Evaluation of Assisted Reproductive Technology Health Insurance Coverage for Multiple Pregnancies and Births in Korea

Continuous quality improvement and assisted reproductive technology multiple gestations: some progress, some answers, more questions

BackgroundKorea is encountering major challenges related to its declining birth rate and aging population. Various policies have been introduced to prevent further population decrease and boost the birth rate, but their effectiveness has not been verified. Therefore, this study examined the effects of assisted reproductive technology (ART) insurance coverage on marriage, pregnancy, and childbirth in women of childbearing age.MethodsAll information on marriage, pregnancy, childbirth of women of childbearing age was obtained from Statistics Korea and Korean National Health Insurance Service database. During a total follow-up period of 54 months (July 2015 to December 2019), an average of 12,524,214 women of childbearing age per month, and 29,701 live births per month were included in the analysis. An interrupted time series with segmented regression was performed to analyze the time trend and changes in outcomes.ResultsThe implementation of ART coverage policies had no significant impact on marriage or pregnancy rates. However, it did affect multiple pregnancy and multiple birth rates, which increased by 1.0% (Exp(β3) = 1.010, P-value = 0.0001) and 1.4% (Exp(β3) = 1.014, P-value = < 0.0001), respectively, compared to the pre-intervention period. Although the effect of covering ART treatment on total birth rates were not confirmed, a slightly slower decline was observed after the intervention (Exp(β1) = 0.993, P-value = < 0.0001, Exp(β1 + β3) = 0.996 P-value = 0.012).ConclusionThis study identified the effects of ART health insurance coverage policy on the rates of multiple pregnancies and births. After the policy implementation, the downward trend in the total birth rate reduced slightly. Our findings suggest that interventions to support infertile couples should be expanded to solve the problem of low fertility rates.Plain english summaryTo address the intricate problems related to low birth rates, the Korean government introduced a policy that provides financial support and health insurance coverage for assisted reproductive technology (ART) treatment for infertile couples. As a result of evaluating the effectiveness of the ART coverage policy, it led to higher rates of pregnancies and births. In addition, although the total birth rate has been continuously decreasing over time, the decline may have been slowed down slightly by this policy.

The decreased rates of triplet births: Temporal trends and biologic speculations

After completing this article, readers should be able to: 1. Describe the outcomes of assisted reproductive technologies (ART) for singleton, twin, and other multiple births. 2. Describe the role of fertility in adverse outcomes seen with ART births. 3. Review the association of birth defects with ART. 4. Delineate the association of disease of genomic imprinting with ART. 5. Describe the relationship between ART and the subsequent incidence of neurodevelopmental sequelae. In the 1977 ruling “Carey v. Population Services International,” the United States Supreme Court ruled that the decision to bear children is constitutionally protected. (1) Significant interest already had been shown in the development and improvements of in vitro fertilization (IVF) for infertile couples. The first human pregnancy and human birth using IVF were reported by Steptoe and Edwards in the United Kingdom. (2) Their work resulted in the first baby born via reproductive technologies, Louise Brown, born on July 25, 1978, at Oldham General Hospital in Oldham, United Kingdom. (3) She was born via a planned cesarean section, and her birthweight was 2.61 kg. The first successful viable IVF in the United States was performed by Jones and Seager-Jones in 1981 in Norfolk, Virginia. (4) Assisted reproductive technologies (ART) have seen a recent surge in popularity. The Centers for Disease Control and Prevention (CDC) reported that 122,872 cycles of ART were initiated in 2003, resulting in the delivery of 48,756 neonates, (5) accounting for approximately 1% of all neonates delivered in the United States. The percentage is higher in many countries, including Denmark, where it is estimated that 5% of all deliveries are with the assistance of ART. (6) Couples pursue ART for myriad reasons, including tubal transport factors, ovulatory dysfunction, uterine factors, endometriosis, male- and female-specific factors, and when a cause of infertility is unknown. (5) It would be very …

IntroductionThe purpose of the present study was to estimate the effect of fertility treatment; both assisted reproductive technology (ART) and non-ART ovulation stimulation, on the number and rate of multiple...

