The role of serum kisspeptin level in prediction of EARLYpregnancy outcomes in patients with pregnancy using assistedreproductive techniques

OBJECTIVE: Abortion is the most common complication of first trimester pregnancies and affects one out of every five pregnancies. Especially in the first trimester, cytogenetic abnormality of the developing embryo is associated with impaired implantation and placentation. The β subunit of human chorionic gonadotropin (β-hCG) is the most widely used pregnancy biomarker. Although the diagnosis of abortion is made by ultrasonography and serial β-hCG measurements, there is still no reliable biomarker that accurately predicts the risk of abortion. Due to the wide variability in β-hCG levels in early pregnancy, a single measurement is of limited value in the diagnosis of abortion. Kisspeptins are a family of peptides encoded by the KISS1 gene, which binds to the G protein-coupled "kisspeptin receptor". Recent studies show that kisspeptin has an important role in many aspects of fertility, including puberty, ovulation, and placentation. Kisspeptin is highly expressed in the placenta throughout pregnancy in humans. Circulating kisspeptin levels reach levels approximately 7,000 times higher in the third trimester than in non-pregnant women. It decreases rapidly after birth. Studies suggest that kisspeptin has the potential to be a biomarker for abortion. In our study, it was aimed to determine the role of kisspeptin levels in predicting pregnancy outcomes in cases aged 18-40 years who achieved pregnancy using assisted reproductive techniques and to determine whether it could be used as a biomarker in predicting possible abortion. METHODS: This prospective cohort study was conducted after obtaining the permission of Dokuz Eylul University Faculty of Medicine Non-Invasive Research Ethics Committee. Our study was planned among 28 volunteers who applied to Dokuz Eylul University Medical Faculty Hospital IVF Center between October 2020 and September 2021 and met the inclusion criteria of the study. Kisspeptin level was determined by taking venous blood samples from the patients who applied to our center 3 times, before the start of controlled ovarian stimulation, on the day of embryo transfer and 14 days after the embryo transfer. The number of patients in the case group planned to be included in the study was found to be at least 28 patients in the case of low effect size (0.25), α: 0.05 and power: 80%, by choosing the F test for repetitive measurement comparison in the G-Power 3.1.9.2 program. The significance level for all analyzes was determined as p<0.05. The Statistical Program for Social Sciences (IBM SPSS 22.0) was used for the analysis. RESULTS: Eighteen of the 28 cases included in the study resulted in live birth, and the pregnancies of 10 cases resulted in pregnancy loss. It was observed that kisspeptin measurement averages in cases who had live births changed statistically significantly (χ²=11.44, p=0.003). In this group, kisspeptin values from the first measurement to the second measurement (p=0.043), from the first measurement to the third measurement (p=0.010) and from the second measurement to the third measurement (p=0.006) were found to increase statistically significantly. In addition, the mean values of β-hCG (p=0.049) and KISS3 (p=0.002) in pregnant women who had a live birth were found to be statistically significantly higher than the mean values of patients with pregnancy loss. In cases with pregnancy loss, mean kisspeptin measurements did not change statistically (χ²=2.60, p=0.273), but kisspeptin values decreased statistically from the first measurement to the third measurement in this group (p=0.017). There was a statistically significant positive correlation between β-hCG values and KISS3 values of the patients (r=0.405, p=0.032), and KISS3 values increased the probability of having a live birth by 1.05 times at a statistically significant level (p=0,009 OR=1,05 [%95 CI 1,01-1,09]) was detected. CONCLUSION: In our study, kisspeptin measurements measured during IVF treatment of patients whose pregnancies resulted in live birth showed a statistically significant increase (p=0.003), and it was found that KISS3 values increased the probability of having a live birth statistically (p=0,009 OR=1,05). It was determined that there was a significant decrease (p=0.017) from KISS1 measurement to KISS3 measurement in patients who experienced pregnancy loss. In conclusion, in our study, it was shown that the increase in kisspeptin level in IVF treatment is associated with cases resulting in live birth, and studies with larger series are needed to predict live birth and to determine the threshold value of the increase in kisspeptin value. KEYWORDS: Kisspeptin, Abortion, Assisted Reproductive Techniques