The Impact of Health Benefit Design on Patients With Infertility

ABSTRACT

Objectives: Assisted reproductive technology (ART) is a treatment option available to patients diagnosed with infertility. This study evaluated the impact of infertility benefit coverage on ART utilization and pregnancy-related outcomes, addressing a gap in previous research.

Study Design: Retrospective analysis.

Methods: This study utilized the Workpartners Research Reference Database containing claims from self-insured employers in the US from 2010 to 2022. Women aged 18 to 42 years with at least 1 infertility diagnosis and at least 2 years of continuous enrollment after the initial infertility diagnosis were classified into 1 of 2 cohorts: high cohort (those with both infertility diagnostic and treatment coverage) or low cohort (those with only diagnostic coverage or no diagnostic nor treatment coverage). Binary outcomes were analyzed using logistic regression and continuous outcomes were analyzed using 2-stage stepwise regressions. Models controlled for differences in employee demographics, job-related variables (exempt status, full-time status, hourly vs salary, annual salary), and number of insured dependents.

Results: Of the 10,820 women who met the inclusion criteria, 7589 (70.1%) were in the high cohort and 3231 (29.9%) were in the low cohort, with mean (SE) ages of 34.4 (0.06) vs 33.5 (0.11) years, respectively (P < .0001). The high cohort had a higher adjusted likelihood than the low cohort of using ART medications (P < .0001) and having ART procedures performed (P < .0001). The high cohort also used a higher number of unique ART medications and procedures. The likelihood of becoming pregnant with any ART utilization was 69.6% for the high cohort and 65.3% for the low cohort (P = .0089). The only significant difference in pregnancy-related complications was claims for oligohydramnios (9.3% vs 7.2%, respectively; P = .0294).

Conclusions: Health benefit design that includes infertility treatment coverage resulted in significantly higher use of unique ART medications, number of ART procedures performed, and successful pregnancy outcomes.

Am J Manag Care. 2025;31(8):In Press

Takeaway Points

Assisted reproductive technology (ART) is increasingly used to treat patients with infertility. Although previous studies have outlined trends in ART usage, the current utilization data may lag behind current treatment patterns and not account for the impact of health benefit design on treatment patterns.

• This research found that health benefit designs that cover infertility treatments significantly affect utilization of these treatments and successful pregnancy outcomes.
• Infertility treatment coverage led to an increase in ART utilization and an increased likelihood of becoming pregnant.
• ART was associated with a slight increase in the likelihood of oligohydramnios. No other significant complications were observed.

Infertility is defined as the inability to achieve a successful pregnancy after at least 12 months of regular unprotected sexual intercourse.¹ It is considered one of the most common health conditions among individuals of reproductive age.² Although the precise number of individuals or couples affected by infertility is unknown, it is estimated to range from 48.5 million to 186 million globally.³ Furthermore, the World Health Organization estimates the lifetime prevalence of infertility to be 17.5%.^4,5 The CDC estimates that approximately 19% of women with no prior births are affected by infertility, as are 6% of women with 1 or more prior births.⁶

Infertility is commonly caused by ovulatory dysfunction, male infertility, or tubal disease; it can also be due to unexplained causes.¹ Infertility and common causes of infertility are associated with other health complications in women, including mental health conditions, endometrial cancer, cardiovascular disease, and diabetes.⁷ In addition to these health concerns, infertility can have a profound impact on other aspects of personal lives and society as a whole, and it is frequently considered a personal tragedy with negative psychosocial consequences.⁸