Insurance mandates and trends in infertility treatments

There is no national law in the United States concerning the number of embryos that can be transferred into the uterus following fertilization in vitro. However, the American Fertility Society (AFS) (later the American Society for Reproductive Medicine) (ASRM) first referred to a limitation of numbers to transfer in 1994 (Ethics Committee, American Fertility Society). The recommendation did not specify specific numbers but charged programs to transfer a number which would eliminate quadruplets and limit triplets to no more than 1-2%. These recommendations were later converted into specific numbers and the guidelines have been revised from time to time since then. The 2009 revision is the first to mention, much less recommend, SET in “favorable patients” under the age of 35 years (Table 1). Table I. Recommended limits on the numbers of embryos to transfer. It is not easy to correlate the effect of the ever restricting guidelines with the incidence of multiple pregnancies from IVF. From 1996 through 2006, there was a very modest decrease in the percentage of multiple births from IVF as compared to total births from IVF (Fig. 1). Nevertheless, in 2006, multiples still accounted for 25.1% of live births from IVF (2006 CDC Assisted Reproductive Technology Report). Fig. 1 Percentage of IVF cycles that resulted in multiple infant live births by type of ART cycle 1996-2006 (2006 Assisted Reproductive Technology [ART] report. The situation is further complicated by the fact that in the United States there is no tabulation of the use of selective reduction. It is necessary to consider the possibility that the modest decrease in multiple births shown in figure 1 is almost entirely the consequence of selective reduction. A complete understanding of the multiple pregnancy problem in the United States is incomplete without considering the role of ovulation induction and ovulation enhancement (OI/OE). There is no reporting requirement but an estimate of the role of OI/OE can be made on the basis of the National Vital Statistics which tabulate multiple births as well as the total number of births as reported on birth certificates which by law are required to be filed. Using these data, it can be derived that multiple births from OI/OE can be ascertained by subtracting from the total number of multiple births those multiple births estimated to occur naturally and those births reported to the Center for Disease Control for IVF. When this is done for the years 2000-2003, IVF accounts for about 8% of twin births, OI/OE about 30%, and natural twinning the remainder. For triplets, IVF accounts for 15%, OI/OE 65%, and natural twinning for the residual 20% (Jones, 2007). A final background point is that nationally triplets as a percentage of total births peaked in 1998 and have declined definitely but slightly since that time. However, triplets still accounted for 1.5/1,000 live births compared to a natural incidence of less than 0.5/1,000 live births (Fig. 2). Furthermore, twins as a percentage of all births peaked in 2004 and have plateaued in the remaining years of data available. As of 2006, twins for the entire U.S. population were 1.8 times as frequent as could be expected from spontaneous twinning (Fig. 2). Fig. 2 Twin and triplet birth rates for the entire United States as a percentage of total births (U.S. Vital Statistics). While there has been only limited support for SET by any national organization in the United States, there have been individual voices promoting the concept. Thus, Gardner and Lane (2003) advocated the use of blastocysts rather than earlier stages if SET were to be applied. In addition, the Shady Grove Center reported results from 784 eSET using blastocysts in a selected group of patients. The twinning for this class of patients dropped from 44% to 1% (Stillman et al., 2009).

Do assisted reproductive technologies cause adverse fetal outcomes?

Reducing the number of embryos transferred per ART procedure and increasing use of eSET, when clinically appropriate (typically for women aged <35 years), could help reduce multiple births, particularly ART-conceived twin infants, and related adverse consequences of ART. Because twins account for the majority of ART-conceived multiple births, improved patient education and counseling on the maternal and infant health risks of having twins is needed. Although ART contributes to high rates of multiple births, other factors not investigated in this report (e.g., delayed childbearing and non-ART fertility treatments) also contribute to multiple births and warrant further study.

The concern of ART treatment on maternal transport cases in the tertiary perinatal center

Towards the global coverage of a unified registry of IVF outcomes.

Problem/ConditionSince the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015.Period Covered2015.Description of SystemIn 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102–493 [October 24, 1992]). Data are collected through the National ART Surveillance System, a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico).ResultsIn 2015, a total of 182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the intent to transfer at least one embryo were performed in 464 U.S. fertility clinics and reported to CDC. These procedures resulted in 59,334 live-birth deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born (range: 68 in Wyoming to 9,176 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15–44 years), a proxy measure of the ART utilization rate, was 2,832. ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia).Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.6 among women aged <35 years, 1.8 among women aged 35–37 years, and 2.3 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in Delaware).In 2015, ART contributed to 1.7% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants, and 22.2% of all triplets and higher-order infants. The percentage of multiple-birth infants was higher among infants conceived with ART (35.3%) than among all infants born in the total birth population (3.4%). Approximately 34.0% of ART-conceived infants were twins and 1.0% were triplets and higher-order infants.Nationally, infants conceived with ART contributed to 5.1% of all low birthweight infants. Among ART-conceived infants, 25.5% had low birthweight, compared with 8.1% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (31.2%) than among all infants born in the total birth population (9.7%). Among singletons, the percentage of ART-conceived infants who had low birthweight was 8.7% compared with 6.4% among all infants born. The percentage of ART-conceived infants who were born preterm was 13.4% among singletons compared with 7.9% among all infants.InterpretationMultiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged <35 years, who are typically considered good candidates for eSET, the national average of 1.6 embryos was transferred per ART procedure. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance coverage has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states.Public Health ActionTwins account for the majority of ART-conceived multiple births. Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences for both mothers and infants. State-based surveillance of ART might be useful for monitoring and evaluating maternal and infant health outcomes of ART in states with high ART use.

