49. McCarthy-Keith DM, Schisterman EF, Robinson RD, O'Leary K, Lucidi RS, Armstrong AY. Will decreasing assisted reproduction technology costs improve utilization and outcomes among minority women? Fertil Steril 2010;94(7):2587-9. 50. Lashen H, Afnan M, Sharif K. A controlled comparison of ovarian response to controlled stimulation in first generation Asian women compared with white Caucasians undergoing in vitro fertilisation. Br J Obstet Gynaecol 1999;106(5):407-9. 51. Shahine LK, Lamb JD, Lathi RB, Milki AA, Langen E, Westphal LM. Poor prognosis with in vitro fertilization in Indian women compared to Caucasian women despite similar embryo quality. PLoS One 2009;4(10):e7599. 52. Kan A, Leung P, Luo K, Fay L, Tan CL. Do Asian women do as well as their Caucasian counterparts in IVF treatment: Cohort study. J Obstet Gynaecol Res 2015;41(6):946-51. 53. Mahmud G, Lopez Bernal A, Yudkin P, Ledger W, Barlow DH. A controlled assessment of the in vitro fertilization performance of British women of Indian origin compared with white women. Fertil Steril 1995;64(1):103-6. 54. Sharara FI, Fouany MR, Sharara YF, Abdo G. Racial differences in ART outcome between white and South Asian women. Middle East Fertil Soc J 2012;17(2):89-92. 55. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity among adults: United States, 2011-2012. NCHS Data Brief 2013(131):1-8. 56. Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. Racial and ethnic disparities in assisted reproductive technology pregnancy and live birth rates within body mass index categories. Fertil Steril 2011;95(5):1661-6. 57. Bausenwein J, Serke H, Eberle K, Hirrlinger J, Jogschies P, Hmeidan FA, et al. Elevated levels of oxidized low-density lipoprotein and of catalase activity in follicular fluid of obese women. Mol Hum Reprod 2010;16(2):117-24. 58. Norman RJ, Noakes M, Wu R, Davies MJ, Moran L, Wang JX. Improving reproductive performance in overweight/obese women with effective weight management. Hum Reprod Update 2004;10(3):267-80.

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59. Luzzo KM, Wang Q, Purcell SH, Chi M, Jimenez PT, Grindler N, et al. High fat diet induced developmental defects in the mouse: oocyte meiotic aneuploidy and fetal growth retardation/brain defects. PLoS One 2012;7(11):e49217. 60. Luke B, Brown MB, Stern JE, Missmer SA, Fujimoto VY, Leach R. Female obesity adversely affects assisted reproductive technology (ART) pregnancy and live birth rates. Hum Reprod 2011;26(1):245-52. 61. Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, et al. The FMR1 premutation and reproduction. Fertil Steril 2007;87(3):456-65. 62. Gleicher N, Weghofer A, Lee IH, Barad DH. Association of FMR1 genotypes with in vitro fertilization (IVF) outcomes based on ethnicity/race. PLoS One 2011;6(4):e18781. 63. Luborsky JL, Meyer P, Sowers MF, Gold EB, Santoro N. Premature menopause in a multi-ethnic population study of the menopause transition. Hum Reprod 2003;18(1):199-206. 64. Schuh-Huerta SM, Johnson NA, Rosen MP, Sternfeld B, Cedars MI, Reijo Pera RA. Genetic variants and environmental factors associated with hormonal markers of ovarian reserve in Caucasian and African American women. Hum Reprod 2012;27(2):594-608. 65. Bleil ME, Gregorich SE, Adler NE, Sternfeld B, Rosen MP, Cedars MI. Race/ethnic disparities in reproductive age: an examination of ovarian reserve estimates across four race/ethnic groups of healthy, regularly cycling women. Fertil Steril 2014;101(1):199-207. 66. Seifer DB, Golub ET, Lambert-Messerlian G, Benning L, Anastos K, Watts DH, et al. Variations in serum mullerian inhibiting substance between white, black, and Hispanic women. Fertil Steril 2009;92(5):1674-8. 67. Kuijper EA, Blankenstein MA, Luttikhof LJ, Roek SJ, Overbeek A, Hompes PG, et al. Frequency distribution of polymorphisms in the FSH receptor gene in infertility patients of different ethnicity. Reprod Biomed Online 2011;22 Suppl 1:S60-5. 68. Simoni M, Casarini L. Mechanisms in endocrinology: Genetics of FSH action: a 2014-and-beyond view. Eur J Endocrinol 2014;170(3):R91-107.

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TABLES

Clinic Outcome Reporting System (SART CORS).

