Kisspeptin In Different Ovarian Reserves Dynamics During Controlled Ovarian Hyperstimulation And Correlations With Clinical Outcomes

Objective:Kisspeptin is a 145 amino acid polypeptide encoded by the KISS1 gene that is present in many tissues of the body.Recent studies have found that kisspeptin plays an important role in the field of reproductive endocrinology.Kisspeptin binds to receptor GPR54 and stimulates the release of gonadotropin-releasing hormone?Gn RH?,which in turn regulates the hypothalamic-pituitary-ovarian axis?HPO-A?.Ovarian theca cells,granulosa cells and luteal cells express kisspeptin periodically and participate in the regulation of different ovarian functions.To investigate the changes and reasons of serum kisspeptin levels during controlled hyperstimulation in infertility patients with different ovarian reserve.To analyze the relationship between different ovarian reserve functions and kisspeptin.To explore the correlation between kisspeptin and outcomes of COH and to evluate the effect of kisspeptin in follicular fluid on oocytes.Methods:A total of 58 eligible IVF/ICSI-ET cycles owing to the Polyclinic ovarian syndrome?PCOS?,tube and/or male factors and ovarian dysfunction from March.2017 to Dec.2017 were studied,which divided into three groups according to the anti-Mullerian hormone?AMH?and PCOS Rotterdam criteria,including 20 cases of PCOS,22 cases of normal ovarian function,and 16 cases of ovarian dysfunction.All three groups used the same ovulation-promoting regimen,that is,menstrual cycle or retreating bleeding on the 2nd/3rd day using human menopausal gonadotropin?HMG?and letrozole?LE?for ovulation.Serum kisspeptin levels were measured at the day of Gn starting?baseline?,day 5 of Gn stimulation?Gn5?,day of h CG administration?dh CG?.On the day of oocyte retrieval,the follicular fluid with a diameter of?18mm was collected.We record and compared the FSH,LH,E₂,P,kisspeptin on the day of Gn,the dosage of Gn,E₂ levels on h CG,retrieved oocytes,numbers of MII,2PN of fertilization,avaliable embryos,top quality embryos in the three groups.And to analyse the relationship of kisspeptin levels of serum and follicular fluid among ofthe dosage of Gn,E₂levelson h CG,tetrieved oocytes,numbers of MII,2PN of fertilization,top quality embryos?avaliable embryos.Results:1.Comparison of basic situationThere was no significant difference in the baseline E₂ and P levels between the three groups?P>0.05?.The level of basal FSH was lower in the ovarian dysfunction group?9.36±1.41m IU/ml?than in the PCOS group?5.48±1.74m IU/ml?and the ovarian normal function group?6.69±2.25 m IU/ml?.There was a statistical difference among the three groups?P<0.05?.The level of kisspeptin in the PCOS group?1.44±0.43ng/ml?was significantly higher than that in the ovarian hypofunction group?0.85±0.45 ng/ml?on the basic day?P<0.05?,and higher than that in the ovarian normal group?0.92±0.42ng/ml??P<0.05?.The level of basic LH in the PCOS group?7.81±1.77m IU/ml?was higher than that in the ovarian hypofunction group?3.92±1.86m IU/ml?and the normal ovarian function group?3.00±1.31m IU/ml?.There was a statistical difference between the three groups?P<0.05?.2.Comparision of correlated parametes about COHThe dosage of Gn of ovarian dysfunction group?2746.88±603.92IU?was higher than the normal ovarian function group?2346.59±550.68IU?and PCOS group?1980.00±520.76IU?,and the normal ovarian function group was higher than the PCOS group.There was a statistical difference between the three groups?P<0.05?.E₂ level on hCG of PCOS group?5776.30±2494.63pg/ml?was higher than that of ovarian dysfunc-tion group?1212.95±417.90pg/ml?and the normal ovarian function grou?4344.45±2169.84pg/ml?,and that of the normal ovarian function group was higher than that of ovarian dysfunction group.There was a statistical difference between the three groups?P<0.05?.Significant differences in numbers of retrieved oocytes,MII,high-quality embryos and available embryos among three groups were seen,and these of PCOS group?18.00±5.31,15.70±5.77,5.20±2.33,4.70±0.95?were higher than those in the normal ovarian function group?12.36±4.59,14.82±4.73,4.09±1.76,2.45±1.04?,while those in the normal ovarian function group were higher than those in the ovarian dysfunction group?5.19±3.90,3.75±1.98,2.63±1.15,1.63±0.91??P<0.05?.The numbers of 2PN fertilization in PCOS group?12.20±2.20?and normal ovarian function group?11.18±2.27?were higher than that in ovarian dysfunction group?3.50±2.07??P<0.05?.There was no significant difference between PCOS group and normal ovarian function group?P>0.05?.3.Kisspeptin levels of serum in COHThe concentration of kisspeptin showed an upward trend in the three groups of COH,and the serum kisspeptin level was highest on the hCG day.4.Correlations of kisspeptin with COH laboratory outcomeSerum kisspeptin levels on Gn day,Gn5 day,hCG day and follicular fluid kisspeptin level were positively correlated with h CG day E₂ level?r=0.405;r=0.136;r=0.270;r=0.536;P<0.05?and numbers of MII?r=0.193;r=0.072;r=0.154;r=0.577;P<0.05?Conclusions:Serum kisspeptin levels were increasing during COH.Kisspeptin levels of the PCOS group in the serum and follicular fluid on baseline was significantly higher than that of the normal ovarian function group,suggesting that kisspeptin may participate in the pathogenesis and development of PCOS.Changes in the level of kisspeptin during COH may predict ovulation and egg maturation.