Efficacy of in vitro fertilization and embryo transfer

A Cochrane review «In vitro fertilisation for unexplained subfertility»1 «Sunkara SK, Kamath MS, Pandian Z et al. In vitro fertilisation for unexplained subfertility. Cochrane Database Syst Rev 2023;9(9):CD003357. »1 included 9 studies involving a total of 2191 subjects. Live-birth rates (LBR) per woman was higher with in vitro fertilisation (IVF) (45.8%) than expectant management (3.7%) (OR 22.00; 95% CI 2.56 to 189.37; 1 RCT, n=51). In studies comparing IVF versus ovarian stimulation plus intrauterine insemination (OS-IUI), LBR per woman did not differ significantly between the groups. Assuming 42% LBR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 26% LBR with IUI + gonadotropins (1 IVF to 1 IUI cycle), LBR would be 39% to 54% and 24% to 51% with IVF. There was no evidence of a significant difference in multiple pregnancy rate or ovarian hyperstimulation syndrome between the two treatments.

Another Cochrane review «»2 and a network meta-analysis «Wang R, Danhof NA, Tjon-Kon-Fat RI et al. Interventions for unexplained infertility: a systematic review and network meta-analysis. Cochrane Database Syst Rev 2023;(9):CD012692. »2 included 27 RCTs with 4 349 couples. Ten RCTs including 2 725 couples reported on live birth. For differences between OS, IUI, OS-IUI, or vitro fertilisation with or without intracytoplasmic (IVF/ICSI) versus expectant management see table (table «Expectant management vs other interventions for infertility»1). This suggests that if the chance of live birth following expectant management is assumed to be 17%, the chance following OS, IUI, OS-IUI, and IVF would be 9% to 28%, 11% to 33%, 15% to 37%, and 14% to 47%, respectively. When only including couples with poor prognosis of natural conception (3 trials, 725 couples) OS-IUI and IVF/ICSI increased LBR compared to expectant management (OR 4.48, 95% CI 2.00 to 10.1; moderate-certainty evidence; OR 4.99, 95 CI 2.07 to 12.04; moderate-certainty evidence), while there was insufficient evidence of a difference between IVF/ICSI and OS-IUI (OR 1.11, 95% CI 0.78 to 1.60; low-certainty evidence). Compared to expectant management, other treatments increased the odds of multiple pregnancy (11 RCTs, 2564 couples).

An individual participant data (IPD) meta-analysis «Lai S, Wang R, van Wely M, et al. IVF versus IUI with ovarian stimulation for unexplained infertility: a collaborative individual participant data meta-analysis. Hum Reprod Update 2024;30(2):174-185. »3 included 4 RCTs (IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS). Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81 to 1.74; 4 trials, n=908; I²=42%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41 to 1.50; 3 trials, n=890; I²=0.0%).

A systematic review and meta-analysis «Nandi A, Raja G, White D, et al. Intrauterine insemination + controlled ovarian hyperstimulation versus in vitro fertilisation in unexplained infertility: a systematic review and meta-analysis. Arch G»4 included 8 RCTs. Compared with IUI, IVF was associated with a statistically significant higher live birth rate with no significant difference in multiple pregnancy rate or OHSS rate. However, sensitivity analysis based on women's age and a history of previous IUI or IVF treatment showed no significant difference in the live birth rates (RR 1.01, 95% CI 0.88 to 1.15, I²=0%, 3 RCTs) in treatment-naïve women younger than 38 years. In women over 38 years, the live birth rates were significantly higher in the IVF group (RR 2.15, 95% CI 1.16 to 4.0, I²=42%, 1 RCT).

Comment: The certainty of the evidence is downgraded by risk of bias (no blinding).