Year

Setting

Race/Ethnicity Data

(Jan 2004-Dec

225,889 cycles Unknown

Repeated cycles; Fresh

Confounders a

Maternal age, embryos

distribution of White,

transferred, assisted

Black, Asian, Hispanic,

hatching, ICSI, previous

Other/mixed, Unknown

term birth, prior preterm

TE D

2006)

M AN U

SART CORS

EP

2010

AC C

Baker et al

Adjustment for

Cycle Info

SC

Reference

RI PT

Table 1. Characteristics of five studies that analyzed IVF cycle data from the Society for Assisted Reproductive Technology

birth, prior spontaneous abortion, infertility diagnosis (male factor, ovulation disorders, diminished ovarian reserve, tubal factors, uterine factors, other factors,

24

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unexplained factors) SART CORS

139,027 cycles

(2004-2006)

White (n=107,484) Asian (n=13,671)

M AN U

Black (n=8,903)

Repeated cycles; Fresh

RI PT

2010

SC

Fujimoto et al

a

Maternal age, embryos

transferred, infertility diagnosis (male factor, endometriosis, PCOS, diminished ovarian reserve, tubal factors, other factors)

Hispanic (n=8,969) 158,693 cycles

(2004-2006)

Fresh:

TE D

SART CORS

White (n=120,994)

EP

2010

Black (n=10,354)

AC C

Seifer et al

First cycles and

a

repeated cycles

spontaneous abortion,

Maternal age, parity, prior

(subgroups); Fresh and embryos transferred, ICSI, cryopreserved; clinics

infertility diagnosis (tubal

providing ≥50

factor, male factor, uterine

cycles/yr and reporting factors, diminished ovarian

Cryopreserved: White (n=25,412)

race for >95% of

reserve, other ovarian

cycles

disorder, endometriosis)

25

ACCEPTED MANUSCRIPT

Black (n=1,933) 2008

SART CORS

72,272 cycles

(1999-2000)

Fresh:

First cycles and

RI PT

Seifer et al

repeated cycles

a

Maternal age, parity, prior

spontaneous abortion, day

White (n=58,459)

cryopreserved; clinics

transferred, infertility

providing ≥50

diagnosis (tubal factor,

M AN U

Black (n=3,116)

SC

(subgroups); Fresh and 3 FSH ratio, embryos

cycles/yr and reporting male factor, uterine factor,

Cryopreserved:

endometriosis, diminished

cycles

ovarian reserve, other

TE D

White (n=10,147)

race for >95% of

ovulation disorders, other

Black (n=550)

Purcell et al

2007

AC C

EP

factors, idiopathic), clinic

(a) SART

CORS (1999-

(a) 27,272 cycles White (n = 25,843)

2000)

Asian (n = 1,429)

volume, clinic success rate (a) First cycles only;

a

from clinics providing

gravidity, parity, embryos

≥50 cycles/yr and

transferred, history of

reported race for

spontaneous or therapeutic

(a) Maternal age,

26

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of California,

(b) 567 cycles White (n = 370)

San Francisco Asian (n = 197)

abortion, day 3 FSH and

clinics)

E2 levels, ICSI, infertility

(b) Repeated cycles

SC

(Jan 2001-Dec

>95% of cycles (187

RI PT

(b) University

AC C

EP

TE D

M AN U

2003)

diagnosis (diminished ovarian reserve, other ovulation disorders, male factor, unexplained) (b) Maternal age, primary or secondary infertility, number of previous IVF attempts, stimulation protocol, prior spontaneous or therapeutic abortion, infertility diagnosis (diminished ovarian reserve, ovulatory dysfunction, or

27

ACCEPTED MANUSCRIPT

unexplained infertility),

a

M AN U

SC

RI PT

days of stimulation, E2

Multivariable analysis

level, endometrial thickness, embryo fragmentation score, physician, difficulty of embryo transfer

EP AC C

hormone

TE D

Abbreviations: ICSI, intracytoplasmic sperm injection; PCOS, polycystic ovarian syndrome; E2, estradiol; FSH, follicle-stimulating

28

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Table 2. Characteristics of 19 studies with site-specific data from IVF clinics. Race/Ethnicity Year

Setting

Cycle Info Data

al

Fertility Centers of

4,045 women

First cycles only; *Age, BMI, day 3 FSH, smoking status,

Illinois (Jan 2010-

White (n=3,003)

Fresh

Dec 2012)

Black (n=213)

SC

2015

infertility diagnosis

M AN U

McQueen et

Adjustment for Confounders

RI PT

Reference

Asian (n=541)

Hispanic (n=288) 2015

IVF Australia, Sydney

2,594 women

TE D

Kan et al

Asian (n=522)

(January 2001-Dec

First cycles only; *Age, duration of infertility Fresh

Caucasian

EP

2010)

Rudick et al

2012

AC C

(n=2072)

University of

Southern California

188 women White (n=100)

First cycles only;

a

Fresh

diagnosis of diminished ovarian reserve

Age, embryos transferred, embryo quality,

(USC) Fertility Clinic

29

ACCEPTED MANUSCRIPT

(Jan 2006-Aug 2009)

Asian (n=49)

RI PT

Hispanic (n=26) Other (n=13) Virginia Center for Reproductive

292 cycles

First cycles only; No adjustment for observed differences in

White (n=238) South Asian

Walter Reed Army Medical Center

(n=54)

TE D

(Jan 2004-Dec 2009)

169 women

EP

Fresh:

(Jan 2003-Dec 2008)

White (n = 68)

AC C

2011

Fresh blastocyst

maternal age, FSH, PCOS

transfers (day 5

Medicine

Csokmay et al

SC

2012

M AN U

Sharara et al

AA (n=30)

only) in women < 40 yr

Unspecified

No adjustment for observed differences in

cycle number;

leiomyoma

Fresh and cryopreserved blastocyst transfers

Cryopreserved: (subgroup

30

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White (n=119)

analysis)

