The Importance Of Determination Of Ovulation In Women Undergoing Ovulation Induction Şebnem ALANYA TOSUN, MD Assistant Professor of Obstetrics and Gynecology Department of Obstetrics and Gynecology Giresun University, School of Medicine Giresun/TURKEY Şebnem Alanya Tosun1, Mehmet Bülent Ergun2, Mustafa Kemal Ozel3, Enis Ozkaya4 1Giresun University School of Medicine, Department of Obstetrics and Gynecology, Giresun Turkey 2Istanbul University School of Medicine, Department of Obstetrics and Gynecology, Istanbul Turkey 3Islahiye State Hospital, Department of Obstetrics and Gynecology, Gaziantep Turkey 4Zeynep Kamil Maternity and Children’s Hospital, Department of Obstetrics and Gynecology, Istanbul Turkey Dear Professors, dear colleagues, first of all I am thankful to everyone who volunteered their time. It is great honor for me to be here. Our research title is “The Importance of determination of ovulation in women undergoing ovulation induction”

Objective To determine the ovulation by using progesterone levels and ultrasonography findings in the luteal phase in cases of unexplained infertility or anovulation undergoing OI+IUI treatment. Does it improve the rate of implantation and pregnancy outcome? In this study Our objective is To determine the ovulation by using progesterone(P) levels and ultrasonography findings in the luteal phase in cases of unexplained infertility or anovulation undergoing OI and intrauterine insemination(IUI) treatment. Our main question is: Does it improve the rate of implantation and pregnancy outcome?

Study Design Prospective observational study At an university setting For 10 months Approved by the local ethics commitee This prospective observational study was carried out in İstanbul University School of Medicine for 10 months and has been approved by the local ethics commitee. 

Material-Methods 107 women with unexplained infertility or who were anovulatory 46 patients received CC+IUI treatment 61 patients received GN+IUI treatment 250mcg of r-hCG was administered when the dominant follicle was >18mm in diameter Progesterone (P) on the hCG injection day. re-measured 72-96 hours after hCG injection IUI was performed 36 hours after hCG injection. Ovulation was observed via vaginal ultrasound . Biochemical (β-hCG level >5 mIU/ml) and clinical (presence of fetal heartbeat confirmed by vaginal ultrasound at the 6th week of gestation) pregnancy rates in the treatment cycles were recorded. 107 women with unexplained infertility or who were anovulatory were included in this study. 46 patients received clomifen citrate plus IUI treatment, while 61 patients received gonadotropin plus IUI treatment. 250mcg of r-hCG was administered when the dominant follicle measured bigger than 18mm in diameter, confirmed by serial vaginal ultrasound scanning starting on the 8th day of the menstrual cycle. Progesterone (P) was measured on the hCG injection day. IUI was performed 36 hours after hCG injection. Progesterone was re-measured 72-96 hours after hCG injection. Ovulation was observed via vaginal ultrasound which is applied after 72-96 hours of hCG injection. Biochemical pregnancy which means β-hCG level above 5 mIU/ml and clinical pregnancy rates which means the presence of fetal heartbeat confirmed by vaginal ultrasound at the 6th week of gestation, were recorded.

Statistics SPSS (Statistical Package for Social Sciences) for Windows 15.0 Definitive statistical techniques Correlation analysis Regression analysis Pearson correlation test Spearman’s rho test ROC (Receiver Operating Characteristic ) Curves P<0.05 was considered statistically significant SPSS (Statistical Package for Social Sciences) for Windows 15.0 was used Definitive statistical techniques, correlation analysis, regression analysis were used for to measure the relations of two or more variables. Pearson correlation test was used to show the relationship between parameters with normal distribution Spearman’s rho test was used to show the relationship between parameters with abnormal distribution ROC curves were performed to evaluate and compare the performance of diagnostic test And finally p smaller than 0.05 was considered statistically significant

The distribution of patients according to primary/secondary infertility subgrup and treatment subgrup This is the table about The distribution of patients according to primary/secondary infertility subgrup and treatment subgrup. There were 107 patients totally and 71% of these were in primary infertility subgroup whereas 29% of these were in secondary infertility subgroup. Also we can see the distribution of CC plus IUI and gonadotropin plus IUI numbers.

