# On the cost and prevention of iatrogenic multiple pregnancies

Reproductive BioMedicine Online, 3, 29, pages 281 - 285

### Abstract

Multiple pregnancies are an undesirable complication of IVF and of ovulation induction and/or ovulation enhancement without IVF. Studies based on published population data and data from the Centers for Disease Control and Prevention indicate that savings from the mitigation of iatrogenic multiples would save money in the billions (109) of US dollars on a national basis. The aim of this study was to determine whether, using real data from a major regional insurance carrier for the interval 2005–2009 covering obstetric costs requiring hospitalization and neonatal costs through the first year, it was possible to show that the cost saved by eliminating iatrogenic multiple births would be adequate to fund a protocol to minimize iatrogenic multiple births. The net savings on an annual basis for the study group of 13,478 was about US$4.4 million. Applying the regional findings to national data suggests savings of approximately US$6.3 billion if national iatrogenic multiples were eliminated. These findings indicate that the health insurance industry should be able to offer infertility coverage at a lower rate by requiring a treatment algorithm designed to essentially eliminate iatrogenic multiple pregnancies. It is concluded that efforts should be made to assure a singleton birth when treating infertility.

Keywords: iatrogenic multiple births, intrauterine insemination, IVF, multiple births, single-embryo transfer.

### Introduction

A previous communication reliant on publicly available data by this research group postulated that the elimination of outmoded forms of infertility therapy, restricted use of intrauterine insemination (IUI) and requirement for single-embryo transfer would essentially eliminate iatrogenic multiple births and greatly reduce the costs thereof ( Jones and Allen, 2009 ). It was further noted that the attendant cost savings would be more than sufficient to underwrite the insurance premiums for the provision of cutting-edge infertility therapy to all women between the ages of 15–44 years in the USA. The analysis reported herein seeks to put the aforementioned thesis to the test by reviewing the claims data of a single leading health plan for the 2005–2009 interval. Special efforts were made to establish the costs associated with iatrogenic multiple births and the complications thereof.

### Materials and methods

To protect the identity of any and all of the patients under study, the health plan in question required that it remain anonymous. Two Institutional Review Board exemptions for this study were secured from Sterling Institutional Review Board, Atlanta, Georgia (reference nos. 4117 and 4189, approved 7 August 2012 and 8 November 2012).

The health plan under study made use of a comprehensive database replete with the following codes: Current Procedural Terminology, International Classification of Diseases revision 9, Diagnosis-Related Group and facility revenue codes. Thus, this work was informed of all payments prior to and including delivery costs and the costs associated with the first year of the baby's/babies’ life/lives. For the mother, this included all inpatient costs immediately prior to and including delivery (there were no antepartum costs for the mother). These costs included inpatient care, physician charges and delivery and anaesthetic charges. Her hospital costs included her daily inpatient charge, blood and laboratory cost, ultrasound cost and medications. All charges when the mother was an inpatient were included. For the infant(s), all delivery costs included neonatal, intensive care, laboratory, ultrasounds, medications and physician services including paediatrician and any other specialists. After neonatal discharge, any services including readmission were covered to age 1.

Using the billing codes, the health plan was able to accurately identify all of the enrolled patients who gave birth, including multiple births, during the 2005–2009 interval. Use was made of the comprehensive list of Current Procedural Terminology procedure codes and Healthcare Common Procedure Coding and System procedure codes with an eye towards identifying the provision of infertility treatment services. In each and every case of multiple birth, the health plan further searched for the month and year of the billing codes indicative of the provision of infertility services for up to 12 months prior to delivery. Most notably, this analysis was limited to the provision of IUI and IVF services in light of their known association with the genesis of multiple births. Insurance payment data do not specify whether ovarian stimulation was used before IUI. The patients requiring treatment for infertility were used to identify which multiple births were deemed iatrogenic.

The case inclusion criteria consisted of the following: (i) the mother must have been enrolled for at least 12 member months with the health plan prior to delivery in order to determine the frequency of infertility therapy; (ii) the baby/babies must have been enrolled for at least 12 member months with the health plan post delivery in order to determine the cost of neonatal therapy; and (iii) the patient must have given birth to at least one live infant. Over half (54%) of the enrollees encompassed by this study were excluded for failure to meet the inclusion criteria.

Multiple births noted within the birth cohort were deemed iatrogenic if and when associated with a treatment code for IUI or IVF within a month prior to the pregnancy. It is possible that some singletons had IUI or IVF but these were not identifiable. Their identification would have had no influence on the conclusion of the study. To compare the regional group with national figures, national multiple ratios were applied to the regional group. For national data, iatrogenic multiples were identified by subtracting from all multiples those multiples that were considered to be spontaneous, using the national singleton, twin and higher-order birth rates for 1980.