Center for Human

339 women

Reproduction in New York (dates not

Caucasian (n=232)

Unspecified

a

Age, BMI, FMR1 genotype, AMH levels

cycle number in

SC

2011

consecutive IVF

AA (n=59)

M AN U

Gleicher et al

RI PT

AA (n=50)

available)

patients

Asian (n=48) 2011

University of Texas Health Science

435 women

TE D

Shuler et al

White (n=301)

Center, South Texas

First cycles only; No adjustment for observed differences in Fresh

tubal infertility

First cycles only;

a

Fresh

endometrial thickness

Hispanic (n=134)

EP

Fertility Center

Langen et al

2010

AC C

(Jan 1998-Jan 2008) Stanford University Medical Center

180 cycles White (n=112)

Gravidity, BMI, history of prior IVF,

31

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Keith et al

Walter Reed Army

2,050 cycles

Medical Center,

White (n=1280)

Wilford Hall Medical

First cycles only; No adjustment for observed differences in

RI PT

2010

Asian (n=68)

Fresh; in women

infertility diagnosis

< 42 yr with AA (n=353)

Center and Tripler

SC

McCarthy-

(Jan 2005-Dec 2006)

FSH levels on

M AN U

day 3 or 10 ≤12

Army Medical Center

mIU/mL

(Jan 2000-Dec 2005) 2009

George Washington University Medical

Center

a

Day 3 embryo

dose of gonadotropins

BMI, uterine fibroids, tubal factor infertility,

transfers

AA (n=71)

AC C

Fertility and IVF

Caucasian (n=180)

First cycles only;

EP

Faculty Associates

251 cycles

TE D

Dayal et al

(Jan 2004-Dec 2005) Shahine et al

2009

Stanford University

225 women

First cycles only;

a

Maternal age, stimulation protocol, PCOS

32

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Caucasian (n=145)

Day 5 or 6

Indian (n=80)

blastocyst transfers

et al

Feinberg et al

University of Leeds, England

2006

Unspecified

608 cycles Caucasian (n=420)

(2000-2004)

Asian (n=188)

Walter Reed Army

1,387 women

Medical Center

TE D

Caucasian (n=974)

(1999-2003)

AA (n=253)

Feinberg et al

2007

AC C

EP

Hispanic (n=56)

Walter Reed Army Medical Center

1,387 women Caucasian (n=974)

a

Maternal age, LH, and gonadotropin dose

SC

2007

cycle number; Fresh

M AN U

Palep-Singh

RI PT

(Jan 2005-June 2007)

First cycles only; Presence of uterine fibroids (stratified for in women < 42

AA vs. Caucasian)

yr with FSH levels on day 3 or 10 ≤12 mIU/mL First cycles only; NA in women < 42 yr with FSH

33

ACCEPTED MANUSCRIPT

AA (n=253) Hispanic (n=56)

levels on day 3 or 10 ≤12 mIU/mL

al

Boston IVF

1,135 cycles

Collaborative Clinics

White (n=1,039)

First cycles only

SC

2005

M AN U

Bendikson et

RI PT

(1999-2003)

(1994-1998)

No adjustment for observed differences in BMI, gravidity, duration of infertility, infertility diagnosis

Black (n=43) Asian (n=35)

2001

Greenville Hospital System

Sharara and

2000

Repeated cycles

a

First cycles and

No adjustment for observed differences in

Parity, BMI, tubal factor infertility

White (n=333)

AC C

(Nov 1996-June 2000)

358 cycles

EP

Nichols et al

TE D

Hispanic (n=18)

University-based,

Black (n=25)

168 cycles

34

ACCEPTED MANUSCRIPT

Maryland

White (n=121)

(Apr 1997-July 1999)

Black (n=47)

repeated cycles

BMI, infertility diagnosis, duration of

(subgroups); in

infertility, protocol variation

RI PT

McClamrock

women ≤ 40 yr,

(Excludes day 3

SC

FSH>10,

(Matched for maternal age, early FSH, infertility diagnosis, gonadotropin dose, treatment yr)

M AN U

hydrosalpinges,

and intracavitary uterine

Lashen et al

1999

Birmingham

TE D

abnormalities)

324 women

England

(Matched for age, day 3 FSH, gonadotropin

AC C

Asian (n=108)

dose, indication)

(1994-1997) Mahmud et al

1995

Oxford University, England

132 women White (n=88)

No adjustment for observed differences in duration of infertility, infertility diagnosis

Caucasian (n=216)

EP

Women’s Hospital,

First cycles only

First cycles and

No adjustment for observed differences in

repeated cycles

duration of fertility, primary vs. secondary

35

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(Apr 1987-Dec 1993)

Indian (n=44)

(subgroups)

infertility, infertility diagnosis

RI PT

(Matched for maternal age, BMI, treatment yr)

Multivariable analysis

SC

a

M AN U

Abbreviations: AA, African American; PCOS, polycystic ovarian syndrome; BMI, body mass index; FSH, follicle-stimulating

AC C

EP

TE D

hormone; AMH, anti-Müllerian hormone.

