The Effect Of Different Timing Of R-LH Addition In Follicular Phase Long-acting Regimen On IVF-ET Clinical Outcomes

Objective:To investigate the effect of different timing of recombinant luteinizing hormone(r-LH)addition on in vitro fertilization-embryo transfer(IVF-ET)outcomes in patients with low luteinizing hormone(LH)levels after pituitary downregulation in a long follicular phase protocol.Methods:The retrospective study was conducted from March 2020 to March 2022 in the Department of Reproductive Medicine of the First Affiliated Hospital of Gannan Medical University using the long follicular phase protocol.Patients with gonadotropin-releasing hormone agonist(Gn RH-a)down-regulation followed by gonadotropin(Gn)initiation day serum LH <1.2 m IU/ml were selected as study subjects,and a total of 112 patients met the inclusion and exclusionc criteria and had complete medical records and follow-up information.The patients were divided into two groups according to the timing of r-LH addition: group A(n=54),where r-LH was added on the initiation date of Gn;and group B(n=58),where r-LH was added after five days of Gn.The patients were followed up for a long period of time,and the data of the two groups were recorded and compared,including: general data and related indicators,superovulation,Gn administration,embryonic indicators and pregnancy outcome.Results:1.Comparison of the general data of the two groups: age,body mass index(BMI),anti-mullerian hormone(AMH),antral follicle count(AFC)and serum follicle stimulating hormone(FSH),LH and estradiol(E2)levels on the day of Gn initiation were not statistically different between groups A and B(P>0.05).2.Comparison of superovulation in the two groups: the duration of Gn use was shorter in group A(10.76±1.40 days)compared with group B(11.76±1.70 days),the difference was statistically significant(P<0.05);the differences between groups A and B in the number of returns to hospital during Gn and the differences in serum LH,E2,progesterone(P)and endometrial thickness on the trigger day were not statistically different(P>0.05).3.Comparison of Gn medication use between the two groups: total Gn medication and total medication cost were higher in Group A than in Group B,but the difference was not statistically significant(p>0.05).4.Comparison of embryonic indicators between the two groups: the normal fertilization rate(74.5%)and the transferable embryo rate(95.4%)were significantly higher in group A than in group B(68.6%,91.2%),with statistically significant differences(P<0.05).The number of eggs obtained in group A was lower than that in group B.However,the number of Metaphase II(MII),2 pronucleus(PN)fertilization,2PN oogenesis,day 3(D3)post fertilization quality embryos,transferable embryos and D3 quality embryo rate were all higher in group A than in group B.None of the above indicators were statistically different(P>0.05).5.Comparison of pregnancy outcomes between the two groups: the rates of whole embryo freezing and miscarriage were lower in Group A than in Group B,while the rates of clinical pregnancy and sustained pregnancy were higher than in Group B.However,the differences in pregnancy outcomes between the two groups were not statistically different(p>0.05).Conclusion:In patients with low LH levels after Gn RH-a downregulation in the long follicular phase protocol,the addition of r-LH from the Gn initiation date may shorten the number of days of Gn use and increase the rate of normal fertilisation and transferable embryos compared to the addition of r-LH from the mid-Gn onwards during ovulation promotion.It is recommended that patients with low LH levels after Gn RH-a downregulation start adding r-LH on the Gn initiation date,but whether the total amount and cost of Gn drugs added to r-LH on the Gn initiation date is increased still needs to be further explored in an expanded sample selection prospective randomised controlled study.