Results In 58 patients (54.2%), ovulation was detected at luteal phase P level of >10ng/mL. This level is found statistically significant in detection of ovulation (p<0.001). Ovulation was confirmed by luteal phase P level 47.8% of patients that received CC+IUI treatment 59% of patients that received GN+IUI treatment - The difference between these sub-groups was not statistically significant(p=0.238). In 58 patients (54.2%), ovulation was detected at luteal phase P level of >10ng/mL. This level was regarded as statistically significant in detection of ovulation (p<0.001). Ovulation was confirmed by luteal phase P level in 47.8% of patients that received CC+IUI treatment, while in 59% of patients that received GN+IUI treatment. The difference between these sub-groups was not statistically significant(p=0.238).

This is the table from the statistical analysis This is the table from the statistical analysis. Predictor is luteal phase progesterone. For threshold value of 10.3, area under curve to predict ovulation is statistically significant. It has 98% sensitivity.

Results-2 Vaginal ultrasound confirmed ovulation in 50 out of the 58 patients that had confirmed ovulation via luteal phase P level. In total, vaginal ultrasound detected ovulation in 89 out of 107 patients. Vaginal ultrasound confirmed ovulation in 50 out of the 58 patients that had confirmed ovulation via luteal phase P level. In total, vaginal ultrasound detected ovulation in 89 out of 107 patients.

Vaginal ultrasound findings versus ovulation with luteal phase progesterone As I told you before We performed vaginal ultrasound 72-96 hours later than hcg injection. At ultrasound findings we accepted thick wall cyst, corpus luteum, heterojen cyst or lost folikül as ovulation positive, while anechoic and thin wall cyst as ovulation negatif.

Results-3 Implantation was observed in 13 patients (excluding ectopic pregnancies). In two patients, ectopic pregnancy occurred. Implantation did not take place in 92 patients. In 5 patients, in the CC+IUI treatment sub-group and in 5 patients, in GN+IUI sub-group, presence of fetal heartbeat was observed via ultrasound. Implantation was observed in 13 patients (excluding ectopic pregnancies). In two patients, ectopic pregnancy occurred. Implantation did not take place in 92 patients. In 5 patients, in the CC+IUI treatment sub-group and in 5 patients, in GN+IUI sub-group, presence of fetal heartbeat was observed via ultrasound.

Pregnancies This table shows number of biochemical and clinical pregnancies. All pregnancies are in ovulatory group according to LFP

This table shows that all biochemical pregnancies were in the ovulatory group confirmed by luteal phase progesterone and it is statistically significant

Results-4 In all pregnancies, luteal phase P level was detected >10ng/ml. In 12 patients, hCG day P level was >1ng/mL and none of these patients became pregnant. HCG day P level >1ng/ml is found significant to predict implantation failure(AUK=0.679,p=0.04). Luteal phase P level suggested significant implantation (AUC=0.750,p=0.004). According to ROC analysis, at 77% of sensitivity and 61% of specificity, value of luteal phase P was 21.5 for implantation. Having a value of luteal phase P that is >21.5 is strongly associated with implantation (OR=9.9;CI=2.4-41.2).  In all pregnancies, luteal phase P level was detected >10ng/ml. In 12 patients, hCG day P level was >1ng/mL and none of these patients became pregnant. HCG day P level >1ng/ml is found significant to predict implantation failure(AUK=0.679,p=0.04). Luteal phase P level suggested significant implantation (AUC=0.750,p=0.004). According to ROC analysis, at 77% of sensitivity and 61% of specificity, value of luteal phase P was 21.5 for implantation. Having a value of luteal phase P that is >21.5 is strongly associated with implantation (OR=9.9;CI=2.4-41.2). 

Conclusion In patients that received OI+IUI treatment, ovulation was confirmed in only 54.2% via luteal phase P level. All pregnancies were in this group. In 45.8% of the patients, ovulation did not occur even with the ovulation induction treatment. In detecting ovulation, a luteal phase P level of >10ng/mL was found highly sensitive (98%). Luteal phase P>21.5 is strongly associated with implantation.

Suggestions P evaluation in hCG day and at luteal phase are convenient and inexpensive measurements. By combining them with ultrasound scanning 72-96 hours after hCG injection day, we can find the most optimal treatment for the infertility patients in their next cycle.

Thank you…