Effect Of The Time Interval Between Miscarriage After In Vitro Fertilization-Embryo Transfer And Next Embryo Transfer On Pregnancy Outcomes

BackgroundAbout 10-20%of pregnancies after in vitro fertilization-embryo transfer ended up with miscarriage.Women with other risk factors,such as women with advanced age or women with polycystic ovary syndrome had an even higher incidence of miscarriage.The optimal time interval between miscarriage and the next embryo transfer is still unclear.At present,the relevant evidence was rare and controversial.Further research is warranted.Based on limited evidence,the World Health Organization recommends waiting for six months after a natural pregnancy miscarriage before attempting another pregnancy.However,there is currently very little evidence on how long to wait after a miscarriage in women who require assisted reproductive technology for pregnancy.ObjectiveComparing the effects of different time intervals between the miscarriage after the previous embryo transfer and the subsequent embryo transfer on pregnancy outcome.MethodsThe data on the next embryo transfer for patients with a clinical pregnancy loss after in vitro fertilization/Intracytoplasmic sperm injection-embryo transfer in the Center for Reproductive Medicine affiliated with Shandong University from June 2017 to September 2021 were retrieved.Women with recurrent spontaneous abortion,repeated implantation failure,uterine abnormalities,planning to undergo preimplantation genetic testing(PGT),planning to transfer embryos that have been frozen twice or more,those who used donor oocytes,and those with unhealthy hobbies were excluded.Patients have divided into three groups based on the time interval between previous miscarriage and subsequent embryo transfer:Group Ⅰ(<90 days),Group Ⅱ(90-180 days),and Group Ⅲ(>180 days).Pregnancy outcomes between the three groups were compared,and logistic regression was used to adjust for confounding factors such as age,duration of infertility,education level,the indication of ART,body mass index(BMI),polycystic ovary syndrome,mode of previous abortion,stage of previous abortion,endometrial thickness before the subsequent embryo transfer,bilateral antral follicle count,,anti-Müllerian hormone level,gravidity,embryo fertilization method,embryo type,and number of embryos transferred to analyze the effect of the time interval between previous miscarriage and subsequent embryo transfer on the outcome of subsequent pregnancy.Result(s)A total of 2,760 patients were included in the analysis,with 307(11.1%)in GroupⅠ(<90 days),1342(48.6%)in Group Ⅱ(90-180 days),and 1111(40.3%)in Group Ⅲ(>180 days).The clinical pregnancy rates of Group I(<90 days),Group Ⅱ(90-180 days),and Group Ⅲ(>180 days)were,respectively,51%,55%,and 58%,respectively(P=0.104);the live birth rates were 39%,43%,and 46%,respectively,(P=0.07).Although the between-group differences in clinical pregnancy rates and live birth rates were not statistically significant,there was a dose-response trend with increasing time intervals.The singleton live birth rates of Groups Ⅰ,Ⅱ,and Ⅲ were 36%,40%,and 44%,respectively(P=0.036),with a statistically significant between-group difference.As the time interval increased,there was a dose-response increase in singleton live birth rates.The rates of pregnancy loss in the three groups were 38%,33%,and 31%,respectively(P=0.16).Although the between-group differences were not statistically significant,there was a dose-response decrease with increasing time intervals.After adjusting for potential confounding factors,the clinical pregnancy rates,live birth rates,and singleton live birth rates of Group I were significantly lower than those of Group Ⅲ,with adjusted odds ratios(ORs)and 95%confidence intervals(CIs)of 0.75(0.57-0.97),0.75(0.57-0.98),and 0.71(0.54-0.93),respectively.The biochemical pregnancy rates,clinical pregnancy rates,live birth rates,and singleton live birth rates of Group Ⅱ were also significantly lower than those of Group Ⅲ after adjustment,with ORs and 95%CIs of 0.83(0.69-0.98),0.81(0.69-0.96),0.81(0.69-0.96),and 0.79(0.67-0.93),respectively.Conclusion(s)Patients who experience clinical pregnancy loss after IVF or ICSI embryo transfer may have reduced pregnancy and live birth rates if they undergo embryo transfer again within a short interval.Waiting for at least 6 months before undergoing another embryo transfer may result in better pregnancy outcomes,but further prospective studies are needed to confirm these findings.