A short versus a long time interval between semen collection and intrauterine insemination: a randomized controlled clinical trial

Abstract

STUDY QUESTION Does a short interval (i.e. ≤90 min), compared to a long interval (i.e. ≥180 min), between semen collection and intrauterine insemination (IUI) increase the cumulative chance of an ongoing pregnancy after six IUI cycles? SUMMARY ANSWER A long interval between semen collection and IUI resulted in a borderline significant improvement in cumulative ongoing pregnancies and a statistically significant shorter time to pregnancy. WHAT IS KNOWN ALREADY Retrospective studies assessing the effect of the time interval between semen collection and IUI on pregnancy outcomes have shown inconclusive results. Some studies have indicated a beneficial effect of a short interval between semen collection and IUI on IUI outcomes, while others have not found any differences. To date, no prospective trials have been published on this subject. STUDY DESIGN, SIZE, DURATION The study was performed as a non-blinded, single-center RCT with 297 couples undergoing IUI treatment in a natural or stimulated cycle. The study was conducted between February 2012 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples with unexplained or mild male subfertility and an indication for IUI were randomly assigned for up to six IUI cycles into either the control group (long interval, i.e. 180 min or more between semen collection and insemination) or the study group (short interval, i.e. insemination as soon as possible after semen processing and within 90 min of semen collection). The study was carried out in an academic hospital-based IVF center in the Netherlands. The primary endpoint of the study was ongoing pregnancy rate per couple, defined as a viable intrauterine pregnancy at 10 weeks after insemination. MAIN RESULTS AND THE ROLE OF CHANCE In the short interval group, 142 couples were analyzed versus 138 couples in the long interval group. In the intention-to-treat (ITT) analysis, the cumulative ongoing pregnancy rate was significantly higher in the long interval group (71/138; 51.4%) compared to that in the short interval group (56/142; 39.4%; relative risks 0.77; 95% CI 0.59–0.99; P = 0.044). The time to pregnancy was significantly shorter in the long interval group (log-rank test, P = 0.012). A Cox regression analysis showed similar results (adjusted hazard ratio 1.528, 95% CI 1.074–2.174, P = 0.019). LIMITATIONS, REASONS FOR CAUTION Limitations of our study are the non-blinded design, the long inclusion and follow-up period of nearly seven years and the large number of protocol violations, especially because they predominantly occurred in the short interval group. The non-significant results in the per-protocol (PP) analyses and the weaknesses of the study should be taken into account in the assessment of the borderline significance of the results in the ITT analyses. WIDER IMPLICATIONS OF THE FINDINGS Because it is not necessary to perform the IUI immediately after semen processing, there can be more time available to choose the optimum work-flow and clinic occupancy. Clinics and laboratories should find their optimal timing of insemination, considering the time between human chorionic gonadotropin injection and insemination in relation to the sperm preparation techniques used as well as the storage time and conditions until insemination. STUDY FUNDING/COMPETING INTEREST(S) There were no external funding and no competing interests to declare. TRIAL REGISTRATION NUMBER Dutch trial registry, trial registration number NTR3144. TRIAL REGISTRATION DATE 14 November 2011. DATE OF FIRST PATIENT’S ENROLLMENT 5 February 2012.

Infertilidade

“…Para as abordagens de baixa complexidade, existem as opções que são: coito programado que é a programação de quando a relação sexual deverá acontecer entre o casal, dentro do período fértil da mulher, a inseminação intrauterina (IIU) que corresponde a injeção do sêmen na cavidade uterina, após uma seleção dos espermatozoides, ocorrendo a fertilização no organismo da mulher (STATEMA-LOHMEIJER et al, 2023), e a indução de ovulação que se refere à utilização de fármacos para induzir a ovulação como o citrato de clomifeno que atua seletivamente no receptor de estrogênio inibindo o efeito de feedback negativo do estradiol e, com isso, leva ao aumento da secreção do hormônio liberador de gonadotrofina (GnRh) hipotalâmico, consequentemente estimulando a produção hipofisária de FSH e do LH, o que induz o crescimento do folículo ovariano (MEJIA et al, 2019). Outro medicamento utilizado é o letrozol com ação de inibir a aromatase, enzima capaz de catalisar a conversão de andrógenos em estradiol, reduzindo os níveis séricos de estrogênio, o que bloqueia o feedback negativo no hipotálamo e na hipófise haverá aumento na produção do FSH e LH estimulando o crescimento do folículo ovariano (DAHLBERG et al, 2023, ASRM Practice Committee, 2020.…”