Abstract

Abstract Study question Is there an optimal number of intrauterine inseminations before offering another treatment for unexplained infertility, taking into account cumulative pregnancy rate and drop out? Summary answer Up to 3-4 intrauterine inseminations are advisable for unexplained and mild male infertility, as this will provide the optimal chances for the patient. What is known already Intrauterine insemination has been used as a first line treatment for unexplained infertility and mild male subfertility. However, during the years great debate and only few randomised controlled studies has been published supporting this. It has been shown that up to 3 inseminations are comparable to an IVF cycle. Further, multiple gestations can be managed and reduced in inseminations as well. Thus, up to 3 cycles of intrauterine inseminations can increase the chances of a healthy offspring and in controlled trials are comparable to an IVF cycle. Study design, size, duration The study is a retrospective cohort study including all patients in treatment for unexplained infertility, anovulation disorders or mild male factor from 2005 to 2022 in a single fertility clinic. Inclusion criteria: more than 1 year of infertility, normal or moderate sperm parameters. A total of 3729 women were included and all followed until pregnancy or drop out. A total of 9459 cycles were included. Participants/materials, setting, methods Women between 18 and 40 years were included. All had more than 1 year of infertility and suffered from unexplained infertility, mild male factor or ovulation disorders. All women received a mild oral tamoxifen or clomiphene stimulation for 5 days and when the leading follicle was 17 mm in diameter an ovulation induction with Fyrmadel 0,25 mg was used. All inseminations after Percoll centrifugation. Pregnancy in 12 weeks were recorded including number of gestations. Main results and the role of chance We found a cumulative pregnancy rate for 3 cycles to be 29%, for 4 cycles 32%, for 5 cycles 35%, for 6 cycles 37%, and a corresponding cumulative drop out of; for 3 cycles; 33%, for 4 cycles;43% for 5 cycles; 50%, for 6 cycles 55%. Multiple gestations were found to be 4%. Using this large data material, we found that 3-4 intrauterine inseminations were acceptable due to the cumulative pregnancy rate and drop numbers. Increasing the number to more cycles did not benefit the patient’s chance significantly and should not be recommended. The study was able to identify all cycles from any individual person starting the treatment and therefore the drop out form a main fertility clinic could be estimated properly. No hyperstimulation’s syndrome were identified and a multiple gestational risk of 4 % were identified. Limitations, reasons for caution A retrospective study from 2005 to 2021 with the limitations that a retrospective carries. The lab procedure/stimulation protocol were the same which makes the results robust. This study involved a large number of patients (3729) every cycle were followed until they got pregnant and dropped out until the 6th cycle. Wider implications of the findings Intrauterine insemination is a safe and efficient treatment option for a group of infertile women. This study describes the relative high drops out after 4-5 cycles and a cumulative pregnancy rate of 30-33% following 3-4 cycles. hereafter the cumulative pregnancy rate does not rise significantly and drop out increases. Trial registration number na

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