Early evaluation is recommended for women 35 years and older who have not achieved pregnancy in 6 months, and immediate evaluation is recommended for women older than 40 years.¹ The choice of treatment will be dependent on the underlying cause of infertility and can include timed intercourse, ovulation induction, ovarian stimulation (OS), intrauterine insemination (IUI), or in vitro fertilization (IVF).¹ The American Society for Reproductive Medicine (ASRM) guidelines for evidence-based infertility treatments recommend OS with clomiphene citrate or letrozole with IUI treatments as first-line treatment for couples with unexplained infertility, but pregnancy rates generally plateau after 3 to 4 cycles of OS-IUI due to undiagnosed and heterogeneous factors impairing reproductive function in these women.^9-11 As a result, many women with unexplained infertility utilize IVF to achieve pregnancy as IVF is considered the most effective treatment option for unexplained infertility.⁹

There is an urgent need for solutions that bridge the gap between the high cost associated with effective infertility treatments and the prevalence and negative impact of infertility on individuals’ health. Thus, the ASRM guidelines emphasize the importance of future research to evaluate barriers to assisted reproductive technology (ART) treatments.⁹

Few studies have evaluated the impact of ART health care coverage on pregnancy outcomes, including live births and maternal and perinatal complications. The goals of this study were to identify ART treatment patterns and outcomes in patients with differing levels of infertility benefit coverage and the associated clinical aspects of patient care within the realm of ART in the US.

METHODS

Study Design

This retrospective regression-based cohort analysis utilized health care information extracted from claims data of deidentified US employees, partners, and dependents included in the Workpartners Research Reference Database (RRDb) to evaluate the clinical and financial impact of health care benefit design on ART utilization, pregnancy outcomes, and complications. The Workpartners RRDb captures data from almost 4 million employees from a wide variety of industries and their insured family members across the US. There are more than 500 commercially self-insured employers in the RRDb in the retail, service, manufacturing, transportation, energy, technology, financial, and utilities industries. The RRDb is a person-centric integrated database that includes medical, pharmaceutical, absence, and disability claims from self-insured employers. In addition, the RRDb integrates data from human resource information systems, benefits, and attendance. Benefit information includes comprehensive plan design information for medical care, pharmaceuticals, co-pays, deductibles, out-of-pocket costs, and coverage information for specific benefits such as reproductive health, dental, and vision care. Workpartners receives this information from all the insurers providing benefits to the covered employee based on employee identifier and allowing tracking of patients after changes in insurance.

Patient characteristics, employment information, and infertility-related coverage benefits were extracted for analysis. The baseline patient characteristics included age, race, marital status, geographical location by zip code, relation to the employee, and comorbid conditions. Employment information gathered comprised tenure (time with current employer in years), exempt status (eligible for overtime), mean annual salary, and full-time employment status. The study was exempt from institutional review board review and approval, as the data were deidentified and the study did not involve patient care.

Patient Selection

Data from female employees, employee partners, and dependents of employees were extracted from the Workpartners RRDb from January 2010 to December 2022 using the flowchart in Figure 1. Women with infertility were identified by International Classification of Diseases, Ninth Revision code 628.X and Tenth Revision code N97.X for infertility (eAppendix Table [eAppendix available at ajmc.com]). The date of the initial diagnosis of infertility was the index date. Patients younger than 18 years or older than 42 years at the index date were excluded. All patients had at least 2 years of continuous coverage for medical and pharmacy benefits following their index date. Patients who met the inclusion criteria were categorized into 2 cohorts (high or low infertility benefit coverage) based on their infertility treatment benefit. The Workpartners analytics team reviewed written plan summaries and coding to determine benefit levels. Health plans with high infertility benefit coverage were defined as plans that cover both diagnostic services and any level of infertility treatment, whereas plans with only diagnostic coverage or no coverage of either infertility diagnostic services or treatment were categorized as having low infertility benefit coverage.

Outcomes

Primary outcomes, including successful pregnancy outcomes, use of ART medications and procedures, maternal complications, and perinatal and pediatric complications, were compared between the high and low infertility benefit coverage cohorts.