36

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Table 3. Clinical pregnancy and live birth rates among black women undergoing IVF compared with white women. LBR (%)

RI PT

CPR (%) Significance Black

White

Baker et al

32.2

40.5

Fujimoto et al

32.0

(No prior ART) (Prior ART)

Significance

Black

White

OR 0.76, CI [0.72-0.80]

75.1b

83.7

OR 0.62 CI [0.56-0.68]

40.1

OR 1.09, CI [0.99-1.2]

75.0a

83.7

OR 0.62 CI [0.56-0.68]

29.3

38.3

P<0.001

76.9a

84.8

RR 1.31d, CI [1.26-1.37]

25.0

32.4

P<0.001

71.0a

81.6

RR 1.33d, CI [1.24-1.42]

(No prior ART)

27.7

33.6

P<0.001

20.7c

28.4

RR 1.24d, CI [1.12-1.36]

(Prior ART)

22.1

28.9

TE D

Reference

P<0.001

15.7c

23.7

RR 1.38d, CI [1.20-1.57]

Sharara and McClamrock

19.1

42.1

P<0.01

14.9c

38.8

P<0.01

McCarthy-Keith et al

46.1

52.6

RR 0.88, CI [0.78-0.99]

33.7c

45.7

RR 0.74, CI [0.63-0.91]

Csokmay et al

40

50

P=0.39

16.7c

39.7

OR 0.30, CI [0.10-0.89]

Feinberg et al

39.5

42.6

RR 0.93, CI [0.78-1.1]

29.6c

35.8

RR 0.83, CI [0.67-1.02]

McQueen et al

24.4

36.2

OR 0.63, CI [0.44-0.88]

16.9^

30.7

OR 0.50, CI [0.33-0.72]

AC C

EP

Seifer et al (2008)

M AN U

Seifer et al (2010)

SC

Fresh cycles

37

ACCEPTED MANUSCRIPT

10.2

25.9

OR 0.27, CI [0.10–0.72]

-

-

-

Dayal et al

34

28

P=0.48

25c

24

P=0.99

Nichols et al

70.8

48

OR 3.3, CI [1.3-8.6]

-

Bendikson et al

-

-

-

20.1c

Seifer et al (2010)

31.8

31.8

P=0.43

Seifer et al (2008)

22.7

20.2

P=0.145

Csokmay et al

42.0

39.5

P=0.86

per clinical intrauterine gestation (CIG)

b

d

Risk of not having live birth

71.8a

80.3

RR 1.10d, CI [1.00-1.21]

16.5c

16.0

RR 1.03, p=0.718

28.0a

30.2

P=0.85

EP

per cycle

Not significant

AC C

c

18.3

TE D

per CIG + heterotopic

-

M AN U

a

-

SC

Cryopreserved cycles

RI PT

Gleicher et al

38

ACCEPTED MANUSCRIPT

Table 4. Clinical pregnancy and live birth rates among Asian women undergoing IVF compared with white women. LBR (%)

Reference

Significance White

Baker et al

31.2

40.5

OR 0.74, CI [0.71-0.77]

Fujimoto et al

30.9

40.1

OR 0.86 [0.80-0.93]

SART data

33.3

41.3

Site-specific data

37.1

McQueen et al

Significance

Asian

White

81.5b

83.7

OR 0.89, [0.82-0.97]

81.6a

83.7

OR 0.90, CI [0.82-0.97]

OR 0.71, CI [0.64-0.80]d

26.9c

34.9

OR 0.76, CI [0.66-0.88]

45.9

OR 0.59, CI [0.37– 0.94]

28.6c

37.5

OR 0.67, CI [0.46-0.98]d

31.4

36.2

OR 0.73, CI [0.60-0.90]

24.0^

30.7

OR 0.64, CI [0.51-0.80]

Kan et al

20.2

30.6

P=0.091

15.3^

22.5

P=0.077

Langen et al

43

59

OR 0.52, CI [0.28-0.95]d

30.9c

48.2

OR 0.48, CI [0.24-0.96]

Shahine et al

36

52

P=0.02

24c

41

OR 0.56, CI [0.40–0.79]

26.9c

33.6

-

31.7

Tubal factor:

33.3

Mahmud et al

18.2

Lashen et al

15.7

TE D EP

PCOS:

39.5

AC C

Palep-Singh et al

M AN U

Purcell et al

SC

Asian

RI PT

CPR (%)

For Caucasians: RR 2.5, CI [1.25-5.0]

33.5

-

25c

31

-

27.3

Not significant

9.1c

22.7

OR 0.34, CI [0.11-1.1]

22.6

Not significant

-

-

-

39

ACCEPTED MANUSCRIPT

-

-

20.0c

18.3

Not significant

Rudick et al

35

43

-

26c

35

-

Sharara et al

62.9

65.5

Not significant

48.2c

57.6

Not significant

Gleicher et al

29.2

25.9

-

-

-

-

per clinical intrauterine gestation (CIG)

b

per CIG + heterotopic

TE D

unadjusted OR

EP

d

M AN U

per cycle

AC C

c

RI PT

-

SC

a

Bendikson et al

40

ACCEPTED MANUSCRIPT

Table 5. Clinical pregnancy and live birth rates among Hispanic women undergoing IVF compared with white women. CPR (%) White

