Expectant management, IUI/OS, and IVF are the three therapeutic options for unexplained infertility. Farquhar et al demonstrated that three cycles of IUI/OS outperformed three cycles of expectant care in CLBR for unexplained infertility .However, the efficacy of IVF as compared to IUI is highly debated. When evaluating treatment options, five factors must be considered: The first is effectiveness (i.e., live birth rate or CLBR); the second is cost (including medical and non-medical costs); the third is time spending (time to live birth and time spent on treatment); the fourth is the patients' physical and psychological burden; and the last is maternal, fetal, and neonatal safety.
Several studies have been conducted to compare the efficacy of IVF with IUI. Angelique and her colleagues compared six cycles of IVF against six cycles of IUI and six cycles of IUI/OS. They observed that, whereas the IVF group had a higher live birth rate each cycle (12.2% vs. 7.4% and 8.7%, respectively; P = 0.09), the total live birth rates were comparable across the three groups. The dropout rate in the IVF group, on the other hand, was as high as 45% which would have an impact on the efficacy of IVF. Three more studies[3, 10, 11] compared the efficacy of one cycle of IVF to three cycles of IUI/OS and discovered no benefit to IVF. However, the first two studies[3, 11] failed to determine the sample size required to detect the difference in the primary outcome. The sample size in each group was only 58 and may be too small to make the difference significant. Although the third study calculated the sample size and planed 125 couples for each arm, the study ended when only 207 couples were enrolled because of fund withdrawal. Therefore, these three studies were of low quality and the conclusions were not convincing enough.
The preceding trials were done at a time when the live birth rate of IVF was much lower (12-24.7%) than it is now (42.23% in China in 2018). The live birth rate of IUI has been pretty stable over the last two decades: 7–10% in the studies mentioned above vs. 10.7% in China in 2018. As a result, with the current state of ART, it is critical to reassess the effectiveness of IVF vs. IUI/OS. According to the Chinese Society of Reproductive Medicine's (CSRM) 2018 Annual Report on Assisted Reproductive Technology (ART), poor ovarian reserve (POR) accounted for 11.84% of IVF indications. POR patients who do not have additional infertility problems are a subset of individuals with unexplained infertility who have impaired ovarian function. Although POR has become an important indication for IVF, it is still uncertain if IVF is better than IUI for patients with unexplained infertility and POR (UIPOR). As a result, we conducted this study to compare the efficacy of IVF with IUI in patients with UIPOR.
We looked at patients in Poseidon group 3 (age < 35 and AMH < 1.2 ng/mL) who had no other known reasons for infertility. To equalize the baseline features of the two groups, we employed the PSM. In the ITT analysis, our study found that the live birth rate in the IVF group was substantially higher than the CLBR in the IUI group (22.6 % vs. 11.3%, RR 2.00, 95% CI 1.20–3.32, P = 0.006). However, the mean cycles in the IUI groups were just 1.69. Because this is a retrospective, real-world study, comparing the efficacy of one IVF cycle with three IUI cycles is challenging, as it would be in a well-designed RCT. Because of their low ovarian reserve, POR patients are frequently concerned about their prognosis. They would prefer IVF as their first-line treatment since they feel it has a significantly greater pregnancy rate than IUI. As a result, UIPOR patients decline IUI after 1–2 unsuccessful cycles. IVF had a live birth rate of 22.6% per begun cycle, compared to 6.7% per initiated cycle in the IUI group. The CLBR of three cycles of IUI is thought to be equivalent to one cycle of IVF. In our facility, individuals with unexplained infertility are advised to undergo two cycles of IUI before doing IVF. So, we compared the CLBR of two IUI cycles in 87 patients to the LBR of one IVF cycle and discovered that the LBRs were identical in both groups: 20.7 % vs. 23.0% (P = 0.675). We should be very careful about this conclusion since individuals who had only one IUI cycle were omitted from the research, and their prognosis may have been poorer.
When evaluating a treatment approach, a cost-effectiveness analysis is critical. Goverde et al examined the CLBR for 6 cycles of IVF, 6 cycles of IUI, and 6 cycles of IUI/OS. They discovered that the IUI with natural cycle was the least expensive of the three procedures. Tjon-Kon-Fat et al evaluate the expenses of three IVF-SET cycles to six IVF-MNC cycles vs. six IUI/OS cycles. When compared to IUI-COH (€5070), the mean expenses per couple for IVF-MNC (€8206) and IVF-SET (€7187) were substantially higher. When compared to IUI/OS, the cost of an extra live birth via IVF-SET would be €43 375. Nandi et al. compared the efficacy of one IVF cycle to 3 IUI/OS cycles and determined that the expenses per livebirth for IVF were higher than for IUI, with a cost ratio of 1.3:1.
All three of the preceding studies solely analyzed medical expenses, demonstrating that IVF was more expensive than IUI. They did, however, overlook non-medical expenditures such as transportation, lodging, and time away from work. When we assessed the medical expenditures per live birth in our study, the costs for IVF were ¥10 676 greater than the costs for IUI. When the overall expenses per live birth, which included non-medical charges, were assessed, the prices for IVF and IUI were relatively similar. Our system didn't record the expenses beyond enrollment; therefore, we only computed the total expenditures from enrollment until the time of biochemical pregnancy.
Time to live birth and hospital visits on the therapy are two indicators used to assess the amount of time spent on fertility treatment. We didn't utilize the criterion "time to live birth" since it only included patients who had a live delivery and ignored the time spent by those who didn't. Because of the intricacy of IVF, the time to live delivery may be longer than with IUI. To compare the time spent for the two procedures, we utilized the Kaplan-Meier curves, which is recommended for evaluating the CLBR across time in clinical investigations. The findings showed that when the two groups were censored at 180 days, the live birth rates were not substantially different. However, when censored at 365 days, IVF had a higher live birth rate than IUI (log-rank test χ²= 6.025; P = 0.014). There have been no prior studies that focused on hospital visits for fertility treatment. We tallied the hospital visits and discovered that IUI patients required more hospital visits per live delivery than IVF patients (85 vs. 48). The majority of patients have employment, and they frequently have to request time off for treatment, which has a detrimental impact on their productivity and income. Furthermore, repeated hospital visits exhaust and stress them. From this perspective, IUI is less patient-friendly than IVF.
The safety aspects included: complications of ovarian stimulation (e.g., ovarian hyperstimulation, OHSS), oocyte aspiration (e.g., pelvic hemorrhage), maternal and fetal problems during pregnancy (mostly multiple pregnancies and birth abnormalities), and natal complications (e.g., premature delivery). There were two occurrences of late OHSS in the IVF group and none in the IUI group in the current research. Except for 6 twins and one birth defect in the IVF group and 1 fetal death in the IUI group, the neonatal results were similar between the two groups.
The current study has the following advantages: first, it is the first to assess treatment options for Poseidon group 3 and unexplained infertility patients. Second, PSM was utilized to equalize the baseline features of the two groups, reducing the impact of baseline on live birth. Third, while assessing cost-effectiveness, we included non-medical expenditures, which represent the couples' real costs. Finally, we compute the number of hospital visits per live birth, which represents the patients' physical and psychological stress.
The drawbacks are as follows: first, because this is retrospective research, it cannot adequately evaluate the efficacy of one IVF cycle with three cycles of IUI. In our study, the average number of IUI cycles was only 1.67. However, it is real-world research that represents the patients' and physicians' actual alternatives. Second, while assessing cost-effectiveness, the expenditures associated with pregnancy and delivery was not considered. Because there were six twin pregnancies in the IVF group, the expenses of IVF will be underestimated.