Statistical Analyses

The 2 cohorts were compared using t tests for continuous outcomes and χ² tests for binary outcomes. For binary outcomes, an OR was calculated and represents the odds that an outcome will occur in the high benefit cohort divided by the odds of the outcome occurring in the low benefit cohort. For primary outcomes, both unadjusted comparisons using t tests and χ² tests and regression-adjusted comparisons were made. The number of unique ART medications and procedures was modeled using Poisson regression, whereas the likelihood of ART treatments and likelihood of becoming pregnant were modeled using logistic regression. The models were adjusted for the following covariates and were built using a stepwise selection process. Employee-related covariates included employee/nonemployee indicator, tenure, exempt status, full-time status, hourly vs salary compensation, and annual salary. Other covariates included maternal age, marital status, self-reported race, geographical location by first zip code digit, maternal comorbidities (hypertension, pulmonary hypertension, any cardiac condition, Von Willebrand disease, sickle cell disease, diabetes, depression, posttraumatic stress disorder, anxiety, anemia, any fibroid condition, myomectomy, obesity, smoking status), and number of dependent children in the health plan. Employee-related covariates were obtained for the female employee patients in the cohorts and employed spouses of the female nonemployee patients in the cohorts. Age, sex, and pregnancy-related comorbidities were obtained for all employee and nonemployee patients in the cohorts.

RESULTS

Patient Demographics

The analysis included 10,820 patients who met the patient selection criteria; 70.1% (n = 7589) of patients had high infertility coverage, and 29.9% (n = 3231) of patients had low infertility coverage. Patients in the high cohort were older than in the low cohort (mean [SE] age, 34.4 [0.06] vs 33.5 [0.11] years; P < .0001). There were significant differences in all employment information variables between the high and low cohorts. The employed patients from the high cohort had longer tenure with their employers (mean [SE], 5.3 [0.07] vs 4.5 [0.1] years; P < .0001) with an annual salary difference of $29,403 ($83,428 [$1242] vs $54,025 [$913]; P < .0001). Other baseline characteristic differences in all patients included comorbidity prevalence differences in sickle cell disease, fibroid conditions, obesity, depression, and posttraumatic stress disorder (Table 1).

ART Use

Individuals in the high infertility coverage cohort were more likely to use ART medications and procedures, and they also utilized a greater number of ART medications and procedures (unadjusted data are shown in Table 2). The adjusted likelihood of patients using ART medication was 47.5% in the high cohort compared with 25.9% in the low cohort (OR, 2.59; 95% CI, 2.37-2.85; P < .0001). Similarly, the adjusted likelihood of patients having ART procedures performed was higher in the high cohort, with a rate of 38.2%, compared with 19.8% in the low cohort (OR, 2.50; 95% CI, 2.28-2.77; P < .0001) (Figure 2 [A]). Further, those in the high cohort also used a higher number of unique ART medications (mean [SE], 1.2 [0.01] vs 0.45 [0.01]; P < .0001) and unique ART procedures (0.87 [0.01] vs 0.37 [0.01]; P < .0001) on average. There were significant differences in the adjusted use of any ART medications and procedures between the 2 cohorts (Figure 2 [B]).

Pregnancy Outcomes

In addition to high infertility treatment health benefit coverage being associated with higher rates of utilization of ART medications or procedures, it also was associated with a higher percentage of patients becoming pregnant given ART utilization (high vs low, 69.6% vs 65.3%; OR, 1.22; 95% CI, 1.06-1.40; P = .0089) and a higher likelihood of becoming pregnant regardless of ART use (59.9% vs 56.4%; OR, 1.15; 95% CI, 1.06-1.25; P = .0014) (Figure 3). There was no significant difference in the unadjusted mean time to pregnancy (high vs low, 230 [2.68] vs 234 [4.58] days).

Pregnancy, Maternal, and Pediatric Complications

The only significant difference in complications between the 2 cohorts was in the adjusted percentage of patients with claims for oligohydramnios (high vs low, 9.3% vs 7.2%; OR, 1.32; 95% CI, 1.03-1.71; P = .0294). There were no significant differences in other pregnancy complications or maternal complications, such as cesarean delivery, preeclampsia, placenta previa, placental abruption, postpartum depression, or cardiovascular disease. Additionally, infertility benefit coverage was not associated with any significant differences in pediatric complications, such as multiple births or perinatal mortality, including stillbirths and fetal death.