### Results

In the course of the 5-year study, the health plan reported a total of 29,168 deliveries. Of those, 15,690 deliveries were excluded for failure to meet the required inclusion criteria. In 7715 deliveries, the mother was not enrolled with the health plan for at least 12 member months prior to delivery. In 7901 deliveries, the infants born were not enrolled with the health plan for at least 12 member months post delivery. In 74 deliveries, no live infant was born.

Among the 13,478 deliveries that met the inclusion criteria ( Table 1 ), 406 constituted multiple births. In effect, these 406 deliveries represented 405 patients in that one of the patients in question gave birth twice to twins during the study period.

Table 1 Numbers of twins and triplets or more based on a US regional health plan, national data for 1980 and national from data for 2005–2009.

2005 2006 2007 2008 2009 Total Twins versus triplets or more (%)
Regional health plan data for 2005–2009
Total births 3105 2885 2590 2552 2346 13,478
Singletons 3010 2783 2518 2470 2291 13,072
Total twins 88 101 69 78 51 387
Natural twins 35 53 36 35 20 179 46
Iatrogenic twins a 53 48 33 43 31 208 54
Total triplets or more 7 1 3 4 4 19
Natural triplets or more 1 0 0 2 1 4 21
Iatrogenic triplets or more a 6 1 3 2 3 15 79
National data for 1980
Natural twins b 61 56 51 50 46 263 68
Iatrogenic twins 27 45 18 28 5 124 32
Natural triplets b 1 1 1 1 1 4 20
Iatrogenic triplets 6 0 2 3 3 15 80
National data for 2005–2009
Total births 4,138,349 4,265,555 4,316,233 4,247,694 4,130,665 21,098,496
Singletons 3,998,533 4,121,930 4,170,845 4,102,766 3,987,108 20,381,182
Total twins 133,122 137,085 138,961 138,660 137,217 685,045
Natural twins b 80,698 83,178 84,167 82,830 80,548 411,421 60
Iatrogenic twins 52,424 53,907 54,794 55,830 56,669 273,624 40
Total triplets or more 6694 6540 6427 6268 6340 32,269
Natural triplets b 1159 1194 1209 1189 1157 5908 18
Iatrogenic triplets 5535 5346 5218 5079 5183 26,361 82

a Iatrogenic pregnancies identified by having had an IUI or IVF immediately before the pregnancy.

b Based on 1980 rate (prior to IVF and wide clinical use of ovulation induction): twin rate 1.95% and triplet rate 0.028% (US Bureau of Vital Statistics).

Values arenunless otherwise indicated.

Column totals may not sum accurately due to rounding.

Broken down by multiplicity and the cost per delivery (as incurred by the health plan) the 13,478 deliveries which met the required inclusion criteria segregated as follows: singletons 13,072 (US$18,244 per delivery); twins 387 (US$97,987 per delivery); triplets and higher-order multiples 19 (US$391,700 per delivery) ( Table 2 ). Multiple births constituted 3% of the 13,478 births that met the required inclusion criteria but accounted for 15.9% of the total cost paid by the health plan to both physician and hospital providers for medical services rendered. Table 2 Cost and saving for elimination of iatrogenic multiple pregnancies over 5 years for the regional group (2005–2009). Scenario Cost (US$)
Iatrogenic twins (n = 208)
Twin insurance cost estimated by this study 97,987
Total twin cost 20,381,296
Iatrogenic triplets (n = 15)
Triplet insurance cost estimated by this study 391,700
Total triplet cost 5,875,500
Total iatrogenic multiples (n = 223)
Total iatrogenic multiples cost 26,256,796
Cost if all multiples were singletons (US$18,244.00 per singleton) 4,068,412 Net saving if all were singletons 22,188,384 Net saving if all were singletons (1 year) 4,437,677 The insurance company search for the specified infertility treatment billing codes among multiple pregnancies for 12 months prior to mothers’ deliveries revealed the following: 183 with no treatment codes had 179 twins and four triplets or more (presumably spontaneous); 52 with the treatment code IUI had 46 twins and six triplets or more (presumable iatrogenic); and 171 with the treatment code IVF had 162 twins and nine triplets or more (presumably iatrogenic). The cost of the iatrogenic twins was US$20,381,296 and for the iatrogenic triplets or more was US$5,875,500. The total was US$26,256,796. If these multiples had been singletons at a total cost of US$4,068,412, the annual savings would have been US$4,437,677 ( Table 2 ).