Baker et al

37.5

40.5

OR 0.87 CI [0.83-0.91]

82.1b

Fujimoto et al

37.3

40.1

OR 1.06 CI [0.96-1.16]

82.2a

McQueen et al

34.0

36.2

OR 0.82, (0.62-1.07)

28.5^

Rudick et al

38

43

-

Shuler et al

26.1

26.6

P=0.60

McCarthyKeith et al

43.2

52.6

-

Feinberg et al

42.9

42.6

Bendikson et al

-

-

b

per CIG + heterotopic

c

per cycle

Significance

White

OR 0.87 CI [0.79-0.96]

83.7

OR 0.87 CI [0.79-0.96]

30.7

OR 0.80, CI [0.601.06)

27c

35

-

20.1c

24.3

P=0.30

33.3

45.7

-

Not significant

33.9c

35.8

Not significant

-

16.7c

18.3

Not significant

TE D

M AN U

SC

83.7

EP

per clinical intrauterine gestation (CIG)

Hispanic

AC C

a

Significance Hispanic

RI PT

Reference

LBR (%)

41

ACCEPTED MANUSCRIPT

FIGURE LEGENDS 1. Flow diagram of the literature search for studies of clinical pregnancy and live birth outcomes after in

AC C

EP

TE D

M AN U

SC

RI PT

vitro fertilization, according to race/ethnicity.

42

AC C

EP

TE D

M AN U

SC

RI PT

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT Supplemental A1. Full list of search terms and database results. PUBMED: 632 records "Fertilization in Vitro"[Mesh] OR "Embryo Transfer"[Mesh] OR "Sperm Injections, Intracytoplasmic"[Mesh] OR fertilization in vitro[tiab] OR fertilisation in vitro[tiab] OR in vitro fertilization[tiab] OR in vitro fertilisation[tiab] OR IVF[tiab] OR ICSI[tiab] OR intracytoplasmic sperm*[tiab] OR embryo transfer*[tiab] OR blastocyst transfer*[tiab] OR zygote transfer*[tiab]

RI PT

"African Continental Ancestry Group"[Mesh] OR "American Native Continental Ancestry Group"[Mesh] OR "Asian Continental Ancestry Group"[Mesh] OR "European Continental Ancestry Group"[Mesh] OR "Oceanic Ancestry Group"[Mesh] OR "Ethnic Groups"[mesh] OR "Minority Health"[Mesh] OR "Healthcare Disparities"[Mesh] OR "Health Status Disparities"[Mesh] OR ethnic*[tiab] OR minorit*[tiab] OR cultural group*[tiab] OR race[tiab] OR racial[tiab] OR Caucasian*[tiab] OR White*[tiab] OR African American*[tiab] OR non-white*[tiab] OR Black*[tiab] OR Hispanic*[tiab] OR Latino*[tiab] OR Latina*[tiab] OR Mexican*[tiab] OR Spanish[tiab] OR Chicano*[tiab] OR Puerto Rican*[tiab] OR Cuban*[tiab] OR Asian*[tiab] OR Chinese[tiab] OR Japanese[tiab] OR Korean*[tiab] OR Philippine[tiab] OR Filipino*[tiab] OR Vietnamese[tiab] OR Cambodian*[tiab] OR Guamanian*[tiab] OR Samoan*[tiab] OR Indian*[tiab] OR Pacific Islander*[tiab] OR Arab[tiab] OR Arabs[tiab] OR Arabian[tiab] OR Native*[tiab] OR Aborigin*[tiab] OR Indigenous[tiab] OR underrepresented[tiab] OR "of color"[tiab] OR "of colour"[tiab] OR disparit*[tiab]

SC

"Treatment Outcome"[Mesh] OR "Pregnancy"[Mesh] OR "Pregnancy Rate"[Mesh] OR "Live Birth"[Mesh] OR outcome*[tiab] OR birth*[tiab] OR childbirth*[tiab] OR pregnan*[tiab] OR success*[tiab] NOT ("animals"[mesh] NOT "humans"[mesh]) EMBASE: 1177 records

M AN U

'fertilization in vitro'/exp OR 'intracytoplasmic sperm injection'/exp OR 'embryo transfer'/exp OR (fertili?ation NEAR/1 'in vitro'):ti,ab OR IVF:ti,ab OR ICSI:ti,ab OR 'intracytoplasmic sperm':ti,ab OR ((embryo OR blastocyst OR zygote) NEXT/1 transfer*):ti,ab