DISCUSSION

The current study presents the first comparison of the level of nationwide infertility health care benefit coverage on ART utilization and pregnancy-related outcomes in the US. Infertility benefit coverage in the high cohort was associated with an increased likelihood of utilizing ART medications and procedures. The high cohort exhibited a higher usage of unique ART medications, and IVF was more frequently performed than IUI in this cohort. Patients in the high cohort were not only more likely to become pregnant but also were even more likely to achieve pregnancy with ART utilization. Patients and their partners in this study may have selected employers providing high infertility benefit coverage. Recognizing that unique number of ART medications and procedures does not correspond directly to the frequency of attempted infertility treatment underscores an important area for future research within ART. A previous study found that women with IVF insurance coverage were more likely to attempt IVF again. The portion of women with coverage returning for a second cycle of IVF was significantly greater than that of women who self-paid for their IVF treatments, leading to a greater cumulative likelihood of live births.¹²

The use of ART treatments and the number of infants born as a result of ART have steadily increased. The CDC reported that more than 9 million women received infertility services in 2018, with ART-conceived live births representing approximately 2% of infants born.^2,13 In Europe, ART accounts for 3% of births, and the European Society of Human Reproduction and Embryology estimated the demand for ART at more than 1500 cycles per million people per year.^2,14 The US met only 40% of the presumed national demand for ART compared with 62% in the United Kingdom and more than 100% in Scandinavia and Australia.^2,15,16 The ASRM estimates that only 24% of couples with infertility in the US can access the comprehensive range of services required to achieve a successful pregnancy.^2,17 The US differs from other countries with centralized health insurance systems due to the substantial variations in insurance access, coverage, and health disparities related to race and socioeconomic status.¹⁸ A landmark study published by Jain et al in 2002 demonstrated that complete insurance coverage for IVF was associated with a utilization rate 277% higher than in states that did not require any coverage.¹⁹ This underscores the issue that cost of infertility treatment remains a significant barrier to accessing infertility care in the US.

Many states have passed legislative mandates to increase access to infertility treatments, but benefits vary.²⁰ Previous research has evaluated the impact of legislative insurance mandates on infertility and found a nearly 3-fold increase in utilization of infertility services, as well as a significant 19% increase in first-birth rates among older women resulting from these mandates.^19,20 Kelley et al observed that women with infertility benefits are more likely to seek infertility care than their uninsured counterparts.²¹ Similarly, a retrospective cohort study using data from the National ART Surveillance System analyzed trends in ART use and birth outcomes before and after infertility insurance mandates in New Jersey and Connecticut and nonmandate states.²² The authors reported an increase in ART treatment associated with infertility insurance mandates in the 2 states. The ART use ratio increased by 27.9% from 2001 to 2002 in New Jersey and 23.4% from 2005 to 2006 in Connecticut. The present study reports the regions of the country with high and low benefit coverage based on the patient’s first zip code digit (Table 1 [A]). There were significant differences, with a higher percentage showing high coverage in zip codes beginning with 1 and 9 and a higher percentage with low coverage in zip codes beginning with 2 and 6.

The present study found that use of ART resulted in pregnancy rates of 69.6% for those in the high cohort and 65.3% for those in the low cohort among women with documented infertility. Following successful pregnancy, those in the high benefit cohort, associated with greater utilization of ART medications and procedures, did not exhibit a significant increase in pregnancy complications or maternal and pediatric complications. Therefore, infertility benefit coverage in this study did not result in significant differences in pregnancy-related complications between those with and without coverage. However, it is worth noting that insurance coverage has been reported to impact patient outcomes. A survey involving more than 400 infertility specialists practicing in states without an insurance mandate reported worse outcomes for patients with tubal factor infertility who lacked insurance coverage when they opted for self-pay IVF.^23,24

