Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility
Karande VC , Vishvanath Karande , Rinehart J
John S. Rinehart , Norbert Gleicher, M Balin , K Dohn , A Korn , R Morris, R Rao
To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility.
Design
Prospective, randomized clinical study.
Setting
University-affiliated infertility clinic.
PATIENT(S): Couples with newly diagnosed infertility and no prior treatment.
INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility.
MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy.
RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same.
CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.
IVF versus standard treatment algorithm first-line infertility, randomized trial IVF cost effectiveness, traditional infertility treatment versus in vitro fertilization, first-line therapy couples infertility pregnancy rates, cost per pregnancy IVF versus conventional treatment, Karande Gleicher IVF randomized clinical study, stepwise infertility treatment algorithm outcomes, newly diagnosed infertility treatment approach comparison, IVF appropriateness first-line therapy cost analysis, standard infertility treatment higher pregnancy rate lower cost
PMID 10065784 10065784 DOI 10.1016/s0015-0282(98)00490-7 10.1016/s0015-0282(98)00490-7 Karande et al. 1999, Karande 1999
Cite this article
Karande, V. C., Korn, A., Morris, R., Rao, R., Balin, M., Rinehart, J., Dohn, K., & Gleicher, N. (1999). Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility. Fertility and sterility, 71(3), 468-475. https://doi.org/10.1016/s0015-0282(98)00490-7
Karande VC, Korn A, Morris R, Rao R, Balin M, Rinehart J, et al. Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility. Fertil Steril. 1999;71(3):468-475. doi:10.1016/s0015-0282(98)00490-7
Karande, V. C., et al. "Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility." Fertility and sterility, vol. 71, no. 3, 1999, pp. 468-475.
Restorative Reproductive Medicine (RRM) aims to restore fertility by diagnosing and treating the underlying causes of infertility. RRM is frequently promoted as an alternative to assisted reproductive technology (ART), despite uncertainty regarding its comparative effectiveness and safety. Where delayed childbearing and infertility are becoming more common, reliance on optimization of natural physiology alone may delay effective treatment and compromise reproductive outcomes. A systematic review of the current evidence comparing RRM to either ART or unassisted conception is, therefore, essential to inform clinical practice, guideline development, and shared decision-making for patients experiencing infertility. To assess the effectiveness and safety of RRM approaches, evaluated as a whole, rather than as individual components, compared with ART and medically unassisted conception in couples experiencing infertility. A systematic literature search of MEDLINE, Embase, CENTRAL and the Journal of Restorative Reproductive Medicine from inception to 28 November 2025. We included randomized control trials (RCTs) or nonrandomized comparative studies evaluating reproductive and safety outcomes of RRM as a unified treatment, compared with either ART or expectant management (attempted medically unassisted conception). Two reviewers independently screened titles, abstracts and full texts with disagreements resolved by a third reviewer. We retrieved 724 records, of which 16 studies underwent full-text review. No RCTs or comparative observational studies were identified. All 16 full-text studies were excluded for an ineligible study design (no control group); most were cohort studies in which all participants underwent RRM. Ten studies reported reproductive outcomes; nine of these made claims regarding the benefits or effectiveness of RRM. None of these claims were supported by the study designs used, as the lack of a comparison group precludes reliable estimation of treatment effects. Consequently, these studies cannot provide valid estimates of RRM success rates, nor permit any meaningful inference about its effectiveness relative to unassisted conception or ART. Large-scale RCTs or prospective cohort studies reporting effectiveness and safety outcomes are required to inform evidence-based fertility guidelines. There are no comparative studies to support reliable estimates of the safety and effectiveness of RRM compared with ART or medically unassisted conception for couples experiencing infertility.
To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). Decision analytic model comparing costs and clinical outcomes. Academic recurrent pregnancy loss programs. PATIENT(S): Women with unexplained RPL. INTERVENTION(S): IVF/PGS with 24-chromosome screening and expectant management. MAIN OUTCOMES MEASURE(S): Cost per live birth. RESULT(S): The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. CONCLUSION(S): In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management.
Schliep KC et al., 2015·Fertil Steril·
Open Access
To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes.
Prospective cohort study.
University fertility center. PATIENT(S): All couples undergoing first fresh IVF cycles, 2005-2010, for whom male and female weight and height information were available (n = 721 couples). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryologic parameters, clinical pregnancy, and live birth incidence. RESULT(S): The average male BMI among the study population was 27.5 ± 4.8 kg/m(2) (range, 17.3-49.3 kg/m(2)), while the average female BMI (n = 721) was 25.2 ± 5.9 kg/m(2) (range, 16.2-50.7 kg/m(2)). Neither male nor female overweight (25-29.9 kg/m(2)), class I obese (30-34.9 kg/m(2)), or class II/III obese (≥35 kg/m(2)) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5-24.9 kg/m(2)) status after adjusting for male and female age, partner BMI, and parity. Similar null findings were found between combined couple BMI categories and IVF success. CONCLUSION(S): Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed.
Racial disparity in assisted reproductive technology (ART) outcomes has been reported but remains controversial. Reasons for the disparity are unclear, and access to care has been suggested as a causative factor. In this study, we sought to examine minority utilization of ART in the Department of Defense (DoD) compared with minority utilization in the U.S. ART population. Outcomes from ART were compared between Caucasian (Cau) and African American (AA) patients, and etiologies of disparity were examined. Retrospective cohort study. University-based ART program. PATIENT(S): A total of 1,457 patients undergoing first-cycle fresh, nondonor ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, live birth rate, implantation rate, spontaneous abortion rate. RESULT(S): Within the DoD population, AA women had a fourfold increase in utilization of ART services relative to the U.S. ART population. In this equal-access-to-care setting, AA women experienced a clinically significant decrease in live birth rate that did not reach statistical significance (29.6% vs. 35.8%, risk ratio [RR] 0.83, 95% confidence interval [CI] 0.67-1.02) and a statistically significant increase in spontaneous abortions compared with Cau women (25% vs. 15.9%, RR 1.57, 95% CI 1.05-2.36). This might be explained, in part, by a higher prevalence of uterine leiomyomas in AA women (30.8% AA vs. 10.7% Cau, RR 2.85, 95% CI 2.06-3.95). For both AA and Cau women, the presence of fibroids at baseline ultrasound was associated with reductions in clinical pregnancy rates (35% with leiomyomas vs. 43.2% without leiomyomas, RR 0.74, 95% CI 0.51-0.98), live birth rates (26.2% vs. 36.0%, RR 0.63, 95% CI 0.44-0.90), and implantation rates (25.6% vs. 31.1% RR 0.82, 95% CI 0.69-0.98). CONCLUSION(S): Utilization of ART services among AA women increased when access to care was improved. A clinically significant reduction in live birth rate and statistically significant increase in spontaneous abortion rate was observed in AA women compared with Cau women. Leiomyomas were three times more prevalent in AA women and reduced ART success, regardless of race. The persistence of racial differences in an equal-access-to-care environment might be explained, in part, by the increased prevalence of leiomyomas in AA women.