Using the twin insurance cost as estimated by this study (US$97,987) and applying this cost to the national number of iatrogenic twins between 2005–2009 (273,624) yielded a twin cost of US$26,811,594,888 ( Table 3 ). Applying the same method for triplets, which according to the study cost US$391,700, to the 26,446 iatrogenic triplets gave a triplet cost of US$10,358,898,200. According to this study, the cost of a singleton delivery was US$18,244. Thus, if all multiples had been singletons, the total cost would have been US$5,474,477,080. Thus, the savings if all deliveries had been singletons would have been US$37,170,493,088 minus US$5,474,477,080, or US$31,696,016,008. This annualizes for the USA at US$6,339,203,202 ( Table 3 ).

Table 3 Cost and saving for elimination of iatrogenic multiple pregnancies over 5 years for national data (2005–2009).

Scenario Cost (US$) Iatrogenic twins (n = 273,624) Twin insurance cost estimated by this study 97,987 Total twin cost 26,811,594,888 Iatrogenic triplets (n = 26,446) Triplet insurance cost estimated by this study 391,700 Total triplet cost 10,358,898,200 Total iatrogenic multiples (n = 300,070) Total iatrogenic multiples cost 37,170,493,088 Cost if all otherwise multiples were singletons (US$18,244.00 per singleton) 5,474,477,080
Net saving if all otherwise multiples were singletons 31,696,016,008
Net saving if all otherwise multiples were singletons (1 year) 6,339,203,202

The proposed treatment plan calls for a maximum of four cycles of clomiphene citrate/IUI. This anticipates a live birth rate of 28.2% ( Dankert et al., 2007 ), which would have yielded 63 singletons in the 223 patients identified as having iatrogenic multiple pregnancies in this report. The residual 160 patients would have received IVF with cryopreservation. The IVF cost of US$13,000 is taken from a recent survey ( Chambes et al., 2013 ). Drug costs are included. The current work estimated the IUI cost of US$500 per attempt on the basis of the authors’ personal experience. Furthermore, all patients were assigned four attempts. This is surely excessive as most patients who achieve pregnancy with IUI achieve pregnancy with fewer trials. Cryopreservation cost was estimated at US$1000. The savings if all multiples had been singletons was US$22,188,384 ( Table 2 ). The calculation of net savings requires the subtraction of costs assuring a singleton: this amounted to US$2,686,000 ( Table 4 ). Thus, the net saving was US$19,502,384, or US$3,900,477 per annum ( Table 4 ). Table 4 Costs and savings of maximizing probability of singletons over 5 years for 223 otherwise multiples in the regional group. Scenario Cost (US$)
IUI cost (US$500 × 223 × 4) 446,000 IVF cost (@ US$13,000 × 160) 2,080,000
Cryopreservation cost (US$1000 × 160) 160,000 Total cost to maximize a singleton 2,686,000 Saving if all iatrogenic multiples had been singletons ( Table 2 ) 22,188,384 Net saving if all otherwise multiples were singletons 19,502,384 Net saving if all otherwise multiples were singletons (1 year) 3,900,477 Data are based on live birth rate 28.2% for clomiphene citrate/IUI requiring IVF with cryopreservation. The calculations assumed only one cycle of treatment for each patient in the multiple pregnancy group, which would be sufficient for most of the multiple group with demonstrated fertility. However, if one-third required additional treatment it would be reasonable to go directly to IVF. For these 74 patients, the additional costs were US$962,000 for IVF and US$74,000 for cryopreservation. The total additional cost for the 5 years was US$1,036,000, or US$207,200 per annum, and this would have reduced the net savings for 5 years to US$18,466,380, or US$3,693,277 per annum ( Table 5 ). Table 5 Costs and savings of maximizing probability of singletons over 5 years if a third of 223 otherwise multiples (n= 74) require a second IVF attempt with cryopreservation. Scenario Cost (US$)
IVF cost (@ US$13,000 × 74) 962,000 Cryopreservation cost (US$1000 × 74) 74,000
Additional cost to maximize live birth 1,036,000
Additional cost to maximize live birth (1 year) 207,200
Net saving if 74 otherwise multiples were singletons (US$19,502,384 ( Table 4 ) – US$1,036,000) 18,466,380
Net saving if 74 otherwise multiples were singletons (1 year) 3,693,277

### Discussion

The conclusions herein resulted from an opportunity to study the cost of iatrogenic multiple pregnancies using real numbers from a major health insurance company. The tabulated cost is minimal because there are some items not included in insurance coverage and therefore could not be added to the tabulated cost. Examples are provider cost prior to delivery and baby cost after 1 year. Multiples are particularly prone to long-range cost. An example might be cerebral palsy, which is 5-times more common in twins and 20-times more common in triplets as compared with singletons ( Pharoah and Cook, 1996 ).