TE D

'ethnic and racial groups'/exp OR 'minority health'/exp OR 'health care disparity'/exp OR 'health disparity'/exp OR ethnic*:ti,ab OR minorit*:ti,ab OR 'cultural group':ti,ab OR 'cultural groups':ti,ab OR race:ti,ab OR racial:ti,ab OR Caucasian*:ti,ab OR White*:ti,ab OR 'African American':ti,ab OR 'African Americans':ti,ab OR 'non-white':ti,ab OR 'non-whites':ti,ab OR Black*:ti,ab OR Hispanic*:ti,ab OR Latino*:ti,ab OR Latina*:ti,ab OR Mexican*:ti,ab OR Spanish:ti,ab OR Chicano*:ti,ab OR 'Puerto Rican':ti,ab OR 'Puerto Ricans':ti,ab OR Cuban*:ti,ab OR Asian*:ti,ab OR Chinese:ti,ab OR Japanese:ti,ab OR Korean*:ti,ab OR Philippine:ti,ab OR Filipino*:ti,ab OR Vietnamese:ti,ab OR Cambodian*:ti,ab OR Guamanian*:ti,ab OR Samoan*:ti,ab OR Indian*:ti,ab OR 'Pacific Islander':ti,ab OR 'Pacific Islanders':ti,ab OR Arab:ti,ab OR Arabs:ti,ab OR Arabian:ti,ab OR Native*:ti,ab OR Aborigin*:ti,ab OR Indigenous:ti,ab OR underrepresented:ti,ab OR 'of color':ti,ab OR 'of colour':ti,ab OR disparit*:ti,ab 'treatment outcome'/exp OR 'pregnancy'/exp OR 'pregnancy rate'/exp OR 'live birth'/exp OR outcome*:ti,ab OR birth*:ti,ab OR childbirth*:ti,ab OR pregnan*:ti,ab OR success*:ti,ab NOT ([humans]/lim NOT [animals]/lim) WEB OF SCIENCE: 948 Records

EP

TS=(((fertilization OR fertilisation) NEAR/1 "in vitro") OR IVF OR ICSI OR "intracytoplasmic sperm" OR ((embryo OR blastocyst OR zygote) NEAR/1 transfer*))

AC C

TS=(ethnic* OR minorit* OR "cultural group" OR "cultural groups" OR race OR racial OR Caucasian* OR White* OR "African American" OR "African Americans" OR "non-white" OR "non-whites" OR Black* OR Hispanic* OR Latino* OR Latina* OR Mexican* OR Spanish OR Chicano* OR "Puerto Rican" OR "Puerto Ricans" OR Cuban* OR Asian* OR Chinese OR Japanese OR Korean* OR Philippine OR Filipino* OR Vietnamese OR Cambodian* OR Guamanian* OR Samoan* OR Indian* OR "Pacific Islander" OR "Pacific Islanders" OR Arab OR Arabs OR Arabian OR Native* OR Aborigin* OR Indigenous OR underrepresented OR "of color" OR "of colour" OR disparit*) TS=(outcome* OR birth* OR childbirth* OR pregnan* OR success*) POPLINE: 40 records

"fertilization in vitro" OR "fertilisation in Vitro" OR "in vitro fertilization" OR "in vitro fertilisation" OR IVF OR ICSI OR "intracytoplasmic sperm" OR "embryo transfer" OR "embryo transfers" OR "blastocyst transfer" OR "blastocyst transfers" OR "zygote transfer" OR "zygote transfers" (ethnic* OR minorit* OR "cultural group" OR "cultural groups" OR race OR racial OR Caucasian* OR White* OR "African American" OR "African Americans" OR "non-white" OR "non-whites" OR Black* OR Hispanic* OR Latino* OR Latina* OR Mexican* OR Spanish OR Chicano* OR "Puerto Rican" OR "Puerto Ricans" OR Cuban* OR Asian* OR Chinese OR Japanese OR Korean* OR Philippine OR Filipino* OR Vietnamese OR Cambodian* OR Guamanian* OR Samoan* OR Indian* OR "Pacific Islander" OR "Pacific Islanders" OR Arab OR Arabs OR Arabian OR Native* OR Aborigin* OR Indigenous OR underrepresented OR "of color" OR "of colour" OR disparit*) (outcome* OR birth* OR childbirth* OR pregnan* OR success*)

ACCEPTED MANUSCRIPT COCHRANE CENTRAL: 61 records TI ("fertilization in vitro" OR "fertilisation in Vitro" OR "in vitro fertilization" OR "in vitro fertilisation" OR IVF OR ICSI OR "intracytoplasmic sperm" OR "embryo transfer" OR "embryo transfers" OR "blastocyst transfer" OR "blastocyst transfers" OR "zygote transfer" OR "zygote transfers") OR AB ("fertilization in vitro" OR "fertilisation in Vitro" OR "in vitro fertilization" OR "in vitro fertilisation" OR IVF OR ICSI OR "intracytoplasmic sperm" OR "embryo transfer" OR "embryo transfers" OR "blastocyst transfer" OR "blastocyst transfers" OR "zygote transfer" OR "zygote transfers")

RI PT

TI (outcome* OR birth* OR childbirth* OR pregnan* OR success*) OR AB (outcome* OR birth* OR childbirth* OR pregnan* OR success*)