Improvements in purification techniques enabled the development of highly purified human menopausal gonadotropin, which is 1 of the 2 most frequently used gonadotropin products used for infertility treatments, along with recombinant follicle-stimulating hormone as monotherapies or mixed protocols.²⁵ Ensuring patient access to the most effective infertility treatments is crucial, with insurance coverage playing a pivotal role in ensuring affordability and accessibility. Incorporating emerging and highly effective ART treatments not only broadens patient access but also improves the likelihood of achieving a successful pregnancy, ultimately enabling patients to exercise their fundamental human rights to reproduce and establish families.

Strengths and Limitations

This study has several strengths. It includes a comprehensive data set that captures a wide variety of industries, employees, and their insured family members across the US. The linkage between parent and child in the Workpartners RRDb is lacking in many other databases. Additionally, the study successfully identified patterns in ART treatment (medications and procedures) and pregnancy-related complications. However, consistent with the use of information provided by databases, there are inherent limitations in using claims data. These limitations include the ability to account for unmeasured confounders, potential for data entry errors, recording bias secondary to financial incentives, and temporal changes in billing codes. The Workpartners RRDb covers self-insured employers throughout the US, and during the 12-year study period, new employers were added to the RRDb. The RRDb would not be representative of the Bureau of Labor Statistics or Census Bureau data, as those databases would contain nonemployees, employees from employers that do not provide absence benefits, and employees from fully insured employers. Statistical efforts were made to remove the impact of confounders through regression modeling. The use of an insurance claims database based on self-insured commercial employers is dependent on its completeness and correctness, with intrinsic limitations regarding data assurance. Lastly, as this study used a US claims database, the findings may not be generalizable to health care systems in other countries.

CONCLUSIONS

Infertility poses a significant challenge for individuals, families, and health care providers, with increasing prevalence and profound effects on the individuals and communities. Furthermore, access to infertility treatments remains the primary barrier to infertility care in the US. Future research should explore the impact of state mandates on IVF treatment rates, resulting pregnancies, and the likelihood of patients changing insurance or employers to gain coverage. Health care benefits that include infertility treatments were associated with higher utilization of unique ART medications, more ART procedures performed, and improved pregnancy outcomes without compromising maternal or pediatric outcomes. 

Author Affiliations: Better Health Worldwide, Inc, Newfoundland, NJ (RAB), St Augustine, FL (TG), and Paso Robles, CA (NLK); Ferring Pharmaceuticals, Inc (SS), Parsippany, NJ; Workpartners, LLC, Loveland, CO (IAB), and Pittsburgh, PA (EMR); Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine (ESJ), Chicago, IL.

Source of Funding: Ferring Pharmaceuticals, Inc.

Author Disclosures: Mr Brook is the president of Better Health Worldwide. Dr Seo is employed by Ferring Pharmaceuticals, Inc. Mr Beren is employed by Workpartners. Dr Ghanjanasak was paid by Better Health Worldwide for preparation of this manuscript. Dr Kleinman has received consulting fees from Better Health Worldwide and Workpartners. The remaining authors report no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

Authorship Information: Concept and design (RAB, IAB, NLK, EMR, ESJ); acquisition of data (RAB, EMR); analysis and interpretation of data (RAB, SS, IAB, TG, NLK, EMR, ESJ); drafting of the manuscript (RAB, SS, TG, EMR); critical revision of the manuscript for important intellectual content (RAB, SS, TG, NLK, ESJ); statistical analysis (IAB); provision of patients or study materials (IAB, EMR); obtaining funding (RAB); administrative, technical, or logistic support (RAB, SS); and supervision (RAB).

Address Correspondence to: Richard A. Brook, MS, MBA, Better Health Worldwide, Inc, 18 Hirth Dr, Newfoundland, NJ 07435-1710. Email: Rich@BH-WW.com.

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