Effect Of Bromocriptime On IVF/ICSI Outcomes In Patients With Hyperprolactinemia With Unclear Etiology Or PCOS

Background Hyperprolactinemia can lead to fertility disorders such as amenorrhea,ovulation disorder and luteal insufficiency in women.The prevalence rate is about 19.5%in infertile people and 10%-30%in patients with polycystic ovary syndrome(PCOS).However,the relationship between PCOS and hyperprolactinemia is not very clear.In addition,the etiology of hyperprolactinemia of about 40%of patients is unclear,which is called idiopathic hyperprolactinemia.Most of these patients have no obvious clinical symptoms while the application of assisted reproductive technology(ART)has significantly improved the detection rate of it.The previous guidelines on hyperprolactinemia did not specify whether patients with idiopathic hyperprolactinemia and patients with PCOS as well as hyperprolactinemia need to use drugs to reduce PRL level during pregnancy assistance treatment,and there are few relevant research data at present.Considering the differences between artificial assisted pregnancy and natural pregnancy in follicular development,maturation,ovulation,fertilization and luteal support,the research results among natural pregnant women may not be applicable to women undergoing ART.In the process of clinical diagnosis and treatment,due to the lack of unified diagnosis and treatment standards,doctors often use bromocriptine to reduce the hormone level of patients with hyperprolactinemia according to experience,but whether it helps to improve the pregnancy outcome is unclear,and there are few deterministic reports.Therefore,it is of significance to explore whether bromocriptine is beneficial to the pregnancy outcome in infertile patients with hyperprolactinemia with unclear etiology or PCOS.Objective To analyze the effect of bromocriptine treatment on in vitro fertilization or intracytoplasmic sperm injection in patients with idiopathic hyperprolactinemia or PCOS patients with hyperprolactinemia(30ng/ml ≤ PRL<100ng/ml),and to explore whether it is helpful to improve pregnancy outcome and the necessity of clinical application.Method The present study comprised of 795 patients with hyperprolactinemia with unclear etiology or PCOS(30ng/ml≤PRL<100ng/ml)undergoing IVF/ICSI between December 2016 and December 2020 in our unit.The patients were further divided into treatment group and control group according to whether used bromocriptine.According to the baseline indexes of patients in the treatment group and the control group,the final inclusion object is determined after the propensity score matching(PSM)is carried out in the ratio of 1:1,and the PCOS and non PCOS patients are analyzed respectively.The index of IVF/ICSI outcomes were compared between the treatment group and control group.Result The study included a total of 795 patients,including 680 non-PCOS patients(438 patients in the treatment group and 242 patients in the control group)and 115 PCOS patients(74 patients in the treatment group and 41 patients in the control group).Through propensity score matching according to the ratio of 1:1,444 non-PCOS patients and 60 PCOS patients were finally included.1.Comparison of IVF/ICSI outcomes in non-PCOS patientsCompared with the control group,the duration and total dosage of gonadotropin in the treatment group were less(9.18±1.77 vs.9.42±1.81;1765.26 ± 772.76 vs.1823.99 ± 667.42,P<0.05).However,in the treatment group,the clinical pregnancy rate(54.95%vs.65.32%),embryo implantation rate(41.84%vs.52.26%),live birth rate(44.14%vs.59.46%)and fullterm birth rate(37.39%vs.47.30%)were lower,while the abortion rate(18.03%vs.7.59%)was higher.There was significant difference in the above indexes between the two groups(P<0.05).Logistic regression analysis showed that bromocriptine treatment was an independent factor affecting embryo implantation rate(aOR:0.677;95%CI:0.501～0.916),live birth rate(aOR:0.527;95%CI:0.348～0.799)and abortion rate(aOR:aOR:2.850;95%CI:1.239～6.559).2.Subgroup analysis of non-PCOS patientsConsidering that the effect of bromocriptine treatment on idiopathic hyperprolactinemia may change with the increase of PRL level,or there may be an "inflection point",we further analyzed the two groups of patients according to the PRL level(≤40ng/ml and>40ng/ml).When PRL level is between 30ng/ml to 40ng/ml,compared with the control group,the duration and total dosage of gonadotropin in the treatment group were less(9.14±1.75 vs.9.41±1.77,1730.98 ± 717.62 vs.1844.45 ± 697.70,P<0.05).But in the control group,the clinical pregnancy rate(66.27%vs.52.76%,P<0.05),embryo implantation rate(52.13%vs.39.65%,P<0.05),live birth rate(60.36%vs.41.1%,P<0.05)and full-term birth rate(49.11%vs.33.74%,P<0.05)were higher,while the abortion rate(7.14%vs.19.77%,P<0.05)was lower.Logistic regression analysis showed that bromocriptine treatment was an independent factor affecting clinical pregnancy rate(aOR:0.512;95%CI:0.306～0.855),embryo implantation rate(aOR:0.545;95%CI:0.377～0.788),live birth rate(aOR:0.437;95%CI:0.264～0.722),full-term birth rate(aOR:0.581;95%CI:0.349～0.965)and abortion rate(aOR:3.297;95%CI:1.244～8.738).When PRL>40ng/ml,there was no significant difference in pregnancy related indexes and pregnancy outcomes between the treatment group and the control group(P>0.05).3.Comparison of IVF/ICSI outcomes in patients with PCOS.Compared with the control group,the amount of high-quality embryos(5.67 ± 3.11 vs.7.40 ± 3.21,P<0.05)and frozen embryos(2.23 ± 2.22 vs.3.67 ± 2.82.P<0.05)in the treatment group were less.But the pregnancy outcomes among the two groups didn’t show significant difference.Conclusions1.Bromocriptine treatment cannot improve fertility outcomes in infertile women with idiopathic hyperprolactinemia or PCOS patients with hyperprolactinemia(30ng/ml ≤ PRL<100ng/ml)when undergoing assisted reproductive therapy.2.For infertile women with idiopathic hyperprolactinemia with blood PRL level of 30ng/ml40ng/ml,no treatment is allowed in IVF/ICSI treatment if there are no obvious clinical symptoms,but it needs to be further demonstrated by larger sample size research.