M AN U

SC

TI (ethnic* OR minorit* OR "cultural group" OR "cultural groups" OR race OR racial OR Caucasian* OR White* OR "African American" OR "African Americans" OR "non-white" OR "non-whites" OR Black* OR Hispanic* OR Latino* OR Latina* OR Mexican* OR Spanish OR Chicano* OR "Puerto Rican" OR "Puerto Ricans" OR Cuban* OR Asian* OR Chinese OR Japanese OR Korean* OR Philippine OR Filipino* OR Vietnamese OR Cambodian* OR Guamanian* OR Samoan* OR Indian* OR "Pacific Islander" OR "Pacific Islanders" OR Arab OR Arabs OR Arabian OR Native* OR Aborigin* OR Indigenous OR underrepresented OR "of color" OR "of colour" OR disparit*) OR AB (ethnic* OR minorit* OR "cultural group" OR "cultural groups" OR race OR racial OR Caucasian* OR White* OR "African American" OR "African Americans" OR "non-white" OR "non-whites" OR Black* OR Hispanic* OR Latino* OR Latina* OR Mexican* OR Spanish OR Chicano* OR "Puerto Rican" OR "Puerto Ricans" OR Cuban* OR Asian* OR Chinese OR Japanese OR Korean* OR Philippine OR Filipino* OR Vietnamese OR Cambodian* OR Guamanian* OR Samoan* OR Indian* OR "Pacific Islander" OR "Pacific Islanders" OR Arab OR Arabs OR Arabian OR Native* OR Aborigin* OR Indigenous OR underrepresented OR "of color" OR "of colour" OR disparit*)

CINAHL: 104 records

MH ("Fertilization in Vitro" OR "Embryo Transfer") OR TI ("fertilization in vitro" OR "fertilisation in Vitro" OR "in vitro fertilization" OR "in vitro fertilisation" OR IVF OR ICSI OR "intracytoplasmic sperm" OR "embryo transfer" OR "embryo transfers" OR "blastocyst transfer" OR "blastocyst transfers" OR "zygote transfer" OR "zygote transfers") OR AB ("fertilization in vitro" OR "fertilisation in Vitro" OR "in vitro fertilization" OR "in vitro fertilisation" OR IVF OR ICSI OR "intracytoplasmic sperm" OR "embryo transfer" OR "embryo transfers" OR "blastocyst transfer" OR "blastocyst transfers" OR "zygote transfer" OR "zygote transfers")

EP

TE D

MH ("Ethnic Groups+" OR "Minority Groups" OR "Healthcare Disparities" OR "Health Status Disparities") OR TI (ethnic* OR minorit* OR "cultural group" OR "cultural groups" OR race OR racial OR Caucasian* OR White* OR "African American" OR "African Americans" OR "non-white" OR "non-whites" OR Black* OR Hispanic* OR Latino* OR Latina* OR Mexican* OR Spanish OR Chicano* OR "Puerto Rican" OR "Puerto Ricans" OR Cuban* OR Asian* OR Chinese OR Japanese OR Korean* OR Philippine OR Filipino* OR Vietnamese OR Cambodian* OR Guamanian* OR Samoan* OR Indian* OR "Pacific Islander" OR "Pacific Islanders" OR Arab OR Arabs OR Arabian OR Native* OR Aborigin* OR Indigenous OR underrepresented OR "of color" OR "of colour" OR disparit*) OR AB (ethnic* OR minorit* OR "cultural group" OR "cultural groups" OR race OR racial OR Caucasian* OR White* OR "African American" OR "African Americans" OR "non-white" OR "non-whites" OR Black* OR Hispanic* OR Latino* OR Latina* OR Mexican* OR Spanish OR Chicano* OR "Puerto Rican" OR "Puerto Ricans" OR Cuban* OR Asian* OR Chinese OR Japanese OR Korean* OR Philippine OR Filipino* OR Vietnamese OR Cambodian* OR Guamanian* OR Samoan* OR Indian* OR "Pacific Islander" OR "Pacific Islanders" OR Arab OR Arabs OR Arabian OR Native* OR Aborigin* OR Indigenous OR underrepresented OR "of color" OR "of colour" OR disparit*)

AC C

MH ("Treatment Outcomes" OR "Pregnancy+" OR "Pregnancy Outcomes") OR TI (outcome* OR birth* OR childbirth* OR pregnan* OR success*) OR AB (outcome* OR birth* OR childbirth* OR pregnan* OR success*)

ACCEPTED MANUSCRIPT Supplemental A2: List of meeting abstracts excluded due to lack of a full-text manuscript.

7. 8. 9. 10. 11. 12. 13. 14.

15.

RI PT

6.

SC

5.

M AN U

4.

TE D

3.

EP

2.