The data from the regional group were applied to multiple pregnancy data for the entire USA with a suitable correction for spontaneous multiples. For the regional group, iatrogenic triplets accounted for 79% of all triplets ( Table 1 ). For the 1980 group using national percentages for singleton, twins and triplets, iatrogenic triplets accounted for 80% of all triplets ( Table 1 ). For the national group, iatrogenic triplets accounted for 82% of all triplets ( Table 1 ). The similarity of these numbers is striking. This suggests that the application of regional group costs to the national figures is not unreasonable. For iatrogenic twins, the regional group twins accounted for 54% of multiples ( Table 1 ); for the national group, the total was 40% ( Table 1 ). The increased percentage of twins in the regional group as compared with the national group may represent the availability of infertility services in a mandated state, one of which is among the states covered by the company.

This work estimated the infertility costs required for the 223 multiples in this series instead of having a singleton. These figures are unrelated to any insurance claims data in the series in question as the insurance policy under study did not cover costs prior to delivery. In a previous paper ( Jones and Allen, 2009 ), it was postulated that the elimination of multiple pregnancies for all women in the USA between the ages of 15 and 44 would provide savings to cover infertility benefits according to a defined algorithm. The actual amount equalled US$70 per woman. This was considered to be several times a possible insurance premium for that defined algorithm. The elimination of iatrogenic multiples at the national level would provide US$6,339,203,202 ( Table 3 ). This is sufficient to cover premiums for infertility benefits with a defined algorithm to minimize or eliminate iatrogenic multiple pregnancies. The actual amount for each of the 62,110,666 women between the ages of 15 and 44, according to the US Bureau of Vital Statistics for 2007, was US$102.06. It is impossible to cite a premium for such an algorithm because, as far as is known, no such insurance option exists. However, with over US$100 available per woman, it is very likely that this would cover such a premium 5–10-times over. To be sure, if this concept of insurance coverage with single-embryo transfer is employed by an insurance carrier, each item of the calculus will necessarily be re-evaluated. Changes will be required to update the concept, i.e. give account to inflation or to the possibility that, before application, it will become possible to identify the fertilized egg with pregnancy potential. This would surely change the treatment algorithm.

It must be realized that there are uncertainties when regional data, as used in this paper, are applied to national data, as also done in this paper. Thus, practice expenses are geographically variable. For example, practice costs in New York City would be far more than practice costs in a rural state in the mid-west. Furthermore, malpractice expenses are regional. For these and other causes, insurance reimbursement can and does vary regionally. Thus, in the application of regional data to national figures, some uncertainties may be introduced.

The elimination of iatrogenic multiples is one of the very few examples in medicine where better medicine is associated with reduced cost.

### References

• Chambes G.M., Adamson G.D., Eijkemans M.J. Acceptable cost for the patient and society. Fertil. Steril. 2013;100:319-327
• Dankert T., Kremer J.A., Cohlen B.J., Hamilton C.J., Pasker-de Jong P.C., Straatman H., van Dop P.A. A randomized clinical trial of clomiphene citrate versus low dose recombinant FSH for ovarian hyperstimulation in intrauterine insemination cycles for unexplained and male subfertility. Hum. Reprod. 2007;22:792-797
• Jones H.W. Jr., Allen B. Strategies for designing an efficient insurance fertility benefit: a 21st century approach. Fertil. Steril. 2009;91:2295-2297
• Pharoah P.O., Cook T. Cerebral palsy and multiple births. Arch. Dis. Child. Fetal Neonatal Ed. 1996;75:F174-F177

• Bromer et al, 2011 Bromer J.G., Ata B., Seli M. Preterm deliveries that result from multiple pregnancies associated with assisted reproductive technologies in the USA: a cost analysis. Curr. Opin. Obstet. Gynecol. 2011;23:168-173 Crossref
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Brian D Allen, BGS has over 28 years of experience in the health insurance industry working as a liaison between patients, medical providers and healthcare payers regarding infertility benefits. His accomplishments include authoring two patient education booklets, coauthoring many cost-related infertility medical articles and negotiating contemporary infertility benefits, including pay-for-performance incentives, with healthcare payers. Brian is the founder and president of Allen Consulting, a medical billing and coding consulting company that consults with reproductive medicine and obstetrics/gynaecology practices throughout the country.

### Footnotes

a Allen Consulting, Inc., 2003 Springdale Court, Coralville, IA 52241, USA

b The Warren Alpert Medical School, Brown University, Providence, RI 02912, USA

c Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, 601 Colley Avenue, Norfolk, VA 23507, USA

* Corresponding author.