İntrauterin İnseminasyon Sikluslarında Ovulasyonun Tetiklenmesinden 5 ve 7 Gün Sonra Ölçülen Serum Progesteron Düzeylerinin Devam Eden Gebelik Oranı Üzerine Etkisinin Araştırılması
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Orhan N., The effect of early and mid-luteal serum progesterone level on ongoing pregnancy rate in intrauterine insemination cycles, Hacettepe University, Department of Obstetrics and Gynecology, Dissertation, Ankara 2021. The definition of luteal phase insufficiency in natural cycles is controversial and might be encountered ~10% of infertile couples. Serum progesterone (P4) level measurement is a still the most feasible method for luteal phase monitoring. In last decade, although some research groups have been focusing on monitoring luteal phase in in-vitro fertilization cycles (IVF), there is scarce of evidence about luteal phase characteristics and serum P4 values in intrauterine insemination (IUI) cycles. In this study, a total of 230 cycles of 179 patients who underwent IUI treatment in Hacettepe University Faculty of Medicine, Department of Obstetrics and Gynecology, Andrology Unit between June 2020 and May 2021 were included. The primary outcome measure was the ongoing pregnancy rate. For ovarian stimulation, according to the clinician's preference, in 69 cycles only gonadotropin was used and in 161 cycles clomiphene citrate and gonadotropin were used consecutively. No luteal phase support was given. Human chorionic gonadotropin (hCG) was used to trigger ovulation and serum P4 levels were measured on the 5th (hCG+5) and 7th (hCG+7) days after hCG triggering. Of the 230 cycles 17 (7.4%) were resulted with ongoing pregnancy. In order to investigate the effect of low serum P4 levels on the ongoing pregnancy rate, patients were divided into groups as ≤10th percentile and >10th percentile according to serum P4 levels measured on hCG+5 and hCG+7 days. While ≤10 percentile value of serum P4 was calculated as ≤5.6 ng/ml for hGG+5 day, this value was ≤8.46 ng/ml for hCG+7 day. In the univariate analysis, the ongoing pregnancy rates of the hCG+5 and hCG+7 serum P4 ≤10th percentile and >10th percentile groups were 10.5% (2/19) versus 5.5% (9/164) (p=0.80) and 0% (0/16) versus 7.5% (n=11/145) (p=0.24), respectively. When the serum P4 level dynamics were observed between hCG+5 and hCG+7, it was found that serum P4 levels decreased in 16.7% (26/156) of the cycles. The ΔP4 value was calculated by subtracting the serum P4 level measured on hCG+5 from the serum P4 level measured on day hCG+7 (ΔP4= hCG+7 – hCG+5). While none of the 26 patients with negative ΔP4 had ongoing pregnancy, 8 (6.2%) of 130 patients with positive ΔP4 had ongoing pregnancy (p=0.194). In the multivariate-GEE (generalized estimating equation) analysis, ΔP4 was found to be an independent predictor of ongoing pregnancy alone (ß:0.137, 95% CI= 0.020-0.254, p=0.02). In conclusion, it has been shown that early luteal phase (hCG+5) serum P4 level was not a predictor of ongoing pregnancy rate, however, in mid-luteal (hCG+7) low (≤8.46 ng/ml) serum P4 level was associated with lower ongoing pregnancy rates. It also has been determined that a drop in serum P4 (negative ΔP4) between early and midluteal phase was an independent predictor of ongoing pregnancy. As a wider implication, supporting the luteal phase in all IUI cycles may be a one strategy. Alternatively, monitoring the luteal phase and rescuing the cycle with exogenous progesterone supplementation in patients with low mid-luteal (hCG+7) serum P4 (≤8.46) level or in patient with negative ΔP4 level may be another strategy. Randomized controlled trials are urgently needed to test the efficacy of suggested strategies.