Jayaprakasan K, Pandian D, Hopkisson J, Campbell B, and Maalouf W. Effect of ethnicity on IVF/ICSI outcome. Hum Reprod 2013: 28; 358-358. Shastri, S. M., M. Werner, et al. (2012). "Comparison of clinical outcomes between genetically similar groups of in vitro fertilization patients." Fertility and Sterility 98(3): S26. Ressler, I. B., B. Scoccia, et al. (2010). "Race significantlyaffects multiple pregnancy outcomes in an IVF program." Fertility and Sterility 94(4): S259. Grainger DA, Seifer DB, Frazier LM, Rall MJ, Tjaden BL, and Merrill JC. Racial disparity in clinical outcomes from women using advanced reproductive technologies (ART): Analysis of 80,196 ART cycles from the SART database 1999 and 2000. Fertil Steril 2004: 82; s37-s38. Omurtag, K. O. and E. S. Jungheim (2012). "IVF insurance coverage influences fertility treatment and decision-making for african american women." Fertility and Sterility 98(3): S97-S98. Moon, K. S., J. M. Csokmay, et al. (2010). "Elevated estradiol levels in African-American women may explain the reduced live birth rates following assisted reproduction." Fertility and Sterility 94(4): S242. Mitwally, M. F., M. M. Leduc, et al. (2006). "The effect of body mass index (BMI) on the outcome of IVF and embryo transfer in women of different ethnic backgrounds." Fertility and Sterility 86: S68-S69. James CE, Hammond KR, and Steinkampf MP. Race and assisted reproduction: A case-controlled study of outcomes in African-American and Caucasian women. Fertil Steril 2002: 78; S123. Bullough, S., T. Girish, et al. (2011). "A retrospective analysis of the performance of both Caucasian and Asian women undergoing in-vitro fertilisation and intracytoplasmic sperm injection treatment." Human Fertility 14(2): 75-76. Fisher, S. L., E. S. Langen, et al. (2011). "Asian ethnicity and comparable outcomes after frozen blastocyst transfer." Fertility and Sterility 95(4): S15. Richardson, K., T. Tang, et al. (2010). "Outcome of IVF treatment in Asian population." Human Fertility 13: 11. Smikle, C., S. P. Willman, et al. (2002). "Comparison of intracytoplasmic sperm injection pregnancy rates in Eastern Indian and Caucasian women." Fertility and Sterility 78(3): S148-S148. Shah, M., et al. (2015). "In vitro fertilization outcomes after frozen embryo transfer in South Asian compared to caucasian women." Fertility and Sterility 103(2): e34. Kukreja, S. M., et al. (2013). "An ongoing comparison of treatment outcomes and antimullerian hormone (AMH) levels in South Asian and Caucasian women undergoing in vitro fertilisation." BJOG: An International Journal of Obstetrics and Gynaecology 120: 188-189. Zarek, S. M., et al. (2013). "Race/ethnicity associated with increased peak endometrial thickness and decreased live birth rate: An analysis of 4,086 assisted reproductive technology (ART) cycles." Fertility and Sterility 100(3): S81.

AC C

1.

ACCEPTED MANUSCRIPT Supplemental A3. Abstract-only data showing pregnancy and live birth outcomes after IVF across race/ethnicity groups. Year

Sample Size and Info

Pregnancy and Live Birth Outcomes

Multiple Races/Ethnicities Jayaprakasan et al 2013

LBRs (p<0.05 for all) 43.8% 38.0% 23.3% 21.4% LBRs (p<0.05 for Caucasian v. Asian and AA) 41% 36% 34% 42% No significant differences in pregnancy outcome

Caucasian (n=1,291) South East Asian (n=179) Afro-Caribbean (n=30) Middle East (n=14) Zarek et al

2013 Caucasian (n=2,866) African American (n=487) Asian (n=568) Hispanic (n=165)

Shastri et al

2012

RI PT

Reference

2010

No significant differences in LBRs White (n=145) Black (n=64) Asian (n=21) Hispanic (n=58)

Grainger et al

2004 White (n=68,607) Black (n=3,666) Asian (n=3,585) Hispanic (n=4,338) [first and repeated cycles, including frozen-thawed]

Black women Omurtag et al

White (n=995) African American (n=58) Moon et al

2010

Caucasian (n=731) African American (n=202) Mitwally et al

2006

2002

EP

White (n=161) African American (n=22) James et al

AC C

Caucasian (n=87) African American (n=41) Asian women Shah et al

2015

Caucasian (n=155) South Asian (n=79)

Kukreja et al

2013

Caucasian (n=42) South Asian (n=49)

Bullough et al

2011

Caucasian (n=273) Asian (n=87)

Fisher et al

2011 White (n=34) Asian (n=24)

Richardson et al

2010 Caucasian (n=1,493) Asian (n=249)

Smikle et al

LBRs (p<0.001 for all age groups) 26.3% 18.7% 20.7% 26.7% [No differences in LBRs of frozen embryo transfers]

CPRs LBRs (No significant differences) 44% 33% 41% 38% No significant differences in LBRs 45.1% 37.8% No statistical comparison reported CPRs 45.3% 31.8% CPRs LBRs (No significant differences) 36.8% 29.9% 31.7% 22.0%

TE D

2012

M AN U

Ressler et al

SC

Northwestern European (n=256) Southern European (n=256), Black (n=30) Asian Indian (n=71) Mexican (n=41) Chinese (n=37)

2002 Caucasian (n=108) East Indian (n=41)

CPRs LBRs 64% 45% (p=0.54) 68% 49% (p=0.61) CPRs (p=0.105) 60.4% 42.0% CPRs (No statistical comparison reported) 18.1% 23.0% CPRs LBRs (No significant differences) 32.3% 23.5% 37.5% 33.3% CPRs (p<0.001) 34.0% 22.9% CPRs (p=0.02) 37.0% 12.5%