Ovarian stimulation and intrauterine insemination at the quarter centennial: implications for the multiple births epidemic

Pericentric inversion of chromosome 9 [inv (9)] is a common chromosomal polymorphism found in approximately 1-2% of the population. While inv(9) has been generally considered a benign variant, its potential effects on reproductive outcomes, especially in the context of assisted reproductive technology (ART), remain unclear. This study aimed to evaluate whether inv(9) affects embryologic and reproductive outcomes in ART cycles. This retrospective cohort study included 40,502 ART cycles conducted between September 2008 to December 2023, of which 903 involved couples carrying inv(9) and 39,599 involved couples with normal karyotypes (NK). Propensity score matching (PSM) was used to balance baseline characteristics. The primary outcome was live birth rate (LBR), and secondary outcomes included biochemical and clinical pregnancy, miscarriage, and neonatal outcomes among live births (multiple births and low birth weight), and cycle parameters (oocyte yield, fertilization, and blastocyst formation rates). After 1:2 PSM, baseline characteristics were balanced between inv(9) and NK groups. Cycle outcomes, including oocytes retrieved (10.0 ± 7.8 vs 9.9 ± 7.5), fertilization, and blastocyst formation rates, were comparable. In fresh embryo transfer (ET) cycles, inv(9) carriers had a modestly higher live birth rate compared to NK couples (46.4% vs 41.2%; aRR = 1.13; 95% CI 1.01-1.27), while no significant differences were observed in frozen embryo transfer (FET) cycles (41.1% vs 40.0%; aRR = 1.04; 95% CI 0.93-1.17). Other pregnancy outcomes (multiple births, low birth weight, biochemical pregnancy, clinical pregnancy, and miscarriage) were similar between groups. No significant differences in live birth, clinical pregnancy, miscarriage, multiple births, or low birth weight were observed between male and female inv(9) carriers in either fresh or frozen cycles. Pericentric inversion of chromosome 9 was not associated with adverse embryologic or reproductive outcomes in ART. These findings support the classification of inv(9) as a benign chromosomal variant and provide reassurance that its presence does not warrant additional intervention in couples undergoing ART.

BackgroundThe burden of rare diseases on society and patients’ families has increased in Korea. However, because of the infrequency of rare diseases, there is a lack of resources and information to address these cases and inadequate funding for the management of these patients. We investigated the average annual cumulative incidence of rare diseases and the trends in annual cumulative incidence from 2011 to 2015 in Korea by using nationwide administrative data from the Korean National Health Insurance Service (NHIS) database for patients registered with the co-payment assistance policy for rare and incurable diseases. Annual cumulative incidence per 10,000,000 was calculated as the total number of newly enrolled patients with the Korean Standard Classification of Diseases (KCD)-7 code in the register, divided by the number of residents with health insurance coverage during each year. We employed simple linear regression analysis to evaluate the trends in annual cumulative incidence/10,000,000 population per year for each rare disease.ResultsOverall, national support was provided for patients with 415 KCD codes listed among the targeted rare diseases. The total number of newly enrolled patients with rare diseases was 53,831 in 2011, 52,658 in 2012, 52,955 in 2013, 71,530 in 2014, and 70,559 in 2015. The number of rare diseases with an average annual cumulative incidence of 100/10,000,000 and above was 22 (5.30%), while there were 227 (54.70%) and 148 (35.66%) with an average cumulative incidence between 1/10,000,000 and 100/10,000,000 and less than 1/10,000,000, respectively. The trends in the annual cumulative incidence for 43 rare diseases were statistically significant (p-value < 0.05). The rare diseases for which the incremental trend per year was statistically significant were sarcoidosis (D86, D86.0, D86.1, D86.2, D86.3, D86.8, D86.9), Parkinson’s disease (G20), Guillain-Barré syndrome (G61.0), primary biliary cirrhosis (K74.3) and Sjogren’s syndrome (M35.0).ConclusionsThe number of rare diseases showing an increasing trend in annual cumulative incidence was higher than the number of diseases showing a decreasing trend in annual cumulative incidence. Given that the definition and diagnosis vary based on country and that there is difficulty in identifying valid cases, further detection strategies are needed to establish the incidence of each rare disease considering the importance of establishing a health policy based on the actual incidence of the targeted diseases.